Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which ...Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.展开更多
The collapse pressure is a key parameter when RTPs are applied in harsh deep-water environments.To investigate the collapse of RTPs,numerical simulations and hydrostatic pressure tests are conducted.For the numerical ...The collapse pressure is a key parameter when RTPs are applied in harsh deep-water environments.To investigate the collapse of RTPs,numerical simulations and hydrostatic pressure tests are conducted.For the numerical simulations,the eigenvalue analysis and Riks analysis are combined,in which the Hashin failure criterion and fracture energy stiffness degradation model are used to simulate the progressive failure of composites,and the“infinite”boundary conditions are applied to eliminate the boundary effects.As for the hydrostatic pressure tests,RTP specimens were placed in a hydrostatic chamber after filled with water.It has been observed that the cross-section of the middle part collapses when it reaches the maximum pressure.The collapse pressure obtained from the numerical simulations agrees well with that in the experiment.Meanwhile,the applicability of NASA SP-8007 formula on the collapse pressure prediction was also discussed.It has a relatively greater difference because of the ignorance of the progressive failure of composites.For the parametric study,it is found that RTPs have much higher first-ply-failure pressure when the winding angles are between 50°and 70°.Besides,the effect of debonding and initial ovality,and the contribution of the liner and coating are also discussed.展开更多
BACKGROUND Neutrophil-lymphocyte ratio(NLR),fibrosis index based on four factors(Fib4),aspartate aminotransferase-to-platelet ratio index(APRI)can be used for prognostic evaluation of hepatocellular carcinoma.However,...BACKGROUND Neutrophil-lymphocyte ratio(NLR),fibrosis index based on four factors(Fib4),aspartate aminotransferase-to-platelet ratio index(APRI)can be used for prognostic evaluation of hepatocellular carcinoma.However,no study has established an individualized prediction model for the prognosis of hepatocellular carcinoma based on these factors.AIM To screen the factors that affect the prognosis of hepatocellular carcinoma and establish a nomogram model that predicts postoperative liver failure after hepatic resection in patients with hepatocellular carcinoma.METHODS In total,220 patients with hepatocellular carcinoma treated in our hospital from January 2022 to January 2023 were selected.They were divided into 154 participants in the modeling cohort,and 66 in the validation cohort.Comparative analysis of the changes in NLR,Fib4,and APRI levels in 154 patients with hepatocellular carcinoma before liver resection and at 3 mo,6 mo,and 12 mo postoperatively was conducted.Binary logistic regression to analyze the influencing factors on the occurrence of liver failure in hepatocellular carcinoma patients,roadmap prediction modeling,and validation,patient work characteristic curves(ROCs)to evaluate the predictive efficacy of the model,calibration curves to assess the consistency,and decision curve analysis(DCA)to evaluate the model’s validity were also conducted.RESULTS Binary logistic regression showed that Child-Pugh grading,Surgical site,NLR,Fib4,and APRI were all risk factors for liver failure after hepatic resection in patients with hepatocellular carcinoma.The modeling cohort built a column-line graph model,and the area under the ROC curve was 0.986[95%confidence in terval(CI):0.963-1.000].The patients in the validation cohort utilized the column-line graph to predict the probability of survival in the validation cohort and plotted the ROC curve with an area under the curve of the model of 0.692(95%CI:0.548-0.837).The deviation of the actual outcome curves from the calibration curves of the column-line plots generated by the modeling and validation cohorts was small,and the DCA confirmed the validity.CONCLUSION NLR,Fib4,and APRI independently influence posthepatectomy liver failure in patients with hepatocellular carcinoma.The column-line graph prediction model exhibited strong prognostic capability,with substantial concordance between predicted and actual events.展开更多
BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore...BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore the validity of electromechanical resynchronization,clinical and echocardiographic response of LBBP-CRT.METHODS Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section.RESULTS In our analysis,the success rate of LBBP-CRT was determined to be 91.1%.LBBP CRT significantly shortened QRS duration,with significant improvement in echocardiographic parameters,including left ventricular ejection fraction,left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT.CONCLUSION A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group.Lastly,the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.展开更多
BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple b...BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.展开更多
Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia(HK),there is therefore a need to establish a multi-specialty approach to optimal renin angiotension-aldos...Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia(HK),there is therefore a need to establish a multi-specialty approach to optimal renin angiotension-aldosterone system inhibitors(RAASi)usage and HK management in patients with chronic kidney disease(CKD)&heart failure(HF).This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF.Methods A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique.The group then created a list of 41 statements for a consensus questionnaire,which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China.Consensus was assessed using a modified Delphi technique,with agreement defined as"strong"(≥75%and<90%)and"very strong"(≥90%).The steering group,data collection,and analysis were aided by an independent facilitator.Results A total of 150 responses from 21 provinces across China were recruited in the survey.Respondents were comprised of an even split(n=75,50%)between cardiologists and nephrologists.All 41 statements achieved the 75%consensus agreement threshold,of which 27 statements attained very strong consensus(≥90%agreement)and 14 attained strong consensus(agreement between 75%and 90%).Conclusion Based on the agreement levels from respondents,the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.展开更多
Background: Venous thromboembolism (VTE) is a major public health problem due to its increasing frequency, mortality and management cost. This cost may require major financial efforts from patients, especially in deve...Background: Venous thromboembolism (VTE) is a major public health problem due to its increasing frequency, mortality and management cost. This cost may require major financial efforts from patients, especially in developing countries like ours where less than 7% of the population has health insurance. This study aimed to estimate the direct cost of managing VTE in three reference hospitals in Yaoundé. Methods: This was a cross-sectional retrospective study over a three-year period (from January 1st 2018 to December 31 2020) carried out in the Cardiology departments of the Central and General Hospitals, and the Emergency Centre of the city of Yaoundé. All patients managed during the study period for deep vein thrombosis and pulmonary embolism confirmed by venous ultrasound coupled with Doppler and computed tomography pulmonary angiography respectively were included. For each patient, we collected sociodemographic and clinical data as well as data on the cost of consultation, hospital stay, workups and medications. These data were analysed using SPSS version 23.0. Results: A total of 92 patient’s records were analysed. The median age was 60 years [48 - 68] with a sex ratio of 0.53. The median direct cost of management of venous thromboembolism was 766,375 CFAF [536,455 - 1,029,745] or $1415 USD. Management of pulmonary embolism associated with deep vein thrombosis was more costly than isolated pulmonary embolism or deep vein thrombosis. Factors influencing the direct cost of management of venous thromboembolism were: hospital structure (p = 0.015), health insurance (p 0.001), type of pulmonary embolism (p = 0.021), and length of hospital stay (p = 0.001). Conclusion: Management of VTE is a major financial burden for our patients and this burden is influenced by the hospital structure, health insurance, type of pulmonary embolism and length of hospital stay.展开更多
Accurate software cost estimation in Global Software Development(GSD)remains challenging due to reliance on historical data and expert judgments.Traditional models,such as the Constructive Cost Model(COCOMO II),rely h...Accurate software cost estimation in Global Software Development(GSD)remains challenging due to reliance on historical data and expert judgments.Traditional models,such as the Constructive Cost Model(COCOMO II),rely heavily on historical and accurate data.In addition,expert judgment is required to set many input parameters,which can introduce subjectivity and variability in the estimation process.Consequently,there is a need to improve the current GSD models to mitigate reliance on historical data,subjectivity in expert judgment,inadequate consideration of GSD-based cost drivers and limited integration of modern technologies with cost overruns.This study introduces a novel hybrid model that synergizes the COCOMO II with Artificial Neural Networks(ANN)to address these challenges.The proposed hybrid model integrates additional GSD-based cost drivers identified through a systematic literature review and further vetted by industry experts.This article compares the effectiveness of the proposedmodelwith state-of-the-artmachine learning-basedmodels for software cost estimation.Evaluating the NASA 93 dataset by adopting twenty-six GSD-based cost drivers reveals that our hybrid model achieves superior accuracy,outperforming existing state-of-the-artmodels.The findings indicate the potential of combining COCOMO II,ANN,and additional GSD-based cost drivers to transform cost estimation in GSD.展开更多
Only simplified two-dimensional model and a single failure mode are adopted to calculate the ultimate pullout capacity(UPC)of anchor cables in most previous research.This study focuses on a more comprehensive combinat...Only simplified two-dimensional model and a single failure mode are adopted to calculate the ultimate pullout capacity(UPC)of anchor cables in most previous research.This study focuses on a more comprehensive combination failure mode that consists of bond failure of an anchorage body and failure of an anchored rock mass.The three-dimensional ultimate pullout capacity of the anchor cables is calculated based on the Hoek-Brown failure criterion and variation analysis method.The numerical solution for the curvilinear function in fracture plane is obtained based on the finite difference theory,which more accurately reflects the failure state of the anchor cable,as opposed to that being assumed in advance.The results reveal that relying solely on a single failure mode for UPC calculations has limitations,as changes in parameter values not only directly impact the UPC value but also can alter the failure model and thus the calculation method.展开更多
Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of pu...Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the catastrophic costs DRTB patients incur.展开更多
Background: Emerging evidence has recognized that anemia and iron deficiency are recurrent comorbidities in chronic heart failure (HF) and several trials have established that iron administration improves myocardial a...Background: Emerging evidence has recognized that anemia and iron deficiency are recurrent comorbidities in chronic heart failure (HF) and several trials have established that iron administration improves myocardial asset and clinical scenario in HF. Purpose: Recent acquisitions suggest that iron deficiency represents a concrete bias in the pathogenetic mechanism of chronic HF, so we have investigated the putative role of the hepcidin/ferroportin axis in the cardiovascular setting to advocate novel pharmacological and clinical approaches. Methods: Here, after an excursus on iron metabolism, we first reviewed the ongoing studies on novel iron targeted compounds. Then, we summarize large clinical interventional studies conducted on patient suffering from iron deficiency and HF which have tested the effects of drugging iron regard QoL, hospitalizations and cardiovascular death. Results: Novel compounds such as hepcidin agonist (PTG 300), synthetic human hepcidin (LJPC-401) and anti FPN (Vamifeport) are ongoing in iron overloaded patients, while the hepcidin blocker (PRS-080) is under investigation in anemic patients. Noteworthy, novel insights could arise from the results of a Phase IV interventional study regarding the modification of hepcidin pathway in a large cohort of HF patients (n = 1992) by sodium glucose cotransporter 2 inhibitors. To date, several studies highlight the beneficial effect of iron administration in cardiovascular setting and latest evidences consider hepcidin level as a novel biomarker of cardiac injury and atherosclerosis. Conclusions: We advocate that data from ongoing studies will suggest novel iron targeted therapies for diagnosis, prognosis and therapy transferable in selected heart failed patients.展开更多
Introduction: Heart failure is a major public health pandemic, particularly in Africa, where its prevalence continues to increase. In northern Mali, few data exist, hence the interest of this study with the objective ...Introduction: Heart failure is a major public health pandemic, particularly in Africa, where its prevalence continues to increase. In northern Mali, few data exist, hence the interest of this study with the objective of studying the epidemiological, clinical and therapeutic and evolutionary aspects of Heart failure at the regional hospital of Gao. Patients and Methods: This was a cross-sectional, descriptive study that took place from July 2022 to June 2023 in the medical department at Gao Hospital. Results: The hospital prevalence of heart failure was 44.1%. The mean age was 47.30 ± 20 years (range: 16-88). Hypertension was the most common with 46.1%, followed by a sedentary lifestyle, and diabetes with 18.2% and 8.3% respectively;NYHA stage III-IV dyspnea was found in 83.9%. Reduced EF heart failure was present in 110 patients (76.9%), seventeen cases with moderately reduced EF (11.9%) and sixteen patients had preserved EF (11.2%). Global heart failure was the dominant (91.6%). The main etiologies of heart failure were dominated by hypertensive heart disease in 46 patients (32.2%), followed by postpartum cardiomyopathy with 43 cases (30.1%), primary dilated cardiomyopathy in 18 patients (12.6%), ischemic heart disease in 16 patients with 11.2%. Seven cases of valvular heart disease, or 4.9%. The evolution was favorable under treatment in 104 patients or 72.7%. In-hospital mortality was 14.7%. Conclusion: Heart failure is a common condition in sub-Saharan Africa, particularly in our country.展开更多
In practical engineering,due to the noncontinuity characteristics of joints in rock slopes,in addition to plane failure,stepped sliding failure may occur for intermittently jointed rock slopes.Especially for intermitt...In practical engineering,due to the noncontinuity characteristics of joints in rock slopes,in addition to plane failure,stepped sliding failure may occur for intermittently jointed rock slopes.Especially for intermittently bedding jointed rock slopes,the correlation and difference in strength parameters between joints and rock bridges,along with the various failure modes and intermittency of rock bridges,contribute to the complexity of stepped failure modes and the unpredictability of failure regions.Based on the upper-bound limit analysis method and multi-sliders step-path failure mode,considering the shear and tensile failure of rock bridges and the weakened relationship between the strength parameters of rock bridges and jointed surfaces,by introducing the modified M-C failure criterion and the formula for calculating the energy consumption of tensile failure of rock bridges,two failure mechanisms are constructed to obtain the safety factor(F_(s))of intermittently jointed rock slopes.The sequential quadratic programming method is used to obtain the optimal upper-bound solution for F_(s).The influence of multiple key parameters(slope height H,horizontal distance L,Slope angleβ,shear strength parameters of the rock bridgeφr and cr,Dimensionless parameter u,weakening coefficients of the internal friction angle and cohesion between the rock bridges and joint surfaces Kφand Kc)on the stability analysis of intermittently jointed rock slopes under the shear failure mode of rock bridges as well as under the tensile failure mode is also explored.The reliability of the failure mechanisms is verified by comparative analysis with theoretical results,numerical results,and landslide cases,and the variation rules of F_(s)with each key parameter are obtained.The results show that F_(s) varies linearly withφr and cr of the rock bridge and with K_(φ)and K_(c),whereas F_(s)changes nonlinearly with H and L.In particular,with the increase in Kφand Kc,Fs increases by approximately 52.78%and 171.02%on average,respectively.For rock bridge tensile failure,F_(s) shows a nonlinearly positive correlation withφr,cr,Kφand Kc.In particular,with the increase in Kφand Kc,Fs increases by approximately 13%and 61.69%on average,respectively.Fs decreases rapidly with increasing slope gradientβand decreasing dimensionless parameterμ.When Kφand Kc are both less than 1.0,the stepped sliding surface occurs more easily than the plane failure surface,especially in the case of tensile failure of the rock bridge.In addition,rock slopes with higher strength parameters,taller heights,and greater weakening coefficients are prone to rock bridge tension failure with lower Fs,and more attention should be given to the occurrence of such accidents in actual engineering.展开更多
Aphis gossypii has become increasingly difficult to manage due to its strong insecticide resistance.In the laboratory,we established sulfoxaflor-resistant and acetamiprid-resistant strains in two A.gossypii population...Aphis gossypii has become increasingly difficult to manage due to its strong insecticide resistance.In the laboratory,we established sulfoxaflor-resistant and acetamiprid-resistant strains in two A.gossypii populations with different basal insecticide resistance levels,and evaluated the effects of basal insecticide resistance on the resistance development and cross-resistance,as well as differences in fitness.Under the same selection pressure,Yarkant A.gossypii(with low basal insecticide resistance)evolved resistance to sulfoxaflor and acetamiprid more quickly than Jinghe A.gossypii(with high basal insecticide resistance),and the evolution of A.gossypii resistance to sulfoxaflor developed faster than acetamiprid in both Yarkant and Jinghe,Xingjiang,China.The sulfoxaflor-resistant strains selected from Yarkant and Jinghe developed significant cross-resistance to acetamiprid,imidacloprid,thiamethoxam and pymetrozine;while the acetamiprid-resistant strains developed significant cross-resistance to sulfoxaflor,imidacloprid,thiamethoxam,pymetrozine,and chlorpyrifos.The relative fitness of A.gossypii decreased as the resistance to sulfoxaflor and acetamiprid developed.The relative fitness levels of the sulfoxaflor-resistant strains(Yarkant-SulR and Jinghe-SulR)were lower than those of the acetamipridresistant strains(Yarkant-AceR and Jinghe-AceR).In addition,the relative fitness levels of sulfoxaflor-and acetamiprid-resistant strains were lower in Jinghe than in Yarkant.In summary,basal insecticide resistance of A.gossypii and insecticide type affected the evolution of resistance to insecticides in A.gossypii,as well as cross-resistance to other insecticides.The sulfoxaflor-and acetamiprid-resistant A.gossypii strains had obvious fitness costs.The results of this work will contribute to the insecticide resistance management and integrated management of A.gossypii.展开更多
As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish(D...As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish(Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species,27℃, to lower temperatures of 22℃, 20℃, and 13℃ over a period of two weeks. Comparative metabolomic(six biological replicates for each temperature) and transcriptomic(four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production,antioxidant function, and lipid and protein catabolism.Disrupted reproductive hormones, increased proteolysis,and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.展开更多
Medicinal leeches have been utilized in therapy for thousands of years. However, the adaptation physiology between leeches and hosts is not fully understand. To disclose the molecular mechanisms of adaptation between ...Medicinal leeches have been utilized in therapy for thousands of years. However, the adaptation physiology between leeches and hosts is not fully understand. To disclose the molecular mechanisms of adaptation between leech and host, the body transcriptomes of hunger and fed blood-sucking Poecilobdella javanica, Haemadipsa cavatuses, and Hirudo nipponia leeches were obtained by RNA sequencing, after comparison, a stratified unigenes group was obtained, which closely correlated to body distension. In the group, Rfamide receptor decreased significantly (P < 0.05) while serotonin receptor increased significantly (P < 0.05). Moreover, four KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, including cardiac muscle contraction, complement and coagulation cascades, renin-angiotensin system, and hypertrophic cardiomyopathy were significantly enriched. The unigenes annotation, neuroregulators correlation analysis and induced function of the KEGG pathways, were consistently supported the same result as: vasoconstriction and systole reaction enhance in hunger leeches and vice versa vasodilation and diastole increase in fed leeches, meanwhile, Interspecific comparison and correlative analyses of physiological function showed that the strongest reaction of induced heart failure from four KEGG occur in strongest reaction of systole in hungry P. javanica and in strongest reaction of diastole in fed H. nipponia. Overall, heart failure is likely a physiological function involved in feeding behaviour.展开更多
A seismic-induced landslide is a common geological catastrophe that occurs in nature.The Wangjiayan landslide,which was triggered by the Wenchuan earthquake,is a typical case in point.The Wanjiayan landslide caused ma...A seismic-induced landslide is a common geological catastrophe that occurs in nature.The Wangjiayan landslide,which was triggered by the Wenchuan earthquake,is a typical case in point.The Wanjiayan landslide caused many casualties and resulted in enormous property loss.This study constructs a simple surficial failure model based on the upper bound approach of three-dimensional(3D)limit analysis to evaluate the slope stability of the Wangjiayan case,while a traditional two-dimensional(2D)analysis is also conducted as a reference for comparison with the results of the 3D analysis.A quasi-static calculation is used to study the effect of the earthquake in terms of horizontal ground acceleration,while a parametric study is conducted to evaluate the critical cohesion of slopes.Rather than employing a 3D analysis,using the 2D analysis yields an underestimation regarding the safety factor.In the Wangjiayan landslide,the difference in the factors of safety between the 3D and 2D analyses can reach 20%.The sliding surface morphology as determined by the 3D method is similar to actual morphology,and the parameters of both are also compared to analyze the reliability of the proposed 3D method.展开更多
Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among...Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among the 30 countries with the highest TB burden. Objective: The study aimed to estimate the average direct medical cost of treating drug-resistant tuberculosis in 19 health centers in Maputo City, Mozambique. Methods: A retrospective analysis of direct medical costs was conducted on patients aged 18 and older who completed 20-month drug-resistant tuberculosis treatment regimens in Maputo City in 2019. Results: This analysis covered 140 patients who completed a 20-month treatment regimen, with 64.3% (78) being male and 35.7% (62) female. Approximately 50% of the participants were aged between 29 and 47. The average direct medical cost of DRTB treatment was $4789.43, reaching up to $6568.00, with a standard deviation of $753.26, including clinical interventions and treatment. Conclusion: The direct medical costs for a basic treatment package for a patient with drug-resistant TB in Mozambique equal 36 minimum wages. Developing alternative and innovative funding mechanisms and identifying ways to mitigate costs through the use of generic medicines would be beneficial.展开更多
Red clay landslides are widely distributed worldwide,resulting in severe loss of life and property.Although rainfall-induced red clay slopes have received extensive attention,the role of cracks in the evolutionary pro...Red clay landslides are widely distributed worldwide,resulting in severe loss of life and property.Although rainfall-induced red clay slopes have received extensive attention,the role of cracks in the evolutionary process of red clay slopes and their connection to failure mechanisms is still poorly understood.A comprehensive approach integrating field investigation,laboratory tests,and numerical simulations was conducted to study the 168 red clay landslides in Xinshao County,China.The results show that red clay is prone to forming cracks at high moisture content due to its low swelling and high shrinkage properties.The failure mode of red clay slopes can be summarized in three stages:crack generation,slope excavation,and slope failure.Furthermore,the retrospective analysis and numerical simulations of the typical landslide in Guanchong indicated that intense rainfall primarily impacts the shallow layer of soil within approximately 0.5 m on the intact slope.However,cracks change the pattern of rainfall infiltration in the slope.Rainwater infiltrates rapidly through the preferential channels induced by the cracks rather than uniformly and slowly from the slope surface.This results in a significant increase in both the depth of infiltration and the saturated zone area of the cracked slope,reaching 3.8 m and 36.2 m^(2),respectively.Consequently,the factor of safety of the slope decreases by 13.4%compared to the intact slope,ultimately triggering landslides.This study can provide valuable insights into understanding the failure mechanisms of red clay slopes in China and other regions with similar geological settings.展开更多
Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the...Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community.展开更多
基金supported by the grant from the National Natural Science Foundation of China (82070609)
文摘Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.
基金financially supported by National Natural Science Foundation of China(Grant Nos.52088102,51879249)Fundamental Research Funds for the Central Universities(Grant No.202261055)。
文摘The collapse pressure is a key parameter when RTPs are applied in harsh deep-water environments.To investigate the collapse of RTPs,numerical simulations and hydrostatic pressure tests are conducted.For the numerical simulations,the eigenvalue analysis and Riks analysis are combined,in which the Hashin failure criterion and fracture energy stiffness degradation model are used to simulate the progressive failure of composites,and the“infinite”boundary conditions are applied to eliminate the boundary effects.As for the hydrostatic pressure tests,RTP specimens were placed in a hydrostatic chamber after filled with water.It has been observed that the cross-section of the middle part collapses when it reaches the maximum pressure.The collapse pressure obtained from the numerical simulations agrees well with that in the experiment.Meanwhile,the applicability of NASA SP-8007 formula on the collapse pressure prediction was also discussed.It has a relatively greater difference because of the ignorance of the progressive failure of composites.For the parametric study,it is found that RTPs have much higher first-ply-failure pressure when the winding angles are between 50°and 70°.Besides,the effect of debonding and initial ovality,and the contribution of the liner and coating are also discussed.
文摘BACKGROUND Neutrophil-lymphocyte ratio(NLR),fibrosis index based on four factors(Fib4),aspartate aminotransferase-to-platelet ratio index(APRI)can be used for prognostic evaluation of hepatocellular carcinoma.However,no study has established an individualized prediction model for the prognosis of hepatocellular carcinoma based on these factors.AIM To screen the factors that affect the prognosis of hepatocellular carcinoma and establish a nomogram model that predicts postoperative liver failure after hepatic resection in patients with hepatocellular carcinoma.METHODS In total,220 patients with hepatocellular carcinoma treated in our hospital from January 2022 to January 2023 were selected.They were divided into 154 participants in the modeling cohort,and 66 in the validation cohort.Comparative analysis of the changes in NLR,Fib4,and APRI levels in 154 patients with hepatocellular carcinoma before liver resection and at 3 mo,6 mo,and 12 mo postoperatively was conducted.Binary logistic regression to analyze the influencing factors on the occurrence of liver failure in hepatocellular carcinoma patients,roadmap prediction modeling,and validation,patient work characteristic curves(ROCs)to evaluate the predictive efficacy of the model,calibration curves to assess the consistency,and decision curve analysis(DCA)to evaluate the model’s validity were also conducted.RESULTS Binary logistic regression showed that Child-Pugh grading,Surgical site,NLR,Fib4,and APRI were all risk factors for liver failure after hepatic resection in patients with hepatocellular carcinoma.The modeling cohort built a column-line graph model,and the area under the ROC curve was 0.986[95%confidence in terval(CI):0.963-1.000].The patients in the validation cohort utilized the column-line graph to predict the probability of survival in the validation cohort and plotted the ROC curve with an area under the curve of the model of 0.692(95%CI:0.548-0.837).The deviation of the actual outcome curves from the calibration curves of the column-line plots generated by the modeling and validation cohorts was small,and the DCA confirmed the validity.CONCLUSION NLR,Fib4,and APRI independently influence posthepatectomy liver failure in patients with hepatocellular carcinoma.The column-line graph prediction model exhibited strong prognostic capability,with substantial concordance between predicted and actual events.
文摘BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore the validity of electromechanical resynchronization,clinical and echocardiographic response of LBBP-CRT.METHODS Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section.RESULTS In our analysis,the success rate of LBBP-CRT was determined to be 91.1%.LBBP CRT significantly shortened QRS duration,with significant improvement in echocardiographic parameters,including left ventricular ejection fraction,left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT.CONCLUSION A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group.Lastly,the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.
基金Supported by National Natural Science Foundation of China,No.82060123Doctoral Start-up Fund of Affiliated Hospital of Guizhou Medical University,No.gysybsky-2021-28+1 种基金Fund Project of Guizhou Provincial Science and Technology Department,No.[2020]1Y299Guizhou Provincial Health Commission,No.gzwjk2019-1-082。
文摘BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.
文摘Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia(HK),there is therefore a need to establish a multi-specialty approach to optimal renin angiotension-aldosterone system inhibitors(RAASi)usage and HK management in patients with chronic kidney disease(CKD)&heart failure(HF).This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF.Methods A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique.The group then created a list of 41 statements for a consensus questionnaire,which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China.Consensus was assessed using a modified Delphi technique,with agreement defined as"strong"(≥75%and<90%)and"very strong"(≥90%).The steering group,data collection,and analysis were aided by an independent facilitator.Results A total of 150 responses from 21 provinces across China were recruited in the survey.Respondents were comprised of an even split(n=75,50%)between cardiologists and nephrologists.All 41 statements achieved the 75%consensus agreement threshold,of which 27 statements attained very strong consensus(≥90%agreement)and 14 attained strong consensus(agreement between 75%and 90%).Conclusion Based on the agreement levels from respondents,the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.
文摘Background: Venous thromboembolism (VTE) is a major public health problem due to its increasing frequency, mortality and management cost. This cost may require major financial efforts from patients, especially in developing countries like ours where less than 7% of the population has health insurance. This study aimed to estimate the direct cost of managing VTE in three reference hospitals in Yaoundé. Methods: This was a cross-sectional retrospective study over a three-year period (from January 1st 2018 to December 31 2020) carried out in the Cardiology departments of the Central and General Hospitals, and the Emergency Centre of the city of Yaoundé. All patients managed during the study period for deep vein thrombosis and pulmonary embolism confirmed by venous ultrasound coupled with Doppler and computed tomography pulmonary angiography respectively were included. For each patient, we collected sociodemographic and clinical data as well as data on the cost of consultation, hospital stay, workups and medications. These data were analysed using SPSS version 23.0. Results: A total of 92 patient’s records were analysed. The median age was 60 years [48 - 68] with a sex ratio of 0.53. The median direct cost of management of venous thromboembolism was 766,375 CFAF [536,455 - 1,029,745] or $1415 USD. Management of pulmonary embolism associated with deep vein thrombosis was more costly than isolated pulmonary embolism or deep vein thrombosis. Factors influencing the direct cost of management of venous thromboembolism were: hospital structure (p = 0.015), health insurance (p 0.001), type of pulmonary embolism (p = 0.021), and length of hospital stay (p = 0.001). Conclusion: Management of VTE is a major financial burden for our patients and this burden is influenced by the hospital structure, health insurance, type of pulmonary embolism and length of hospital stay.
文摘Accurate software cost estimation in Global Software Development(GSD)remains challenging due to reliance on historical data and expert judgments.Traditional models,such as the Constructive Cost Model(COCOMO II),rely heavily on historical and accurate data.In addition,expert judgment is required to set many input parameters,which can introduce subjectivity and variability in the estimation process.Consequently,there is a need to improve the current GSD models to mitigate reliance on historical data,subjectivity in expert judgment,inadequate consideration of GSD-based cost drivers and limited integration of modern technologies with cost overruns.This study introduces a novel hybrid model that synergizes the COCOMO II with Artificial Neural Networks(ANN)to address these challenges.The proposed hybrid model integrates additional GSD-based cost drivers identified through a systematic literature review and further vetted by industry experts.This article compares the effectiveness of the proposedmodelwith state-of-the-artmachine learning-basedmodels for software cost estimation.Evaluating the NASA 93 dataset by adopting twenty-six GSD-based cost drivers reveals that our hybrid model achieves superior accuracy,outperforming existing state-of-the-artmodels.The findings indicate the potential of combining COCOMO II,ANN,and additional GSD-based cost drivers to transform cost estimation in GSD.
基金supported by the Natural Science Foundation of Hunan Province(2023JJ40078)the Scientific Research Project of Hunan Provincial Education Department(No.22C0573)+2 种基金the National Natural Science Foundation of China(51478477,51878668)Guizhou Provincial Department of Transportation Foundation(2017-122058)Foundation of Guizhou Provincial Science and Technology Department([2018]2815).
文摘Only simplified two-dimensional model and a single failure mode are adopted to calculate the ultimate pullout capacity(UPC)of anchor cables in most previous research.This study focuses on a more comprehensive combination failure mode that consists of bond failure of an anchorage body and failure of an anchored rock mass.The three-dimensional ultimate pullout capacity of the anchor cables is calculated based on the Hoek-Brown failure criterion and variation analysis method.The numerical solution for the curvilinear function in fracture plane is obtained based on the finite difference theory,which more accurately reflects the failure state of the anchor cable,as opposed to that being assumed in advance.The results reveal that relying solely on a single failure mode for UPC calculations has limitations,as changes in parameter values not only directly impact the UPC value but also can alter the failure model and thus the calculation method.
文摘Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the catastrophic costs DRTB patients incur.
文摘Background: Emerging evidence has recognized that anemia and iron deficiency are recurrent comorbidities in chronic heart failure (HF) and several trials have established that iron administration improves myocardial asset and clinical scenario in HF. Purpose: Recent acquisitions suggest that iron deficiency represents a concrete bias in the pathogenetic mechanism of chronic HF, so we have investigated the putative role of the hepcidin/ferroportin axis in the cardiovascular setting to advocate novel pharmacological and clinical approaches. Methods: Here, after an excursus on iron metabolism, we first reviewed the ongoing studies on novel iron targeted compounds. Then, we summarize large clinical interventional studies conducted on patient suffering from iron deficiency and HF which have tested the effects of drugging iron regard QoL, hospitalizations and cardiovascular death. Results: Novel compounds such as hepcidin agonist (PTG 300), synthetic human hepcidin (LJPC-401) and anti FPN (Vamifeport) are ongoing in iron overloaded patients, while the hepcidin blocker (PRS-080) is under investigation in anemic patients. Noteworthy, novel insights could arise from the results of a Phase IV interventional study regarding the modification of hepcidin pathway in a large cohort of HF patients (n = 1992) by sodium glucose cotransporter 2 inhibitors. To date, several studies highlight the beneficial effect of iron administration in cardiovascular setting and latest evidences consider hepcidin level as a novel biomarker of cardiac injury and atherosclerosis. Conclusions: We advocate that data from ongoing studies will suggest novel iron targeted therapies for diagnosis, prognosis and therapy transferable in selected heart failed patients.
文摘Introduction: Heart failure is a major public health pandemic, particularly in Africa, where its prevalence continues to increase. In northern Mali, few data exist, hence the interest of this study with the objective of studying the epidemiological, clinical and therapeutic and evolutionary aspects of Heart failure at the regional hospital of Gao. Patients and Methods: This was a cross-sectional, descriptive study that took place from July 2022 to June 2023 in the medical department at Gao Hospital. Results: The hospital prevalence of heart failure was 44.1%. The mean age was 47.30 ± 20 years (range: 16-88). Hypertension was the most common with 46.1%, followed by a sedentary lifestyle, and diabetes with 18.2% and 8.3% respectively;NYHA stage III-IV dyspnea was found in 83.9%. Reduced EF heart failure was present in 110 patients (76.9%), seventeen cases with moderately reduced EF (11.9%) and sixteen patients had preserved EF (11.2%). Global heart failure was the dominant (91.6%). The main etiologies of heart failure were dominated by hypertensive heart disease in 46 patients (32.2%), followed by postpartum cardiomyopathy with 43 cases (30.1%), primary dilated cardiomyopathy in 18 patients (12.6%), ischemic heart disease in 16 patients with 11.2%. Seven cases of valvular heart disease, or 4.9%. The evolution was favorable under treatment in 104 patients or 72.7%. In-hospital mortality was 14.7%. Conclusion: Heart failure is a common condition in sub-Saharan Africa, particularly in our country.
基金supported by the National Natural Science Foundation of China(Nos.52208369,52309138,52209142,51978666)the Department of Science and Technology of Sichuan Province(2023NSFSC0284).
文摘In practical engineering,due to the noncontinuity characteristics of joints in rock slopes,in addition to plane failure,stepped sliding failure may occur for intermittently jointed rock slopes.Especially for intermittently bedding jointed rock slopes,the correlation and difference in strength parameters between joints and rock bridges,along with the various failure modes and intermittency of rock bridges,contribute to the complexity of stepped failure modes and the unpredictability of failure regions.Based on the upper-bound limit analysis method and multi-sliders step-path failure mode,considering the shear and tensile failure of rock bridges and the weakened relationship between the strength parameters of rock bridges and jointed surfaces,by introducing the modified M-C failure criterion and the formula for calculating the energy consumption of tensile failure of rock bridges,two failure mechanisms are constructed to obtain the safety factor(F_(s))of intermittently jointed rock slopes.The sequential quadratic programming method is used to obtain the optimal upper-bound solution for F_(s).The influence of multiple key parameters(slope height H,horizontal distance L,Slope angleβ,shear strength parameters of the rock bridgeφr and cr,Dimensionless parameter u,weakening coefficients of the internal friction angle and cohesion between the rock bridges and joint surfaces Kφand Kc)on the stability analysis of intermittently jointed rock slopes under the shear failure mode of rock bridges as well as under the tensile failure mode is also explored.The reliability of the failure mechanisms is verified by comparative analysis with theoretical results,numerical results,and landslide cases,and the variation rules of F_(s)with each key parameter are obtained.The results show that F_(s) varies linearly withφr and cr of the rock bridge and with K_(φ)and K_(c),whereas F_(s)changes nonlinearly with H and L.In particular,with the increase in Kφand Kc,Fs increases by approximately 52.78%and 171.02%on average,respectively.For rock bridge tensile failure,F_(s) shows a nonlinearly positive correlation withφr,cr,Kφand Kc.In particular,with the increase in Kφand Kc,Fs increases by approximately 13%and 61.69%on average,respectively.Fs decreases rapidly with increasing slope gradientβand decreasing dimensionless parameterμ.When Kφand Kc are both less than 1.0,the stepped sliding surface occurs more easily than the plane failure surface,especially in the case of tensile failure of the rock bridge.In addition,rock slopes with higher strength parameters,taller heights,and greater weakening coefficients are prone to rock bridge tension failure with lower Fs,and more attention should be given to the occurrence of such accidents in actual engineering.
基金supported by the National Key R&D Program of China(2022YFD1400300)the Open Fund of Key Laboratory of Integrated Pest Management on Crops in Northwestern Oasis,Ministry of Agriculture and Rural Affairs of China(KFJJ202204)the China Agriculture Research System(CARS-15-20)。
文摘Aphis gossypii has become increasingly difficult to manage due to its strong insecticide resistance.In the laboratory,we established sulfoxaflor-resistant and acetamiprid-resistant strains in two A.gossypii populations with different basal insecticide resistance levels,and evaluated the effects of basal insecticide resistance on the resistance development and cross-resistance,as well as differences in fitness.Under the same selection pressure,Yarkant A.gossypii(with low basal insecticide resistance)evolved resistance to sulfoxaflor and acetamiprid more quickly than Jinghe A.gossypii(with high basal insecticide resistance),and the evolution of A.gossypii resistance to sulfoxaflor developed faster than acetamiprid in both Yarkant and Jinghe,Xingjiang,China.The sulfoxaflor-resistant strains selected from Yarkant and Jinghe developed significant cross-resistance to acetamiprid,imidacloprid,thiamethoxam and pymetrozine;while the acetamiprid-resistant strains developed significant cross-resistance to sulfoxaflor,imidacloprid,thiamethoxam,pymetrozine,and chlorpyrifos.The relative fitness of A.gossypii decreased as the resistance to sulfoxaflor and acetamiprid developed.The relative fitness levels of the sulfoxaflor-resistant strains(Yarkant-SulR and Jinghe-SulR)were lower than those of the acetamipridresistant strains(Yarkant-AceR and Jinghe-AceR).In addition,the relative fitness levels of sulfoxaflor-and acetamiprid-resistant strains were lower in Jinghe than in Yarkant.In summary,basal insecticide resistance of A.gossypii and insecticide type affected the evolution of resistance to insecticides in A.gossypii,as well as cross-resistance to other insecticides.The sulfoxaflor-and acetamiprid-resistant A.gossypii strains had obvious fitness costs.The results of this work will contribute to the insecticide resistance management and integrated management of A.gossypii.
基金National Natural Science Foundation of China(32130109)Open Project Fund from Laboratory for Marine Biology and Biotechnology,Qingdao National Laboratory for Marine Science(OF2019NO01)。
文摘As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish(Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species,27℃, to lower temperatures of 22℃, 20℃, and 13℃ over a period of two weeks. Comparative metabolomic(six biological replicates for each temperature) and transcriptomic(four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production,antioxidant function, and lipid and protein catabolism.Disrupted reproductive hormones, increased proteolysis,and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.
文摘Medicinal leeches have been utilized in therapy for thousands of years. However, the adaptation physiology between leeches and hosts is not fully understand. To disclose the molecular mechanisms of adaptation between leech and host, the body transcriptomes of hunger and fed blood-sucking Poecilobdella javanica, Haemadipsa cavatuses, and Hirudo nipponia leeches were obtained by RNA sequencing, after comparison, a stratified unigenes group was obtained, which closely correlated to body distension. In the group, Rfamide receptor decreased significantly (P < 0.05) while serotonin receptor increased significantly (P < 0.05). Moreover, four KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, including cardiac muscle contraction, complement and coagulation cascades, renin-angiotensin system, and hypertrophic cardiomyopathy were significantly enriched. The unigenes annotation, neuroregulators correlation analysis and induced function of the KEGG pathways, were consistently supported the same result as: vasoconstriction and systole reaction enhance in hunger leeches and vice versa vasodilation and diastole increase in fed leeches, meanwhile, Interspecific comparison and correlative analyses of physiological function showed that the strongest reaction of induced heart failure from four KEGG occur in strongest reaction of systole in hungry P. javanica and in strongest reaction of diastole in fed H. nipponia. Overall, heart failure is likely a physiological function involved in feeding behaviour.
基金National Natural Science Foundation of China under Grant Nos.52378335 and 52322808.
文摘A seismic-induced landslide is a common geological catastrophe that occurs in nature.The Wangjiayan landslide,which was triggered by the Wenchuan earthquake,is a typical case in point.The Wanjiayan landslide caused many casualties and resulted in enormous property loss.This study constructs a simple surficial failure model based on the upper bound approach of three-dimensional(3D)limit analysis to evaluate the slope stability of the Wangjiayan case,while a traditional two-dimensional(2D)analysis is also conducted as a reference for comparison with the results of the 3D analysis.A quasi-static calculation is used to study the effect of the earthquake in terms of horizontal ground acceleration,while a parametric study is conducted to evaluate the critical cohesion of slopes.Rather than employing a 3D analysis,using the 2D analysis yields an underestimation regarding the safety factor.In the Wangjiayan landslide,the difference in the factors of safety between the 3D and 2D analyses can reach 20%.The sliding surface morphology as determined by the 3D method is similar to actual morphology,and the parameters of both are also compared to analyze the reliability of the proposed 3D method.
文摘Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among the 30 countries with the highest TB burden. Objective: The study aimed to estimate the average direct medical cost of treating drug-resistant tuberculosis in 19 health centers in Maputo City, Mozambique. Methods: A retrospective analysis of direct medical costs was conducted on patients aged 18 and older who completed 20-month drug-resistant tuberculosis treatment regimens in Maputo City in 2019. Results: This analysis covered 140 patients who completed a 20-month treatment regimen, with 64.3% (78) being male and 35.7% (62) female. Approximately 50% of the participants were aged between 29 and 47. The average direct medical cost of DRTB treatment was $4789.43, reaching up to $6568.00, with a standard deviation of $753.26, including clinical interventions and treatment. Conclusion: The direct medical costs for a basic treatment package for a patient with drug-resistant TB in Mozambique equal 36 minimum wages. Developing alternative and innovative funding mechanisms and identifying ways to mitigate costs through the use of generic medicines would be beneficial.
基金supported by the National Natural Science Foundation of China(Project No.41920104007 and 41772334).
文摘Red clay landslides are widely distributed worldwide,resulting in severe loss of life and property.Although rainfall-induced red clay slopes have received extensive attention,the role of cracks in the evolutionary process of red clay slopes and their connection to failure mechanisms is still poorly understood.A comprehensive approach integrating field investigation,laboratory tests,and numerical simulations was conducted to study the 168 red clay landslides in Xinshao County,China.The results show that red clay is prone to forming cracks at high moisture content due to its low swelling and high shrinkage properties.The failure mode of red clay slopes can be summarized in three stages:crack generation,slope excavation,and slope failure.Furthermore,the retrospective analysis and numerical simulations of the typical landslide in Guanchong indicated that intense rainfall primarily impacts the shallow layer of soil within approximately 0.5 m on the intact slope.However,cracks change the pattern of rainfall infiltration in the slope.Rainwater infiltrates rapidly through the preferential channels induced by the cracks rather than uniformly and slowly from the slope surface.This results in a significant increase in both the depth of infiltration and the saturated zone area of the cracked slope,reaching 3.8 m and 36.2 m^(2),respectively.Consequently,the factor of safety of the slope decreases by 13.4%compared to the intact slope,ultimately triggering landslides.This study can provide valuable insights into understanding the failure mechanisms of red clay slopes in China and other regions with similar geological settings.
文摘Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community.