BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and co...BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)analysis.METHODS Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and cognition.In this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger methods.Additionally,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on cognition.IVW served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger methods.RESULTS In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger analyses.MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition,presenting a challenge in identifying the effect.Notably,this study did not demonstrate any significant impact of guilty feelings,nervous feelings,miserableness,or loneliness/isolation on cognition.Due to a limited number of instrumental variables for happiness,this study was unable to analyze the relationship between happiness and cognition.CONCLUSION This MR study finds that sensitivity/hurt feelings are associated with cognitive decline,while the link between worrier/anxious feelings and cognition remains inconclusive.Insufficient evidence supports direct associations between happiness,guilty feelings,nervous feelings,miserableness,loneliness/isolation,and cognition.展开更多
Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify...Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy.The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population,and to evaluate whether these patients are suitable for adjuvant targeted therapy.Methods:Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed.Results:A total of 201 patients were included in the study.The multivariate Cox analysis suggested that preoperative alpha-fetoprotein(AFP)>200μg/L(HR=2.666,95%CI:1.515-4.690;P=0.001),glutamyl transferase(GGT)>96 U/L(HR=1.807,95%CI:1.012-3.224;P=0.045),and exceeding the Hangzhou criteria(HR=2.129,95%CI:1.158-3.914;P=0.015)were independent risk factors for poor disease-free survival(DFS)in patients with HCC who underwent LT.We established an AFP-GGT-Hangzhou(AGH)scoring system based on these factors,and divided cases into high-,moderate-,and low-risk groups.The differences in overall survival(OS)and disease-free survival(DFS)rates among the three groups were significant(P<0.05).The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria,UCSF criteria,Milan criteria,and TNM stage.Only in the high-risk group,we found that lenvatinib significantly improved prognosis compared with that of the control group(P<0.05).Conclusions:The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China.Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.展开更多
The Hengduan Mountains region of south-west China is a noted biodiversity,hotspot, but the geographic origins and historical assembly of its rich endemic flora, including the sky-island species ofSolms-laubachia Musch...The Hengduan Mountains region of south-west China is a noted biodiversity,hotspot, but the geographic origins and historical assembly of its rich endemic flora, including the sky-island species ofSolms-laubachia Muschl. (Brassicaceae), have been little studied. Previous molecular studies on the phylogeny of Solms-laubachia showed it to be paraphyletic, leading to considerable expansion not only of its taxonomic limits, but also its geographic range, with the inclusion of taxa from outside the Hengduan region. However, these studies provided little resolution of interspecific relationships, preventing inferences about historical biogeography within the clade. In the present study, new sequence data from two nuclear genes (LEAFY and G3pdh) and two chloroplast intergenic spacers (petN-psbM and psbM-trnD) were combined with existing markers to increase phylogenetic signals. Phaeonychium villosum (Maxim.) Al-Shehbaz was found to be nested within Solms-laubachia s.l. In general, phylogenetic relationships appear to be a good predictor of geography, with the Hengduan Mountain endemics embedded in a paraphyletic grade of species from the western Himalayas and central Asia, but they also imply morphological homoplasy, lncongruence was detected between the nuclear and chloroplast gene trees, perhaps resulting from incomplete lineage sorting of ancestral polymorphisms. The crown age ofSolms-laubachia s.l. was estimated to be approximately 1.42-3.68 mya, using Bayesian relaxed molecular clock analysis. Historical biogeographic analysis using a parametric dispersalextinction-cladogenesis model inferred central Asia and the western Himalayas as most probable ancestral range of Solms-laubachia s.l., and estimated higher rates of eastward expansion than westward during the diversification of descendant lineages. In summary, our results suggest that Solms-laubachia s.l. originated during the Pliocene in central Asia, and subsequently migrated eastward into the Hengduan Mountains, colonizing sky-island, alpine scree-slope habitats that may have provided novel ecological opportunity and accelerated speciation, ultimately establishing this region as the present center of diversity of the genus.展开更多
Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predi...Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate(e GFR), the model for end-stage liver disease(MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients(35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of e GFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of e GFR within the first year after surgery.展开更多
AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7 was c...AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plasmid, viral protein (HBV surface antigen and HBV e antigen) secretion was detected by enzyme-linked immunosorbent assay, and HBV RNA was analyzed by real-time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-B (NF- B) activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Transwell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS: Viral protein secretion was significantly reduced by 57% (P < 0.05), and the level of total HBV RNA was reduced by 67% (P < 0.05). The viral core particle-associated DNA was also dramatically down-regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-B signaling was essential for DAI to elicit antiviral response in Huh7 cells. When the NF-B signaling pathway was blocked by a NF-B signaling suppressor (I B -SR), the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was independent of IRF3 signaling and secreted cytokines. CONCLUSION: This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is associated with activation of NF-B but independent of IRF3 and secreted cytokines.展开更多
AIM: To investigate the relationship between Helicobacter pylori(H pylori) infection, microsatellite instability and the expressions of the p53 in gastritis, intestinal metaplasia and gastric adenocarcinoma and to elu...AIM: To investigate the relationship between Helicobacter pylori(H pylori) infection, microsatellite instability and the expressions of the p53 in gastritis, intestinal metaplasia and gastric adenocarcinoma and to elucidate the mechanism of gastric carcinogenesis relating to H pylori infection.METHODS: One hundred and eight endoscopic biopsies and gastric adenocarcinoma were available for the study including 33 cases of normal, 45 cases of gastritis, 30 cases of intestinal metaplasia, and 46 cases of gastric adenocarcinoma. Peripheral blood samples of these patients were also collected. H pyloriinfection and p53 expressions were detected by means of streptavidin-peroxidase (SP)immunohistochemical method. Microsatellite loci were studied by PCR-SSCP-CE using the markers BAT-26,D17S261, D3S1283, D2S123, and D3S1611. MSI was defined as the peak shift in the DNA of the gastric tissue compared with that of the peripheral blood samples. Based on the number of mutated MSI markers, specimens were charac-terized as high MSI (MSI-H) if they manifested instability at two or more markers, low MSI (MSI-L) if unstable at only one marker, and microsatellite stable (MSS) if they showed no instability at any marker.RESULTS: H pyloriinfection was detected in the samples of gastritis, intestinal metaplasia, and gastric adenocarcinoma and the infection frequencies were 84.4%, 76.7%, and 65.2%, respectively, whereas no H pylori infection was detected in the samples of normal control. There was a significant difference in the infection rates between gastritis and carcinoma samples (P = 0.035). No MSI was detected in gastritis samples, one MSI-H and two MSI-L were detected among the 30 intestinal metaplasia samples, and 12 MSI-H and 3 MSI-L were detected in the 46 gastric carcinomas.In those gastric carcinomas, the MSI-H frequency in H pyloripositive group was significantly higher than that in H pylorinegative group. No p53 expression was detected in the normal and gastritis samples from dyspeptic patients. P53-positive immunohistochemical staining was detected in 13.3% of intestinal metaplasia samples and in 43.5% of gastric carcinoma samples. The levels of p53 in H pyloripositive samples were higher than those in the negative group when the carcinoma samples were subdivided into H pylori-positive and -negative groups (P = 0.013). Eight samples were detected with positive p53 expression out of the 11 MSI-H carcinomas with H pylorl infection and no p53 expression could be seen in the H pylori-negative samples.CONCLUSION: H pylori affect the p53 pattern in gastric mucosa when MMR system fails to work. Mutations of the p53 gene seem to be an early event in gastric carcinogenesis.展开更多
Hydraulic fracturing technology plays a key role in improving the recovery rate of shale gas.The improvement of permeability in relation to hydraulic fracturing depends on changes brought about by the proppant on the ...Hydraulic fracturing technology plays a key role in improving the recovery rate of shale gas.The improvement of permeability in relation to hydraulic fracturing depends on changes brought about by the proppant on the fracture structure in reservoirs.Then it is of great significance to describe the microscopic changes during this process by means of an accurate theoretical model.In this study,based on the heterogeneity of shale fracture and the compaction and embedment of a proppant,we proposed a permeability model to examine the combined effects of a proppant and stress to describe the change mechanism in permeability.Further,changes in fracture width and porosity were considered,and a calculation model of fracture compressibility under proppant compaction and embedment was proposed.The difference from previous studies is that the compressibility and permeability of supported fractures can be further quantified and analyzed by this model.Moreover,its rationality was verified by publicly released test data.The results show that,the compressive effect of stress and the embedding of proppant both have a negative impact on shale permeability.展开更多
Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipie...Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.展开更多
Objective:To investigate the effects of minimally invasive craniotomy combined with edaravone on cerebral oxygen metabolism, cerebrovascular function and oxidative stress in patients with acute cerebral hemorrhage.Met...Objective:To investigate the effects of minimally invasive craniotomy combined with edaravone on cerebral oxygen metabolism, cerebrovascular function and oxidative stress in patients with acute cerebral hemorrhage.Methods:A total of 100 patients with acute cerebral hemorrhage treated in our hospital from March 2015 to February 2017 were randomly divided into control group and observation group. 50 patients in the control group were treated with minimally invasive craniotomy. On the basis of control group, patients in the observation group were treated with edaravone. Cerebral oxygen metabolism, cerebrovascular function and oxidative stress were measured later in both groups.Results:After treatment, the levels of SOD in both groups increased significantly and MDA levels decreased significantly, and SOD level in the observation group was (97.34±1.95) U/mL, which was significantly higher than the control group, MDA level was (2.77±0.11) mol/L and significantly lower than that of the control group after treatment;After treatment, the levels of ET in both groups were significantly lower than those before treatment, and the levels of CGRP were significantly higher than those before treatment. ET level in observation group was (3.24±0.22) μg/L after treatment, which was significantly lower than that in control group (59.67±0.79) pg/mL, which was significantly higher than the control group;After treatment, the levels of SjvO2, CjvO2 and PbtO2 in both groups were significantly increased compared with before treatment, the levels of Da-jvO2 and CEO2 were significantly lower than the level of before treatment, and the levels of SjvO2, The levels of CjvO2 and PbtO2 were (62.93±1.63)%, (99.31±0.94) mL/L and (28.56±1.55) mmHg, which were significantly higher than the control group. Da-jvO2 and CEO2 levels were (51.31±1.13) mL/L and (30.52±0.43)%, which were significantly lower than the control group.Conclusion: Edaravone combined with minimally invasive craniotomy can effectively reduce the level of oxidative stress, improve endothelial function and cerebral oxygen metabolism, and has reliable curative effect. It is worth further clinical application.展开更多
BACKGROUND Thoracic surgery for radical resection of lung tumor requires deep anesthesia which can lead to an adverse inflammatory response,loss of hemodynamic stability,and decreased immune function.Herein,we evaluat...BACKGROUND Thoracic surgery for radical resection of lung tumor requires deep anesthesia which can lead to an adverse inflammatory response,loss of hemodynamic stability,and decreased immune function.Herein,we evaluated the feasibility and benefits of ultrasound-guided paravertebral nerve block anesthesia,in combination with general anesthesia,for thoracic surgery for lung cancer.The block was performed by diffusion of anesthetic drugs along the paravertebral space to achieve unilateral multi-segment intercostal nerve and dorsal branch nerve block.AIM To evaluate the application of ultrasound-guided paravertebral nerve block anesthesia for lung cancer surgery to inform practice.METHODS The analysis was based on 140 patients who underwent thoracic surgery for lung cancer at our hospital between January 2018 and May 2020.Patients were randomly allocated to the peripheral+general anesthesia(observation)group(n=74)or to the general anesthesia(control)group(n=66).Patients in the observation group received ultrasound-guided paravertebral nerve block anesthesia combined with general anesthesia,with those in the control group receiving an epidural block combined with general anesthesia.Measured outcomes included the operative and anesthesia times,as well as the mean arterial pressure(MAP),heart rate(HR),and blood oxygen saturation(SpO;)measured before surgery,15 min after anesthesia(T1),after intubation,5 min after skin incision,and before extubation(T4).RESULTS The dose of intra-operative use of remifentanil and propofol and the postoperative use of sufentanil was lower in the observation group(1.48±0.43 mg,760.50±92.28 mg,and 72.50±16.62 mg,respectively)than control group(P<0.05).At the four time points of measurement(T1 through T4),MAP and HR values were higher in the observation than control group(MAP,90.20±9.15 mmHg,85.50±7.22 mmHg,88.59±8.15 mmHg,and 90.02±10.02 mmHg,respectively;and HR,72.39±8.22 beats/min,69.03±9.03 beats/min,70.12±8.11 beats/min,and 71.24±9.01 beats/min,respectively;P<0.05).There was no difference in SpO;between the two groups(P>0.05).Postoperative levels of epinephrine,norepinephrine,and dopamine used were significantly lower in the observation than control group(210.20±40.41 pg/mL,230.30±65.58 pg/mL,and 54.49±13.32 pg/mL,respectively;P<0.05).Similarly,the postoperative tumor necrosis factor-αand interleukin-6 levels were lower in the observation(2.43±0.44 pg/mL and 170.03±35.54 pg/mL,respectively)than control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).CONCLUSION Ultrasound-guided paravertebral nerve block anesthesia improved the stress and hemodynamic response in patients undergoing thoracic surgery for lung cancer,with no increase in the rate of adverse events.展开更多
In coastal areas with complicated flow movement, deposition and scour readily occur in submarine excavation projects. In this study, a smallscale model, with a high resolution in the vertical direction, was used to si...In coastal areas with complicated flow movement, deposition and scour readily occur in submarine excavation projects. In this study, a smallscale model, with a high resolution in the vertical direction, was used to simulate the tidal current around a submarine excavation project. The finite volume method was used to solve Navier-Stokes equations and the Reynolds stress transport equation, and the entire process of the tidal current was simulated with unstructured meshes, generated in the irregular shape area, and structured meshes, generated in other water areas.The meshes near the bottom and free surface were densified with a minimum layer thickness of 0.05 m. The volume of fluid method was used to track the free surface, the volume fraction of cells on the upstream boundary was obtained from the volume fraction of adjacent cells, and that on the downstream boundary was determined by the water level process. The numerical results agree with the observed data, and some conclusions can be drawn: after the foundation trench excavation, the flow velocity decreases quite a bit through the foundation trench, with reverse flow occurring on the lee slope in the foundation trench; the swirling flow impedes inflow, leading to the occurrence of dammed water above the foundation trench; the turbulent motion is stronger during ebbing than in other tidal stages, the range with the maximum value of turbulent viscosity, occurring on the south side of the foundation trench at maximum ebbing, is greater than those in other tidal stages in a tidal cycle, and the maximum value of Reynolds shear stress occurs on the south side of the foundation trench at maximum ebbing in a tidal cycle. The numerical calculation method shows a strong performance in simulation of the hydrodynamic characteristics of tidal currents in the foundation trench, providing a basis for submarine engineering construction in coastal areas.展开更多
A (t, n) threshold signature scheme distributes the secret key and hence the signing ability to n players in a way that any set of t+1 or more honest players can collaborate to sign, while any set of t players cannot....A (t, n) threshold signature scheme distributes the secret key and hence the signing ability to n players in a way that any set of t+1 or more honest players can collaborate to sign, while any set of t players cannot. In this paper we propose an iden- tity-based threshold signature (IBTHS) scheme from bilinear pairings. The signing phase of our scheme is non-interactive, meaning that the signing players do not need to talk to each other. We prove our scheme secure (i.e., unforgeable and robust) in the standard model (i.e., without random oracles). No earlier proposed IBTHS scheme achieved even one of the features of being non-interactive (in the signing phase) and secure in the standard model.展开更多
Summary:Renal cancer is a common genitourinary malignance,of which clear cell renal cell carcinoma(ccRCC)has high aggressiveness and leads to most cancer-related deaths.Identification of sensitive and reliable biomark...Summary:Renal cancer is a common genitourinary malignance,of which clear cell renal cell carcinoma(ccRCC)has high aggressiveness and leads to most cancer-related deaths.Identification of sensitive and reliable biomarkers for predicting tumorigenesis and progression has great significance in guiding the diagnosis and treatment of ccRCC.Here,we identified 2397 common difTerentially expressed genes(DEGs)using paired normal and tumor ccRCC tissues from GSE53757 and The Cancer Genome Atlas(TCGA).Then,we performed weighted gene co-expression network analysis and protein-protein interaction network analysis,17 candidate hub genes were identified.These candidate hub genes were further validated in GSE36895 and Oncomine database and 14 real hub genes were identified.All the hub genes were up-regulated and significantly positively correlated with pathological stage and histologic grade of ccRCC.Survival analysis showed that the higher expression level of each hub gene tended to predict a worse clinical outcome.ROC analysis showed that all the hub genes can accurately distinguish between tumor and normal samples,and between early stage and advanced stage ccRCC.Moreover,all the hub genes were positively associated with distant metastasis,lymph node infiltration,tumor recurrence and the expression of MKi67,suggesting these genes might promote tumor proliferation,invasion and metastasis.Furthermore,the functional annotation demonstrated that most genes were enriched in cell-cycle related biological function.In summary,our study identified 14 potential biomarkers for predicting tumorigenesis and progression,which might contribute to early diagnosis,prognosis prediction and therapeutic intervention.展开更多
文摘BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)analysis.METHODS Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and cognition.In this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger methods.Additionally,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on cognition.IVW served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger methods.RESULTS In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger analyses.MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition,presenting a challenge in identifying the effect.Notably,this study did not demonstrate any significant impact of guilty feelings,nervous feelings,miserableness,or loneliness/isolation on cognition.Due to a limited number of instrumental variables for happiness,this study was unable to analyze the relationship between happiness and cognition.CONCLUSION This MR study finds that sensitivity/hurt feelings are associated with cognitive decline,while the link between worrier/anxious feelings and cognition remains inconclusive.Insufficient evidence supports direct associations between happiness,guilty feelings,nervous feelings,miserableness,loneliness/isolation,and cognition.
基金supported by grants from the National Natural Science Foundation of China(81873874 and 82071797)Clinical Research Plan of SHDC(SHDC2020CR2021B and SHDC2020CR5012)+1 种基金Foundation of Science and Technology Commission of Shanghai Municipality(20Y11908500)Foundation of Shanghai Municipal Health Commission(201940032)。
文摘Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy.The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population,and to evaluate whether these patients are suitable for adjuvant targeted therapy.Methods:Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed.Results:A total of 201 patients were included in the study.The multivariate Cox analysis suggested that preoperative alpha-fetoprotein(AFP)>200μg/L(HR=2.666,95%CI:1.515-4.690;P=0.001),glutamyl transferase(GGT)>96 U/L(HR=1.807,95%CI:1.012-3.224;P=0.045),and exceeding the Hangzhou criteria(HR=2.129,95%CI:1.158-3.914;P=0.015)were independent risk factors for poor disease-free survival(DFS)in patients with HCC who underwent LT.We established an AFP-GGT-Hangzhou(AGH)scoring system based on these factors,and divided cases into high-,moderate-,and low-risk groups.The differences in overall survival(OS)and disease-free survival(DFS)rates among the three groups were significant(P<0.05).The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria,UCSF criteria,Milan criteria,and TNM stage.Only in the high-risk group,we found that lenvatinib significantly improved prognosis compared with that of the control group(P<0.05).Conclusions:The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China.Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.
基金supported by the Chinese National Natural Science Foundation (grants no.30625004,40771073 to HS)the Yunnan Natural Science Foundation (2008CC013 to HS)+4 种基金the US National Science Foundation (grant no. DEB-0321846,to DEB)the John D. and Catherine T. MacArthur Foundation (grant to JW,RR,and GM)the Innovation Project of the Chinese Academy of Sciences (KSCX2-YW-Z-030)a Mercer Fellowship from the Arnold Arboretum (to JPY)supported by the National Geographic Society (grant no.7405-03)
文摘The Hengduan Mountains region of south-west China is a noted biodiversity,hotspot, but the geographic origins and historical assembly of its rich endemic flora, including the sky-island species ofSolms-laubachia Muschl. (Brassicaceae), have been little studied. Previous molecular studies on the phylogeny of Solms-laubachia showed it to be paraphyletic, leading to considerable expansion not only of its taxonomic limits, but also its geographic range, with the inclusion of taxa from outside the Hengduan region. However, these studies provided little resolution of interspecific relationships, preventing inferences about historical biogeography within the clade. In the present study, new sequence data from two nuclear genes (LEAFY and G3pdh) and two chloroplast intergenic spacers (petN-psbM and psbM-trnD) were combined with existing markers to increase phylogenetic signals. Phaeonychium villosum (Maxim.) Al-Shehbaz was found to be nested within Solms-laubachia s.l. In general, phylogenetic relationships appear to be a good predictor of geography, with the Hengduan Mountain endemics embedded in a paraphyletic grade of species from the western Himalayas and central Asia, but they also imply morphological homoplasy, lncongruence was detected between the nuclear and chloroplast gene trees, perhaps resulting from incomplete lineage sorting of ancestral polymorphisms. The crown age ofSolms-laubachia s.l. was estimated to be approximately 1.42-3.68 mya, using Bayesian relaxed molecular clock analysis. Historical biogeographic analysis using a parametric dispersalextinction-cladogenesis model inferred central Asia and the western Himalayas as most probable ancestral range of Solms-laubachia s.l., and estimated higher rates of eastward expansion than westward during the diversification of descendant lineages. In summary, our results suggest that Solms-laubachia s.l. originated during the Pliocene in central Asia, and subsequently migrated eastward into the Hengduan Mountains, colonizing sky-island, alpine scree-slope habitats that may have provided novel ecological opportunity and accelerated speciation, ultimately establishing this region as the present center of diversity of the genus.
基金supported by grants from the National Natural Science Foundation of China (81700591, 81520108006, and 81930120)。
文摘Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate(e GFR), the model for end-stage liver disease(MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients(35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of e GFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of e GFR within the first year after surgery.
基金Supported by Grants of The Chinese State Basic Research, No.2009CB522504National Mega Projects for Infectious Diseases, No. 2008ZX10203
文摘AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plasmid, viral protein (HBV surface antigen and HBV e antigen) secretion was detected by enzyme-linked immunosorbent assay, and HBV RNA was analyzed by real-time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-B (NF- B) activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Transwell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS: Viral protein secretion was significantly reduced by 57% (P < 0.05), and the level of total HBV RNA was reduced by 67% (P < 0.05). The viral core particle-associated DNA was also dramatically down-regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-B signaling was essential for DAI to elicit antiviral response in Huh7 cells. When the NF-B signaling pathway was blocked by a NF-B signaling suppressor (I B -SR), the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was independent of IRF3 signaling and secreted cytokines. CONCLUSION: This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is associated with activation of NF-B but independent of IRF3 and secreted cytokines.
文摘AIM: To investigate the relationship between Helicobacter pylori(H pylori) infection, microsatellite instability and the expressions of the p53 in gastritis, intestinal metaplasia and gastric adenocarcinoma and to elucidate the mechanism of gastric carcinogenesis relating to H pylori infection.METHODS: One hundred and eight endoscopic biopsies and gastric adenocarcinoma were available for the study including 33 cases of normal, 45 cases of gastritis, 30 cases of intestinal metaplasia, and 46 cases of gastric adenocarcinoma. Peripheral blood samples of these patients were also collected. H pyloriinfection and p53 expressions were detected by means of streptavidin-peroxidase (SP)immunohistochemical method. Microsatellite loci were studied by PCR-SSCP-CE using the markers BAT-26,D17S261, D3S1283, D2S123, and D3S1611. MSI was defined as the peak shift in the DNA of the gastric tissue compared with that of the peripheral blood samples. Based on the number of mutated MSI markers, specimens were charac-terized as high MSI (MSI-H) if they manifested instability at two or more markers, low MSI (MSI-L) if unstable at only one marker, and microsatellite stable (MSS) if they showed no instability at any marker.RESULTS: H pyloriinfection was detected in the samples of gastritis, intestinal metaplasia, and gastric adenocarcinoma and the infection frequencies were 84.4%, 76.7%, and 65.2%, respectively, whereas no H pylori infection was detected in the samples of normal control. There was a significant difference in the infection rates between gastritis and carcinoma samples (P = 0.035). No MSI was detected in gastritis samples, one MSI-H and two MSI-L were detected among the 30 intestinal metaplasia samples, and 12 MSI-H and 3 MSI-L were detected in the 46 gastric carcinomas.In those gastric carcinomas, the MSI-H frequency in H pyloripositive group was significantly higher than that in H pylorinegative group. No p53 expression was detected in the normal and gastritis samples from dyspeptic patients. P53-positive immunohistochemical staining was detected in 13.3% of intestinal metaplasia samples and in 43.5% of gastric carcinoma samples. The levels of p53 in H pyloripositive samples were higher than those in the negative group when the carcinoma samples were subdivided into H pylori-positive and -negative groups (P = 0.013). Eight samples were detected with positive p53 expression out of the 11 MSI-H carcinomas with H pylorl infection and no p53 expression could be seen in the H pylori-negative samples.CONCLUSION: H pylori affect the p53 pattern in gastric mucosa when MMR system fails to work. Mutations of the p53 gene seem to be an early event in gastric carcinogenesis.
基金financially supported by the National Natural Science Foundation of China(Grants No.52064007,51804085,and 51911530203)supported by Guizhou Provincial Science and Technology Projects(Qianke Combination Foundation-ZK[2021]Key 052)
文摘Hydraulic fracturing technology plays a key role in improving the recovery rate of shale gas.The improvement of permeability in relation to hydraulic fracturing depends on changes brought about by the proppant on the fracture structure in reservoirs.Then it is of great significance to describe the microscopic changes during this process by means of an accurate theoretical model.In this study,based on the heterogeneity of shale fracture and the compaction and embedment of a proppant,we proposed a permeability model to examine the combined effects of a proppant and stress to describe the change mechanism in permeability.Further,changes in fracture width and porosity were considered,and a calculation model of fracture compressibility under proppant compaction and embedment was proposed.The difference from previous studies is that the compressibility and permeability of supported fractures can be further quantified and analyzed by this model.Moreover,its rationality was verified by publicly released test data.The results show that,the compressive effect of stress and the embedding of proppant both have a negative impact on shale permeability.
基金supported by grants from the National S&T Major Project (2017ZX10203205)Key Program,National Natural Science Foundation of China (81930016)Zhejiang Provincial Natural Science Foundation of China (LY21H160026)。
文摘Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.
基金This study was supported by National Natural Science Foundation(81371345).
文摘Objective:To investigate the effects of minimally invasive craniotomy combined with edaravone on cerebral oxygen metabolism, cerebrovascular function and oxidative stress in patients with acute cerebral hemorrhage.Methods:A total of 100 patients with acute cerebral hemorrhage treated in our hospital from March 2015 to February 2017 were randomly divided into control group and observation group. 50 patients in the control group were treated with minimally invasive craniotomy. On the basis of control group, patients in the observation group were treated with edaravone. Cerebral oxygen metabolism, cerebrovascular function and oxidative stress were measured later in both groups.Results:After treatment, the levels of SOD in both groups increased significantly and MDA levels decreased significantly, and SOD level in the observation group was (97.34±1.95) U/mL, which was significantly higher than the control group, MDA level was (2.77±0.11) mol/L and significantly lower than that of the control group after treatment;After treatment, the levels of ET in both groups were significantly lower than those before treatment, and the levels of CGRP were significantly higher than those before treatment. ET level in observation group was (3.24±0.22) μg/L after treatment, which was significantly lower than that in control group (59.67±0.79) pg/mL, which was significantly higher than the control group;After treatment, the levels of SjvO2, CjvO2 and PbtO2 in both groups were significantly increased compared with before treatment, the levels of Da-jvO2 and CEO2 were significantly lower than the level of before treatment, and the levels of SjvO2, The levels of CjvO2 and PbtO2 were (62.93±1.63)%, (99.31±0.94) mL/L and (28.56±1.55) mmHg, which were significantly higher than the control group. Da-jvO2 and CEO2 levels were (51.31±1.13) mL/L and (30.52±0.43)%, which were significantly lower than the control group.Conclusion: Edaravone combined with minimally invasive craniotomy can effectively reduce the level of oxidative stress, improve endothelial function and cerebral oxygen metabolism, and has reliable curative effect. It is worth further clinical application.
文摘BACKGROUND Thoracic surgery for radical resection of lung tumor requires deep anesthesia which can lead to an adverse inflammatory response,loss of hemodynamic stability,and decreased immune function.Herein,we evaluated the feasibility and benefits of ultrasound-guided paravertebral nerve block anesthesia,in combination with general anesthesia,for thoracic surgery for lung cancer.The block was performed by diffusion of anesthetic drugs along the paravertebral space to achieve unilateral multi-segment intercostal nerve and dorsal branch nerve block.AIM To evaluate the application of ultrasound-guided paravertebral nerve block anesthesia for lung cancer surgery to inform practice.METHODS The analysis was based on 140 patients who underwent thoracic surgery for lung cancer at our hospital between January 2018 and May 2020.Patients were randomly allocated to the peripheral+general anesthesia(observation)group(n=74)or to the general anesthesia(control)group(n=66).Patients in the observation group received ultrasound-guided paravertebral nerve block anesthesia combined with general anesthesia,with those in the control group receiving an epidural block combined with general anesthesia.Measured outcomes included the operative and anesthesia times,as well as the mean arterial pressure(MAP),heart rate(HR),and blood oxygen saturation(SpO;)measured before surgery,15 min after anesthesia(T1),after intubation,5 min after skin incision,and before extubation(T4).RESULTS The dose of intra-operative use of remifentanil and propofol and the postoperative use of sufentanil was lower in the observation group(1.48±0.43 mg,760.50±92.28 mg,and 72.50±16.62 mg,respectively)than control group(P<0.05).At the four time points of measurement(T1 through T4),MAP and HR values were higher in the observation than control group(MAP,90.20±9.15 mmHg,85.50±7.22 mmHg,88.59±8.15 mmHg,and 90.02±10.02 mmHg,respectively;and HR,72.39±8.22 beats/min,69.03±9.03 beats/min,70.12±8.11 beats/min,and 71.24±9.01 beats/min,respectively;P<0.05).There was no difference in SpO;between the two groups(P>0.05).Postoperative levels of epinephrine,norepinephrine,and dopamine used were significantly lower in the observation than control group(210.20±40.41 pg/mL,230.30±65.58 pg/mL,and 54.49±13.32 pg/mL,respectively;P<0.05).Similarly,the postoperative tumor necrosis factor-αand interleukin-6 levels were lower in the observation(2.43±0.44 pg/mL and 170.03±35.54 pg/mL,respectively)than control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).CONCLUSION Ultrasound-guided paravertebral nerve block anesthesia improved the stress and hemodynamic response in patients undergoing thoracic surgery for lung cancer,with no increase in the rate of adverse events.
基金supported by the National Natural Science Foundation of China(Grant No.41406005)
文摘In coastal areas with complicated flow movement, deposition and scour readily occur in submarine excavation projects. In this study, a smallscale model, with a high resolution in the vertical direction, was used to simulate the tidal current around a submarine excavation project. The finite volume method was used to solve Navier-Stokes equations and the Reynolds stress transport equation, and the entire process of the tidal current was simulated with unstructured meshes, generated in the irregular shape area, and structured meshes, generated in other water areas.The meshes near the bottom and free surface were densified with a minimum layer thickness of 0.05 m. The volume of fluid method was used to track the free surface, the volume fraction of cells on the upstream boundary was obtained from the volume fraction of adjacent cells, and that on the downstream boundary was determined by the water level process. The numerical results agree with the observed data, and some conclusions can be drawn: after the foundation trench excavation, the flow velocity decreases quite a bit through the foundation trench, with reverse flow occurring on the lee slope in the foundation trench; the swirling flow impedes inflow, leading to the occurrence of dammed water above the foundation trench; the turbulent motion is stronger during ebbing than in other tidal stages, the range with the maximum value of turbulent viscosity, occurring on the south side of the foundation trench at maximum ebbing, is greater than those in other tidal stages in a tidal cycle, and the maximum value of Reynolds shear stress occurs on the south side of the foundation trench at maximum ebbing in a tidal cycle. The numerical calculation method shows a strong performance in simulation of the hydrodynamic characteristics of tidal currents in the foundation trench, providing a basis for submarine engineering construction in coastal areas.
基金Project (No. 2005AA145110) supported by the Hi-Tech Research and Development Program (863) of China
文摘A (t, n) threshold signature scheme distributes the secret key and hence the signing ability to n players in a way that any set of t+1 or more honest players can collaborate to sign, while any set of t players cannot. In this paper we propose an iden- tity-based threshold signature (IBTHS) scheme from bilinear pairings. The signing phase of our scheme is non-interactive, meaning that the signing players do not need to talk to each other. We prove our scheme secure (i.e., unforgeable and robust) in the standard model (i.e., without random oracles). No earlier proposed IBTHS scheme achieved even one of the features of being non-interactive (in the signing phase) and secure in the standard model.
基金The work described in this paper was supported by National Key Research and Development Program of China (2016QY01W0104) and National Natural Science Foundation of China (61771310).
基金This work was supported by grants from the National Natural Science Foundation of China(No.81270354)Natural Science for Youth Foundation(No.81300213).
文摘Summary:Renal cancer is a common genitourinary malignance,of which clear cell renal cell carcinoma(ccRCC)has high aggressiveness and leads to most cancer-related deaths.Identification of sensitive and reliable biomarkers for predicting tumorigenesis and progression has great significance in guiding the diagnosis and treatment of ccRCC.Here,we identified 2397 common difTerentially expressed genes(DEGs)using paired normal and tumor ccRCC tissues from GSE53757 and The Cancer Genome Atlas(TCGA).Then,we performed weighted gene co-expression network analysis and protein-protein interaction network analysis,17 candidate hub genes were identified.These candidate hub genes were further validated in GSE36895 and Oncomine database and 14 real hub genes were identified.All the hub genes were up-regulated and significantly positively correlated with pathological stage and histologic grade of ccRCC.Survival analysis showed that the higher expression level of each hub gene tended to predict a worse clinical outcome.ROC analysis showed that all the hub genes can accurately distinguish between tumor and normal samples,and between early stage and advanced stage ccRCC.Moreover,all the hub genes were positively associated with distant metastasis,lymph node infiltration,tumor recurrence and the expression of MKi67,suggesting these genes might promote tumor proliferation,invasion and metastasis.Furthermore,the functional annotation demonstrated that most genes were enriched in cell-cycle related biological function.In summary,our study identified 14 potential biomarkers for predicting tumorigenesis and progression,which might contribute to early diagnosis,prognosis prediction and therapeutic intervention.