沉默MPZL1调控β-catenin对A549/Tax细胞干性及耐药性的影响

目的探讨髓磷脂蛋白零样蛋白1(MPZL1)沉默后是否通过调控β-catenin表达对A549/Tax耐药性和细胞干性产生影响。方法采用不同浓度阿霉素和紫杉醇处理A549和A549紫杉醇耐药性(A549/Tax)细胞,观察两种细胞的耐药性差异。实时荧光定量聚合酶链式反应(qRT-PCR)和Western blot检测A549和A549/Tax细胞中MPZL1的表达量差异。对A549/Tax细胞沉默或者过表达MPZL1,进一步将细胞分为对照(control)组、短发卡RNA阴性对照(sh-NC)组、MPZL1沉默(sh-MPZL1)组、过表达阴性对照(OE-NC)组、MPZL1过表达(OE-MPZL1)组,运用细胞计数试剂盒8(CCK-8)和平板克隆实验分别检测MPZL1的表达变化对A549/Tax细胞增殖和克隆形成能力的影响。Western blot检测Wnt/β-catenin抑制剂XAV939和激活剂CHIR-99201处理细胞后,不同蛋白的表达变化。结果A549/Tax细胞对阿霉素和紫杉醇的半数抑制浓度(IC 50)较A549细胞明显增加(P<0.01)。MPZL1在A549/Tax中呈更高的表达趋势。MPZL1敲除后A549/Tax对阿霉素和紫杉醇的IC 50分别为2.731 mg/ml和4.939μg/ml,较阴性对照组的4.541 mg/ml和13.55μg/ml降低(P<0.01)。CCK-8和克隆形成实验结果显示,MPZL1敲除抑制肺癌A549/Tax细胞的增殖活力和克隆形成能力(P<0.05);Western blot结果显示,与阴性对照组相比,MPZL1、肿瘤干性相关蛋白(CD44和CD133)、多药耐药蛋白1(MDR1)、肺耐药相关蛋白(LRP)和β-catenin在sh-MPZL1中的表达水平明显减少(P<0.01)。此外,XAV939可抑制MPZL1、CD44、CD133、MDR1、LRP和β-catenin的表达。CHIR-99201处理细胞后部分逆转敲除MPZL1对上述蛋白的抑制作用。结论MPZL1在肺癌A549/Tax细胞中高表达。敲除MPZL1可抑制肿瘤干性和细胞增殖,增强肺癌A549/Tax细胞对阿霉素和紫杉醇的敏感性。

The burden of depression,anxiety and schizophrenia among the older population in ageing and aged countries:an analysis of the Global Burden of Disease Study 2019

Background Depression,anxiety and schizophrenia among older persons have become global public health challenges.However,the burden of these disorders in ageing and aged countries has not been analysed.Aims To investigate the burden of depression,anxiety and schizophrenia among older adults in ageing and aged countries.Methods Using data from the Global Burden of Disease Study 2019,we calculated the estimated annual percentage change(EAPC)in the age-standardised incidence rates(ASiR)and age-standardised disability-adjusted life years(DALYs)rates(ASDR)for depression,anxiety and schizophrenia of older people in ageing countries(China,India,Indonesia)and aged countries(Japan,Italy,Portugal)between 1990 and 2019.Trends in incidence and DALYs were analysed by gender and age.Results In 2019,the highest incidence of depression,anxiety and schizophrenia in the older population in aged countries was in Japan(927271.3(752552.3-1125796.5),51498.2(37625.7-70487.3)and 126.0(61.0-223.2),respectively),while the highest incidence in ageing countries was in China(5797556.9(4599403.4-7133006.5),330256.1(246448.9-445987.4)and 1067.7(556.2-1775.9),respectively).DALYs for these disorders were similar,with the highest in Japan and China.From 1990 to 2019,the ASIR for depressive disorders decreased in aged countries but increased in ageing countries;the ASIR for anxiety disorders and schizophrenia declined in both ageing and aged countries.The ASDR for depressive disorders was consistent with the ASIR but not for anxiety disorders and schizophrenia.The ASIR for depressive disorders was higher in older women,while the opposite was observed in anxiety disorders and schizophrenia.Notably,the conditions of burden of depressive disorders,anxiety disorders and schizophrenia in the 65-70-year-old age group were the most burdensome.Conclusions The incidence and DALYs of these three mental disorders increased while exhibiting differences between ageing and aged countries.Raising awareness about formulating health policies for preventing and treating mental disorders in the older population is necessary to reduce the future burden posed by the ageing challenge.

High-chromium vanadium-titanium magnetite all-pellet integrated burden optimization and softening-melting behavior based on flux pellets

High-chromium vanadium-titanium magnetite(HVTM)is a crucial polymetallic-associated resource to be developed.The allpellet operation is a blast furnace trend that aims to reduce carbon dioxide emissions in the future.By referencing the production data of vanadium-titanium magnetite blast furnaces,this study explored the softening-melting behavior of high-chromium vanadium-titanium magnetite and obtained the optimal integrated burden based on flux pellets.The results show that the burden with a composition of 70wt%flux pellets and 30wt%acid pellets exhibits the best softening-melting properties.In comparison to that of the single burden,the softening-melting characteristic temperature of this burden composition was higher.The melting interval first increased from 307 to 362℃and then decreased to 282℃.The maximum pressure drop(ΔPmax)decreased from 26.76 to 19.01 kPa.The permeability index(S)dropped from 4643.5 to 2446.8 kPa·℃.The softening-melting properties of the integrated burden were apparently improved.The acid pellets played a role in withstanding load during the softening process.The flux pellets in the integrated burden exhibited a higher slag melting point,which increased the melting temperature during the melting process.The slag homogeneity and the TiC produced by over-reduction led to the gas permeability deterioration of the single burden.The segregation of the flux and acid pellets in the HVTM proportion and basicity mainly led to the better softening-melting properties of the integrated burden.

Burden of gallstone disease in the United States population:Prepandemic rates and trends

BACKGROUND Gallstone disease is one of the most common digestive disorders in the United States and leads to significant morbidity,mortality,and health care utilization.AIM To expand on earlier findings and investigate prepandemic rates and trends in the gallstone disease burden in the United States using national survey and claims databases.METHODS The National Ambulatory Medical Care Survey,National Inpatient Sample,Nationwide Emergency Department Sample,Nationwide Ambulatory Surgery Sample,Vital Statistics of the United States,Optum Clinformatics®Data Mart,and Centers for Medicare and Medicaid Services Medicare 5%Sample and Medicaid files were used to estimate claims-based prevalence,medical care including cholecystectomy,and mortality with a primary or other gallstone diagnosis.Rates were age-adjusted(for national databases)and shown per 100000 population.RESULTS Gallstone disease prevalence(claims-based,2019)was 0.70%among commercial insurance enrollees,1.03%among Medicaid beneficiaries,and 2.09%among Medicare beneficiaries and rose over the previous decade.Recently,in the United States population,gallstone disease contributed to approximately 2.2 million ambulatory care visits,1.2 million emergency department visits,625000 hospital discharges,and 2000 deaths annually.Women had higher medical care rates with a gallstone disease diagnosis,but mortality rates were higher among men.Hispanics had higher ambulatory care visit and hospital discharge rates compared with Whites,but not mortality rates.Blacks had lower ambulatory care visit and mortality rates,but similar hospital discharge rates compared with whites.During the study period,ambulatory care and emergency department visit rates with a gallstone disease diagnosis rose,while hospital discharge and mortality rates declined.Among commercial insurance enrollees,rates were higher compared with national data for ambulatory care visits and hospitalizations,but lower for emergency department visits.Cholecystectomies performed in the United States included 605000 ambulatory laparoscopic,280000 inpatient laparoscopic,and 49000 inpatient open procedures annually.Among commercial insurance enrollees,rates were higher compared with national data for laparoscopic procedures.CONCLUSION The gallstone disease burden in the United States is substantial and increasing,particularly among women,Hispanics,and older adults with laparoscopic cholecystectomy as the mainstay treatment.Current practice patterns should be monitored for better health care access.

Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer

BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

Cardiovascular risk burden and disability:findings from the International Mobility in Aging Study(IMIAS)

BACKGROUND The association of cardiovascular risk burden with disability is unclear.We examined the association between trajectories of the Framingham general cardiovascular disease risk score(FGCRS)with the trajectories of limitations of physical function in older adults.METHODS A total of 1219 participants with no disabilities from the International Mobility in Aging Study(IMIAS)study who had up to three repeated measures of FGCRS between 2012–2016 and without a history of stroke or coronary heart disease at baseline and follow-up were included.FGCRS at baseline was assessed and categorized into tertiles.Physical function was evaluated with the Short Physical Performance Battery(SPPB).The data were analyzed using linear mixed-effects models.RESULTS At baseline,FGCRS ranged between 3–94(mean score:24±15.8),participants were 32(2.6%),502(41.2%)and 685(56.2%)in lowest,middle,and highest tertiles,respectively.In the trajectories of limitations of physical function,the lowest FGCRS had no differences,while the middle and highest had a decrease in physical performance between 2012–2014(P=0.0001).Age,being female,living in Andes Mountains,having middle and highest FGCRS,higher alcohol consumption,being obese,lack of exercise and cognitive impairment increase the probability of disability(P<0.05).Alternatively,living in more developed regions and having a higher educational level reduced the probability of disability during the follow-up time(P<0.05).CONCLUSIONS Higher cardiovascular risk burden is associated with decreased physical performance,especially in gait.Results suggest SPPB may provide a measure of cardiovascular health in older adults.

Cardiovascular risk burden,dementia risk and brain structural imaging markers:a study from UK Biobank

Background Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure,while the role of genetics and incident cardiovascular disease(CVD)remains unclear.Aims To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample,and to explore the role of genetics and CVD onset.Methods A prospective study among 354 654 participants free of CVD and dementia(2006-2010,mean age 56.4 years)was conducted within the UK Biobank,with brain magnetic resonance imaging(MRl)measurement availablefor 15104participants since 2014.CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score(FGCRS).Dementia diagnosis was ascertained from inpatient and death register data.Results Overamedian 12.0-yearfollow-up,3998 all-cause dementia cases were identified.Higher FGCRS was associated with increasedall-cause dementia risk after adjusting for demographic,major lifestyle,clinical factors and the polygenic risk score(PRS)of Alzheimer's disease.Comparing the high versus low tertile of FGCRS,the odds ratios(ORs)and 95%confidence intervals(Cls)were 1.26(1.12 to 1.41)for all-cause dementia,1.67(1.33 to 2.09)for Alzheimer's disease and 1.53(1.07 to 2.16)for vascular dementia(all p_(treng)<0.05).Incident stroke and coronary heart disease accounted for 14%(95%Cl:9% to 21%)of the association between FGCRS and all-cause dementia.Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype.We observed an 83%(95%Cl:47%to 128%)higher all-cause dementia risk comparing the high-high versus low-low FGCRS-PRS category.For brain volumes,higher FGCRS was associated with greater log-transformed white matter hyperintensities,smaller cortical volume and smaller grey matter volume.Conclusions Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes.The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.

Global, regional, and national burden of early-onset gastric cancer

Objective: The burden of gastric cancer(GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to 2017.Methods: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates(ASIRs) were evaluated using cancer registry data from volumes X±XII of the Cancer Incidence in Five Continents(CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate(ASMR) and the Human Development Index(HDI).Results: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008±2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially females.Conclusions: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.

Beyond Stitches: Analysis of Disease Burden in a Bangladeshi RMG Factory

Introduction: Bangladesh has experienced remarkable growth in RMG over the past 25 years. With the knitwear industry providing more than 4 million direct jobs, providing better occupational health and safety of workers remains a challenge. Aim of the study: The aim of the study was to analyze the disease burden of a RMG factory, and to highlight occupational health risks. Methods: A cross-sectional study design was employed for this analysis. A 17-month data entry (January 2020 - May 2021) was gathered from the factory in-house clinic. The socio-demographic and clinical diagnosis entries of 8421 entries were analyzed. Result: The population of the factory workers is 5370, where 40% (2148) are female workers and 60% (3222) are male workers. The mean age of respondents is 30 years, with a SD of ±7 years. Among the chief complaints, the most common was vomiting (14%;2262) fever (14%;2247), runny nose (11%;1842), cough (9%;1465), and loose motion (8%;1364). In the diagnosis categories, gastrointestinal diseases were more predominantly diagnosed (35%;2978), followed by viral fever (21%;1772), neurological diseases (16.5%;1389) and musculoskeletal disorders (9%;768). The average cost of medicine for each respondent is BDT 36. The factory covered costs of all medication for 99% (8380) of respondents. Only 0.5% (37) was referred to a tertiary hospital for further evaluation. Conclusion: Garments workers suffer mostly from long-term occupational health hazards. Factory owners and policy makers can contribute in various ways to improving primary healthcare options for workers.

Factors influencing the employed caregiver burden for patients with dementia residing in nursing homes:A cross-sectional study from China

Objective:The institutionalization of care for patients with dementia is becoming a trend.Understanding the burden on employed caregivers and exploring associated factors are of great importance in practice.Therefore,this study aimed to examine the relationship between basic attributes,caring ability,and caregiver burden in employed caregivers practicing in nursing homes.Methods:This cross-sectional study included 541 employed caregivers in 11 four-star nursing homes in Zhejiang Province from April to December 2022.Caregiver burden was assessed using the Zarit Burden Interview(ZBI).Demographic characteristics of participants,characteristics of the older patients with dementia,caring characteristics,training in dementia care,and caring abilities were collected for analysis of influencing factors.A hierarchical multiple regression analysis was conducted to explore the factors influencing the burden on employed caregivers in nursing homes.Results:The ZBI score of employed caregivers in nursing homes was 40.42±10.18,representing a moderate caregiver burden.Factors such as age(U=27.82,P<0.001),residence(U=7.89,P<0.001),educational level(H=55.81,P<0.001),self-care of older patients with dementia(H=85.21,P<0.001),daily care hours(H=73.25,P<0.001),number of older people with dementia cared for(H=14.56,P<0.012)and training in dementia care(U=-9.43,P<0.001)were significantly associated with caregiver burden.Caring ability was negatively associated with caregiver burden(r=-0.22,P<0.01).Furthermore,after controlling for demographic characteristics,the characteristics of older people with dementia,caring characteristics,training in dementia care,and caring ability explained 8.5%,5.8%,and 4.8%of the caregiver burden,respectively.Conclusion:The burden of employed caregivers on patients with dementia in nursing homes can be attributed to various factors.We recommend tailored interventions,such as dementia care training and reviewing the number and duration of hours worked to reduce the burden experienced by caregivers.

Changes on Stroke Burden Attributable to Ambient Fine Particulate Matter in China

Objective In recent decades,China has implemented a series of policies to address air pollution.We aimed to assess the health effects of these policies on stroke burden attributable to ambient fine particulate matter(PM_(2.5)).Methods Joinpoint regression was applied to explore the temporal tendency of stroke burden based on data from the Global Burden of Disease 2019 study.Results The age-standardized rates of disability-adjusted life year(DALY)for stroke attributable to ambient PM2.5 in China,increased dramatically during 1990-2012,subsequently decreased at an annual percentage change(APC)of-1.98[95% confidence interval(CI):-2.26,-1.71]during 2012-2019.For ischemic stroke(IS),the age-standardized DALY rates doubled from 1990 to 2014,and decreased at an APC of-0.83(95%CI:-1.33,-0.33)during 2014-2019.Intracerebral hemorrhage(ICH)showed a substantial increase in age-standardized DALY rates from 1990 to 2003,followed by declining trends,with APCs of-1.46(95%CI:-2.74,-0.16)during 2003-2007 and-3.33(95%CI:-3.61,-3.06)during 2011-2019,respectively.Conversely,the age-standardized DALY rates for subarachnoid hemorrhage(SAH)generally declined during 1990-2019.Conclusion Our results clarified the dynamic changes of the ambient PM_(2.5)-attributable stroke burden in China during 1990-2019,highlighting the health effects of air quality improvement policies.

Burden of gastrointestinal cancers among working-age population over past thirty years in China

BACKGROUND Although gastrointestinal(GI)cancers have been becoming a great public health concern in China,there is currently a lack of comprehensive literature on the overall burden and changing trends of GI cancers in the working-age population.AIM To assess the burden of GI cancers and to examine the overall,age-and genderspecific trends among the working-age population in China from 1990 to 2019.METHODS Data were extracted from the Global Burden of Disease Study 2019.The burden of GI cancers was indicated by incidence,mortality,disability-adjusted life-years(DALYs),age-standardized incidence rate(ASIR),age-standardized mortality rate,and age-standardized DALYs rate.Trends in the burden of GI cancers from 1990 to 2019 were examined using annual percent change and average annual percent change with Joinpoint regression models.RESULTS For overall GI cancers,a declining trend was observed in the ASIR,age-standardized mortality rate,and agestandardized DALYs rate,with reductions of 0.74%,2.23%,and 2.22%,respectively,from 1999 to 2019 in the Chinese working-age population.However,an increasing trend was observed in the ASIR for overall GI cancers from 2016-2019.The number of either incident cases,mortality cases,and DALYs was higher for colon/rectum cancer and liver cancer in younger participants but lower for esophageal,gallbladder,biliary tract,pancreatic,and stomach cancer among older subjects.Moreover,sex disparity in the GI cancers burden was also examined over 30 years.CONCLUSION The total burden of GI cancers remained heavy among the working-age population in China,although declining trends were observed from 1999 to 2019.Disparities in the GI cancers burden existed between sexes,age groups,and cancer types.Population-based precision prevention strategies are needed to tackle GI cancers among working-age individuals,considering the age,sex,and cancer type disparities in China.

A Novel Sensing Imaging Equipment Under Extremely Dim Light for Blast Furnace Burden Surface:Starlight High-Temperature Industrial Endoscope

Blast furnace(BF)burden surface contains the most abundant,intuitive and credible smelting information and acquiring high-definition and high-brightness optical images of which is essential to realize precise material charging control,optimize gas flow distribution and improve ironmaking efficiency.It has been challengeable to obtain high-quality optical burden surface images under high-temperature,high-dust,and extremelydim(less than 0.001 Lux)environment.Based on a novel endoscopic sensing detection idea,a reverse telephoto structure starlight imaging system with large field of view and large aperture is designed.Combined with a water-air dual cooling intelligent self-maintenance protection device and the imaging system,a starlight high-temperature industrial endoscope is developed to obtain clear optical burden surface images stably under the harsh environment.Based on an endoscope imaging area model,a material flow trajectory model and a gas-dust coupling distribution model,an optimal installation position and posture configuration method for the endoscope is proposed,which maximizes the effective imaging area and ensures large-area,safe and stable imaging of the device in a confined space.Industrial experiments and applications indicate that the proposed method obtains clear and reliable large-area optical burden surface images and reveals new BF conditions,providing key data support for green iron smelting.

Global Burden of Fungal Infections and Antifungal Resistance from 1961 to 2024: Findings and Future Implications

Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.

Burden landscape of hepatobiliary and pancreatic cancers in Chinese young adults:30 years’overview and forecasted trends

BACKGROUND Hepatobiliary and pancreatic(HBP)cancers impose a considerable burden on young populations(aged 15 to 49 years),resulting in a substantial number of new cases and fatalities each year.In young populations,the HBP cancers shows extensive variance worldwide and the updated data in China is lacking.AIM To investigate the current status,trends,projections,and underlying risk factors of HBP cancers among young populations in China.METHODS The Global Burden of Disease Study 2019 provided data on the annual incidence,mortality,disability-adjusted life years(DALYs),age-standardized incidence rate(ASIR),mortality rate(ASMR),and DALYs rate(ASDR)of HBP cancers in young Chinese adults between 1990 and 2019.Temporal trends were assessed using estimated annual percentage change and hierarchical clustering.Sex-specific mortality and DALYs caused by various risks were analyzed across China and other regions,with future trends until 2035 projected using the Bayesian age-period-cohort model.RESULTS From 1990 to 2019,incident cases,deaths,DALYs,ASIR,ASMR,and ASDR for liver cancer(LC)in young Chinese individuals decreased,classified into'significant decrease'group.Conversely,cases of gallbladder and biliary tract cancer and pancreatic cancer rose,categorized as either'significant increase'or'minor increase'groups.The contribution of risk factors to mortality and DALYs for HBP tumors increased to varying degrees.Healthy lifestyle behaviors,such as tobacco control,weight management,alcohol moderation,and drug avoidance,could lower HBP cancers incidence.Moreover,except for LC in females,which is likely to initially decline slightly and then rise,the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young adults.CONCLUSION HBP cancers burden among young adults in China is expected to increase until 2035,necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these cancers.

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance

Autophagy plays a pivotal role in diverse biological processes,including the maintenance and differentiation of neural stem cells(NSCs).Interestingly,while complete deletion of Fip200 severely impairs NSC maintenance and differentiation,inhibiting canonical autophagy via deletion of core genes,such as Atg5,Atg16l1,and Atg7,or blockade of canonical interactions between FIP200 and ATG13(designated as FIP200-4A mutant or FIP200 KI)does not produce comparable detrimental effects.This highlights the likely critical involvement of the non-canonical functions of FIP200,the mechanisms of which have remained elusive.Here,utilizing genetic mouse models,we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1,primarily via TAX1BP1 in NSCs.Conditional deletion of Tax1bp1 in fip200hGFAP conditional knock-in(cKI)mice led to NSC deficiency,resembling the fip200hGFAP conditional knockout(cKO)mouse phenotype.Notably,reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation.Conversely,a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration.Furthermore,conditional deletion of Tax1bp1 in fip200hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200hGFAP cKO mice.Collectively,these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function,presenting novel therapeutic targets for neurodegenerative diseases.

Economic Burden of Illness of the Cervical Cancer Treatment Protocol in Bangladesh

Background: Cervical cancer is a significant health concern in Bangladesh, with high mortality rates due to limited awareness and costly treatments. The disease stages influence treatment protocols, ranging from surgery and radiotherapy for early stages to chemotherapy and radiation for advanced stages, but survival rates decrease as the cancer progresses. Objective: The objective of this study is to determine the economic impact of the disease and recommend cost-efficient strategies for prevention and treatment. Methods: A population-based, cross-sectional study was conducted with a stratified sample of cervical cancer patients from selected healthcare facilities across Bangladesh. Data collection involved structured interviews and validated questionnaires. The study measured the economic impact, treatment costs, and other related expenses. Quantitative data analysis was performed using SPSS v22, MS-Excel, and R Programming, with Multivariate regression analysis and Post Hoc tests, including the chi-square test, applied to selected indicators. Results: All respondents in the study were female, aged 34 - 75, with 72.3% aged 40 - 50. Most were illiterate (38.6%) and housewives (95.0%). Additionally, 98% were married, 85.10% married before age 18, and 46.50% experienced their first menstruation before age 12. Families typically had a monthly income of 10,000 - 30,000 Taka, spending similar amounts on treatment. Significant relationships were found between educational qualifications, occupation, personal hygiene practices, history of oral contraceptive use, and age of marriage (p Conclusion: The article emphasizes the impact of monthly family income on cervical cancer treatment costs, stressing the need for comprehensive support services to address the financial and emotional burdens faced by patients. Improving access to quality care and implementing measures can enhance outcomes for cervical cancer patients in Bangladesh.

Effect of Property Tax on Optimization and Upgrading of Industrial Structure

China's economic growth and economic development has entered a new stage,and the optimization and upgrading of industrial structure is the core driving force for China to achieve high-quality economic development during the"14 th Five-Year Plan"period.Property tax has a conductive effect on the upgrading of industrial structure.Therefore,from the perspective of property tax and industrial structure adjustment and the relationship between them,this study summarizes the relevant research of domestic and foreign scholars.On the basis of the research,the paper puts forward some relevant policy suggestions on improving China's property tax and promoting the optimization and upgrading of China's industrial structure.

The burden and psychosocial impact on immediate caregivers of patients with spinal cord injury in a tertiary health facility,Edo State,Nigeria

Objective:This study aimed to assess the burden and psychosocial impact of spinal cord injury on the immediate caregivers at a tertiary health facility in Benin City,Edo State.Materials and Methods:A descriptive cross-sectional survey design was adopted among 73 family caregivers in the neurological ward of a tertiary health facility using a structured questionnaire as instrument of data collection.Data collected were analyzed using descriptive statistics and multiple logistic regression.Results:Findings revealed that an overall mean of 2.73 indicates that the burden on the caregivers was moderate with a moderate psychological impact(m=2.88)and a high sociological impact(m=3.12).Factors affecting the caregiving provided by immediate caregivers include social and household responsibilities(94.5%),financial situation(89.0%),family support(83.6%),and health status of the caregiver(80.8%).Age(odds ratio[OR]=5.67,95%confidence interval[CI]:1.23-27.17,P=0.027),education(OR=3.75,95%CI:1.05-13.39,P=0.041),and“others”(spouses,siblings,friends,or extended family members)(OR=3.167,95%CI:1.583-6.337,P=0.001)were predictors for high psychological impact while education(OR=0.074;95%CI:0.015-0.370,P=0.001)and caregiving role(OR=3.167;95%CI:0.1.583-6.337,P=0.001)high sociological impact.Conclusion:Majority of the caregivers experience moderate burden,moderate psychological impact,and high sociological impact.Understanding these factors is essential for developing targeted interventions and support services to address the unique needs of caregivers and mitigate the burden of caregiving on their psychosocial health.

Colorectal cancer’s burden attributable to a diet high in processed meat in the Belt and Road Initiative countries

BACKGROUND Colorectal cancer(CRC)plays a significant role in morbidity,mortality,and economic cost in the Belt and Road Initiative(“B and R”)countries.In addition,these countries have a substantial consumption of processed meat.However,the burden and trend of CRC in relation to the consumption of a diet high in processed meat(DHPM-CRC)in these“B and R”countries remain unknown.AIM To analyze the burden and trend of DHPM-CRC in the“B and R”countries from 1990 to 2019.METHODS We used the 2019 Global Burden of Disease Study to collate information regarding the burden of DHPM-CRC.Numbers and age-standardized rates(ASRs)of deaths along with the disability-adjusted life years(DALYs)were determined among the“B and R”countries in 1990 and 2019.Using joinpoint regression analysis,the average annual percent change(AAPC)was used to analyze the temporal trends of age-standardized DALYs rate(ASDALR)from 1990 to 2019 and in the final decade(2010–2019).RESULTS We found geographical differences in the burden of DHPM-CRC among“B and R”countries,with the three highest-ranking countries being the Russian Federation,China,and Ukraine in 1990,and China,the Russian Federation,and Poland in 2019.The burden of DHPM-CRC generally increased in most member countries from 1990 to 2019(all P<0.05).The absolute number of deaths and DALYs in DHPM-CRC were 3151.15[95%uncertainty interval(UI)665.74-5696.64]and 83249.31(95%UI 15628.64-151956.31)in China in 2019.However,the number of deaths(2627.57-2528.51)and DALYs(65867.39-55378.65)for DHPM-CRC in the Russian Federation has declined.The fastest increase in ASDALR for DHPM-CRC was observed in Vietnam,Southeast Asia,with an AAPC value of 3.90%[95%confidence interval(CI):3.63%-4.16%],whereas the fastest decline was observed in Kyrgyzstan,Central Asia,with an AAPC value of-2.05%(95%CI:-2.37%to-1.73%).A substantial upward trend in ASR of mortality,years lived with disability,years of life lost,and DALYs from DHPM-CRC changes in 1990-2019 and the final decade(2010-2019)for most Maritime Silk Route members in East Asia,South Asia,Southeast Asia,North Africa,and the Middle East,as well as Central Europe,while those of the most Land Silk Route members in Central Asia and Eastern Europe have decreased markedly(all P<0.05).The ASDALR for DHPM-CRC increased more in males than in females(all P<0.05).For those aged 50-74 years,the ASDALR for DHPM-CRC in 40 members exhibited an increasing trend,except for 20 members,including 7 members in Central Asia,Maldives,and 12 high or high-middle social development index(SDI)members in other regions(all P<0.05).CONCLUSION The burden of DHPM-CRC varies substantially across“B and R”countries and threatens public health.Relevant evidence-based policies and interventions tailored to the different trends of countries in SDIs or Silk Routes should be adopted to reduce the future burden of CRC in“B and R”countries via extensive collaboration.