Objective:To analyze and summarize the key points of design and implementation of new drug clinical trials for ankylosing spondylitis.Methods:The platform for drug clinical trial registration and information published on the official website of center for drug review and evaluation of national medical products administration (CDE) was searched to obtain data and classified statistics was conducted then. The Mean±SD and M ( Q1, Q3) were used for quantitative data for statistical description, and the rate, composition or relative ratio of qualitative data were used for statistical description. Results:A total of 23 clinical trials meeting the requirements were screened, among which 19 were biological products included in nine phase Ⅲ clinical trials. Among the four chemical drugs, two were phase Ⅱ clinical trials. One of the clinical trials on AS adopted the 1966 New York classification criteria, accounting for 4%. Nineteen of the trials adopted the1984 New York classification criteria, accounting for 83%. Three other trials adopted unspecified classification criteria, accounting for 13%. In one of these clinical trials, the age of patients included was older than 16 years old, 9 trials were 18 to 65 years old, 6 were 18 years old but without upper limit. In the definition of active AS, 19 trials took BASDAI≥4 as the cut-off value for active disease, and BASDAI, total back pain, spinal pain and morning stiffness were regarded as active disease in 4.Conclusion:The number of dosestic AS clinical trial projects continnes to rise. The 1984 classification criteria is adopted as the classification criteria in clinical trials. The minimum age in the inclusion criteria is 18 years old, there is no upper limit in age for inclusion. Disease activity can be evaluated by BASDAI score, combined with comprehensive indicators such as night-time back pain, global spinal pain and morning stiffness.

Climate change has led to an increasing frequency and intensity of extreme climate events such as heat and drought extremes with considerable global public health burden. This systematic review collected 87 domestic and international studies from 2000 to 2023, considering the impacts of heat extremes, drought extremes, and compound hot-dry events on infectious diseases attributable to various transmission pathways such as waterborne, foodborne, insect-borne, airborne, and contact-transmitted diseases. Our results showed that high temperature was associated with increased transmission risks of waterborne and foodborne diseases including infectious diarrheal diseases (cholera, dysentery, typhoid, and paratyphoid) and infectious gastroenteritis; vector-borne diseases including dengue fever, Zika virus (ZIKV) disease, chikungunya fever, malaria, West Nile fever, and Rift Valley fever; airborne diseases including influenza-like diseases, influenza A, measles, and mumps; and contact-transmitted diseases including HIV/AIDS, schistosomiasis, and leptospirosis. Additionally, drought conditions also amplified the transmission risks of waterborne and foodborne diseases including cholera, Escherichia coli infection, rotavirus infection, and hepatitis E; vector-borne diseases such as scrub typhus, schistosomiasis, hemorrhagic fever with renal syndrome, and West Nile fever; airborne diseases including meningococcal meningitis, pertussis, measles, and upper respiratory infections; and contact-transmitted diseases such as HIV/AIDS. Along with global warming, the frequency of compound high temperature and drought events shows a considerably increasing trend, causing more adverse health effects than heat or drought alone. However, there is limited research quantifying their effects on infectious diseases. These associations may be mediated through temperature and precipitation on infectious disease pathogens, transmission vectors, population susceptibility, public health services, and behaviors. In the context of climate change, the increasing occurrence of compound events of high temperatures and droughts raises health concerns, and further studies are needed to enhance our understanding of the impacts of climate change on infectious diseases and improve human adaption to climate change.

ObjectiveTo investigate the infection and genotypes of Wolbachia in Aedes albopictus. MethodsAdult and larval samples of Aedes albopictus were collected from different residential and wild areas from 2020 to 2021， Wolbachia surface protein （wsp） gene was amplified and genotyped for wAlbA and wAlbB by PCR， and sequenced for phylogenetic analysis. The difference of detection rate among different habitats， male and female adult mosquitoes， adult and larvae was compared by χ² analysis. ResultsThe detection rate of Wolbachia in adult and larvae of Aedes albopictus were 43.5% （77/177） and 70.4% （190/270）， respectively， with a statistically significant difference （χ²=32.086，P<0.001）， and wAlbA and wAlbB were mainly detected together. The detection rate of Wolbachia in female and male Aedes albopictus were 50.7% （76/150） and 3.7% （1/27）， respectively， with a statistically significant difference（χ²=20.533，P<0.001）. The detection rate of adult Aedes albopictus in Songjiang wild area， residential area and Hongkou residential area were 91.7% （55/60）， 18.8% （22/117） and 41.7% （30/72）， respectively， with a statistically significant difference （χ²=54.322，P<0.001）. Genotyping and phylogenetic analysis showed that adult and larvae of Aedes albopictus infected with Wolbachia were mainly wAlb A and wAlb B. In addition， some sequences formed clades independently， and the genetic distance from other sequences was relatively large. ConclusionInfection of Wolbachia in Aedes albopictus is relatively common in Songjiang District. The main genotypes are wAlb A and wAlb B and there may be other subtypes， which are worthy of further exploration and research.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

AIM: To quantitatively analyze the changes of the peripapillary capillary vessel density(ppVD)and the peripapillary retina nerve fiber layer(pRNFL)thickness in patients with monocular retinal vein occlusion(RVO)by optical coherence tomography angiography(OCTA), and further analyze the correlation between the ppVD and the pRNFL thickness.METHODS: Prospective observational research. A total of 43 patients diagnosed with monocular RVO were enrolled in the Department of Ophthalmology of the First Affiliated Hospital of Anhui University of Science and Technology from January to December 2021, among which 43 RVO eyes were regarded as the affected group and 43 fellow eyes were regarded as the contralateral group. At the same time, 21 healthy volunteers(42 eyes)matching the age and gender with RVO patients were regarded as the control group. The vessel density(VD)of inside optic disc, the whole VD of around disc and the ppVD and pRNFL thickness around the optic disc were measured by OCTA, including peripapillary superior(pS), peripapillary inferior(pI), temporal superior(TS), superior temporal(ST), superior nasal(SN), nasal superior(NS), nasal inferior(NI), inferior nasal(IN), inferior temporal(IT), and temporal inferior(TI). The characteristic changes of ppVD and pRNFL thickness and theirs correlation in the three groups were analyzed.RESULTS: The VD of inside optic disc, the whole VD of around disc and the ppVD in the pS, pI, TI, ST and SN side of the affected group were all significantly decreased compared with the control group(all P<0.05). But only VD of the inside disc in contralateral group was decreased(all P<0.05). Compared with the control group, the pRNFL thickness in the TS side of the affected group was increased, and the ST and IT side pRNFL thickness of the contralateral group were decreased(all P<0.01). The canonical correlation analysis revealed that ppVD and pRNFL thickness were provided with a strong correlation between the two comprehensive variables. There were 2 pairs of canonical correlation variables in affected group and contralateral group, and 3 pairs of canonical correlation variables in control group.CONCLUSION: The VD in the optic disc area of the affected group was decreased in patients with monocular RVO, and the pRNFL thickness in ST and IT side of the contralateral group was thinner. There was a strong positive correlation between ppVD and pRNFL thickness as a whole. The changes of ppVD and pRNFL thickness in the optic disc area were mostly manifested in the superior quadrant of the affected group and the inferior quadrant of the contralateral group.

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

Humans ; Serotonin ; Cardiovascular Diseases

With the continuous development of evidence-based medicine, increasing attention has been paid to the construction of a large medical database to ensure a source of high quality real-world data. The Chinese Medical Association Colorectal Surgery Group created the Chinese Colorectal Cancer Surgery Database (CCCD), whose objective is to promote the development of colorectal surgery and improve patient prognosis with evidence-based medicine theory. Compared to major databases around the world, CCCD contains more comprehensive information on colorectal cancer surgical cases, recording the main epidemiological characteristics and detailed surgical information, but perioperative treatment data still need to be strengthened. It is necessary to continuously expand the coverage, enrich perioperative data and strengthen data, quality control. In the future, CCCD is expected to play a role in promoting homogenization of medical services, promoting smooth and effective graded diagnosis and treatment, giving full role to the characteristics of each center to achieve integrated development, and connecting real-world data and artificial intelligence.