OBJECTIVE To evaluate the efficacy， safety and economics of the centrally procured generic versus original esomeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding （ANVUGIB）. METHODS A retrospective collection of real-world clinical data was conducted for ANVUGIB patients who received treatment at Shenzhen People’s Hospital and University of Hong Kong-Shenzhen Hospital from January 2018 to March 2024. Patients were divided into imported original drug group （original drug group， 221 cases） and centrally procured generic drug group （generic drug group， 75 cases） according to the types of drug used. Propensity score matching （PSM） was performed at a ratio of 3∶1 to compare the clinical efficacy， safety and economics between the two groups. RESULTS Totally 241 patients were included after PSM， with 170 in the original drug group and 71 in the generic drug group. There were no significant differences between the two groups in terms of rebleeding rate， rate of second endoscopic intervention， blood transfusion rate， length of hospital stay， mortality due to gastrointestinal bleeding， 30-day readmission due to rebleeding， and overall survival rate （P＞0.05）. The incidence of adverse events among all patients in both groups also showed no statistically significant difference （P＞0.05）； furthermore， the adverse events reported by the respective hospitals to the National Center for ADR Monitoring were comparable between the two groups. After PSM， the median total drug cost and high-dose esomeprazole cost in the generic drug group were significantly lower than those in the original drug group， while the median nursing fee and bed fee were significantly higher than those in the original drug group （P＜0.05）. There was no statistically significant difference between the two groups in terms of median total hospitalization expenses， total treatment costs， laboratory fees， examination fees， material costs， or consultation fees （P＞0.05）. CONCLUSIONS The clinical efficacy and safety of centrally procured generic esomeprazole in the treatment of ANVUGIB are comparable to those of the original drug， and it is more economical.

Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

ObjectiveTo investigate the epidemic characteristics and influencing factors of acute conjunctivitis caused by human adenovirus（HAdv）in Yantian District of Shenzhen City， Guangdong Province from 2014 to 2022， and to provide evidence for formulating effective prevention and control measures. MethodsDescriptive epidemiology was used to analyze the epidemiological characteristics of acute hemorrhagic conjunctivitis （AHC） cases reported from the Chinese disease prevention and control information system. Etiological characteristics of laboratory-confirmed cases were analyzed， and a case-control study method of test-negative design （TND） was conducted as well. According to the result of HAdv detection， analysis was used to identify the influencing factors of morbidity. ResultsA total of 1 005 AHC cases were reported in Yantian District， Shenzhen City from 2014 to 2022， with an average annual incidence rate of 49.49/10⁵. The incidence rate ranged from 4.67/10⁵ to 117.28/10⁵. The peak incidence occurred from July to October each year， with a male-to-female ratio of 1.42∶1. The median （P₂₅，P₇₅） age of onset was 29（12，40） years. A total of 716 eye swabs were collected for etiological detection from 2014 to 2022. HAdv positive detection rate was 36.45% （263/716）， Cox 24v positive detection rate was 0.28% （2/716）， while EV70 was not detected. The longest viral shedding time in eye swabs was 10 days， with a median of 2 days. The highest HAdv positive detection rate （47.47%） was observed when the sampling-to-onset interval was 4‒5 days， and the difference was statistically significant （P<0.05）， with a trend of first increasing and then decreasing. Multivariate logistic regressing analysis showed that aged 18‒ years， and average temperature higher than 24.90 ℃ 3 days before onset （P<0.05） were the risk factors for acute HAdv conjunctivitis. ConclusionAHC in Yantian District， Shenzhen City showed a low level of prevalence from 2014 to 2022， with HAdv being the predominant pathogen. The peak period of viral shedding occurred on the 4th to 5th day after symptom onset， suggesting the importance of adherence to strict home isolation for infected persons. Aged18‒ years and average temperature increased 3 days before onset are associated with an increased risk of adenoviral conjunctivitis. It is recommended to strengthen personal protection and keep doing a good job of AHC surveillance and early warning， so as to timely prevent the outbreaks of AHC.

Three carboline fluorescent probes F1-F3 were designed and synthesized, based on lead compound JYJ-19, an antifungal compound discovered previously by our group. The antifungal activity in vitro results showed that compound F1 had moderate antifungal activity (MIC₈₀ = 32 μg·mL^-1). The stokes shift of F1 is 70 nm. The fluorescent probe F1 has good optical properties and can be used for fluorescence imaging research. Subcellular localization experiments results showed that F1 was enriched in the mitochondria of fungal cells. The detection of intracellular reactive oxygen species levels shows that JYJ-19 enhances intracellular reactive oxygen species levels. The above results indicated that carboline compounds could exert antifungal effects by acting on fungal mitochondria.

Objective:To explore the characteristics and patterns of gene mutations in tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML) patients and their relationship with TKI-resistant CML.Methods:A retrospective case series study was performed. Clinical data and next-generation sequencing results from TKI-resistant CML patients in Nanfang Hospital of Southern Medical University and Yuebei People's Hospital of Shantou University Medical College from August 2018 to November 2022 were retrospectively analyzed, and the gene mutations of the patients in general and at different disease stages were analyzed.Results:Sixty patients were enrolled, with the age [ M ( Q1, Q3)] of 41.5 years old (32 years old, 53 years old); 38 cases (63.33%) were male and 22 cases (36.67%) were female; 43 cases were in the chronic stage, and 17 cases were in the progression stage (3 cases were in the accelerated stage and 14 cases were in the blast stage). non-ABL1 mutations were detected in 30 patients (50.00%) including 45 times of 15 non-ABL1 genes. The number of non-ABL1 mutation gene was 1 (0, 2) in 60 patients. Of the 60 patients, 21 (35.00%) had ASXL1 mutations, 5 (8.33%) had DNMT3A mutations, 5 (8.33%) had RUNX1 mutations, and 3 (5.00%) had SETBP1 mutations; the proportions of patients with 1 and ≥2 non-ABL1 mutations were 33.33% (20/60) and 16.67% (10/60), respectively. The total detection rates of non-ABL1 mutations were 52.94% (9/17) and 48.84% (21/43), and the detection rates of ≥2 non-ABL1 mutations were 23.53% (4/17) and 13.95% (6/43) in patients with progression and patients with chronic disease, and the differences were not statistically significant ( χ2 = 0.08, P = 0.774; χ2 = 0.80, P = 0.370). Seventeen of 60 patients (28.33%) had mutations in the ABL1 kinase region, of which 14 (82.35%) had non-ABL1 mutations; of these 17 cases, 6 patients with progressive disease all had non-ABL1 mutations, in 11 patients with chronic disease, 8 patients had non-ABL1 mutations, and the difference was not statistically significant ( P = 0.452). Conclusions:Patients with TKI-resistant CML have high frequencies of non-ABL1 mutations, and there is a trend for higher mutation rates in patients with progressive disease than in patients with chronic disease, and these may be related to the abnormal activation of ABL1 kinase by BCR-ABL1 fusion gene in patients with drug-resistant CML, which leads to the genome-level and epigenome-level mutations, and driving disease progression from chronic phase to accelerated or blast phase.

Objective:Investigate the expression of thioredoxin(TXN)in pancreatic cancer and its impact on the proliferation,invasion,migration,and apoptosis of pancreatic cancer cells.Methods:By collecting pan-cancer and TCGA pancreatic cancer transcriptome and clinical data,the expression levels of the TXN gene family were analyzed.The expression levels of TXN in cancer tissues,adjacent tissues,and different cell lines were detected by fluorescence quantitative PCR(RT-qPCR)and Western blotting.The expression of the TXN gene in Panc-1 and BxPC-3 pancre-atic cancer cells was inhibited using small interfering RNA(siRNA),and control experiments were conducted with Panc-1 and BxPC-3 cells with unblocked TXN gene expression to explore the ef-fects of TXN on the proliferation,migration,invasion,and apoptosis of these two types of cells.Transcriptional data and survival outcome data were used to divide TXN expression into two groups based on the median value,and survival curves of the high and low TXN expression groups were plotted.Results:In pancreatic cancer tissues and cells,the expression level of TXN was signifi-cantly higher than that in adjacent tissues and normal cells(P＜0.05).After inhibiting the expression of TXN in pancreatic cancer cells,the proliferation rate,invasion cell number,and healing rate of pancreatic cancer cells with low TXN expression were lower than those of the control group,and their apoptosis rate was significantly higher than that of normal pancreatic cancer cells(P＜0.05).The higher the expression level of TXN in the tumors of pancreatic cancer patients,the shorter their survival time(P＜0.05).Conclusion:TXN can enhance the proliferation,migration,and invasion ability of pancreatic cancer cells and weaken the degree of cell apoptosis;the higher the expression level of TXN in pancreatic cancer tissues,the worse the prognosis.

ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.

Objective:To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong).Methods:The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4.Results:A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m 2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions:The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m 2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.