OBJECTIVE To investigate and analyze the current management of drug clinical trial institutions in Jiangxi Province and the situation of undertaking drug clinical trials after the implementation of the filing system. METHODS A survey was conducted on 38 new institutions （obtained qualifications during the implementation of the filing system） and old institutions （obtained qualifications during the implementation of the recognition system） that had completed drug clinical trial institution qualification filing for more than one year in Jiangxi Province. The survey focused on the basic information of the institutions， the number of registered principal investigator （PI）， institutional hardware and information construction， personnel allocation and training， and drug registration clinical trials undertaken by the institutions. RESULTS Of 38 institutions surveyed， there were 22 general hospitals and 16 specialized hospitals； there were 24 old institutions and 14 new institutions. Whether in general hospitals or specialized hospitals， the old institutions were better than the new institutions in the number of approved beds， the number of outpatients， the number of inpatients， the number of specialties， and the number of PI； both old and new institutions had separate offices； all new institutions were set up with GCP pharmacy. The adoption of clinical trial management system in new institutions is significantly less than in old institutions. In the general hospital， both the number of full-time managers and the number of quality controllers in old institutions were significantly more than in the new institutions， while the opposite was true at the level of specialized hospitals. In terms of centralized training on GCP， new institutions were all better than the old ones. Whether in general hospitals or specialized hospitals， the number of drug registration clinical trial projects undertaken by new institutions was significantly less than that of old ones. CONCLUSIONS The new institutions are worse than the old institutions in comprehensive strength and information construction of hospitals， and the number of clinical trials undertaken by new institutions is also less than old institutions.

Objective To explore the effect and potential mechanisms of melatonin combined with gemcitabine on the chemosensitivity of human pancreatic cancer cell line PANC-1.Methods Human pancreatic cancer cell line PANC-1 was trea-ted with gemcitabine alone or in combination with melatonin.Cell viability was assessed using CCK-8.Effect of melatonin and gem-citabine alone or in combination on the clonogenic capacity of PANC-1 cells were observed through colony formation experiments.Scratch assays and transwell experiments were conducted to evaluate cell migration ability.Reactive oxygen species(ROS)and mitochondrial membrane point JC-1 assay kit were used to determine reactive oxygen species synthesis and membrane potential levels.Intracellular Fe2+level was measured using ferrous ion fluorescent probe.The protein expression levels of LC3,P62,GPX4 and SLC7A11 in different treatment groups were detected by immunofluorescence and Western blotting.Results CCK-8 results showed that the viability of PANC-1 cells was inhibited by gemcitabine alone after 48 h and 72 h of treatment in a time-and dose-dependent manner.The cell viability of gemcitabine combined with melatonin group was significantly lower than that of gemcitabine group,and the cell viability decreased with the increase of melatonin concentration.Scratch assays,transwell experiments,and plate colony formation assay results demonstrated that the proliferation and migration of cells in the gemcitabine combined with the me-latonin group were significantly inhibited compared with the gemcitabine group.The levels of reactive oxygen species and Fe2+in PANC-1 in gemcitabine combined with the melatonin group were higher than those in the gemcitabine group,and the mitochondri-al membrane potential was significantly decreased(P＜0.01).Western blotting and immunofluorescence results showed that the ra-tio of autophagy-related protein LC3-Ⅱ/LC3-Ⅰ in gemcitabine combined with the melatonin group was lower than that in the gem-citabine group,and the expression of P62 was up-regulated,and the expression of anti-iron death-related protein GPX4 and SLC7A11 was significantly inhibited(P＜0.05),suggesting that melatonin combined with gemcitabine can inhibit autophagy and promote ferroptosis in PANC-1 cells.Conclusion Melatonin enhances the chemosensitivity of pancreatic cancer cell PANC-1 to gemcitabine by inhibiting autophagy and promoting ferroptosis of tumor cells.

Objective To investigate the relationship between the single nucleotide polymorphism of PPARG rs2290449 and the efficacy of combination therapy in sepsis patients with MODS.Methods 382 cases of sepsis with MODS were selected and divided into the effective group and the ineffective group,and a case-control study was conducted.PCR-RFLP and Sequenom MassARRAY were used to detect the genotype and allele frequencies of the loci.Unconditional Logistic regression was used to calculate odds ratio(OR)and 95％confidence interval(CI)to evaluate the efficacy of combination therapy for sepsis with MODS in patients with different genotypes.Re-sults There were G and A alleles in PPARG rs2290449 locus,GG、GA and AA genotype.Non-conditional Logis-tic regression analysis showed that compared with the GG genotype group,the GA genotype group had a significant correlation with the efficacy of combination therapy for sepsis with MODS(OR=0.449,95％CI=0.280-0.722,P=0.001).In the dominant model,there was a significant correlation between the GA+AA genotype and the effi-cacy of combination therapy compared with the GG genotype(OR=2.104,95％CI=1.332-3.321,P=0.001).After adjusting for confounding factors,unconditional Logistic regression analysis showed that compared with the GG genotype,the GA+AA genotype was significantly correlated with the efficacy of combination therapy in sepsis pa-tients with MODS(OR=2.307,95％CI=1.438-3.701,P=0.001).Stratified analysis showed that compared with the population carrying GG genotype,the population carrying GA+AA genotype was significantly correlated with the efficacy of combination therapy in sepsis with MODS in the stratified analysis of age,gender and ethnicity.Conclusion PPARG rs2290449 single nucleotide polymorphism is significantly correlated with the efficacy of com-bination therapy in sepsis patients with MODS in Yanbian area.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective:To investigate the expressions of MUC1, MUC4, MUC5AC and MUC16 in patients with first diagnosis of dry eye and their correlation with dry eye symptoms and signs.Methods:A cross-sectional study was conducted.Sixty-nine dry eye patients (69 eyes) as dry eye group and 40 normal volunteers (40 eyes) as normal control group were recruited in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Puotuo District Center Hospital from December 2016 to May 2018.Symptoms were evaluated by Chinese dry eye questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-Life Score Questionnaire (DEQS). Signs were assessed by tear film breakup time (TBUT), keratoconjunctival fluorescein sodium staining, and Schirmer I test.Conjunctival cells were collected by conjunctival impression cytology.The expression levels of MUC1, MUC4, MUC5AC and MUC16 mRNA in the two groups were determined by real-time fluorescence quantitative PCR.The correlation between the mRNA levels of conjunctival mucins and dry eye symptoms and signs were analyzed by Spearman correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Puotuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from each subject before any medical examination.Results:The expression levels of MUC1 and MUC16 mRNA in dry eye patients were 3.277(0.568, 5.790) and 1.815(1.048, 3.694), which were higher than 1.055(0.550, 2.010) and 1.024(0.541, 1.965) in normal control group (Z=819.00, P=0.008; Z=861.00, P=0.002). According to OSDI scores, MUC1 was mainly increased to 3.277(1.161, 6.226) in mild to moderate (12-32 points) dry eye patients (Z=9.04, P=0.029), and MUC16 was mainly increased to 1.968(1.074, 3.726) in severe (>32 points) dry eye patients (Z=12.24, P=0.007). MUC1 expression was positively correlated with TBUT, and was negatively correlated with corneal staining scoring and keratoconjunctival staining scoring ( r s=0.270, P=0.025; r s=-0.331, P=0.006; r s=-0.325, P=0.007). MUC16 expression was positively correlated with TBUT, and was negatively correlated with blurred vision scoring, symptom exacerbation scoring during reading, impact scoring of driving at night, impact scoring of computer and impact scoring of TV use ( r s=0.249, P=0.039; r s=-0.359, P=0.047; r s=-0.370, P=0.034; r s=-0.558, P=0.016; r s=-0.498, P=0.006; rs=-0.515, P=0.002). Conclusions:The gene expressions of MUC1 and MUC16 are higher in conjunctiva of dry eye patients.MUC1 mRNA expression is related to patients' signs.MUC16 mRNA expression is related to the quality of life of patients.

Ulcerative colitis （UC） is a common inflammatory bowel disease （IBD） in clinical practice， characterized by symptoms such as abdominal pain， diarrhea， and bloody mucus in the stool. It is difficult to cure and has a high recurrence rate. The pathogenesis of UC is related to abnormal immune response， oxidative stress in intestinal tissues， and inflammatory reactions. As reported， the abnormal activation of the NOD-like receptor pyrin domain-containing protein 3 （NLRP3） inflammasome is involved in the pathological process of UC. This activation triggers pathological mechanisms such as oxidative stress， pyroptosis， and inflammation in intestinal epithelial cells. Therefore， blocking the abnormal activation of NLRP3 is beneficial for alleviating UC. Currently， western medicine treatment for UC mainly includes salicylic acid derivatives， corticosteroids， and biologics， but the overall efficacy is unsatisfactory. Traditional Chinese medicine （TCM） treatment of this disease has the advantages of significant efficacy and low recurrence rate. In recent years， great advances have been made in the basic research of using TCM methods to treat UC. Studies have found that TCM intervention targeting the NLRP3 inflammasome can significantly promote intestinal mucosal healing and treat UC， and the mechanism of action involves multiple targets， levels， and pathways. This article summarized the experimental research on the impact of TCM targeting the NLRP3 inflammasome on UC in recent years， and found that NLRP3 interacted with factors such as Caspase-1 and nuclear factor-κB （NF-κB）， thereby promoting the release of pro-inflammatory factors and cell pyroptosis in intestinal epithelial cells. This activation triggered oxidative stress， inflammatory reactions， and other pathological mechanisms. TCM acted on the NLRP3 inflammasome and its upstream and downstream factors to block the pathological process of UC， inhibit the pathological damage to the intestinal mucosa， and thereby alleviate colonic ulcers. The findings of this study provide a theoretical basis for the prevention and treatment of UC and further drug development.

Background Prolonged awkward postures during occupational activities can lead to excessive musculoskeletal load on the wrist of workers and symptoms such as wrist pain or discomfort. Objective To survey the prevalence of wrist pain among workers in 10 key industries and analyze its correlation with wrist working postures. Methods By using stratified cluster sampling method, workers from 10 key industries, such as footwear manufacturing industry, shipbuilding manufacturing industry, and automobile manufacturing industry, were selected from seven regions in North China, East China, Central China, South China, Southwest China, Northwest China, and Northeast China. The demographic information, wrist working postures, pain in wrist of the workers were collected through a cross-sectional survey. Pearson χ² test was used to compare prevalence by selected factors, trend χ² test for between group comparison, and unconditional logistic regression models for the association of wrist working postures with wrist pain. Results There were 64052 workers enrolled in this survey, and 56286 provided valid questionnaires (the effective rate was 87.8%). According to the survey, the prevalence of wrist pain was 23.3% (13112/56286), and the industries with higher prevalences were footwear manufacturing (27.1%, 1927/7106), automobile manufacturing (24.9%, 5378/21560), and shipbuilding and related equipment manufacturing (24.4%, 850/3488) industries. Finger pinching (OR=2.09, 95%CI: 1.95-2.24), frequent wrist bending (OR=2.03, 95%CI: 1.92-2.15), fixed wrist bending (OR=1.77, 95%CI: 1.69-1.85), wrist on hard edge (OR=1.34, 95%CI: 1.28-1.40), and arms over shoulders (OR=1.11, 95%CI: 1.05-1.17) increased the risk of reporting wrist pain. Conclusion Awkward postures are related to wrist pain among workers in selected 10 key industries. The related factors are wrist on hard edge, frequent wrist bending, finger pinching, fixed wrist bending, and arms over shoulders.

Objective:To investigate the effect of septic shock rapid response team (SSRRT) on the compliance and prognosis of hour-1 bundle therapy strategy in emergency department patients with septic shock.Methods:This study was conducted on emergency patients with septic shock who were admitted to Huai’an First Hospital Affiliated to Nanjing Medical University from January 2020 to December 2021. The inclusion criteria were emergency patients with septic shock who met the international guideline for surviving sepsis campaigns (Sepsis 3.0). Exclusion criteria: age<18 years, pregnant patients, patients transferred from another hospital who had received fluid resuscitation and/or vasoactive drugs, patients requiring emergency surgery, patients with emergency detention time<1 h, patients who refused to place central venous catheterization or had contraindications for catheterization, and patients who refused to give informed consent. SSRRT was established in January 2021. According to the establishment of SSRRT, patients were divided into the pre-SSRRT intervention group and the post-SSRRT intervention group. The general clinical data of the enrolled patients were collected, including vital signs, lactate, fluid resuscitation volume, maximum vasoactive drug pumping rate at the diagnosis of septic shock, implementation of hour-1 bundle therapy strategies, and ICU and 28-day mortality. Statistical software SPSS 25.0 was used. Pearson chi-squared test was used to compare categorical variables between groups, and Mann-Whitney U test was used to compare continuous variables between groups.Results:A total of 289 emergency patients met the inclusion criteria, 115 patients were excluded, and 174 patients were eventually included, including 83 patients in the pre-SSRRT group and 91 patients in the post-SSRRT group. Compared with the pre-SSRRT group, the proportion of lactate monitoring (54.2% vs. 100.0%, P<0.001), blood culture (27.7% vs. 93.4%, P<0.001), antibiotics (57.8% vs. 97.8%, P<0.001), fluid resuscitation volume ≥ 30 mL/kg (4.8% vs. 34.1%, P<0.001), and mean arterial pressure ≥ 65 mmHg (49.4% vs. 68.1%, P<0.001) were significantly increased. There was no significant difference in ICU mortality (50.6% vs. 37.4%, P=0.079) or 28-day mortality (53.0% vs. 38.5%, P=0.054) between the two groups. Conclusions:SSRRT can significantly improve the compliance of hour-1 bundle therapy strategy implementation in patients with emergency septic shock, and has a trend of decreasing mortality.

Objective:To analyze the clinical manifestations and signs of the first diagnosed dry eye patients, and to explore the concordance between the Chinese dry eye diagnostic criteria and the Asian dry eye diagnostic criteria.Methods:A cross-sectional multicenter study was conducted.One hundred and forty-one eyes of 141 patients who were diagnosed as dry eye for the first time were included in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Putuo District Center Hospital from December 2016 to May 2018.All patients completed the Chinese Dry Eye Questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) to evaluate the symptoms of dry eye.Tear film breakup time (BUT), keratoconjunctival fluorescein staining, meibomian gland morphology and function examination, and Schirmer Ⅰ test were performed to evaluate dry eye signs and the association between dry eye symptoms and signs.The eyes were divided into corneal staining positive and negative group according to the presence or absence of corneal fluorescein staining, and the dry eye symptoms of the two groups were assessed by the three questionnaires.The eyes were divided into tear-deficient dry eye, evaporative dry eye, mixed dry eye and abnormal tear dynamics dry eye to compare the difference of dry eye signs among the groups.This study adhered to the Declaration of Helsinki.The study protocol complied with Chinese regulations and rules on clinical trial research and was approved by Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Putuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from patients before entering the cohort.Results:The total score of Chinese Dry Eye Questionnaire, OSDI questionnaire and DEQS questionnaire was 12.00(7.00, 16.00), 25.00(17.50, 36.93) and 32.02(15.77, 52.34), respectively.It was found that 130 eyes (92.2%) had dryness, and 109 eyes (77.3%) had ocular fatigue and 108 eyes (76.6%) had foreign body sensation.Dryness, foreign body sensation, photophobia and poor vision were weakly positively correlated with corneal staining ( r=0.177、0.297、0.172, all at P<0.05). Pain, photophobia and poor vision were negatively correlated with tear secretion ( r=-0.178, -0.197, -0.174; all at P<0.05). It was found that 43.3% of dry eye patients had used visual display terminals.Among the 141 eyes, 75 eyes (53.2%) were with over evaporation dry eye, 43 eyes (30.5%) with mixed dry eye, 18 eyes (12.8%) with aqueous-deficient dry eye and 3 eyes (2.1%) with abnormal tear dynamics dry eyes. Conclusions:Initial diagnosis of dry eye patients is mainly mild to moderate.Dry eye signs and symptoms are correlated.Over evaporation dry eye is the most common type of dry eye.The concordance between the Chinese dry eye diagnostic criteria and the Asian Dry Eye Society diagnostic criteria reaches 97.2%.

Objective:To analyze the effect of chlorpyrifos on the expression of autophagy related proteins in rat hippocampal neurons, and to explore the role of autophagy in central nerve injury caused by acute chlorpyrifos poisoning.Methods:In October 2018, 35 male clean grade SD rats were randomly divided into 7 groups according to the observation time point, namely 0.5 d, 1 d, 2 d, 3 d, 5 d and 7 d groups and the control group, with 5 rats in each group. Each observation group was given 81.5 mg/kg chlorpyrifos by gavage, and the control group was given olive oil by gavage. The general conditions and poisoning symptoms of rats were observed continuously after exposure. The expressions of autophagy related proteins Beclin1, P62/SQSTM1 and LC3 in hippocampus were detected by Western blot. The cell morphology and LC3 expression in brain were observed by immunohistochemical staining.Results:Western blot results showed that compared with the control group, the expression of Beclin1 protein in hippocampal neurons of rats in the 1 d, 2 d, and 3 d groups increased, while the expression of P62/SQSTM1 protein in the 0.5 d, 1 d, and 2 d groups decreased, and the expression of LC3 protein was decreased in the 2 d group, and the differences were statistically significant ( P<0.05) . The results of immunohistochemistry showed that the hippocampal neurons of rats in the 5 d group were arranged disorderly, and some nuclei contours disappeared, especially in the 7 d group. The LC3 protein was expressed in the cytoplasm, and the expression level gradually increased, reaching a peak on the second day. Conclusion:The early activation of autophagy in rats with acute chlorpyrifos poisoning may be involved in chlorpyrifos induced hippocampal neuronal injury.