OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

Objective:To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS).Methods:The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis.Results:A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95% CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95% CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR=0.62,95% CI 0.40-0.97 ,P=0.033) and second endpoint ( HR=0.56, 95% CI 0.37-0.87, P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion:On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

Objective:To understand the current situation of knowledge, attitude and practice of nasointestinal tube nursing among emergency department nurses and analyze its influencing factors.Methods:A total of 470 emergency department nurses from 35 hospitals with nasoenteric tube technology in Beijing were selected as the survey objects by the convenient sampling method from December 2023 to January 2024. The general data questionnaire and Knowledge, Attitude and Practice Questionnaire on Nasointestinal Tube Nursing among Emergency Department Nurses were used to investigate. Multiple linear regression analysis was used to analyze influencing factors on the knowledge, attitude and practice level of nurses in nasointestinal tube nursing.Results:A total of 470 questionnaires were sent out and 470 were effectively collected, with the effective recovery rate of 100.0%. The scores of knowledge, attitude and practice dimensions and total score of emergency department nurses in nasointestinal tube nursing were (25.14±6.80), (44.55±6.94), (79.33±11.73) and (149.03±18.35), respectively. The results of multiple linear regression analysis showed that the education level of emergency department nurses, whether they were teachers, whether they had systematically cared for nasointestinal tubes and whether they had encountered nasointestinal tube blockage were the influencing factors of knowledge dimension ( P<0.05), the professional title of nurses was the influencing factor of attitude dimension ( P<0.05), and hospital level, whether they systematically studied and whether they could independently complete nasointestinal tube placement were the influencing factors of practice dimension ( P<0.05) . Conclusions:The nasointestinal tube nursing level of nurses in the emergency department still needs to be improved and is affected by various factors. Nursing managers should strengthen the training and guidance of nasointestinal tube nursing, train clinical nutrition specialized nurses, formulate targeted training plans and carry out quality supervision combining various methods to comprehensively promote the improvement of nurses' nasointestinal tube nursing level.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective:Upper gastrointestinal bleeding (UGIB) is a common gastrointestinal disease in the emergency department. Identifying low-risk patients suitable for outpatient treatment is the focus of clinical and research. A simple predictive model was developed to identify patients with UGIB who could safely avoid hospitalization, thus providing a feasible basis for triage by emergency physicians.Methods:A retrospective cohort study was conducted on patients with UGIB treated at Zhongda Hospital Southeast University from January 2015 to December 2020. Baseline demographic data and clinical parameters at the initial presentation were recorded. Multivariate logistic regression model was performed to identify predictors of safe discharge.Results:Six hundred and twelve patients (45.9%) were not safely discharged. There were significant differences in age, Charlson comorbidity index, systolic blood pressure, pulse rate, hemoglobin, albumin, blood urea nitrogen, creatinine and international normalized ratio between the safe discharge group and the non-safe discharge group ( P<0.05). Using multivariate logistic regression analysis, a total of 7 variables were included in the clinical prediction model of UGIB risk stratification: Charlson comorbidity index > 2, systolic blood pressure < 90 mmHg, hemoglobin < 10 g/dL, blood urea nitrogen ≥6.5 mmol/L, albumin <30 g/L, pulse ≥100 beats/min and international normalized ratio ≥1.5. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting unsafe discharge were 98.37%, 24.10%, 52.3%, and 94.6%, respectively, with the best cutoff value ≥1. The area under the receiver operating characteristic (AUROC) curve was 0.822, which was significantly higher than Glasgow Blatchford score (GBS) 0.786 (95% CI: 0.752-0.820, P< 0.01) and AIMS65 0.676 (95% CI: 0.638-0.714, P< 0.01). Conclusions:The predictive model has a reliable predictive value, which can provide references for emergency medical staff to triage patients with UGIB, thereby reducing medical expenses and having certain social and economic benefits.

【Objective】 To explore the correlation between serum trace elements and systolic and diastolic blood pressure in healthy population and patients with hypertension. 【Methods】 The health examination data of the subjects from our hospital from September 2018 to May 2021 were selected. They consisted of 3430 healthy people with no history of chronic diseases and 216 patients with hypertension previously diagnosed. We measured the levels of serum zinc， iron， calcium， magnesium， lead， copper and cadmium and analyzed their correlation with systolic blood pressure （SBP） and diastolic blood pressure （DBP）. 【Results】 The incidence of low zinc （9.5%） and hypomagnesemia （1.8%） was relatively low， while hypomagnesemia （27.8%） was relatively common in the healthy population. Logistic regression analysis showed that age， BMI and serum albumin were associated with increased SBP and DBP. Fasting blood glucose （OR=1.095， 95% CI： 1.007-1.191） and blood lead （OR=1.006， 95% CI： 1.000-1.012） were risk factors for SBP. Serum total cholesterol （OR=1.244， 95% CI： 1.095-1.412）， serum iron （OR=1.275， 95% CI： 1.114-1.460） and blood lead （OR=1.010， 95% CI： 1.004-1.015） were risk factors， while serum magnesium （OR=0.488， 95% CI： 0.266-0.894） acted as a protective factor for DBP. After adjusting for age， gender， BMI， waist-hip ratio， and smoking history， there was no significant difference in serum trace element levels between the hypertension and healthy control groups. 【Conclusion】 SBP is correlated with serum lead， while DBP is positively correlated with serum iron and lead， but negatively correlated with serum magnesium in normal healthy population. There was no significant difference in serum trace element content between hypertensive patients and healthy control group， but the conclusion still needs to be further verified.

Objective:To analyze differentially expressed microRNAs (miRNAs) and target genes in human respiratory epithelial cells (16HBE) after enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) infection using high-throughput sequencing.Methods:TargetScan and miRDB databases were used to predict the target genes of miRNAs that were both up-regulated or down-regulated after EV71 and CVA16 infection. The genes that were both up-regulated and down-regulated were screened out. GO and pathway analysis of the target genes were conducted to screen immune-related target genes and their corresponding miRNAs. The target genes and their corresponding miRNAs that were up-regulated or down-regulated in both immune-related GO and pathway were further screened. Some miRNAs and their target genes were selected for qRT-PCR verification.Results:There were 598 target genes of up-regulated miRNAs and 1 311 target genes of down-regulated miRNAs and 62 target genes that might be up-regulated or down-regulated simultaneously were screened out. The number of up-regulated target genes involved in immune-related GO and pathway were 17 and 13, respectively, and the number of corresponding miRNAs were 15 and 17, respectively. There were 58 and 47 down-regulated target genes involved in immune-related GO and pathway, respectively, and the number of corresponding miRNAs were 30 and 42, respectively. Three up-regulated target genes were involved in both immune-related GO and pathway and regulated by four miRNAs. Nine down-regulated target genes were involved in both immune-related GO and pathway and regulated by 13 miRNAs.Conclusions:This study was conducive to elucidate the host-pathogen interaction after EV71 and CVA16 infection, and provided reference for studying the pathogenesis of hand, foot and mouth disease.

Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan