Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

Cocaine,as a widely abused and highly addictive drug,has a serious impact on the physical and mental health of individuals and carries a certain degree of social harm and economic burden.Acupuncture can assist in the treatment of cocaine addiction with fewer side effects.However,a well-defined mode of stimulation is an important factor in elucidating the various mechanisms by which acupuncture treats disease.This paper summarizes the problems in the mechanism of cocaine addiction,such as different parameters of stimulation,unstable depth of acupuncture,different acupoint selection,and different lengths of acupuncture time.To standardize the intervention measures of acupuncture experiments,it is suggested that in future research,the stimulation method should explore the best parameters,the selection of acupoints should be based on clinical practice,the timing of acupuncture should be objective,and the treatment course should consider the effects of acupuncture.

Objective:Operational efficiency and influencing factors of China's basic medical insurance system from 2020 to 2021 is conducted to provide reference for improving the operational efficiency and optimizing the input-output relationship.Methods:The super-efficiency SBM model based on unexpected output and the Malmquist index are used to measure the static and dynamic efficiency of resident medical insurance in 31 provinces in China,and Tobit regression analysis is employed to analyze the influencing factors.Results:The overall operational efficiency of resident medical insurance still needs improvement.The operational efficiency of resident medical insurance in the central and western regions is lower than that in the eastern region,and the gap is significant.Different levels and regions have differentiated main constraints on the operational efficiency of resident medical insurance.In terms of dynamic efficiency,the total factor productivity of resident medical insurance operation shows an increasing trend,mainly due to technological progress.In terms of influencing factors,the degree of aging,the level of medical expenses and the level of medical insurance supervision have a significant impact on the operational efficiency.Suggestions:Efforts should be made to bridge regional disparities,promote the equitable development of medical insurance,reasonably control the level of medical expenses,strengthen the supervision of medical insurance funds,and implement active aging policies.

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

The uniqueness of the location of large general hospitals in urban areas determines that the contradiction between space constraints and medical expansion has become a problem of management bottleneck.The situation that expert visits are too concentrated on a certain working day morning has been significantly improved by carrying out peak load shifting in the visiting arrangements and visiting units of large general hospitals through the Total Quality Management theory and continuous improvement of work mode,greatly alleviating public transportation congestion around the hospital.Through the internal construction of the quality of outpatient clinics,it can effectively improve the patients'sense of access to health care.

Objective:To evaluate the effects of different intervention measures on duration of mechanical ventilation and the length of intensive care unit (ICU) stay in critically ill patients using network Meta-analysis.Methods:Randomized controlled trial (RCT) on the effects of different intervention measures on duration of mechanical ventilation and the length of ICU stay in critically ill patients were systematically searched in PubMed, Embase, China Biomedical Literature Database, CNKI, and other databases. The search time limit was from the establishment of the database to November 2023. Literature screening, quality assessment, and data extraction were independently conducted by two researchers. Network Meta-analysis was employed to assess the effects of each intervention on duration of mechanical ventilation and the length of ICU stay, and funnel plots were generated.Results:A total of 37 RCTs were included, involving 3?977 severe patients, 2?041 in the intervention group and 1?936 in the control group. Thirteen types of interventions were analyzed, including usual care (UC), early activity (EA), early comprehensive rehabilitation (ECR), early pulmonary rehabilitation (EPR), cluster intervention strategy (CS), sedation, analgesia and cluster nursing (SACN), music therapy (MT), neuromuscular electrical stimulation (NMES), modified education and visitation (MV), virtual reality (VR), auricular point sticking (APS), acupoint acupuncture (AA), and concerted intervention (COR). Network Meta-analysis showed that MV significantly better than COR [standardized mean difference ( SMD) = -2.35, 95% confidence interval (95% CI) was -4.30 to -0.39], EPR ( SMD = -2.59, 95% CI was -4.81 to -0.37), and UC ( SMD = -4.10, 95% CI was -5.71 to -2.49) in improving duration of mechanical ventilation in critically ill patients. COR was significantly better than UC in shortened length of ICU stay ( SMD = -5.72, 95% CI was -10.07 to -1.37). The efficacy ranking results showed that for duration of mechanical ventilation, the surface under the cumulative ranking curve (SUCRA) was highest for MV (85.4%) and EA (85.4%), followed by AA (74.9%), NMES (63.1%), ECR (51.7%), CS (48.8%), SACN (34.3%), COR (29.4%), EPR (26.1%), and UC (0.7%). For the length of ICU stay, COR had the highest SUCRA (82.3%), followed by APS (79.7%), MV (77.7%), EPR (68.0%), NMES (57.6%), CS (54.4%), ECR (51.1%), SACN (41.9%), MT (39.8%), EA (39.3%), AA (33.0%), VR (15.4%), and UC (9.8%). The funnel plot results of ICU stay showed that the publication bias between studies were relatively small. Conclusions:MV and COR appear to be effective interventions for reducing mechanical ventilation time and ICU stay in critically ill patients. However, due to the number and quality of included studies, these findings require confirmation through additional high-quality research.

Objective To explore the relationship between relationship between gastric juice pH,epidermal growth factor(EGF)and prostaglandin E2(PGE2)levels with the effectiveness of endoscopic treatment and gastrointestinal function in patients with gastric ulcer bleeding.Methods 67 patients with gastric ulcer bleeding who underwent digestive endoscopy treatment at Zhongnan Hospital of Wuhan University from January 2022 to May 2024 were selected.The levels of pH,EGF and PGE2 in gastric juice collected during endoscopic treatment of patients were detected.The effectiveness of disease treatment for patients was evaluated.The levels of gastric juice pH,EGF and PGE2 in patients with different therapeutic effects were copared,and the area under the ROC curve was used in the evaluation of gastric juice pH,EGF and PGE2 levels in early evaluation of treatment efficacy of digestive endoscopy treatment.The postoperative gastrointestinal function and recovery indicators such as bowel sound recovery time,anal exhaust time,hemostasis time,hospital stay time,and ulcer healing time for patients were selected,and the relationship between postoperative gastrointestinal function and recovery indicators with the levels of gastric juice pH,EGF and PGE2 were analyzed by Pearson correlation method and.Results The clinical treatment effectiveness rate of 67 patients with gastric ulcer bleeding was 71.64％(48/67).Compared with those of patients with effective treatment result,patients with ineffective treatment result had lower levels of gastric juice pH,EGF and PGE2(P＜0.05).The ROC curve analysis results showed that the levels of gastric juice pH,EGF and PGE2 have certain predictive value for the effectiveness of digestive endoscopy treatment,and the combined detection of the three had the best early evaluation efficacy.The postoperative recovery time of bowel sounds,anal exhaust time,hemostasis time,hospital stay time,and ulcer healing time of patients were(7.16±2.38)minutes,(26.96±6.41)hours,(20.66±4.37)hours,(4.52±1.16)days,and(23.14±4.18)days,respectively.The Pearson correlation analysis results showed that the levels of pH,EGF and PGE2 in gastric juice of patients with gastric ulcer bleeding were negatively correlated with postoperative gastrointestinal function and recovery indicators such as bowel sound recovery time,anal exhaust time,hemostasis time,hospital stay time,and ulcer healing time(P＜0.05).Conclusion The levels of gastric juice pH,EGF and PGE2 in patients with gastric ulcer bleeding are correlated with the effectiveness of endoscopic treatment,postoperative gastrointestinal function,and recovery time.They can be used as early evaluation reference indicators for the efficacy of endoscopic treatment of gastric ulcer bleeding patients.

The complex chemical composition and limited research ideas of traditional Chinese medicine （TCM） have led to the unclear material basis and mechanism of the medicinal effects， which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study， we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore， a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM， thus promoting the modern research and the innovative development of TCM.

ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics. MethodOn the basis of the previous in vitro screening study， we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge， the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids， a study of structure-activity omics was carried out to summarize the rules of their connection. ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo， involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain， and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction （PPI） and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine， and the core targets were prostaglandin endoperoxide synthase 2 （PTGS2）， glutamate receptor metabotropic 5 （GRM5）， estrogen receptor 1 （ESR1）， solute carrier family 6 member 4 （SLC6A4）， and fusion oncoproteins （FOS）. According to the differences of mother nucleus， the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories， including protoberberine， berberine， and aporphine， which had high binding affinities with PTGS2， GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine， appropriate substituents with hydroxyl， alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine， the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues， which greatly improves the binding affinity. ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma， and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E₂ （PGE₂） in the mouse model， showcasing a significant inhibitory effect on the inflammatory pain caused by PGE₂. Nine components and 39 targets of saikosaponins， as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out， and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction （PPI） analysis showed that the main active components of Bupleurum Radix were saikosaponins a， b₁， b₂， b₃， c， d， e， f， and v， and the key targets were fms-related receptor tyrosine kinase 1 （FLT1）， kinase insert domain receptor （KDR）， fibroblast growth factor 2 （FGF2）， vascular endothelial growth factor A （VEGFA）， and signal transducer and activator of transcription 3 （STAT3）. Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks， including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo， providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.