In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

ObjectiveTo construct a cough model induced by chemical stimuli by whole-body plethysmography （WBP） for counting coughs based on cough waveforms， and use this model to explore the antitussive effect of GK-A. MethodDifferent chemical stimuli were used to induce coughs in mice or guinea pigs. Respiratory waveforms were monitored by WBP， and the recognizable and typical cough waveforms were selected for cough counting. Guinea pigs were induced to cough with different concentrations of citric acid or capsaicin， and cough waveforms were used to optimize the stimulation conditions. The optimized guinea pig model of cough was validated with dextromethorphan， and the optimized guinea pig model of capsaicin-induced cough was used to evaluate the antitussive effect of GK-A. ResultWBP could count the coughs induced by capsaicin and citric acid in guinea pigs by recognizable and typical respiratory waveforms. The optimized stimulation conditions were capsaicin concentration of 100 µmol·L^-1 and nebulization for 2 min. The validation results showed that compared with the model group， the dextromethorphan group of guinea pigs had reduced coughs （P<0.05） and prolonged cough latency （P<0.01）. GK-A prolonged the cough latency （P<0.05） and reduced coughs （P<0.05） in the mouse model of ammonia-induced cough. In the guinea pig model of capsaicin-induced cough， GK-A prolonged cough latency （P<0.05）， reduced coughs （P<0.05）， and decreased substance P （SP） content in the guinea pig serum （P<0.05， P<0.01）. ConclusionA guinea pig model of capsaicin-induced cough was successfully established based on cough waveform counting， which provided an objective and accurate cough counting method. GK-A has antitussive effects， possibly by inhibiting the neuropeptide SP.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

Objective To observe the protective effects of codonopsis pilosulae polysaccharide on lung tissues in mice with acute lung injury(ALI)induced by lipopolysaccharide(LPS)and its mechanism.Methods Fifty male Kunming mice were randomly divided into control group,model group,dexamethasone group,codonopsis polysaccharide high-dose group(300 mg/kg)and codonopsis polysaccharide low-dose group(150 mg/kg).The ALI model was established by intraperitoneal injection of LPS.All mice were given gavage administration according to the grouping except for the control group.0.3 s force expiratory volume(FEV 0.3)and force spirometry(FVC)and their ratios were measured using multiparametric lung function test system.The histopathology change of mouse lung was detected by hematoxylin-eosin(HE)staining,and the classification and count of inflammatory cells in alveolar lavage fluid(BALF)was detected by Richter-Giemsa staining.Levels of IL-1β,IL-6,MPO and TNF-α were measured by ELISA in BALF,and Western blot was used to detect the protein expression level of p-p38,p-IκB-α and p-p65.Results Compared with those in the control group,lung histopathological damage was more pronounced in the model mice,with significantly lower FEV 0.3,FVC,FEV0.3/FVC assay value,but signifi-cantly higher lung tissue wet mass/dry mass(W/D),neutrophils,lymphocytes,IL-1β,IL-6,MPO,TNF-α,p-p38 MAPK,p-IκB-α,and p-p65(P<0.05);while codonopsis pilosulae polysaccharide could significantly reverse these effects.Conclusion Codonopsis pilosulae polysaccharide plays a protective role against LPS-induced ALI via inhibiting MAPK/NF-κB pathway to reduce the pathological damage of lung tissue,and the level of inflammatory factors,thus to improve lung function in ALI model mice.

Objective To summarize and analyze the clinical diagnosis, surgical treatment and prognosis of multiple pulmonary nodules (MPNs). Methods The clinical data of lung cancer patients who received surgical treatment in our hospital from 2018 to 2020 were collected. The short-term efficacy of surgical treatment for MPNs was analyzed. Results A total of 97 patients were enrolled, including 30 males and 67 females with an average age of 56.1±10.0 years at onset ill. There were 62 patients with double lesions, 22 patients with three lesions, 4 patients with four lesions, and 9 patients with more than four lesions. A total of 213 lesions were surgically treated, including 88 pure ground-glass nodules, 81 partially solid nodules, and 7 solid nodules. There were 87 simultaneous surgeries and 10 staged surgeries, with an average operation interval of 5.2 months. The pathological combination type included adenocarcinoma-adenocarcinoma in 96 (99.0%) patients, squamous cell carcinoma-squamous cell carcinoma in 1 (1.0%) patient, and no lymph node metastasis was found. The 2-year disease-free survival (DFS) rate was 92.1%, and the overall survival (OS) rate was 100.0%. Univariate analysis showed that high-risk lesion size>2 cm (P=0.316), residual lesions (P=0.782) and pathological combination type (P=0.913) had statistical effect on the 2-year DFS rate. Conclusion MPNs are mainly diagnosed with multiple primary lung cancers, and the pathological combination is mostly adenocarcinoma-adenocarcinoma combination. Imaging examination is of great help to the surgical approach selection, diagnosis and differential diagnosis of MPNs. During the operation, maximal preservation of lung function and complete resection of high-risk nodules should be taken as the principle, and the prognosis is satisfactory.

This paper systematically combed and verified the name， origin， producing area， quality evaluation， harvesting， processing of Euryales Semen in famous classical formulas by consulting relevant ancient materia medica， medical books， prescription books and modern literature. The results showed that Euryales Semen was first collected by materia medica under the name of Jitoushi， and since the Ming dynasty， Qianshi has been used as a proper name and continues to this day， with other aliases such as Yanhuishi. Euryale ferox， a plant of the Nymphaeaceae family， is the same as that used in the past dynasties. However， due to long-term artificial domestication， the varieties vary with the origin， including Beiqian and Suqian. The medicinal part of Euryales Semen is mature seed kernel， its origin of ancient records mainly includes Shandong， Jiangsu， Henan and other places， since the Ming and Qing dynasties， Euryales Semen produced in Suzhou has been highly praised. Since modern times， it has gradually summarized and formed the best quality evaluation method of Euryales Semen with full grains， white cross-section， powdery enough and no broken powder. The harvesting time in the past dynasties was mainly August or in autumn. The main processing methods in the past dynasties included peeling for powder， pounding powder after steaming， drying and frying. Up to now， two mainstream processing methods of cleansing and stir-frying have been formed. Based on the research results， it is recommended that the mature seed kernel of E. ferox be used in famous classical formula Yihuangtang. Combined with the processing requirements of the original formula， it is suggested to refer to the stir-frying method in the general principles of processing of the current edition of Chinese Pharmacopoeia.

BACKGROUND:This study aims to explore whether Xuebijing(XBJ)can improve intestinal microcirculation dysfunction in sepsis and its mechanism. METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ+axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate)were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(P13K),phosphorylated P13K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt)in the small intestine was analyzed via Western blotting. RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total P13K,and p-Akt/total Akt in the rat small intestine. CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

Objective:To evaluate the quality of test papers and to analyze students'mastery of knowledge through the analysis of test papers,so as to provide reference for the reform of test proposition and correction teaching.Methods:Using paper analysis software(Ver 2.0),the paper quality,the students'scores and the answers to the questions of the final exam paper of Physiology of grade 2021 students majoring in nursing were analyzed.Results:The composition of the test paper was consistent with the requirements of the teaching programme,the difficulty of subjective and objective test questions was moderate,the differentiation of subjective test questions was good,the differentiation of objective test questions was general,and the reliability and validity were good.The overall performance was basically normal distribution.The full score ratio of objective test questions was higher than that of subjective test questions,and the zero score test questions were mostly concentrated in chapter 10 and chapter 4.Conclusion:Test paper analysis can feedback the problems and shortcomings of test paper proposition and teaching process,promote the quality of test paper and teaching model innovation,and improve the quality of teaching.