The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

Lung function serves as a clinical indicator reflecting respiratory system function,ai-ding in the diagnosis and monitoring of pulmonary diseases.Both genetic and environmental factors ex-ert significant influences on lung function.A comprehensive understanding of the role of genetic factors in lung function is crucial for gaining deeper insights into the regulatory mechanisms of lung function.In recent years,with the application of advanced technologies such as genome-wide association stud-ies,whole-exome sequencing,whole-genome sequencing,and epigenome-wide association studies,numerous genetic loci related to lung function have been identified.This review aimed to summarize the current research progress in genetics related to lung function,providing a reference for subsequent in-depth exploration of the pathological and physiological mechanisms affecting lung function.

Objective To determine the effects of cardiac resynchronization therapy at different pacing sites on electrocardiogram(ECG),left ventricular(LV)function and adverse events in elderly patients with heart failure(HF).Methods A total of 214 elderly HF patients admitted to our department between July 2021 and July 2024 were retrospectively recruited.According to different pacing sites in cardiac resynchronization therapy,they were divided into His bundle group(102 cases)and left bundle branch group(112 cases).Their grades of New York Heart Association(NYHA)cardiac function,duration of QRS complex,pacing parameters(pacing threshold,pacing perception,pacing resistance),cardiac function indicators,LV function,LV systolic synchrony[standard deviation of time to peak longitudinal strain,to peak radial strain and to peak circumferential strain(Tls-SD,Trs-SD and Tcs-SD)],and incidence of adverse events were compared between the two groups before and at 6 months after cardiac pacemaker implantation.Results In 6 months after surgery the left bundle branch group had significantly lower N-terminal pro-B-type natriuretic peptide level,smaller LV end-diastolic diameter and LV end-systolic diameter,decreased Tls-SD,Trs-SD and Tcs-SD,and shorter duration of QRS complex,but higher LV ejection fraction,cardiac index and cardiac output when compared with the His bundle group(P＜0.01).The incidence of adverse events was obviously lower in the left bundle branch group than the His bundle group(6.25％vs 15.69％,P＜0.05).Conclusion Left bundle branch pacing shows significant improvement for cardiac function in elderly HF patients,and can effectively maintain ECG stability and improve LV function.It is a safe and effective cardiac resynchronization therapy.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Objective:To investigate the prognostic value of 18F-FDG PET/CT-based habitat radiomics combined with stacking ensemble learning model in overall survival (OS) of patients with hepatocellular carcinoma (HCC). Methods:A total of 136 HCC patients (114 males, 22 females, age (55.3±10.4) years) who underwent 18F-FDG PET/CT before treatment between January 2018 and January 2023 were retrospectively analyzed. Eighty-five cases from Tianjin First Central Hospital and 51 cases from Tianjin Medical University Cancer Institute and Hospital were used as a training cohort and an external validation cohort, respectively. The tumor volume of interest (VOI) was delineated on PET and CT images, and a total of 4 habitats were segmented by using the Otsu algorithm, including PET high ∩ CT low, PET low ∩ CT low, PET high ∩ CT high, and PET low ∩ CT high. After the feature selection, a total of 36 stacking ensemble learning models were established, and the optimal model was selected based on the calculated concordance index (C-index). Moreover, a combined model was developed by integrating the optimal model with clinical information. The predictive efficacy of those models was assessed by time-dependent ROC curves. Results:The model based on PET high ∩ CT high habitat radiomics features with multilayer perceptron (MLP) classifier had the highest C-index (0.770) in the external validation cohort, and it was regarded as the optimal radiomics model. The combined model incorporating this model with clinical information achieved an improved C-index of 0.815 in the external validation cohort. The combined model outperformed the other models for OS prediction, with a time-dependent AUC of 0.919, 0.900, and 0.862 in predicting the 1-year, 2-year, and 3-year OS, respectively. Conclusions:18F-FDG PET/CT-based habitat analysis outperforms traditional radiomics in OS prediction for HCC patients. By integrating the optimal habitat model with the clinical model, the combined model is able to improve the predictive efficacy.

Objective To investigate the effect of triglyceride-glucose index(TyG)on the short-term prognosis of patients with initial acute ischemic stroke.Methods A total of 391 patients with initial acute ischemic stroke who were hospitalized in Kunshan Second People's Hospital and The Affiliated Suzhou Hospital of Nanjing Medical University from Jun.2020 to Jun.2023 were retrospectively included.According to the modified Rankin scale(mRS)scores at 90 d follow-up,they were assigned to good prognosis group(286 cases)or poor prognosis group(105 cases).Logistic regression and receiver operating characteristic(ROC)curve were used to evaluate the effect of TyG on the short-term prognosis of patients with initial acute ischemic stroke.Results Compared with the good prognosis group,the patients of poor prognosis group had older age,higher proportion of atrial fibrillation,higher levels of homocysteine,triglyceride,total cholesterol,low-density lipoprotein,and TyG,and higher National Institutes of Health stroke scale(NIHSS)score(all P＜0.05).Multivariate logistic regression analysis showed that age,homocysteine,TyG and NIHSS score were independent risk factors for poor prognosis in patients with initial acute ischemic stroke(all P＜0.05).ROC curve analysis showed that TyG combined with NIHSS score had good predictive value for poor prognosis of patients with initial acute ischemic stroke,and the area under curve value was 0.795.Conclusion The combination of TyG and NIHSS score is an independent influencing factor for poor short-term prognosis in patients with initial acute ischemic stroke.

BACKGROUND:Patch clamp technique has been developed for more than 40 years as the"gold standard"for the study of ion channels.However,the research content of scientific research institutions is relatively independent,and the existing research results are not systematically summarized,which leads to the phenomenon of high repeatability and weak innovation in the existing research.Therefore,it is urgent to make a comprehensive review of patch clamp technology to clarify the current research status,hot spots,and future development direction.OBJECTIVE:To summarize the research status and development trend of patch clamp technique in recent 10 years.METHODS:Publications on patch clamp technology from 2013 to 2023 were collected using the Web of Science core collection database.CiteSpace and VOSviewer software were used to quantify the number of publications and analyze the network of literature entries,including countries,institutions,journals,authors,keywords,highly cited literature,and co-cited references.RESULTS AND CONCLUSION:(1)In recent 10 years,the research in the field of patch clamp technology has gradually entered a stage of stable development.(2)China and the United States are the leading countries in this regard.The Chinese Academy of Sciences is an institution with core influence.Journal of Neuroscience is the main publication.Park,Won Sun team(Jeonbuk National University)and Chu,Li team(Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease)have made outstanding contributions in this field,but there is less collaboration and communication between the teams and no network cooperation model has been formed.(3)Patch clamp technology is mainly used in the electrophysiological characteristics of the nervous system and the pathological mechanism of the disease,which is the focus of researchers'continuous attention.(4)In the study of electrophysiological characteristics of cardiovascular system and its pathological mechanism,the electrophysiological characteristics of primary cardiomyocytes and induced pluripotent stem cell-derived cardiomyocytes and the pathological mechanism of atrial fibrillation,cardiotoxicity,sudden cardiac death,hypertension and other cardiovascular diseases have been the focus of research in recent years.(5)In the application of patch clamp technology combined with other biotechnology,it will be an important research direction to focus on the cross fusion with optogenetics,two-photon calcium imaging and other technologies.(6)In the research of drug screening and identification of therapeutic targets,especially the research of patch clamp technology and traditional Chinese medicine compound,it will become a great help in the future research of component traditional Chinese medicine.

Objective To explore the correlation between serum angiotensin-converting enzyme(SACE),matrix metalloproteinase-9(MMP-9)and haptoglobin(HPT)with pulmonary infection in patients with schizophrenia.Methods A total of 83 patients with schizophrenia were selected and divided into the infected group(40 cases)and the non-infected group(43 cases)according to whether they had pulmonary infection.Data of antipsychotic drugs,length of hospital stay,course of disease and electroconvulsive therapy were collected.Serum SACE,MMP-9 and HPT levels were detected by enzyme-linked immunosorbent assay.Spearman correlation analysis was used to determine serum SACE,MMP-9 and HPT and pulmonary infection in patients with schizophrenia.Logistic regression was used to analyze risk factors for pulmonary infection in patients with schizophrenia,and receiver operating characteristic(ROC)curves were used to evaluate the predictive value of serum SACE,MMP-9 and HPT in patients with pulmonary infection.Results Before treatment,the types of antipsychotic drugs≥2,the proportion of electroconvulsive therapy,serum SACE,MMP-9 and HPT levels were higher in the infected group than those in the non-infected group(P＜0.05).After treatment,there were no significant differences in serum SACE,MMP-9 and HPT levels between the infected group and the non-infected group(P＞0.05).Serum SACE,MMP-9 and HPT were positively correlated with pulmonary infection in patients with schizophrenia(P＜0.05).More than 2 types of antipsychotic drugs,electroconvulsive therapy and elevated SACE,MMP-9 and HPT were risk factors for pulmonary infection in schizophrenia patients(P＜0.05).The ROC curve analysis showed that the combined serum SACE,MMP-9 and HPT for pneumonia in schizophrenic patients were better than each of these indicators alone in predicting pulmonary infection in patients with schizophrenia.Conclusion Serum SACE,MMP-9 and HPT are related with pulmonary infection in patients with schizophrenia,and which can be used as potential indicators for predicting pulmonary infection in patients with schizophrenia.