Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective To construct a risk prediction model for liver cancer in patients with chronic hepatitis C based on seven different machine learning algorithms and select the optimal model. Methods A total of 236 patients with chronic hepatitis C were selected as the research subjects. Patients were divided into a case group and a control group according to whether liver cancer occurs. Prediction models were constructed based on seven machine learning algorithms including classification and regression tree, random forest, gradient boosting decision tree, extreme gradient boosting (XGBoost), logistic regression, K-near neighbor, and support vector machine. The Shapley additive explanations (SHAP) algorithm was used to interpret the best prediction model. Results Among the seven models, the XGBoost model had the best comprehensive prediction performance (accuracy of 0.933, sensitivity of 0.775, specificity of 0.960, area under the ROC curve of 0.956, F1 score of 0.764). The SHAP algorithm suggested that AFP, age, AST, diabetes, BMI, PLT, ALT, liver cysts, FIB-4, and gender contributed to the model decision and are the risk factors for liver cancer in patients with chronic hepatitis C. Conclusion This study develops an interpretable machine learning model based on the XGBoost algorithm, which has a good reference value for individualized monitoring of liver cancer in patients with chronic hepatitis C.

OBJECTIVE To identify and classify the chemical components and components absorbed into blood of Sishen Pills u-sing ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry.METHODS SD rats were divided into blank group and drug administration group.The rats in drug administration group were given water extract of Sishen Pills formula intragastrically,and blank and drug-containing plasma were collected respectively.A Hypersil GOLD VANQUISH column(2.1 mm×100 mm,1.9 μm)was used,with 0.1%formic acid water acetonitrile as the mobile phase,gradient elution,volume flow rate of 0.3 mL·min-1,and column temperature of 35℃.Electrospray ion source(ESI)with positive and negative ion scanning mode was used for chromatographic separation and mass spectrometry data acquisition.The chemical components of Sishen Pills were identi-fied by comparing the exact molecular mass,fragment ion information and relative retention time with the map of reference substance,matching with the self-established database and combining with literature reports.On this basis,the components absorbed into blood of Sishen Pills were analyzed by comparing the blank plasma and drug-containing plasma.RESULTS A total of 181 chemical compo-nents were identified from Sishen Pills,mainly including flavonoids,alkaloids,lignans and other components.A total of 49 prototype blood components were identified from the plasma samples,mainly including flavonoids,alkaloids and other components.CONCLU-SION A variety of chemical components in Sishen Pills and drug-containing plasma are comprehensively,accurately and quickly i-dentified,and all of them are assigned to the various medicinal materials in the prescription.This study provides reference for the qual-ity control,basic research on medicinal effect materials and clinical application of Sishen Pills.

Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

Objective To evaluate the effect of exercise-diet behavior intervention based on the transtheoretical model in patients undergoing weight loss surgery.Methods By convenience sampling,72 patients undergoing weight loss surgery in a tertiary general hospital in Xinxiang City,Henan Province from February 2021 to October 2022 were selected as the research subjects.By a random number table method,they were divided into a test group and a control group,with 36 cases in each group.The test group received exercise-diet behavior intervention based on the trans-theoretical model,while the control group received conventional intervention.The intervention began on the first day after admission and ended 6 months after surgery.The body mass index,body fat,lean body mass,diastolic blood pressure,systolic blood pressure,fasting blood glucose,insulin resistance index(HOMA-IR),Health Promoting Lifestyle Profile-Ⅱ(HPLP-Ⅱ)score,and Short-Form-36 Health Survey(SF-36)score were compared between the 2 groups before and after surgery for 3 and 6 months,as well as the complications within 6 weeks after surgery.Results The results of repeated measures analysis of variance showed that there was an interaction between the 2 groups in terms of anthropometric measurements,blood pressure and blood glucose,HPLP-Ⅱ scores,and SF-36 scores,with statistically significant differences(P＜0.001).After 6 months of surgery,the body mass index(23.32±2.32),body fat(24.10±3.46)kg,and lean body mass(41.64±3.24)kg in the test group were lower than(27.32±3.64),(28.46±4.18)kg,and(46.68±4.65)kg in the control group,and the differences were statistically significant(P＜0.001).At 3 and 6 months after operation,the diastolic blood pressure,systolic blood pressure,fasting blood glucose and HOMA-IR of the test group were lower than those of the control group,and the differences were statistically significant(P＜0.05).The HPLP-Ⅱ score of the test group was higher than that of the control group at 3 and 6 months after operation(P＜0.001).The SF-36 score of the test group was significantly higher than that of the control group at 6 months after operation(P＜0.05).The incidence of complications in the test group was 2.56％,which was not significantly different from 19.44％in the control group(P＞0.05).Conclusion The exercise-dietary behavior intervention based on the transtheoretical model can promote the formation of healthy behaviors in patients undergoing weight loss surgery,maintain weight loss effects,improve blood pressure and blood glucose levels,and enhance the quality of life of patients.

Chronic atrophic gastritis is a common and frequent disease in clinical practice. The symptoms of this disease can be attributed to the categories of " gastric pain" and " plumpness" in traditional Chinese medicine,and its pathogenesis is closely related to the dysfunction of xuanfu,qi-fluids,and stomach collaterals. In this study,we systematically rationalize the historical origin of the xuanfu,qi-fluids,and stomach collaterals and the relationship between them. According to the structure,physiological function and pathological characteristics of " xuanfu-qi-fluids-stomach collaterals",combined with the evolution of the chronic atrophic gastritis disease process,xuanfu depression and closure is believed to be the direct cause of chronic atrophic gastritis occurrence. The disharmony between qi and fluids is the core of the progression of chronic atrophic gastritis. Collateral deficiency and toxin damage are the root causes of the progression of chronic atrophic gastritis. Based on the mechanism of "xuanfu depression and closure-the disharmony between qi and fluids-collateral deficiency and toxin damage",it is proposed to open the xuanfu,restore the pivotal mechanism,activate blood circulation and diuresis,propagate qi and fluids,and supplement deficiency to unblock collaterals. From the perspective of "xuanfu-qi-fluids-stomach collaterals ",a more systematic and comprehensive understanding of the dynamic development process of chronic atrophic gastritis can be achieved,which will provide new ideas for the treatment of this disease in traditional Chinese medicine.

A clinically serious illness with a high death and morbidity rate is sepsis.Electro-acupuncture is a significant adjuvant treatment for sepsis,lowering the inflammatory response to sepsis,regulating the patient's immunological function,and preventing multi-system organ damage.However,no comprehensive study has been published.In order to review the clinical application of electro-acupuncture in the field of sepsis and its complications,analyze its clinical efficacy,and summarize effective acupuncture point prescriptions,we systematically compiled the clinical research literature on electro-acupuncture in the treatment of sepsis and its complications by searching PubMed,CNKI,and other databases.It was found that effective clinical evidence had been gathered for the administration of electro-acupuncture in uncomplicated sepsis as well as in sepsis aggravated by gastrointestinal,pulmonary,cardiac,and brain injury.The following successful acupoint prescriptions were indicated:①Simple sepsis was treated with"Zusanli+Guanyuan"or"Zusanli+Tianshu+Shangjuxu+Xiajuxu";②Combined gastrointestinal injury was treated with"Zusanli+Shangjuxu+Tianshu"or"Zusanli+Tianshu+Shangjuxu+Xiajuxu";③ Combined lung injury was treated with"Zusanli+Chize";④Combined myocardial injury was treated with"Neiguan+Zusanli+Shenmen+Taichong+Xuehai+Geshu+Sanyinjiao+Hegu";⑤Combined brain injury was treated with"Baihui+Shuigou".The study's findings can offer preliminary clinical direction for using electro-acupuncture to treat sepsis and associated complications in patients.

Mastering the structure,composition and working principle of digital subtraction angiography(DSA)equipment is an important prerequisite for medical engineers to carry out daily maintenance and repair management.By analyzing the structural composition and functional components of DSA from the aspects of X-ray source,mechanical drive,host control and image output,the working process of subtraction imaging was described according to Beer-Lambert law,and the influencing factors of DSA image quality were summarized.At the same time,taking the Allura XPer FD20 DSA equipment as an example,the failure cases of examination bed,rack and temperature control that occurred in clinical use were analyzed,and the fault investigation and processing were carried out from the hardware structure and circuit module of the equipment,and the equipment fault alarm information was solved in time to ensure the operation quality of the equipment and improve the efficiency of fault maintenance.

Objective To explore the role of intestinal sympathetic nerve in the improvement of obesity-related hypertension(OH)by carotid baroreceptor stimulation(CBS).Methods Twenty male SD rats were randomly divided into four groups:normal control(C-sham)group,OH-sham group,OH-CBS group and OH-6-OHDA-sham group,with 5 rats in each group.The OH model was in-duced by feeding with high-fat diet and 10％fructose water for 4 weeks.All rats were implanted with CBS stimulator at the end of the 4th week.The OH-CBS group received electrical stimulation,while the OH-sham,C-sham and OH-6-OHDA-sham groups received no stimulation.The OH-6-OHDA-sham group was intraperitoneally injected with 6-OHDA at the 6th week.Blood pressure and body weight of all rats were measured weekly.After 12 weeks,the weight of visceral fat was recorded,and serum glucose and lipid metabolism indexes were detected.Immunofluorescence staining was used to detect tyrosine hydroxylase(TH),mucin-2(MUC2),and zonula oc-cludens-1(ZO-1)in the ileum.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect MUC2,ZO-1 and interleukin-22(IL-22).Results Compared with the C-sham group,the OH-sham group had significant in-creases in blood pressure,the intestinal TH was overexpressed in OH-sham group(P＜0.05),blood pressure,body weight,visceral fat content,serum low-density lipoprotein,glucose,free fatty acid,triglyceride,and total cholesterol were significantly increased(P＜0.05),and serum high-density lipoprotein,IL-22,MUC2,and ZO-1 were decreased(P＜0.05).The TH overexpression was sig-nificantly reduced,the blood pressure,body weight,visceral fat content,serum low-density lipoprotein,glucose,free fatty acid,triglyc-eride,total cholesterol of OH rats were significantly decreased,the expression of serum high-density lipoprotein,IL-22,MUC2 and ZO-1 were also increased in OH-CBS group and OH-6-OHDA-sham group under high-fat and high-sugar feeding.Conclusion Intestinal sympathetic nerve plays an important role in the improvement of OH by CBS.

Objective To observe the clinical efficacy of dynamic joint mobilization combined with core stability training in the treatment of nonspecific low back pain.Methods 60 patients with nonspecific low back pain were randomly assigned into either the treatment group or control group.Each group had 30 patients.The treatment group received a therapeutic regimen combining dynamic joint mobilization and core stability training,while the control group only received core stability training.Both groups were evaluated for therapeutic effectiveness using the Visual Analogue Scale(VAS)for pain,the Oswestry Disability Index(ODI),and the range of motion(ROM)of the lumbar spine before treatment,and at the 1st,3rd,and 6th weeks after treatment.At the conclusion of the treatment,a thorough assessment of the overall therapeutic efficacy was performed.Results At the 1st,3rd,and 6th weeks post-treatment,both groups showed statistically significant differences in VAS scores,ODI scores,and ROM scores over time(P＜0.05).The improvements in these indices were significantly greater in the treatment group compared to the control group(P＜0.05).The treatment group had considerably higher therapeutic effective-ness compared to the control group(P＜0.05).Conclusions Dynamic joint mobilization combined with core stabil-ity training is effective in treating nonspecific low back pain.It can help with pain relief,lumbar and back function restoration,and lumbar and back mobility improvement.This approach is worthy of clinical application and promotion.