Abstract:The diagnosis and treatment of aortic diseases has always been the focus of research in the cardio-vascular field.The small aortic annulus brings great challenges to the treatment of aortic diseases and is closely related to the poor prognosis of patients.At present,there is no consensus on the surgical treatment of small aortic annulus at home and abroad.For this special group,the existing treatment methods including aortic root enlargement,transcatheter aortic valve replacement,stentless biological valve,aortic-free valve and new technology have been developed to improve valve hemodynamics and clinical outcomes.However,there are controversies on the choice of treatment methods and valves,and there is also a lack of long-term clinical evidence for the application of new technology.The purpose of this review is to summarize the latest progress in surgical treatment of small aortic valve,and to explore the surgical treatment strategy and application prospect of new techniques for small aortic annulus.

Abstract:Objective To investigate the effect of compound Taxus capsule combined with vinorelbine+cisplatin(NP)regimen in the treatment of advanced non-small cell lung cancer(NSCLC)and its influence on tumor markers and immune function.Methods A total of 104 patients with advanced NSCLC admitted to Chinese People's Liberation Army Northern Theater General Hospital from June 2022 to January 2024 were prospectively selected.According to the random number table method,they were divided into observation group and control group,with 52 cases in each group.The control group was treated with NP regimen,and the observation group was treated with compound Taxus capsule on the basis of the control group.Both groups were treated for 6 courses.The clinical efficacy,tumor markers,immune function,quality of life and safety were compared between the two groups.Results The objective remission rate and disease control rate of the observation group were higher than those of the control group[38.5％(20/52)vs 19.2％(10/52)and 78.8％(32/52)vs 40.4％(21/52)](both P＜0.05).After treatment,the serum carcinoembryonic antigen,cytokeratin 19 fragment antigen and squamous cell carcinoma antigen in the observation group were lower than those before treatment,and those in the observation group were lower than those in the control group(all P＜0.05).After treatment,the levels of CD3+and CD4+and CD4+/CD8+ratio in the two groups were higher than those before treatment,and those in the observation group were higher than those in the control group,and the CD8+level was lower than that before treatment,and that in the observation group was lower than that in the control group(all P＜0.05).After treatment,the scores of the lung cancer quality of life scale in the observation group were higher than those in the control group(all P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The effect of compound Taxus capsule combined with NP regimen in the treatment of advanced NSCLC is satisfactory,which can reduce the level of tumor markers,improve the immune function of patients,and improve the quality of life of patients.

Abstract:Objective To investigate the changes and diagnostic value of serum neuropeptide FF receptor 2(NPFFR2),Zonulin and X-box binding protein 1(XBP1)in patients with preeclampsia(PE).Methods A total of 58 PE patients(PE group)and 59 healthy pregnant women(control group)in the First Affiliated Hospital of Harbin Medical University from December 2021 to December 2023 were selected as the research subjects.According to the clinical symptoms of PE patients,the PE group was divided into mild group(31 cases)and severe group(27 cases).The clinical data and serum indexes of the research subjects were compared.Multivariate Logistic regression was used to analyze the influencing factors of PE.The receiver operating characteristic curve was used to evaluate the value of serum NPFFR2,Zonulin and XBP1 in the diagnosis of PE.Results The serum levels of NPFFR2,Zonulin and XBP1 in the PE group were higher than those in the control group(all P＜0.05).Multivariate Logistic regression analysis showed that serum NPFFR2,Zonulin and XBP1 levels were influencing factors for PE(all P＜0.05).The area under the curve(AUC)of NPFFR2,Zonulin,and XBP1 in the diagnosis of PE were 0.789,0.798,and 0.801,respectively.The AUC of combined diagnosis of PE was 0.912,and the AUC of combined diagnosis was higher than that of individual diagnosis(all P＜0.05).The serum levels of NPFFR2,fibronectin and XBP1 in the severe group were higher than those in the mild group(all P＜0.05).Conclusion The serum levels of NPFFR2,Zonulin and XBP1 in PE patients are increased,and the combined diagnosis of PE has a high efficacy,which can assist clinical diagnosis.

Abstract:Objective To investigate the value of protocadherin alpha 4(PCDHA4)gene methylation detection in cervical cancer screening,and to provide a new method and basis for the early diagnosis of cervical cancer.Methods From September 2019 to June 2024,the cervical exfoliated cells of 186 female patients[included 90 cases of cervical intraepithelial neoplasia(CIN)grade 1(CIN 1 group),34 cases of CIN grade 2(CIN 2 group),28 cases of CIN grade 3(CIN 3 group),and 34 cases of cervical cancer(cervical cancer group)]and 52 healthy women(control group)who were treated in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected.Then the genomic DNA was extracted for human papilloma virus(HPV)detection and PCDHA4 gene methylation-specific PCR detection,and the diagnostic performance of PCDHA4 gene methylation detection in cervical cancer or precancerous lesions was analyzed.Results The positive rate of PCDHA4 gene methylation in CIN 3 and cervical cancer was significantly higher than that in CIN 2,CIN 1 and control group[89.3％(25/28),94.1％(32/34)vs 61.8％(21/34),36.7％(33/90),40.4％(21/52)],and the differences between the groups were statistically significant(all P＜0.05).The PCDHA4 △Ct in CIN 2,CIN 3 and cervical cancer group was significantly lower than that in CIN 1 and control group,and the difference between groups was statistically significant(all P＜0.05).The performance of PCDHA4 △Ct(when the cut-off was 6.34,the sensitivity was 64.6％,and the specificity was 91.5％)in the diagnosis of CIN grade 2 and above lesions was significantly better than of Thinprep cytologic test(TCT),HPV16/18,hrHPV and PCDHA4(all P＜0.05).The performance of PCDHA4 △Ct(when the cut-off was 5.45,the sensitivity was 74.2％and the specificity was 92.6％)in the diagnosis of CIN grade 3 and above lesions was also significantly better than that of TCT,HPV16/18,hrHPV and PCDHA4(all P＜0.05).PCDHA4 △Ct had better performance than TCT as a triage for non-16/18 hrHPV-positive women(all P＜0.05).Conclusions The detection of PCDHA4 gene methylation can serve as a potential biomarker for cervical cancer screening,which is helpful for the triage of hrHPV-positive population,and is of great significance for the early diagnosis of cervical cancer.

Abstract:Rheumatoid arthritis(RA)is a chronic,systemic autoimmune disease characterized by erosive arthritis.With the application of biological agents and targeted synthetic disease-modifying antirheumatic drugs,as well as the promotion of"treatment to target"strategy,the treatment of RA has made significant progress,and most patients can achieve disease remission or low disease activity.However,there are still a significant number of patients with persistent disease activity or refractory symptoms despite receiving multiple drug therapies with different mechanisms of action,which are called refractory RA or refractory inflammatory arthritis.In recent years,the European League against Rheumatism has proposed the concept and definition of refractory RA,which provides a clearer definition for this patient group.The refractory RA patient population is heterogeneous.The causes of persistent symptoms may include persistent inflammatory activity,and may also involve non-inflammatory factors,such as central sensitization,concurrent fibromyalgia,and psychological factors.In order to guide clinical diagnosis and treatment more accurately,some scholars have proposed that refractory RA should be further divided into persistent inflammatory refractory RA(PIRRA)and non-inflammatory refractory RA(NIRRA).The aim of this review is to systematically review the progress in the diagnosis and treatment of refractory RA,with a focus on the definition,characteristics,diagnosis,treatment and future research directions of PIRRA and NIRRA subtypes.

Abstract:Objective To investigate the effect of dapagliflozin combined with sacubitril/valsartan sodium on ventricular remodeling in patients with heart failure with reduced ejection fraction(HFrEF).Methods A total of 120 HFrEF patients admitted to Baotou Central Hospital of Inner Mongolia Autonomous Region from April 2023 to March 2024 were selected and divided into observation group(60 cases)and control group(60 cases)according to the random number table method.A double-blind,placebo-controlled design was adopted.Both groups received standard drug treatment.On this basis,the control group was treated with sacubitril/valsartan sodium+placebo,and the observation group was treated with sacubitril/valsartan sodium+dapagliflozin,with continuous treatment for 12 months.The clinical efficacy,ventricular remodeling and cardiac function[left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),interventricular septal end-diastolic thickness(IVST),early/late diastolic maximum flow velocity of mitral valve(E/A)],exercise capacity and quality of life[6 min walk test distance,minnesota living with heart failure questionnaire(MLHFQ)score],myocardial injury and myocardial fibrosis indexes[N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin I(cTnI),laminin(LN),procollagen Ⅲ peptide(PⅢP)],as well as serum levels of soluble suppression of tumorigenicity 2(sST2),pentraxin 3(PTX-3)and inflammatory indexes[C-reactive protein(CRP),interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)],and the incidence of clinical adverse events during treatment were compared between the two groups.Results The clinical effective rate of the observation group was higher than that of the control group[95.0％(57/60)vs 83.3％(50/60)](P=0.040).Compared with before treatment,after treatment,LVEDD,LVESD and IVST decreased,serum levels of NT-proBNP,cTnI,LN,PⅢP,CRP,IL-6,IL-1βand TNF-αreduced in both groups,with the observation group lower than the control group;LVEF and E/A increased,with the observation group higher than the control group(all P<0.05).Compared with before treatment,after treatment,6 min walk test distance increased and MLHFQ score decreased in both groups,with the observation group having longer walk distance and lower score than the control group(all P<0.05).Compared with before treatment,after treatment,serum sST2 and PTX-3 levels decreased in both groups[observation group:(19±4)μg/L vs(48±10)μg/L,(3.1±0.6)ng/L vs(5.8±0.9)ng/L;control group:(24±3)μg/L vs(48±8)μg/L,(3.6±0.7)ng/L vs(5.9±0.8)ng/L],with the observation group lower than the control group(all P<0.05).During treatment,there was no significant difference in the total incidence of cardiovascular adverse events between the two groups(P=0.752).Conclusion Dapagliflozin combined with sacubitril/valsartan sodium in the treatment of patients with HFrEF can effectively inhibit ventricular remodeling,reduce myocardial injury and inflammatory response,significantly improve cardiac function,and enhance exercise tolerance and quality of life.

Abstract:Objective To investigate the relationship between intraoperative hypotension load(HL)and 7 d postoperative composite adverse outcomes[MOFD-7,defined as the requirement for mechanical ventilation(invasive or non-invasive),hemodynamic support with vasoactive agents,or continuous renal replacement therapy on the 7th postoperative day,or death within 7 d after surgery]in patients undergoing open surgical repair(OSR)for ruptured abdominal aortic aneurysm(rAAA).Methods A retrospective analysis was conducted on 50 patients with rAAA who underwent OSR in Beijing Anzhen Hospital,Capital Medical University from August 2005 to November 2020.HL was defined as the cumulative area under the curve of mean arterial pressure(MAP)<65 mmHg(1 mmHg=0.133 kPa).Patients were divided into the non-MOFD-7 group(30 cases)and the MOFD-7 development group(20 cases)according to the occurrence of MOFD-7.Logistic regression analysis and receiver operating characteristic(ROC)curve were used to analyze the relationship between HL and MOFD-7,with MOFD-7 as the primary outcome.Results The incidence of MOFD-7 was 40.0％(20/50)among the 50 rAAA patients undergoing OSR,and the 30 d all-cause mortality was 10.0％(5/50),and all deaths occurred in the MOFD-7 development group.The proportion of preoperative hemorrhagic shock,preoperative serum creatinine and lactic acid levels in the MOFD-7 development group were significantly higher than those in the non-MOFD-7 group(all P<0.05).In terms of perioperative management,HL,norepinephrine equivalent,and the first postoperative lactic acid level in the MOFD-7 development group were significantly higher than those in the non-MOFD-7 group;intraoperative fluid infusion volume,intraoperative blood loss,and intraoperative blood transfusion volume(including intraoperative red blood cell transfusion volume and intraoperative plasma transfusion volume)in the MOFD-7 development group were significantly greater than those in the non-MOFD-7 group(all P<0.05).Multivariate Logistic regression analysis showed that after adjusting for age,gender,preoperative serum creatinine and preoperative lactic acid,HL(per 100 mmHg·min increase)was still independently associated with MOFD-7(odds ratio=1.298,95％confidence interval:1.034-1.630,P=0.025).The area under the curve of HL alone and the multivariate model for predicting MOFD-7 were 0.770 and 0.870,respectively.Restricted cubic spline analysis indicated an approximately monotonic increasing relationship between HL and the risk of MOFD-7;when HL exceeded approximately 75 mmHg·min,the risk of adverse outcomes increased significantly with further elevation of HL.Conclusion In patients undergoing OSR for rAAA,a higher intraoperative HL is associated with an increased risk of MOFD-7.Perioperative management should aim to minimize HL to improve early prognosis.

Abstract:Objective To investigate the species identification and drug resistance of non-tuberculous mycobacteria(NTM).Methods A total of 189 NTM isolates from 189 patients with NTM disease admitted to Hebei Chest Hospital from January 2021 to December 2023 were selected,and the species identification was carried out.The distribution of bacterial infection in patients with different genders and ages was analyzed,and the drug resistance of main NTM infected strains to common drugs was analyzed.Results Among the 189 NTM strains analyzed,the proportion of Mycobacterium intracellulare was the highest(52.9％),followed by Mycobacterium kansasii(22.2％),Mycobacterium abscessus(16.4％),Mycobacterium avium(5.3％),Mycobacterium gordonae(1.1％),Mycobacterium fortuitum(1.1％),Mycobacterium chelonae(0.5％)and Mycobacterium massiliense(0.5％).There were significant differences in the distribution of species in NTM patients with different genders and ages(both P＜0.001).The drug resistance rates of Mycobacterium intracellulare,Mycobacterium abscessus and Mycobacterium avium to isoniazid,rifampicin,ethambutol,streptomycin,kanamycin,capreomycin,p-aminosalicyl acid and ofloxacin were high,and the drug resistance rates of Mycobacterium kansasii to rifampicin and other drugs were low.Conclusions Mycobacterium intracellulare,Mycobacterium kansasii,Mycobacterium abscessus and Mycobacterium avium were common NTM strains in Hebei Chest Hospital.The distribution of NTM strains showed certain age and gender characteristics,and there were some differences in drug resistance among different NTM strains.It is necessary to strengthen the analysis of species distribution and drug resistance to guide clinical medication.

Abstract:Objective To investigate the correlation and diagnostic value of plasma trimethylamine oxide(TMAO)and its precursors with heart failure with preserved ejection fraction(HFpEF).Methods A total of 66 patients with chronic heart failure in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from August to December 2015 were selected as the research objects.According to the diagnostic criteria of heart failure,they were divided into HFpEF group(32 cases)and HFrEF group(34 cases).At the same time,40 patients with non-heart failure(NHF)admitted to our hospital during the same period were selected as the NHF group.The levels of TMAO,trimethylamine,choline,betaine and L-carnitine in plasma were detected by liquid chromatography-mass spectrometry.Combined with echocardiographic indicators and biomarkers,Pearson correlation analysis and receiver operating characteristic(ROC)curve were used to evaluate the diagnostic value of TMAO and its precursors for HFpEF.Results Compared with NHF group,the plasma levels of TMAO,trimethylamine and choline in HFpEF and HFrEF group were significantly increased,and those in HFpEF group were higher than HFrEF group(all P＜0.05).The level of L-carnitine in HFpEF group was significantly higher than that in NHF group(P＜0.05).There was no significant difference in betaine levels among the three groups(P＞0.05).Correlation analysis showed that TMAO level was positively correlated with tissue inhibitor of metalloproteinase-1(r=0.360,P＜0.05)and negatively correlated with estimated glomerular filtration rate(r=-0.449,P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of TMAO for the diagnosis of HFpEF was 0.812,the sensitivity was 90.6％,and the specificity was 67.5％.The AUC of trimethylamine in the diagnosis of HFpEF was 0.920,the sensitivity was 87.5％,and the specificity was 87.5％.The AUC of choline in the diagnosis of HFpEF was 0.941,the sensitivity was 87.5％,and the specificity was 97.5％.The AUC of L-carnitine in the diagnosis of HFpEF was 0.694,the sensitivity was 65.6％,and the specificity was 70.0％.Conclusion TMAO and its precursors(trimethylamine,choline,L-carnitine)are correlated with HFpEF and may be potential biomarkers for the auxiliary diagnosis of HFpEF,but their clinical application needs to be further verified.

Abstract:Objective To explore the role of spliceosome inhibitor combined with epigenetic remodeling drugs in myocardial reprogramming.Methods One-day-old C57BL/6J mice were divided into dimethyl sulfoxide(DMSO)group,CRFV(a core small-molecule drug for transdifferentiation,abbreviated as CRFV)group,and CRFV+PLaB(a spliceosome inhibitor)group,with 3 mice in each group.Mouse cardiac fibroblasts were extracted for transcriptome sequencing.The differentially expressed genes were analyzed based on P-value and expression change,and some differentially expressed genes were verified by real-time quantitative polymerase chain reaction.Functional enrichment analysis and signaling pathway enrichment analysis of significantly up-regulated and down-regulated genes were performed to reveal the functional regulation of drug treatment on fibroblasts,respec-tively.Results Transcriptome sequencing analysis showed that the heart-related genes Tnnt2,Actn2,Myh6,and Gata4 were significantly increased,and the fibroblast-related genes Col1a1,Col1a2,and S100a4 were significantly decreased in primary cardiac fibroblasts treated with combined drugs for 7 d.Enrichment analysis showed that up-regulated genes were closely related to actin filament formation and cell morphogenesis.Down-regulated genes were related to extracellular matrix formation and cardiac hypertrophy.Real-time fluorescence quantitative results showed that the expression of fibroblast-specific markers(Col1a1 and Col1a2)was decreased,and the expression of cardiomyocyte-specific markers(Tnnt2,Actn2,and Myh6)was significantly increased.Conclusion Spliceosome inhibitor and epigenetic remodeling drugs promote the reprogramming of cardiac fibroblasts into cardiomyocyte-like cells.

Abstract:M1 macrophages and T helper cell 17(Th17)play an important regulatory role in the immune microenvironment.Both of them have a profound impact on immune response,inflammatory response and the occurrence and development of autoimmune diseases.In recent years,with the in-depth understanding of the immune system,the study of M1 macrophages and Th 17 cells has gradually become a hot topic.However,there are still many unsolved mysteries in the specific mechanism,mutual regulatory relationship and clinical application of the two in different disease models.This article reviews the latest research progress of M1 macrophages and Th17 in the regulation of immune microenvironment,focusing on the mechanism of action of both in a variety of diseases,and discussing the limitations of current research and possible future research directions,in order to provide certain reference for future basic research and clinical immunotherapy.

Abstract:Objective To explore the combined effects of systemic immune-inflammation index(SII)and different obesity phenotypes on cardiometabolic comorbidity(CMM)in a physical examination population.Methods Based on the data of 5 036 participants who underwent physical examination in the Physical Examination Center of Xiyuan Hospital of CACMS from January 2020 to December 2024,their demographic data,physical examination and laboratory indicators were analyzed.SII was calculated and participants were divided into metabol-ically healthy non-overweight/obese(MHNO),metabolically healthy overweight/obese(MHO),metabolically healthy non-overweight/obese(MANO),and metabolically abnormal overweight/obese(MAO)according to metabolic status and body mass index.Multivariate Logistic regression analysis was used to explore the combined effect of SII and different obesity phenotypes on CMM.Restricted cubic spline(RCS)curve was used to explore the relationship between them,and odds ratio=1 was determined as the threshold.Results There were 395 CMM patients in 5 036 subjects(7.8％).The results of multivariate Logistic regression analysis showed that after fully adjusting for confounding factors,the MAO group had an increased risk of CMM compared with the MHNO group(P＜0.05),and the high SII group had an increased risk of CMM compared with the low SII group(P＜0.05).Compared with the low-SII combined MHNO group,both the low-SII combined MAO group and the high-SII combined MAO group showed a higher risk of CMM.After controlling for different confounding factors,the RCS curve showed a linear dose-response relationship between SII and the risk of CMM in MAO participants(P＜0.05),and the threshold of odds ratio=1 was 340.71.Conclusion High levels of SII and MAO are closely related to the risk of CMM.Special attention should be paid to MAO participants with SII＞340.71 to reduce the risk of CMM.

Abstract:Objective To explore the clinical effect of governor vessel moxibustion combined with Bushen Huoxue acupuncture in the treatment of postmenopausal osteoporosis of kidney deficiency and blood stasis type.Methods A total of 120 patients with postmenopausal osteoporosis of kidney deficiency and blood stasis type admitted to the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from October 2022 to December 2023 were selected,and they were divided into control group and study group according to the two-color ball method,with 60 cases in each group.Both groups received basic treatment and conventional western medicine treatment.The control group was additionally treated with Bushen Huoxue acupuncture,and the study group was additionally treated with governor vessel moxibustion on the basis of the control group.The clinical efficacy,quality of life,bone mineral density,bone metabolism,traditional Chinese medicine syndrome score,clinical symptoms and adverse reactions were compared between the two groups.Results The total effective rate of the study group was higher than that of the control group[91.7％(55/60)vs 76.7％(46/60)](x2=5.065,P=0.024).After treatment,the short form health survey scores,bone mineral density values of axial bone and distal 1/3 radius,serum total N-terminal propeptide of type Ⅰ collagen,bone morphogenetic protein and osteocalcin levels were higher than those before treatment in both groups,and those in the study group were higher than those in the control group(all P＜0.05).After treatment,the visual analogue scale score,Oswestry disability index score,β-collagen special sequence level and traditional Chinese medicine syndrome score of the two groups were lower than those before treatment,and those of the study group were lower than those of the control group(all P＜0.05).There was no significant difference in the total incidence of adverse reactions between the two groups(P＞0.05).Conclusions The combined application of governor vessel moxibustion and Bushen Huoxue acupuncture in the treatment of postmenopausal osteoporosis with kidney deficiency and blood stasis can effectively increase bone mineral density,improve bone metabolism,improve their quality of life,and reduce clinical symptoms.

Abstract:Exosomes are nanoscale membrane vesicles secreted by cells,which play a crucial role in cell communication and are involved in various physiological and pathological processes of the human body.Among them,exosomal microRNA-148 exerts an important regulatory effect on the occurrence and development of gastric diseases.This review summarizes the research on the regulatory mechanisms of exosomal microRNA-148 in common gastric diseases such as gastritis,gastric ulcer and gastric cancer,as well as the intervention effects of traditional Chinese medicine on it.It is found that exosomes can transfer biomolecules including DNA,coding RNA,non-coding RNA,lipids and proteins between cells,regulate related signaling pathways,and exert important values in the occurrence,development,diagnosis,treatment,prognosis and other aspects of various gastric diseases.In the prevention and treatment of gastric diseases,traditional Chinese medicine can also regulate the physiological and pathological processes of the body by affecting the secretion of exosomes and the expression of biomolecules such as non-coding RNA carried by them.This review aims to provide new ideas and theoretical basis for the treatment of gastric diseases.

Abstract:Coronary atherosclerotic heart disease and malignant tumors,as two major common chronic diseases,have an increasingly prevalent comorbidity,which severely impacts patient prognosis.This article systematically reviews the research progress on intervention strategies for coronary atherosclerotic heart disease complicated with malignant tumors,covering three key aspects:primary prevention,assessment and optimization of cardiovascular risks associated with cancer treatment,and long-term management of cancer survivors.It focuses on lifestyle and pharmacological interventions,the application of biomarkers and multimodal imaging technologies,management of cardiovascular toxicity induced by radiotherapy,chemotherapy,and targeted therapy,as well as multidisciplinary collaboration and perioperative strategies.Despite significant advancements,high-quality evidence-based medicine and standardized management pathways remain lacking in this field.This review aims to provide a comprehensive clinical reference for physicians and promote the standardized and individualized development of comorbidity management.

Abstract:Liver fibrosis is a key stage in the progression of chronic liver injury to cirrhosis.Its pathological mechanism mainly involves excessive deposition of extracellular matrix and abnormal activation of hepatic stellate cells.As an important homeostatic regulatory mechanism in cells,autophagy maintains cell function by degradation of abnormal components,but it shows cell type dependence in liver fibrosis.Inhibition of autophagy in hepatocytes leads to lipotoxicity,while excessive activation of autophagy in hepatic stellate cells promotes fibrosis.The phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)pathway is a key regulatory axis of autophagy,and its abnormal activation can destroy autophagic homeostasis and accelerate the process of fibrosis.Guishao Wujia decoction,as a traditional Chinese medicine compound,has shown multi-target regulatory potential in anti-liver fibrosis by its therapeutic principle of"fixing the middle Jiao,tonifying the liver and kidney,and removing blood stasis".Studies have shown that the compound can inhibit the activity of PI3K/Akt/mTOR pathway,up-regulate the expression of autophagy-related proteins(such as Beclin-1),enhance hepatocyte autophagy and inhibit the activation of hepatic stellate cells,thereby reducing extracellular matrix deposition.In addition,its components(such as panax notoginseng saponins,oyster oligopeptide and total gluco-sides of paeony)can reduce oxidative stress and inflammatory injury and improve liver pathological changes through anti-oxidation,anti-inflammation and multi-pathway synergistic action.This review systematically elaborated the dual role of autophagy homeostasis imbalance in liver fibrosis,and revealed the mechanism of autophagy regulation mediated by Guishao Wujia decoction through the PI3K/Akt/mTOR pathway.This review provides a molecular theoretical basis for the treatment of liver fibrosis with traditional Chinese medicine compound,which has important clinical transformation value.

Abstract:Objective To explore the effect of YZG-331 on pain threshold and sleep quality in a mouse model of pain and its potential mechanism.Methods Thirty-six male specific pathogen-free 8-week-old C57BL/6J mice were selected.They were randomly divided into sham operation group,operation group and observation group,with 12 mice in each group.In the sham operation group,the skin was only cut and sutured after disinfection with iodophor.In the operation group and the observation group,L4/L5 dorsal root ganglion was cut and scraped under microscopic conditions to establish a pain mouse model.The mice in the observation group were intraperitoneally injected with YZG-331 at a concentration of 10 mg/kg on day 1,2,and 3 after operation,and the solvent was sodi-um carboxymethyl cellulose.The mice in the operation group and the sham operation group were given the same vol-ume of sodium carboxymethyl cellulose.Patch clamp was used to detect neuronal electrical signals,and proteomics analysis,molecular docking and kinetic simulation electrophysiological experiments were performed to evaluate the activity of N-methyl-D-aspartate(NMDA)receptor and the mechanism of YZG-331 on it.Results YZG-331 significantly increased the prickling and thermal pain thresholds,improved sleep quality,and inhibited pain-induced abnormalities in brain electrical activity in mice.Proteomics sequencing,molecular docking and electrophysiological experiments showed that YZG-331 stably bound to NMDA receptors.The docking score of YZG-331 with NMDA was-4.742,and the result of generalized Born surface area analysis was-33.08 kcal/mol.It penetrated deep into the receptor active pocket and formed a variety of interactions with key amino acid residues to inhibit NMDA receptor-mediated neurotoxicity and regulate cellular excitability balance.Conclusion The present findings provide strong experimental evidence for YZG-331 as a potential therapeutic agent for pain and sleep disorders.

Abstract:Intermuscular adipose tissue(IMAT)is an ectopic fat deposited between skeletal muscles.It causes mitochondrial dysfunction by secreting a variety of bioactive substances,interferes with insulin signaling pathway,and eventually leads to insulin resistance(IR).A large number of studies have shown that IMAT is considered as a key factor affecting skeletal muscle and whole body insulin sensitivity due to its unique anatomical location and active metabolic function.The association is affected by many factors,such as age,gender,race and lifestyle.Lifestyle intervention,drug therapy and surgery can reduce IMAT and affect the occurrence and development of IR.Future studies need to further analyze the differentiation and secretion regulation mechanism of IMAT cells,promote its application in individualized efficacy prediction and non-invasive evaluation,and provide new targets for the prevention and treatment of IR.

Abstract:Objective To investigate the predictive value of serum long non-coding RNA(lncRNA)HOX transcript antisense RNA(HOTAIR)and small nucleolar RNA host gene 16(SNHG16)expression on coronary no-reflow(CNR)during percutaneous coronary intervention(PCI)in patients with acute myocardial infarction(AMI).Methods A total of 80 AMI patients who underwent PCI in Qingdao Municipal Hospital,Shandong Province from May 2020 to December 2023 were selected.According to the occurrence of CNR,AMI patients were divided into CNR group(18 cases)and coronary reflow group(62 cases).The serum levels of lncRNA HOTAIR and lncRNA SNHG16 were detected before PCI.The clinical data of the two groups were compared,and the influ-encing factors of CNR during PCI were analyzed.The receiver operating characteristic curve was used to analyze the value of lncRNA HOTAIR and lncRNA SNHG16 in predicting CNR in AMI patients during PCI.Results The time from onset to PCI ≥6 h,the proportion of lesion vessel length ≥20 mm,and the expression level of serum lncRNA SNHG16 in the CNR group were higher than those in the coronary reflow group,and the expression level of serum lncRNA HOTAIR was lower than that in the coronary reflow group(all P＜0.05).Logistic regression analysis showed that the length of diseased vessels ≥20 mm and high lncRNA SNHG16 were risk factors for CNR in AMI patients undergoing PCI,and high lncRNA HOTAIR was a protective factor for CNR in AMI patients undergoing PCI(all P＜0.05).The area under the curve of lncRNA HOTAIR and lncRNA SNHG16 in predicting CNR in AMI patients during PCI was 0.726 and 0.735,respectively,and the area under the curve of the combination of lncrna HOTAIR and lncrna SNHG16 was 0.947,which was higher than that of single prediction(Z=2.560,P=0.011;Z=3.035,P=0.002).Conclusion The decreased expression of lncRNA HOTAIR in AMI patients,and the increased expression of lncRNA SNHG16 is related to the CNR during PCI,which can be used as a marker to predict the CNR during PCI.

Abstract:Objective To explore the effects of ultrasonographic characteristics of the second stage of labor on delivery mode and pregnancy outcome of pregnant women with hypertensive disorders complicating pregnancy(HDCP).Methods A total of 106 pregnant women with HDCP who were hospitalized and delivered in Shaanxi Provincial People's Hospital from January 2023 to September 2024 were retrospectively selected as the research objects.The angle of fetal head progression(AOP),the distance between fetal head and perineum(HPD),and the distance between fetal head and pubic symphysis(HSD)were measured by intrapartum ultrasound during the second stage of labor.The delivery mode and pregnancy outcome were recorded.Multivariate Logistic regression was used to analyze the related factors affecting natural delivery in pregnant women with HDCP.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of AOP,HPD,and HSD for the delivery mode of pregnant women with HDCP.The differences of ultrasonographic characteristics of the second stage of labor among different delivery methods and different pregnancy outcomes were compared.Results A total of 67 women had natural delivery,15 women had assisted delivery,and 24 women converted to cesarean section.The AOP of the midwifery or cesarean section group was lower than that of the natural delivery group[(102±9)° vs(138±14)°],and the HPD and HSD were higher than those of the natural delivery group[(5.6±1.4)cm vs(3.1±0.6)cm,(2.52±0.42)cm vs(1.21±0.26)cm](all P＜0.05).The prolonged duration of the second stage of labor,large HPD and large HSD were risk factors for midwifery or cesarean section,and large AOP was a protective factor for natural delivery in pregnant women with HDCP(all P＜0.05).The critical values of AOP,HPD,and HSD in predicting the delivery mode of HDCP pregnant women were 125°,4 cm,and 1.5 cm,respec-tively,and the area under the curve was 0.780,0.761,and 0.744,respectively.The area under the curve of the combined prediction of the three was 0.915,which was greater than that of the individual prediction(all P＜0.05).The natural delivery rate of AOP＜125° group,HPD ≥4 cm group and HSD≥ 1.5 cm group was lower than that of AOP≥125° group,HPD＜4 cm group and HSD＜1.5 cm group,respectively(all P＜0.05).There were 12 cases of adverse pregnancy outcomes.The AOP of the poor pregnancy outcome group was lower than that of the good pregnancy outcome group,and the HPD and HSD were higher than that of the good pregnancy outcome group(all P＜0.05).Conclusion The reduce of AOP and the increase of HPD and HSD during the second stage of labor are related to the midwifery or cesarean section and adverse pregnancy outcomes of HDCP pregnant women.The combination of AOP,HPD and HSD can effectively predict the delivery mode of HDCP pregnant women.