The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

Objective To establish and evaluate a nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer.Methods A retrospective study was conducted on 1298 patients with HBV-related primary liver cancer hospitalized in the Kunming Third People's Hospital from January 2012 to December 2022.General data and serological indicators were collected,and patients were divided into infection group(n=262)and control group(n=1036)based on the occurrence of spontaneous peritonitis.Univariate and LASSO regression analyses were used to screen variables,followed by binary logistic regression to analyze the influencing factors of spontaneous peritonitis in HBV-related primary liver cancer patients,leading to the establishment of a nomogram prediction model.Finally,the Hosmer-lemeshow(H-L)goodness of fit test,receiver operating characteristic(ROC)curve,calibration curve,decision curve analysis(DCA)and clinical impact curve(CIC)were utilized to evaluate the fit degree,accuracy,calibration,and clinical practicability of the nomogram prediction model.Results Single factor analysis revealed significant differences between infection group and control group in portal vein cancer thrombus(PVTT),Child-Pugh grade,China Liver Cancer Staging(CNLC)stage,alcohol consumption history,smoking history,white blood cell count(WBC),neutrophil count(NE),hemoglobin(Hb),fibrinogen(FIB),abnormal prothrombin(PIVKA-Ⅱ),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total protein(TP),prealbumin(PA),γ-glutamyltransferase(GGT),alkaline phosphatase(ALP),cholinesterase(CHE),total bile acid(TBA),total cholesterol(TC),low density lipoprotein(LDL),creatinine(Cr),HBV DNA,CD3+T cells count,CD4+T cells count,CD8+T cells count,CD4+T cells/CD8+T cells ratio,procalcitonin(PCT),serum amyloid A(SAA),interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP),alpha-fetoprotein(AFP),and IL-4(P＜0.05).LASSO regression analysis identified 5 variables:Child-Pugh grade,PVTT,WBC,CHE and hs-CRP.Binary logistic regression analysis indicated that Child-Pugh grade(Grade B:OR=5.780,95％CI 3.271-10.213,P＜0.001;Grade C:OR=14.818,95％CI 7.697-28.526,P＜0.001),PVTT(OR=2.893,95％CI 2.037-4.108,P＜0.001),WBC(OR=1.088,95％CI 1.031-1.148,P=0.002),and hs-CRP(OR=1.005,95％CI 1.001-1.010,P=0.026)were the independent risk factors of spontaneous peritonitis in HBV-related primary liver cancer patients.Using these 4 variables,a nomogram prediction model was constructed and evaluated.The P-value of the H-L goodness of fit test was 0.760.Moreover,the area under ROC curve(AUC)was 0.866,with a sensitivity of 0.870 and a specificity of 0.716.The average absolute error of the calibration curve is 0.022.DCA and CIC analyses demonstrated that the nomogram prediction model possessed some clinical utility.Conclusion The nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer patients,constructed using Child-Pugh grade,PVTT,WBC and hs-CRP,exhibits a high fitting degree and accuracy,with the prediction probability highly consistent with the actual occurrence probability,and possesses certain clinical practicability.

Objective To explore the clinical and genetic characteristics of children with holocarboxylase synthetase(HLCS)deficiency.Methods A retrospective analysis was conducted on the clinical data of 3 children with HLCS deficiency who were admitted to Children's Hospital Affiliated to Zhengzhou University from December 2014 to January 2024.Relevant literature indexed in CNKI,Wanfang Data,PubMed and other databases was reviewed to summarize the clinical characteristics and HLCS gene mutations of children with HLCS deficiency.Results All 3 children were male,with onset age of 4-6 months.The main clinical manifestations included shortness of breath,vomiting,diarrhea,and poor mental state,and partial cases were complicated by growth retardation and neurological symptoms.Laboratory tests showed metabolic acidosis in all cases,blood amino acid and acylcarnitine profiles as well as urinary organic acid analysis suggested multiple carboxylase deficiency.Genetic testing revealed compound heterozygous mutation in the HLCS gene of all 3 children,among which the c.1892delT(p.L631X)mutation was previously unreported.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG),the c.1892delT(p.L631X)mutation was rated as pathogenic mutation(PVS1+PM2_supporting+PM3).Biotin supplementation was effective in all cases.Literature review included 27 English literatures and 29 Chinese literatures,reporting a total of 133 children with HLCS deficiency caused by HLCS gene mutation.Common clinical manifestations included metabolic acidosis,skin lesions,vomiting,feeding difficulties,dyspnea,diarrhea,and neurological symptoms,etc.Conclusions Blood amino acid and acylcarnitine profiles,urine organic acid analysis,and gene testing are helpful for the diagnosis of HLCS deficiency.Timely biotin supplementation leads to a good prognosis.The mutation of HLCS gene is considered as the genetic etiology of HLCS deficiency in 3 children,among which the c.1892delT(p.L631X)mutation is a newly discovered mutation.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

Objective To investigate the clinical efficacy of percutaneous closure of foramen ovale guided by transthoracic echocardio-graphy with simply delivery sheath.Methods The clinical data of patients with patent foramen ovale underwent interventional closure and percutaneous closure guided by transthoracic echocardiography with simply delivery sheath in our hospital from January 2020 to December 2022 were analyzed retrospectively,the patients were divided into interventional closure group(40 cases)and simply delivery sheath group(39 cases).The operation time,incidence of surgical complications,and surgical success rates of patients in the two groups were compared.The closure effect were evaluated by ultrasound immediately after surgery.All the patients were followed up for 6 months after surgery to evaluate remission of the symptoms.Results The surgical success rate of simply delivery sheath group(100%)was higher than that of interventional closure group(90.0%),with statistically significant difference(P<0.05).The operation time of simply delivery sheath group was longer than that of interventional closure group,with statistically significant difference(P<0.05).One patient in the interventional closure group had small amount of pericardial effusion during the operation.Two patients had decreased blood pressure and slowed heart rate in simply delivery sheath group,and symptoms disappeared after treatment.There was no significant difference in the incidence of complications between the two groups(P>0.05).After 6-month follow-up,all occluders were in good position and no residual leakage was found.The symptoms of headache or dizziness disappeared in 28 patients in interventional closure group,significantly relieved in 8 patients;the symptoms of headache or dizziness disappeared in 30 patients in simply delivery sheath group,and significantly relieved in 9 patients.Conclusion Percutaneous closure for patent foramen ovale under the guidence of transthoracic echocardiography with simply delivery sheath is safe and feasible with satisfactory efficacy and higher successful rate without radiation hazard.It is worthy of clinical promotion.

Peroxisome proliferator-activated receptor gamma(PPAR-γ)is a member of the ligand-activated nuclear tran-scription factor superfamily.Activated PPAR-γ is involved in the regulation of many central nervous system(CNS)events,and is involved in cholesterol metabolism by inducing or inhibi-ting a series of gene pathways,thereby inhibiting the deposition of β-amyloid protein(Aβ).It plays an important neuroprotec-tive role in Alzheimer's disease(AD),improves memory and cognition in AD,and is a potential target for AD.Drug develop-ment aimed at restoring cholesterol homeostasis may be a poten-tial strategy to counteract AD.By analyzing the distribution and structure of PPAR-γ,focusing on the biological correlation be-tween PPAR-γ-mediated cholesterol metabolism and AD,this paper describes the mechanism regulation of PPAR-γ on key proteins,genes and their corresponding molecules,providing a new reference for the treatment of AD.

Objective:To investigate the current status of the use and management of medical devices in various primary medical and health institutions under hierarchical medical diagnosis and treatment.Methods:A stratified random cluster sampling method was used to select 450 medical personnel from 50 township and urban primary medical and health institutions of Shijiazhuang from May to August 2023 and a questionnaire network survey on the use and management of medical devices was conducted,which covered 16 items across three dimensions including the use of commonly used medical devices in primary medical institutions,maintenance and quality control management.Results:A total of 450 questionnaires were distributed and 450 valid questionnaires were collected,including 239 from township primary level medical institutions and 211 from urban primary level ones.According to the results of 211 urban primary level questionnaires,the proportions of the training and examination carried out by the medical staff of urban grass-roots medical and health institutions prior to the use of medical devices,understanding parameters of medical devices and timely detection of malfunction of medical devices were 62.6%(132/211),77.7%(164/211)and 70.1%(148/211),respectively,which were higher than those at the township primary level,the difference was statistically significant(x2=17.750,29.649,22.384,P<0.05).The proportions of urban primary medical and health institutions with maintenance system,inspection and maintenance standards,regular calibration provisions,and equipment calibration standards were 64.0%(135/211),53.6%(112/211),55.9%(118/211)and 55.0%(116/211),respectively,which were higher than those of the township primary level,the difference was statistically significant(x2=5.834,34.728,6.004,25.540,P<0.05).The difference was not statistically significant between urban primary level and township primary level in each item of quality control management(P>0.05).Conclusion:Primary medical and health institutions were required to strengthen training and assessment before medical and health personnel use medical devices;improve related system and standards for medical device maintenance;formulate quality control management system for commonly used medical devices;strengthen analysis and discussion processes after quality control,and promote continuous improvement of medical device quality management.

Objective:To explore the effects of hypoxia on traumatic brain swelling (TBS) in rats with acute subdural hematoma (ASDH).Methods:Forty-five SD rats were divided into 5 groups according to the random number table method, with 9 rats in each group: sham surgery normal oxygen group which underwent sham surgical procedures and were placed in a closed container with ventilation, sham surgery hypoxia group which underwent sham surgical procedures and were placed in a closed container with oxygen volume fraction of 8% for hypoxia induction, ASDH normal oxygen group which made into the ASDH model and placed in a closed container with ventilation, ASDH hypoxia group were made into the ASDH models and placed in a closed container with oxygen volume fraction of 8% for hypoxia induction, and ASDH hypoxia+oxygen inhalation group which inhaled oxygen continuously with oxygen volume fraction of 40% after being made into the ASDH models and induced for hypoxia. Six rats were selected from each group immediately after the modeling and craniotomy was performed to observe the brain swelling during the surgery and evaluate the degree of TBS. Microvascular blood flow was observed by laser speckle imaging system before modeling, before craniotomy, and immediately after craniotomy. The remaining 3 rats in each group were killed directly after modeling and brain tissue specimens were collected. The expression levels of pericellular protein α-smooth muscle actin (α-SMA) and platelet-derived growth factor receptor-β (PDGFR-β) at 0, 30 and 60 minutes after modeling were detected through Western blot analysis. The expression levels of α-SMA, PDGFR-β and microvascular marker platelet-endothelial cell adhesion molecule 31 (CD31) at 0 minute after modeling were tested through immunofluorescent staining.Results:No brain bulge was observed in the sham surgery normal oxygen group. The height of brain bulge in sham surgery hypoxia group was 0.5(0.0, 1.0)mm, with no significant difference from that in the sham surgery normal oxygen group ( P>0.05); it was 2.2(2, 2.5)mm in the ASDH normal oxygen group, significantly higher than that in the sham surgery normal oxygen group and sham surgery hypoxia group ( P<0.01), it was 3.1(2.9, 3.2)mm in the ASDH hypoxia group, significantly higher than that in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.01); it was 2.8(2.7, 2.9)mm in the ASDH hypoxia+oxygen inhalation group, not statistically different from that in the ASDH hypoxia group ( P>0.05), but significantly increased compared with that in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.01). Before modeling, before craniotomy and after craniotomy, the microvascular blood flow was 224.2±49.7, 224.8±50.3, 225.1±50.3 respectively in the sham surgery normal oxygen group and 224.7±43.7, 220.9±45.9, 221.8±45.5 respectively in the sham surgery hypoxia group, with no significant difference between the two groups ( P>0.05); it was 226.5±52.7, 173.4±40.7, 172.0±40.7 respectively in the ASDH normal oxygen group, significantly decreased compared with that in the sham surgery normal oxygen group and sham surgery hypoxia group ( P<0.05); it was 225.7±46.4, 131.4±23.6 and 131.0±23.5 respectively in the ASDH hypoxia group, significantly decreased compared with that in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.05); it was 226.2±56.1, 132.6±21.7 and 131.7±21.9 respectively in ASDH hypoxia+oxygen inhalation group, significantly decreased compared with that in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.05), with no significant difference from that in the ASDH hypoxia group ( P>0.05). At 0, 30 and 60 minutes after modeling, the expression levels of α-SMA and PDGFR-β were 0.70±0.02, 0.67±0.01, 0.55±0.05 and 0.65±0.03, 0.56±0.03 and 0.59±0.02 respectively in the sham surgery normal oxygen group and were 0.63±0.04, 0.60±0.01 0.55±0.05 and 0.62±0.01, 0.51±0.01 and 0.60±0.02 respectively in the sham surgery hypoxia group, with no significant difference between the two groups ( P>0.05); they were 0.88±0.06, 0.87±0.05, 0.82±0.03 and 0.85±0.03, 0.85±0.03, 0.88±0.04 respectively in the ASDH normal oxygen group, significantly higher than those in the sham surgery normal oxygen group and sham surgery hypoxia group ( P<0.01); they were 1.19±0.08, 1.10±0.10, 0.97±0.04 and 1.04±0.06, 1.19±0.07, 1.27±0.08 respectively in the ASDH hypoxia group, significantly higher than those in sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.05 or 0.01); they were 1.20±0.07, 1.10±0.04, 0.96±0.04 and 1.04±0.05, 1.15±0.11, 1.20±0.07 respectively in ASDH hypoxia+oxygen inhalation group, significantly higher than those in sham surgery normal oxygen group, sham surgery normal group and ASDH normal oxygen group ( P<0.01), but with no significant difference from those in ASDH hypoxia group ( P>0.05). At 0 minute after modeling, the fluorescence expression of α-SMA and PDGFR-β was weaker in the sham surgery normal oxygen group and the fluorescence expression of CD31 was stronger. There was no significant difference in the fluorescence expressions of α-SMA, PDGFR-β and CD31 between the sham surgery hypoxia group and sham surgery normal oxygen group. The fluorescence expressions of α-SMA and PDGFR-β in the ASDH normal oxygen group were stronger than those in the sham surgery normal oxygen group and sham surgery hypoxia group, while the fluorescence expression of CD31 was weaker. The fluorescence expressions of α-SMA and PDGFR-β in ASDH hypoxia group were stronger than those in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group, while the fluorescence expression of CD31 was weaker. The fluorescence expressions of α-SMA and PDGFR-β in the ASDH hypoxia+oxygen inhalation group were stronger than those in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group, while the fluorescence expression of CD31 was weaker, with no significant difference from the fluorescence expressions of α-SMA, PDGFR-β and CD31 in ASDH hypoxia group. Conclusions:Hypoxia in ASDH rats will stimulate pericytes contraction, which causes cerebral microcirculatory disturbance, thus leading to TBS. Short-term inhalation of oxygen of medium concentration cannot dilate pericytes or microcirculation vessels, with no obvious effect on improving the conditions of TBS.