Objective To investigate the mechanism of Guizhi Fuling Pills in the treatment of polycystic ovary syndrome(PCOS)and endometriosis(EMT).Methods TCMSP was utilized to obtain the active ingredients and related targets of the constituent Chinese medicines of Guizhi Fuling Pills.GeneCards,PharmGKB,and TTD databases were used to screen PCOS and EMT disease targets,respectively.The Venn R diagram was drawn after obtaining the intersecting targets of drugs and diseases using the Venn R package in R software,the drug-active ingredient-potential target interactions network diagram was made in Cytoscape,the intersecting target protein-protein interactions(PPI)network diagram was drawn in the STRING platform,and Cytoscape was used to optimize the PPI network and screen the core targets.R language was applied for Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and AutoDockTools was for molecular docking.Results A total of 85 active ingredients and 191 corresponding targets of Guizhi Fuling Pills were obtained,and 77 potential targets of Guizhi Fuling Pills for the treatment of PCOS and EMT.The core active ingredients of Guizhi Fuling Pills for PCOS and EMT were quercetin,β-sitosterol,kaempferol,hederagenin,baicalein,and the core targets were AKT1,EGFR,IL-6,TNF,and TP53.GO functional analysis yielded 2 020 biological process,34 cellular components,126 molecular functions,and KEGG enrichment analysis yielded 165 signaling pathways.Molecular docking showed that the core components in the formula docked well with the targets.Conclusion Guizhi Fuling Pills may regulate the signaling pathways of lipid and atherosclerosis,AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,and chemical carcinogenesis-receptor activation through quercetin,β-sitosterol,kaempferol,hederagenin,and baicalein,and act on AKT1,EGFR,IL-6,TNF,and TP53,thus treating PCOS and EMT with homotherapy for heteropathy.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

ObjectiveTo investigate the clinical appropriateness and application value of the peroxidase （POD） method for the detection of unbound bilirubin （UB） in neonatal serum. MethodsHydrogen peroxide （0.33 mol/L） and three different final concentrations （0.019， 0.038， 0.075 μg/mL） of horseradish peroxidase （HRP） were added to standard bilirubin solution （1， 2， 3 μmol/L） to obtain a standardized HRP primary rate constant Kp. Then 25 μL of neonatal serum was diluted by 41.6 fold， and measured with 2.4 and 4.8 μg/mL HRP at 37 ℃ under the dark， to determine the UB concentration. The accuracy， precision， and stability of the methodology were validated. The clinical characteristics of 33 jaundiced neonates were collected， including total serum bilirubin （TSB）， indirect bilirubin （IDB）， albumin （ALB）， bilirubin to albumin molar ratio （BAMR）， etc. The experimental data were analyzed by Graphpad Prism 8.0. ResultsA standardized Kp of （7.20±1.08） mL·μg^-1·min^-1 was determined at pH 7.4±0.2， 37 ℃ in the dark. The HRP activity and UB concentrations remained stable at -20 ℃ for 3 weeks and a week， respectively. The mean intra-day and inter-day coefficients of variation of the serum samples with different UB concentrations were less than 10%. In this study， the UB concentrations in 33 jaundiced neonates （gestational age ≥35 weeks） were measured by the POD method in the range of （0.32～1.20） μg/dL， which was positively correlated with TSB， IDB and BAMR. Of the five infants whose UB concentrations measured more than 1 μg/dL， three received intensive phototherapy （60%）. ConclusionsThe POD method combined with a standard equipment spectrophotometer to detect serum UB concentrations in neonates is easy to operate， rapid to detect， and low cost. This method has good accuracy and precision， which is convenient for clinical implementation. Moreover， the measurement of serum UB may assist us in better management of neonatal jaundice in clinical practice.

Humans ; RNA-Binding Protein EWS/genetics* ; Histiocytoma, Malignant Fibrous/pathology* ; Oncogene Proteins, Fusion/genetics* ; Biomarkers, Tumor ; Cyclic AMP Response Element-Binding Protein/genetics*

Objective Asymptomatic carotid stenosis (ACS) is closely associated to the incidence of severe cerebrovascular diseases. Early identifying the individuals with ACS and its associated risk factors could be beneficial for primary prevention of stroke. This study aimed to investigate a machine-learning algorithm for the detection of ACS among high-risk population of stroke based on the associated risk factors.Methods A novel model of machine learning was utilized to screen the associated predictors of ACS based on 30 potential risk factors. The algorithm of this model adopted a random forest pattern based on the training data and then was verified using the testing data. All of the original data were retrieved from the China National Stroke Screening and Prevention Project (CNSSPP), including demographic, clinical and laboratory characteristics. The individuals with high risk of stroke were enrolled and randomly divided into a training group and a testing group at a ratio of 4:1. The identification of carotid stenosis by carotid artery duplex scans was set as the golden standard. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was used to evaluate the efficacy of the model in detecting ACS.Results Of 2841 high risk individual of stroke enrolled, 326 (11.6%) were diagnosed as ACS by ultrasonography. The top five risk factors contributing to ACS in this model were identified as family history of dyslipidemia, high level of low-density lipoprotein cholesterol (LDL-c), low level of high-density lipoprotein cholesterol (HDL-c), aging, and low body mass index (BMI). Their weights were 11.8%, 7.6%, 7.1%, 6.1%, and 6.1%, respectively. The total weight of the top 15 risk factors was 85.5%. The AUC values of the model for detecting ACS with training dataset and testing dataset were 0.927 and 0.888, respectively.Conclusions This study demonstrated that the machine-learning algorithm could be used to identify the risk factors for ACS among high risk population of stroke. Family history of dyslipidemia may be the most important risk factor for ACS. This model could be a suitable tool to optimize the clinical approach for the primary prevention of stroke.

Objective To investigate the changes of serum anti-schistosome antibody titers in schistosomiasis japonica pa-tients after treatment,in order to provide the evidence for formulating the schistosomiasis surveillance program in marshland and lake regions.Methods Upon prospective cohort study,the stool examination positive schistosomiasis patients and blood exami-nation positive suspected patients(the titer was more than 1:80,including 1:80)were selected as the research objects in Jian-gling County in 2014,and they received the 2-day praziquantel therapy.Half year,one year and two years after the treatment, their blood samples and fecal samples were collected for IHA anti-schistosome antibody detections and schistosome egg and mira-cidium detections. Results In 2014,the stool examination positives were 251,and the majority of them were over 41 years old,accounting for 93.23%(234/251);581 cases of high antibody titers were detected by the IHA method,and the majority of them were over 41 years old,accounting for 89.16%(518/581).Half year,one year and two years after the treatment,among the stool examination positives,the negative conversion rates of stool positives were 99.60%(250/251),100%(239/239)and 100%(234/234)respectively and the negative conversion rates of antibody positives were 21.91%(55/251),64.11%(156/239)and 76.89%(193/234)respectively.In the high antibody titer positives,the negative conversion rates were 38.04%(221/581),64.11%(359/560),and 77.86%(429/551)respectively,Half year,one year and two years after the treatment.There were statistically significant differences among the antibody negative conversion rates by χ2test(χ2=77.538,183.412,25.469 respectively,all P<0.001).The geometric mean values of antibody titers of different durations between 2 groups were analyzed by 2-independent-samples T test,and the geometric mean values of antibody titers between the 2 groups were different before the treatment(t=23.576,P<0.01),but the geometric mean values of antibody titers between the 2 groups were not different 6 months,1 year and 2 years after the treatment(t=-0.046,1.165, -0.132,P=0.964, 0.245,0.895 respectively). Conclu-sions The levels of serum anti-schistosome antibody degrade slowly in schistosomiasis japonica patients after the treatment, and the results of IHA tests cannot distinguish the current schistosome infection from previous schistosome infection.Therefore, it is necessary to develop the specific diagnostic technology for schistosome infection in order to meet the need of monitoring.

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.
Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Expression ; drug effects ; Hepatocytes ; drug effects ; metabolism ; Humans ; Liver ; drug effects ; injuries ; metabolism ; Liver Diseases ; drug therapy ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Pharmacology

Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) has been reported to be effective for local control of different-sized hepatocellular carcinomas. However, it is unclear if these benefits could also be applicable to different-sized liver metastases from gastrointestinal cancers. The aim of this study was to evaluate the outcomes of TACE combined with RFA for liver metastases from gastrointestinal cancers. In this study, we retrospectively analyzed clinical data of 19 consecutive patients who had a total of 26 liver metastatic lesions from gastrointestinal cancers and underwent RFA followed by first-time TACE treatment. The tumor recurrence, overall survival rate and procedure-related complications were evaluated. Moreover, patients' demographics and tumor characteristics were analyzed to determine their impact on the outcomes. The technical success of TACE plus RFA was achieved with 2 major procedure-related complications found. The mean follow-up was 21.3 months. The total 1-, 2-, and 3-year survival rate was 89.4%, 52.6%, and 35.1%, respectively. It was found that the tumor size and the ratio of enhancement area were significant factors that influenced the overall survival. In conclusion, patients with gastrointestinal cancer-derived liver metastatic lesions of smaller size and larger enhancement area are considered appropriate candidates for TACE plus RFA.
Ablation Techniques ; adverse effects ; Adult ; Aged ; Aged, 80 and over ; Chemoembolization, Therapeutic ; adverse effects ; Female ; Gastrointestinal Neoplasms ; pathology ; therapy ; Humans ; Liver Neoplasms ; secondary ; therapy ; Male ; Middle Aged ; Pulsed Radiofrequency Treatment ; adverse effects ; Survival Analysis

OBJECTIVETo investigate the correlation of patients with thrombosis or prothrombotic status with hyperhomocysteinemia (HHcy), activated protein C-resistance(APCR) and gene polymorphism of coagulation factor V.

METHODSThree hundred healthy voluteers were selected as controls, 223 cases of thrombosis (80 cases of cerebral infarction of CT, the MI of 82 cases of myocardial infarction, venous thrombosis of VTE 61 cases), 270 cases of patients with prothrombotic state (76 cases of pregnancy disease of PIH, 62 cases of chronic obstructive pulmonary disease (COPD), 60 cases of diabetes(DM) and 72 cases of cancer) were enrolled in this study. The plasma APCR and hyperhomocysteinemia were detected by APTT coagulation method and cycling enzyme method respectively, and restriction fragment length polymorphism(RFLP) were was used to detect the gene polymorphism of FV G1691-A, G1091-C and A1090-G in the patient and control groups.

RESULTSAPCR positive rate was 62.29% and 7.33%, and the positive hyperhomocysteinemia accounted for 68.42% and 10.00% respectively in the group of the patients with venous thrombosis and the normal control group. 3 cases of heterozygous FV gene mutations were found in the APCR-positive patients with venous thrombosis.

CONCLUSIONHHcy possitive rate of patients with venous thrombosis is signiticantly higher than that in control, the HHcy is one of the important causes resulting in thrombosis, the patients with venous thrombosis have proved to be with APCR, and the possitive APCR may be related with the coagulation factor V gene polymorphism.

OBJECTIVEFabry disease is a rare lysosome storage disease featuring X-linked recessive inheritance. The study was to explore potential mutations of alpha-galactosidase A (GLA) gene and their correlation with clinic manifestations in three Chinese pedigrees with Fabry disease.

METHODSAll exons and flanking sequences of GLA gene were amplified with PCR. Potential mutations were detected with bidirectional DNA sequencing. Correlation between particular mutations and clinic features were analyzed.

RESULTSA unreported missense mutation, c.797A>C (D266A) in GLA exon 5 was identified in pedigree 1. Also in exon 5, a missense mutation c.644A>G (N215S) was found in pedigree 2. In pedigree 3, a nonsense mutation c.355C>T (Q119X) was found in exon 2. The c.797A>C mutation was not detected in 200 unrelated male controls. The probands of pedigrees 1 and 3 had presented mainly with skin damage and chronic renal insufficiency, whilst the proband of pedigree 2 had presented with hypertrophic cardiomyopathy.

CONCLUSIONThe unreported c.797A>C (D266A) mutation is the sixth missense type mutation of the 266th codon of GLA gene, and all other 5 missense mutations reported previously had been confirmed to be responsible for Fabry disease. The c.797A>C mutation, not found in 200 unrelated male controls, may be the causative mutation in pedigree 1. The c.644A>G and c.355C>T mutations were first detected in Chinese patients. Variable phenotypes of Fabry disease may be in part attributed to the natures of particular mutations of GLA gene.

Adult ; Fabry Disease ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; alpha-Galactosidase ; genetics