Aim To study the active ingredients and mechanism of action of Xinkeshu tablets against myo-cardial ischemia by network pharmacology and ze-brafish model.Methods The anti-myocardial ische-mia activity of Xinkeshu tablets was evaluated by iso-prenaline hydrochloride(ISO)-induced zebrafish myo-cardial ischemia model and H2O2-induced H9c2 dam-age model.The active ingredients of Xinkeshu tablets were retrieved using databases such as TCMSP.The potential targets were predicted by PharmaMapper data-base.Myocardial ischemic disease targets were searched by OMIM database.The potential therapeutic targets of Xinkeshu tablets against myocardial ischemia were analyzed.GO and KEGG enrichment analysis were conducted on core targets.The active ingredients were verified by zebrafish and cell model.qRT-PCR was used to detect the expression of key targets.Re-sults Xinkeshu tablets could significantly alleviate ISO-induced pericardial edema and bradycardia.It al-so could increase sinus venous-bulb aortic(SV-BA)distance and improve the cell viability.The 30 poten-tial active ingredients of Xinkeshu tables mainly acted on 30 core targets,including ALB,AKT1 and MAPK1,to regulate 627 GO items,including protein phosphorylation,negative regulation of apoptosis and positive regulation of PI3K signal transduction.KEGG results showed that 117 signaling pathways,including PI3K/Akt,FOXO and Ras,exerted anti-myocardial ischemia effect.Salvianolic acid A,lithospermic acid,rosmarinic acid,salvianolic acid D,salvianolic acid B,ginsenoside Rg2,hyperoside,3'-methoxypuerarin,3'-hydroxypuerarin and ginsenoside Rg1 could alleviate ISO-induced zebrafish myocardial ischemia and im-prove the cell viability.Xinkeshu tablets could upregu-late the expression of genes such as ras and akt1,and downregulate the expression of genes such as mapk1 and mapk8.Conclusion The active ingredients,in-cluding salvianolic acid A in Xinkeshu tablets,exert anti-myocardial ischemia effects by targeting targets,such as AKT1,MAPK1,and regulating signaling path-ways,such as PI3K/Akt,MAPK and Ras.

Aim To disclose the subcellular localiza-tion,expression pattern,cellular physiological function and possible molecular mechanism of C12ORF56,a novel gene located at q14.2 of chromosome 12,in the pathogenesis of lung cancer.Methods ONCOMINE database was applied to investigate the mRNA level dif-fering of C12ORF56 between normal and lung cancer tissues.Analysis based on LinkedOmics,Metascape,String and GSEA database or tools provided indication of potential cellular physiological functions of C12ORF56 in the developing of lung cancer.C12ORF56 was knocked down via siRNA and the pro-liferation of NCI-H1073 cells were observed by EdU and CCK-8 assay.RT-qPCR was used to detect the ex-pression level of C12ORF56 of lung cancer cells on dif-ferent cycle phases.The core sequence regions of pro-moter affecting the transcription of C12ORF56 gene were analyzed by Jaspar online-tools and verified by dual-luciferase assay.Results C12ORF56 was highly expressed in lung cancer cells,especially in squamous cell lung cancer.C12ORF56 correlated with cell cy-cle,cancer immune,DNA replication.Knockdown of C12ORF56 reduced NCI-H1703 cell proliferation.Conclusion The up-regulation of C12ORF56 is in-volved in the development of lung cancer by enhancing lung cancer cell proliferation.

Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and＞0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8％were male.All patients had 30％-70％coronary stenosis.The consistency rate of QFR and FFR was 78.0％(n=184),and the Person correlation coefficient was 0.557(P＜0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P＜0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P＜0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95％CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95％CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P＜0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.

Confirmed cases of Lyme disease(LD)in Ji'an City,Jiangxi Province and the clinical manifestations and region-al distribution were assessed to provide a basis for timely diagnosis and treatment.In total,133 serum samples were collected from patients with suspected LD in Ji'an Central People's Hospital from December 2021 to August 2022.Serum antibodies a-gainst Borrelia burgdorferi were detected with a two-step testing process.In addition,a specific gene of B.burgdorferi in samples was identified by nested PCR.Sequencing analysis was conducted to confirm the positive samples.Overall,25(18.80％)serum samples were positive for B.burgdorferi nucleic acid and antibodies,which included 20(15.04％)positive for antibodies and 6(4.51％)positive for nucleic acids.The sequences of the 5S-23S rRNA gene spacer of 6 samples were con-sistent with the corresponding sequences of Borrelia yangtzensis and one of the six samples was also positive for antibodies.The 25 positive samples were collected from 9 counties in Ji'an City,with the majority in Jizhou District(44％).All positive patients may experience symptoms related to LD,including joint disorders,neurological disorders,infectious fever,der-matitis,and/or chest pain.The most common symptom was joint disorders(72％).Six cases positive for B.yangtzensis nucleic acids were mainly collected in the Jizhou District,of which four had joint lesions and two had infectious fever.This study confirms the existence of LD in Jiangxi Province,which may be the first confirmation of human infection with B.yan-gtzensis in southern China.Hence,doctors in this region should consider the possibility of LD for cases presenting with related symptoms.Although LD may occur in this region,further investigations and monitoring are warranted.

Objective:To analyze the clinical phenotype and gene mutation of a genetic coagulation factor Ⅻ(FⅫ)deficiency pedigree and explore the molecular pathogenesis.Methods:The activated partial thromboplastin time(APTT)and FⅫ activity(FⅫ:C)were detected by clotting method.The FⅫ antigen(FⅫ:Ag)was tested with ELISA.All exons and flanks of F12 gene were determined by Sanger sequencing.ClustalX-2.1-win,PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site,forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.Results:The APTT of the proband prolonged to 71.3 s.The FⅫ:C and FⅫ;Ag were decreased to 5％and 6％,respectively.There were two heterozygous missense mutations c.580G＞T and c.1681G＞A detected in exon 7 and exon 14 of F12 gene,resultingin p.Gly175Cys and p.Gly542Ser,severally.Proband's father carried the p.Gly175Cys heterozygous mutation,while mother,brother and daughter had the p.Gly542Ser heterozygous mutation.Software analysis showed that both Gly175 and Gly542 were conserved,the two mutations were harmful and when mutations had occurred,the corresponding sites affected the protein local structure.Conclusion:The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FⅫ deficiency pedigree.The p.Gly175Cys mutation has been detected for the first time in the world.

Objective:To explore the levels of regulatory T cells(Tregs)and cytokines IL-35,TGF-β and IL-10 in peripheral blood of hemophilia A(HA)patients with F Ⅷ inhibitor and their clinical significance.Methods:43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected,including 6 cases with F Ⅷ inhibitor and 37 cases without FⅧ inhibitor.In addition,20 healthy males who underwent physical examinations were selected as healthy controls.Flow cytometry was used to detect the levels of CD4+CD25+CD127-Tregs in peripheral blood of the HA patients and healthy controls,and ELISA assay was used to detect the expression levels of IL-35,TGF-β and IL-10 in serum,and their differences between different groups were compared.Results:Compared with the healthy control group,the level of Tregs in HA patients was decreased,and the level of Tregs in the FⅧ inhibitor positive group was the lowest,the difference was statistically significant(P＜0.05).There was no significant difference in the expression level of Tregs in HA patients of different severity levels.The serum IL-35,TGF-β,and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group,and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group(all P＜0.05).Conclusion:The decrease of Tregs,IL-35,TGF-β,and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective:To evaluate the diagnostic performance of radiomics model based on contrast-enhanced ultrasound(CEUS) in predicting pathological complete response(pCR) after neoadjuvant chemoradiotherapy(nCRT) in patients with locally advanced rectal cancer(LARC).Methods:One hundred and six patients with LARC who underwent total mesorectal excision after nCRT between April 2018 and April 2023 in the First Affiliated Hospital of Guangxi Medical University were retrospectively included, the patients were randomly divided into a training set of 63(14 pCR patients) and a validation set of 43(12 pCR patients) in a 6∶4 ratios. Radiomics features were extracted from the tumors′ region of interest of CEUS images based on PyRadiomics. Intra-class correlation coefficient(ICC), Mann-Whitney U test, and least absolute shrinkage and selection operator(LASSO) algorithms were used to reduce features dimension. Finally, 7 radiomics features relevanted to pCR were selected to construct an ultrasomics model using elastic network regression, based on the R language. A combined model was constructed by jointing clinical feature. The performance of the models was assessed with the area under the ROC curve(AUC). Results:The AUC of the ultrasomics model and the combined model was 0.695(95% CI=0.532-0.859) and 0.726(95% CI=0.584-0.868) respectively in the training set. The AUC of the ultrasomics model and the combined model was 0.763(95% CI=0.625-0.902) and 0.790(95% CI=0.653-0.928) respectively in the validation set. Both univariate and multivariate Logistic regression analyses showed that CA199( P<0.05) and ultrasomics score( P<0.001) could be an independent predictor of pCR after nCRT in patients with LARC. Conclusions:The CEUS-based radiomics scores has certain predictive value for whether LARC patients achieve pCR after nCRT, and may provide a non-invasive imaging biomarker for predicting LARC patients achieve pCR after nCRT.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.