Objective To comprehensively analyze the effectiveness of exercise training-based respiratory rehabilitation therapy on patients with occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis"). MethodsLiterature on randomized controlled trials of exercise training-based respiratory rehabilitation therapy for pneumoconiosis patients published from the establishment of the database to July 2023 was retrieved from academic systems such as the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Database, and China Biology Medicine using bibliometrics method. The RevMan 5.4 software was used for meta-analysis of the selected literatures. Subgroup analysis was conducted to explore the source of study heterogeneity. The funnel plot method was used to test publication bias. Results A total of 55 articles were included, involving 2 436 pneumoconiosis patients in the experimental group and 2 405 pneumoconiosis patients in the control group. The result of random or fixed effect model showed that the six minutes walking distance, the total score of Short from Health Survey-36, forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), FEV₁/FVC, arterial partial pressure of oxygen of pneumoconiosis patients increased after respiratory rehabilitation therapy (all P<0.05), while the total score of the St. George's Respiratory Questionnaire and arterial partial pressure of carbon dioxide decreased compared with the conventional treatment (all P<0.05). The result of subgroup analysis showed that the total score of the St. George's Respiratory Questionnaire, FEV₁, and the index of arterial partial pressure of oxygen of pneumoconiosis patients was better in the rehabilitation treatment for ≥six months compared with those

Objective To observe the characteristics of infant biliary atresia(BA)missed diagnosis by ultrasound.Methods Data of 72 BA infants missed by ultrasound(false-negative,group A),72 BA infants accurately diagnosed by ultrasound(true-positive,group B)and 72 non BA infants(controls,group C)were retrospectively analyzed.Clinical and ultrasonic features were compared between each 2 groups.Logistic regression analysis was performed to screen the impact factors for diagnosing and missed-diagnosing of BA.Results There were significant differences of total bilirubin,direct bilirubin,gamma glutamyl transpeptidase(GGT)and glutamic-oxaloacetic transaminase(GOT)between group A and C,also of total bilirubin,direct bilirubin and GGT between group B and C(all P＜0.05).Significant differences of the incidences of small gallbladder,gallbladder wall rigidity,poor gallbladder contraction function and fibrous plaques in the hepatic hilum were found between group A and B,of undetected or cystic changes in the gallbladder,gallbladder wall rigidity,poor gallbladder contraction function,fibrous plaques in the hepatic hilum and hepatic hilum cysts were noticed between group A and C(all P＜0.05),as well as of undetected or cystic changes in the gallbladder,small gallbladder,gallbladder wall rigidity,gallbladder wall thickening,poor gallbladder contraction function and fibrous plaques in the hepatic hilum were detected between group B and C(all P＜0.05).There were significant differences of display rate of common bile duct between each 2 groups(all P＜0.05).The lower incidence of fibrous plaques in the hepatic hilum and poor gallbladder contraction function were an impact factors for missed diagnosis of BA(both P＜0.05),while higher GGT,higher incidence of fibrous plaques in the hepatic hilum and poor gallbladder contraction function were all impact factors for diagnosis of BA in group A(all P＜0.05).Conclusion Infant BA missed diagnosis by ultrasound had lower incidence of fibrous plaques in the hepatic hilum and poor gallbladder contractile function.Combining with clinical data was helpful for reducing ultrasonic missed diagnosis of BA in infants.

Objective:To investigate the independent and combined effects of maternal smoking during pregnancy and offspring genetic susceptibility on overall cancer mortality.Methods:Based on the United Kingdom Biobank ( n=419 228) data, the Cox proportional hazard regression model was used to estimate the effect of maternal smoking during pregnancy on offspring overall cancer (including 16 cancers in men and 18 in women) mortality and its combined effect and interaction with offspring genetic factors. Results:Maternal smoking during pregnancy was significantly associated with a 13% increased risk of overall cancer mortality in men [hazard ratio( HR)=1.13, 95% CI: 1.06-1.20] and 19% increased risk in women ( HR=1.19, 95% CI: 1.11-1.27). Participants with high genetic risk had the highest overall cancer mortality than those with low genetic risk (men: HR=1.42, 95% CI: 1.30-1.55; women: HR=1.38, 95% CI: 1.25-1.52). Compared with participants without maternal smoking during pregnancy and low genetic risk, those with maternal smoking during pregnancy and high genetic risk were associated with a 56% increased risk of overall cancer mortality in men ( HR=1.56, 95% CI: 1.37-1.77) and 59% in women ( HR=1.59, 95% CI: 1.39-1.83). Conclusion:Maternal smoking during pregnancy may increase offspring overall cancer mortality and more severe harm in individuals with high genetic risk.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Pancreatobiliary maljunction(PBM)represents a congenital anatomical abnormality of the pancreaticobiliary ductal system,frequently predisposing individuals to recurrent cholangitis and pancreatitis.Accumulating evidence indicates that PBM is a precancerous lesion,and PBM plays an important role in the development and progression of gallbladder cancer(GBC).GBC arising from PBM is designated as PBM-associated GBC.Consequently,early diagnosis and treatment of PBM is paramount in mitigating the risk of GBC.This review outlined the epidemiology and advancements in the diagnosis and management of PBM,along with the clinical features,underlying mechanisms,and therapeutic progressions pertaining to PBM-associated GBC,in order to underscore the clinical significance of early intervention in PBM,so as to reduce the incidence of PBM-associated GBC.

Objective:To investigate the efficacy of liver wedge resection and liver Ⅳb and Ⅴ segmentectomy for T2 gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 168 patients who underwent radical resection of T2 GBC in The First Affiliated Hospital of Xi′an Jiaotong University from January 2011 to December 2021 were collected. There were 59 males and 109 females, aged (65±10)years. Of 168 patients, there were 112 cases in T2a stage and 56 cases in T2b stage. Of 112 patients in T2a stage, 73 cases underwent liver wedge resection and 39 cases underwent liver Ⅳb and Ⅴ segmentectomy. Of 56 patients in T2b stage, 27 cases underwent liver wedge resection and 29 cases underwent liver Ⅳb and Ⅴ segmen-tectomy. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX proportional risk model was used for univariate and multivariate analyses. Results:(1) Clinical data analysis of patients undergoing different extent of hepatic resection for T2 GBC. There was no significant difference in gender, age, cholecystoli-thiasis, preoperative total bilirubin, carcinoembryonic antigen, CA19-9, CA125, incidental GBC, perineural invasion, microvascular invasion, pathological differentiation, histopathological subtypes, N staging, TNM staging between patients with T2a and T2b GBC who underwent different extent of hepatic resection ( P>0.05). (2) Prognostic analysis of T2 GBC patients undergoing different extent of hepatic resection. The 1-, 3- and 5-year cumulative disease-free survival rates of T2 GBC patients undergoing liver wedge resection were 78.0%, 60.1% and 51.4%, respectively, versus 86.8%, 80.0% and 68.0% of T2 GBC patients undergoing liver Ⅳb and Ⅴ segmentectomy, showing a significant difference between them ( χ2 =5.205, P<0.05). The 1-, 3-, and 5-year cumulative overall survival rates of T2 GBC patients undergoing liver wedge resection were 85.0%, 62.5%, and 55.1%, respectively, versus 92.6%, 81.6%, and 68.8% for T2 GBC patients undergoing liver Ⅳb and Ⅴ segmentectomy, showing a significant difference in cumulative overall survival rate between them ( χ2=4.351, P<0.05). The 1-, 3-, and 5-year cumulative disease-free survival rates of T2b GBC patients undergoing liver wedge resection were 70.4%, 45.9% and 39.2%, respectively, versus 89.7%, 71.3% and 54.0% of T2b GBC patients undergoing liver Ⅳb and Ⅴ segmentectomy, showing a significant difference between them ( χ2=5.047, P<0.05). The 1-, 3-, and 5-year cumulative overall survival rates of T2b GBC patients undergoing liver wedge resection were 81.5%, 53.2%, and 41.0%, respectively, versus 89.7%, 77.0%, and 60.7% of T2b GBC patients undergoing liver Ⅳb and Ⅴ segmentectomy, showing no significant difference in cumulative overall survival rate between them ( χ2=4.014, P<0.05). (3) Analysis of factors influencing prognosis of patients undergoing radical resection for T2 GBC. Results of multivariate analysis showed that CA19-9>39.0 U/mL, perineural invasion, N1 and N2 stage were independent risk factors influencing disease-free survival time of patients undergoing radical resection for T2 GBC ( hazard ratio=2.736, 3.496, 2.638, 17.440, 95% confidence interval as 1.195-6.266, 1.213-10.073, 1.429-4.869, 8.362-36.374, P<0.05). Liver Ⅳb and Ⅴ segmentectomy was an independent protective factor influencing disease-free survival time of patients undergoing radical resection for T2 GBC ( hazard ratio=0.418, 95% confidence interval as 0.230-0.759, P<0.05). CA19-9 >39.0 U/mL, perineural invasion, ⅡB stage, ⅢB stage and ⅣB stage of TNM staging were independent risk factors influencing overall survival time of patients undergoing radical resection for T2 GBC ( hazard ratio=2.740, 3.210, 2.037, 3.439, 24.466, 95% confidence interval as 1.127-6.664, 1.049-9.819, 1.004-4.125, 1.730-6.846, 10.733-55.842, P<0.05). Liver Ⅳb and Ⅴ segmentectomy was an independent protective factor influencing overall survival time of patients undergoing radical resec-tion for T2 GBC ( hazard ratio=0.476, 95% confidence interval as 0.261-0.867, P<0.05). (4) Analysis of postoperative complications in patients undergoing different extent of hepatic resection for T2 GBC. There was no significant difference in postoperative complications of patients with T2a and T2b GBC undergoing liver wedge resection or liver Ⅳb and Ⅴ segmentectomy ( P>0.05). Conclusions:Compared to liver wedge resection, liver Ⅳb and Ⅴ segmentectomy can effectively prolong the disease-free survival overall survival time of T2b GBC patients. There is no significant difference in the major complications. Liver Ⅳb and Ⅴ segmentectomy is an independent protective factor for prognosis of patients undergoing radical resection for T2 GBC.

Breast cancer is the most common malignant tumor among women worldwide,with incidence rates rising annually.The treatment of breast cancer has undergone significant transformations,evolving from an initial reliance on a single surgical approach to the incorporation of systemic therapy,and more recently,to subtype-specific therapy.Clinically,breast cancer is classified into luminal,HER2-positive,and triple-negative breast cancer(TNBC)based on the expression of hormone receptor(HR)and human epidermal growth factor receptor 2(HER2),with corresponding treatments including endocrine therapy,anti-HER2 targeted therapy,and chemotherapy.However,the current subtype-based treatment strategies lack personalization,with approximately 30%of patients still facing resistance and relapse.While the overall survival rate of patients with HER2-positive breast cancer has been steadily increasing,significant survival improvements have not been observed in patients with triple-negative and luminal breast cancer.To overcome the clinical bottleneck of"incomplete classification and imprecise treatment",the concept of"subtype-precise"therapy has emerged.This innovative approach involves further subclassification of existing subtypes to identify specific targets for precision treatment,characterized by broad population coverage and high specificity.Over the past decade,the multidisciplinary team at Fudan University Shanghai Cancer Center has established a comprehensive molecular portrait of Chinese Breast Cancer Genome Atlas(CBCGA).They deeply analyzed the molecular characteristics of TNBC,leading to the development of a"Fudan subtype"closely related to clinical outcomes:luminal androgen receptor subtype(LAR),which can be targeted with anti-HER2 and CDK4/6 inhibitors;the immunomodulatory subtype(IM),suitable for immunotherapy;basal-like immune-suppressed subtype(BLIS),which can be treated with platinum-based drugs or poly(ADP-ribose)polymerase(PARP)inhibitors;and mesenchymal-like subtype(MES),which can be treated with anti-cancer stem cell and anti-angiogenic therapies.The team then extended the concept of"subtype-precise"to luminal breast cancer,the subtype with the largest number,the highest proportion and the risk of recurrence for decades.They divided it into four molecular subtypes and proposing corresponding precision treatment strategies:canonical luminal subtype(SNF1),sensitive to endocrine therapy;immunogenic subtype(SNF2),amenable to immunotherapy;proliferative subtype(SNF3),treatable by CDK4/6 inhibitors;and receptor tyrosine kinase-driven subtype(SNF4),targetable with tyrosine kinase inhibitors.The team is currently conducting phase Ⅲ randomized controlled trials to further validate the"subtype-precise"therapy and promote the"subtype-precise"Fudan experience to enhance overall breast cancer treatment efficacy.Looking forward,the integration of emerging diagnostic tools,such as artificial intelligence,coupled with the continuous update of subtype-specific targets and targeted therapies,is expected to further refine and expand"subtype-precise"therapy.This approach holds great promises for enhancing patient prognosis and leading a new revolution in breast cancer treatment.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Polygonum cuspidatum polyketide synthase 1 (PcPKS1) has the catalytic activity of chalcone synthase (CHS) and benzylidene acetone synthase (BAS), which can catalyze the production of polyketides naringenin chalcone and benzylidene acetone, and then catalyze the synthesis of flavonoids or benzylidene acetone. In this study, three amino acid sites (Thr133, Ser134, Ser33) that may affect the function of PcPKS1 were identified by analyzing the sequences of PcPKS1, the BAS from Rheum palmatum and the CHS from Arabidopsis thaliana, as well as the conformation of the catalytic site of the enzyme. Molecular modification of PcPKS1 was carried out by site-directed mutagenesis, and two mutants were successfully obtained. The in vitro enzymatic reactions were carried out, and the differences in activity were detected by high performance liquid chromatography (HPLC). Finally, mutants T133LS134A and S339V with bifunctional activity were obtained. In addition to bifunctional activities of BAS and CHS, the modified PcPKS1 had much higher BAS activity than that of the wild type PcPKS1 under the conditions of pH 7.0 and pH 9.0, respectively. It provides a theoretical basis for future use of PcPKS1 in genetic engineering to regulate the biosynthesis of flavonoids and raspberry ketones.
Amino Acid Sequence ; Fallopia japonica/metabolism* ; Polyketide Synthases/chemistry* ; Acetone ; Mutagenesis, Site-Directed ; Flavonoids/metabolism* ; Acyltransferases/metabolism*