BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

Glaesserella parasuis is the causative agent of Gl?sser's disease in pigs.However,the pathogenic mechanisms underlying its virulence is not yet fully understood.The RuvB protein,a member of the AAA+superfamily,is implicated in various cellular processes,yet its specific role in the virulence of Glaesserella parasuis has not been fully characterized.In this study,we con-structed a RuvB gene deletion mutant,designated ΔRuvB,using the serotype 13 Glaesserella pa-rasuis strain ZJ1208 and a suicide plasmid-mediated natural transformation approach.To elucidate the functional role of the RuvB gene,we comprehensively evaluated the biological characteristics of the ΔRuvB strain through a series of assays,including growth kinetics,colony morphology,bac-terial staining,transmission electron microscopy(TEM),osmotic stress tolerance,high-tempera-ture tolerance,heat shock resistance,UV resistance,capsular polysaccharide quantification,serum bactericidal assays,and murine virulence experiments.Our findings revealed that the growth rate of ΔRuvB showed no significant difference compared to the parental strain.TEM revealed a notable increase in bacterial cell length;however,the number of outer membrane vesicles(OMVs)on the surface of ΔRuvB did not significantly increase.Notably,the ΔRuvB strain displayed a significant reduction in capsular polysaccharide production and serum resistance,as well as diminished toler-ance to UV radiation and high temperatures.Significant alterations were observed in its resistance to osmotic stress or oxidative stress.In the mouse toxicity challenge experiment,in com-parison with the parental strain ZJ1208,the mortality rate dropped by 20 percentage points,suggesting that the virulence of ΔRuvB has been weakened to some extent.Collectively,these results underscore the critical role of the RuvB gene in enhancing the environmental adaptability of Glaesserella parasuis.

The aim of this paper was to investigate the serotypes,virulence factors and drug resist-ance of clinical isolates of Pasteurella rnultocida of porcine origin in recent years.Morphological screening and polymerase chain reaction(PCR)were used to isolate and identify 119 isolates from nasal swabs and lung tissue samples sent from swine farms in Zhejiang Province from 2010 to 2024.The isolates of Pasteurella multocida were subjected to capsular polysaccharide serotyping,lipopolysaccharide serotyping,virulence factor detection and drug resistance analysis by PCR and Kirby-Bauer disc agar diffusion method(K-B).The results showed that there were 64 strains(53.7％)of A-type,54 strains(45.3％)of D-type and 1 strain(0.9％)of F-type among the capsu-lar polysaccharide serotypes,and 10 strains(8.4％)of L1-type,20 strains(16.8％)of L3-type,86 strains(72.2％)of L6-type,and 3 strains(2.6％)of undetermined type among the lipopolysaccha-ride serotypes.The amplification results of 10 virulence genes showed that the detection rate of virulence genes hgbA,higbB and fimA was over 86.0％,the detection rate of toxA was 8.4％,while the virulence gene tbpA was not detected.There were also differences in the distribution vir-ulence genes in different capsular polysaccharide serotypes.Virulence factor pfhA was detected in type A and F but not in type D.The detection rate of adhesin gene tadD in serotype A(92.2％)was significantly higher than that of type D(9.3％),and,on the contrary,the detection rate of ad-hesin gene hsf-l in serotype D(90.7％)was significantly higher than that of type A(20.3％).Drug resistance analysis revealed that Pasteurella multocida showed high susceptibility to antimi-crobial drugs such as amoxicillin,ampicillin,cephalosporins,doxycycline,fosfenicol and ciprofloxa-cin,and showed strong resistance to antimicrobial drugs such as lincomycin,cotrimoxazole,genta-micin and amikacin,and there were 54 multi-drug resistant strains(78.3％).In summary,capsular polysaccharide serotypes were dominated by type A and D,lipopolysaccharide serotypes were dom-inated by L6,the distribution of some virulence genes varied greatly among different serotypes,and the proportion of multi-resistant strains was high,which provide reference for the prevention and control of this disease.

Glaesserella parasuis is the causative agent of Gl?sser's disease in pigs.However,the pathogenic mechanisms underlying its virulence is not yet fully understood.The RuvB protein,a member of the AAA+superfamily,is implicated in various cellular processes,yet its specific role in the virulence of Glaesserella parasuis has not been fully characterized.In this study,we con-structed a RuvB gene deletion mutant,designated ΔRuvB,using the serotype 13 Glaesserella pa-rasuis strain ZJ1208 and a suicide plasmid-mediated natural transformation approach.To elucidate the functional role of the RuvB gene,we comprehensively evaluated the biological characteristics of the ΔRuvB strain through a series of assays,including growth kinetics,colony morphology,bac-terial staining,transmission electron microscopy(TEM),osmotic stress tolerance,high-tempera-ture tolerance,heat shock resistance,UV resistance,capsular polysaccharide quantification,serum bactericidal assays,and murine virulence experiments.Our findings revealed that the growth rate of ΔRuvB showed no significant difference compared to the parental strain.TEM revealed a notable increase in bacterial cell length;however,the number of outer membrane vesicles(OMVs)on the surface of ΔRuvB did not significantly increase.Notably,the ΔRuvB strain displayed a significant reduction in capsular polysaccharide production and serum resistance,as well as diminished toler-ance to UV radiation and high temperatures.Significant alterations were observed in its resistance to osmotic stress or oxidative stress.In the mouse toxicity challenge experiment,in com-parison with the parental strain ZJ1208,the mortality rate dropped by 20 percentage points,suggesting that the virulence of ΔRuvB has been weakened to some extent.Collectively,these results underscore the critical role of the RuvB gene in enhancing the environmental adaptability of Glaesserella parasuis.

The aim of this paper was to investigate the serotypes,virulence factors and drug resist-ance of clinical isolates of Pasteurella rnultocida of porcine origin in recent years.Morphological screening and polymerase chain reaction(PCR)were used to isolate and identify 119 isolates from nasal swabs and lung tissue samples sent from swine farms in Zhejiang Province from 2010 to 2024.The isolates of Pasteurella multocida were subjected to capsular polysaccharide serotyping,lipopolysaccharide serotyping,virulence factor detection and drug resistance analysis by PCR and Kirby-Bauer disc agar diffusion method(K-B).The results showed that there were 64 strains(53.7％)of A-type,54 strains(45.3％)of D-type and 1 strain(0.9％)of F-type among the capsu-lar polysaccharide serotypes,and 10 strains(8.4％)of L1-type,20 strains(16.8％)of L3-type,86 strains(72.2％)of L6-type,and 3 strains(2.6％)of undetermined type among the lipopolysaccha-ride serotypes.The amplification results of 10 virulence genes showed that the detection rate of virulence genes hgbA,higbB and fimA was over 86.0％,the detection rate of toxA was 8.4％,while the virulence gene tbpA was not detected.There were also differences in the distribution vir-ulence genes in different capsular polysaccharide serotypes.Virulence factor pfhA was detected in type A and F but not in type D.The detection rate of adhesin gene tadD in serotype A(92.2％)was significantly higher than that of type D(9.3％),and,on the contrary,the detection rate of ad-hesin gene hsf-l in serotype D(90.7％)was significantly higher than that of type A(20.3％).Drug resistance analysis revealed that Pasteurella multocida showed high susceptibility to antimi-crobial drugs such as amoxicillin,ampicillin,cephalosporins,doxycycline,fosfenicol and ciprofloxa-cin,and showed strong resistance to antimicrobial drugs such as lincomycin,cotrimoxazole,genta-micin and amikacin,and there were 54 multi-drug resistant strains(78.3％).In summary,capsular polysaccharide serotypes were dominated by type A and D,lipopolysaccharide serotypes were dom-inated by L6,the distribution of some virulence genes varied greatly among different serotypes,and the proportion of multi-resistant strains was high,which provide reference for the prevention and control of this disease.

Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.

Objective:To study the efficacy of endoscopic papillary balloon dilatation (EPBD) in the treatment of non-dilated small choledocholithiasis.Methods:Clinical data of 142 patients with non-dilated small choledocholithiasis admitted to Zhanjiang Central People's Hospital from April 2021 to March 2023 were retrospectively analyzed, including 63 males and 79 females, aged (55.1±15.4) years old. Patients were divided into the EPBD group ( n=63) and endoscopic sphincterotomy (EST) group ( n=79). Blood amylase, liver enzymology, liver metabolism, and blood routine were monitored before and 48 hours after treatment. The occurrences of intraoperative bleeding, perforation, post-ERCP pancreatitis (PEP), and cholangitis were compared between the groups. Patients were followed up and screened for stone recurrence by outpatient review 3 to 12 months from discharge. Results:Compared to preoperative data, the white blood cell count, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bili-rubin, and direct bilirubin decreased 48 hours after treatment (all P<0.05). The operation time in EPBD group was slightly longer than that in EST group [(43.1±5.9) min vs. (38.5±4.5) min, P=0.064] without statistical significance. There were no case of perforation in both groups. The incidences of intraopera-tive bleeding [3.17%(2/63) vs. 6.33%(5/79)], PEP [17.46%(11/63) vs. 10.53%(8/79)], and postoperative cholangitis [4.76%(3/63) vs. 1.27%(1/79)] were comparable between the groups (all P>0.05). Conclusion:EPBD could be feasible for non-dilated small choledocholithiasis, which does not increase the operation time and incidence of adverse events compared to EST.

Drug-induced liver injury (DILI) with extrahepatic adverse drug reaction (EHADR) is the injury of extrahepatic organs which is caused by the same drug inducing liver injury and may occur simultaneously or successively with DILI, such as the skin, gastrointestinal tract, blood system, cardiovascular system, and bone and joint system, and it should be taken seriously in clinical practice. DILI with EHADR is not rare, and its pathogenesis may be associated with various factors including the physicochemical properties, distribution, metabolism, excretion, biological activity, and immunological properties of drugs, host genetic background, and underlying diseases. The diagnosis and treatment of DILI with EHADR is more challenging than that of DILI alone.

Objective: To investigate the impact of blood pressure and age on arterial stiffness in general population. Methods: Participants who took part in 2010, 2012 and 2014 Kailuan health examination were included. Data of brachial ankle pulse wave velocity (baPWV) examination were analyzed. According to the WHO criteria of age, participants were divided into 3 age groups: 18-44 years group (n=11 608), 45-59 years group (n=12 757), above 60 years group (n=5 002). Participants were further divided into hypertension group and non-hypertension group according to the diagnostic criteria for hypertension (2010 Chinese guidelines for the managemengt of hypertension). Multiple linear regression analysis was used to analyze the association between systolic blood pressure (SBP) with baPWV in the total participants and then stratified by age groups. Multivariate logistic regression model was used to analyze the influence of blood pressure on arterial stiffness (baPWV≥1 400 cm/s) of various groups. Results: (1)The baseline characteristics of all participants: 35 350 participants completed 2010, 2012 and 2014 Kailuan examinations and took part in baPWV examination. 2 237 participants without blood pressure measurement values were excluded, 1 569 participants with history of peripheral artery disease were excluded, we also excluded 1 016 participants with history of cardiac-cerebral vascular disease. Data from 29 367 participants were analyzed. The age was (48.0±12.4) years old, 21 305 were males (72.5%). (2) Distribution of baPWV in various age groups: baPWV increased with aging. In non-hypertension population, baPWV in 18-44 years group, 45-59 years group, above 60 years group were as follows: 1 299.3, 1 428.7 and 1 704.6 cm/s, respectively. For hypertension participants, the respective values of baPWV were: 1 498.4, 1 640.7 and 1 921.4 cm/s. BaPWV was significantly higher in hypertension group than non-hypertension group of respective age groups (P<0.05). (3) Multiple linear regression analysis defined risk factors of baPWV: Multivariate linear regression analysis showed that baPWV was positively correlated with SBP(t=39.30, P<0.001), and same results were found in the sub-age groups (t-value was 37.72, 27.30, 9.15, all P<0.001, respectively) after adjustment for other confounding factors, including age, sex, pulse pressure(PP), body mass index (BMI), fasting blood glucose (FBG), total cholesterol (TC), smoking, drinking, physical exercise, antihypertensive medications, lipid-lowering medication. (4) Multivariate logistic regression analysis of baPWV-related factors: After adjustment for other confounding factors, including age, sex, PP, BMI, FBG, TC, smoking, drinking, physical exercise, antihypertensive medication, lipid-lowering medication, multivariate logistic regression analysis showed that risks for increased arterial stiffness in hypertension group were higher than those in non-hypertension group, the OR in participants with hypertension was 2.54 (2.35-2.74) in the total participants, and same results were also found in sub-age groups, the ORs were 3.22(2.86-3.63), 2.48(2.23-2.76), and 1.91(1.42-2.56), respectively, in each sub-age group. Conclusion SBP is positively related to arterial stiffness in different age groups, and hypertension is a risk factor for increased arterial stiffness in different age groups. Clinical Trial Registry Chinese Clinical Trial Registry, ChiCTR-TNC-11001489.

Objective:To study the changes of oral health indexes in adolescent orthodontic patients under different brushing time, and to provide basis for the orthodontists to give effective dental health promotion in clinic.Methods:A total of 123 adolescent orthodontic patients were included, and they were divided into 1-3min, 3-5 min, 5-7 min and 7-10 min groups based on the brushing time recorded in the period of orthodontic treatment.The relationship between different brushing time and oral health indexes was evaluated 1,3,and 6 months after experiment, such as sulcus bleeding index(SBI),plaque index(PLI), debris index-simplified(DI-S) and enamel demineralization index(EDI).Results:Compared with 1-3 min and 3-5 min groups, the SBI, PLI, and DI-S of the patients in 5-7 min group were significantly reduced(P<0.05).There was no significant differences of SBI, PLI, DI-S , and EDI between 5-7 min group and 7-10 min group (P>0.05).Conclusion:Brushing teeth more than 5 min can improve the oral hygiene significantly and the best time is 5-7 min;the orthodontists should require the patients to brush teeth at least for 5 min.