Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.

Objective:To analyze the genetic variant and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia (MED).Methods:A MED pedigree which had presented at the Beijing Jishuitan Hospital Affiliated to Capital Medical University on September 13, 2020 was selected as the study subject. Clinical data of the pedigree were collected. Peripheral blood samples were drawn from pedigree members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variant was verified by Sanger sequencing. Wild type and mutant SLC26A2 expression plasmids were constructed and transfected into human primary chondrocytes. The effect of the variants on the protein localization and cell proliferation was determined by immunofluorescence and CCK8 assays. Results:WES and Sanger sequencing revealed that the proband has harbored compound heterozygous variants of the SLC26A2 gene, including a paternally derived c. 484G>T (p.Val162Leu) missense variant and a maternally derived c. 485_486delTG (p.Val162Glyfs*12) frameshifting variant. The SLC26A2 WT and its mutant SLC26A2 Val162Leu and SLC26A2 Val162Glyfs*12 expression plasmids were distributed in the nuclei and cytoplasm of human primary chondrocytes. Compared with SLC26A2 WT, the expressions of SLC26A2 Val162Leu and SLC26A2 Val162Glyfs*12 were decreased, along with reduced proliferation of human primary chondrocytes. Conclusion:The c. 484G>T and c. 485_486delTG compound heterozygous variants of the SLC26A2 gene may affect the proliferation of human primary chondrocytes and underlay the pathogenesis of MED in this pedigree.

Misuse of pyrrolizidine alkaloid (PA)-containing herbs is the major cause of hepatic sinusoidal obstruction syndrome (HSOS) in China. And diuretics are among the most commonly used medications for the treatment of PA-induced HSOS in clinical practice. As a traditional diuretic in traditional Chinese medicine, the diuretic mechanism of Alismatis Rhizoma (AR) has not been fully clarified, and there is no report on AR ameliorating PA-induced HSOS from a diuretic point of view. Therefore, this study aims to investigate the therapeutic potential of alisol B 23-acetate (AB23A) against acute liver injury induced by senecionine (a representative toxic PA) in mice, and to further elucidate its effect on impaired water-liquid balance in mice exposed to PA. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (Registration number: PZSHUTCM220808017). Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Model of mice was induced by a single oral exposure of senecioine (50 mg·kg^-1) (SEN group), and AB23A (40 mg·kg^-1) intervention group (AB23A+SEN group), solvent control group (Ctrl group) and AB23A control group (AB23A group) were set up. The results showed that AB23A could significantly attenuate the levels of serum biochemical indices of liver functions in senecioine-induced acute liver injury mice, as evident by alleviated hepatocyte necrosis and hepatic sinusoidal stasis. AB23A also improved kidney function of mice exposed to senecionine, fascinated urinary excretion and repaired electrolyte disorders, as well as decreased content of senecioine metabolites. Further, the protein and mRNA expression of genes related to the water balance pathway were measured. AB23A could significantly down-regulate the elevated protein and mRNA expression levels of aquaporin 2 (AQP2) and angiotensin II type 1 receptor, and inhibit the transport of AQP2 to the apical plasma membrane induced by senecionine exposure. AB23A also significantly decreased serum levels of angiotensin II. In vitro studies further confirmed that AB23A regulates AQP2 expression in renal inner medullary collecting duct cells 3 (IMCD3). These data indicate that AB23A regulates the expression of AQP2 in renal medulla, thereby affecting its water reabsorption in mice with senecionine-induced acute liver injury. This work achieves a better understanding of the diuretic effect of AR, and provides experimental foundation and theoretical basis for the treatment of PA-induced acute liver injury by AR in clinics.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To study the diagnosis,treatment,and complications of hypophosphatemic rickets(HR)in children,explore effectiveness evaluation indicators for the disease,and understand the pattern in height growth among these patients.Methods A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022.Results Among the 85 children with HR,there were 46 males(54%)and 39 females(46%).The age at initial diagnosis ranged from 6 months to 13 years and 9 months,with a median age of 2.75 years.The average height standard deviation score was-2.0±1.1.At initial diagnosis,children exhibited reduced blood phosphate levels and elevated alkaline phosphatase(ALP),with 99%(84/85)presenting with lower limb deformities.The positive rate for PHEX gene mutations was 93%(55/59).One year post-treatment,there was a significant reduction in ALP levels and the gap between the lower limbs(P<0.05).The fastest height growth occurred in the first year after treatment,at 8.23 cm/year,with a peak height velocity(PHV)phase lasting about two years during puberty.The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children.Major complications included nephrocalcinosis and hyperparathyroidism.The incidence rate of nephrocalcinosis in the first year after treatment was 55%(22/40),which increased with the duration of the disease(P<0.001);an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis(OR=1.740,P<0.001).The incidence of hyperparathyroidism in the first year after treatment was 64%(27/42).Conclusions For children presenting with lower limb deformities,short stature,and slow growth,early testing for blood levels of phosphate,calcium,and ALP,along with imaging examinations of the lower limbs,can aid in the early diagnosis of HR.Genetic testing may be utilized for definitive confirmation when necessary.ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR.Compared to normal children,children with HR demonstrate a lower height increase during the PHV phase,necessitating close follow-up and timely adjustment of treatment plans

Objective To describe the changing trend and related factors of prevalence rates of healthcare-associa-ted infection(HAI)in a tertiary hospital in the past 10 years,and analyze the influencing factors for HAI.Methods A cross-sectional survey on HAI was conducted for 10 consecutive years from 2013 to 2022(one day was selected as the survey day each year),data were collected.The distribution and related factors of prevalence rates of HAI were analyzed by trend-x2 test and Pearson correlation coefficient.Multivariate logistic regression and multilayer percep-tron(MLP)models were constructed to analyze the independent effect and significance of factors.Results From 2013 to 2022,the prevalence rates of HAI ranged from 4.66％to 8.07％in this hospital,showing a linear upward trend.The proportions of ICU patients and utilization rate of central venous catheters within 2 days before the sur-vey showed linear upward trends,while the proportion of patients with urinary catheters within 2 days before the survey and proportion of patients undergoing surgery within 30 days before the survey decreased.The MLP model revealed that the top 3 important factors for HAI were length of hospital stay＞10 days,admission in ICU,and in-dwelling central venous catheters within 2 days before the survey.Multivariate logistic regression model indicated that length of hospital stay＞10 days,indwelling central venous catheters or urinary catheters within 2 days before the survey,surgery within 30 days before the survey,and admission in ICU were independent influencing factors for HAI.Conclusion The incidence of HAI in this hospital presents a linear increase in recent 10 years,the causes should be further analyzed and the direction of intervention should be determined through targeted surveillance.Adopting trend test statistical analysis method,logistic regression,MLP multi-factor model can further explore the data value of HAI prevalence survey.

Objective To analyze the antimicrobial susceptibility,molecular types,serotypes,virulence factors and resistance mechanisms of Streptococcus agalactiae(S.agalactiae)isolated from pregnant women with ad-vanced maternal age in Tangshan City,and provide basic data for the treatment,prevention and control of S.aga-lactiae infection.Methods 42 strains of S.agalactiae isolated from pregnant women with advanced maternal age in North China University of Science and Technology Affiliated Hospital as well as Tangshan Maternal and Child Health Hospital were collected.Detection of antimicrobial susceptibility and whole genome sequencing of 13 antimi-crobial agents were performed.Results The percentage of tetracycline,erythromycin,levofloxacin,and chloram-phenicol concurrently resistant strains was 7.1％,35.7％of the strains presented multidrug resistance to erythro-mycin,clindamycin,and levofloxacin.The carriage rates of resistance genes ermB and tetM were 66.7％and 47.6％,respectively.29 strains(69.0％)exhibited mutations in both gyrA and parC fluoroquinolone resistance determi-nants.42 strains of S.agalactiae belonged to 4 serotypes,namely ⅠB(35.7％),Ⅲ(33.3％),Ⅴ(26.2％),andⅠA(4.8％);and 11 sequence types(STs),with the highest proportion being ST10(35.7％)and ST19(31.0％);as well as 6 clonal complexes(CCs),among which CC19(42.9％)and CC12(35.7％)had the highest proportion.All S.agalactiae carried virulence factor-encoding genes of cfb,cylE,and pavA.Conclusion The molecular types and serotypes of S.agalactiae carried by pregnant women with advanced maternal age in Tangshan City pre-sent polymorphism,with obvious multidrug resistance,and carry multiple types of drug resistance genes and viru-lence genes.