Objective To evaluate the intravascular volume at different levels of edema and disease course by the fractional excretion of filtered sodium(FeNa)of children with primary nephrotic syndrome(PNS).Methods A total of 172 children with newly diagnosed PNS who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2022 to September 2024 were selected and divided into non-e-dema group(n=51),mild edema group(n=43),moderate edema group(n=46)and severe edema group(n=32)according to the degree of edema at the time of admission.A total of 40 healthy children who underwent physical examination during the same period were selected as the healthy control group.Serum creatinine,ser-um sodium were detected before and after treatment.Urine samples were collected to detect urine creatinine,urine sodium,FeNa was calculated and compared according to the results,and the degree of edema was recor-ded.24 h urine samples were collected on the same day to detect 24 h urine protein quantification and 24 h u-rine volume.Results On day 1 to 2 of the course of the disease,about 12%of the PNS children had FeNa<0.2%,indicating insufficient intravascular volume,which was mainly concentrated in the severe edema group.The moderate,severe edema group had a significantly lower FeNa level than the non-edema group,mild edema group,and healthy control group(P<0.01).The moderate edema group had a significant increase in FeNa on days 6 to 7 of the course of the disease,and the severe edema group had a significant increase in Fena on days 11 to 12 of the course of the disease(P<0.01).Conclusion Intravascular volume of PNS children with mod-erate to severe edema is often reduced,and intravascular volume may be insufficient in severe edema.PNS chil-dren with moderate to severe edema have increased intravascular volume with the extension of the course of disease and the improvement of the condition.

The Chinese Pharmacopoeia 2025 Edition added the 9213 Guideline for validation,verification,and transfer of microbiological analytical methods.Based on the characteristics of pharmaceutical microbiological analyt-ical methods and practical applications,it specified definitions of relevant terms and application scenarios,estab-lished technical indicators and acceptance criteria for methodological evaluation,and introduced key statistical tools and evaluation principles.This article systematically elaborates on the drafting background and process of the Guideline,and interprets its key content,aiming to offer theoretical guidance and practical reference for relevant practitioners in applying this guideline.This guideline strengthens the foundation of pharmaceutical microbial analytical methods in China and enhances the scientificity and accuracy of the pharmaceutical microbial standards system.

The Chinese Pharmacopoeia 2025 Edition added the 9213 Guideline for validation,verification,and transfer of microbiological analytical methods.Based on the characteristics of pharmaceutical microbiological analyt-ical methods and practical applications,it specified definitions of relevant terms and application scenarios,estab-lished technical indicators and acceptance criteria for methodological evaluation,and introduced key statistical tools and evaluation principles.This article systematically elaborates on the drafting background and process of the Guideline,and interprets its key content,aiming to offer theoretical guidance and practical reference for relevant practitioners in applying this guideline.This guideline strengthens the foundation of pharmaceutical microbial analytical methods in China and enhances the scientificity and accuracy of the pharmaceutical microbial standards system.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveA rapid enrichment and detection method for Escherichia coli O157∶H7 was developed by using multienzyme isothermal rapid amplification （MIRA） fluorescence method combined with metal organic frameworks immunomagnetic beads. MethodsUsing rfbE gene as the target， the primers， probes and reaction system were screened， and the specificity， sensitivity and practical application of this method were investigated. ResultsThe detection limit of Escherichia coli O157∶H7 was 1.18×10⁵ CFU‧mL^-1， and the detection limit of DNA concentration was 9 pg‧μL^-1. The detection process was completed in 20 minutes. The test results of 47 strains （24 target strains and 23 non-target strains） were consistent with real-time PCR （RT-PCR）. ConclusionA method based on metal-organic framework immunomagnetic beads enrichment combined with MIRA assay is developed in this study. The method is simple， rapid and suitable for rapid enrichment and detection of Escherichia coli O157∶H7 in food.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective:To explore the effect of drug metabolism gene polymorphisms on blood concentration and safety of tacrolimus (TAC) in children with refractory nephrotic syndrome (RNS).Methods:The study was designed as prospective observational clinical study. The subjects were selected from the children with RNS who were hospitalized in Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from September 1, 2018 to August 31, 2019 and planned to receive TAC (first application) at the basis of glucocorticoids treatment. Clinical research files were formed and clinical conditions within 6 months of TAC treatment were recorded in detail for all subjects. The peripheral venous blood of all children was collected on the 7th day after TAC application for TAC blood trough concentration detection, and the TAC dose was adjusted according to the results. Blood samples were collected at the right time during hospitalization and gene polymorphisms of adenosine triphosphate binding cassette transporter B1 (ABCB1), cytochrome P450 (CYP) 2C19, CYP3A4, CYP3A5 and nuclear receptor subfamily 1, group I, member 2 (NR1I2) were detected. Children who completed 6 months of TAC treatment and follow-up were included. According to the genotype detection results, children were divided into wild-type group, heterozygous mutant group, and homozygous mutant group and first dose-adjusted blood trough concentration (C/D) of TAC were compared; they were divided into mutation carrier group (including heterozygous mutation carriers and homozygous mutation carriers) and wild-type group and the incidence of adverse reactions were compared.Results:A total of 39 children were included in the analysis, including 24 males and 15 females, aged 3 to 13 years with a median age of 8 years. The comparison results of the first C/D of TAC among various genotype groups showed that the TAC C/D in children of CYP2C19 homozygous mutant (*2*2) group was higher than that of wild-type (*1*1) group [3.65 (2.78, 7.43) μg/L vs. 1.53 (1.27, 3.33) μg/L, P=0.032], TAC C/D in children of CYP3A5 homozygous mutant (*3*3) group was significantly higher than those of the wild-type (*1*1) group and heterozygous mutation (*1*3) group [3.68 (3.05, 5.14) μg/L vs. 2.10 (0.77, 3.56) μg/L and 1.74 (1.47, 3.25) μg/L, P=0.046, P=0.009], and no significant differences were found in TAC C/D among different genotypes in CYP3A4, ABCB1, or NR1I2 (all P>0.05). A total of 7 children had adverse reactions within 6 months of TAC treatment (Naranjo′s assessment scale, "probable" in 2 children and "possible" in 5 children), including infection, rash, hypertensive encephalopathy, and convulsions in 4, 1, 1, 1 child, respectively. The incidence of adverse reactions in ABCB1 mutation carrying children (CT and TT) was significantly higher than that in children of wild-type (CC) group [30.4% (7/23) vs. 0 (0/16), P=0.033]. Conclusion:CYP2C19 and CYP3A5 gene polymorphisms have significant effects on TAC blood concentration, and ABCB1 gene polymorphisms have significant effects on the safety of TAC application, which should be noticed in clinic.

Objective:To explore the effect of drug metabolism gene polymorphisms on blood concentration and safety of tacrolimus (TAC) in children with refractory nephrotic syndrome (RNS).Methods:The study was designed as prospective observational clinical study. The subjects were selected from the children with RNS who were hospitalized in Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from September 1, 2018 to August 31, 2019 and planned to receive TAC (first application) at the basis of glucocorticoids treatment. Clinical research files were formed and clinical conditions within 6 months of TAC treatment were recorded in detail for all subjects. The peripheral venous blood of all children was collected on the 7th day after TAC application for TAC blood trough concentration detection, and the TAC dose was adjusted according to the results. Blood samples were collected at the right time during hospitalization and gene polymorphisms of adenosine triphosphate binding cassette transporter B1 (ABCB1), cytochrome P450 (CYP) 2C19, CYP3A4, CYP3A5 and nuclear receptor subfamily 1, group I, member 2 (NR1I2) were detected. Children who completed 6 months of TAC treatment and follow-up were included. According to the genotype detection results, children were divided into wild-type group, heterozygous mutant group, and homozygous mutant group and first dose-adjusted blood trough concentration (C/D) of TAC were compared; they were divided into mutation carrier group (including heterozygous mutation carriers and homozygous mutation carriers) and wild-type group and the incidence of adverse reactions were compared.Results:A total of 39 children were included in the analysis, including 24 males and 15 females, aged 3 to 13 years with a median age of 8 years. The comparison results of the first C/D of TAC among various genotype groups showed that the TAC C/D in children of CYP2C19 homozygous mutant (*2*2) group was higher than that of wild-type (*1*1) group [3.65 (2.78, 7.43) μg/L vs. 1.53 (1.27, 3.33) μg/L, P=0.032], TAC C/D in children of CYP3A5 homozygous mutant (*3*3) group was significantly higher than those of the wild-type (*1*1) group and heterozygous mutation (*1*3) group [3.68 (3.05, 5.14) μg/L vs. 2.10 (0.77, 3.56) μg/L and 1.74 (1.47, 3.25) μg/L, P=0.046, P=0.009], and no significant differences were found in TAC C/D among different genotypes in CYP3A4, ABCB1, or NR1I2 (all P>0.05). A total of 7 children had adverse reactions within 6 months of TAC treatment (Naranjo′s assessment scale, "probable" in 2 children and "possible" in 5 children), including infection, rash, hypertensive encephalopathy, and convulsions in 4, 1, 1, 1 child, respectively. The incidence of adverse reactions in ABCB1 mutation carrying children (CT and TT) was significantly higher than that in children of wild-type (CC) group [30.4% (7/23) vs. 0 (0/16), P=0.033]. Conclusion:CYP2C19 and CYP3A5 gene polymorphisms have significant effects on TAC blood concentration, and ABCB1 gene polymorphisms have significant effects on the safety of TAC application, which should be noticed in clinic.

In this study, a new medical microbiology experiment teaching system, which was based on outcome-based education combined with inquiry-based teaching model, was developed and evaluated. According to the professional requirements of doctors, the objectives of emotion and comprehensive experimental ability were added, and the requirement for experimental operation skills was raised. In accordance with the concept of inquiry-based teaching, experimental contents were reorganized, and practical operation contents and comprehensive analytical experiments were increased to facilitate students' abilities of independent thinking and innovation. In addition, the proportion of microbiology laboratory examination was increased, experimental skill examination was focused, the assessment method was reformed, and extracurricular interest groups were established to deepen the learning. The teaching effect was evaluated by questionnaire, performance and follow-up survey. The result showed that the new model increased the students' course scores, improved their capability in innovation, academic writing and clinical working, and strengthened the weakness of traditional teaching in application and exploration, providing a new idea for the reform in medical microbiology experiment teaching.

Objective To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in treatment of IgA nephropathy. Methods The Cochrane library, PubMed, EMBASE, Wanfang Data Knowledge Service Platform, CNKI and VIP were searched from the time when the databases were established to March 31, 2018. Reports on randomized controlled trials (RCTs) on treating IgAN with MMF were collected. Data were extracted and assessed independently by three reviewers and the methodological quality of included RCTs was assessed by the Cochrane collaboration's tool for assessing risk of bias. The Meta analysis of homogeneous RCTs was managed by using Stata 12.0. Results Nine RCTs, of which two RCTs were assessed as A-level studies scoring from 4 to 7 points, six RCTs were assessed as B-level studies scoring from 2 to 3 points, and one RCT was assessed as C-level study with scores less than 2 points, were enrolled in the study. Important outcomes of this systematic review were described as follows: (1) Compared to placebo plus ACEI/ARB or ACEI/ARB monotherapy, MMF plus ACEI/ARB did not reduce the incidence of increased serum creatinine and ESRD, but increased the partial remission rate of urinary protein (OR=2.59, 95％CI 1.01-6.65, P=0.049. (2) No significant difference was detected in the efficacy of reducing urinary protein for MMF monotherapy or MMF plus glucocorticoid (GC) compared to GC monotherapy. (3) MMF showed no significant difference in the efficacy of reducing urinary protein compared to LEF or CTX, but lower incidence rate of serum creatinine increasing than that of CTX group (OR=0.21, 95％CI 0.04-1.07, P=0.043. (4) Different levels of adverse reactions occurred in each treatment group with MMF, but most symptoms were mild, and recovered gradually after reducing or withdrawing MMF. Conclusions MMF monotherapy shows a superiority in curing IgAN compared to ACEI/ARB, but no significant superiority compared to GC. MMF can replace a part of the effect of GC when used in combination with GC and can reduce the dosage of GC compared to GC monotherapy. Additionally, MMF displays no better short-term efficacy than LEF or CTX, but a better long-term efficacy and fewer side effects than CTX. And the side effects occurred in the treatment groups with MMF are mostly mild, and disappear gradually after reducing or stopping the use of the drug. MMF is a safe and effective drug for the treatment of IgAN.