OBJECTIVE To evaluate the anticoagulant efficacy and safety of nafamostat mesylate （NM） in the treatment of uremic patients at high risk of bleeding undergoing continuous veno-venous hemofiltration （CVVH） with different methods （pre- dilution and post-dilution）. METHODS A total of 130 uremic patients at high risk of bleeding who underwent CVVH treatment in the nephrology department of Chongqing University Three Gorges Hospital from July 2023 to September 2024 were selected. They were divided into pre-dilution group and post-dilution group according to the random number table method， with 65 cases in each group. Both groups of patients received CVVH treatment under NM anticoagulation. The pre-dilution group adopted the pre-dilution replacement method， while the post-dilution group adopted the post-dilution replacement method. The coagulation， pressure， and usage duration of the filter and dialysis circuit venous reservoirs were compared between the two groups. The changes in prothrombin time （PT）， prothrombin time-international normalized ratio （PT-INR）， activated partial thromboplastin time （APTT）， and fibrinogen （FIB） in the peripheral venous blood before the heparin pump and after the filter at 1， 4 and 7 h of CVVH treatment， as well as 20 min after the end of treatment， were compared between the two groups. The single-compartment urea clearance rate （spKt/V）， β2-microglobulin （β2-MG） clearance rate and the incidence of adverse reactions were duni2007@foxmail.com compared between the two groups. RESULTS Both the pre-dilution and post-dilution groups had 60 patients who completed the study. The incidence of grade Ⅱ-Ⅲ coagulation of the filter and venous reservoirs， as well as the number of patients with transmembrane and venous pressure alarm intervention in the post- dilution group were significantly higher or more than those in the pre-dilution group （P＜0.05）， while usage time of the filter and the pipeline in the post-dilution group was significantly shorter than that in the pre-dilution group （P＜0.05）. The APTT values before the heparin pump as well as PT and APTT values after the filter at 1 h， 4 h， and 7 h of CVVH treatment in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There were no significant differences in PT， PT- INR， APTT and FIB between the two groups of patients 20 min after the end of treatment （P＞0.05）. The spKt/v and β2-MG clearance rates in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS When NM is used as an anticoagulant in the CVVH treatment of uremic patients at high risk of bleeding， compared with the pre-dilution treatment method， the post-dilution treatment method has a higher incidence of filter and dialysis tubing venous reservoir， a shorter usage time of the filter and pipeline， and a greater impact on extracorporeal coagulation， but has a higher solute clearance rate. Clinically， different dilution methods can be selected according to the different treatment needs of patients.

Objective: To investigate the status of antibiotic exposure in third grade primary school students in Shenzhen,so as to provide evidence for the scientific management of antibiotic use and reduction of population health risks. Methods: From 1 September to 30 October 2021, 200 third grade students from 8 primary schools in Luohu District of Shenzhen were selected by cluster random sampling as research subjects. The body composition was measured, urine samples were collected, and the contents of 35 antibiotics in the samples were detected by mass spectrometry. Relevant dietary habit information of the subjects was collected via questionnaires. The Chi square test was used to compare the detection rate of antibiotics among different genders and weight grades. The Logistic regression model was adopted to evaluate the correlation between the target antibiotic detection rate and dietary habits. Results: At least one type of antibiotic was detected in 198 of the subjects with an overall detection rate of 99.0% . Among the 35 target antibiotics, 23 were detected with detection rates ranging from 0.5%-69.5%. Quinolones had the highest detection rate of 86.5% , followed by macrolides and sulfonamides with detection rates of 77.5% and 76.5%, respectively. The detection rate of antibiotics was 98.3% in boys and 100.0% in girls with no statistically significant difference ( χ 2=1.35, P >0.05). The detection rates of quinolones, macrolides, and sulfonamides varied significantly among children with different BMI categories ( χ 2=38.18, 12.45, 9.76 , all P <0.05). The multivariate Logistic regression model analysis showed that the macrolide detection rate was affected by genders( OR =0.42) and the sulfonamide detection rate was significantly correlated with the frequency of dairy product consumption and being overweight( OR =2.01)(both P <0.05). Enrofloxacin was associated with the weekly consumption frequency of livestock meat such as pork, beef and mutton, as well as the weekly consumption frequency of poultry meat such as chicken, duck and goose ( OR = 2.81,2.17,both P <0.05). Trimethoprim was associated with the weekly frequency of drinking pure milk ( OR =5.49, P < 0.05 ). Conclusions Third grade primary school students in Shenzhen are generally exposed to low dose antibiotics. Macrolides, quinolones, and sulfonamides may be associated with the risk of obesity in primary school students.

Establishing a three-generation family cohort enables the investigation of the effects of genetic, epigenetic, lifestyle, and parenting factors in the grandparental (F0) and parental (F1) generations on the growth, development, and disease onset and progression of the offspring (F2). It facilitates further exploration of the biological mechanisms underlying the impact of intergenerational factors on the health of the offspring (F2), providing evidence for the formulation of public health policies and measures related to child health management and infant and young child care. Currently, the development of multi-generational cohorts in China remains in a preliminary stage, with no systematic multi-generational research framework yet established. Drawing on prior evidence-based scientific research, existing cohort studies, and the practical experience of multidisciplinary experts in maternal and child health, this consensus defines the scope of three-generation family cohorts regarding their definition, significance, key technologies, and application scenarios. It provides technical recommendations for establishing relevant cohorts, aiming to support research areas such as the intergenerational transmission of childhood diseases, the maternal intrauterine environment, and the tracing of family rearing environments. This will facilitate the early prevention and control of diseases manifesting in childhood and adulthood, ultimately promoting the comprehensive and healthy development of children.

OBJECTIVE To investigate the current status of prevalence of hand eczema(HE)among the health care workers,explore the influencing factors and analyze the association with hand hygiene.METHODS A questionnaire survey was conducted for the health care workers.The health care workers who had HE were followed up by the dermatology department and were completed the assessment of severity.Logistic regression analysis was per-formed for the influencing factors.RESULTS The questionnaires were distributed to the health care workers of Shanghai First Peoples Hospital in Jul.2024,and 659 valid questionnaires were recycled.The prevalence rate of HE by self-report was 37.03％in recent almost one year.The finger and dorsal hand were the predilection sites of skin damage,with the symptom dominated by itching;dryness,desquamation and vesicles were the primary man-ifestations of skin damage,most of which(64.81％)were moderate.Wearing gloves in work environment and contact with hand sanitizer and disinfectants could make the HE symptoms ever more severe.The use of hand san-itizer/frequent hand washing with soap lye and prolonged glove-wearing were the leading causes of HE.The nurses were dominant among the health care workers with HE(P=0.003),and the proportion of those with allergic his-tory was even higher(P＜0.001).As for the health care workers who washed hands for surgeries,high volume of daily surgical procedures(OR=1.325,95％CI:1.121 to 1.567)and glove-wearing duration more than 120 min(OR=3.177,95％CI:1.087 to 9.281)were the risk factors for HE.As for the common hand-washing health care workers,daily hand washing more than 15 times(OR=3.199,95％CI:1.014 to 10.137),glove-wearing dura-tion more than 120 min(OR=2.216,95％CI:1.117 to 4.391)and use of powdered latex glove(OR=1.591,95％CI:1.058 to 2.390)were the risk factors for HE.CONCLUSION The prevalence rate of HE is high among the health care workers.It is necessary to attach great importance to the hand skin health of the health care work-ers and take comprehensive intervention measures for prevention of HE such as optimization of hand hygiene pro-cedure,enhancement of barrier protection and stress on occupational health education so as to achieve the dual goals of infection control and skin health.

Objective To explore the effectiveness of"near peer learning"(NPL)in the electromyo-graphy(EMG)teaching module for neurology residents.Methods The Department of Neurology,Peking Union Medical College Hospital implemented an NPL instructional design for a course on EMG for residents from November 2020 to March 2024.This teaching session was held annually,in which senior residents in-structed juniors who were 1 or 2 years earlier in their training.The residents participated in the pre-course/post-course tests and completed a feedback survey at the end of the session.This evaluation method was used to un-derstand the effectiveness of the NPL intervention in EMG teaching.Results Over four years,a total of 83 residents participated.Among them,there were 24 postdoctoral students,52 postgraduates and 7 junior resi-dents.The results showed that the post-course test scores were significantly improved compared with pre-course test scores(74.33±2.43 vs.70.11±2.49,P=0.005),with the most remarkable improvements seen for"tu-tees"(73.84±20.53 vs.70.29±21.46,P=0.020),postgraduates(74.04±22.51 vs.68.97±21.40,P=0.009),first-year residents(70.19±4.02 vs.63.59±3.59,P=0.040)and first-time participating resi-dents(65.23±3.24 vs.60.97±3.21,P=0.030).The post-program feedback showed that both tutors and tu-tees thought highly of NPL,believing that it enabled them to gain knowledge and helped them to improve teaching skills.Conclusions The NPL intervention is suitable for the teaching of EMG,because of its contri-bution to knowledge acquisition and basic clinical skills improvement.The NPL is worth replicating in other teaching and learning programs.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

[Objective] To establish a method for detecting the potency of recombinant human coagulation factor Ⅶa for injection. [Methods] By adding the sample and factor Ⅶ deficient plasma to the sample cup and activating the reaction with prothrombin time assay reagent (PT reagent), the coagulation time of the sample was determined by the change in magnetic bead swing amplitude in the sample cup. The logarithm of coagulation time was inversely proportional to the logarithm of human factor Ⅶa potency. [Results] Under the experimental conditions, the specificity of the methodology was evaluated through spiked recovery, and the recovery rates ranged from 90.0% to 110.0%. Within the range from 0.125 to 1.000 IU/mL, there was a good linear response between the potency and coagulation time of the standard and sample, with correlation coefficients r>0.99. As for the accuracy and repeatability, the recovery rates of various concentrations detected in the stock solution were 101.0%, 100.0% and 112.0%, respectively, with RSD values of 2.6%, 4.0% and 0.0%, respectively. The recovery rates of various concentrations in finished product testing were 104.0%, 94.7% and 112.0%, respectively, with RSD values of 1.9%, 2.4% and 0.0%, respectively. As for the intermediate precision, the RSD were 4.5% and 3.7%, respectively. After treated with sample diluent, the sample was tested at room temperature for 6 hours and still exhibited relatively stable biological activity. [Conclusion] This detection method is accurate, stable, easy to operate and highly automated, and is suitable for detecting the potency of recombinant human coagulation factor Ⅶa for Injection.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.
Humans ; Cerebral Small Vessel Diseases/pathology* ; Inflammation/pathology* ; Cerebral Amyloid Angiopathy/pathology* ; Vasculitis, Central Nervous System/pathology* ; Vasculitis/pathology*

Objective:To explore the clinical features, histopathological morphology, and differential diagnosis of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers.Methods:From 2020 to 2021, 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers diagnosed in Fujian Cancer Hospital (2 cases) and the Second Affiliated Hospital of Fujian Medical University (2 cases) were collected. Different ancillary procedures such as HE, special stains, immunohistochemistry, and in situ hybridization techniques were used to assess the histopathological features and immunophenotypes. The clinical data were collected and literature was reviewed.Results:All 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers were male. They were 32, 45, 67 and 39 years old, respectively. The main clinical manifestations were bloody phlegm, abdominal pain, fatigue and anorexia. The clinical stages at diagnosis were stage Ⅳ (3 cases) and stage Ⅱ (1 case). Cases 2 and 3 had two pathological examinations at different sites, with a total of six pathological examinations. The histomorphology showed singly scattered or nests of tumor cells in a background of abundant small lymphocytes. The tumor cells were enlarged and pleomorphic, some appeared polygonal with inconspicuous cell borders, and they were arranged in a syncytial pattern. There were megakaryocytes, multinucleated tumor cells, and a few spindle-shaped cells seen. Atypical mitosis was commonly noted. By immunohistochemistry, the tumor cells were positive for CKpan(5/6), CK8/18(4/4), CAM5.2(2/5), CK-H(0/4), CK-L(3/4), EMA(4/5), CK5/6(3/6), p63(1/6), p40(1/6), E-cadherin (4/6), SSTR2(6/6), PD-L1(5/5), LCA(0/6), vimentin(5/6), CD2 (6/6), CD23(6/6), CD35(5/6), CXCL-13(4/5) and D2-40(1/5). The Ki-67 proliferative index was 60%-95%. In situ hybridization for EBER were all positive (6/6). Special stain for reticulin showed positive staining surrounding nests of tumor cells.Conclusions:The expression of follicular dendritic cell markers in lymphoepithelioma-like carcinoma is very rare, which may be related to EBV infection. Occasionally, it can overlap with follicular dendritic cell sarcoma by morphology and immunophenotype, which can lead to misdiagnosis. Only by combining clinical information, morphological characteristics and immunophenotype can an appropriate diagnosis be made.