Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

Objective To explore the efficacy and safety of Yuxiao Prescription in the treatment of patients with stage III-IV diabetic kidney disease(DKD)characterized by qi and yin deficiency and phlegm-stasis obstruction in the real world.Methods A total of 112 patients with stage Ⅲ-Ⅳ DKD with qi-yin deficiency and phlegm-stasis obstruction who visited the outpatient department of Beijing Changping Hospital of Traditional Chinese Medicine from April 2022 to June 2024 were selected as the research subjects.They were divided into the control group and the Chinese materia medica group based on whether they were treated with Yuxiao Prescription through prospective cohort research methods.Propensity score matching(PSM)was used to balance the confounding factors between the groups.The control group received standardized Western medicine treatment,while the Chinese materia medica group was treated with Yuxiao Prescription in addition to the treatment of the control group,one dosage per day,twice a day,orally.The treatment for both groups lasted for three months.The clinical efficacy of two groups was observed,and their urinary protein,renal function,blood glucose,blood lipids,body mass index(BMI)and TCM syndrome scores before and after treatment were compared.Adverse reactions of both groups were monitored.Results After PSM,a total of 84 balanced samples were obtained between the two groups,with 42 samples in each group.The total effective rate of Chinese materia medica group was 90.48%(38/42),while the control group was 73.81%(31/42),with statistical significance(P<0.05).Compared with before treatment,the urinary albumin/creatinine ratio,urinary microalbumin,and 24-hour urinary protein quantitative levels decreased in both groups after treatment(P<0.05).Chinese materia medica group showed a decrease in blood creatinine and a significant increase in estimated glomerular filtration rate after treatment(P<0.05);after treatment,the improvement of the above indicators in the Chinese materia medica group was better than that in the control group(P<0.05).Compared with before treatment,both groups showed a decrease in fasting blood glucose,2-hour postprandial blood glucose,glycated hemoglobin(HbA1c),total cholesterol and low-density lipoprotein cholesterol levels after treatment(P<0.05).The BMI of Chinese materia medica group significantly decreased after treatment(P<0.05);after treatment,the HbA1c level and BMI in the Chinese materia medica group were lower than those in the control group(P<0.05).Compared with before treatment,the TCM syndrome scores in both groups decreased after treatment(P<0.05);after treatment,the TCM syndrome score in the Chinese materia medica group was lower than that in the control group(P<0.05).The adverse reaction rate of the Chinese materia medica group was 4.76%(2/42),while that of the control group was 7.14%(3/42),without statistical significance between the two groups(P>0.05).Conclusion The combination of Yuxiao Prescription and conventional therapy can effectively reduce proteinuria,improve renal function,and help improve glucose and lipid metabolism in patients with stage Ⅲ-Ⅳ DKD characterized by qi and yin deficiency and phlegm-stasis obstruction,thereby delaying the progression of the disease.

Objective:To investigate the relationship between protein tyrosine phosphatase non-receptor type 1 (PTPN1) gene polymorphism and the risk of gestational diabetes mellitus (GDM).Methods:In this case-control study, 4 835 pregnant women who delivered from March, 2012 to July, 2014 in the Department of Gynecology and Obstetrics at the First Hospital of Shanxi Medical University were consecutively enrolled. Among them, 789 cases were diagnosed with GDM. A simple random sampling method was used to select 334 pregnant women with GDM as the case group, and 334 healthy pregnant women matched by maternal age, gestation time and residence were set as control. The DNA genotyping was performed in the subjects, and those with genotyping deletions10% were excluded; and finally, 322 and 317 subjects were included in case and control group, respectively. Under the codominant, dominant, recessive, and allelic genetic models, the unconditional logistic regression model was used to check the relationship between 13 candidate single nucleotide polymorphism (snp) loci in PTPN1 gene and the risk of GDM. The Haploview was used to analyze the relationship between haplotypes and risk of GDM, and multiple comparisons were adjusted with the false discovery rate (FDR) method.Results:The age of the 639 pregnant women analyzed in this study was (30.28±4.32) years. The proportions of pre-pregnancy body mass index (BMI)≥24.0 kg/m 2 and having a family history of diabetes were significantly higher in the GDM group compared to those in the control group (29.19% vs 16.72% and 13.04% vs 6.31%, respectively, both P0.05). The rs6096644 locus was positively associated with increased risk of GDM in co-dominant (GG vs AA, OR=2.76, 95% CI: 1.18-6.44) and recessive (GG vs AA+AG, OR=2.78, 95% CI: 1.20-6.46) genetic models (all q0.2). The rs6096655 locus was positively associated with increased risk of GDM in codominant (AA vs GG, OR=5.90, 95% CI: 1.27-27.36) and recessive (AA vs GG+GA, OR=5.50, 95% CI: 1.19-25.38) and alleles (A vs G, OR=1.51, 95% CI: 1.09-2.08) genetic models (all q0.2). The rs6013317 locus was associated with an increased risk of GDM in the allele (A vs G, OR=1.74, 95% CI: 1.15-2.63) genetic model (all q0.2). The GAGG haplotype and GGAG haplotype in haplotype block 1 (rs4811262, rs6096646, rs6096655, rs6013317), and the GGGA haplotype in haplotype block 2 (rs6068018, rs6123105, rs6013324, rs2869621) of the PTPN1 gene were all positively associated with an increased risk of GDM (all P0.05). Conclusion:PTPN1 gene polymorphisms may associated with risk of GDM, moreover, complex haplotype structures within the gene influence the risk of GDM.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.

Objective: To investigate the causes and characteristics of immune hemolytic transfusion reactions (HTRs) triggered by anti-E antibodies, so as to provide a scientific reference for guaranteeing clinical blood transfusion safety. Methods: Five patients who experienced HTRs in our hospital from November 2023 to October 2024 were selected as the research subjects. ABO/RhD blood grouping, antibody screening, antibody identification, and the direct antiglobulin test (DAT) were conducted using the column agglutination method. The causes of HTRs in these patients were investigated using multiple techniques such as the two-step enzyme method, polyethylene glycol (PEG), acid elution technique, and capillary centrifugation method. Results: All five patients tested negative for antibody screening prior to transfusion. However, after transfusion of E+ phenotyped blood, patients 1, 2, 3, and 5 developed delayed haemolytic transfusion reaction (DHTR), while patient 4 experienced acute haemolytic transfusion reaction (AHTR). Anti-E antibodies were detected in all blood samples from the patients after the hemolytic transfusion reaction, including the enzyme-only anti-E antibody in two cases. Conclusion: Anti-E antibody can trigger both intravascular and extravascular hemolysis. It is recommended to conduct ABO/RhD and RhE antigen-matched transfusions and establish a regional blood transfusion database to reduce immune hemolytic transfusion reactions caused by anti-E antibody.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease with high global prevalence and long course, which affects more than 30% of the population and seriously endangers human health. Lipid metabolism plays an important role in the occurrence and development of MASLD. An increasing number of studies have shown that active ingredients in traditional Chinese medicine can regulate lipid metabolism to improve MASLD. Due to the obvious advantages of multi-target regulation and fewer side effects, the active ingredients have shown great potential and value for application. However, the pathological mechanism of MASLD is intricate and the active ingredients of traditional Chinese medicine can improve MASLD from multiple aspects, there is currently a lack of systematic discussion on lipid metabolism. Therefore, this review focuses on lipid metabolism and reviews the latest research progress of active ingredients from traditional Chinese medicine in ameliorating MASLD from the aspects of lipid uptake, lipid synthesis, lipid oxidation, lipid secretion, etc., in order to provide more theoretical references for active ingredients of traditional Chinese medicine in regulating lipid metabolism to improve MASLD.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a Chinese pedigree affected with Hereditary dentin dysplasia type II (DD-II) due to variant of dentin sialophosphoprotein (DSPP) gene. METHODS: A child diagnosed with DD- II at the Third Clinical Division of Peking University Hospital of Stomatology in December 2021 and her family members were selected as study subjects. Clinical data were retrospectively analyzed. Saliva samples were collected from the proband, her parents and sister for genomic DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and TOPO-TA cloning sequencing. The candidate variant was also subjected to bioinformatics analysis using Mutation Taster v2021. Secondary and tertiary structures of the wild-type and variant DSPP proteins were predicted with psipred v4.0 and PyMOL v2.3 software, respectively. The pathogenicity of the variant was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Peking University Hospital of Stomatology (Ethics No.: PKUSSIRB-202162021). RESULTS: The proband and her mother and sister had all exhibited typical clinical manifestations of hereditary DD-II. The primary dentition of the proband displayed yellowish brown discoloration, wear, and obliteration in the chamber and root canal, while the permanent teeth of the proband's sister and mother appeared nearly normal in both color and appearance, though with obliteration in the chamber and root canal. Her father showed normal dentition. WES identified a heterozygous c.1915_1918delAAGT, p.(Lys639Glnfs*674) frameshift variant in the DSPP gene. Sanger sequencing and TOPO-TA cloning sequencing confirmed the presence of this variant in the proband, the proband's sister, and the mother, while the proband's father was negative for the variant, indicating an autosomal dominant inheritance pattern. The variant was predicted to be pathogenic by Mutation Taster v2021. Prediction of the secondary structure of the DSPP protein showed that the variant has changed it from coil to helix. The tertiary structure prediction of the DSPP protein showed change of the spatial structure of the variant DSPP, with the loops in the variant region replaced by helices at multiple sites. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP1+PP4). CONCLUSION Phenotypic analysis and genetic testing of this family has clarified the clinical diagnosis of hereditary DD- II. The c.1915_1918delAAGT variant probably underlay the pathogenesis of DD-II in this family. Above results have expanded the phenotypic spectrum of the disease and may contribute to further clinical and genetic research on this disease.
Humans ; Pedigree ; Female ; Extracellular Matrix Proteins/chemistry* ; Male ; Sialoglycoproteins/chemistry* ; Dentin Dysplasia/genetics* ; Asian People/genetics* ; Phosphoproteins/chemistry* ; Child ; Mutation ; China ; Exome Sequencing ; Adult ; East Asian People

Objective To analyze the reasons for the failure of subject screening in clinical trials of antineoplastic drugs and the impact of natriuretic criteria on the entry of subjects into clinical trials,to explore the strategies to improve the suc-cessful enrolment of screened subjects,and to provide reference bases for research institutes and sponsors in the formulation of na-triuretic criteria.Methods This study selected data from 40 drug clinical trials conducted at the Drug Clinical Trial Research Center of the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1,2016,to June 30,2022.It statistically described the collected data on the frequency and percentage composition of screening failures among participants and the inclu-sion and exclusion criteria in the protocols.Results A total of 425 subjects were screened out of 40 clinical trial programmers covering 8 tumor types,with the majority being＜65 years of age(333,78.4％),of which the most important reasons included vol-untary withdrawal(71,16.7％),tumor metastasis(52,12.2％),failure to recover from treatment of pre-existing disease(38,8.9％),failure of bone marrow function(19,4.5％),and non-compliant liver function(15,3.5％).Among the nadir indicators,the age of the subjects(100％),ECOG score(97.5％),bone marrow function(ANC:95.0％,PLT:97.5％,HB:97.5％),liver function(T-BiL:95.0％,ALT:87.5％,AST:95.0％),renal function(CR:80.0％),and viral screening(HIV:80.0％,HBV:70.0％,HCV:62.5％)were relatively stringent.Conclusion The main reasons for subject screening failure in clinical trials in oncology in our hospital are voluntary withdrawal,brain metastasis,and failure of their biochemical test standards,which are close-ly related to the setting of clinical trial nadir criteria.Therefore,an in-depth understanding of subjects'characteristics,accurate set-ting of appropriate nadir criteria,continuous improvement of trial design,and strengthening of communication with subjects to pro-vide more relevant information will help to improve the screening success rate of clinical trials.

Respiratory syncytial virus(RSV)infection is a major respiratory disease threatening the health of infants and immuno-compromised populations worldwide,with no specific therapeutic drugs available.Traditional Chinese medicine(TCM)has shown unique advantages of multi-target and multi-pathway in the prevention and treatment of RSV infection,and its mechanism is closely re-lated to the regulation of cellular signaling pathways.This article systematically reviews the research progress of TCM including mono-mer components and compound prescriptions in intervening RSV infection through nuclear factor-κB(NF-κB),Janus kinase/signal transducer and activator of transcription(JAK/STAT),phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt),mitogen-activated protein kinase(MAPK),nuclear factor E2-related factor 2/heme oxygenase-1(Nrf2/HO-1)and other signaling pathways.Current re-search still has problems such as insufficient analysis of pathway synergy mechanisms,unclear material basis of compounds,and single technical means.Future studies should focus on cross-talk of multiple pathways,identification of active component groups of TCM,and research on"syndrome-type-pathway"association,combined with cutting-edge technologies such as network pharmacology and or-ganoid models,so as to provide a scientific basis for the mechanism and clinical transformation of TCM against RSV infection.

Objective To study the clinical value of stroboscopic laryngoscope combined with narrow band imaging endoscope in the diagnosis of benign and malignant glottic lesions.Methods A total of 60 patients(84 sides of vocal cord)who visited our department from June 2022 to January 2023 with hoarseness as the main complaint and were found to have glottic lesions by electronic nasopharyngoscopy were selected.In all 60 patients with 84 sides of vocal cord degenerative lesions,stroboscopic laryngoscopy and narrow band imaging(NBI)endoscopy were com-pleted.The examination results were evaluated and graded separately.The same operative group performed the re-section biopsy of vocal cord lesions under general anesthesia and laryngoscope respectively,and the pathological re-sults were used as the diagnostic gold standard.With sensitivity,specificity,accuracy,false negative rate,and false positive rate as the main evaluation indexes,the differences in diagnostic accuracy between single test technique and combined application of the two techniques were analyzed.Results Pathological results showed squamous cell carci-noma on 18 sides,carcinoma in situ on 4 sides,severe dysplasia on 4 sides,mild and moderate dysplasia on 13 sides,and papilloma,chronic,mucosal,nflammation,hyperplasia,hypokeratosis,hyperkeratosis on 45 sides.The sensitivity of strobe laryngoscopy detection was 53.06％and specificity was 60.34％.The sensitivity of NBI endo-scopic detection was 88.46％,and the specificity was 89.66％.The sensitivity of strobe laryngoscopy combined with NBI endoscopy was 96.15％,and the specificity was 94.83％.The areas under the ROC curve of strobe laryn-goscopy,NBI endoscopy and white light imaging combined with narrowband imaging were 0.888(95％CI:0.820～0.957),0.943(95％CI:0.885～1),0.970(95％CI:0.942～0.999),respectively.The area under the curve of the combined method was higher than that of the single method,and the difference was statistically significant(P＜0.05).Conclusion Stroboscopic laryngoscope combined with NBI endoscope can improve the diagnostic accuracy of benign and malignant glottic lesions.