OBJECTIVE To investigate the ameliorating effect and mechanism of the effective substance groups from Artemisia ordosica（Abbreviated as HSH） on rheumatoid arthritis （RA） based on cluster of differentiation 4/lymphocyte cell-specific protein- tyrosine kinase/zeta-chain-associated protein kinase of 70 kDa/interleukin-17（CD4/LCK/ZAP70/IL-17） signaling pathway. METHODS The rats were divided into normal group， model group， HSH low-dose， medium-dose and high-dose groups （2.7， 10.8， 21.6 mg/kg） and positive control group （Tripterygium glycosides tablet， 6.3 mg/kg）， with 10 rats in each group. Except for normal group， RA rat model was induced by complete Freund’s adjuvant in other groups. After modeling， each group was given relevant medicine or normal saline intragastrically， once a day， for 28 consecutive days. The changes in ankle joint swelling and arthritis index in rats were determined； the pathological changes of ankle joint tissue were observed； the levels of inflammatory factors [IL-1β， IL-21， IL-17A， IL-2， interferon-γ （IFN-γ） and IL-6] in serum and joint fluid of rats were determined； the levels of Th1， Th17 and Treg cells in the whole blood and spleen of rats were detected； protein and mRNA expressions of LCK， proto-oncogene tyrosine-protein kinase Fyn （Fyn）， ZAP70， CD45， RAR-related orphan receptor γt （RORγt）， and forkhead box protein 3 （Foxp3） in ankle synovial tissue were determined. RESULTS Compared with normal group， the changes in ankle joint swelling， arthritis index， the levels of IL-1β， IL-21， IL-17A， IL-2， IFN-γ and IL-6 in serum and joint fluid， the levels of Th1， Th17 cells and Th17/Treg value in whole blood and spleen， and the protein and mRNA expression levels of LCK， Fyn， ZAP70， CD45， and RORγt in ankle joint synovium were all significantly increased/elevated （P＜0.05）. The level of Treg cells in the spleen， as well as the protein and mRNA expression levels of Foxp3 in the ankle joint synovium were significantly decreased （P＜0.05）. Compared with model group， most of the above-mentioned indicators were significantly reversed in the positive control group and all dose groups of HSH （P＜0.05）. The degree of pathological changes in ankle joint tissues was markedly improved， and inflammation was alleviated. CONCLUSIONS HSH can regulate the cascade reactions in the CD4/LCK/ZAP70/IL-17 pathway within the T-cell receptor signaling pathway， thereby modulating the Th17/Treg balance. This leads to the suppression of inflammatory responses and the alleviation of synovial tissue damage in rats with RA.

Objective: To analyze the implementation status and challenges of sex education in special education schools, so as to provide a scientific basis for formulating effective promotion strategies. Methods: From November 2023 to January 2024, a census survey was conducted among 120 in service teachers from 7 special education schools in Luzhou. The questionnaire covered the current status of sex education in schools, teachers attitudes and knowledge toward sex education, and their coping methods for students inappropriate sexual behaviors. Results: About 77.5% of teachers reported having provided sex education to students, but 93.2% indicated a lack of specialized sex education textbooks for special children, 90.4% reported no full time teachers for sex education, and the methods of sex education were relatively limited (50.0% mainly based on lecture method). Nearly 95.8% of teachers held a positive attitude toward sex education, with 98.3% supporting its implementation. Only 26.7% of teachers demonstrated a good grasp of sex education knowledge, with the best understood topic being "recognition and protection of private parts" (21.6%). When dealing with students inappropriate sexual behaviors, the active response rate of teachers was 23.9%, with the highest active response rate observed for "intentionally hugging or kissing the opposite sex" (39.7%). Conclusions The special education schools in Luzhou lack comprehensive sex education curricula, teaching materials and full time teachers, sufficient knowledge among teachers, and adequate proactive responses to students inappropriate sexual behaviors. Greater emphasis should be placed on sex education for special children, including the training of dedicated teachers, to provide comprehensive and high quality sex education services for special children.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

OBJECTIVE To evaluate the economics of trastuzumab deruxtecan versus the physician-selected chemotherapy （TPC） regimen in the second-line treatment of advanced breast cancer with epidermal growth factor receptor 2 （HER-2） low expression from the perspective of the Chinese healthcare system. METHODS Based on the data of DESTINY-Breast04 clinical trial， the dynamic Markov model was constructed. The time frame of the model simulation was 10 years， and the cycle was 3 weeks. Taking cost， quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） as the model output indicators， the discount rate of 5% was applied， and 3 times China’s per capita gross domestic product （GDP） in 2023 was taken as the willingness-to-pay （WTP） threshold value. Cost-utility analysis was used to evaluate the economics of the two treatment regiments in the hormone receptor-positive cohort and all patient cohorts， and uncertainty analysis was used to verify the robustness of the basic analysis result. RESULTS The results of the basic analysis showed that compared with the TPC regimen， the ICER value of trastuzumab deruxtecan regimen edu.cn were 1 045 655.76 and 906 404.99 yuan/QALY in the hormone receptor-positive cohort and all patients， respectively， both exceeding the WTP threshold （268 074 yuan/QALY）. The results of single factor sensitivity analysis showed that progression-free survival utility value， the price of trastuzumab deruxtecan and progression disease utility had a significant influence on the model results. The results of probability sensitivity analysis showed that when the WTP threshold was 3 times China’s per capita GDP in 2023， the probability of economic viability of trastuzumab deruxtecan was 0. The results of scenario analysis showed that when the patient assistance program for trastuzumab deruxtecan was considered， the probability of trastuzumab deruxtecan regimen being economical was 0. However， when the price of trastuzumab deruxtecan was reduced by 70%， the probability of its being cost-effective was significantly increased to 82.80%. CONCLUSIONS At a WTP threshold of 3 times China’s per capita GDP in 2023， the trastuzumab deruxtecan regimen is not cost-effective compared to TPC regimen for the second-line treatment of advanced breast cancer with HER-2 low expression. Reducing the price of trastuzumab deruxtecan by region can improve its cost-effectiveness.

Objective To investigate the effect and mechanism of melatonin on the epithelial-mesenchymal transition(EMT)of human peritoneal mesothelial cells.Methods A human peritoneal mesoepithelial cell line(HMrSV5)was cultured.Decorin(DCN)overex-pression and knockout plasmids were constructed.The cells were divided into the normal,TGF-β1,TGF-β1+melatonin,TGF-β1+mela-tonin+siDCN,TGF-β1+melatonin+siNC,and TGF-β1+DCN groups.The cell proliferation and survival rates were determined using Cell Counting Kit-8(CCK-8).The protein and mRNA expression levels of DCN,TGF-β1,Smad2,and E-cadherin were detected by Western blotting and real-time polymerase chain reaction(PCR),respectively.Results The CCK-8 assay showed that the cell survival rates were higher in the TGF-β1+melatonin,TGF-β1+melatonin+siDCN,and TGF-β1+DCN groups than the TGF-β1 group(P＜0.05).The cell sur-vival rate was higher for the TGF-β1+melatonin group than the TGF-β1+melatonin+siDCN group(P＜0.05).Western blotting and real-time PCR showed DCN and that E-cadherin were significantly down-regulated in the TGF-β1 group compared with the control group(P＜0.05).Compared with the TGF-β1 group,the TGF-β1+melatonin and TGF-β1+melatonin+siDCN groups showed up-regulated E-cadherin and DCN expression levels and down-regulated TGF-β1 and Smad2 expression levels(P＜0.05).Compared with the TGF-β1+melato-nin+siDCN group,the TGF-β1+melatonin+siDCN group showed up-regulated E-cadherin and DCN expression levels and down-regulated TGF-β1 and Smad2 expression levels(P＜0.05).Conclusion Melatonin can delay the EMT of human peritoneal mesoepithelial cells,and the DCNgene may be an important target to inhibit the EMT of these cells.

Objective:To explore the risk factors for recurrence of intussusception in children after successful ultrasound-guided saline enema reduction.Methods:The clinical and follow up data of 355 hospitalized children with intussusception at the First Affiliated Hospital of Zhengzhou University from Feb 2018 to Feb 2023 were reviewed.Patients were divided into two groups by recurrence develped and the differences were compared, Data with significant differences were incorporated into multi-factor logistic analysis.Results:The overall recurrence rate was 15.8% (56/355). By univariate variable analysis model, there were statistically significant differences between the two groups in age, previous intussusception history, vomiting, maximum diameter of concentric circles shown by ultrasound, and concurrent bowel organic diseases (lead points) (all P<0.05). In multivariate Logistic regression model, age, previous intussusception history, maximum diameter of concentric circles, and lead points were independent risk factors for recurrent intussusception after saline enema.The optimal cut-off values for age and maximum diameter of concentric circles were 2 years and 33.5 mm, respectively, according to ROC curve analysis. Conclusion:Age older than 2 years, previous intussusception history, maximum diameter of concentric circles longer than 33.5 mm, and lead points are independent risk factors for recurrence after saline enema.

The ethical dilemma in scientific research exists at all stages of the scientific research activities among medical graduate students,mainly involving conflicts of interest,clinical trials,animal experiments,and the relationship between teachers and students.If medical graduate students are in the ethical dilemma in scientific research for a long time,their research activities will be greatly affected.By discussing the connotation,evaluation tools,current situation,influencing factors,and improvement measures of ethical dilemmas in scientific research,this paper proposed some suggestions,such as comprehensively investigating the influencing factors of ethical dilemmas in scientific research,and formulating targeted improvement measures,with a view to helping medical graduate students identify and get rid of ethical dilemmas in scientific research,and promote the stability of research activities.

Objective The study aimed to compare the diagnostic efficacy of QuantiFERON-TB Gold(QFT-TB)detection of specific cellular immune IGRAs in tuberculosis diagnostic laboratory for pulmonary tuberculosis,extrapulmonary tuberculosis and special population samples in vitro,which may provide evidence for clinical diagnosis and treatment.Methods A total of 546 patients with tuberculosis(AFB + 146 cases,AFB-247 cases),117 patients with molecular biology positive tuberculosis(Xpert 69 cases,TB-DNA 48 cases)and 36 patients with histopathological positive were collected from January to July 2023.There were 72 cases of extrapulmonary tuberculosis,276 cases of pleural effusion and 25 cases of ascites.QFT-TB method was used for detection,chi-square test was applied for com-parison between groups,and the methodological evaluation of positive rate and coincidence rate were all compared.Results The positive rates of QFT-TB in pulmonary tuberculosis,extrapulmonary tuberculosis and close contacts were 83.69%,69.44%,and 32.41%,respectively.The coincidence rates of QFT-TB in AFB +,GeneXpert,TB-DNA and pathological confirmed tuberculosis patients were 91.09%,88.40%,81.25%,and 72.22%,respectively.The positive rate of pleural effusion in patients with tuberculous pleurisy was 60.50%,and the uncertainty rate was 29.71%.The positive rate of ascites was 44.00%and the uncertainty was 36.00%.Conclusion QFT-TB test has good value in the auxiliary diagnosis of pulmonary tuberculosis,and has certain reference significance for the diagnosis of extrapulmonary tuberculosis based on the detection of pleural fluids and ascites.

Objective:To analyze the seroepidemiological characteristics of hepatitis B virus (HBV) infection among adolescents aged 0-14 years in Henan Province and to evaluate the effectiveness of the childhood hepatitis B vaccine (HepB) immunization program.Methods:From September 2021 to March 2022, a total of 4 883 adolescents aged 0-14 years were selected from 25 villages or communities of 18 provincial-level cities in Henan Province by using the multi-stage random cluster sampling method. Demographic data were collected through questionnaires. The 3 ml of blood samples were collected from individuals aged 0-4 years and 5 ml of blood samples were collected from individuals aged 5-14 years to test HBsAg, HBcAb and HBsAb. Data on vaccination were collected through Henan Provincial Immunization Information System and hepatitis B cases in Henan Province were collected through China Infectious Disease Reporting System. The effectiveness of the childhood HepB immunization program was analyzed.Results:The average age of 4 883 subjects was (7.32±2.81) years old. The positive rates of HBsAg and HBcAb were 0.1% (7/4 883) and 1.0% (50/4 883), and the population standardized rates were 0.3% and 1.7%. In 2002, the positive rate of HBsAg among adolescents aged 0-14 years in Henan Province was 3.39%. Compared with that in 2002, the number of chronic HBV infections among adolescents in Henan Province in 2022 decreased by about 0.7 million. In 2002, the vaccination rate of newborns who completed all three doses of vaccine was 6.26%. In 2003, the vaccination rate of the hepatitis B vaccine rose rapidly, reaching 90% in 2013 for the first time. After 2014, the vaccination rate in Henan Province continued to remain above 95%. The proportion of cases among children aged 1-4 years in clinical reports decreased from 0.43% (1 108/256 566) in 2006 to 0.01% (78/80 655) in 2021. The proportion of cases among adolescents aged 5-19 years decreased from 18.21% (46 710/256 566) in 2006 to 1.1% (827/80 655) in 2021.Conclusions:From 2002 to 2022, the positive rate of HBsAg among adolescents aged 0-14 years has decreased significantly in Henan Province. The effectiveness of the HepB immunization program for children is good.

Objective:To explore the relationship between periprosthetic infection and preoperative serum levels of human β-defensin 3 (HBd-3) and interleukin-12 (IL-12) in patients with femoral neck fracture after hip replacement surgery.Methods:A prospective study was conducted to 268 patients with femoral neck fracture who underwent hip replacement surgery at Chengde Central Hospital from April 2020 to April 2022. They were divided into an infected group and an uninfected group based on whether they had periprosthetic infection within 2 weeks after surgery. The baseline data and preoperative laboratory indicators of the two groups were compared, and the relationship between preoperative serum HBd-3 and IL-12 levels and postoperative periprosthetic infection in patients was mainly analyzed.Results:Seventeen out of 268 patients with femoral neck fractures experienced periprosthetic infections after hip replacement surgery, with an infection rate of 6.34%(17/268). The body mass index, operation time, postoperative drainage time and IL-12 in the infected group were higher than those in the uninfected group: (23.75 ± 2.18) kg/m 2 vs. (21.86 ± 1.95) kg/m 2, (124.82 ± 15.93) min vs. (116.92 ± 14.75) min, (57.41±7.81) min vs. (49.65 ± 5.73) min, (64.82 ± 11.59) ng/L vs. (54.23 ± 9.55) ng/L, the preoperative albumin and HBd-3 were lower than those in the uninfected group: (32.56±4.63) g/L vs. (37.25 ± 5.81) g/L, (38.03 ± 6.74) μg/L vs. (46.84 ± 8.93) μg/L, and the differences were statistically significant ( P<0.05). The results of Logistic regression analysis showed that high body mass index, long surgical and postoperative drainage time, and high preoperative IL-12 levels were risk factors for periprosthetic infection after hip replacement surgery in patients with femoral neck fractures ( OR>1, P<0.05), while preoperative serum albumin and HBd-3 levels were protective factors ( OR<1, P<0.05). Receiver operating characteristic curve results showed that preoperative serum HBd-3 and IL-12 alone and in combination predict AUC>0.70 for periprosthetic infection in patients with femoral neck fracture after hip replacement surgery, which had certain predictive value. The restricted cubic spline method combining spline function and Logistic regression was used for analysis, and the results showed a linear dose-response relationship between the levels of HBd-3 and IL-12 and the strength of the association with periprosthetic infection after hip replacement surgery in patients with femoral neck fracture ( P<0.05). Conclusions:Preoperative serum HBd-3 and IL-12 levels are associated with periprosthetic infection in patients with femoral neck fracture after hip replacement surgery, and can serve as predictive indicators for infection occurrence.