Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Objective To explore the efficacy and technical points of complete preservation of female reproductive organ in radical cystectomy.Methods In 2020 and 2021,two female patients with bladder cancer undergoing radical cystectomy in The First Affiliated Hospital of Naval Medical University were selected.The clinical conditions of the patients were evaluated before surgery,and the reproductive organs were completely preserved according to the patients'wishes during the operation.The patients were regularly followed up after surgery.The efficacy and prognosis of patients were evaluated.Results The operation was successful and the two patients recovered well without surgery-related complications.The follow-up time for two patients were 22 months and 36 months.During the follow-up period,no tumor recurrence was found,and the scores of sexual function and quality of life were good.One patient was successfully pregnant at 17 months after surgery,and routine prenatal examination and non-invasive fetal DNA testing showed no abnormalities.Conclusions Under the premise of strictly grasping the surgical indications,the complete preservation of female reproductive organs in radical cystectomy can improve patients'quality of life after surgery,especially protect the reproductive function of women of childbearing age.

AIM:To investigate the effects of Xiaozhong-Zhitong mixture(XZZT)on M2 polarization and Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway in mouse microglia(BV2 cells).METHODS:The BV2 cells were divided into 5 groups:blank group,model group[lipo-polysaccharide(LPS)+hypoxia],TAK-242(resatorvid,a TLR4 inhibitor)group(LPS+hypoxia+TAK-242),XZZT group(LPS+hypoxia+XZZT),and TAK-242+XZZT group(LPS+hypoxia+TAK-242+XZZT).Flow cytometry was used to detect early apoptosis and cell cycle of BV2 cells,and immunofluorescence staining was employed to detect the positive expres-sion of M1-type marker inducible nitric oxide synthase(iNOS)and M2-type marker CD206.Western blot was utilized to detect the expression of TLR4/MyD88/NF-κB signaling pathway-related proteins,including TLR4,MyD88,NF-κB p65,phosphorylated p65(p-p65),phosphorylated transforming growth factor-β-activated kinase 1(p-TAK1),and phosphory-lated IκB kinase α/β(p-IKKα/β).RT-qPCR was used to detect the mRNA expression of interleukin-1β(IL-1β),IL-10,tumor necrosis factor-α(TNF-α),TLR4,MyD88,and NF-κB p65.RESULTS:Compared with model group,the rate of early apoptosis was significantly decreased in XZZT group(P<0.01),the percentage of cells arrested in the S phase was significantly increased(P<0.01),and the protein levels of TLR4,MyD88,NF-κB p65,p-IKKα/β,p-p65,and p-TAK1 were significantly decreased(P<0.05 or P<0.01).Additionally,IL-1β,TNF-α,TLR4,MyD88 and NF-κB p65 mRNA expression levels were significantly decreased(P<0.05 or P<0.01),while IL-10 mRNA expression was significantly in-creased(P<0.05).Compared with TAK-242 group,the average percentage of iNOS positive area was significantly de-creased,while CD206 was significantly increased in TAK-242+XZZT group(P<0.01).CONCLUSION:The XZZT has the effect of inducing M2 polarization of mouse microglia,and the mechanism may be linked to the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Objective:To investigate the potential risk factors for cryptogenic stroke (CS) in patients with patent foramen ovale (PFO).Methods:Patients underwent PFO closure in the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from June 2018 to December 2021 were enrolled retrospectively. Transesophageal echocardiography was used to evaluate the morphological characteristics of foramen ovale and right-to-left shunt (RLS). Multivariate logistic regression analysis was used to determine the independent risk factors for CS in patients with PFO. Results:A total of 203 patients with PFO were enrolled. Their age was 41.9±14.3, and 116 patients (57.1%) were male. There were 102 patients in CS group and 101 patients in non-stroke group. The age, body mass index, systolic blood pressure and diastolic blood pressure, and the constituent ratios of male, hypertension, diabetes, hyperlipidemia and smoking of the CS group were significant higher than those of the non-stroke group (all P<0.05). The PFO channel of the CS group was longer, wider and more combined with resting RLS (all P<0.05). Multivariate logistic regression analysis showed that systolic blood pressure (odds ratio [ OR] 1.065, 95% confidence interval [ CI] 1.022-1.111; P=0.003), PFO length ( OR 1.124, 95% CI 1.004-1.258; P=0.043) and resting RLS ( OR 5.449, 95% CI 2.283-13.004; P<0.001) were the independent risk factors for CS in patients with PFO. Conclusion:Systolic blood pressure, PFO length and the presence of resting RLS are the independent risk factors for CS in patients with PFO.

Objective:To investigate the prevalence of overactive bladder (OAB) in Chinese boys and risk factors, and to evaluate the psychological and behavioral status of OAB patients.Methods:Cross-sectional study.From October 2020 to July 2021, 2 800 boys aged 6-15 years from 6 primary and secondary schools in a county of Henan Province were selected by stratified random cluster sampling method.An anonymous questionnaire was used to investigate the epidemiological situation of OAB, including the basic information, lower urinary tract symptoms, Overactive Bladder Score Scale (OABSS) scores, pediatric sleep questionnaire (PSQ) and strengths and difficulties questionnaire (SDQ). In addition, the correlation between OAB and residence, body mass index (BMI), nocturnal enuresis (NE), overuse of diapers, history of urinary tract infection, abnormal stool, phimosis, redundant prepuce, and concealed penis by Chi- square test, Logistic multivariate regression analysis, and t-test. Results:A total of 2 333 valid questionnaires were collected.The overall prevalence of OAB in boys was 6.0%(141/2 333 cases). NE, history of urinary tract infection, abnormal stool, overuse of diapers, phimosis, redundant prepuce, concealed penis were risk factors for OAB in boys ( OR>1, P<0.05), while BMI was not a risk factor for OAB in boys ( OR<1, P>0.05). The emotional symptoms[ (7.64±2.03) scores vs.(6.51±2.53) scores], conduct problems [(8.14±1.62) scores vs.(7.31±1.88) scores], hyperactivity[(5.64±2.27) scores vs.(4.98±2.03) scores], peer communication problems [(7.16±1.63) scores vs.(6.59±1.60) scores], difficulty scores[(30.26±6.48) scores vs.(27.69±6.44) scores] and PSQ scores [(5.36±3.00) scores vs.(3.94±2.53) scores] in OAB group were significantly higher than those of non-OAB group ( t=-5.117, -5.005, -3.310, -4.056, -4.553, -5.006, respectively, all P<0.05). Conclusions:OAB in boys is common and affects mental health and sleep quality.Meanwhile, NE, history of urinary tract infection, abnormal stool, overuse of diapers, phimosis, redundant prepuce, or concealed penis are the risk factors for OAB in boys.

Objective:To explore the effect of multiple intelligences theory combined with the analysis, design, development, implementation, and evaluation (ADDIE) model in surgical clinical practice teaching.Methods:A total of 100 residents trained in Department of Gastrointestinal Surgery of Heping Hospital Affiliated to Changzhi Medical College from July 2019 to April 2020 were randomly divided into the control group ( n=50) and the observation group ( n=50). The control group used the ADDIE model, and the observation group adopted the multiple intelligences theory combined with the ADDIE model. The teaching assessment of the two groups was compared, and the core competence, critical thinking ability, self-evaluation, and teaching satisfaction of the two groups were evaluated. SPSS 22.0 was used for Chi-square test and t-test. Results:The scores of basic knowledges of gastrointestinal surgery, surgical clinical thinking and case analysis, routine skills and operations, and the total scores in the observation group were higher than those in the control group ( P<0.05). The scores of professional knowledge and skills, patient safety and rights, scientific research and academic ability, professional ethics, teamwork, personal and professional development ability in the observation group were higher than those in the control group ( P<0.05). While, there was no significant difference in the mastering of knowledge between the two groups ( P>0.05). The four dimensions of learning interest, self-learning ability, innovation ability, and clinical thinking establishment in the observation group were higher than those in the control group ( P<0.05). Conclusion:Multiple intelligences theory combined with ADDIE model in surgical clinical practice teaching can improve the teaching assessment results, significantly enhance the core competence, stimulate the learning interest, cultivate the self-learning ability and innovation ability of residents, and help them to establish clinical thinking ability.

Objective To investigate the characteristics of notifiable infectious diseases reported from a hospital during 2014-2018,and to provide a scientific basis for the epidemic management and department management in the hospital.Methods The descriptive epideniological method was used to analyze the information on notifiable infectious diseases in the China Information System for Disease Control and Prevention,which was reported from the general hospital during 2014-2018.Results During 2014-2018,the number of reported infectious disease cases reached the peak during June to August every year,and the most common diseases were hand,foot and mouth disease,bacillary dysentery,and other infectious diarrhea.There were more male than female cases,with the former accounting for 56.9％.The proportion of children aged 0-14 years was the highest among all age groups.The reported cases were mainly from the enteric diseases clinic,emergency department,and pediatric department.Conclusions Infectious diseases have seasonality in occurrence.During 2014-2018,intestinal infectious diseases were most common among all reported infectious disease cases;the number of cases of respiratory infectious diseases showed an increasing trend;the proportion of cases with viral infectious diseases increased.Much attention should be paid to the monitoring and control of infectious diseases in children.