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.

ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange （LPE） in patients with acute-on-chronic liver failure （ACLF）. MethodsA prospective cohort study was designed， and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment， the patients in the DPMAS+LPE group received DPMAS and LPE treatment， and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results， liver function parameters， renal function markers， electrolytes， coagulation function parameters， cytokines， adverse events， and 28-day prognosis before surgery （baseline）， during surgery （DPMAS or CA280）， and after surgery （after sequential LPE treatment）. The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group， and the independent-samples t test was used for comparison between groups； the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group， and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment， the ACLF patients had significant reductions in the levels of cytokines （IL-6， IL-8， IL-10， TNF-α， and IFN-γ）， liver function parameters （ALT， AST， ALP， TBil， DBil， Alb， and glutathione reductase）， and the renal function marker urea nitrogen （all P<0.05）， and in terms of coagulation function parameters， there were significant increases in prothrombin time， activated partial thromboplastin time （APTT）， thrombin time， and international normalized ratio （INR） and significant reductions in prothrombin activity （PTA） and fibrinogen （FIB） （all P<0.05）. Compared with the DPMAS+LPE group， the CA280+LPE group showed better improvements in the serum cytokines IL-8 （Z=-2.63， P=0.009）， IL-10 （Z=-3.94， P<0.001）， and TNF-α （Z=-1.53， P=0.023）， and the two artificial liver support systems had a similar effect in improving liver function （ALT， AST， GGT， GR， TBil， and DBil） （all P >0.05）， but the CA280+LPE group showed a significantly greater reduction in Alb （Z=-2.08， P=0.037）. CA280+LPE was more effective in reducing uric acid （Z=-2.97， P=0.003）. Compared with DPMAS+LPE， CA280+LPE treatment resulted in a significant reduction in INR （Z=-4.01， P<0.001）， a significant increase in APTT （Z=-2.53， P=0.011）， and significant greater increases in PTA （Z=-6.28， P<0.001） and FIB （Z=-3.93， P<0.001）. There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups （all P>0.05）. The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC （r=0.22， P=0.042）， TBil （r=0.29， P=0.005）， and FIB （r=-0.33， P=0.003）； IL-8 was positively correlated with APTT （r=0.37， P<0.001） and INR （r=0.25， P=0.013）； TNF-α was significantly correlated with WBC （r=0.40， P<0.001） and TBil （r=0.34， P<0.001）. ConclusionCompared with DPMAS， CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients， but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients， but further studies are needed to verify its long-term efficacy.

The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE-/-mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE-/-mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species declining.Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis development.Furthermore,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was observed.The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular health.In conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD incidence.These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To build a sensitive quality index system of dental clinic nursing.Methods:Based on the Donabedian "structure-process-results" three-dimensional quality model, the indicators at all levels of the sensitive quality index system of dental clinic nursing was preliminarily constructed through literature review. The Delphi method was used to develop a system of sensitive quality indicators for dental outpatient care through two rounds of correspondence with 15 experts from the fields of dental care management, oral health care, quality of care management, and health policy.Results:The effective response rates of the two rounds of expert inquiry questionnaires were 100% (15/15), and the average authority coefficient of the experts was 0.93. The Kendall's harmony coefficients of the overall indicators were 0.115 and 0.141, respectively ( P<0.05). A sensitive quality indicator system for dental clinic nursing was finally determined, including 3 primary indicators, 7 secondary indicators and 19 tertiary indicators. Conclusions:The sensitive quality indicator system for dental clinic nursing constructed in this research is scientific and reliable. After verification through future research, it can serve as a basis for improving the quality of dental clinic nursing.

Objective:To investigate clinicopathological features and prognosis of transformed mycosis fungoides (TMF) .Methods:A retrospective analysis was performed on clinicopathological data collected from 24 patients with TMF, as well as on flow cytometry results of 16 peripheral blood samples obtained from 11 of the 24 patients, who visited Hospital of Dermatology, Chinese Academy of Medical Sciences between 2014 and 2020.Results:Among the 24 patients, 11 were males and 13 were females. Their average age at diagnosis of TMF was 50.0 years (range: 18 - 77 years), and patients with early-stage TMF (9 cases) and tumor-stage TMF (15 cases) were aged 44.8 and 52.6 years on average, respectively. The average time interval from diagnosis of MF to large cell transformation was 3.7 years, and 8 patients were diagnosed with TMF at the initial visit. Histopathologically, large cells infiltrated in a diffuse pattern in 20 cases, as well as in a multifocal pattern in 4, and the proportion of large cells in 7 cases was greater than 75%. Immunohistochemically, 18 patients showed positive staining for CD30, and the proportion of CD30-positive large cells was greater than 75% in 9; negative staining for CD30 was observed in 6. Flow cytometry of 16 peripheral blood samples showed the presence of cell subsets expressing clonal T cell receptor (TCR) -vβ in 2 of 4 patients with early-stage TMF and 10 of 12 with tumor-stage TMF, and tumor cells with higher forward scatter than normal lymphocytes were detected in 16 samples. During the follow-up, among the patients with early-stage TMF, 3 progressed to tumor-stage TMF 3.3 years on average after large cell transformation, 1 progressed to erythrodermic MF in stage IIIA, and the other 4 still showed an indolent course; among the patients with tumor-stage TMF, 1 progressed to stage-IV TMF, and 5 died 3.3 (1.5 - 6) years after large cell transformation.Conclusion:Large cell transformation may occur in patients with MF in any stage, some patients have poor prognosis, so close follow-up is needed for patients with TMF.

Objective:To investigate the prevalence of work-related musculoskeletal disorders among nurses in ClassⅢ Grade A stomatology hospitals.Methods:Using the convenient sampling method, a cross-sectional survey was conducted on general information, prevalence of work-related musculoskeletal disorders and working factors of 496 front-line nurses from two ClassⅢ Grade A stomatology hospitals in Beijing from November 14 to 27, 2019 by using the revised electronic version of Nordic Musculoskeletal Disorders Questionnaire revised based on the Chinese population.Results:A total of 496 questionnaires were collected and 483 were valid. The annual prevalence rate of work-related musculoskeletal disorders among dental nurses was 68.3% (330/483) . Among the 9 body parts, the top 4 affected parts were neck, shoulder, lower back and upper back. Education level was an independent risk factor for work-related musculoskeletal disorders ( P<0.01) , while physical exercise was a protective factor ( P<0.05) . Conclusions:The incidence of work-related musculoskeletal disorders among dental nurses is not optimistic.It is necessary to screen high-risk groups as soon as possible, encourage nurses to strengthen physical exercise and carry out key interventions for neck, shoulder and back musculoskeletal diseases to avoid irreversible decline in musculoskeletal function, which may affect the physical health and career development of dental nurses.

Objective:To analyze the clinical and imaging characteristics of pulmonary artery sling (PAS) in children and to explore its diagnosis and treatment strategies and risk factors.Method:s A retrospective study was performed in 98 pediatric patients with PAS who were admitted to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University, from January 2011 to October 2018.All their clinical features, imaging examination, treatment and prognosis were reviewed and analyzed.Result:s (1) Among the 98 patients with PAS, 56 cases were male and 42 cases were female.The age range of onset was 0-19 months with the median age of 2 months, and the age range of diagnosis was 0-84 months with the median age of 4 months.(2) The main clinical manifestations were cough (61/98 cases, 62.24%), recurrent wheezing(47/98 cases, 47.96%), shortness of breath (43/98 cases, 43.88%), cyanosis (19/98 cases, 19.39%), and laryngeal stridor (8/98 cases, 8.16%) and so on.(3) Ninety-six patients underwent cardiac ultrasonography, and the diagnostic rate was 87.50%(84/96 cases), and 62 cases (62/96 cases, 64.58%) of them were found to be associated with other congenital cardiovascular anomalies, among which atrial septal defect was the most common (32/96 cases, 33.33%). (4) Chest CT and three-dimensional reconstruction were performed in 92 PAS children, and the diagnostic rate was 100.00%.Airway stenosis was mainly in the middle and lower sections of the main bronchus (76/92 cases, 82.61%), and bronchobridge was found in 13 cases (13/92 cases, 39.13%). Bronchoscopy was performed in 77 children with PAS, showing complete tracheal cartilage ring in 43 cases (43/77 cases, 55.84%), and tracheobronchomalacia in 13 cases (13/77 cases, 16.88%). (5) Among 67 cases who had received left pulmonary artery (LPA) reimplantation, 5 cases died after operation because of airway stenosis and weaning failure (LPA reconstruction was performed in 1 case, and both LPA reconstruction and tracheal intervention were performed in the other 4 cases), 24 cases lost to follow-up, 38 cases survived, and the respiratory symptoms were improved in 2 to 96 months of follow-up.There were 31 cases of non-surgical treatment, of which 18 cases died of respiratory failure, 7 cases lost to follow-up, and the rest 6 cases showed respiratory symptoms of different degrees in the follow-up period.(6) Multivariate regression analysis showed that conservative treatment was an independent risk factor affecting the prognosis of PAS ( OR=7.45, 95% CI: 1.23-48.68). Conclusions:The combination of cardiac ultrasound, chest CT and bronchoscopy is important to the diagnosis of PAS.LPA reconstruction is the main method to treat PAS, which can improve respiratory symptoms, but its fusion with tracheal intervention poses a high risk of death.Conservative treatment is an independent risk factor that affects the prognosis of PAS children.

BACKGROUND: Intestinal and lymphoid tissues constitute an important part of intestinal immunity, which plays an important regulatory role in spleen deficiency and hydronephrosis. OBJECTIVE: To observe the effect of acupuncture on T lymphocyte subsets in lymph nodes of rats with spleen deficiency, and to investigate the correlation of spleen deficiency with intestinal immunity and the mechanism of acupuncture for spleen deficiency syndrome. METHODS: Thirty-six female Sprague-Dawley rats were randomly divided into three groups: model, acupuncture and blank control groups. The rat model of spleen deficiency was established by fatigue-induced spleen injury plus abnormal diet for 31 days. Afterwards, the rats in the acupuncture group received acupuncture at Zusanli(ST 36).Urine D-xylose excretion rate was detected during modeling and treatment.Then, the mesenteric lymph nodes were removed, and the changes in T lymphocyte subsets in the mesentericlymph nodes were observed by immunohistochemistry. RESULTS AND CONCLUSION: Urine D-xylose excretion rate under spleen deficiency in the modeling and acupuncture groups was significantly lower than that in the blank control group (P < 0.05 or P < 0.01); after acupuncture, the urine D-xylose excretion rate was significantly increased compared with the modeling group (P < 0.01), but still lower than that in the blank control group (P < 0.05). The count of CD4+T lymphocytes, count of CD8+T lymphocytes and ratio of CD4+/CD8+T lymphocytes were ranked as follows: blank control group >acupuncture group>modeling group(P<0.01 or P<0.05).These results suggest that acupuncture at Zusanli can improve the urine D-xylose excretion rate, regulate the balance of T lymphocyte subsets in mesenteric lymph node of rats with spleen deficiency, thus improving the intestinal immune function, spleen deficiency systems, disorder of intestinal digestive function, intestinal digestion and absorption, as well as anorexia, loose stool, diarrhea and other symptoms of the digestive system.