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.

Objective To investigate the potential core target and its mechanism of Simiao San(SMS)in the treatment of rheumatoid arthritis(RA)using network pharmacology and animal experiments.Methods Active components and corresponding SMS targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and cross-referenced with the Universal Protein(UniProt)database.RA-related targets were screened from The Human Gene Database(GeneCards),Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),DrugBank,and Disease Gene Network(DisGeNet).Protein-protein interaction(PPI)networks were constructed for shared targets between SMS and RA using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses via The Database for Annotation,Visualization and Integrated Discovery(DAVID).A"herb active component-disease target-signaling pathway"network was established to predict the mechanism of SMS in RA treatment.Molecular docking was performed between aryl hydrocarbon receptor(AHR)and the core active components of SMS to identify AHR-targeting constituents.For animal experiments,30 female SPF-grade C57/BL mice were randomly divided into normal,model,methotrexate(1.52 mg/kg,every 3 days),and SMS(12.48 g/kg,daily)groups with a 30-day intervention.Ankle diameter and arthritis index scores were measured.HE staining was used to assess joint inflammation,whereas immunohistochemistry(IHC)was used to measure cytochrome P450 1A1(CYP1A1),nuclear factor kappa B subunit p65(p65),and phosphorylated p65(p-p65)protein expression levels.Multiplex immunofluorescence(mIHC)was used to evaluate forkhead box protein P3(FOXP3)and interleukin-17A(IL-17A)protein expression.Results Forty-one active components and 228 targets of SMS were identified from TCMSP,whereas 1,207 RA-related targets were extracted from GeneCards,OMIM,TTD,DrugBank,and DisGeNet.Ninety-four overlapping targets were analyzed,yielding 612 GO terms and 143 KEGG pathways.Molecular docking of the ligand-binding domain of AHR with the top 10 Degree values of compounds of SMS(quercetin,stigmasterol,wogonin,beta-sitosterol,kaempferol,baicalein,et al.)revealed that stigmasterol,beta-sitosterol,(S)-canadine,and isocorypalmine was able to bind to AHR stably.In vivo,compared to the model group,the mice of the SMS and methotrexate groups joint swelling and arthritis index scores reduced(P<0.01).IHC indicated elevated CYP1A1 protein and decreased p65 and p-p65 protein levels in the SMS and methotrexate groups(P<0.05,P<0.01).mIHC demonstrated reduced IL-17A and increased FOXP3 protein expression in the SMS and methotrexate groups(P<0.05,P<0.01).Conclusion SMS alleviates joint inflammation in RA mice,potentially by targeting AHR,one of the core targets.SMS may suppress excessive inflammatory responses by activating AHR and inhibiting p65 phosphorylation.Additionally,SMS modulates the helper T cells 17/regulatory T cells balance by downregulating IL-17A and upregulating FOXP3.These results suggest that AHR is a key mediator in T-cell immune regulation.

Objective To investigate the potential core target and its mechanism of Simiao San(SMS)in the treatment of rheumatoid arthritis(RA)using network pharmacology and animal experiments.Methods Active components and corresponding SMS targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and cross-referenced with the Universal Protein(UniProt)database.RA-related targets were screened from The Human Gene Database(GeneCards),Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),DrugBank,and Disease Gene Network(DisGeNet).Protein-protein interaction(PPI)networks were constructed for shared targets between SMS and RA using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses via The Database for Annotation,Visualization and Integrated Discovery(DAVID).A"herb active component-disease target-signaling pathway"network was established to predict the mechanism of SMS in RA treatment.Molecular docking was performed between aryl hydrocarbon receptor(AHR)and the core active components of SMS to identify AHR-targeting constituents.For animal experiments,30 female SPF-grade C57/BL mice were randomly divided into normal,model,methotrexate(1.52 mg/kg,every 3 days),and SMS(12.48 g/kg,daily)groups with a 30-day intervention.Ankle diameter and arthritis index scores were measured.HE staining was used to assess joint inflammation,whereas immunohistochemistry(IHC)was used to measure cytochrome P450 1A1(CYP1A1),nuclear factor kappa B subunit p65(p65),and phosphorylated p65(p-p65)protein expression levels.Multiplex immunofluorescence(mIHC)was used to evaluate forkhead box protein P3(FOXP3)and interleukin-17A(IL-17A)protein expression.Results Forty-one active components and 228 targets of SMS were identified from TCMSP,whereas 1,207 RA-related targets were extracted from GeneCards,OMIM,TTD,DrugBank,and DisGeNet.Ninety-four overlapping targets were analyzed,yielding 612 GO terms and 143 KEGG pathways.Molecular docking of the ligand-binding domain of AHR with the top 10 Degree values of compounds of SMS(quercetin,stigmasterol,wogonin,beta-sitosterol,kaempferol,baicalein,et al.)revealed that stigmasterol,beta-sitosterol,(S)-canadine,and isocorypalmine was able to bind to AHR stably.In vivo,compared to the model group,the mice of the SMS and methotrexate groups joint swelling and arthritis index scores reduced(P<0.01).IHC indicated elevated CYP1A1 protein and decreased p65 and p-p65 protein levels in the SMS and methotrexate groups(P<0.05,P<0.01).mIHC demonstrated reduced IL-17A and increased FOXP3 protein expression in the SMS and methotrexate groups(P<0.05,P<0.01).Conclusion SMS alleviates joint inflammation in RA mice,potentially by targeting AHR,one of the core targets.SMS may suppress excessive inflammatory responses by activating AHR and inhibiting p65 phosphorylation.Additionally,SMS modulates the helper T cells 17/regulatory T cells balance by downregulating IL-17A and upregulating FOXP3.These results suggest that AHR is a key mediator in T-cell immune regulation.

Rheumatoid arthritis （RA） is a systemic autoimmune disease with local joint pain as the main clinical manifestation. It is one of the diseases specifically responding to traditional Chinese medicine （TCM）. The occurrence of RA is not only related to innate factors like genetic disorder but also associated with environmental factors， such as diets and microbial infection. The intestine， a vital human organ with digestive and immune functions， is a place where microorganisms colonize and exert intestinal metabolism-improving， barrier-protecting， and immunomodulatory effects. As the research on the onset and treatment of RA is deepening， the potential relationship of intestinal structural and functional abnormalities with the pathogenesis and progression of RA has been revealed. As clinical and experimental studies indicated， joint inflammation coexists with the impaired barrier function， imbalanced immune cells， and disordered gut microbiota. The theory of the gut-joint axis in the pathogenesis， progression， and treatment of RA is highly consistent with the holistic view in TCM. The recent pharmacological studies have shown that Chinese medicine prescriptions and active components can inhibit inflammation， protect joints， and maintain the intestinal function. This article summarizes the basic connotation of the gut-joint axis in RA and the mechanism by which TCM protect the intestinal barrier and modulate the immunity by regulating the gut microbiota structure and improving microbial metabolism in the treatment of RA. This review gives insights into the future research on the gut-joint axis in RA.

Objective:To explore the ovarian function and its influencing factors in women of child-bearing age with systemic lupus erythematosus(SLE).Methods:A total of 107 female patients diag-nosed with SLE at Peking University People's Hospital from January 2017 to May 2024,aged between 20 and 40 years,were included in the study.At the same time,40 matched healthy women aged between 20 and 40 years were selected as controls.Serum levels of anti-Müllerian hormone(AMH)were measured using the chemiluminescence method in both the control group and the SLE patients.The general clinical characteristics and medication history(including hormones,immunosuppressants,and biological agents)of the SLE patients were obtained through case retrieval.Changes in serum AMH levels before and after treatment with biological agents in the SLE patients were analyzed.Results:(1)The AMH levels in the SLE patients were significantly lower than those in the healthy control group[1.475(0.344,3.030)μg/L vs.2.934(1.893,4.761)μg/L,P＜0.001].(2)The level of AMH in the SLE patients with normal menstruation was significantly higher than that in the patients with irregular menstruation[1.931(0.638,3.414)μg/L vs.0.335(0.159,1.527)μg/L,P=0.004].No statistical differences were found in clinical characteristics and laboratory indicators between the groups with decreased AMH group and normal AMH group.(3)The multivariate logistic regression analysis revealed that age(OR=1.124,95％CI:1.033-1.224,P=0.007)and disease duration(OR=1.100,95％CI:1.017-1.190,P=0.018)were identified as significant risk factors for the decline in AMH levels.(4)After 6 months of treatment with telitacicept,the AMH level was significantly higher than that before treatment[2.050(0.763,4.259)μg/L vs.1.988(0.473,2.822)μg/L,P=0.043].There was no signifi-cant difference in AMH level between patients receiving rituximab treatment for 6 months[2.026(0.376,2.267)μg/L vs.1.545(0.503,3.414)μg/L,P=0.127].Conclusion:Ovarian function is decreased in SLE patients of childbearing age,and age and disease duration are the risk factors.The utilization of biological agents demonstrates favorable safety profiles regarding ovarian function in child-bearing-age patients with SLE.

In recent years, in vitro fertilization and embryo transfer (IVF-ET) improves the pregnancy rates in patients with recurrent implantation failure (RIF). However, some patients did not get pregnant successfully after IVF-ET. Improving the pregnancy rates in patients with RIF becomes a difficult problem to be solved. Intrauterine administration of autologous human chorionic gonadotropin (hCG)-activated peripheral blood mononuclear cell (PBMC) is a new treatment to improve pregnancy outcome and plays an important role in improving endometrial receptivity and intrauterine microenvironments. This article reviews the application of intrauterine administration of autologous hCG-activated PBMC in RIF, in order to discuss the mechanism of improving the pregnancy outcome of RIF.

In recent years, in vitro fertilization and embryo transfer (IVF-ET) improves the pregnancy rates in patients with recurrent implantation failure (RIF). However, some patients did not get pregnant successfully after IVF-ET. Improving the pregnancy rates in patients with RIF becomes a difficult problem to be solved. Intrauterine administration of autologous human chorionic gonadotropin (hCG)-activated peripheral blood mononuclear cell (PBMC) is a new treatment to improve pregnancy outcome and plays an important role in improving endometrial receptivity and intrauterine microenvironments. This article reviews the application of intrauterine administration of autologous hCG-activated PBMC in RIF, in order to discuss the mechanism of improving the pregnancy outcome of RIF.

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

Objective To investigate the prevalence of nonalcoholic fatty liver disease and the risk factors in Jingyuan county of Ningxia Autonomous Region.Methods The population proportionate sampling method was applied to enroll a representative sample of 10 639 adults in Jingyuan county and the study was conducted using questionnaires and physical examinations.A total of 10 553 people were included in the analysis after excluding those with missing data.High-resolution ultrasound was used to examine the liver and fasting blood was collected in the morning for measurement of blood glucose,blood lipid,and uric acid.The participants were divided into two groups of those with and without nonalcoholic fatty liver disease;the difference in blood biochemical indexes between fatty liver and non-fatty liver groups was compared,and the logistic regression model was used to explore the risk factors affecting the prevalence of fatty liver.Results The prevalence of nonalcoholic fatty liver disease was 7.60％.The prevalence of thyroid nodules was higher in men than in women (8.60％ vs.6.82％,x2=1 1.772,P=0.001).The prevalence rate of fatty liver increased with age (x2=57.336,P＜0.001),the prevalence rates among ≥18 years-＜29 years,≥30 years-＜39 years,≥40years-＜49 years,≥50 years-＜59 years,≥60 years-＜69 years,and above 70 years were 2.92％,6.50％,8.81％,9.59％,8.08％,and 4.77％ respectively.The detection rate of overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperuricemia,and dyslipidemia were higher in nonalcoholic fatty liver disease group than in the normal group (P＜0.05).Logistic regression analysis showed that nonalcoholic fatty liver disease group had a higher risk for overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperurcemia,and dyslipidemia (OR=5.41,12.45,2.99,1.85,2.05,3.30,1.41,2.23,and 1.98).Conclusion The incidence of nonalcoholic fatty liver in Jingyuan county of Ningxia Autonomous Region was higher.The groups of overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperuricemia,and dyslipidemia were high risk factors for nonalcoholic fatty liver disease.

Objective To investigate the clinical features and disease-causing mutations of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.Methods In February 2016,a 24 year old female patient with left kidney stone and nephrocalcinosis in bilateral kidneys was admitted to our hospital.One month prior to this admission,she had been treated by PCNL to remove the most part of left kidney stone in otherhospital.Mter admission,She was found hypomagnesaemia (serum magnesium 0.65 mmol/ L) and hypercalciuria (24h urine calcium 364.0 mg) but with normal renal function (serum creatinine 101.5μmol/L).And the remained part of left kidney stone was removed by flexible ureteroscope.As she was considered probably with an autosomal recessive FHHNC,an analysis of CLDN16 and CLDN19 gene mutations was performed using her and her parents'peripheral white blood cells.Results Mutation analysis revealed this patient had two heterozygous mutations in the CLDN16.One is an one-base deletion mutation in the 123th codon in exon 2:368delA.The other is a missense mutation in the 139th codon in exon 2:416C →T which resulted in an amino acid change Ala139Val.Her parents respectively had one of each heterozygous mutation.In the six months follow-up,an oral administration with hvdrochlorothiazide,potassium citrate,and calcium magesium supplements significantly reduced her hypomagnesaemia (serum magnesiun 1.0 mmol/L) and hypercalciuria (24-h urine calcium 156.0 mg),and no stone recurrence and aggravation of nephrocalcinosis and renal dysfunction occurred.Conclusions We diagnosed a patient with FHHNC who had a novel compound heterozygous mutation of CLDN16.This rare disease should be suspected if there are three constant clinical features of hypomagnesaemia,hypercalciuria and nephrocalcinosis,and verified with CLDN16 and CLDN19 gene test.Currently the option for treatment of FHHNC is symptomatic treatment until severe deterioration of renal function.The hydrochlorothiazide,potassium citrate,and calcium magesium supplements may have considerable effects on hypomagnesaemia and hypercalciuria.