The interaction between organelles is the focus of re-search in neural development.The contact site of endoplasmic reticulum and mitochondria is the focus of Parkinson's disease(PD)in recent years.The research shows that mitochondria,endoplasmic reticulum(ER),lysosome and other organelles play an important role in neurogenesis.Specifically,metabolic turnover,reactive oxygen species production,mitochondrial dy-namics,mitochondrial autophagy,mitochondria-mediated apop-tosis,and interactions between mitochondria and the ER all play a role in neurogenesis.In PD,abnormal ER-mitochondrial inter-action can affect mitochondrial calcium overload,mitochondrial fission and fusion imbalance,and lipid homeostasis disorder.Therefore,here we review the recent progress in the main regu-latory mechanisms of ER-mitochondrial interaction and address the effects of abnormal ER-mitochondrial interactions on PD.

Aim To investigate the effects of multi-gly-cosides of Tripterygium wilfordii(GTW)on mitochon-drial dynamics-related proteins and the mechanism of nephroprotective effects in IgA nephrophathy(IgAN)rats.Methods SPF grade male SD rats were random-ly divided into the Control group,modelling group,prednisone group(6.25 mg·kg·d-1)and GTW group(6.25 mg·kg·d-1).The IgAN rat model was established by the method of"bovine serum albumin(BSA)+carbon tetrachloride(CCl4)+lipopolysac-charide(LPS)".The total amount of urinary protein(24 h-UTP)and erythrocyte count in urine were meas-ured in 24 h urine.Blood biochemistry of serum albu-min(ALB),alanine aminotransferase(ALT),urea ni-trogen(BUN),and creatinine(Scr)were measured in abdominal aorta of the rats;immunofluorescence and HE staining were used to observe the histopathology of the kidneys;RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of key proteins regulating mitochondrial division and fu-sion:dynamin-related protein 1(Drp1),mitochondrial fusion protein 1(Mfn1),and mitochondrial fusion pro-tein 2(Mfn2),and PTEN-induced putative kinase 1(Pink1),in the kidney tissue of rats.Results GTW significantly reduced urinary erythrocyte count and 24 h-UTP,decreased serum ALT,BUN and Scr levels,in-creased serum ALB levels,improved renal histopatho-logical status in IgAN rats,increased the protein and mRNA expression levels of Mfn1,Mfn2,and Pink1,and decreased the protein and mRNA expression levels of Drp1 in renal tissues.Conclusions GTW may regu-late mitochondrial structure and maintain the dynamic balance of mitochondrial dynamics by promoting the ex-pression of Mfn1,Mfn2,Pink1 and decreasing Drp1.This may result in a reduction in urinary erythrocyte counts and proteinuria,and an improvement in renal function.

Aim To explore the mechanism of action of Tripterygium glycosides tablets on kidney of rats with IgA nephropathy based on inflammation-related path-ways.Methods Forty-five male SD rats of SPF grade were randomly divided into control group and modeling group.In addition to the blank group,the modeling group used the combination of bovine serum albumin(BSA)+carbon tetrachloride(CC14)+lipopolysac-charide(LPS)to establish the IgA nephropathy rat model.Successfully modeled rats were randomly divid-ed into the model group,the prednisone group and Tripterygium glycosides tablets group,and the treat-ment group was given the drug by gavage from the 13 th week,and the 24 hours urine,blood and kidney tis-sues of the rats were collected and examined after 4 weeks of the administration of the drug.Urine erythro-cyte count,quantitative 24-h urine protein(24 h-UTP),urea nitrogen(BUN),and blood creatinine(Scr)were detected in each group;serum interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)were detected by enzyme-linked immunosorbent assay(Elisa);the pathological changes in the renal tissues of the rats in each group were observed by horizontal hematoxylin-eosin(HE)staining;and the renal tis-sues in each group were observed by Western blotting.The expressions of LIGHT,HVEM,LTβR proteins and their mRNAs in rat kidney tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction(RT-PCR).Results Tripterygium glycosides tablets significantly reduced the levels of urinary erythrocyte count,24 h-UTP,BUN,and Scr in IgA nephropathy rats(P＜0.01),improved renal histopathology,lowered the levels of se-rum inflammatory factors IL-1β and TNF-α(P＜0.01),and lowered the levels of LIGHT,HVEM,LTβR proteins and their mRNA expression in renal tis-sues(P＜0.01).Conclusions Tripterygium glyco-sides tablets may inhibit the immune response and re-duce the release of inflammatory factors by down-regu-lating the LIGHT-HVEM/LT(3R pathway,thus reduc-ing the inflammatory response,lowering the urinary e-rythrocytes and urinary proteins,improving the renal nephron pathologic injury,and protecting the renal function.

Aim To investigate the effects of berberine(BBR)combined with 5'-n-ethylformamidoadenosine(NECA)on myocardial H9c2 and HL-1 cell damage induced by hypoxia/reoxygenation(H/R).Methods H9c2 and HL-1 cells were divided into the Control group,BBR group,NECA group,combined administra-tion group,H/R group,BBR+H/R group,NECA+H/R group,and combined administration+H/R group.CCK-8 was used to detect cell viability in each group.The TMRE kit was used to detect MMP.DCFH-DA was used to detect ROS content.The Mito SOX Red fluorescent probe was used to detect mitochondrial su-peroxide.The expressions of COX Ⅳ,Tom20,and Tim23 were detected by Western blot.The expression of COX Ⅳ and Tom20 genes was detected by qRT-PCR.Results In H9c2 cells,the cell viability and TMRE fluorescence intensity in the H/R group were significantly decreased compared with the Control group.The protein expressions of COX Ⅳ,Tom20,and Tim23,gene expressions of COX Ⅳ and Tom20,ROS,and mitochondrial superoxide contents were significant-ly increased.Compared with the H/R group,the cell viability of BBR and NECA were enhanced after ad-ministration alone.The contents of ROS and mitochon-drial superoxide were significantly decreased.In HL-1 cells,cell viability in the H/R group was significantly decreased compared with the Control group.The con-tents of ROS and mitochondrial superoxide were signifi-cantly increased.Compared with the H/R group,BBR and NECA alone and combined administration en-hanced cell viability.The contents of ROS and mito-chondrial superoxide were significantly decreased.Conclusion The administration of BBR and NECA a-lone or in combination can reduce the production of mi-tochondrial superoxide and cell ROS,thereby allevia-ting mitochondrial damage,alleviating oxidative stress damage,and ultimately reducing H/R-induced myocar-dial cell damage.

Transcatheter aortic valve replacement(TAVR)is the use of interventional catheter to transport the artificial heart valve to the aortic valve area through the patient's arterial,venous system or left ventricular apex,then release it to replace the original aortic valve to achieve normal physiological function.The"suicide left ventricle"phenomenon refers to the paradoxical hemodynamic collapse of dynamic left ventricular obstruction caused by left ventricular hypertrophy and hypersystole after the removal of the fixed valve obstruction of aortic stenosis after TAVR.The clinical manifestation is abnormal continuous hypotension that is ineffective to positive inotropic drugs during the operation or within a few hours after the operation.With the indications for transcatheter aortic valve surgery covering patients with low,medium and high risk of severe aortic stenosis,surgery-related complications have been reported to increase gradually."Suicide left ventricle"is worth studying and exploring as a fatal potential complication.This article mainly reviews four aspects of the overview of"suicide left ventricle",pathological mechanism,risk-related indicators,prevention strategies and treatment methods to be highly vigilant and make corresponding emergency plans for patients with aortic stenosis who may have suicide left ventricle risk,so as to minimize perioperative mortality.

This study was aimed at studying the phenotypic and molecular characteristics of a Salmonella Grumpensis isolate from a patient with diarrhea in Shanghai,to provide evi-dence for the prevention of salmonellosis.Biochemical identifi-cation,serum agglutination testing,antimicrobial susceptibility testing,and whole genome sequencing(WGS)were performed on isolate 2023JD76.Global Salmonella Grumpensis genome sequences were searched and downloaded for serotyping predic-tion,multilocus sequence typing(MLST),prediction of anti-microbia resistance genes and virulence genes,and phylogenetic analysis of 2023JD76.The 2023JD76 strain was identified as Salmonella Grumpensis(13,23:d:1,7)with ST2060,and was susceptible to 20 antimicrobial agents.Strain 2023JD76 carried the aminoglycoside resistance gene aac(6')-Iaa and five types of virulence genes:the adhesion genes csg and rat;the secretion and transport genes sip and inv;the typhoid toxin genes cdt and plt;the invasive gene nutrient metabolism factor mgt;and the antimicrobial peptide resistance factor mig.Global S.Grumpensis strains harbored ten types of antimicrobial resistance genes whose prevalence ranged from 58.33％to 100％.The global genome sequences of S.Grumpensis were divided into two lineages.Lineage I was dominated by ST751(88.89％,16/18),and lineage Ⅱ was dominated by ST2060(89.47％,17/19).The genome sequence of strain 2023JD76 belonged to lineage Ⅱ,and was closely related to the genome sequences from human fecal and human cerebrospinal fluid.This study provides the first report of a S.Grumpensis isolate from the stool of a patient with diarrhea in China.Considerable variability in antimicrobial resistance genes was observed among genome sequences from different sources,and the strains harbored a substantial number of virulence genes.Enhanced surveillance should be emphasized to prevent a potential risk of global dissemination.

Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

Objective:To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) .Methods:Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model.Results:Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy ( P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months ( P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL ( HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions:In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.