Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To evaluate the viral composition in respiratory samples from hospitalized children with acute respiratory infections in Yancheng，Jiangsu province，between January 2024 and June 2025 using metagenomic next-generation sequencing（mNGS）.Methods:A total of 247 respiratory specimens，including throat swabs，sputum，and bronchoalveolar lavage fluid，were collected from 247 hospitalized children in Yancheng，Jiangsu province，during the study period. The viral composition in these samples was detected and analyzed using mNGS technology.Results:Among the 247 cases，there were 136 cases of pneumonia（including 4 cases of severe pneumonia），45 cases of bronchopneumonia，27 cases of upper respiratory tract infection，and 39 cases of bronchitis. The ages of the patients ranged from 41 days to 14 years，with a median age of 3 years. High-throughput sequencing results showed that the positive detection rate for viruses in the respiratory samples was 89.88%（222/247），The detection rate of viruses causing respiratory tract infections was 69.23%（171/247），With RNA viruses detected in 71.65%（177/247）of the cases and DNA viruses in 43.32%（107/247）. The top three viruses detected were rhinovirus（24.29%，60/247），human herpesvirus 7（HHV-7）（21.86%，54/247），and influenza A H1N1（20.24%，50/247）. The common detected viruses that cause respiratory infections are rhinovirus（24.29%），influenza A virus H1N1（20.24%），RSV（17.81%），metapneumovirus（10.53%），enterovirus（6.88%），parainfluenza virus（6.07%），bocavirus（6.07%），coronavirus（2.43%），and adenovirus（2.43%）. In children with pneumonia，the top two respiratory viruses detected were rhinovirus（19.85%，27/136）and influenza A H1N1（16.91%，23/136）. In children with bronchopneumonia，the main viruses detected were rhinovirus（31.11%，14/45）and respiratory syncytial virus（24.44%，11/45）. In children with upper respiratory tract infections，the main viruses detected were influenza A H1N1（33.33%，9/27）and rhinovirus（25.93%，7/27）. In children with bronchitis，the main viruses detected were rhinovirus（30.77%，12/39）and respiratory syncytial virus（25.64%，10/39）. Among the 4 cases of severe pneumonia，the viruses detected were influenza A H1N1（2/4），respiratory syncytial virus（1/4），and bocavirus（1/4）.Conclusion:mNGS analysis revealed a high positive detection rate of respiratory viruses（89.88%）in hospitalized children with acute respiratory infections in Yancheng，Jiangsu，from January 2024 to June 2025，with influenza A H1N1 and rhinovirus being the most predominant.

Objective To evaluate the viral composition in respiratory samples from hospitalized children with acute respiratory infections in Yancheng，Jiangsu province，between January 2024 and June 2025 using metagenomic next-generation sequencing（mNGS）.Methods:A total of 247 respiratory specimens，including throat swabs，sputum，and bronchoalveolar lavage fluid，were collected from 247 hospitalized children in Yancheng，Jiangsu province，during the study period. The viral composition in these samples was detected and analyzed using mNGS technology.Results:Among the 247 cases，there were 136 cases of pneumonia（including 4 cases of severe pneumonia），45 cases of bronchopneumonia，27 cases of upper respiratory tract infection，and 39 cases of bronchitis. The ages of the patients ranged from 41 days to 14 years，with a median age of 3 years. High-throughput sequencing results showed that the positive detection rate for viruses in the respiratory samples was 89.88%（222/247），The detection rate of viruses causing respiratory tract infections was 69.23%（171/247），With RNA viruses detected in 71.65%（177/247）of the cases and DNA viruses in 43.32%（107/247）. The top three viruses detected were rhinovirus（24.29%，60/247），human herpesvirus 7（HHV-7）（21.86%，54/247），and influenza A H1N1（20.24%，50/247）. The common detected viruses that cause respiratory infections are rhinovirus（24.29%），influenza A virus H1N1（20.24%），RSV（17.81%），metapneumovirus（10.53%），enterovirus（6.88%），parainfluenza virus（6.07%），bocavirus（6.07%），coronavirus（2.43%），and adenovirus（2.43%）. In children with pneumonia，the top two respiratory viruses detected were rhinovirus（19.85%，27/136）and influenza A H1N1（16.91%，23/136）. In children with bronchopneumonia，the main viruses detected were rhinovirus（31.11%，14/45）and respiratory syncytial virus（24.44%，11/45）. In children with upper respiratory tract infections，the main viruses detected were influenza A H1N1（33.33%，9/27）and rhinovirus（25.93%，7/27）. In children with bronchitis，the main viruses detected were rhinovirus（30.77%，12/39）and respiratory syncytial virus（25.64%，10/39）. Among the 4 cases of severe pneumonia，the viruses detected were influenza A H1N1（2/4），respiratory syncytial virus（1/4），and bocavirus（1/4）.Conclusion:mNGS analysis revealed a high positive detection rate of respiratory viruses（89.88%）in hospitalized children with acute respiratory infections in Yancheng，Jiangsu，from January 2024 to June 2025，with influenza A H1N1 and rhinovirus being the most predominant.

Objective To elucidate the molecular genetic etiology of patients with disorders of sex development(DSD)using whole exome sequencing(WES),thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities.Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021,with an additional family study for one proband.Genomic DNA was extracted from patients for WES analysis.Single nucleotide polymorphism(SNP)and insertions/deletion(InDel)tests were identified using SAMtools software in conjunction with established SNP and InDel databases.Copy number variations(CNVs)at the exon level were detected using ExomeDepth,while the potential pathogenicity of mutations was predicted with PolyPhen-2,Mutation taster and PyMol software,with Sanger sequencing employed for confirmation.Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD.Among the 46,XX DSD patients,the SRY gene was detected in 14 patients.In the remaining 8 patients and a proband's families,single nucleotide site variations(SNVs)of NR5A1,PROKR2 and ANOS1 genes were identified in 2 patients,and CNVs in CYP21A2 gene were found in 4 patients.The pathogenicity of CYP21A2 EX1 Dup has been previously reported,while the remaining 3 CNVs were of uncertain significance,and no DSD-related mutations were detected in 2 patients.In the WES analysis of 46,XY DSD patients,10 pathogenic or likely pathogenic SNVs across 5 genes(SRY,AR,SRD5A2,CYP17A1,and NR5A1)were identified in 14 patients.Additionally,5 likely pathogenic CNVs involving the CYP21A2,AKR1C2,CBX2,and NR5A1 genes were detected in 5 patients,comprising 3 deletions and 2 duplications.Novel SNVs in NR5A1(c.722G>T,c.48C>G)and ANOS1 c.564A>T were identified,with no prior reports in relevant databases.The pathogenicity of CYP21A2 EX1 Dup is documented in related databases,while the remaining CNVs have not been previously reported.Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD,broadened the spectrum of known DSD-related gene mutations,and deepened our comprehension of DSD pathogenesis,offering valuable support for genetic counseling.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.