Plasminogen activator is a kind of enzyme that plays a key role in the process of physiological hemostasis and thrombolysis. Its main function is to convert plasminogen into active plasmin, thereby initiating the dissolution of fibrin and maintaining blood mobility. This article discusses the safety of plasminogen activator in the intraocular application, elaborates on the types, structure, physiological function and mechanism of action of plasminogen activator in the eye. The analysis addresses the ocular tissue damage and systemic adverse reactions that may be caused by the application of plasminogen activator in the eye, and the risks and countermeasures combined with relevant research examples, aiming to provide reference for the safe application of plasminogen activator in clinical practice.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Enteric human adenovirus(HAdV),a common cause of acute viral gastroenteritis in children,frequently triggers spo-radic infections,nosocomial transmissions,and outbreaks in kindergarten settings.This study was aimed at investigating the molecular characteristics and genetic evolution of enteric HAdV among patients with acute gastroenteritis younger than 5 years in China,to pro-vide foundational data for disease prevention and control.A total of 8 074 stool samples were collected from hospitalized or outpatient children younger than 5 years with acute gastroenteritis in China during 2023.HAdV screening was conducted with real-time fluores-cence PCR.Positive samples were sequenced,then subjected to bioinformatics analysis including genotyping,homology assessment,and phylogenetic analysis with GenBank,BioAider,and MEGA11.0.A total of 370 samples(4.58%)tested positive for HAdV.Two enteric HAdV genotypes were identified:HAdV-F41(which predominated,at 98.09%)and HAdV-F40(1.90%).HAdV-F41 was the dominant genotype among patients with acute gastroenteritis younger than 5 years in China.Bioinformatics analysis indicated that the predominant HAdV lineages in China were lineage 1 and 2,whereas European lineage 3 showed no influence.Systematic and long-term surveillance of HAdV should help elucidate its diversity and evolutionary patterns in China,thereby providing scientific evi-dence for developing more effective prevention strategies.

This study investigated the full-genome molecular characteristics of a rotavirus vaccine-derived strain,G1P[8]geno-type A group rotavirus RVA/Human-wt/CHN/HN1140/2021/G1P[8](referred to as HN1140).The gene fragments of the HN1140 strain were amplified with reverse transcription-polymerase chain reaction(RT-PCR)combined with whole-genome primers to obtain the full genome sequence.Genotyping was performed with the online genotyping tool RotaC 2.0,and similarity and genetic evolution analyses for each gene segment were conducted in DNAstar5.1 and MEGA11.0 software.The genotype of the HN1140 strain was deter-mined to be G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis demonstrated that all 11 genomic segments clus-tered closely with the RotaTeq vaccine strains,sharing 99.7%-100%nucleotide sequence similarity.Notably,VP1,VP2,VP6,and NSP2-NSP5 segments showed 100%nucleotide identity with RotaTeq strains.Comparative genomic analysis identified 13 nucleotide and 8 amino acid substitutions between HN1140 and RotaTeq strains,localized within the VP7,VP4,VP1,VP2,VP3,and NSP1 segments.The HN1140 strain exhibited the genotype G1-P[8]-A3-T6-H3,which was consistent with the typical profile of a vaccine-derived reassortant.This strain demonstrated high genetic similarity to RotaTeq vaccine strains,with nucleotide sequence identity ranging from 99.7%to 100%.These findings suggested that HN1140 evolved from RotaTeq vaccine strains through genetic reassortment.

Enteric human adenovirus(HAdV),a common cause of acute viral gastroenteritis in children,frequently triggers spo-radic infections,nosocomial transmissions,and outbreaks in kindergarten settings.This study was aimed at investigating the molecular characteristics and genetic evolution of enteric HAdV among patients with acute gastroenteritis younger than 5 years in China,to pro-vide foundational data for disease prevention and control.A total of 8 074 stool samples were collected from hospitalized or outpatient children younger than 5 years with acute gastroenteritis in China during 2023.HAdV screening was conducted with real-time fluores-cence PCR.Positive samples were sequenced,then subjected to bioinformatics analysis including genotyping,homology assessment,and phylogenetic analysis with GenBank,BioAider,and MEGA11.0.A total of 370 samples(4.58%)tested positive for HAdV.Two enteric HAdV genotypes were identified:HAdV-F41(which predominated,at 98.09%)and HAdV-F40(1.90%).HAdV-F41 was the dominant genotype among patients with acute gastroenteritis younger than 5 years in China.Bioinformatics analysis indicated that the predominant HAdV lineages in China were lineage 1 and 2,whereas European lineage 3 showed no influence.Systematic and long-term surveillance of HAdV should help elucidate its diversity and evolutionary patterns in China,thereby providing scientific evi-dence for developing more effective prevention strategies.

This study investigated the full-genome molecular characteristics of a rotavirus vaccine-derived strain,G1P[8]geno-type A group rotavirus RVA/Human-wt/CHN/HN1140/2021/G1P[8](referred to as HN1140).The gene fragments of the HN1140 strain were amplified with reverse transcription-polymerase chain reaction(RT-PCR)combined with whole-genome primers to obtain the full genome sequence.Genotyping was performed with the online genotyping tool RotaC 2.0,and similarity and genetic evolution analyses for each gene segment were conducted in DNAstar5.1 and MEGA11.0 software.The genotype of the HN1140 strain was deter-mined to be G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis demonstrated that all 11 genomic segments clus-tered closely with the RotaTeq vaccine strains,sharing 99.7%-100%nucleotide sequence similarity.Notably,VP1,VP2,VP6,and NSP2-NSP5 segments showed 100%nucleotide identity with RotaTeq strains.Comparative genomic analysis identified 13 nucleotide and 8 amino acid substitutions between HN1140 and RotaTeq strains,localized within the VP7,VP4,VP1,VP2,VP3,and NSP1 segments.The HN1140 strain exhibited the genotype G1-P[8]-A3-T6-H3,which was consistent with the typical profile of a vaccine-derived reassortant.This strain demonstrated high genetic similarity to RotaTeq vaccine strains,with nucleotide sequence identity ranging from 99.7%to 100%.These findings suggested that HN1140 evolved from RotaTeq vaccine strains through genetic reassortment.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective To investigate the risk factors for the formation of infectious stones among residents in western Fujian Province and construct a nomogram model for preoperative prediction of the risk of infectious stones. Methods Clinical data of 204 patients who received treatment for urinary tract stones at Longyan People′s Hospital Affiliated to Xiamen Medical University from October 2021 to November 2023 were analyzed. All patients underwent stone composition analysis. Univariate and multivariate Logistic regression analysis were used to screen independent risk factors for infectious stones, construct a nomogram model for predicting the risk of infectious stones, and the discriminative power and accuracy of the model was evaluated. Results Based on the results of stone composition analysis, 204 patients were divided into infectious stone group(56 cases) and non-infectious stone group(148 cases). Univariate and multivariate Logistic regression analysis showed that female (OR=2.602, 95%CI, 0.766 to 8.842, P=0.039), diabetes (OR=9.751, 95%CI, 2.547 to 17.332, P=0.001), long diameter of stones (OR=1.123, 95%CI, 1.046 to 4.207, P=0.031), moderate to severe hydronephrosis (OR=4.173, 95%CI, 1.256 to 13.865, P=0.020), high urine pH value (OR=6.078, 95%CI, 1.922 to 19.216, P=0.002), and positive urine culture (OR=6.060, 95%CI, 1.398 to 16.262, P=0.016) were independent risk factors for infectious stones. A nomogram model for predicting the risk of infectious stones was constructed based on independent risk factors. The area under the curve of this model for predicting infectious stones was 0.860, which was significantly larger than the area under the curve predicted by gender, diabetes, stone long diameter, degree of hydronephrosis, urine pH value, and urine culture results (P < 0.05). The model was validated by 1 000 internal resampling, with an average absolute error of 1.8%, indicating a high consistency between the predicted risk of infectious stones and the actual situation. Conclusion Female, diabetes, long diameter of stones, moderate to severe hydronephrosis, high urine pH value, and positive urine culture are independent risk factors for infectious stones among residents in western Fujian Province. The nomogram model constructed based on these factors can predict the risk of infectious stones preoperatively with high predictive efficiency.

Objective To explore the mechanisms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in improvement of renal injury in rats with diabetic nephropathy (DN) by regulating mammalian target of rapamycin (mTOR)/p70 ribosome protein S6 kinase (S6K1)/coiled-coil myosin-like Bcl-2-interacting protein (Beclin 1) pathway. Methods The model of SD rats with DN was established by a method of high-fat diet combined with intraperitoneal injection of streptozotocin, and they were randomly divided into model group, MSC-EVs group, and MSC-EVs+MHY1485 (mTOR activator) group, with 12 rats in each group. Another 12 SD rats were normally fed for 6 weeks and then intraperitoneally injected with an equal dose of sodium citrate solution as controls. After grouping with MSC-EVs and MHY1485, blood glucose and levels of renal function indicators [blood urea nitrogen (BUN), serum creatinine (Scr), and urinary microalbumin (UmALB)] in rats were detected. HE staining was used to detect the pathological morphology of renal tissue in rats of each group; immunohistochemistry was used to detect the expression of mTOR/S6K1/Beclin 1 pathway related proteins in the renal tissues of rats in each group; the Western blot was used to detect the mTOR/S6K1/Beclin 1 pathway and autophagy-related protein expression in the renal tissues of rats in each group. Results Compared with the control group, the renal tissue morphology of rats in the model group were impaired, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, p-mTOR/mTOR, p-S6K1/S6K1 increased significantly (P < 0.05), while microtubule associated protein 1A/1B light chain 3 (LC3) Ⅱ/LC3Ⅰ, expression of Beclin 1 protein, and relative positive expression of Beclin 1 significantly reduced (P < 0.05); compared with the model group, the MSC-EVs group had less impairment in the renal tissue morphology, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, p-mTOR/mTOR, and p-S6K1/S6K1 decreased significantly (P < 0.05), while expression of LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 increased significantly (P < 0.05); compared with the MSC-EVs group, the impairment of the renal tissue morphology was worse in the MSC-EVs+MHY1485 group, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, expression of p-mTOR/mTOR, and p-S6K1/S6K1 increased significantly (P < 0.05), while the expression of LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 decreased significantly (P < 0.05). Conclusion MSC-EVs can enhance autophagy, reduce levels of blood glucose, Scr, BUN and urinary protein in rats with DN, alleviate renal tissue damage, and the mechanism may be achieved by inhibiting the activation of the mTOR/S6K1/Beclin 1 pathway.