ObjectiveTo identify the pathogen species responsible for the wilt disease of Tetradium ruticarpum in Chongqing， investigate there biological characteristics， and screen effective fungicides， so as to provide a theoretical basis for disease control in production. MethodsThe pathogen was isolated via the tissue culture method. Pathogenicity was verified according to Koch's postulates. The pathogen was identified based on morphological characteristics and multi-gene phylogenetic analysis. The mycelial growth rate method was used for biological characterization of the pathogen and fungicide screening. ResultsThe pathogen colonies were nearly circular with irregular edges， white， short， velvety aerial hyphae， and pale purple undersides. Macroconidia were colorless， sickle-shaped， with 3-5 septa， while microconidia were transparent， elliptical， aseptate or with 1-2 septa. Multi-gene phylogenetic analysis showed that the pathogen clustered in the same clade as Fusarium fujikuroi with 100% support， which， combined with morphological characteristics， identified the pathogen causing wilt of T. ruticarpum in Chongqing as F. fujikuroi. The optimal conditions for the mycelial growth of F. fujikuroi were mung bean agar （MBA） with glucose as the carbon source， beef extract and yeast powder as nitrogen sources， 28 ℃， pH 7.0， and alternating light/dark conditions. The optimal conditions for sporulation were potato dextrose agar （PDA） with glucose as the carbon source， beef extract as the nitrogen source， 28 ℃， pH 7.0， and complete darkness. Among chemical fungicides， phenazine-1-carboxylic acid exhibited the strongest inhibitory effect on F. fujikuroi. Shenqinmycin and tetramycin were the most effective bio-fungicides. ConclusionThis study is the first to report F. fujikuroi as the causal agent of wilt disease in T. rutaecarpa. The chemical fungicide phenazine-1-carboxylic acid and the bio-fungicides shenqinmycin and tetramycin showed strong inhibitory effects against F. fujikuroi.

Parkinson's disease （PD） is a common neurodegenerative disorder characterized by motor impairments， with its pathological mechanisms involving multiple processes such as the degeneration of dopaminergic neurons and the abnormal aggregation of α-synuclein. Current Western medical treatments face challenges including diminished long-term efficacy and motor complications. In recent years， Traditional Chinese Medicine （TCM） has demonstrated advantages in the prevention and treatment of PD through its systematic regulatory capabilities， featuring multi-component， multi-target， and multi-pathway approaches.This article systematically reviews the roles of seven key signaling pathways-NF-κB， AMPK/mTOR， PI3K/Akt， MAPKs， Nrf2/ARE， Wnt/β-catenin， and BDNF/TrkB-in the pathological process of PD and the regulatory mechanisms of TCM. Research indicates that active ingredients of Chinese herbs and compound formulations can synergistically modulate these pathways， exerting comprehensive effects in inhibiting neuroinflammation， alleviating oxidative stress， promoting autophagy to clear abnormal proteins， and enhancing neurotrophic support. These signaling pathways form a complex regulatory network through crosstalk among key nodal molecules， constituting an intricate regulatory system in PD pathology. The multi-target intervention characteristics of TCM align well with this network-based regulatory requirement， achieving integrated anti-inflammatory， antioxidant， autophagy-regulating， and neurorestorative effects through synergistic multi-pathway modulation. This article systematically outlines the mechanisms of TCM in the coordinated regulation of multiple pathways， providing a theoretical basis for elucidating the pathological process of PD and the intervention mechanisms of TCM， while also offering new perspectives and directions for modern research on TCM in the prevention and treatment of PD.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.

Objective To analyze the effects of intravenous tirofiban following endovascular treatment on the prognosis of patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization.Methods This retrospective study included consecutive patients with acute anterior circulation ischemic stroke who underwent endovascular treatment but did not achieve successful recanalization.These patients were retrospectively enrolled from the Department of Neurology at Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,the Second Affiliated Hospital of Soochow University,Wuhan No.1 Hospital,and Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College)between January 2015 and April 2023.Baseline and clinical data were collected including age,sex,medical history(hypertension,diabetes,atrial fibrillation,hyperlipidemia),personal history(smoking and drinking),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification(large artery atherosclerosis,cardioembolism,or other types),Alberta stroke program early CT score(ASPECTS)on admission,intravenous thrombolysis,onset-to-puncture time(OTP),collateral circulation status(poor collaterals:American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]score 0-2;good collateral:ASTIN/SIR score 3-4),procedure duration(from femoral or radial artery puncture to device removal),occlusion site,number of passes for thrombus retrieval,and post-procedural modified thrombolysis in cerebral infarction(mTICI)grade.Patients were divided into a tirofiban group and a non-tirofiban group based on whether they received post-procedural intravenous tirofiban.The primary outcome is a favorable functional outcome at 90-day since onset(modified Rankin scale[mRS]score ≤ 3).Safety outcomes included mortality at 90-day since onset(mRS score 6),any intracranial hemorrhage within 24 h post-procedure,and symptomatic intracranial hemorrhage within 24 h post-procedure.1∶1 propensity score matchings using the nearest neighbor method was performed based on variables with P＜0.05 in the comparison between the tirofiban and non-tirofiban groups.Differences in primary and safety outcomes between the matched groups were compared.Univariate and multivariate Logistic regression analyses were conducted with favorable outcomes at 90 days as the dependent variable to evaluate the effect of intravenous tirofiban administration after endovascular therapy on 90-day prognosis in patients without successful recanalization.Results A total of 356 patients without successful recanalization after endovascular treatment were included,comprising 195 males and 161 females,with a median age of 70(61,78)years(32-92 years).Among them,76 and 280patients were assigned to the tirofiban and non-tirofiban groups,respectively.At 90 days,114 patients had favorable outcomes,while 242 had unfavorable outcomes.(1)Before the 1∶1 propensity score matching,significant differences were observed between the tirofiban and non-tirofiban groups in terms of admission NIHSS score,ASPECTS,good collateral circulation,intravenous thrombolysis,and mTICI grade(all P＜0.05).After 1∶1 propensity score matching,66 matched pairs(132 patients)were obtained.No significant differences in the baseline and clinical characteristics were found between the two groups after matching(all P＞0.05).(2)After 1∶1 matching,a significant difference was observed in the rate of favorable outcomes at 90 days between the two groups(48.5％[32/66]vs.30.3％[20/66],P=0.033)after propensity score matching,while no significant differences were found in 90-day mortality,intracranial hemorrhage within 24h,or symptomatic intracranial hemorrhage within 24h(all P＞0.05).(3)Univariate analysis after 1∶1 matching indicated that age,atrial fibrillation,smoking history,admission NIHSS score,M2 segment middle cerebral artery occlusion,good collateral circulation,number of passes for thrombus retrieval,and tirofiban treatment were factors influencing favorable outcomes at 90 days.Multivariate Logistic regression analysis showed that younger age(aOR,0.942,95％CI 0.906-0.978,P=0.002),lower admission NIHSS score(aOR,0.855,95％CI 0.777-0.941,P=0.001),good collateral circulation(aOR,5.534,95％CI 2.141-14.301,P＜0.01),tirofiban treatment(aOR,2.774,95％CI 1.092-7.046,P=0.032),and M2 segment MCA occlusion(reference:internal carotid artery occlusion;aOR,4.874,95％CI 1.428-16.632,P=0.011)were independent predictors of favorable outcomes at 90 days.Conclusions Intravenous tirofiban administration after endovascular therapy may improve 90-day neurological outcomes in patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization without increasing the risk of hemorrhage.Further large-scale randomized controlled trials are warranted to validate these findings.

Objective:To analyze the distribution and epidemiological characteristics of non-bacterial pathogens in hospitalized children with acute respiratory infections at a tertiary pediatric hospital in Shanghai during 2023.Methods:A retrospective study was conducted on 10 591 children with acute respiratory tract infections who were hospitalized in Shanghai Children's Hospital from January to December 2023. A multiplex PCR combined with capillary electrophoresis platform was used to detect 11 common non-bacterial respiratory pathogens（including viruses and atypical pathogens）. Statistical analysis was carried out using SPSS 29.0 software. Qualitative data were presented as numbers and percentages，and the Chi-square test was employed to make comparisons between groups，aiming to analyze the differences in the distribution of different pathogens according to gender，age group，and season. Additionally，based on the severity of the disease，patients were calssified into a severe pneumonia group and a non-severe pneumonia group to further explore the characteristics of the pathogen spectrum of severe pneumonia.Results:The total detection rate of pathogens was 54.39%（5 760/10 591），and the proportion of mixed infections was 12.76%（735/5 760）. The dominant pathogens and their proportions were as follows： Mycoplasma pneumoniae（19.20%，2 034/10 591），human rhinovirus（12.16%，1 288/10 591），influenza A virus（8.31%，880/10 591），and respiratory syncytial virus（8.14%，862/10 591）. Epidemiological characteristics showed that：（1）In terms of age： Mycoplasma pneumoniae was more common in older children（29.55%，901/3 049，in the school-age group，χ 2 = 653.67， P<0.001）. Influenza A virus had a high incidence in the adolescent group（11.34%，45/397，χ 2=48.69， P<0.001）. Respiratory syncytial virus was most susceptible in the infant group（20.94%，280/1 337，χ 2=739.92， P<0.001）. Human rhinovirus showed the characteristic of general susceptibility across all ages.（2）Monthly and seasonal distribution： Mycoplasma pneumoniae had a seasonal epidemic in summer and autumn（it began to rise in May and peaked in October at 34.22%，439/1 283）；influenza A virus had a bimodal distribution in spring and winter（the peak was 37.15% in March，315/848）；respiratory syncytial virus had a dominant epidemic in spring and summer（the detection rate was 21.24% in May，206/970），and human rhinovirus was prevalent throughout the year.（3）Clinical correlation：The detection rate of pathogens in the severe pneumonia group was significantly higher than that in the non-severe group：84.19%（426/506） vs 2.89%（5 334/10 085），χ 2=56.23， P<0.001. Conclusions:In 2023，the pathogen spectrum of hospitalized children with acute respiratory infections in the Shanghai area exhibits an epidemic pattern dominated by Mycoplasma pneumoniae，and its transmission dynamics are significantly age-dependent. This study delineates the pathogen-host-environment tripartite interactions，establishing an evidence-based foundation for formulating precision diagnostic-therapeutic algorithms and seasonal nosocomial infection prevention frameworks.

Conventional X-ray coronary angiography using iodinated contrast media is the gold standard technique for diagnosing coronary artery disease and determining treatment strategies,including percutaneous coronary intervention(PCI).However,severe allergy to iodinated contrast agents and renal insufficiency,as well as severely hyperthyroid patients,limit the use of iodinated contrast agents,especially in the face of acute coronary syndromes requiring emergency PCI.Gadolinium-based contrast agent is mainly developed for use in magnetic resonance imaging examinations,and there are few studies on whether it can be used for coronary angiography.We report a case of a patient who had a severe allergic reaction to an iodine contrast agent,and ultimately had a successful complex coronary intervention guided by the application of Gadolinium-based contrast agent combined with intravascular ultrasound.This case and a review of the relevant literature provide new ideas for coronary artery examination and treatment in patients with contraindications to iodine.

BACKGROUND:Basement membrane genes are closely related to the occurrence and development of rheumatoid arthritis,but the role of basement membrane-related genes in the pathogenesis of rheumatoid arthritis under different traditional Chinese medicine patterns is not yet clear.OBJECTIVE:To explore the differences in the pathogenesis of rheumatoid arthritis with five different traditional Chinese medicine syndromes based on the analysis of basement membrane-related genes and transcriptomics,and to predict potential therapeutic drugs.METHODS:Rheumatoid arthritis-related traditional Chinese medicine syndrome microarray data and basement membrane-related genes were collected from the GEO database.The differentially expressed genes were screened using the R-limma package,and the expression trends were analyzed using the Mfuzz package.The protein-protein interaction network was constructed using the STRING database and key genes were selected using UPset.The differentially expressed genes were subjected to gene set enrichment analysis(GSEA)and enrichment analysis using the R-clusterProfiler package.Receiver operating characteristics curves were plotted to evaluate the diagnostic value of core basement membrane-related targets for each of the five syndromes.The immune infiltration of each syndrome was calculated using the CIBERSORT algorithm.Finally,potential traditional Chinese medicines and small molecule drugs targeting core basement membrane-related genes for the treatment of different traditional Chinese medicine syndromes of rheumatoid arthritis were predicted using SymMap and COREMINE databases.RESULTS AND CONCLUSION:(1)67,47,59,57,and 55 basement membrane-related differentially expressed genes were screened for the five traditional Chinese medicine syndromes of rheumatoid arthritis(obstruction syndrome,cold-dampness obstruction syndrome,liver-kidney deficiency syndrome,qi-blood deficiency syndrome,and blood stasis obstructing collaterals syndrome),with 5,7,5,3,and 5 key targets identified,respectively.(2)The most enriched biological processes in each syndrome were extracellular matrix adhesion,immune cell migration,collagen metabolism,and extracellular matrix receptor interaction,PI3K-Akt,focal adhesion,and Rap1 signaling pathways.(3)According to the predictions,Smilax glabra,Sargentodoxa cuneata,and Polygonatum sibiricum have the most potential as traditional Chinese medicines for the treatment of the five traditional Chinese medicine syndromes of rheumatoid arthritis by affecting basement membrane-related genes.(4)These results indicate that abnormal expression of basement membrane-related genes may affect the occurrence and development of rheumatoid arthritis through the regulation of cell adhesion,immune cell migration,and inflammatory reactions,among other pathways.These effects vary among different syndromes,with ITGA6 serving as a common diagnostic marker for the five traditional Chinese medicine syndromes of rheumatoid arthritis.Traditional Chinese medicines with heat-clearing and detoxifying properties may be potential effective drugs for the treatment of different syndromes of rheumatoid arthritis.

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.