OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

This article reports the diagnosis and treatment of one patient with fascioliasis of the common bile duct, aiming to provide reference for the clinical diagnosis and treatment of this disease. The patient sought medical attention due to long-term symptoms such as abdominal pain, abdominal distension, nausea, and vomiting. Imaging examinations displayed dilatation of the common bile duct and intrahepatic bile ducts, and the patient was admitted to the hospital with a diagnosis of “common bile duct stone”. Through endoscopic retrograde cholangiopancreatography and choledochoscopy, two worms were collected from the common bile duct, which were identified as Fasciola hepatica by high-throughput sequencing.

ObjectiveTo analyze the effects of the progestin-primed ovarian stimulation （PPOS） protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation genetic testing for aneuploidy （PGT-A） cycles were selected as study participants （a total of 656 cycles and 3 081 blastocysts）. Participants were divided into two age groups （≤35 years and >35 years） and further stratified by ovarian stimulation protocol： the Progestin-Primed Ovarian Stimulation （PPOS） group （n=48 and 60， respectively）， the Luteal Phase Long Protocol （LP） group （n=160 and 57， respectively）， and the Gonadotropin-Releasing Hormone Antagonist Protocol （AP） group （n=220 and 111， respectively）. Baseline characteristics， ovarian stimulation outcomes， and embryo development parameters were compared among the three protocols within each age group. Additionally， clinical pregnancy outcomes of the first frozen embryo transfer （FET） cycle were compared. The primary outcome measure was the embryo euploidy rate. Results① In the ≤35 years age group， baseline follicle-stimulating hormone （bFSH） levels were significantly higher in the PPOS group compared to the LP and AP groups， and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group （P < 0.05）. In the >35 years age group， bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group （P < 0.05）.② In the ≤35 years group， there were no significant differences in the rates of metaphase II （MII） oocytes， 2-pronuclei （2 PN） zygotes， cleavage， 2 PN cleavage， blastocyst formation， high-quality embryos， or embryo euploidy between the PPOS group and either the LP or AP groups. However， the PPOS group showed significantly lower values for the following parameters compared to the other two groups： total oocytes retrieved， number of MII oocytes， number of 2 PN zygotes， number of cleaved embryos， number of 2 PN cleaved embryos， number of blastocysts formed， number of high-quality embryos， number of high-grade blastocysts， number of transferable embryos， number of cryopreserved embryos， number of biopsied blastocysts， number of euploid embryos， and the rate of obtaining at least one euploid embryo. In the >35 years group， no significant differences were observed among the PPOS， LP， and AP groups in the rates of MII oocytes， 2 PN cleavage， blastocyst formation， or in the number of euploid embryos， euploidy rate， and the rate of obtaining at least one euploid embryo. However， the PPOS group had significantly lower numbers of total oocytes retrieved， MII oocytes， 2 PN zygotes， cleaved embryos， 2 PN cleaved embryos， blastocysts formed， transferable embryos， and cryopreserved embryos compared to the LP group （P<0.05）. The high-quality embryo rate was significantly lower in the PPOS group than in the AP group （P<0.05）. The numbers of high-quality embryos， high-grade blastocysts， and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups （P<0.05）. Notably， the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group， and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups （P<0.05）.③ No significant differences were found among the three groups in the biochemical pregnancy rate， clinical pregnancy rate， live birth rate， early miscarriage rate， and late miscarriage rate following the first FET cycle. ConclusionCompared to the other two protocols， the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However， in freeze-all cycles with PGT-A， the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women， but it can be considered as a viable option for women of advanced maternal age.

N-acetylcysteine (NAC) is an acetylated derivative of cysteine that exerts multiple biological activities, including antioxidant, anti-inflammatory, antimicrobial, and mucolytic effects, and has been widely used clinically for the treatment of respiratory diseases. NAC not only directly scavenges reactive oxygen and nitrogen species and strengthens endogenous antioxidant defenses by promoting glutathione synthesis but also modulates immune responses and suppresses inflammatory signaling pathways such as nuclear factor kappa B, thereby attenuating inflammation. In addition, NAC disrupts biofilm architecture by cleaving disulfide bonds, reduces microbial virulence, and enhances the penetration of antimicrobial agents, conferring robust antibacterial and antibiofilm activities. The initiation and progression of oral diseases—including dental caries, periodontal disease, pulpal-periapical disease, and infectious oral mucositis—are closely associated with pathogenic infection, oxidative stress, and dysregulated immune-inflammatory responses. NAC can inhibit Streptococcus mutans adhesion and biofilm formation, thereby reducing cariogenic virulence; mitigate periodontal tissue destruction through antimicrobial, anti-inflammatory, and antioxidant actions, and may modulate bone metabolism; enhance the clearance of Enterococcus faecalis biofilms and improve the efficacy of antimicrobial therapy; and inhibit the growth and hyphal formation of Candida albicans. Collectively, NAC is emerging as a promising agent for the prevention and treatment of oral infectious diseases. This review systematically summarizes the major bioactivities of NAC, its mechanistic actions in oral infectious diseases, and its therapeutic prospects, with the aim of providing a theoretical basis for future basic and clinical investigations.

The child, male,11 years old, Han nationality, student of Qiandongnan Miao Autonomous Prefecture, Guizhou Province, visited the General Hospital of Hunan Medical University on October 1,2024 due to“cough, chest tightness for 10 days and pericardial effusion was found for 8 days.”The child has a history of eating raw crabs. Admission examination: shortness of breath, slightly cyanotic lips, mild trifoveal symptoms, low heart sound, and routine blood showed significant eosinophil elevation. Serological examination showed that pulmonary fluke antibody IgG was positive, chest and abdomen CT and cardiac ultrasound showed a large amount of pericardial effusion, medium pleural effusion on the right side with lower right lung insufficiency, small pleural effusion on the left side, small effusion on the abdominal cavity, three-point Slight reflux of the valve. Considering that it is a clinical diagnosis case of complication flukesomyces disease, the child was given a praziquantel tablet,25 mg/kg,3 times a day, for 3 consecutive days. The treatment was treated at the above dose for 1 week interval for 1 course of treatment, and 3 courses were given. After three months, the child recovered well after the follow-up visit. The child did not complain of special discomfort, and the CT showed a small amount of effusion.

AIM:To investigate the mechanism of action of Tamarix chinensis Lour.on streptozotocin-induced type 2 diabetes mellitus(T2DM)through network pharmacology,molecular docking and ex-perimental validation.METHODS:Using the TCSMP database and Swiss Target Prediction tools screen the active components and predict potential tar-gets in Tamarix chinensis Lour..Retrieving potential disease targets associated with T2DM from data-bases such as GeneCards,OMIM,and DisGeNET.The intersection targets of Tamarix chinensis Lour.and T2DM disease was obtained through Venny platform.The STRING database was used to con-structed PPI network,and Cytoscape 3.8.0 soft-ware was use to visualized.GO function enrich-ment and KEGG pathway enrichment analysis were performed through the Metascape database.Dock-ing of important target proteins and compounds was carried out by AutoDock software.SPF grade male rats were randomly divided into normal group,model group,MET group(88.5 mg/kg),TE high-dose(800 mg/kg)group,TE medium-dose(400 mg/kg)group and TE low-dose(200 mg/kg)group(n=10).High-fat and high sugar feed com-bined with low dose STZ(45 mg/kg)was used to in-duce T2DM rat model,and the rats were adminis-tered orally for 5 weeks.Fasting blood glucose(FBG),insulin(FINS)level and HOMA-IR index,bio-chemical indicators[superoxide dismutase(SOD),malondialdehyde(MDA),glycosylated hemoglobin A1c(HbA1c)and inflammatory factor[interleukin-1β(IL-1β),tumor necrosis factor α(TNF-α),vascu-lar cell adhesion molecular(VCAM-1)levels of the rats were also observed;morphological changes of renal tissue was observe by HE staining.RESULTS:Based on the screening conditions of oral bioavail-ability(OB)≥ 30％and drug like properties(DL)≥0.18,a total of 19 main active ingredients with po-tential therapeutic effects on T2DM were screened from Tamarix chinensis Lour.,including ergosta-5,24(28)-dien-3,7,16-triol,quercetin-3,3'-dimethyl ether,kaempferol,quercetin,and others.By analyz-ing the potential targets of Tamarix chinensis Lour.for treating T2DM,a total of 185 potential target genes were screened,including SRC,EGFR,HSP90AA1,AKT1,ESR1,H1F1A,TNF,PIK3R1,etc,in-volving cancer signaling pathways,insulin resis-tance,MAPK signaling pathways,PI3K Akt signaling pathways,etc.Molecular docking results showed that the binding energies were all less than-5.0 kcal/mol,indicating that a strong binding abili-ty between the active ingredients screened by Tam-arix chinensis Lour.and the potential targets for the treatment of T2DM.The animal experiment re-sults showed that compared with the model group,the weight loss of rats in the MET and TE groups was slowed down,and the levels of FBG,FINS,MDA,HbA1c,IL-1β,TNF-α,VCAM-1,HOMA-IR in-dex were reduced,the SOD level was increased,and the differences were statistically significant(P＜0.05,P＜0.01),Renal tissue cellular morphology also showed notable improvement.Most importantly,all these results demonstrating dose-dependent ef-fects.CONCLUSION:Tamarix chinensis Lour.dis-plays a significant therapeutic effect on T2DM through multi-component,multi-target,and multi-pathway synergistic actions to improve blood glu-cose levels.The findings of this study provide a the-oretical basis for the clinical application of Tamarix chinensis Lour.in the treatment of T2DM.

Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53％(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P＜0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P＞0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P＜0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62％of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P＜0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.

Objective:To screen the genes of suspected Mediterranean anemia patients (thalassemia) among the Bouyei in Qianxinan Bouyei and Miao Autonomous Prefecture (referred to as Qianxinan Prefecture) and to learn about the genotype and spatial distribution of thalassemia.Methods:The study subjects were Bouyei suspected thalassemia patients who visited Qianxinan Prefecture People's Hospital from November 2020 to September 2024 ( n = 4 055). Gap polymerase chain reaction (Gap-PCR) and high-throughput sequencing were used to screen for genetic variations in thalassemia. Based on the screening data, ArcMap 10.8.2 software was used to draw a spatial distribution map of thalassemia. Results:A total of 2 467 cases of thalassemia genes were detected, with an overall detection rate of 60.84%. Among them, 1 474 cases of α-thalassemia were detected, with a detection rate of 36.35%; 757 cases of β-thalassemia were detected, with a detection rate of 18.67%; and 236 cases of αβ-combined thalassemia were detected, with a detection rate of 5.82%. The spatial distribution showed that the overall detection rate of thalassemia among Bouyei in Zhenfeng County was the highest (66.83%, 268/401), the detection rate of α-thalassemia in Xingyi City was the highest (39.20%, 305/778), the detection rate of β-thalassemia in Anlong County was the highest (23.71%, 55/232), while the detection rate of αβ-combined thalassemia in Ceheng County was the highest (7.75%, 95/1 226).Conclusions:The detection rate of suspected thalassemia genes in Bouyei patients in Qianxinan Prefecture is relatively high, with α-thalassemia being predominant, and there are significant spatial distribution differences.

Meniere's disease represents an idiopathic inner ear disorder characterized by endolymphatic hy-drops.Currently,the research methods for identifying genes associated with this disease mainly involve first-genera-tion sequencing and second-generation sequencing.This article reviews research on the genetic study of Meniere's disease,mainly summarizing the candidate genes with repeated pedigree validation in familial Meniere's disease,as well as those frequently reported in sporadic Meniere's disease.

Objective:To establish a TaqMan-MGB probe-based method for detecting the polymorphic loci C677T and A1298C of the MTHFR gene.Methods:Specific primers and TaqMan-MGB probes targeting the C677T and A1298C polymorphic loci of the MTHFR gene were designed and optimized based on the gene sequence information.A real-time quantitative PCR detection system was established.Gradient dilution experiments were conducted to determine the limit of detection,and reproducibility experiments were performed to evaluate detection consistency.Specificity was validated using wild-type and mutant plasmid templates.The method was applied to detect 56 clinical samples,and its accuracy and practicality were assessed through comparison with traditional Sanger sequencing.Results:The TaqMan-MGB probe method demonstrated high specificity for detecting the C677T and A1298C loci,with no cross-reactivity between wild-type and mutant probes,enabling accurate genotype differentiation.Sensitivity experiments revealed detection limits of 1.13 × 103 copies/μL for C677T and 8.39 × 101 copies/μL for A1298C.Reproducibility experiments showed coefficients of variation below 1％,indicating stable and reliable results.Among the 56 clinical samples,the overall detection rate for the C677T locus was 86.99％,and for the A1298C locus,it was 97.92％.The TaqMan-MGB method exhibited good concordance with Sanger sequencing results.Conclusion:The TaqMan-MGB method exhibits high specificity,sensitivity,and excellent reproducibility in detecting the polymorphic loci C677T and A1298C of the MTHFR gene,making it suitable for rapid detection in large-scale clinical samples.This method provides an effective molecular diagnostic tool for the early diagnosis and prevention of folate-related diseases.