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.

Objective To analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

Objective:With the help of the advanced ACD Labs/AutoChrom method development software,param-eter simulation design was carried out.Based on the results of software simulation and actual investigation,an HPLC method for the determination of related impurities in safinamide mesylate raw material drug was established.Methods:A Waters Atlantis T3 column(4.6 mm ×250 mm,5 μm)was used.The phosphate buffer with a pH of 7.0 was used as mobile phase A,and acetonitrile was used as mobile phase B.Gradient elution was performed at a flow rate of 1.3 mL·min-1,the detection wavelength was 228 nm,the column temperature was 35 ℃,and the injection volume was 10 μL.Results:Impurities 1-12 in safinamide mesylate could be effectively separated from the main component.The linear ranges were 0.102 1-5.329,0.102 9-5.379 7,0.106 8-4.972 9,0.102 1-5.135,0.103 8-5.314 7,0.097 7-4.869 8,0.095 2-4.760 5,0.095 3-5.109 5,0.050 5-5.287 5,0.098 7-4.885 6,0.102 4-4.997 5,0.050 8-5.134 7 μg·mL-1,respectively.The limits of detection(LOD)were 0.051,0.051 4,0.053 4,0.051 1,0.051 9,0.048 8,0.047 6,0.047 7,0.025 3,0.049 3,0.051 2,0.025 4 μg·mL-1,and the limits of quantification(LOQ)were 0.102 1,0.102 9,0.106 8,0.102 1,0.103 8,0.097 7,0.095 2,0.095 3,0.050 5,0.098 7,0.102 4,0.050 8 μg·mL-1.The accuracy,preci-sion and durability all met the requirements.Conclusion:This method is suitable for the determination and quality control of the related substances of 12 impurities in safinamide mesylate raw materials.

Purpose This study aims to analyze the clinical,pathological,and molecular genetic characteristics of nodal follicular helper T-cell lymphoma,follicular type(nTFHL-F).Methods 7 cases of nTFHL-F were re-viewed.Clinical data were collected,tissue morphology was summarized,and immunohistochemical staining and mo-lecular testing were performed.Results The median age of patients was 62 years with a male-to-female ratio of 6:1.The initial symptoms included neck lymphadenectasis in 6 cases and abdominal discomfort in one.Six cases were in ad-vanced stages,while 1 case was in the localized stage.The tumors exhibited a vague,irregular follicular nodular pat-tern,without significant polymorphic inflammatory background or high endothelial vascular proliferation.Five cases showed a progressive transformation resembling germinal center pattern,and two cases exhibited a follicular lymphoma-like growth pattern.Tumor cells presented three distinct morphologies:centrocyte-like appearance,monocytoid B cell-like appearance,and atypical cells with abundant,transparent cytoplasm.Tumor cells expressed at least three follicu-lar T-cell markers.Testing for ITK::SYK gene fusion was negative in all cases(0/7).Next generation sequencing i-dentified mutations in TET2 gene in two cases(2/2),the RHOA gene in one case(1/2),and VAV1 gene in one case(1/2).The follow-up duration ranged from 2 to 64 months,with three deaths(3/7),and a median survival time of 37 months.Conclusion nTFHL-F predominantly occurs in middle-aged to elderly males,presenting with advanced clinical stages,and has a poor prognosis.nTFHL-F is closely associated with nodal follicular helper T-cell lymphoma,angioimmunoblastic type,and mya coexist within the same individual.

Objective To study the change of common bile duct pressure after laparoscopic common bile duct exploration in patients with common bile duct stones.Methods Clinical data of 17 patients with common bile duct stones treated in our hospital from January 2022 to December 2022 were collected.All patients underwent laparoscopic common bile duct exploration and common bile duct pressure measurement.The patients were followed up for 8 weeks after operation,and the common bile duct pressure was measured by indwelling T tube at 2,3,4 and 8 weeks.Results Among the 17 patients,1 patient showed persistent high common bile duct pressure due to residual common bile duct stones.In the remaining 16 patients,there were no significant difference between the initial common bile duct pressure(19.7 cm H2O)and the common bile duct pressure at postoperative(17.0 cm H2O)and week 1(15.5cmH2O)(P＞0.05).There were significant differences between the initial common bile duct pressure and the common bile duct pressure at week 2(13.5 cm H2O),3(12.2 cm H2O),4(11.1 cm H2O)and 8(10.0cmH2O)(P＜0.05).Conclusion Compared to initial common bile duct pressure,the pressure of common bile duct began to decrease significantly from 2 weeks after laparoscopic common bile duct exploration in patients with common bile duct stones.

Objective:To formulate a community teacher standard for the training of general practitioner program (direction in hospice care).Methods:This was a qualitative study. Twenty-nine experts in general practice and hospice care from various teaching hospitals and community health service centers were invited to participate in two rounds of Delphi consultation from April to August 2022. Based on the results of the consultation, a standard for community faculty training in comprehensive care and end-of-life care for general practitioners was formulated, and the weight coefficients of the indicators were calculated.Results:Of the 29 experts, 11 (37.9%) were male, their age was (52.9±8.9) years, and their working life was (17.0±7.2) years. In the two rounds of expert consultation, the expert positive coefficient was 100.0% (29/29) and 96.6% (28/29), the expert authority coefficient was 0.789 and 0.851, and the expert opinion coordination coefficient W of the importance of all indicators was 0.124 and 0.131, respectively ( χ2=123.01, 131.71, P<0.05). Finally, a set of community-based teacher standard for general practitioner specialty training (direction in hospice care) was established, which consisted of 4 first-level indicators and 30 second-level indicators. The four first-level indicators were basic literacy, clinical qualification and ability, teaching qualification and ability, and scientific research ability, all with the weight coefficients of 0.254, 0.254, 0.252 and 0.240, respectively. Conclusion:The standard of teachers in the community base of general practitioner specialty training (direction in hospice care) established in this study is more scientific, which is conducive to the comprehensive evaluation of teachers in the community training base.