Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.

To investigate the pathogenic mechanisms of a patient with type 1 diabetes mellitus (T1DM) complicated with fibrocalculous pancreatic diabetes at Tianjin Medical University General Hospital Airport Site in June 2024, clinical and genetic characteristic analyses were performed. Potential pathogenic genes were screened by whole-exome sequencing (WES), and Sanger sequencing validated the identified genetic variants within the family. The proband exhibited elevated blood glucose levels and positivity for tyrosine phosphatase antibodies, suggesting a diagnosis of T1DM. Multiple calcifications in the pancreas were observed in the proband. Genetic testing revealed that the proband carried two variants in the serine peptidase inhibitor Kazal type 1 (SPINK1) gene, namely, c.194+2T>C and c.-215G>A. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.194+2T>C mutation is preliminarily classified as pathogenic, while the c.-215G>A variant is classified as a variant of uncertain significance (VUS). Bioinformatics analysis indicated that the c.194+2T>C variant in the SPINK1 gene results in a truncated protein, affecting the three-dimensional structure and activity of the protein. This mutation is in complete linkage disequilibrium with the c.-215G>A variant, which may have a protective function and influence the clinical phenotype. Given that the patient also has T1DM and FCPD, there should be increased awareness of the co-occurrence of both types of diabetes to prevent misdiagnosis and underdiagnosis.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.

To investigate the pathogenic mechanisms of a patient with type 1 diabetes mellitus (T1DM) complicated with fibrocalculous pancreatic diabetes at Tianjin Medical University General Hospital Airport Site in June 2024, clinical and genetic characteristic analyses were performed. Potential pathogenic genes were screened by whole-exome sequencing (WES), and Sanger sequencing validated the identified genetic variants within the family. The proband exhibited elevated blood glucose levels and positivity for tyrosine phosphatase antibodies, suggesting a diagnosis of T1DM. Multiple calcifications in the pancreas were observed in the proband. Genetic testing revealed that the proband carried two variants in the serine peptidase inhibitor Kazal type 1 (SPINK1) gene, namely, c.194+2T>C and c.-215G>A. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.194+2T>C mutation is preliminarily classified as pathogenic, while the c.-215G>A variant is classified as a variant of uncertain significance (VUS). Bioinformatics analysis indicated that the c.194+2T>C variant in the SPINK1 gene results in a truncated protein, affecting the three-dimensional structure and activity of the protein. This mutation is in complete linkage disequilibrium with the c.-215G>A variant, which may have a protective function and influence the clinical phenotype. Given that the patient also has T1DM and FCPD, there should be increased awareness of the co-occurrence of both types of diabetes to prevent misdiagnosis and underdiagnosis.

Objective:To investigate the influencing factors for lymph node metastasis and prognosis in stage T1 and T2 esophageal squamous cell carcinoma after radical surgery and construct nomogram prediction models.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 672 patients with T1 and T2 esophageal squamous cell carcinoma who were admitted to the Affiliated Hospital of North Sichuan Medical College from January 2014 to December 2019 were collected. There were 464 males and 208 females, aged (65±8)years. All patients under-went radical esophagectomy+2 or 3 field lymph node dissection. Observation indicators: (1) lymph node dissection, metastasis and follow-up. (2) risk factors for lymph node metastasis of esophageal cancer after radical resection. (3) prognostic factors of esophageal cancer after radical resection. (4) construction and evaluation of the prediction models of lymph node metastasis and prognosis of esophageal cancer after radical resection. Follow-up was conducted using outpatient examination, telephone and internet consultations to detect survival of patients up to April 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to calculate survival rate and draw survival curve. Log-Rank test was used for survival analysis. Logistic regression model was used for univariate and multivariate analyses of risk for lymph node metastasis, and COX regression model was used for univariate and multivariate analyses of prognosis. Based on the results of multi-variate analysis, the nomogram prediction models for lymph node metastasis and prognosis predic-tion were constructed. The prediction discrimination of the nomogram models were evaluated using the area under curve (AUC) of the receiver operating characteristic curve (ROC). The calibration curve was used to evaluate the prediction consistency of the models. Results:(1) Lymph node dissection, metastasis and follow-up. The number of lymph node dissected was 14±8 and the number of lymph node metastasis was 2(range, 1?19) in 672 patients. Of the 672 patients, there were 182 cases had lymph node metastasis, including 58 cases in T1 stage and 124 cases in T2 stage. All 672 patients were followed up for 38 (range, 1?85)months. The average overall survival time of 672 patients was 65 months, with the 1-, 3-, 5-year overall survival rate as 89.0%, 74.3%, 66.0%, respectively. The average overall survival time of 325 patients in T1 stage and 347 patients in T2 stage were 70 months and 61 months. The 1-, 3-, 5-year overall survival rate of 325 patients in T1 stage and 347 patients in T2 stage were 95.0%, 83.5%, 73.4% and 87.4%, 69.9%, 59.2%, respectively, showing a significant difference in survival between them ( χ2=14.51, P<0.05). (2) Risk factors for lymph node metastasis of esophageal cancer after radical resection. Results of univariate analysis showed that tumor location, tumor histological grade, tumor T staging were related factors affecting lymph node metastasis of esophageal cancer after radical resection ( odds ratio=1.40, 1.54, 2.56, 95% confidence interval as 1.07?1.85, 1.20?1.99, 1.79-3.67, P<0.05). Results of multivariate analysis showed that tumor location, tumor histological grade, tumor T staging were independent factors affecting lymph node metastasis ( odds ratio=1.42, 1.61, 2.63, 95% confidence interval as 1.07?1.89, 1.25?2.09, 1.82?3.78, P<0.05). (3) Prognostic factors of esophageal cancer after radical resection. Results of univariate analysis showed that preoperative comorbidities, postoperative complications, tumor histological grade (G3), tumor T staging, tumor N staging (N1 stage, N2 stage, N3 stage), tumor TNM staging (Ⅲ stage, Ⅳ stage) were related factors affecting prognosis of esophageal cancer after radical resection ( hazard ratio= 1.48, 1.64, 2.23, 1.85, 2.09, 4.48, 4.97, 3.54, 5.53, 95% confidence interval as 1.08?2.03, 1.20?2.23, 1.47?3.39, 1.34?2.54, 1.44?3.04, 2.89?6.95, 1.57?15.73, 2.48?5.05, 1.73?17.68, P<0.05). Results of multivariate analysis showed that preoperative comorbidities, G3 of tumor histological grade, T2 stage of tumor T staging, N1 stage, N2 stage, N3 stage of tumor N staging were independent risk factors affecting prognosis of esophageal cancer after radical resection ( hazard ratio=1.57, 1.89, 1.63, 1.71, 3.72, 3.90, 95% confidence interval as 1.14?2.16, 1.23?2.91, 1.17?2.26, 1.16?2.51, 2.37?5.83, 1.22?12.45, P<0.05). (4) Construction and evaluation of the prediction models of lymph node metastasis and prognosis of esophageal cancer after radical resection. Based on the results of multivariate analysis, tumor location, tumor histological grade, tumor T staging were applied to construct a nomo-gram model for lymph node metastasis prediction of esophageal cancer after radical resection, the score of tumor location, tumor histological grade, tumor T staging were 82, 100, 100, respectively, and the sum of the scores corresponding to the lymph node metastasis rate. Preoperative comor-bidity, tumor histological grade, tumor T staging, tumor N staging were applied to construct a nomo-gram model for 1-, 3-, 5-year overall survival rate prediction of esophageal cancer after radical resection, the score of preoperative comorbidity, tumor histological grade, tumor T staging, tumor N staging were 23, 38, 27, 100, respectively, and the sum of the scores corres-ponding to the 1-, 3-, 5-year overall survival rate. Results of ROC showed that the AUC of nomogram model for lymph node metastasis prediction after radical esophagectomy was 0.66 (95% confidence interval as 0.62?0.71, P<0.05). The AUC of nomogram model for 1-, 3-, 5-year overall survival rate prediction after radical esophagectomy were 0.73, 0.74, 0.71 (95% confidence intervals as 0.66?0.80, 0.68?0.79, 0.65?0.78, P<0.05). Results of calibration curve showed that the predicted lymph node metastasis rate and the predicted 1-, 3-, 5-year overall survival rate by nomogram models were consistent with the actual lymph node metastasis rate and 1-, 3-, 5-year overall survival rate. Conclusions:Tumor location, tumor histological grade, tumor T staging are independent factors affecting lymph node metastasis in T1 and T2 esophageal squamous cell carcinoma after radical surgery and nomogram model constructed by these indicators can predict the lymph node metas-tasis rate. Preoperative comor-bidities, G3 of tumor histological grade, T2 stage of tumor T staging, N1 stage, N2 stage, N3 stage of tumor N staging are independent risk factors affecting prognosis and nomogram model constructed by these indicators can predict the overall survival rate of patients after surgery.

OBJECTIVES: To coat a zirconia surface with silica-zirconia using a dip-coating technique and evaluate its effect on resin-zirconia shear bond strength (SBS). METHODS: A silica-zirconia suspension was prepared and used to coat a zirconia surface using a dip-coating technique. One hundred and eighty-nine zirconia disks were divided into three groups according to their different surface treatments (polishing, sandblasting, and silica-zirconia coating). Scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and X-ray diffraction (XRD) were used to analyze the differently treated zirconia surfaces. Different primer treatments (Monobond N, Z-PRIME Plus, and no primer) were also applied to the zirconia surfaces. Subsequently, 180 composite resin cylinders (Filtek Z350) were cemented onto the zirconia disks with resin cement (RelyX Ultimate). The SBS was measured after water storage for 24 h or 6 months. The data were analyzed by two-way analysis of variance (ANOVA). RESULTS: SEM and EDX showed that the silica-zirconia coating produced a porous layer with additional Si, and XRD showed that only tetragonal zirconia was on the silica-zirconia-coating surface. Compared with the control group, the resin-zirconia SBSs of the sandblasting group and silica-zirconia-coating group were significantly increased ( CONCLUSIONS Dip-coating with silica-zirconia might be a feasible way to improve resin-zirconia bonding.

Objective:To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia (CBF-AML) who achieved first complete remission after induction chemotherapy.Methods:The study, which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University, comprised 195 newly diagnosed patients with CBF-AML, including 190 patients who achieved first complete remission after induction chemotherapy. The cohort included 134 patients with RUNX1-RUNXIT1 + AML and 56 patients with CBFβ-MYH11 + AML. The cohort age ranged from 15 to 64 years, with a median follow-up of 43.6 months. Overall survival (OS) and disease-free survival (DFS) were assessed by the log-rank test, and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis. Results:The most common genetic mutations were in KIT (47.6% ) , followed by NRAS (20.0% ) , FLT3 (18.4% ) , ASXL2 (14.3% ) , KRAS (10.7% ) , and ASXL1 (9.7% ) . The most common mutations involved genes affecting tyrosine kinase signaling (76.4% ) , followed by chromatin modifiers (29.7% ) . Among the patients receiving intensive consolidation therapy, the OS tended to be better in patients with CBFβ-MYH11 + AML than in those with RUNX1-RUNXIT1 + AML ( P=0.062) . Gene mutations related to chromatin modification, which were detected only in patients with RUNX1-RUNXIT1 + AML, did not affect DFS ( P=0.557) . The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation (allo-HSCT) achieved the best prognosis. Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1 + AML ( P<0.001) , and allo-HSCT significantly prolonged DFS in these patients ( P=0.010) . Conclusions:KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1 + AML. Allo-HSCT may improve prognosis in these patients, whereas allo-HSCT might also improve prognosis in patients with mutations in genes related to chromatin modifications.

Objective:To explore whether autophagy is involved in dysfunction of vascular endothelial induced by sodium arsenite (NaAsO 2). Methods:Human primary umbilical vein endothelial cells were isolated and cultured. The cells were treated with different levels of NaAsO 2 [0 (control)), 2, 5, 10, 20, 30, 50 μmol/L] for 24 h, and cell viability was determined using CCK8. According to the results of CCK8, the levels of arsenite used in subsequent experiments were determined, intracellular nitric oxide (NO) content (incubated by NaAsO 2 for 4 h) was detected by flow cytometry, LC3 levels (incubated by NaAsO 2 for 0, 6, 12 and 24 h) was detected using Western blotting, and autophagosome (incubated by NaAsO 2 for 12 h) was observed by electron microscope. At the same time, human primary umbilical vein endothelial cells were pretreated with 0.1 mmol/L 3-MA (autophagy inhibitor) for 2 h, and induced by 30 μmol/L NaAsO 2, and the above detection indicators were compared with those of the 30 μmol/L NaAsO 2 group. Results:Human primary umbilical vein endothelial cells were successfully isolated and cultured. Compared with the control group [cell viability: (99.97 ± 5.33)%, NO content: 42 048.34 ± 789.61], the cell viability [(73.00 ± 0.86)%] and NO content (23 353.97 ± 971.85) of 30 μmol/L NaAsO 2 group were remarkably lower, and the differences were statistically significant ( P < 0.01). Incubated with 30 μmol/L NaAsO 2 at different time points 6, 12, 24 h, LC3Ⅱ levels (5.782 ± 2.789, 9.692 ± 2.222, 5.573 ± 2.941) were significantly elevated than those of control group (1.000 ± 0.383, P < 0.05), and the LC3 Ⅱ level was the highest at 12 h. After treatment with 30 μmol/L NaAsO 2 for 12 h, the number of autophagosome in cells observed under electron microscope was significantly higher than that of the control group. Compared with 30 μmol/L NaAsO 2 group [cell viability: (68.78 ± 1.55)%, LC3 Ⅱ level: 5.680 ± 0.545, NO content: 13 025.78 ± 962.61], cell viability [ (79.54 ± 4.99) %] in 3-MA+ NaAsO 2 group was increased, the LC3Ⅱ level (3.956 ± 0.398) was decreased, and the differences were statistically significant ( P < 0.05); intracellular NO content (13 988.51 ± 1 671.07) increased, whereas the difference was not statistically significant ( P > 0.05). Conclusion:Autophagy is involved in the vascular endothelial dysfunction induced by arsenic.