Objective: To validate the performance of the Procleix UltrioPlex E assay (Grifols, Spain) on the Procleix Panther automated nucleic acid detection platform, which employs the TMA method to simultaneously detect HIV-1/HIV-2/HCV/HBV/HEV viruses, and to evaluate its value for screening transfusion-associated infectious diseases. Methods: In accordance with the requirements of ISO15189"Application of the Guidelines for the Accreditation of Quality and Capabilities of Medical Laboratories in the Field of Molecular Diagnostics (CNAS-CL02-A009: 2018)", "Guidelines for Performance Validation of Molecular Diagnostic Testing Procedures (CNAS-GL039: 2019)", and the "Technical Operating Procedures for Blood Banks (2019 Edition)", this study validated the reagent's performance in terms of analytical sensitivity validation, performance consistency validation, interference resistance, and cross-contamination resistance. Results: Probit analysis revealed that the 95% detection limits (95% confidence interval) for HBV, HCV, HIV, and HEV were 2.0 IU/mL, 1.5 IU/mL, 18.0 IU/mL and 3.7 IU/mL, respectively, which were consistent with the minimum detection limits stated in the kit's package insert and were comparable to the Procleix Ultrio Elite kit. Both kits were used to test the performance validation serum plate simultaneously, yielding results consistent with the serum plate (Kappa=1), indicating stable performance. Detection of medium-and low-concentration lipemia and weakly positive hemolysis samples demonstrated good interference resistance. Cross-contamination performance validation showed that the kit exhibited excellent cross-contamination resistance. Conclusion: The Procleix UltrioPlex E nucleic acid detection kit enables combined detection of HIV-1, HIV-2, HCV, HBV, and HEV, allowing single-test screening for multiple viruses in donor blood. The kit's analytical performance is stable and meets basic laboratory requirements, making it suitable for screening transfusion-associated infectious diseases in blood banks.

Objective To investigate the reproductive and developmental effects of Clothianidin in rats. Methods Clothianidin was administrated by diet to both parental and first filial (F 1) generations of rats at the dosages of 0, 30.51, 110.84 and 304.26 mg/(kg·d) in females, and 0, 26.45, 92.69 and 279.42 mg/(kg·d) in males. Clothianidin was administered through diet to male and female rats for 8 weeks before mating. Clothianidin was administered to female rats in the parental and F1 generations during mating, gestation and lactation periods. During the test, toxicity performance was observed, reproduction index was calculated, and pathological examination was carried out. Results The body weights of rats in the parent and F1 generations in the high-dose group were lower than those in the control group during pre-mating exposure and at various time points during pregnancy and lactation (P<0.05). The pregnancy rates of parental and F1 generations in the high-dose group were lower than those of the control group (48.57% vs 71.43%, 45.71% vs 80.00%, P＜0. 05). Sperm concentration and sperm motility of the parental generation were lower than those of the control group [(42.55±12.87) vs (53.84±7.65) ×106/ml, (58.94±10.59) vs (65.59±6.03), （P＜0.05）]. Sperm concentration and sperm motility of the F1 generation were lower than those of the control group [(41.64±12.42) vs (53.09±9.48), (55.13±9.19) vs (64.53±6.31), (P＜0.05). Conclusion Exposure to clothianidin has reproductive toxicity to Wistar rats, and the no-observed adverse effect level (NOAEL) in the two-generation reproductive toxicity test is 92.69 mg/kg·BW for males and 110.84 mg/kg·BW for females in Wistar rats.

To analyze the treatment strategy for a 78-year-old female patient with mismatch repair deficient (dMMR) gastric cancer who achieved long-term survival. After third-line chemotherapy failed, gene testing showed ARID1A p.Gln748fs, c.2733-1G＞T variation, with PD-L1 TPS 30%, CPS 60%. The nivolumab was employed, and two weeks later, the best response was partial response (PR). During the fourth-line immunotherapy maintenance treatment, progression of left adrenal metastasis was observed. The expression of human epidermal growth factor receptor-2 (HER-2) was positive, and the antibody drug conjugate disitamab vedotin (RC48) was chosen for treatment. After 10 months of treatment with nivolumab combined with RC48, the best efficacy was assessed as stable disease (SD), with a progression free survival (PFS) of up to 12 months. Radiotherapy was employed, and immunotherapy was maintained, allowing the patient to achieve a PFS of 18 months again. During immunotherapy, a clinical pharmacist developed a personalized pharmaceutical care plan for this patient. At the last follow-up, this patient achieved 78 months of long-term survival.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

OBJECTIVES: To explore the impact of different treatment attitudes on the survival status of extremely preterm infants (EPIs) and evaluate the mortality and occurrence of severe complications in actively treated infants, as well as their risk factors. METHODS: A retrospective analysis was conducted on perinatal data of EPIs born between January 1, 2016, and December 31, 2023, who were admitted to the neonatal intensive care unit of Nanjing Women and Children's Healthcare Hospital within 24 hours after birth. The analysis focused on the attributable risk of mortality associated with different treatment attitudes in EPIs of varying gestational ages and birth weights. A multivariate logistic regression model was used to analyze the risk factors for mortality and severe complications in the actively treated group. RESULTS: A total of 485 EPIs were included. As gestational age or birth weight increased, the attributable risk of mortality with care withdrawal increased. Active treatment significantly improved the survival status of EPIs born at a gestational age of ≥24 weeks. Multivariate logistic regression analysis indicated that lower gestational age and the need for mechanical ventilation within 72 hours after birth were independent risk factors for mortality or severe complications in EPIs (P<0.05). CONCLUSIONS Active treatment can significantly extend the survival time of EPIs born at a gestational age of ≥24 weeks. Lower gestational age and the need for mechanical ventilation within 72 hours after birth are closely associated with poor survival outcomes in EPIs.
Humans ; Retrospective Studies ; Infant, Extremely Premature ; Risk Factors ; Infant, Newborn ; Female ; Male ; Gestational Age ; Logistic Models ; Birth Weight

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.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To investigate the relationship between kinase insert domain receptor(KDR)rs2305948 polymorphism and clopidogrel resistance(CR)in patients with acute coronary syndrome after receiving percutaneous coronary intervention(PCI).Methods A total of 468 patients with acute coronary syndrome,who were admitted to the Zhangjiakou Municipal First Hospital of China from September 2022 to September 2023,were selected as the subjects of study.All patients received PCI treatment and took medication of clopidogrel after the treatment.The occurrence of CR was recorded.The factors influencing the occurrence of CR were analyzed.The clinical significance of KDR rs2305948 polymorphism in predicting CR in patients with acute coronary syndrome after receiving PCI was evaluated.Results Of 468 patients with acute coronary syndrome,116(24.79％)developed CR.Logistic multivariate regression analysis indicated that low-density lipoprotein cholesterol(LDL-C,95％CI=1.420-8.390,OR=3.452),type 2 vascular endothelial growth factor receptor(VEGFR-2,95％CI=1.374-8.118,OR=3.340),KDR rs2305948 T/T genotype(95％CI=1.677-9.905,OR=4.076),and T allele(95％CI=1.390-8.207,OR=3.377)were the independent factors influencing the occurrence of CR inpatients with acute coronary syndrome after receiving PCI(all P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity,specificity,and area under ROC curve(AUC)of the T/T genotype of KDR rs2305948 in predicting CR in patients with acute coronary syndrome after receiving PCI were 75.86％,70.45％,and 0.773(95％CI=0.666-0.880)respectively.Conclusion In patients with acute coronary syndrome after receiving PCI,the risk of developing CR is higher.The KDR rs2305948 polymorphism is correlated with CR in patients with acute coronary syndrome after receiving PCI,and it has a certain predictive value for CR.

Objective:In the context of China's cardiovascular disease(CVD)high-risk population screening and intervention project,this study systematically evaluates the applicability of the EQ-5D-5L and SF-6Dv2 instruments among individuals at high risk of CVD.Methods:Convergent validity was assessed using Spearman's correlation coefficient.Measurement agreement was evaluated through intraclass correlation coefficients(ICC)and Bland-Altman plots.Factors influencing utility differences were explored using multiple linear regression analysis.Kruskal-Wallis test and t-test were used to examine discriminant validity.Sensitivity was compared by effect size(ES),relative efficiency(RE),and the area under the receiver operating characteristic curve(ROC-AUC).Floor and ceiling effects were also compared.Results:Among 5,415 individuals at high risk of CVD,the two instruments showed moderate overall correlation and acceptable convergent validity,but dimension-specific correlations were weak,and measurement consistency was low(ICC=0.367).Both instruments effectively distinguished different health states,yet the SF-6Dv2 demonstrated superior sensitivity and a milder ceiling effect.Conclusion:When measuring the health utility value of CVD patients,scale selection should be cautious,especially for high-risk groups,and SF-6Dv2 is more appropriate.