Objective: To systematically analyze the confirmatory positivity of different combinations of HBsAg screening results in blood testing, providing data to support the optimization of blood donor eligibility management. Methods: A retrospective analysis was conducted on blood screening data from 174 266 voluntary blood donor samples at the Chongqing Blood Center between October 2021 and September 2022. Samples with inconsistent results between the two HBsAg enzymelinked immunosorbent assays (ELISA) and individual donor nucleic acid testing (NAT) were confirmed using an electrochemiluminescence immunoassay (ECLIA) and a neutralization test. The detection efficacy of four different HBsAg ELISA reagents was compared using the HBsAg-confirmed positive samples. Results: A total of 767(0.44%) HBV-reactive (HB-sAg and/or HBV DNA reactive) samples were detected. Among them, 344 samples with discordant serological and NAT results were collected, of which 64(18.6%) were confirmed positive by neutralization test. Additionally, 5 samples that were neutralization-negative but double-reactive for HBsAg and HBV DNA were confirmed as positive according to FDA guidance, resulting in a total of 69(20.1%) confirmed HBsAg-positive samples. There were significant differences in the neutralization test confirmation rates among different screening result categories (P<0.05): The group with dual HBsAg reagent reactivity (double reactive) & NAT-negative had the highest confirmation rate (96.9%, 31/32); the group reactive to only reagent 2 (single reactive) had a rate of 25.7% (29/113); while the confirmation rates for samples reactive to only reagent 1 and samples with isolated HBV DNA positivity were extremely low [0(0/34) and 2.4%(4/165), respectively]. The four commercial reagents showed significant differences in their ability to detect confirmed positive samples that were initially single reactive (P<0.05). Conclusion: Given the performance variations among HBsAg screening reagents, thorough performance verification is essential before implementation. When NAT is negative, dual HBsAg reactivity in screening can serve as a basis for confirming infection and directly deferring blood donors. However, confirming infection in donors with single HBsAg reactivity is more challenging, necessitating supplementary tests to rule out infection risk.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

AIM:To analyze the influencing factors of visual outcome after vitrectomy for polypoidal choroidal vasculopathy(PCV)combined with vitreous hemorrhage and establish a predictive model.METHODS: A retrospective analysis was conducted on the clinical data of 129 cases(129 eyes)of patients who underwent vitrectomy for PCV combined with vitreous hemorrhage from June 2021 to January 2024 in our hospital. They were divided into elevated group(71 eyes)and non-elevated group(58 eyes)according to visual outcome at early posoperative stage(within 24 mo). Another 30 cases(30 eyes)of PCV with vitreous hemorrhage undergoing vitrectomy were selected as external validation data. The predictive value of the model for the postoperative visual outcomes of both internal and external populations was evaluated.RESULTS: The non-elevated group had a higher proportion of patients aged ≥60 years, diabetes, continuous abnormalities of the ellipsoid zone(EZ)during surgery, bleeding involving the macular fovea, and postoperative retinal scar formation than the elevated group were independent factors affecting postoperative visual acuity(all P<0.05). The AUC of the predictive model for predicting the postoperative visual outcomes of internal and external populations was 0.824(95%CI: 0.750-0.898)and 0.809(95%CI: 0.723-0.865), respectively.CONCLUSION:Patients aged ≥60 years, diabetes, intraoperative continuous abnormalities of EZ, bleeding involving the macular fovea, and postoperative retinal scar formation are influencing factors for visual outcome after vitrectomy in patients with PCV combined with vitreous hemorrhage. A predictive model based on those factors has been established, which has a certain predictive value for postoperative visual outcome.

Nasopharyngeal carcinoma is rare in children and adolescents, but the prognosis is relatively good. More and more studies focus on the growth and development, as well as the quality of life of patients after treatment. Certain progress has been made in the research of nasopharyngeal carcinoma in children and adolescents, covering multiple aspects such as etiology, clinical characteristics, treatment regimens and prognosis. The factors causing nasopharyngeal carcinoma include viral infection, genetic susceptibility and environmental factors, etc. The main treatment methods are radiotherapy, chemotherapy, targeted therapy, immunotherapy and surgery. In addition, traditional Chinese medicine has also shown its unique efficacy and potential in the adjuvant therapy of nasopharyngeal carcinoma, providing more treatment options for patients. Further exploration of the factors influencing the occurrence of nasopharyngeal carcinoma in children and adolescents, and analysis of the effects and applications of different treatment methods, can provide new perspectives and references for future research.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

Dopamine(DA)is an essential neurotransmitter.Research on its dynamic concentration fluctuations,particularly within the extracellular microenvironment,is crucial for elucidating neural signaling mechanisms and pathogenesis of related disorders.Among DA detection methods,fluorescence probe-based imaging offers advantages such as high sensitivity,high specificity,and non-invasiveness.However,the application of these probes for in situ DA monitoring has been limited by the challenges including probe internalization and difficulties in labeling across cells.Here,leveraging the programmability and high stability of DNA nanostructures,a DNA prism-based probe for imaging DA release at the single-cell level was designed and constructed.This probe utilized surface-modified cholesterol for efficient membrane anchoring and a DA aptamer-based"turn-on"sensing module to detect DA directly on the cell membrane.Using this probe,rapid DA release triggered by high K+stimulation was observed,with the released DA concentration increasing over time and peaking at 8 min post-stimulation.More notably,exploiting the probe's ability to simultaneously anchor to two cells,thereby forming cell clusters,revealed that the distribution of DA within the intercellular space was significantly higher than that in the cell body regions.This probe not only provided a method for DA imaging on the cell membrane but also laid a theoretical foundation for developing broader neurotransmitter detection platforms,holding significant scientific merit and application potential.

Objective To explore the correlation between fasting blood glucose(FBG)level and fractional flow reserve(FFR)in patients with borderline coronary artery disease,and to clarify its potential influence on FFR measurement.Methods From August 2020 to August 2023,the data of 135 patients with coronary atherosclerotic heart disease who received coronary angiography and FFR evaluation in the Fourth Affiliated Hospital of Harbin Medical University were retrospectively collected.According to the exclusion and inclusion criteria,85 cases of borderline diseased vessels of single coronary artery with stenosis degree of 50％-80％were screened out,and they were divided into FBG≥6.1 mmol/L group(47 cases)and FBG＜6.1 mmol/L group(38 cases).The baseline data,angiographic and functional indexes of the two groups were compared,and the correlation between FBG and FFR was analyzed.Results Compared with the FBG＜6.1 mmol/L group,the FBG≥6.1 mmol/L group had a higher proportion of FFR negative results(72.3％vs.23.7％,P＜0.001),and the FFR measurement values were generally increased[0.84(0.80,0.90)vs.0.75(0.68,0.80),P＜0.001],with statistically significant differences.Pearson correlation analysis was performed on all lesions,and FFR＞0.80(negative result)was positively correlated with FBG≥6.1 mmol/L(r=0.484,P＜0.001).Conclusions Among the patients with borderline coronary artery disease(50％-80％stenosis)included in this study,FBG≥6.1 mmol/L is significantly correlated with FFR＞0.80.For patients with borderline coronary lesions with elevated FBG,the influence of blood glucose factors should be carefully considered in clinical interpretation of FFR results.

Objective:To explore the clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris(UAP)and type 2 diabetes mellitus(T2DM)using meta-analysis.Methods:We searched the databases including Pubmed,Web of Science,EMbase,EBSCO,Cochrane,CBM,CNKI and Wanfang for randomized controlled trials(RCTs)about the therapeutic effect of Shexiang Baoxin pill on patients with UAP and T2DM from the establish-ment to January 20th,2023.RevMan 5.3 software was used to perform meta-analysis to investigate the effect of Shexiang Baoxin pill on angina improvement and blood glucose fluctuation in patients with UAP and T2DM.Results:Six eligible literatures were included,including 346 patients in Shexiang Baoxin pill group and control group respec-tively.The results of meta-analysis showed that compared to participants in control group,those in Shexiang Baox-in pill group had significantly higher clinical overall efficiency(OR=3.13,95％CI 2.01～4.89,P＜0.001),and significantly lower angina attack frequency(MD=-0.66,95％CI-0.79～-0.52,P＜0.001),duration of angi-na(MD=-3.10,95％CI-4.11～-2.09,P＜0.001),and 2-hour postprandial blood glucose(MD=-1.79,95％CI-2.00～-1.57,P＜0.001).Conclusion:Shexiang Baoxin pill could improve clinical overall efficiency,an-gina attack frequency and duration,and reduce 2-hour postprandial blood glucose in patients with unstable angina pectoris and type 2 diabetes mellitus.

This study aims to integrate data mining techniques of single cell transcriptomics and spatial transcriptomics, along with animal experiment validation, so as to systematically characterize the protective effects of Jianpi Tongluo Formula(JTF) on the cartilage in knee osteoarthritis(KOA) and elucidate the underlying molecular mechanisms. Single cell transcriptomics and spatial transcriptomics datasets(GSE254844 and GSE255460) of the cartilage tissue obtained from KOA patients were analyzed to map the single cell-spatial heterogeneity and identify key pathogenic factors. After that, a KOA rat model was established via knee joint injection of papain. The intervention effects of JTF on the expression features of these key factors were assessed through real-time quantitative polymerase chain reaction(PCR), Western blot, and immunohistochemical staining. As a result, the integrated single cell and spatial transcriptomics data identified distinct cell subsets with different pathological changes in different regions of the inflamed cartilage tissue in KOA, and their differentiation trajectories were closely related to the inflammatory fibrosis-like pathological changes of chondrocytes. Accordingly, the expression levels of the two key effect targets, namely nuclear receptor coactivator 4(NCOA4) and high mobility group box 1(HMGB1) were significantly reduced in the articular surface and superficial zone of the inflamed joints when JTF effectively alleviated various pathological changes in KOA rats, thus reversing the abnormal chondrocyte autophagy level, relieving the inflammatory responses and fibrosis-like pathological changes, and promoting the repair of chondrocyte function. Collectively, this study revealed the heterogeneous characteristics and dynamic changes of inflamed cartilage tissue in different regions and different cell subsets in KOA patients. It is worth noting that NCOA4 and HMGB1 were crucial in regulating chondrocyte autophagy and inflammatory reaction, while JTF could reverse the regulation of NCOA4 and HMGB1 and correct the abnormal molecular signal axis in the target cells of the inflamed joints. The research can provide a new research idea and scientific basis for developing a personalized therapeutic schedule targeting the spatiotemporal heterogeneity characteristics of KOA.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Osteoarthritis, Knee/pathology* ; Humans ; Male ; Cartilage, Articular/metabolism* ; Chondrocytes/metabolism* ; Rats, Sprague-Dawley ; Female ; Protective Agents/administration & dosage* ; Single-Cell Analysis ; Middle Aged ; HMGB1 Protein/metabolism*

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical