OBJECTIVE To provide a scientific basis for the quality evaluation and clinical application of Qingwen hufei granules. METHODS Fourteen batches of Qingwen hufei granules were used as samples to establish high-performance liquid chromatography （HPLC） fingerprints using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 Edition）. The chromatographic peaks were identified and the similarity was evaluated. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to conduct chemical pattern recognition analysis on the 14 batches of samples. Meanwhile， the contents of neochlorogenic acid （NGA）， chlorogenic acid （CHA）， cryptochlorogenic acid （CGA）， forsythoside A （FTA）， 3，5-O-dicaffeoylquinic acid （3，5-O- DA）， 4，5-O-dicaffeoylquinic acid （4，5-O-DA）， and angoroside C （AGC） in the samples were determined by HPLC. RESULTS The methodological investigation results of both the fingerprint and the content determination complied with the relevant requirements. Fourteen common peaks were indicated in the HPLC fingerprints of the 14 batches of samples， and 7 of them were identified [NGA （peak 2）， CHA （peak 3）， CGA （peak 5）， FTA （peak 11）， 3，5-O-DA （peak 12）， 4，5-O-DA （peak 13）， and AGC （peak 14）]； the similarity of each sample was greater than 0.94. The results of CA and PCA showed that the samples could be classified into 3 categories； the results of OPLS-DA indicated that peak 4 （unknown）， peak 11 （FTA）， peak 8 （unknown）， peak 9 （unknown）， and peak 1 （unknown） were the differential components. The content ranges of NGA， CHA， CGA， 3，5-O-DA， FTA， 4，5-O-DA and AGC in the 14 batches of samples were 0.210 4-0.458 7， 0.269 1-0.506 3， 0.228 1-0.461 1， 0.443 9-1.044 6， 0.066 7-0.155 7， 0.062 8-0.143 8， and 0.057 4-0.105 7 mg/g， respectively. CONCLUSIONS The HPLC fingerprint and multi-component content determination methods established in this study are efficient and reliable， and can be used for the quality evaluation of Qingwen hufei granules.

Objective To investigate the post-discharge exercise behavior and factors influencing moderate to vigorous intensity physical activity (MVPA) in patients undergoing lung surgery. Methods A total of 2874 patients from the large prospective, observational perioperative lung symptom study cohort (CN-PRO-Lung 3) in the Department of Thoracic Surgery at Sichuan Cancer Hospital between April 7, 2021, and January 31, 2024, were selected as the survey subjects. A survey was conducted using the Investigation of Exercise Behavior after Lung Surgery questionnaire and the International Physical Activity Questionnaire-Short Form (IPAQ-SF) among patients who underwent lung surgery. Binary logistic regression was used to analyze the factors influencing patients’ engagement in MVPA. Results A total of 702 patients were surveyed, including 252 males and 450 females, with an average age of (52.4±10.2) years. Patients with lung cancer accounted for 85.9%. Only 36.0% of the patients had regular exercise habits, while 42.3% did not engage in any physical activity. The three main barriers for postoperative exercise were physical discomfort (pain, coughing, shortness of breath, etc, 54.7%), lack of professional guidance (41.7%), and concerns about the surgical wound (28.9%). The proportions of patients engaging in vigorous, moderate, and low-intensity physical activity were 5.7%, 28.2%, and 66.1%, respectively. Multivariate analysis showed that patients with a personal annual income ≥50000 yuan (OR=1.52, 95%CI 1.01-2.29, P=0.044), high school education or above (OR=1.92, 95%CI 1.33-2.76, P<0.001), and lobectomy (OR=1.44, 95%CI 1.02-2.03, P=0.037) engaged in more MVPA. Conclusion Patients undergoing lung surgery have inadequate physical activity after discharge, particularly lacking in MVPA. Patients with higher income, higher educational levels, and lobectomy are more frequently engaged in MVPA. Measures such as symptom control, providing exercise guidance, and enhancing education on wound care may potentially improve the inadequate physical activity in lung surgery patients after discharge.

Objective: To investigate the damaging effects of red blood cell supernatant (RBC-S) stored for different durations (7 d, 14 d, and 28 d) on vascular endothelial cells, and to explore the underlying mechanisms using bioinformatics analysis, so as to provide references for optimizing red blood cell transfusion strategies. Methods: Human umbilical vein endothelial cells (HUVECs) were co-cultured with RBC-S stored for 7, 14 and 28 days, designated as the 7 d group, 14 d group and 28 d group respectively, which were collectively defined as the experimental groups. Cell damage was evaluated by cell proliferation assay (Cell Counting Kit8, CCK8), lactate dehydrogenase (LDH) release assay, 4′, 6diamidino2phenylindole (DAPI) staining, and flow cytometry for apoptosis and reactive oxygen species (ROS) levels. The damage degree of RBC-S on vascular endothelial cells was assessed by statistical analysis of damage data among different groups. Since the damage effect reached a plateau at all time points, the 28 d storage group was selected as the representative for further mechanistic studies. Transcriptomic analysis was performed to explore the role of frizzled class receptor 1 (FZD1) and Wnt signaling pathway in red blood cell storagerelated endothelial dysfunction. Results: Compared with the control group, the storage groups treated with 7 d, 14 d, and 28 d RBC-S showed significantly decreased cell proliferation rates [control group 100%, 7 d group (69.51±2.30)%, 14 d group (74.54±2.89)%, 28 d group (73.59±2.36)%, P<0.05], significantly reduced numbers of DAPI-stained cell nuclei [control group (213±12.5) per field, 7 d group (140.33±17.04) per field, 14 d group (152.00±23.72) per field, 28 d group (144.33±19.09) per field, P<0.05] and significantly increased LDH release [control group (1), 7 d group (8.33±1.41), 14 d group (9.23±0.83), 28 d group (9.16±0.60), P<0.05]. There was no significant difference in the degree of damage caused by RBC-S among different storage groups (P>0.05). With the prolongation of storage time, free hemoglobin (FHb) gradually increased [control group (not detected), 7 d (16.57±6.38) mg/L, 14 d (76.80±22.83) mg/L, 28 d (286.97±29.02) mg/L, P<0.05]. The apoptotic rate (20.53±2.94)% and ROS relative intensity (5.13±0.91) in the 28 d storage group were significantly higher than those in the control group (P<0.05). Transcriptomic analysis showed that FZD1 played a key role in vascular endothelial dysfunction induced by red blood cell storage and was closely related to the Wnt signaling regulatory network. Conclusion: RBC-S stored for 7 d, 14 d, or 28 d can all significantly damage vascular endothelial cells, and the damaging effect reaches a plateau at 7 d of storage. Mechanistic investigation of the 28 d group indicated that the downregulation of the FZD1/Wnt signaling pathway may play a critical role in vascular endothelial dysfunction induced by red blood cell storage, providing a theoretical basis for further optimizing red blood cell storage and transfusion strategies.

Objective: To explore whether digital facial and tongue diagnostic technologies can support the assessment of coronary heart disease (CHD) patients for coronary artery stenosis severity, and examine potential associations between digital tongue diagnosis features and myocardial biomarkers. Methods: The TFDA-1 face and tongue diagnosis instrument and the TDAS analysis system were used to perform intelligent visual examination and analysis of the facial and tongue in CHD patients who attended the Department of Cardiology at Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine between October 2, 2023 and July 31, 2024. Variables were screened using principal component analysis (PCA) and multicollinearity analysis to construct four machine learning models, including random forest, LightGBM, decision tree, and naive Bayes, for the early prediction of coronary artery stenosis severity. Model performance metrics, including sensitivity, specificity, precision, F1 score, accuracy, and the area under the receiver operating characteristic (ROC) curve (AUC), were evaluated. Visual analyses were performed using the SHapley Additive exPlanations (SHAP) interpreter and decision curve analysis. For patients after percutaneous coronary intervention (PCI), a conceptual model linking cardiac biomarkers and tongue diagnosis was constructed using the partial least squares structural equation modeling (PLS-SEM), and its validity was assessed. Results: A total of 459 CHD patients were enrolled and assigned to a PCI group and a non-PCI group (which comprised two subgroups: mild stenosis or less group, moderate stenosis or greater group). For sublingual vein (SV) features, the PCI group had lower SV-a and SV-b than the other groups (P < 0.01 and P < 0.05, respectively). For tongue surface features, the PCI group had significantly higher tongue body (TB)-L, TB-a, and TB-b (P < 0.05, P < 0.01, and P < 0.001, respectively), as well as higher tongue coating (TC)-a and TC-b (P < 0.01 and P < 0.001, respectively). Age, SV-a, SV-b, creatine kinase-myocardial band (CK-MB), CK, TC-a, lip-L, and lip-b were incorporated in the machine learning models. The random forest model performed best, with an AUC of 0.924, an F1 score of 0.839, precision of 0.807, accuracy of 0.864, sensitivity of 0.873, and specificity of 0.839. Decision curve analysis indicated that both LightGBM and random forest had clinical utility. PLS-SEM confirmed the pathway relationships: myocardial biomarkers → TB and myocardial biomarkers → TC (coefficient = – 0.238, t = 2.239, P = 0.025, and coefficient = – 0.270, t = 2.522, P = 0.012, respectively). Conclusion This study developed a noninvasive early warning model for coronary artery stenosis in patients with CHD. It applied PLS-SEM to investigate the association between post-PCI cardiac biomarkers and tongue diagnosis, and validated the proposed association chain. These findings suggest that intelligent traditional Chinese medicine (TCM) visual diagnosis integrated with modern digital technology may support CHD risk assessment and comprehensive health management.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

BACKGROUND:Metal-organic frameworks exhibited great potential for bone tissue engineering and bone disease treatment because of its unique merits including tunable porosity,a large specific surface area,good biocompatibility,and easy structure modification. OBJECTIVE:To review the advancements,application,strengths,and weaknesses of metal-organic framework materials in bone repair,arthritis,bone infection,and bone tumors,offering guidance and strategies for future research. METHODS:Web of Science,PubMed,and CNKI databases were searched using Chinese and English keywords"metal-organic frameworks,MOFs,orthopedics,bone repair,bone regeneration,orthopaedic applications,bone tissue engineering,bone infection,arthritis,bone tumor,osteosarcoma"for related literature published from 2015 to 2023.Following initial screening based on inclusion and exclusion criteria,72 articles were finally included for review. RESULTS AND CONCLUSION:(1)During bone repair,metal ions of metal-organic frameworks can induce bone formation by activating specific signaling pathways,which include stimulating osteogenic gene expression,inhibiting osteoclasts,encouraging blood vessel formation,and speeding up bone mineralization.Hence,metal-organic frameworks with metals like calcium,strontium,cobalt,copper,and magnesium ions show significant potential in enhancing bone implant performance.(2)Metal-organic framework materials,especially zinc/cobalt-based metal-organic frameworks,exhibit enzyme-like activities and promote cartilage regeneration by scavenging reactive oxygen species.Compared with natural enzymes,it has the advantages of not easy inactivation and better stability.(3)Zinc-based metal-organic framework materials characterized with wide band gaps,efficient separation and migration of photogenerated carriers,and high stability,the enhancement of photocatalytic activity results from enhancing the excited electron-hole widely used for the eradication of bacteria and tumor cells.(4)Bimetallic metal-organic frameworks,the doping of additional metals,showed critical advantages in optimizing structural performance,such as zinc/magnesium-based metal-organic framework 74 offering increased stability for durable antibacterial activity,and the light absorption capacity and photocatalytic efficiency of tantalum/zirconium-based metal-organic framework greatly improved and thus enhancing the radiation therapy.(5)However,metal-organic framework materials still face challenges in clinical applications,such as the uncertainty of drug release,in vivo safety,and potential immune responses from long-term presence.

ObjectiveTo investigate the influence of entecavir （ETV） versus tenofovir alafenamide fumarate （TAF） on renal function in previously untreated patients with chronic hepatitis B （CHB）. MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023， and according to the antiviral drug used， they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data， propensity score matching （PSM） was used for matching and analysis at a ratio of 2∶1， and the two groups were compared in terms of estimated glomerular filtration rate （eGFR） and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48， the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function， and the receiver operating characteristic （ROC） curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function， and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching， there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group （all P>0.05）， with an eGFR level of 112.29±9.92 mL/min/1.73 m² in the ETV group and 114.72±12.15 mL/min/1.73 m² in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups， and compared with the TAF group at week 48， the ETV group had a significantly lower eGFR （106.42±14.12 mL/min/1.73 m² vs 112.25±13.44 mL/min/1.73 m²， t=-2.422， P=0.017） and a significantly higher incidence rate of abnormal renal function （17.00% vs 4.00%， χ²=5.092， P=0.024）. After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients， the univariate analysis showed that there were significant differences between the two groups in age （Z=-2.039， P=0.041）， treatment drug （ETV/TAF） （χ²=5.092， P=0.024）， and baseline eGFR level （t=4.023， P<0.001）， and the multivariate Logistic regression analysis showed that baseline eGFR （odds ratio ［OR］=0.896， 95% confidence interval ［CI］： 0.841 — 0.955， P<0.001） and treatment drug （OR=5.589， 95%CI： 1.136 — 27.492， P=0.034） were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients， with a cut-off value of 105.24 mL/min/1.73 m²， a sensitivity of 73.68%， and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m² had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m² （χ²=22.330， P<0.001）， and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group （χ²=4.961， P=0.026）. With the initiation of antiviral therapy， both the ETV group and the TAF group had a significant reduction in eGFR （F=5.259， P<0.001）， but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 （t=-2.422， P=0.017）； both the baseline eGFR≤105.24 mL/min/1.73 m² group and the baseline eGFR>105.24 mL/min/1.73 m² group had a significant reduction in eGFR （F=5.712， P<0.001）， and there was a significant difference in eGFR between the two groups at baseline and weeks 12， 24， 36， and 48 （t=-13.927， -9.780， -8.835， -9.489， and -8.953， all P<0.001）. ConclusionFor CHB patients initially treated with ETV or TAF， ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for diagnosing malignant adnexal tumors.Methods Totally 112 patients with single adnexal masse were retrospectively enrolled and divided into benign adnexal tumor group(benign group,n=73)and malignant adnexal tumor group(malignant group,n=39).Clinical data,laboratory indicators,ovarian-adnexal ultrasound reporting and data system(O-RADS)classification based on conventional ultrasound(US),CEUS manifestations and CEUS classification of benign and malignant tumors were compared between groups.Multivariable logistic regression analysis of clinical and laboratory indicators being statistically different between groups,as well as US O-RADS classification and CEUS classification was performed to screen the independent predictors of malignant adnexal tumors,and combined models were constructed using forward stepwise regression method.The efficacy of each independent predictor and combined model for diagnosing malignant adnexal tumors was analyzed.Results Statistical differences of carbohydrate antigen 125(CA125),US O-RADS classification,enhancement time and level of CEUS,as well as CEUS classification were found between groups(all P＜0.05).CA125,US O-RADS classification and CEUS classification were all independent predictors of malignant adnexal tumors(all P＜0.05).Combined model Ⅰ,Ⅱ and Ⅲ were constructed based on CA125+CEUS classification,US O-RADS classification+CEUS classification and CA125+US O-RADS classification+CEUS classification,respectively.The area under the curve(AUC)of single CA125 level,US O-RADS classification,CEUS classification and combined model Ⅰ,Ⅱ and Ⅲ for diagnosing malignant adnexal tumor was 0.708,0.809,0.908,0.918,0.945 and 0.954,respectively.AUC of combined model Ⅲ was higher than that of combined model Ⅰ(Z=-2.142,P=0.032),while no significant difference of AUC was found between combined model Ⅱ and Ⅰ nor Ⅱ and Ⅲ(both P＞0.05).Conclusion CEUS could be used to effectively diagnose malignant adnexal tumor.Combining with CA125 level and US O-RADS classification could significantly improve its diagnostic efficacy.

Excessive ionizing radiation can disrupt the molecular structures of organisms,leading to health issues such as acute radiation syndrome and cancer,posing serious threats to human health.The development of radioprotective drugs holds significant importance for mitigating ionizing radiation damage and safeguarding public health,yet its research process faces multidimensional ethical challenges.This paper systematically explores the ethical issues involved in the full lifecycle of radioprotective drug development,focusing on the ethical particularities of animal experimentation,ethical dilemmas in human trials,data privacy and security risks,as well as challenges in managing conflicts of interest.Targeted solutions are proposed,including strengthening ethical review mechanisms,promoting interdisciplinary collaboration,constructing data security management systems,and establishing conflict-of-interest mediation mechanisms.These comprehensive measures aim to build a scientifically rigorous ethical framework for radioprotective drug research,fostering sustainable development in this field.