Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective:To investigate the pathological characteristics of post-cholecystectomy specimens from patients with benign gallbladder diseases.Methods:This retrospective case series study analyzed clinical and pathological data from 1 712 patients who underwent cholecystectomy for benign gallbladder diseases at the Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between September 2022 and August 2024. The cohort included 757 males and 955 females, with an age ( M(IQR)) of 57(23) years (range: 14 to 91 years). Clinical and pathological features were analyzed. The χ2 test was used to compare clinical characteristics between patients with neoplastic and non-neoplastic polyps. Factors statistically significant in the χ2 test were subsequently included in a binary logistic regression analysis. Results:Postoperative pathological examination revealed gallbladder cancer in 7 patients (0.41%). These 7 cases, including 2 with pT3 stage cancer, were not detected preoperatively by various imaging examinations (ultrasound+magnetic resonance cholangiopancreatography/MRI plain scan in 3 cases, ultrasound+enhanced MRI in 1 case, ultrasound+enhanced CT in 2 cases, enhanced CT+enhanced MRI in 1 case). Gallbladder adenoma was found in 23 cases (1.34%), neoplastic polyps (including cholesterol polyps with dysplasia) in 29 cases (1.69%), and non-neoplastic polyps in 154 cases (9.00%). Statistically significant differences were observed in age and polyp number between patients with neoplastic and non-neoplastic polyps ( χ2=10.436 and 8.030; both P<0.05). Binary logistic regression analysis identified age ≥60 years ( P=0.003) and solitary polyps ( P=0.009) as risk factors for neoplastic polyps. Mucosal dysplasia was present in 164 cases (9.58%), including 9 cases of severe dysplasia, 4 of which exhibited focal carcinomatous transformation. Gallbladder polyps combined with stones were found in 90 cases (5.26%), among which 10 were associated with adenoma and mucosal dysplasia, and 2 showed focal carcinomatous transformation. Conclusions:The incidence of incidental gallbladder carcinoma was 0.41%. Intraoperative bile spillage can severely compromise prognosis. Preoperative imaging demonstrates a low detection rate for neoplastic polyps. Particular vigilance for neoplastic polyps is warranted in patients aged ≥60 years or with solitary polyps. Cholecystectomy should be performed promptly for benign gallbladder diseases meeting surgical indications.

Objective:To investigate the pathological characteristics of post-cholecystectomy specimens from patients with benign gallbladder diseases.Methods:This retrospective case series study analyzed clinical and pathological data from 1 712 patients who underwent cholecystectomy for benign gallbladder diseases at the Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between September 2022 and August 2024. The cohort included 757 males and 955 females, with an age ( M(IQR)) of 57(23) years (range: 14 to 91 years). Clinical and pathological features were analyzed. The χ2 test was used to compare clinical characteristics between patients with neoplastic and non-neoplastic polyps. Factors statistically significant in the χ2 test were subsequently included in a binary logistic regression analysis. Results:Postoperative pathological examination revealed gallbladder cancer in 7 patients (0.41%). These 7 cases, including 2 with pT3 stage cancer, were not detected preoperatively by various imaging examinations (ultrasound+magnetic resonance cholangiopancreatography/MRI plain scan in 3 cases, ultrasound+enhanced MRI in 1 case, ultrasound+enhanced CT in 2 cases, enhanced CT+enhanced MRI in 1 case). Gallbladder adenoma was found in 23 cases (1.34%), neoplastic polyps (including cholesterol polyps with dysplasia) in 29 cases (1.69%), and non-neoplastic polyps in 154 cases (9.00%). Statistically significant differences were observed in age and polyp number between patients with neoplastic and non-neoplastic polyps ( χ2=10.436 and 8.030; both P<0.05). Binary logistic regression analysis identified age ≥60 years ( P=0.003) and solitary polyps ( P=0.009) as risk factors for neoplastic polyps. Mucosal dysplasia was present in 164 cases (9.58%), including 9 cases of severe dysplasia, 4 of which exhibited focal carcinomatous transformation. Gallbladder polyps combined with stones were found in 90 cases (5.26%), among which 10 were associated with adenoma and mucosal dysplasia, and 2 showed focal carcinomatous transformation. Conclusions:The incidence of incidental gallbladder carcinoma was 0.41%. Intraoperative bile spillage can severely compromise prognosis. Preoperative imaging demonstrates a low detection rate for neoplastic polyps. Particular vigilance for neoplastic polyps is warranted in patients aged ≥60 years or with solitary polyps. Cholecystectomy should be performed promptly for benign gallbladder diseases meeting surgical indications.

Objective: Some regions in China have lowered the minimum interval for whole blood donation to 3 months through local regulations: Hainan, effective from March 1, 2012, allows men to donate at intervals of≥3 months and women at intervals of≥4 months; Shenzhen, effective from November 1, 1995, allows whole blood donation at intervals of≥3 months. The aim of this study was to evaluate the impact of shortening the whole blood donation interval on blood donation adverse reactions and donation behavior, thereby providing scientific evidence for policy evaluation and revision of relevant regulations. Methods: This was a multicenter, retrospective cohort study based on blood donation registry data from Shenzhen and Hainan. Data were obtained from the blood information management systems of Hainan Province (1991-2025) and Shenzhen City (2018-2024). Eligible participants were donors aged 18-65 years who had donated whole blood at least twice and met health eligibility criteria. The exposure was defined as a shorter donation interval (whole-blood interval≥3 months and<6 months) and was treated as a time-varying variable. The primary outcome was blood donation adverse reactions. Negative binomial regression with person-years as an offset was used to estimate incidence rate ratios for adverse reactions. Marginal standardization was used to estimate the adjusted incidence rate difference, and donor-level bootstrap resampling was used to estimate the 95% confidence interval of the adjusted incidence rate difference. Non-inferiority was assessed by comparing the upper limit of the 95% confidence interval with the prespecified non-inferiority margin of Δ=0.00 070 per person-year. In addition, Andersen-Gill models were used to analyze adverse reaction-free probability for recurrent events. Secondary outcomes were donation behavior, including annual repeat donation rate, annual donation frequency, mean donation interval, and annual whole-blood donation volume. These were analyzed using logistic regression, negative binomial regression, and linear regression models, respectively, with adjustment for age, sex, region, and donation site. This study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (Approval No.2025011) and registered in the Chinese Clinical Trial Registry (ChiCTR2500114968). Results: A total of 375 075 repeat whole-blood donors were included, contributing 1 292 748 whole-blood donations. Among them, 119 993 had ever donated at a shorter interval and 255 082 had never done so. Over 1 281 842 person-years of follow-up in the dynamic cohort, 2 100 blood donation adverse reactions were recorded. The incidence rates of adverse reactions were 1.76 and 1.58 per 1 000 person-years in the ever-short interval and never-short interval groups, respectively. After adjustment for age, sex, province, and donation site, the ever-short interval group had a slightly higher adverse reaction rate than the never-short interval group (IRR=1.28, 95%CI: 1.15-1.41, P<0.001). Marginal standardization showed that the adjusted incidence rates were 1.73 and 2.21 per 1 000 person-years in the never-short interval and ever-short interval groups, respectively. The adjusted incidence rate difference was 0.000 48 per person-year, with a bootstrap 95%CI of 0.000 26-0.000 69 per person-year; the upper limit of the 95%CI was below the prespecified non-inferiority margin. Andersen-Gill recurrent-event analysis showed that the ever-short interval group had a higher probability of remaining adverse reaction-free. Analysis of donation behavior showed that among donors followed for at least 365 days, the ever-short interval group had a higher annual repeat donation rate than the never-short interval group (74.2% vs 18.3%; adjusted OR=12.5, 95%CI: 12.3-12.7, P<0.001). They also had a higher annual whole-blood donation rate (adjusted RR=1.98, 95%CI: 1.97-1.98, P<0.001), a shorter mean whole-blood donation interval (β=-239 days, 95%CI: -242 to -237 days, P<0.001), and a higher annual whole-blood donation volume (adjusted RR=2.14, 95%CI: 2.13-2.15, P<0.001). Conclusion: Based on real-world data from repeat whole-blood donors in Shenzhen and Hainan, lowering the minimum whole blood donation interval to 3 months did not show an absolute increase in blood donation adverse reactions exceeding the prespecified margin within the scope of this outcome. Shorter whole-blood donation interval behavior was also associated with greater repeat-donation activity, higher annual donation frequency, and higher annual whole-blood donation volume. Given the observational nature of this study and the lack of long-term donor health indicators such as iron status and longitudinal hemoglobin changes, the long-term safety of setting the minimum whole blood donation interval at 3 months requires further evaluation.

OBJECTIVE To investigate the characteristics and safety of finerenone use in hospitalized patients with acute heart failure （AHF）.METHODS A single-center retrospective cohort study was conducted， enrolling 171 AHF patients who initiated finerenone therapy during hospitalization at The First Affiliated Hospital of University of Science and Technology of China between November 2023 and April 2026. Baseline characteristics， finerenone use patterns，in-hospital major and minor safety endpoints were collected. Univariate intergroup analysis， univariate and multivariate Logistic regression were performed to identify predictive factors （Firth’s penalized likelihood method was used when events were sparse）. Propensity score matching （PSM） and stabilized inverse probability of treatment weighting （sIPTW） were employed to compare the safety differences between early initiation （≤3 d） and intermediate-to-late initiation （＞3 d） of finerenone. Sensitivity analysis was conducted to verify the robustness of the hyperkalemia-related results.RESULTS A total of 171 hospitalized patients with AHF were included， with 63.7% having heart failure with preserved ejection fraction. The median time to finerenone initiation was 2 d after admission， with early initiation accounting for 64.3%， an initial dose of 10 mg once daily accounting for 83.0%， and concomitant use of sodium-glucose cotransporter 2 inhibitor （SGLT2i） accounting for 83.6%. In the overall cohort， the incidence of hyperkalemia was 3.5%， the incidence of acute kidney injury was 13.5%， and the incidence of the composite endpoint was 21.6%. Concomitant SGLT2i use was associated with a lower risk of hyperkalemia in univariable Logistic regression （OR＝0.18， 95%CI of 0.04-0.86， P ＝0.032） and showed a trend toward a protective association after multivariable Logistic regression adjustment， although this did not reach statistical significance （OR＝0.24， 95%CI of 0.05-1.21， P ＝0.084）； after multivariable Logistic regression adjustment，baseline serum potassium was independently associated with the risk of the composite endpoint （OR＝2.01， 95%CI of 1.06-3.82， P ＝0.032）. Both PSM（OR＝0.70， 95%CI of 0.27-1.83）and sIPTW（OR＝0.70， 95%CI of 0.32-1.52）analyses showed that early initiation of finerenone did not increase the risk of the composite endpoint. Sensitivity analysis results were consistent with the overall cohort analysis.CONCLUSIONS The enrolled patients initiated finerenone early with reasonable starting doses， and a high proportion received concomitant SGLT2i therapy； early initiation did not increase the risk of in-hospital hyperkalemia or acute kidney injury， with an overall favorable safety profile， and concomitant SGLT2i use showed a protective trend with respect to hyperkalemia risk.

Hepatitis E is an acute and self-limiting viral hepatitis caused by the hepatitis E virus (HEV). It has a higher mortality rate among immunosuppressed patients and pregnant women infected with HEV. Although HEV infections in humans are mostly caused by contaminated water or food worldwide, the incidence of transfusion-transmitted hepatitis E is continuously rising. Additionally, the prevalence of serum anti-HEV IgG in the blood donors in China is at a relatively high level, making it worth considering screening blood donors for HEV. This article briefly reviews the globally reported cases of transfusion-transmitted hepatitis E and the HEV screening strategies for blood donations.

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Objective: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86％,95.16％,and 95.10％,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90％.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59％,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24％,53.39％,and 62.37％for junior technicians,and to 92.06％,83.24％,and 83.12％for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46％,10.61％,and 3.71％for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13％)of red blood cell diseases,5 cases(0.16％)of platelet diseases,2 343 cases(76.90％)of infection-related disea-ses,and 28 cases(0.92％)of malignant hematological diseases.In addition,332 cases(10.90％)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.