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 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: 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.

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.

Objective:To investigate the correlation between plasma Dickkopf-1 (DKK1) and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke.Methods:Consecutive patients with first-ever acute ischemic stroke admitted to the Department of Neurology, Nanjing Jiangbei Hospital from March 2023 to February 2024 were included prospectively. Enzyme-linked immunosorbent assay was used to detect plasma DKK1 within 24 hours of onset. The Montreal Cognitive Assessment Scale was used to evaluate cognitive function at 3 months after onset. A score ≤22 was defined as PSCI. Multivariate logistic regression analysis was used to determine the correlation between DKK1 and PSCI. The relationship between DKK1 and PSCI risks was evaluated through restrictive cubic spline analysis. Results:A total of 205 patients with acute ischemic stroke were enrolled, including 106 males (51.7%), aged 67.0±9.4 years; 61 patients (29.8%) experienced PSCI. Multivariate logistic regression analysis showed that after adjusting for age, gender, education level, and other confounding factors, there was a significant independent correlation between higher plasma DKK1 and PSCI (odds ratio 1.778, 95% confidence interval 1.313-2.408; P=0.001). Subgroup analysis showed that age, gender, etiological classification of stroke, and education level had no significant effect on the above correlation. Restrictive cubic spline analysis showed plasma DKK1 had a linear relationship with the risk of PSCI ( P=0.003). Conclusion:Higher plasma DKK1 level is significantly correlated with PSCI in patients with acute ischemic stroke at 90 days after onset.

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 assess the impact of long-term antiretroviral therapy (ART) on human immunodeficiency virus (HIV) blood screening outcomes in post-exposure prophylaxis (PEP) failure cases through a longitudinal analysis of blood screening results over a 7-year period in a patient with HIV PEP failure. Methods: This study conducted 13 follow-up assessments for a high-risk individual who initiated ART shortly after exposure. The effectiveness of various blood screening methods, including immunological assays and nucleic acid testing (NAT), was analyzed. Blood samples were also tested with HIV RNA quantification testing, Western blot (WB) confirmation testing, chemiluminescence immunoassay (CLIA), and HIV rapid tests utilizing gold and selenium labels. A comprehensive analysis was performed to evaluate the changes in diagnostic capabilities of different testing methods for HIV biomarkers over an extended period following PEP failure. Results: The patient had two high-risk exposures: one day before ART initiation (BA1) and seven days preceding treatment (BA7). On the first day after the ART treatment (AA1), the HIV RNA concentration (viral load) was 9.07×10 copies/mL; by day five (AA5), the viral load decreased to 1.04×10 copies/mL. At day eleven (AA11), NAT and ELISA tests were both positive, with the WB result remaining indeterminate (gp160+). At day 48 (AA48), the S/CO value of the fourth generation ELISA reagent was 1.07, while results from a 6-sample pool and quantitative NAT were negative. However, a single sample NAT returned a positive result and WB tests indicated positivity for p17, p24, and gp160. At AA74, the quantitative NAT rebounded to 2.83×10 copies/mL, with positive NAT results for single and 6-sample pool NAT tests. The S/CO values of the imported and domestic ELISA reagents were 3.39 and 23.44, respectively. At AA201, 6-sample pool and quantitative NAT were negative again, while single sample NAT remained positive. From AA319 to AA2221, all NAT results have remained consistently below the minimum detection limit. At AA2221, S/CO values of the imported and domestic ELISA reagents were 3.47 and 23.44, respectively. Conclusion: The findings indicate that patients experiencing PEP failure after high-risk HIV exposure are at a higher risk of being missed by mixed-sample NAT pools and individual serological tests. Nonetheless, anti-HIV antibody levels are sustained at elevated values for an extended duration, underscoring antibody testing as an effective measure for blood screening.

Biliary tract cancer (BTC) represents a group of highly malignant solid tumors with a five-year survival rate of only 10%. For patients with unresectable BTC, gemcitabine combined with cisplatin has been the conventional first-line treatment regimen. With the remarkable efficacy of immunotherapy and targeted therapy observed in other solid tumors, numerous studies have investigated their potential in unresectable BTC. This article provides an overview of the current status of targeted and immunotherapeutic approaches for unresectable BTC, with a focus on research advancements in immune checkpoint inhibitor (ICI) and targeted agents against fibroblast growth factor receptor(FGFR), isocitrate dehydrogenase(IDH), and human epidermal growth factor receptor 2(HER2), as well as future trends in immunotherapy and targeted therapy, aiming to contribute to the development of more effective treatment strategies.