Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Objective:To analyze the clinical and epidemiological characteristics of adult carotid body tumors (CBTs) in Northwest China to provide references for early diagnosis and treatment of CBTs.Methods:A multicenter, retrospective, non-intervention epidemiological investigation was conducted on adult CBTs patients who were hospitalized from January 1, 2011 to June 30, 2023 in 7 Class A tertiary hospitals in Northwest China (Departments of Neurosurgery, First Affiliated Hospital of Air Force Medical University, Second Affiliated Hospital of Lanzhou University, People's Hospital of Gansu Province, 940 th Hospital of PLA Joint Logistic Support Force, People's Hospital of Qinghai Province, General Hospital of Ningxia Medical University, People's Hospital of Ningxia Hui Autonomous Region). Medical records were collected in these patients, and they were divided into 2 groups according to their average altitude residence: high altitude group (≥1 500 m) and low altitude group (<1 500 m); meanwhile, these patients were divided into Shamblin type I, type II and type III groups according to Shamblin classification criteria; differences in general data and clinical features among patients from different altitude groups or Shamblin subgroups were compared. Independent influencing factors for Shamblin type III CBTs were analyzed by multivariate ordered Logistic regression. Results:(1) A total of 359 patients were enrolled in the study, including 276 females and 83 males, aged (48.80±12.07) years; 211 patients were into the high altitude group and 148 into the low altitude group; 165 patients were into Shamblin type I group, 146 into Shamblin type II group, and 48 into Shamblin type III group. (2) Compared with those in the low altitude group, patients in the high altitude group had higher proportion of females, older age, lower proportion of Han nationality, higher proportion of Shamblin type I, smaller tumor volume, lower platelet count, higher red blood cell count, hematocrit, hemoglobin level, platelet distribution width and mean platelet volume, and higher large platelet percentage, with significant differences ( P<0.05). (3) Compared with those in the Shamblin type I group, patients in the Shamblin type III group had younger age, lower resident altitude, larger tumor volume, longer time interval from onset to diagnosis, higher proportion of unintentional tumor discovery, larger volume of intraoperative blood loss, lower hemoglobin level, hematocrit, mean erythrocyte volume, and mean hemoglobin concentration, decreased erythrocyte distribution width variable coefficient, and increased platelet count, with significant differences ( P<0.05). Compared with those in the Shamblin type II group, patients in Shamblin type III group had younger age, larger tumor volume, longer time interval from onset to diagnosis, larger volume of intraoperative blood loss, lower hemoglobin, hematocrit and mean erythrocyte volume, higher erythrocyte distribution width variable coefficient and platelet count, with significant differences ( P<0.05). (4) Age ( OR=0.960, 95% CI: 0.942-0.977, P<0.001), residence altitude ( OR=0.992, 95% CI: 0.990-0.999, P=0.020) and time interval from onset to diagnosis ( OR=1.009, 95% CI: 1.005-1.014, P<0.001) were independent influencing factors for Shamblin type III CBTs. Conclusions:More females than males are noted in patients with adult CBTs in Northwest China, and more CBTs patients live at high altitude, with Shamblin type I enjoying the highest proportion. More female and old patients lived at high altitude is noted than those lived at low altitude; patients with Shamblin type III have the youngest age, lowest altitude, and longest time interval from onset to diagnosis. CBTs patients with young age, low residence altitude, and long time interval from onset to diagnosis are more likely to develop Shamblin type III.

Objective To observe and analyze the application of project achievement style quality control circle in constructing an outpatient intelligent pharmacy pre-job training model,and provide new ideas and systematic solutions for pre-job training of new pharmacists in intelligent pharmacies.Methods 70 pharmacists who were newly employed in outpatient pharmacy of Yantai Yuhuangding Hospital from January 2023 to March 2024 and had no working experience in this position were selected and divided into two groups(the control group and the experimental group)by random draw method.The control group implemented the traditional training mode,and the experimental group adopted the new mode of pre-job training of outpatient intelligent pharmacy constructed by project achievement style quality control circle.The theoretical,skill,and practical examination results at the end of the training period and the satisfaction with training of the newly-appointed pharmacists were collected.Results The assessment scores of theory,skills and practice,and the results of satisfaction with the training of newly recruited pharmacists in the experimental group were significantly higher than those of the control group(P＜0.05).Conclusion The new model of pre-job training for new pharmacists in the outpatient intelligent pharmacy has great advantages in the design of the training program,standardization of the training content,reasonable arrangement of the training cycle,and innovation of the training mode,which improves the pharmacists'satisfaction with the training and achieves good training results.

Objective:To explore the influence of pancreatic stents of different lengths on the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP).Methods:Data of 299 patients with biliary tract diseases who received endoscopic retrograde cholangiopancreatography (ERCP) and 5 Fr prophylactic pancreatic stents placement at the First Affiliated Hospital of Air Force Medical University from January 2013 to January 2022 were retrospectively analyzed. Patients were divided into the short-stent group (<5 cm, n=163) and the long-stent group (>5 cm, n=136). Baseline data, intraoperative procedures, and postoperative outcomes were compared between the two groups and propensity score matching (PSM) was used for complementary analysis. The primary endpoint was the incidence of PEP. The risk factors for PEP in patients with prophylactic pancreatic stents placement was explored by logistic regression analysis . Results:The overall PEP incidence was 11.0% (33/299). There was no significant difference in the PEP incidence [11.7% (19/163) VS 10.3% (14/136), χ 2=0.140, P=0.708], moderate-to-severe PEP incidence [1.8% (3/163) VS 2.2% (3/136), χ 2=0.000, P=1.000], or spontaneous stent dislodgement rate within two weeks [81.7% (103/126) VS 78.4% (87/111), χ 2=0.421, P=0.516] between the two groups. After PSM, 123 patients were included in each group, and the overall PEP incidence was 8.9% (22/246). There was no significant difference in PEP incidence [8.9% (11/123) VS 8.9% (11/123), χ 2=0.000, P=1.000], moderate-to-severe PEP incidence [0.8% (1/123) VS 1.6% (2/123), χ 2=0.000, P=1.000], or spontaneous stent dislodgement rate within two weeks [80.6% (75/93) VS 78.6% (77/98), χ 2=0.126, P=0.722] between the two groups. Logistic regression analysis showed that normal liver function ( OR=2.36, 95% CI:1.01-5.51, P=0.046) and failed bile duct cannulation ( OR=7.51, 95% CI:2.18-25.96, P=0.001) were independent risk factors for PEP in patients with biliary tract diseases who received prophylactic pancreatic stents placement. Conclusion:Longer 5 Fr pancreatic stents (>5 cm) do not further reduce the overall risk of PEP or moderate-to-severe PEP compared with 5Fr-5 cm stent. Normal liver function and failure of bile duct intubation were independent risk factors for PEP after prophylactic pancreatic stent placement in patients with biliary diseases.

Objective:To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) after pancreaticoduodenectomy and endoscopic selection strategies.Methods:Clinical data of 34 patients treated with ERCP after pancreaticoduodenectomy at the Endoscopic Center of the First Affiliated Hospital of Air Force Medical University from January 2013 to December 2021 were retrospectively analyzed. The success rates of endoscopic insertion, diagnosis, treatment and ERCP, and the incidence of adverse events were analyzed.Results:Fifty ERCP treatments were performed in 34 patients. The success rates of endoscopic insertion, diagnosis, treatment, and ERCP after pancreaticoduodenectomy were 92.0% (46/50), 93.5% (43/46), 88.4% (38/43) and 76.0% (38/50), respectively. The success rates of ERCP assisted with colonoscope and balloon-assisted enterosocpe were 76.0% (19/25) and 75.0% (18/24), respectively. There were 3 adverse events, including 1 case of anastomotic mucosa tear during surgery, 1 case of cardiopulmonary arrest and 1 case of postoperative cholangitis.Conclusion:ERCP is effective and safe after pancreaticoduodenectomy in general. ERCP assisted with colonoscope and balloon-assisted colonoscope shows similar success rate after pancreaticoduodenectomy.

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis

Objective:To explore the ability of sequential immunization regimen inducing neutralizing antibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Wuhan-Hu1 and Omicron variants in mice.Methods:Groups of 6-8-week-old BALB/c mice were primed with two doses of Wuhan-Hu-1 inactivated vaccine, and then boosted with Omicron or Wuhan-Hu-1 inactivated vaccine, respectively. Binding antibodies were tested by enzyme linked immunosorbent assay; and neutralizing antibodies against Wuhan-Hu1 and Omicron variants were analyzed by vesicular stomatitis virus pseudovirus assay system; SARS-CoV-2 specific cellular immune responses were quantified by enzyme-linked immunosorbent spot assay.Results:IgG antibodies against Wuhan-Hu1, Delta and Omicron RBD were enhanced after the second dose of Wuhan-Hu1 inactivated vaccine. Compared with Wuhan-Hu1 inactivated vaccine, the group boosted with Omicron inactivated vaccine improved Wu-RBD and Omic-RBD specific IgG antibodies 1.41 and 1.26 times, and serum neutralizing antibodies against BA.1, BA.2, BA.4/5 and BF.7 were elevated 4.5, 3.4, 12.1 and 6.5 folds, respectively, by sequential immunization. After booster immunization with inactivated Wuhan-Hu1 or Omicron vaccines, Wu-RBD IgA titer was significantly higher than that of one dose inactivated Wuhan-Hu1 vaccine ( P=0.005 7, P=0.006 1). Conclusions:Neutralizing antibodies against Omicron variants were enhanced by sequential immunization with Omicron inactivated vaccine. Specific IgA was significantly enhanced after the third dose of inactivated vaccine.

Objectives:To investigate the prevalence and related factors of cardiovascular diseases (CVD) and psychological problems in Chinese science and technology workers.Methods:The investigation was organized and conducted by the Innovative and Development Institute of China Association of Senior Scientists and Technologists and Capital Medical University Affiliated Beijing Anzhen Hospital, and included science and technology workers from research institutions and medical institutions in China by random sampling methods through face-to-face and online questionnaire investigation from July 1, 2019 to March 31, 2021. Information including age, sex, work stress status, CVD history, sleep, depression, and anxiety were included in the questionnaire.Results:This survey included 14 552 subjects. Among them, 25.5% were suffered from CVD, 48.6% were with insomnia, 28.8% experienced depression/anxiety (including only depression, only anxiety, depression combined with anxiety), and 15.6% had CVD in combined with depression/anxiety. Taking those without CVD and depression/anxiety as reference group, multiple logistic regression analyses showed that work stress increased the risk of depression/anxiety in subjects without CVD (manageable work stress, OR=2.253, 95 %CI 1.583-3.206, overwhelming work stress OR=7.899, 95 %CI 5.094-12.250), and drinking increased the risk of CVD ( OR=1.978, 95 %CI 1.382-2.833). Moreover, overwhelming work stress ( OR=4.012, 95 %CI 2.515-6.399) and smoking ( OR=2.342, 95 %CI 1.603-3.421) increased the risk of depression/anxiety in subjects with CVD (all P<0.001). Conclusion:The high morbidities of depression/anxiety, CVD, and CVD in combination with depression/anxiety urge us to take actions to protect the heart and mental health of scientific and technological workers.

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis