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*

Objective:Exploring the changes in the expression of transient receptor potential vanilloid 1 (TRPV1) in the peripheral and central nervous system in rats temporomandibular joint osteoarthritis (TMJOA) and its relationship with TMJOA pain .Methods:From February 2024 to April 2025, 48 healthy male Sprague Dawley rats were randomly divided into a control group and an experimental group, with 24 rats in each group. The modeling periods for both groups were 2, 4, and 6 weeks, with 8 rats per group at each time point. After bilateral injection of monosodium iodoacetate (MIA) into the temporomandibular joint (TMJ) cavity to establish a TMJOA model, the TMJ condyle, trigeminal ganglion (TG), trigeminal nucleus caudate (TNC), and hippocampal tissue were collected. Pain threshold detector von Frey silk was used to evaluate the head withdrawal threshold (HWT) of rats, and HE staining and micro-CT scanning were used to observe the histological changes of TMJ. Immunohistochemical staining was used to detect the expression of TRPV1 in TG and hippocampal tissues, as well as the expression of glial fibrillar acidic protein (GFAP) in TNC.Results:On the first day after modeling, the HWT of rats significantly decreased and then gradually increased. From day 7 to day 14, HWT decreased again, and after day 14, HWT gradually increased. Statistically significant differences were observed between the experimental group and the control group at each time point ( P<0.001). HE staining and micro-CT revealed that in the second week after modeling, the arrangement of condylar bone trabeculae was disordered, the trabeculae became thinner, the bone marrow cavity became larger, and then the trabeculae became thicker and the bone marrow cavity became smaller. The number of TRPV1 positive cells in TG of TMJOA rats reached its peak in the second week of modeling, and then gradually decreased in the fourth and sixth weeks ( P<0.001), with no statistically significant difference in the control group ( P=0.941). The number of GFAP positive cells in TNCs of TMJOA rats significantly increased, reaching its peak in the second week of modeling and gradually decreasing in the fourth and sixth weeks ( P<0.001). There was no statistically significant difference between the control group ( P=0.720). The number of TRPV1 positive cells in the hippocampus of TMJOA rats significantly increased. The number of TRPV1 positive cells reached its peak in the second week of modeling, and then gradually decreased in the fourth and sixth weeks ( P<0.001). There was no statistically significant difference between the control group ( P=0.776). Conclusions:In the MIA induced rat TMJOA model, the expression of TRPV1 in TG and hippocampal tissue, as well as the expression of GFAP in TNC, were upregulated, which may be involved in the occurrence and development of TMJOA pain and related to the development of TMJOA lesions.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the mosquito-borne viruses carried by mosquito specimens collected from Huachuan county and Huanan county in Heilongjiang province.Methods:Mosquito samples were collected locally in 2023 and processed in the laboratory. Homogenates of the mosquitoes were inoculated into cells for virus isolation, followed by molecular and bioinformatics analyses of the viral isolates.Results:In 2023, ten viral isolates were obtained from Anopheles sinensis specimens collected in Heilongjiang province, China. Among these isolates, one was identified as Culex flavivirus (CxFV), one as Menghai rhabdovirus (MRV), and eight as Nam Dinh virus (NDiV). The phylogenetic analysis showed that CxFV belongs to genotype I and is clustered with the strains isolated from Liaoning province in 2011 and Ningxia Hui autonomous Region in 2019 in the same evolutionary branch, with amino acid similarity ranging from 98.2% to 99.2% and nucleotide similarity ranging from 98.8% to 99.2%. The MRV strain belongs to the same evolutionary subclade as the strain detected in Guangdong, with both nucleotide and amino acid similarity of 98.0%. Eight NDiV isolates clustered with the South Korean isolates on the same evolutionary branch, forming an independent evolutionary sub-branch. The nucleotide similarity among these eight isolates ranged from 98.5% to 99.7%, while the amino acid similarity ranged from 98.1% to 99.7%. In comparison, when matched with other NDiV isolates from China, the nucleotide similarity of these eight isolates ranged from 94.1% to 97.8%, and the amino acid similarity ranged from 93.5% to 97.7%.Conclusions:This study represents the first isolation of CxFV, MRV, and NDiV in Heilongjiang province, China, and the findings provide fundamental data for the prevention and control of mosquito-borne viral diseases in this region.

OBJECTIVE To report a case of hepatitis B virus （HBV） reactivation induced by iparomlimab and tuvonralimab， summarize the clinical characteristics and potential mechanisms of such adverse reactions induced by immune-checkpoint inhibitors （ICIs）， and provide references for clinical application. METHODS From the perspective of a clinical pharmacist， a retrospective analysis was conducted on the treatment course of a patient with metastatic cervical cancer who experienced HBV reactivation after receiving iparomlimab and tuvonralimab. Additionally， an analysis of the correlation with adverse reactions was performed， and the clinical characteristics， risk factors， potential mechanisms， key points of treatment approaches and pharmaceutical care associated with HBV reactivation induced by ICIs were summarized. RESULTS & CONCLUSIONS The patient developed HBV reactivation and severe liver injury after using iparomlimab and tuvonralimab. The condition improved following drug discontinuation， and symptomatic treatment such as glucocorticoids. According to Naranjo’s Assessment Scale and China’s Measures for the Reporting and Monitoring of Adverse Drug Reactions， the association between iparomlimab and tuvonralimab and HBV reactivation was judged as “highly probable”， and it was identified as a new adverse reaction； the correlation between iparomlimab and tuvonralimab， paclitaxel and liver injury was “highly probable”. HBV reactivation in hepatitis B patients receiving standardized antiviral therapy is very rare after ICIs treatment； HBV reactivation is related to the overactivation of the immune system and disruption of immune balance induced by ICIs. For such patients， glucocorticoids should be administered for treatment， accompanied by pharmaceutical care， including pre- medication risk assessment and monitoring of relevant indicators during treatment.

Objective:To investigate the diagnostic and prognostic value of systemic immune inflammatory index (SII) for severe traumatic brain injury secondary to acute lung injury (sTBI-ALI).Methods:A retrospective study was conducted on patients with severe traumatic brain injury admitted to the trauma center of the First Affiliated Hospital of Soochow University from January 2021 to November 2023. Patients received standard treatments including hemostasis and intracranial pressure management. Vital signs and blood routine data were collected upon admission. Patients were categorized into sTBI group and sTBI-ALI group based on established clinical diagnostic criteria for ALI to evaluate the diagnostic utility of SII. Subsequently, within the sTBI-ALI group, patients were stratified into survival and non-survival groups based on their 30-day outcomes to assess the prognostic value of SII.Results:A total of 260 sTBI patients were enrolled, of whom 113 developed ALI. Among the sTBI-ALI patients, 73 survived at 30 days. Compared to the sTBI group, the sTBI-ALI group exhibited significantly higher respiratory rates, heart rates, white blood cell counts, neutrophil counts, platelet counts, and SII levels (all P<0.05). Multivariate logistic regression analysis showed that SII index ( OR=1.003, 95% CI: 1.002-1.004, P<0.001) was an independent risk factor for ALI development in sTBI patients. The combined predictive model incorporating SII and heart rate yielded an AUC of 0.801 (95% CI: 0.740-0.862). The non-survival group had significantly higher neutrophil counts and SII levels, and significantly lower Glasgow Coma Scale scores than the survival group (all P<0.05). Multifactorial regression analysis indicated that SII index ( OR=1.002, P=0.004, 95% CI: 1.000-1.003) served as an independent risk factor for 30-day mortality in sTBI-ALI patients. The combined predictive model of SII and GCS achieved an AUC of 0.904 (95% CI: 0.848-0.960). Conclusions:SII demonstrates potential as a biomarker for predicting the development of ALI following sTBI. Furthermore, incorporating SII into predictive models significantly enhances the ability to forecast mortality risk in sTBI-ALI patients.

Objective To investigate the effects of miR-483-3p on hypoxia/reoxygenation(H/R)-induced apoptosis and pyroptosis of H9c2 cardiomyocytes and its possible mechanism.Methods Rat H9c2 cardiomyocytes were cultured in vitro,adeno-associated virus-infected H9c2 and the H/R model were constructed by triple-air incuba-tor,and the cells were randomly divided into blank control(Sham)group,model(H/R)group,AAV-miR-483-3p mimic+H/R(AAV-miR-483-3p)group,AAV-miR-483-3p negative control+H/R(AAV-NC)group.The growth status of cells in each group was observed using an inverted microscope;cell proliferation activity was detected by cell counting kit-8(CCK-8);LDH release by lactate dehydrogenase(LDH)kit;apoptosis rate by flow cytometry;apoptosis by notched end labeling(TUNEL).Western blot(WB)was used to detect the expression levels of IL-1β and GSDMD proteins in each group.Results Compared with the Sham group,the H/R group showed abnormal cell status and increased cell death,decreased cell activity,increased LDH release,increased apoptosis rate and apopto-sis level,and increased expression levels of IL-1β and GSDMD proteins(P<0.05);compared with the H/R group,the AAV-miR-483-3p group showed improved cell status and less cell death,increased cell proliferation activity,increased LDH release,and increased IL-1β and GSDMD protein expression levels(P<0.05).Compared with the H/R group,the AAV-miR-483-3p group showed improved cell status and less cell death,increased cell proliferation activity,decreased LDH release,decreased apoptosis rate and apoptosis level,and decreased expression of IL-1β and GSDMD proteins(P<0.05).Conclusion Over-expression of miR-483-3p can improve H/R-inducedH9c2 cardiomyocyte injury by enhancing cell activity and cell metabolism,and inhibiting apoptosis and cell charring.

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.

Objective:Exploring the changes in the expression of transient receptor potential vanilloid 1 (TRPV1) in the peripheral and central nervous system in rats temporomandibular joint osteoarthritis (TMJOA) and its relationship with TMJOA pain .Methods:From February 2024 to April 2025, 48 healthy male Sprague Dawley rats were randomly divided into a control group and an experimental group, with 24 rats in each group. The modeling periods for both groups were 2, 4, and 6 weeks, with 8 rats per group at each time point. After bilateral injection of monosodium iodoacetate (MIA) into the temporomandibular joint (TMJ) cavity to establish a TMJOA model, the TMJ condyle, trigeminal ganglion (TG), trigeminal nucleus caudate (TNC), and hippocampal tissue were collected. Pain threshold detector von Frey silk was used to evaluate the head withdrawal threshold (HWT) of rats, and HE staining and micro-CT scanning were used to observe the histological changes of TMJ. Immunohistochemical staining was used to detect the expression of TRPV1 in TG and hippocampal tissues, as well as the expression of glial fibrillar acidic protein (GFAP) in TNC.Results:On the first day after modeling, the HWT of rats significantly decreased and then gradually increased. From day 7 to day 14, HWT decreased again, and after day 14, HWT gradually increased. Statistically significant differences were observed between the experimental group and the control group at each time point ( P<0.001). HE staining and micro-CT revealed that in the second week after modeling, the arrangement of condylar bone trabeculae was disordered, the trabeculae became thinner, the bone marrow cavity became larger, and then the trabeculae became thicker and the bone marrow cavity became smaller. The number of TRPV1 positive cells in TG of TMJOA rats reached its peak in the second week of modeling, and then gradually decreased in the fourth and sixth weeks ( P<0.001), with no statistically significant difference in the control group ( P=0.941). The number of GFAP positive cells in TNCs of TMJOA rats significantly increased, reaching its peak in the second week of modeling and gradually decreasing in the fourth and sixth weeks ( P<0.001). There was no statistically significant difference between the control group ( P=0.720). The number of TRPV1 positive cells in the hippocampus of TMJOA rats significantly increased. The number of TRPV1 positive cells reached its peak in the second week of modeling, and then gradually decreased in the fourth and sixth weeks ( P<0.001). There was no statistically significant difference between the control group ( P=0.776). Conclusions:In the MIA induced rat TMJOA model, the expression of TRPV1 in TG and hippocampal tissue, as well as the expression of GFAP in TNC, were upregulated, which may be involved in the occurrence and development of TMJOA pain and related to the development of TMJOA lesions.

Objective:To develop an early exercise rehabilitation nursing for elderly patients undergoing total hip arthroplasty (THA) based on the best evidence, and explore its clinical effects.Methods:This study was a randomized controlled trial. From August to December 2022, convenience sampling was used to select 126 elderly THA patients admitted to the Department of Orthopedics of the First Affiliated Hospital of Naval Medical University as participants. Patients were divided into observation group and control group using a random number table method, with 63 cases in each group. Control group was treated with a usual exercise rehabilitation nursing, while observation group was treated with an early exercise rehabilitation nursing for elderly THA patients based on the best evidence. Changhai Pain Rating Scale, Harris Hip Score, and Barthel Index were used to evaluate pain, hip function, and activities of daily living in two groups of patients. The first time off the bed, hospital stay, and incidence of complications were recorded and compared between the two groups.Results:The Harris Hip scores of observation group patients three days after surgery and on the day of discharge were (61.13±4.82) and (77.84±4.43), respectively, which were higher than those of control group (50.75±6.19) and (70.25±7.47), and the differences were statistically significant ( t=10.502, 6.937; both P<0.01). Barthel Index scores of observation group patients were higher than those of control group on the day of surgery, three days after surgery, and the day of discharge, and the differences were statistically significant ( t=3.531, 4.609, 10.112; all P<0.01). The incidence of postoperative complications in observation group was 11.11% (7/63), while in control group it was 42.86% (27/63), with a statistically significant difference (χ 2=16.113, P<0.01). There were no statistically significant differences in the resting pain score and exercise pain score between the two groups of patients on the day after surgery ( t=-1.693, -1.354; both P>0.05). The resting pain score and exercise pain score of observation group were lower than those of control group three days after surgery and on the day of discharge, and the differences were statistically significant (all P<0.05). Observation group had a shorter first time off the bed and hospital stay (1.34±0.37) and (5.48±0.66) days compared to control group (2.13±0.48) and (6.29±0.83) days, with statistically significant differences ( t=-10.346, -6.063; both P<0.01) . Conclusions:An evidence-based early exercise rehabilitation nursing for elderly THA patients can reduce the degree of pain, minimize the occurrence of complications, shorten the first time off the bed and hospital stay, and promote recovery of elderly patient.