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 To explore the correlation between central venous oxygen saturation(ScvO2)-re-lated indexes at different time points and the occurrence of low cardiac output syndrome(LCOS)after con-genital heart disease(CHD)correction surgery.Methods A total of 73 children who underwent CHD correc-tion surgery in this hospital from July 1st,2021 to July 1st,2024 were selected as the research subjects.The clinical data,preoperative conditions,and postoperative conditions of the children were collected.The ScvO2 and arterial lactate(Lac)levels of the children at different time points(the 1st,6th,12th,and 24th hours after surgery)were monitored,and the ScvO2/Lac at different time points and the change rate of ScvO2 in different time periods were calculated.The correlation between ScvO2-related indexes and LCOS after CHD correction surgery was analyzed.Results ScvO2 at the 6th hour after surgery,ScvO2 at the 12th hour after surgery,Sc-vO2/Lac at the 12th hour after surgery,the change rate of ScvO2 from the 1st to the 24th hour after surgery,the change rate of ScvO2 from the 6th to the 12th hour after surgery,and the change rate of ScvO2 from the 12th to the 24th hour after surgery were independent influencing factors of LCOS occurrence after CHD cor-rection surgery(P＜0.05).There was a negative correlation between ScvO2 at the 12th hour after surgery,ScvO2/Lac and LCOS occurrence after CHD correction surgery(r=-0.543,-0.523,P＜0.05).The area under the curve(AUC)of ScvO2 at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.938(95％CI:0.865-1.000);the AUC of ScvO2/Lac at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.922(95％CI:0.851-0.994).Conclusion ScvO2 and ScvO2/Lac at the 12th hour after surgery have good predictive potential for LCOS occurrence af-ter CHD correction surgery.

OBJECTIVE Optimizing the water extraction technology of Xiangqin jiere granules. METHODS The orthogonal test of 3 factors and 3 levels was designed， and comprehensive scoring was conducted for the above indexes by using G1-entropy weight to obtain the optimized water extraction technology of Xiangqin jiere granules with water addition ratio， extraction time and extraction times as factors， using the contents of forsythoside A， baicalin， phillyrin， oroxylin A-7-O-β-D-glycoside， wogonoside， baicalein and wogonin， and extraction rate as evaluation indexes. BP neural network modeling was used to optimize the network model and water extraction process using the results of 9 groups of orthogonal tests as test and training data， the water addition multiple， decocting time and extraction times as input nodes， and the comprehensive score as output nodes. Then the two analysis methods were compared by verification test to find the best water extraction process parameters. RESULTS The water extraction technology optimized by the orthogonal test was 8-fold water， extracting 3 times， extracting for 1 h each time. Comprehensive score was 96.84 （RSD＝0.90%）. The optimal water extraction technology obtained by BP neural network modeling included 12-fold water， extracting 4 times， extracting for 0.5 h each time. The comprehensive score was 92.72 （RSD＝0.77%）， which was slightly lower than that of the orthogonal test. CONCLUSIONS The water extraction technology of Xiangqin jiere granules is optimized successfully in the study， which includes adding 8-fold water， extracting 3 times， and extracting for 1 hour each time.

ObjectiveTo investigate the effect of Yunkang oral liquid on postpartum kidney deficiency in mice. MethodPostpartum mice were randomized into model and low-dose （6 mL·kg^-1）， medium-dose （9 mL·kg^-1）， and high-dose （12 mL·kg^-1） Yunkang oral liquid groups. The mouse model of postpartum kidney deficiency was established by sleep deprivation combined with forced swimming. Another 9 female ICR mice were selected as the normal control group. The mice were administrated with Yunkang oral liquid during the period of modeling. The levels of estradiol （E₂）， progesterone （P）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） in the serum were measured by the enzyme-linked immunosorbent assay. The morphological changes of ovaries and uterus were observed by hematoxylin-eosin （HE） staining， and the expression of transforming growth factor （TGF）-β and Smad2/3 was determined by immunohistochemistry and Western blotting. ResultThe mice in the model group showed prolonged estrous cycle， reduced voluntary activity， dorsal temperature， grip strength， and bone strength， and whitening tongue coating. Compared with the model group， Yunkang oral liquid shortened the estrous cycle， increased the voluntary activity， dorsal temperature， grip strength， and bone strength， and alleviated the whitening of tongue coating. Moreover， it elevated the E₂ and P levels and lowered the FSH and LH levels in the serum， decreased ovarian follicular atresia rate， promoted uterine repair， and down-regulated the expression of TGF-β and Smad2/3 in the ovarian and uterine tissues. ConclusionYunkang oral liquid can ameliorate postpartum kidney deficiency in mice by regulating the TGF-β/Smads signaling pathway.

Objective To investigate the relationship between systemic immune-inflammation index (SII)and lower extremity vascular disease in patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional study was conducted on 390 T2DM patients admitted in our department from January 2013 to January 2024.According to the diagnostic criteria for lower extremity vascular disease in T2DM patients,they were divided into a lower extremity vascular disease group (n=158)and a control group (n=232).General data and results of laboratory tests were compared between the 2 groups.Spearman correlation analysis was used to identify the related factors for lower extremity vascular diseases in T2DM patients.The correlation between SII and lower extremity vascular diseases in T2DM patients was analyzed using the Row Mean Scores and Cochran-Armitage Trend analysis.Multivariate logistic regression analysis was applied to identify the risk factors for lower limb vascular lesions in T2DM patients.Receiver operating characteristic (ROC)curve was plotted to evaluate the diagnostic efficacy of SII for lower extremity vascular disease in the patients.Results Compared with T2DMpatients without lower extremity vascular disease,those with lower extremity vascular disease were older,had higher levels of total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),SII,larger proportion of carotid vascular lesions,and increased proportion of no-taking statins.The lower extremity vascular disease in T2DM patients was positively correlated with SII/100 (r=0.429,P<0.001),age (r=0.517,P<0.001),TC (r=0.161,P=0.001),LDL-C (r=0.117,P=0.021),carotid artery lesions (r=0.101,P=0.047),no-taking statins (r=0.266,P<0.001).Logistic regression analysis showed that SII,age,LDL-C,and no-taking statins were the risk factors for lower extremity vascular lesions in T2DM patients (P<0.01).The area under the curve (AUC)value of SII combined with age,LDL-C,and no-taking statins in predicting lower extremity vascular disease in T2DM patients was 0.896.Conclusion SII is not only a risk factor,but also a simple marker for lower extremity vascular disease in T2DM patients,suggesting that inflammatory response plays an important role in the occurrence and development of lower extremity vascular disease in T2DM.

Objective:To understand the real experience and needs of early exercise rehabilitation in elderly patients with total hip arthroplasty (THA), so as to provide a preliminary basis for intervention research to meet the needs of patients.Methods:Using the purposive sampling method, a total of 12 elderly patients with THA from the First Affiliated Hospital of Naval Medical University from June to September 2021 were selected as the research objects for semi-structured in-depth interviews. Colaizzi 7-step method was used to analyze, summarize and extract the data.Results:The early exercise rehabilitation experience and needs of elderly THA patients could be summarized into four themes such as postoperative exercise being a difficult journey, the need for professional support, the need for external support and internally driven needs and 14 sub themes.Conclusions:There are various problems and needs for early exercise rehabilitation in elderly patients undergoing THA. It is necessary to strengthen communication among doctors, nurses and patients, understand their true feelings and provide personalized care and rehabilitation guidance to improve their treatment experience and enhance their satisfaction.

With the rapid development of information technology and the change in military education policy in the new era, online teaching has gradually become one of the main approaches to implement the clinical medical education in military teaching hospitals. In this study, the online teaching was performed mainly by pre-recorded teaching, supplemented by online live teaching. Massive open online courses (MOOCs) and the seminar-style teaching were advocated to be used in advanced disciplines. The quality of online teaching was guaranteed through infrastructure provision, teacher arrangement, teaching preparation, teaching interactivity, after-class test, teaching evaluation, supervision, and summary of teaching, which ultimately achieved a good effect. The results of the two-way questionnaires of 26 teachers and 129 students showed that 23.26% (30/129) of students and 65.38% (17/26) of teachers believed that students' learning ability was insufficient. 34.88% (45/129) of students and 23.08% (6/26) of teachers thought that the existing technology could not meet the requirements of online teaching. 55.04% (71/129) of students and 69.23% (18/26) of teachers held the view that the effect of online teaching was inferior to face-to-face teaching. 28.68% (37/129) of students and 57.69% (15/26) of faculty asked for the return of face-to-face education. Therefore, it is necessary to strengthen the construction of smart classroom platforms, establish a well-developed online teaching quality evaluation system, and integrate various innovative teaching modes with the online teaching. In these ways, it is expected to optimize the online teaching of clinical medicine and achieve the goal of online teaching.

Malaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of

Objective:To investigate the differences of gastric mucosa microbiota between children with chronic gastritis and duodenal ulcer under the condition of Helicobacter pylori (Hp) infection. Methods:This prospective cohort study involved 57 children with Hp infection diagnosed by gastric endoscopy who were admitted to the Children′s Hospital of Zhejiang University School of Medicine due to "abdominal pain, abdominal distension and vomiting" between January 2018 to August 2018. According to gastroscopy and pathological examination, the children were divided into chronic gastritis group and duodenal ulcer group. Gastric mucosa from Hp infected patients were sampled, and the flora DNA was analyzed by high-throughput sequencing. The statistical difference of α diversity, β diversity between two groups were analyzed. The relative abundance of the two groups in each taxonomic level was analyzed statistically. T test, Rank sum test or χ 2 test was used for comparison between the two groups. Results:A total of 57 children diagnosed with Hp infection were enrolled in this study, including 42 cases of chronic gastritis (the age was (9.3±2.8) years, 22 males and 20 females) and 15 cases of duodenal ulcer (the age was (11.1±3.3) years, 9 males and 6 females). Alpha diversity index Chao and ACE in Hp infected chronic gastritis group were significantly higher than those in Hp infected duodenal ulcer group (217±50 vs. 183±64, t=2.088, P=0.009;218±47 vs. 192±76, t=1.566, P=0.016, respectively). The Beta-diversity index such as nonmetric multidimensional scaling (NMDS) analysis were significantly different in the two groups (analysis of similarity R=0.304, P=0.028). Among the main bacteria genera, there were 6 genera with significant differences between the two groups, which were Prevotella (0.190% (0.008%-1.983%) vs. 0.021% (0.005%-2.398%), Z=-2.537, P=0.011), Alloprevotella (0.097% (0.010%-0.813%) vs. 0.015% (0.003%-0.576%), Z=-2.492, P=0.013), Haemophilus (0.109% (0.004%-0.985%) vs. 0.014% (0.004%-0.356%), Z=-2.900, P=0.004), Neisseria (0.074% (0.004%-0.999%) vs. 0.024% (0.003%-0.255%), Z=-2.718, P=0.007), Streptococcus (0.166% (0.008%-1.869%) vs. 0.045% (0.006%-0.879%), Z=-2.537, P=0.010), and an unclassified- Microbacteriaceae (0.214% (0.060%-1.762%) vs. 0.117% (0.010%-0.954%), Z=-2.120, P=0.034). Linear discriminant analysis (LDA) effect sized analysis showed that at the genus level, only Prevotella was significantly enriched in the duodenal ulcer group (LDA=2.90, P=0.010), while Streptococcus, Neisseria and Haemophilus were significantly enriched in the chronic gastritis group (LDA=2.83, 2.82, 2.69, P=0.011, 0.007, 0.004, respectively). Conclusions:The gastric mucosal microbiota in duodenal ulcer associated with Hp is significantly different from that in chronic gastritis. Hp may promote the occurrence of peptic ulcer together with gastric microbiota.

Objective:To observe the changes of peri-implant tissue around the individualized abutment that was grinded from zirconia provisional crown in one year.Methods:In this research, a prosthodontic-driven virtual implant planning and immediate provisionalization were conducted in computer assisted design software. And computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate the zirconia provisional crown and surgical guide template before surgery. The implant was accurately placed with the surgical guide, and the zirconia provisional crown was immediately delivered after surgery. Three months later, the implant osseointegration was completed, and zirconia provisional crown was prepared intraorally to generate customized zirconia abutment for final prosthesis. The study included 30 patients with single anterior tooth loss, including 18 males and 12 females, aged from 26 to 50 years old, and the mean age was (36.2±6.1) years old. The patients were from the Center of Oral Implantology, The First Affiliated Hospital of Zhejiang University Medical College from January 2017 to February 2018. After cementation of the final prosthesis, the cases were followed up at 6 and 12 months time intervals. Implant survival rate, probing depth, bleeding on probing, marginal bone level loss and papilla index score (PIS) were recorded in every appointment.Results:The survival rate of 30 implants was 100%, and the probing depths were less than 5 mm. The bone resorption at 6 and 12 months follow-up after the final delivery was 0 (0, 0) mm and 0 (-0.2, 0) mm, respectively, and the difference was not statistically significant ( P>0.05). The PIS was 3.0 (2.0, 4.0), 3.0 (2.8, 4.0) and 3.0 (3.0, 4.0) on the final delivery, 6 and 12 months after final delivery, respectively. Conclusions:Marginal bone level and bone loss were stable with this new implant clinical protocol at the one-year follow-up.