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 feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals. Methods: We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets. Results: The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%. Conclusion Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.

Objective:To investigate the impact of small extracellular vesicles(sEVs) derived from perirenal adipose cells on the biological behavior of renal tubular epithelial cells under diabetic conditions and the underlying molecular mechanisms.Methods:Primary perirenal adipose cells were extracted from db/m and db/db mice for in vitro culture. The culture supernatant was collected and sEVs(NDM-sEVs PRAT-Adipo, DM-sEVs PRAT-Adipo) were extracted by ultracentrifugation. The sEVs were incubated with human renal tubular epithelial cell line(HK-2) to observe changes in their proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition(EMT) levels. The protein composition of sEVs was analyzed using mass spectrometry to explore the molecular mechanisms. Results:CCK8 results showed that the proliferation level of HK-2 cells after DM-sEVs PRAT-Adipo intervention did not change significantly compared with the two control groups(Ctrl group and NDM-sEVs PRAT-Adipo intervention group). Western Blot(WB) results indicated that there were no significant changes in apoptosis levels(Bcl-2, Cleaved-caspase 3, Caspase 3) and autophagy levels(p62, LC3BⅠ, LC3BⅡ) in the DM-sEVs PRAT-Adipo intervention group compared with the two control groups. WB and immunofluorescence results demonstrated that DM-sEVs PRAT-Adipo intervention upregulated the expression levels of mesenchymal cell marker proteins(Vimentin, α-SMA, Snail2) and downregulated the expression level of epithelial cell marker protein ZO-1 in HK-2 cells compared with the two control groups. Mass spectrometry analysis of sEVs revealed that the differential proteins between DM-sEVs PRAT-Adipo and NDM-sEVs PRAT-Adipo were enriched in EMT-related pathways. Among them, the enrichment of thrombospondin(THBS1) in DM-sEVs PRAT-Adipo might be involved in the regulation of EMT in HK-2 cells. Conclusion:Under diabetic conditions, sEVs secreted by PRAT-derived adipocytes promote the upregulation of EMT in renal tubular epithelial cells, a process that may be mediated by the enrichment of THBS1 in sEVs.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Objective:To test the reliability and validity of a multi-dimensional, quantitative video evaluation system (the Multi-dimensional system) for evaluating hand dysfunction among stroke survivors so as to provide an objective basis for its clinical application.Methods:Sixty stroke survivors with single dysfunctional hand were evaluated using the Multi-dimensional system and also using the Fugl-Meyer Upper Extremity Assessment (FMA-UE) and the Action Research Arm Test (ARAT) and in terms of their active range of hand motion (AROM-H). The Multi-dimensional system′s internal consistency, composite reliability, split-half reliability, parallel-forms reliability as well as intra- and inter-observer reliability were quantified. Its validity was tested in terms of content validity, structural validity, convergent validity and criterion validity.Results:The system′s Cronbach′s α was determined to be 0.86. Its one-dimension composite reliability was 0.939, its split-half reliability coefficient was 0.88 and its parallel-forms reliability was 0.922. The inter-evaluator reliability was between 0.965 and 0.998 [95%CI= (0.919, 0.999)], and the single evaluator ICC value was 0.973 to 0.998 [95%CI= (0.937, 0.999)]. The validity test produced a content validity index of 1, and the Pearson correlation coefficients between each sub-item and the total score were all greater than 0.60. The KMO value for structural validity was 0.882, and there was a common factor in the component matrix which reflected 60.9% of the information in the original variables. The system′s convergent validity AVE was 0.609 with Pearson correlation coefficients between the multidimensional system and the FMA-UE and ARAT both > 0.70.Conclusion:The multi-dimensional quantitative video evaluation system has good reliability and validity in the evaluation of stroke survivors with hand dysfunction.

OBJECTIVE:To establish a method for the determination of related substances in Cabazitaxel injection. METHODS:HPLC method was used. The determination was performed on Agilent Eclipse XDB-C18column with mobile phase consisted of water-acetonitrile-ethanol(gradient elution)at the flow rate of 1.0 mL/min. The column temperature was 35 ℃,and the detection wavelength was set at 230 nm. The sample size was 20 μ L. Established method was used to determine related substances in 3 batches of Cabazitaxel injection. RESULTS:The linear relationship of cabazitaxel were 0.039-11.60 μ g/mL(r=0.999 8,n=7). The detection limit was 2×10-4μg,and quantitation limit was 8×10-4μg. RSD of precision and reproducibility tests were all lower than 10.0%(n=6). The amount of single impurity in 3 batches of samples ranged 0.07%-0.08%,and total amount of impurities were 0.26%-0.29%. CONCLUSIONS:Established method is simple,accurate and reliable,can be used for the determination of related substances in Cabazitaxel injection.

Objective To observe the effects of free-posture parturition on the parturition outcomes and pelvic floor function of puerperae. Methods Totally 270 pregnant women who met the requirements were divided into an observation group (n=135) and a control group (n=135) by the prospective randomized controlled clinic trail. Pregnant women in the observation group adopted free-posture parturition, while pregnant women in the control group delivered in the frequently used supine position. The pregnant women in both groups were managed according to the existing labor standards, and the effects of free-posture parturition on their parturition outcomes and pelvic floor function were observed. Results Totally 133 pregnant women in the observation group delivered naturally and 2 transferred to cesarean parturition in the process, while 102 pregnant women in the control group delivered naturally and 33 transferred to cesarean parturition in the process (χ2=31.55, P<0.001). The uniparae in the observation group spent less time in the first and second stages of labor as well as the whole parturition than the uniparea in the control group (P<0.001). There was no statistically significant difference in the duration of labor stage between the multiparae in the two groups (P> 0.05). The uniparae in the observation group were less likely to show reduced typeⅠand typeⅡ muscle fiber strength than the uniparae in the control group (P<0.05), while there was no statistically significant difference in the incidence of reduced typeⅠand type Ⅱ muscle fiber strength between the multiparae in the two groups (P>0.05). There was no statistically significant difference in the incidence of urinary incontinence between the puerparae in the two groups (P>0.05). Conclusions The use of free-posture parturition can reduce the possibility of cesarean parturition substantially. The duration of labor stage in uniparae can be shortened significantly, and their pelvic floor muscle strength is better than that of the puerparea in the control group. Free-posture parturition does not contribute to negative outcomes of maternals and fetals.

Objective To investigate the effects of AGEs-RAGE on the apoptosis of GLUTag cells and explore the possiblc mechanism.Methods GLUTag cells treated with 0、100、200、300μg/ml of AGEs for 24h were examined for gene and protein expression of RAGE using RT-PCR and western blotting,respectively.GLUTag cells were randomly divided into four groups:control,200μg/ml AGEs,AGEs+siRNA-RAGE and AGEs+apocynin.The protein expression of p22phox、p47phox 、Bcl-2、Bax in the cells were detected with western blotting.The reactive oxygen species (ROS) levels were examined using 2'7'-dichlorodihydroflur-rescein diacetate (DCFH-DA) and the apoptosis of L cells were tested by AnnexinV-FITC/PI.Results AGEs increased thc cxpression of RAGE in a dose dependent manner.Treatment with AGEs induced a significant increase in the expression of p22phox,p47phoxand the activity of ROS,caused up-regulation of Bax and down-regulation of Bcl-2,which enhanced the apoptosis of GLUTag cells.Apocynin,the inhibitor of NADPH oxidase,prevented those responses and the effects caused by AGEs were abolished by inhibition of RAGE activity with siRNA.Conclusion AGEs positively regulate the exprcssion of NADPH oxidase-derived ROS and its down-steam signaling pathway p53/Bax by targeting RAGE,leading to the apoptosis of GLUTag cells.

Objective To observe the changes in levels of plasma leukocyte cell-derived chemnotaxin 2 (LECT2) in patients with newly diagnosed type 2 diabetes (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD),and to investigate the clinical significance.Methods A total of 137 subjects were enrolled in the study,including 50 patients with newly diagnosed T2DM complicated with NAFLD,47 patients with newly diagnosed T2DM with non-NAFLD and 40 healthy subjects.The level of plasma LECT2 was determined by ELISA.Anthropometric data and other biochemical indicators were measured in three groups.The body mass index (BMI) and waist-to-hip ratio (WHR) were calculated.Insulin resistance and pancreas β-cell function were determined by homeostasis model assessment (HOMA-IR,HOMA-％β).Results Plasma concentration of LECT2 in patients with newly diagnosed T2DM complicated with non-NAFLD was higher than that in type 2 diabetic patients with non-NAFLD [(32.95 ± 10.11 vs 29.08 ± 7.54) ng/mL,P ＜ 0.01].Plasma LECT2 levels in both groups were significantly higher than that in normal control group [(22.38 ± 4.40) ng/mL,P ＜ 0.01].Plasma LECT2 level was positively correlated with BMI,FPG,FINS,C peptide,HbA1c,GGT,TG and HOMA-IR,while negatively with HDL-C and HOMA-％ β (all P ＜ 0.01).Multivariate regression analysis showed that levels of BMI,FPG and HDL-C were important factors affecting plasma LECT2 level.Conclusions Plasma LECT2 concentration significantly elevates in patients with newly diagnosed T2DM complicated with non-NAFLD.Plasma level of LECT2 is closely correlated with insulin resistance and glycolipid metabolism.LECT2 may play an important role in the patho genesis of insulin resistance and T2DM.

Objective To investigate the improvement of postpartum pelvic floor by rehabilitation training assessed with three-dimensional transperineal ultrasound . Methods One hundred cases of healthy postpartum women were randomly divided into two groups :control group and training group .The control group received the customary education ,and the training group received pelvic floor rehabilitation training . At 6 and 12 weeks postpartum ,levator hiatus area ,thickness of the levator ani muscle ,bladder neck mobility ,and bladder posterior horn were measured with three-dimensional transperineal ultrasound in all the subjects . Meanwhile ,the muscle strength situations were tested . Results At 12 weeks postpartum ,the anal levator hiatal area ,bladder neck mobility and bladder posterior horn in the training group were lower than those of the control group[ ( 21 .6 ± 3 .2) cm 2 vs ( 25 .6 ± 2 .4 ) cm 2 ,( 27 .9 ± 5 .3) mm vs ( 31 .5 ± 5 .9) mm ,( 126 .3 ± 21 .2)° vs (135 .3 ± 11 .6)°] ( P < 0 .05) . Compared with control group ,the thickness of the levator ani muscle increased in training group [ ( 13 .6 ± 2 .3) mm vs ( 15 .3 ± 2 .5) mm ] ( P < 0 .05) . The incidence of stress urinary incontinence in the training group ( 5% ) was significantly lower than the control group ( 12 .5% ) at 12 weeks postpartum ( χ2 = 5 .487 , P = 0 .025) . The muscle strength had no significant difference at 6 weeks postpartum . At 12 weeks postpartum ,the pass rate of class Ⅰ muscle fiber was 78 .5% ,and that of class Ⅱ muscle fiber was 83 .3% in the training group ;the pass rate of class Ⅰ muscle fiber was 28 .5% ,and class Ⅱ muscle fiber was 37 .3% in the control group , the improvement was significant at 12 weeks postpartum . Conclusions The result of the transperineal real-time ultrasonographic evaluation of post-natal pelvic floor rehabilitation training has high consistency with the measurement of muscle strength . The ultrasound examination is simple and accurate ,and has highly applicable value in evaluating the effect of post-pelvic rehabilitation training .