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 investigate the relationship between peripheral blood circular RNA Bardet-Biedl syndrome 9 (circBBS9) and circRNA catenin beta 1 (circCTNNB1) and weaning failure of mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A prospective, observational cohort study was conducted. The patients with AECOPD who received invasive mechanical ventilation and passed the spontaneous breathing test (SBT) admitted to the First Affiliated Hospital of Hebei North University from January 2022 to February 2024 were selected as the study subjects. According to the outcome of weaning, the patients were divided into failed weaning group and successful weaning group. At admission and before SBT, the expression levels of circBBS9 and circCTNNB1 in peripheral blood were detected by fluorescence quantitative polymerase chain reaction (PCR). General information, acute physiology and chronic health evaluation II (APACHEII) score within 24 hours of admission, vital signs before SBT and the most recent laboratory indicators before SBT of the patients were collected. The differences in circBBS9 and circCTNNB1 expression levels and clinical data between the two groups were compared. Multivariate Logistic regression was used to analyze the influencing factors of the weaning failure. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of each index on weaning failure. RESULTS: Ultimately, 132 patients with AECOPD who underwent invasive mechanical ventilation and passed the SBT were enrolled in the study. Among them, 82 patients were successfully weaned from mechanical ventilation, while 50 patients failed to be weaned, resulting in a weaning failure rate of 37.88%. There was no statistically significant difference in the expression levels of circBBS9 and circCTNNB1 in the peripheral blood at admission of patients between the two groups. The expression level of circBBS9 in the peripheral blood before SBT of patients in the failed weaning group was significantly higher than that in the successful weaning group (2^-ΔΔCt: 131.64±30.24 vs. 100.00±21.32), and the expression level of circCTNNB1 was significantly lower than that in the successful weaning group (2^-ΔΔCt: 79.90±16.82 vs. 100.00±26.43), and the differences were statistically significant (both P < 0.05). The APACHEII score within 24 hours of admission and the levels of RSBI, SCr, and PCT before SBT in the failed weaning group were significantly higher than those in the successful weaning group [APACHEII score: 22.54±4.62 vs. 16.56±4.58, RSBI: 81.90±16.56 vs. 63.25±17.00, SCr (μmol/L): 100.20±17.27 vs. 89.93±26.29, PCT (μg/L): 1.08±0.18 vs. 0.87±0.22], and the Alb level before SBT was significantly lower than that in the successful weaning group (g/L: 29.71±2.73 vs. 33.93±2.89), and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in other clinical data between the two groups. Multivariate Logistic regression analysis showed that circBBS9 [odds ratio (OR) = 1.291, 95% confidence interval (95%CI) was 1.049-1.588] and APACHEII score (OR = 2.897, 95%CI was 1.004-8.353), RSBI (OR = 1.413, 95%CI was 1.057-1.890) were independent risk factors for weaning failure (all P < 0.05), and circCTNNB1 (OR = 0.812, 95%CI was 0.688-0.959) and Alb (OR = 0.149, 95%CI was 0.036-0.614) were protective factors (both P < 0.05). ROC curve analysis showed that circBBS9, circCTNNB1, APACHEII score, RSBI, and Alb all had certain value for predicting weaning failure. The area under the ROC curve (AUC) and 95%CI were 0.820 (0.750-0.890), 0.755 (0.674-0.835), 0.827 (0.757-0.897), 0.795 (0.715-0.876), and 0.854 (0.791-0.919), respectively. Using the multivariate Logistic regression equation as the combined indicator, the AUC for predicting weaning failure reached 0.997 (95%CI was 0.993-1.000), which was significantly higher than that of the single indicators including circBBS9, circCTNNB1, APACHEII score, RSBI, and Alb (the Z value was 5.582, 6.093, 5.771, 5.932, and 5.182, respectively, all P < 0.05). CONCLUSIONS High expression of circBBS9 and low expression of circCTNNB1 in the peripheral blood of AECOPD patients receiving invasive mechanical ventilation before SBT are associated with weaning failure. circBBS9, circCTNNB1 combined with APACHEII score, RSBI and Alb are helpful for predicting the failure of weaning in these patients.
Humans ; Pulmonary Disease, Chronic Obstructive/blood* ; Prospective Studies ; Ventilator Weaning ; RNA, Circular/blood* ; Respiration, Artificial ; Male ; Female ; Aged

Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Bacterial resistance and excessive inflammation are common issues that hinder wound healing.Antimicrobial peptides(AMPs)offer a promising and versatile antibacterial option compared to traditional antibiotics,with additional anti-inflammatory properties.However,the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation.TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs.Therefore,in this study,a composite hydrogel(HAMA/t-GL13K)was prepared via the photocross-linking method,in which tFNAs carry GL13K.The hydrogel was injectable,biocompatible,and could be instantly photocured.It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS.Thereby,the hydrogel inhibited bacterial infection,shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring.The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.

Objective:To explore the correlation between serum nitric oxide synthase (NOS) levels and readmission due to acute exacerbation within 30 days in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A prospective cohort study was conducted. The AECOPD patients admitted to the First Affiliated Hospital of Hebei North University from January 2020 to December 2022 were enrolled as the research subjects. The general data such as gender, age, body mass index (BMI), chronic obstructive pulmonary disease (COPD) course, smoking history, and basic diseases were collected. The laboratory indicators, serum NOS level [inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS)] and acute physiology and chronic health evaluationⅡ (APACHEⅡ) score within 24 hours after admission and total length of hospital stay were also collected, and whether patients were readmitted due to acute exacerbation within 30 days after discharge were recorded. The differences in the above clinical indexes between the readmitted and non-readmitted patients within 30 days were compared. Multivariate Logistic regression analysis was used to screen the influencing factors of readmission within 30 days after discharge in AECOPD patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of various influencing factors on readmission.Results:A total of 168 patients were enrolled, 38 patients were readmitted due to acute aggravation within 30 days after discharge, and 130 were not readmitted. Compared with the non-readmission group, the levels of white blood cell count (WBC), C-reactive protein (CRP), APACHEⅡ score, and serum iNOS and eNOS levels within 24 hours after admission in the readmission group were significantly increased [WBC (×10 9/L): 14.19 (12.88, 16.12) vs. 11.81 (10.63, 14.11), CRP (mg/L): 51.41±12.35 vs. 40.12±7.79, APACHEⅡ score: 22.0 (19.0, 25.0) vs. 18.0 (14.0,20.5), iNOS (μg/L): 5.87±1.36 vs. 4.52±0.89, eNOS (μg/L): 4.40±1.00 vs. 3.51±1.08, all P < 0.01], and the levels of hemoglobin (Hb) and albumin (Alb) were significantly decreased [Hb (g/L): 108.82±22.06 vs. 123.98±24.26, Alb (g/L): 30.28±3.27 vs. 33.68±2.76, both P < 0.01]. There were no significant differences in gender, age, BMI, COPD course, smoking history, basic diseases, total length of hospital stay and serum nNOS level between the two groups. Multivariate Logistic regression analysis showed that CRP [odds ratio ( OR) = 1.201, 95% confidence interval (95% CI) was 1.075-1.341], APACHEⅡ score ( OR = 1.335, 95% CI was 1.120-1.590), and serum iNOS ( OR = 5.496, 95% CI was 2.143-14.095) and eNOS ( OR = 3.366, 95% CI was 1.272-8.090) were the independent risk factors for readmission within 30 days after discharge in AECOPD patients (all P < 0.05), and Hb ( OR = 0.965, 95% CI was 0.933-0.997) and Alb ( OR = 0.551, 95% CI was 0.380-0.799) were protective factors (both P < 0.05). ROC curve analysis showed that serum iNOS and eNOS levels had predictive value for readmission within 30 days after discharge in AECOPD patients, and the area under the ROC curve (AUC) was 0.791 (95% CI was 0.694-0.887) and 0.742 (95% CI was 0.660-0.823), respectively. When the optimal cut-off value was 5.22 μg/L and 3.82 μg/L, the sensitivity was 81.54% and 69.23%, and the specificity was 71.05% and 81.58%, respectively. The AUC of serum iNOS and eNOS levels combined with Hb, Alb, CRP and APACHEⅡ score for predicting the readmission was 0.979 (95% CI was 0.958-1.000), the sensitivity was 91.54%, and the specificity was 97.37%. Conclusions:The increased serum iNOS and eNOS levels of AECOPD patients correlate with the readmission due to acute exacerbation within 30 days after discharge. Combined detection of Hb, Alb, CRP, serum iNOS and eNOS levels, and evaluation of APACHEⅡ score within 24 hours after admission can effectively predict readmission.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

The methylation of N6-methyladenosine(m6A)is an important gene expression regulation mechanism in eukaryotes.It is mainly regulated by three types of regulators:writers,erasers and readers.With the development of high-throughput sequencing technology and bioinformatics,various methods have been developed to detect and analyze m6A methylation sites.A growing body of research has shown that m6A methylation plays an important role in the occurrence and development of urological tumors,including tumor proliferation,invasion and metastasis.However,the molecular mechanism and role of m6A in different types of urological tumors have not been fully elucidated.This article reviews the main regulatory mechanism of m6A methylation modification as well as the research progress,the prognostic value and the therapeutic resistance of m6A methylation modification in urological tumors.

Objective　To analyze the composition, population density, seasonal trends, and insecticide resistance monitoring results of vector mosquitoes in Liaocheng City from 2020 to 2022, providing a reference basis for further mosquito control measures. Methods　According to the "Implementation Plan for National Vector Biomonitoring", adult mosquito monitoring was carried out using mosquito traps and double-layer stacked nets at two national level monitoring points in Dong’e and Chiping. The Bretu Index method was used for monitoring throughout the city, and the immersion method was used for monitoring mosquito insecticide resistance. The monitoring period for adult mosquitoes was from March to November, and for juvenile mosquitoes was from May to October. Results　From 2020 to 2022, a total of 816 mosquito traps were deployed, capturing 4 717 adult mosquitoes with an average density of 5.78 mosquitoes per trap-night. Among them, 4 232 were Culex pipiens pallens, accounting for 89.72% of the total mosquito population, followed by 15 were Anopheles sinensis, accounting for 0.32%; 10 Aedes albopictus, accounting for 0.21%; 460 other mosquito species, accounting for 9.75%. Mosquito density was higher in rural areas compared to urban areas, with the highest density found in livestock sheds, followed by parks, hospitals, farms, and residential areas. Adult mosquito was first observed in May, with the peak activity occurring from June to August. The double-layer net method captures only Aedes albopictus, with an average net trapping index of 2.99 mosquitoes/(net·h), and their activity was concentrated from June to September. The average Brayton Index (BI) from May to October was 15.95, with a peak occurring in July and gradually decreasing after August. Insecticide resistance monitoring found that Culex pipiens pallens in Liaocheng City exhibited low resistance to permethrin, deltamethrin, dithion, and beta cypermethrin, with beta cypermethrin having the highest resistance. Conclusion　The dominant mosquito species in Liaocheng City is Culex pipiens pallens, followed by Aedes albopictus. The peak activity of adult and juvenile mosquitoes is concentrated between July and September, showing a distinct seasonal trend of growth and decline, posing a risk of dengue fever outbreaks. Culex pipiens pallens exhibits resistance to some insecticides, and timely measures should be taken to prevent the outbreak of mosquito-borne infectious diseases.

Objective:The incidence of prostate cancer is increasing every year,and precision diagnosis and treatment can help reduce unnecessary prostate punctures for prostate cancer patients in the gray area.This study aims to investigate the diagnostic value of 18F-prostate specific membrane antigen(PSMA)imaging combined with prostate specific antigen(PSA)-derived indicators for gray zone prostate cancer. Methods:A total of 107 patients who underwent 18F-PSMA PET/CT imaging for suspicious prostate cancer with tPSA of 4 to 10 μg/L(PSA gray zone)in a hospital were retrospectively included,and were divided into a prostate cancer group and a non-prostate cancer group based on pathological findings.Patients underwent PSA testing,18F-PSMA,and abdominal ultrasound,and age,tPSA,fPSA,f/tPSA,prostate volume,PSA density(PSAD),maximum standardized uptake value(SUVmax),and molecular imaging prostate specific membrane antigen(miPSMA)score were compared between the 2 groups.Multivariate logistic regression was used to analyze the influencing factors the diagnosis of gray zone prostate cancer.Receiver operating characteristic(ROC)curves were constructed to evaluate the efficacy of PSAD and SUVmax alone and in combination in diagnosing gray zone prostate cancer. Results:The volume of the prostate cancer group[42.00(34.00,58.00)cm3 vs 49.00(41.27,60.41)cm3]was smaller than that of the non-prostate cancer group(Z=-2.376,P=0.017),and the PSAD[(0.18±0.06)μg/(L·cm3)vs 0.15±0.05 μg/(L·cm3)]and SUVmax[18.63(8.03,28.57)vs 9.33(5.90,13.52)]were higher than those in the non-prostate cancer group(both P<0.05).The percentage of miPSMA score≥2 in the prostate cancer group was higher than that in the non-prostate cancer group(χ2=40.987,P<0.001).PSAD(OR= 22.154,95%CI 1.430 to 873.751,P=0.042)and SUVmax(OR=1.301,95%CI 1.034 to 1.678,P=0.009)were independent influential factors for the diagnosis of prostate cancer in the gray zone.The optimal cut-off values of PSAD and SUVmax were 0.22 μg/(L·cm3)and 8.02,respectively,and the AUCs for the diagnosis of prostate cancer in the gray zone alone and in combination were 0.628(95%CI 0.530 to 0.720,P<0.05)and 0.806(95%CI 0.718 to 0.876,P<0.05),0.847(95%CI 0.765 to 0.910,P<0.05),with sensitivities of 41.03%,76.92%,and 74.36%and specificities of 79.41%,89.71%,and 92.65%,respectively. Conclusion:PSAD and SUVmax are increased in patients with gray zone prostate cancer,and the combination of PSAD and SUVmax is of high value in diagnosing gray zone prostate cancer.