OBJECTIVE To investigate the efficacy and safety of omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia （MUMPP） in children. METHODS A retrospective study was conducted on children aged 1-18 years old with MUMPP who were hospitalized in the Department of Pediatrics， the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2025. According to the selection of secondary antibiotics after 72 h of initial treatment with macrolides， they were divided into the omadacycline group and the doxycycline group. Based on conventional treatment， children in the omadacycline group were given intravenous infusion of 2.4 mg/kg （once daily） of omadacycline tosylate， while children in the doxycycline group were given oral doxycycline hydrochloride tablets at 2 mg/kg （twice daily）. The efficacy and safety were compared between the two groups of pediatric patients. Univariate analysis and multivariate Logistic regression analysis were performed on clinical efficacy， and subgroup analysis along with multiple sensitivity analyses were conducted to verify the robustness of the conclusions. RESULTS A total of 284 children with MUMPP were included in this study， with 142 in the omadacycline group and 142 in the doxycycline group. In terms of efficacy， although the hospitalization time of children in the omadacycline group was longer than that in the doxycycline group （ P ＜0.05）， the lung lesion absorption rate and clinical efficacy were significantly higher or better than those in the doxycycline group （ P ＜0.05）. The results of multivariate Logistic regression analysis showed that medication （OR＝5.300， 95%CI： 2.526-11.123）， length of hospital stay （OR＝1.348， 95%CI： 1.167-1.556）， and medication duration （OR＝1.422， 95%CI： 1.169-1.729） were influencing factors of clinical efficacy （ P ＜0.05）. The subgroup analysis results showed that the clinical efficacy of omadacycline was significantly better than that of doxycycline in all subgroups （ P ＜0.05）. The results of multiple sensitivity analysis showed that the regression coefficients B of the four models （gradually adjust variables） before and after inverse probability of treatment weighting were significantly greater than 1 （ P ＜0.05）. In terms of safety， there was no statistically significant difference in the inci dence of adverse drug reactions between the two groups of patients （ χ 2 ＝0.447， P ＝0.504）. CONCLUSIONS In the case of hospitalization and prolonged medication， the efficacy of omadacycline in treating childhood MUMPP is superior to that of doxycycline， and its safety is good.

Objective: To construct a prediction model for sleep disorders in shift workers of a chemical fiber enterprise, so as to provide the basis for early identification and prevention of sleep disorders in shift workers. Methods: Shift workers were sampled from a chemical fiber enterprise in Tongxiang City, Zhejiang Province using a cluster sampling method from August 2022 to July 2024. Demographic information, length of service and average weekly working hours were collected through questionnaire surveys. Depressive symptoms, anxiety symptoms and sleep disorders were evaluated using the Pittsburgh Sleep Quality Index, Patient Health Questionnaire and Generalized Anxiety Disorder Questionnaire, respectively. The shift workers were randomly divided into a training set and a validation set at a ratio of 7∶3. Predictive factors were selected using a multivariable logistic regression model based on the training set, and a nomograph model for prediction of sleep disorders in shift workers was established. The predictive values of the model were evaluated using the receiver operating characteristic (ROC) curve and calibration curve based on the training set and validation set. Results: Totally 673 shift workers were included, with a median age of 32 (interquartile range, 12) years. There were 493 males, accounting for 73.25%. There were 471 (69.99%) workers in the training set and 202 (30.01%) workers in the validation set. There were 274 workers with sleep disorders, accounting for 40.71%. The equation for the prediction model was ln[p/(1-p)]=-8.391+1.906×average weekly working hours+1.822×depressive symptoms+1.667×anxiety symptoms. The area under the ROC curve was 0.769 (95%CI: 0.661-0.835) for the training set and 0.655 (95%CI: 0.593-0.737) for the validation set, and Hosmer-Lemeshow test showed a good fitting effect (both P>0.05). Conclusion The nomograph model constructed by average weekly working hours, depressive symptoms and anxiety symptoms can be used to predict the risk of sleep disorders in shift workers of a chemical fiber enterprise.

BACKGROUND:During healing process of chronic wounds,excessive production of reactive oxygen species can impair the function of L929 fibroblasts,thereby delaying wound repair.Therefore,protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE:To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma(CMC-OCS/PRP)hydrogel on L929 cells under H2O2 stimulation. METHODS:CMC-OCS/PRP hydrogels were prepared,and the micromorphology,degradation performance,scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized.L929 cells with good growth state were taken and cultured in five groups.The control group was cultured conventionally.H2O2 was added to the H2O2 group.Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract+H2O2 was added to the CMC-OCS group.Platelet-rich plasma gel extract+H2O2 was added to the PRP group.The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract+H2O2.Each group was treated with hydrogel extract for 6 hours,and then H2O2 for 24 hours.After culture,the levels of active oxygen and malondialdehyde,apoptosis and expression of collagen fiber I protein were detected.In the presence of H2O2,the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours,respectively.Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION:(1)CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability,could effectively remove H2O2 and hydroxyl radicals in vitro,and had good biocompatibility.(2)Compared with the control group,the apoptosis rate,reactive oxygen species,and malondialdehyde levels were increased(P<0.05);the spread area of cells was decreased(P<0.05),and the expression of collagen fiber I protein had no significant changes(P>0.05)in the H2O2 group.Compared with the H2O2 group,reactive oxygen species level was decreased in the CMC-OCS group(P<0.05),malondialdehyde level was decreased(P<0.05),and cell spread area was increased(P<0.05)in the PRP group,CMC-OCS group,and CMC-OCS/PRP group;apoptosis rate was decreased in the CMC-OCS/PRP group(P<0.05),and collagen fiber I protein expression was increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05).(3)Compared with the control group,the number of cell migration was decreased(P<0.05),and the migration area had no significant change(P>0.05)in the H2O2 group.Compared with the H2O2 group,the number and area of cell migration were increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05),and the increase was most significant in the CMC-OCS/PRP group.(4)Under oxidative stress,CMC-OCS/PRP hydrogel can improve the migration ability of fibroblasts,resist cell apoptosis,and preserve cell extension function.

Objective:To summarize the evidence for the application and management of continuous glucose monitoring, providing evidence-based support for the clinical application and management.Methods:BMJ Best Clinical Practice, UpToDate, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang and other databases, Yimaitong and and other guide networks, and diabetes related association websites were searched for the application and management of continuous glucose monitoring, the search time limit was from the establishment of the database to July 7, 2024. Researchers evaluated the quality of the included literature, extracted and summarized the evidence based on the topic.Results:A total of 13 articles were included, including 5 guidelines, 5 expert consensuses, 1 systematic review and 2 randomized controlled trials. The best evidences for the application and management of continuous glucose monitoring were summarized, including 3 themes and 13 aspects, practice norms (before, during, and after wearing), application norms, management norms (personnel, systems, information, materials, methods), with 31 pieces of evidence.Conclusions:This study summarized the evidences for the application management of continuous glucose monitoring, which could standardize the operation process of continuous glucose monitoring, provide response strategies for related nursing issues, and ensure that there were unified and clear management standards to follow.

Objective:To investigate the association between different types of lung nodules and the risk of lung cancer in a population at high risk of lung cancer and to provide an epidemiologic basis for the comprehensive management of lung nodules.Methods:Using the free lung cancer screening program of low-dose CT (LDCT) in Wenling, Zhejiang Province, we collected baseline and imaging information of high-risk groups for lung cancer who underwent LDCT screening from April 2019 to October 2021 and patients with previous history of lung cancer, tuberculosis, pneumoconiosis, and silicosis were excluded. A total of 28 539 study subjects were included in the analysis, and the follow-up ended on 31 December 2023. Based on the characteristics of the detected pulmonary nodules, the study subjects were classified with no nodules, with solid nodules, with pure ground glass nodules, and with part solid nodules groups. The association between different characteristics of lung nodules and the risk of lung cancer development was analyzed using the Cox proportional hazard regression model with a new diagnosis of lung cancer during the follow-up period as the outcome.Results:The overall detection rate of lung nodules with a mean diameter of ≥3 mm was 76.5%, of which 53.7%, 18.2%, and 4.6% were detected in the solid nodule, pure ground glass nodule, and partially solid nodule groups, respectively. There were statistically significant differences between the different nodule groups in terms of age, gender, BMI, history of toxic exposure education level, smoking status, history of lung disease, and family history of lung cancer (all P<0.05). The median follow-up time of the study population was 3.4 years, and 485 new lung cancer cases were diagnosed during the follow-up period. After adjusting for covariates, the results of multifactorial Cox proportional hazard regression model analysis showed that the risk of lung cancer was higher in pure ground glass nodules and part solid nodules compared with solid nodules, with HR values (95% CI) of 1.89 (1.52-2.35) and 6.49 (5.18-8.14), respectively. The results of subgroup analysis showed that patients in the group of part solid nodules had the highest risk of lung cancer in all strata of the population, followed by patients with pure ground glass nodules. Patients in the solid nodule group who were older or had previous lung disease had a higher risk of lung cancer, and the risk of lung cancer in the part solid nodule group differed between genders. Conclusions:The proportion of lung nodules detected is high in the high-risk group of lung cancer, and among them, patients with pure ground glass and part solid nodules have a higher risk of developing lung cancer. Attention should be paid to the annual follow-up management for patients with solid nodules who are older or who have had lung diseases, as well as for female patients with part solid nodules.

Objective:To develop and validate a predictive model for delayed emergence in patients undergoing thoracoscopic radical lung cancer surgery with general anesthesia.Methods:A total of 1 468 patients admitted to the anesthesia recovery room after thoracoscopic radical lung cancer surgery at the First Affiliated Hospital of Zhejiang University School of Medicine from August 2020 to August 2021 were selected via convenience sampling. Patients who underwent surgery between August 2020 and June 2021 ( n=1 213) were assigned to the modeling group, while those from July to August 2021 ( n=255) were used as the validation group. Logistic regression analysis was used to identify risk factors for delayed emergence and to establish a predictive model. The performance of the model was evaluated using the area under the receiver operating characteristic curve ( AUC) and the Hosmer-Lemeshow goodness-of-fit test. Results:Among the modeling group, 200 patients experienced delayed emergence, with an incidence of 16.49% (200/1 213). Logistic regression analysis revealed that the use of reversal agents, use of neostigmine, albumin level, presence of shivering, pain score≥4 points, extubation time, partial pressure of CO 2, partial pressure of oxygen, serum potassium level, and intraoperative fentanyl dosage were significant influencing factors ( P<0.05). The predictive model demonstrated good performance with an AUC of 0.864 [95% CI (0.828, 0.899) ], a Hosmer-Lemeshow test χ 2=5.299 ( P=0.725), cut-off value of 0.442, sensitivity of 0.794, and specificity of 0.769. In the validation group, delayed emergence occurred in 44 cases (17.25%). The model showed good validation performance with an AUC of 0.852 [95% CI (0.826, 0.878) ], Hosmer-Lemeshow χ 2=5.912 ( P=0.336), cut-off value of 0.754, sensitivity of 0.674, and specificity of 0.877. Conclusions:The predictive model constructed in this study demonstrates strong performance and can assist clinicians in the early identification of patients at risk of delayed emergence following thoracoscopic radical lung cancer surgery under general anesthesia.

OBJECTIVES: To investigate the molecular mechanism by which salvianolic acid B (Sal-B) modulates mitochondrial functional homeostasis and alleviates myocardial ischemia-reperfusion (I/R) injury in mice. METHODS: Mouse cardiomyocyte HL-1 cells were pretreated with 5 μmol/L Sal-B with or without sh-Sirt1 transfection before exposure to hypoxia-reoxygenation (HR), and the changes in ATP production, mitochondrial superoxide activity, substrate oxidation level were evaluated. In the animal experiment, 36 C57BL/6J mice were randomized into 3 groups (n=12) for sham operation or ligation of the left anterior coronary artery to induce myocardial I/R injury with or without intravenous injection of Sal-B+I/R (50 mg/kg). In the rescue experiment, 60 adult C57BL/6J mice were randomized into 5 groups (n=12): sham-operated group, myocardial I/R group, Sal-B+I/R group, I/R+Sal-B+Sirt1fl/fl group, and I/R+Sal-B+cKO-Sirt1 group. Myocardial injury was evaluated with HE staining, and cardiac function was assessed by measurement of the ejection fraction and fractional shortening using echocardiography. RESULTS: In HL-1 cells with HR injury, Sal-B pretreatment significantly increased cellular ATP production, reduced mitochondrial superoxide anion levels, and enhanced oxygen consumption level. In the mouse models of myocardial I/R injury, Sal-B pretreatment markedly ameliorated I/R-induced structural disarray of the cardiac myocytes and improved cardiac ejection. Cycloheximide chase with Western blotting and ubiquitination assays after Sirt1-IP showed that Sal-B significantly inhibited Sirt1 degradation in HL-1 cells. Sirt1 knock-down reversed Sal-B-induced increases in ATP production, reduction in superoxide, and elevation of OCR in HL-1 cells. Cardiomyocyte-specific Sirt1 knockout obviously reversed Sal-B-mediated improvement in cardiac ejection function and myocardial structure damage in mice with myocardial I/R injury. CONCLUSIONS Sal-B promotes mitochondrial functional homeostasis in cardiomyocytes with HR injury and improves cardiac function in mice after myocardial I/R by inhibiting Sirt1 protein degradation.
Animals ; Sirtuin 1/metabolism* ; Myocardial Reperfusion Injury/physiopathology* ; Mice, Inbred C57BL ; Mice ; Myocytes, Cardiac/drug effects* ; Benzofurans/pharmacology* ; Homeostasis/drug effects* ; Male ; Mitochondria/drug effects* ; Depsides

Due to the wide application of silver-containing dressings and silver-coated medical devices in clinical treatment; the extensive use of antibacterial agents and heavy metal agents in feed factories, Escherichia coli has formed the tolerance to silver ions. To systematically understand the known silver ion resistance mechanisms of E. coli, this article reviews the complex regulatory network and various physiological mechanisms of silver ion tolerance in E. coli, including the regulation of outer membrane porins, energy metabolism modulation, the role of efflux systems, motility regulation, and silver ion reduction. E. coli reduces the influx of silver ions by missing or mutating outer membrane porins such as OmpR, OmpC, and OmpF. It adapts to high concentrations of silver ions by altering the expression of ArcA/B and enhances the efflux capacity of silver ions under high-concentration silver stress via the endogenous Cus system and exogenous Sil system. Furthermore, the motility of bacteria is related to silver tolerance. E. coli has the ability to reduce silver ions, thereby alleviating the oxidative stress induced by silver ions. These findings provide a new perspective for understanding the formation and spread of bacterial tolerance and provide directions for the development of next-generation silver-based antimicrobials and therapies.
Escherichia coli/genetics* ; Silver/pharmacology* ; Drug Resistance, Bacterial ; Anti-Bacterial Agents/pharmacology* ; Porins/metabolism*

Aim To investigate whether disturbed flow affects endothelial cell function and atherosclerotic plaque formation by regulating histone demethylase KDM5B and epigenetic modification.Methods After partial carotid artery ligation(PCL),single-cell data analysis and immunofluorescence staining were used to investigate the changes of histone methylation level and histone demethylase expression in carotid endothelial cells of wild type mice under perturbed flow.qPCR and Western blot were used to detect the expression of KDM5B and H3K4me3 in endothelial cells exposed to dis-turbed flow.Transcriptome sequencing was used to analyze the effect of KDM5B knockdown on endothelial cell function.Endothelial cell ring formation assay was used to verify the effect of KDM5B on angiogenesis.PCL combined with high-fat diet for 2 weeks was used to establish a carotid artery plaque model to analyze the effect of KDM5B knockdown on plaque formation.Results There was a large amount of H3K4me3 methylation in vascular endothelial cells.Blood disturbed flow reduced the methylation of H3K4me3(P＜0.01)and promoted the expression of histone demethylases KDM5B in endothelial cells(P＜0.05).Compared with control group,inhibition of KDM5B activity or knockdown of KDM5B increased H3K4me3 level in endothelial cells(P＜0.05).Compared with Con313 control group,KDM5B knock-down reduced atherosclerotic plaque formation by 41.45％(Con313 control group:42.17％±1.90％,shKDM5B knock-down group:24.69％±1.60％,P＜0.01)by inhibiting angiogenesis.Conclusions Blood disturbed flow promotes KDM5B expression,reduces H3K4me3 modification,and promotes angiogenesis and atherosclerotic plaque formation.Targeting the KDM5B-H3K4me3 axis can be used as a candidate therapeutic target related to cardiovascular diseases.

Purpose To investigate the relationship between FN1 expression and clinical and pathologic features of laryngeal squamous cell carcinoma(LSCC)and the expression of tumor-associated macrophages(TAMs).Methods LSCC datasets GSE33232 and GSE84957 were analyzed and screened the differentially expressed gene FN1,and draw the receiver operating characteristic(ROC)curve.Bioinformatics analysis of FN1 expression,and prognosis in LSCC was performed.To investigate the effect of down-regulating FN1 expression in TU177 cells on the malignant bio-logical behavior of LSCC,we performed a scratch wound healing assay and a Transwell chamber assay to assess the effect of FN1 on cell proliferation,migration,and invasion in vitro.Immunohistochemical(IHC)staining was per-formed to detect the expression of FN1 and CD 163 in LSCC tissues.Results Analysis of the GSE33232 and GSE84957 datasets and online databases showed that FN1 was significantly overexpressed in LSCC tissues(P＜0.05),and patients with high FN1 expression had a significantly lower recurrence-free survival rate(HR=1.6,P=0.017).After transfection with si-FN1,the expression of FN1 in TU177 cells was significantly reduced(0.34±0.02 vs 1.00±0.03,P＜0.01).Compared with the control group,the down-regulation of FN1 expression inhibited the in vitro migra-tion(56.1±3.1 vs 19.23±1.0)and invasion(480±23 vs 288±20)ability of TU177 cells(both P＜0.01).Im-munohistochemistry findings showed that FN1 was highly expressed in both the tumor parenchyma(nest)and stromal cells of LSCC tissue,with a statistically significant difference[52.1％(24/46)vs 71.7％(33/46),P＜0.001].It was found that high expression of N-FN1 was associated with patients' pathological grade and lymph node metastasis(P＜0.05),while high expression of S-FN1 was associated with patients' age,lymph node metastasis,and TNM stage(P＜0.05).In addition,the co-expression of FN1 and CD163 was correlated with patients' pathological grad-ing,lymph node metastasis,and TNM stage(all P＜0.05).Conclusion FN1 and CD163 exhibit high expression levels in LSCC patients,which are closely associated with malignant progression,including invasion and metastasis.Notably,during LSCC progression,there may be a potential synergistic interaction between FN1 and CD 163-positive macrophages in the tumor microenvironment.