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.

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*

Objective:To understand trends and hotspots of TCM research papers published in journals with high IF basing on a bibliometric analysis.Methods:TCM research papers published between January 1, 2014 and December 31, 2024 from 80 journals with IF higher than 16.0 were retrieved from medical, life sciences and comprehensive journals in Journal Citation Reports of 2024. CiteSpace 6.3.R1 and Excel 2021 were used to analyze and visualize annual publication volume, research fields, features of clinical study, institutes, funds and keywords.Results:A total of 51 papers were included, showing an increasing trend in annual publication volume; the main research areas were pharmacology, acupuncture&moxibustion and internal medicine. Multi-center randomized controlled trials were the main clinical studies; China Academy of Chinese Medical Sciences was the leading institute in terms of publication volume; 84 funds were involved, including National Natural Science Foundation of China. Keywords that appeared most frequently were TCM, efficacy, double blind, electroacupuncture, stimulation and management.Conclusion:The number and quality of TCM research papers are improved simultaneously; future research needs to deepen international cooperation, and pay attention to the integration of TCM diagnosis and treatment characteristics and modern scientific research methods.

PI3K/AKT/mTOR signaling pathway plays a crucial role in cell proliferation, survival, differentiation, motility and intracellular transport. PI3Kδ, an isoform of PI3K, is highly expressed in B lymphocytes and is involved in the malignant progression of B-cell lymphoma. Thus, PI3Kδ has emerged as an attractive target for the development of anti-B-cell lymphoma drugs. Currently, there are several PI3Kδ inhibitors approved by the FDA for the treatment of B-cell lymphoma, each with its own characteristics, but also with varying degrees of adverse effects in clinical practice. Due to the complexity and diversity of the pathogenesis of B-cell lymphoma, single-target PI3Kδ inhibitors often have limited efficacy and are prone to drug resistance, and need to be combined with chemotherapy or other targeted drugs to enhance their efficacy. The future trend is to design novel inhibitors with higher efficacy and lower toxicity or to develop novel combination regimens with other chemotherapy, radiotherapy, and target drugs to acquire better anti-tumor effects with reduced adverse effects. This review summarizes the PI3Kδ inhibitors that have been approved for the treatment of B-cell lymphoma or are still in clinical trials, mainly focusing on their characteristics, adverse effects and combination regimens.

[摘 要] 目的：探究SOX9通过上调长链非编码RNA LINC01503的表达对喉鳞状细胞癌（LSCC）细胞的增殖、迁移、侵袭及肿瘤干细胞干性的影响。方法： 常规培养人LSCC细胞AMC-HN-8、TU177、TU212和TU686，用转染试剂将敲减序列及其对照核酸（si-SOX9-NC、si-SOX9#1、 si-SOX9#2、si-LINC01503-NC、si-LINC01503#1、si-LINC01503#2）或过表达质粒及其对照核酸（pcDNA3.1-SOX-NC、pcDNA3.1-SOX-oe、pcDNA3.1-LIN01503-NC和pcDNA3.1-LIN01503-oe）分别转染至TU177细胞或TU686细胞，记为si-SOX9-NC组、si-SOX9#1组、si-SOX9#2组、si-LINC01503-NC组、si-LINC01503#1组、si-LINC01503#2组；pcDNA3.1-SOX9-NC组、pcDNA3.1-SOX9-oe组、pcDNA3.1-LINC01503-NC组、pcDNA3.1-LINC01503-oe组、si-SOX9-NC + pcDNA3.1-LINC01503-NC组和si-SOX9 + pcDNA3.1-LINC01503-oe组。qPCR法检测SOX9 mRNA和LINC01503 在各组细胞中的表达，生物信息学分析SOX9与LINC0503启动子区的结合位点，双萤光素酶报告基因实验和染色质免疫共沉淀实验验证SOX9与LINC01503启动子区是否直接结合，WB法检测SOX9的敲减效率及LINC01503对TU177和TU686细胞干性标志物表达的影响，MTS法检测各组细胞的增殖活力，划痕愈合和Transwell小室实验检测各组细胞的迁移能力，克隆形成实验检测各组细胞的克隆形成能力。结果：SOX9在各种LSCC细胞中呈高表达（均P < 0.05），数据库数据分析显示，在头颈部鳞状细胞癌中，SOX9与LINC01503表达呈正相关（R = 0.12，P = 0.005 9）；SOX9可与LINC01503启动子区直接结合并促进其转录表达（均P < 0.05）；敲减LINC01503可明显抑制TU177细胞的增殖、迁移、侵袭（均P < 0.05），过表达LINC01503明显促进TU686细胞增殖、迁移、侵袭的能力（均P < 0.05），提高TU686细胞克隆形成能力和细胞干性标志物分子CD133、OCT4、SOX2的mRNA和蛋白水平表达（均P < 0.05），敲减LINC01503则均可抑制TU686细胞的克隆形成和细胞干性标志物的表达（均P < 0.05）；敲减SOX9均可明显抑制TU177细胞的增殖、迁移和侵袭能力，降低其干性细胞标志物的表达（均P < 0.05），同时过表达LINC01503则可部分逆转敲减SOX9对TU177细胞恶性生物学行为和干性标志物表达的抑制作用（均P < 0.05）。结论：SOX9和LINC01503在LSCC细胞中呈高表达，SOX9可能通过上调LINC01503表达提高LSCC细胞增殖、转移和侵袭能力和肿瘤干细胞干性。

Objective To evaluate the effect of modified vertical tooth preparation with full zirconium crown resto-ration in molar area.Methods A randomized study was conducted in 84 patients with all-ceramic crown restoration of posterior teeth.90 full crown restorations were collected and randomly divided into two groups:45 teeth in exper-imental group were treated with modified vertical tooth preparation,while 45 teeth in control group were treated with conventional horizontal tooth preparation with full zirconium crown restoration.When patients wore teeth,the resto-ration effects of the two groups were evaluated respectively,and then the marginal and internal fitness of the two groups were measured by silicone rubber replication method;gingival index(GI)and sulcus bleeding index(SBI)scores were recorded 6 months after wearing teeth.Results The results of chair-side evaluation of the two groups showed that the marginal fitness of the experimental group was better than that of the control group,and the differ-ence was statistically significant(P=0.036);the measured value of marginal fitness of prostheses in experimental group was better than that in control group,and the difference was statistically significant(P＜0.001);after 6 months,there was no mechanical complication between the two groups,and there was no significant difference in GI and SBI scores of periodontal soft tissue indexes.Conclusion Modified vertical tooth preparation abutment can significantly improve the marginal fitness of all-ceramic crown,which will not change the health status of peri-crown gingiva.

ObjectiveTo prepare oral nanoemulsions encapsulating essential oil from Alpinia zerumbet fructus（EOFAZ） and to investigate its pro-absorption effect in vitro and distribution in vivo. MethodThe proteoglycan conjugate polysaccharides of vinegar-processed Bupleuri Radix-bovine serum albumin（VBCP-BSA） was prepared by Maillard reaction of VBCP and BSA. Taking VBCP-BSA as emulsifier， vitamin B₁₂（VB₁₂） as absorption enhancer， and medium chain triglycerides mixed with EOFAZ as oil phase， the nanoemulsions loaded with EOFAZ was prepared by high energy emulsification method. The particle size， particle size distribution， surface Zeta potential， EOFAZ content and appearance and morphology of the nanoemulsions were characterized， and fluorescein tracer method was used to investigate the absorption effect of fluorescein-labeled EOFAZ nanoemulsions in vitro and their distribution in vivo. ResultVBCP-BSA was formed by Maillard reaction for 48 h with high grafting rate. Using VBCP-BSA as emulsifier， the homogeneous pink nanoemulsions was prepared and denoted as EOFAZ@VBCP-BSA/VB₁₂. The particle size of the nanoemulsions was less than 100 nm and the particle size distribution was uniform. The surface of the nanoemulsions was a weak negative charge， and the shape was spherical. The encapsulation rate of the nanoemulsions for EOFAZ was greater than 80%， which had a good absorption effect in vitro and could enhance liver accumulation after oral administration. ConclusionThe designed proteoglycan nanoemulsions can effectively load EOFAZ， promote oral absorption and enhance liver distribution， which can provide experimental basis for the development of oral EOFAZ liver protection preparations.