BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy worldwide, accounting for more than 90% of all oral cancers, and is characterized by high invasiveness and poor long-term prognosis. Its etiology is multifactorial, involving tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Oral leukoplakia and erythroplakia are the main precancerous lesions lesions, with oral leukoplakia being the most common. Both OSCC and premalignant lesions are closely associated with aberrant activation of multiple signaling pathways. Post-translational modifications (such as ubiquitination and deubiquitination) play key roles in regulating these pathways by controlling protein stability and activity. Growing evidence indicates that dysregulated ubiquitination/deubiquitination can mediate OSCC initiation and progression via aberrant activation of signaling pathways. The ubiquitination/deubiquitination process mainly involves E3 ligases (E3s) that catalyze substrate ubiquitination, deubiquitinating enzymes (DUBs) that remove ubiquitin chains, and the 26S proteasome complex that degrades ubiquitinated substrates. Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumor-related proteins, thereby driving OSCC initiation and progression. Therefore, understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components. Here, we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway, Wnt/β-catenin pathway, Hippo pathway, and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways, along with potential drug targets. PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70% of OSCC cases. It is modulated by E3s (e.g., FBXW7 and NEDD4) and DUBs (e.g., USP7 and USP10): FBXW7 and USP10 inhibit signaling, while NEDD4 and USP7 potentiate it. Aberrant activation of the Wnt/β‑catenin pathway leads to β‑catenin nuclear translocation and induction of cell proliferation. This pathway is modulated by E3s (e.g., c-Cbl and RNF43) and DUBs (e.g., USP9X and USP20): c-Cbl and RNF43 inhibit signaling, while USP9X and USP20 potentiate it. Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis. This pathway is modulated by E3s (e.g., CRL4^DCAF1 and SIAH2) and DUBs (e.g., USP1 and USP21): CRL4^DCAF1 and SIAH2 inhibit signaling, while USP1 and USP21 potentiate it. Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance. This pathway is modulated by E3s (e.g., TRAF6 and LUBAC) and DUBs (e.g., A20 and CYLD): A20 and CYLD inhibit signaling, while TRAF6 and LUBAC potentiate it. Targeting these E3s and DUBs provides directions for OSCC drug research. Small-molecule inhibitors such as YCH2823 (a USP7 inhibitor), GSK2643943A (a USP20 inhibitor), and HOIPIN-8 (a LUBAC inhibitor) have shown promising antitumor activity in preclinical models; PROTAC molecules, by binding to surface sites of target proteins and recruiting E3s, achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors, for example, PU7-1-mediated USP7 degradation, offering new strategies to overcome traditional drug limitations. Currently, NX-1607 (a Cbl-b inhibitor) has entered phase I clinical trials, with preliminary results confirming its safety and antitumor activity. Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.

Objective To establish radioresistant human non-small cell lung cancer NCI-H460R model cells and evaluate the sensitivity of these radioresistant cells to a ferroptosis inducer. Methods Radioresistant cell lines, designated as NCI-H460 R20Gy and NCI-H460 R116Gy, were generated by subjecting parental NCI-H460 cells to fractionated irradiation with varying cumulative doses. Both parental cells and the established radioresistant cell lines were each randomly divided into four groups and exposed to irradiation at 0, 2, 4, and 6 Gy, respectively. Successful establishment of the radioresistant cell lines was confirmed by colony formation assay. Subsequently, cells were treated with increasing concentrations of the ferroptosis inducer RSL-3 to assess differential sensitivity between parental and radioresistant cells to ferroptosis. Results In comparison to the parental NCI-H460 cells (D_0WT=1.2), both NCI-H460 R116Gy and NCI-H460 R20Gy cells exhibited radioresistance, with NCI-H460 R116Gy demonstrating a stronger radioresistance (D_0R116Gy=1.5) than NCI-H460 R20Gy (D_0R20Gy=1.4). Furthermore, NCI-H460 R116Gy cells exhibited increased sensitivity to RSL-3 relative to the parental cells (P < 0.001), while NCI-H460 R20Gy cells did not display a significant difference in sensitivity to RSL-3. Conclusion Human non-small cell lung cancer cells with radioresistance induced by a high cumulative irradiation dose exhibit increased sensitivity to the glutathione peroxidase 4-specific ferroptosis inducer RSL-3. This finding provides an experimental basis for optimizing combined treatment regimens involving radiotherapy and RSL-3 for non-small cell lung cancer patients with radiotherapy resistance.

Objectives:To evaluate with meta-analysis the clinical effects of physiotherapeutic scoliosis spe-cific exercises(PSSE)comparing with other conservative treatments in treating adolescent idiopathic scoliosis(AIS).Methods:PubMed,Web of Science,The Cochrane Library,WanFang Data and China National Knowl-edge Infrastructure(CNKI)were searched by computer from their establishments to July 2023.The randomized controlled trials(RCTs)of PSSE therapy(PSSE therapy group)and other conservative treatments(control group)in treating AIS were collected.Two researchers independently screened the literature,extracted data and assessed the risk of bias of the included studies.Meta analysis was performed using RevMan 5.4 software on the Cobb angle,angle of trunk rotation(ATR),and quality of life score of Scoliosis Research Society-22(SRS-22)scale reported in the included literature,and subgroup analysis was carried on according to Cobb angle and treat-ment duration.Results:A total of 14 studies were included,consisting of 16 RCTs(2 studies included 2 RCTs each),involving 944 AIS patients.The quality of the literature was of medium and high.Meta analysis results showed that,comparing with the control group,the PSSE therapy group was superior in reducing Cobb angle of AIS patients(MD=1.64;95％CI:2.78,0.50;P＜0.05)and ATR(MD=1.45;95％CI:-2.58,-0.32;P＜0.05),and improving the SRS-22 quality of life score(MD=0.25;95％CI:0.17,0.33;P＜0.05).The results of subgroup analysis showed that for the AIS patients with duration of treatment ≤6 months(MD=-2.88;95％CI:-3.85,-1.91;P＜0.05)and a Cobb angle＜25° at enrollment(MD=-2.41;95％CI:-3.51,-1.30;P＜0.05),the PSSE therapy group had a better effect with a smaller Cobb angle(P＜0.05)than the control group.In terms of ATR improvement,for the patients with treatment duration ≤6 months(MD=2.63;95％CI:3.30,1.96;P＜0.05),the PSSE therapy group had a lower ATR degree comparing with the control group(P＜0.05).Conclusions:Comparing with other conservative treatments,PSSE therapy has advantages in improving the Cobb angle,re-ducing ATR and improving the quality of life in AIS patients,especially for mild scoliosis patients with Cobb angle＜25°.PSSE therapy has a better therapeutic effect on reducing the Cobb angle and ATR more obvious-ly in AIS patients with duration of treatment ≤6 months.

Objective:To explore the current status and related factors of eHealth literacy in cardiovascular and cerebrovascular patients by selecting an appropriate digital eHealth literacy scale.Methods:From February to May 2023, convenience sampling was used to select 310 cardiovascular and cerebrovascular patients from the Department of Cardiology and Neurology of two ClassⅢ Grade A hospitals in Beijing as study subjects. E-Health Literacy Scale (EHLS), the eHealth Literacy Scale (eHEALS), and the Mobile eHealth Literacy Scale (m-eHEALS) were used to survey patients. Correlation analysis, internal consistency analysis, and structural validity analysis were used to select the main scale for the study. Binomial Logistic regression was used to explore the related factors of eHealth literacy in cardiovascular and cerebrovascular patients.Results:A total of 310 questionnaires were distributed, and 302 were effectively collected, with an effective rate of 97.42%. Among the three scales, the EHLS had good reliability and validity. The EHLS score of 302 patients was (37.73±9.66), with a qualified rate of 13.91% (42/302). Binomial Logistic regression analysis showed that the course of cardiovascular and cerebrovascular disease ( OR=0.615, 95% CI: 0.465-0.813) and the level of concern for one's own health status ( OR=0.669, 95% CI: 0.478-0.937) were related factors for eHealth literacy in cardiovascular and cerebrovascular patient ( P<0.05) . Conclusions:The qualification rate of eHealth literacy for cardiovascular and cerebrovascular patients is relatively low. A short course of disease and a high level of concern for one's own health status are protective factors for eHealth literacy in cardiovascular and cerebrovascular patients.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

Ovarian aging is a reproductive endocrine disease caused by a variety of factors leading to a gradual decline in ovarian function until ovarian failure， which seriously affects women's physical and reproductive health and is a major factor leading to female infertility. Mitochondria， the energy metabolism centers of cells， are critical for ovarian functions. Their structural and functional abnormalities are key pathological factors leading to the declined ovarian function. Mitochondrial quality control is an important endogenous regulatory mechanism for the maintenance of mitochondrial homeostasis and the improvement of mitochondrial functions. Abundant studies have shown that the dysregulation of mitochondrial quality control， characterized by mitochondrial oxidative damage， abnormal mitochondrial biogenesis， abnormal mitochondrial dynamics， abnormal mitochondrial autophagy， and dysregulated calcium homeostasis， is closely associated with the occurrence of ovarian hypofunction. Traditional Chinese medicine （TCM） is a treasure of China's medicine， demonstrating remarkable efficacy in the clinical treatment of ovarian aging-related diseases. In recent years， research progress has been achieved in the TCM treatment of ovarian aging by regulating mitochondrial quality control disorders in a multi-target and multi-pathway manner. However， systematic research remains to be carried out regarding the research progress in this field. Therefore， this article reviews the research progress in the TCM treatment of ovarian aging based on mitochondrial quality control， with a view to providing a theoretical basis for studying the clinical efficacy of TCM in the treatment of ovarian aging and a new strategy for the in-depth research on the prevention and treatment of ovarian aging by TCM.

Background Chronic intermittent hypobaric hypoxia (CIHH) can effectively alleviate type 2 diabetes mellitus (T2DM). In this process, the underlying mechanism in its association with the epigenetic regulation of DNA methylation in the promoter regions of glucose metabolism key enzyme genes remains unclear yet. Objective To investigate the effects of CIHH on expression and promoter region methylation of key enzyme genes related to glucose metabolism in diabetes mice, and to explore the underlying mechanism by which CIHH regulates glucose metabolism. Methods Forty C57BL/6J male mice were divided randomly into a normobaric normoxic control (NN/CON) group, a chronic intermittent hypobaric hypoxia intervention control (CIHH/CON) group, a normobaric normoxic diabetic model (NN/DM) group, and a chronic intermittent hypobaric hypoxia intervention diabetic model (CIHH/DM) group. The mice in the NN/DM and the CIHH/DM groups were fed for 7 weeks with high-fat and high-sugar diet. Subsequently, these mice were intraperitoneally injected consecutively with 50 mmol·L⁻¹ streptozotocin (STZ) for 5 d at a dose of 40 mg·kg⁻¹ (body weight) per day to create T2DM model mice. The mice in the CIHH/DM and the CIHH/CON groups were intervened by simulating hypobaric hypoxia at 5000 m altitude for 6 h per day, while the mice in the NN/DM and the NN/CON groups were always placed in a normobaric normoxic environment. All mice were continuously treated for 4 weeks, and blood glucose were monitored during this period. After the CIHH intervention experiment, the glucose tolerance and insulin sensitivity of mice were evaluated. A set of indicators involved in key glycolytic enzymes glucokinase (GK) and pyruvate kinase (PK), as well as key gluconeogenic enzymes phosphoenolpyruvate carboxyl kinase (PEPCK) and glucose-6-phosphatase (G6P) were measured in the liver of mice, including enzyme activity, relative mRNA expression level, and DNA methylation level in the gene promoter regions. Results Compared with the mice in the NN/DM group, the blood glucose levels of the mice in the CIHH/DM group decreased after the 25^th day of the CIHH intervention (P<0.05). Regarding the diabetic glucose tolerance curves, the area under the curve (AUC) of the mice in the CIHH/DM group was lower than that of the NN/DM group (P<0.05). Compared with the mice in the NN/DM group, the mice in the CIHH/DM group showed that the serum insulin content and HOMA of insulin resistance index (HOMA-IRI) decreased (P<0.05), the enzyme activities of GK and PK increased and the relative mRNA expression levels of their genes were up-regulated (P<0.05), while the enzyme activities of PEPCK and G6P decreased and the relative mRNA expression levels of their genes were down-regulated (P<0.05) in liver. The average DNA methylation levels in the promoter regions of GK, PK, PEPCK, and G6P genes in liver of mice in each group were not significantly different (P>0.05), and their correlations with mRNA expression levels were also not statistically significant (P>0.05). Conclusion CIHH intervention may reduce blood glucose level, improve glucose tolerance, alleviate insulin resistance, and regulate the key enzyme activities of glucose metabolism and the relative mRNA expression of their corresponding genes in T2DM mice, but the above phenomena are not related to the DNA methylation levels in the promoter regions of these key enzymes.

OBJECTIVE:At present,there are a variety of treatment methods for scoliosis using specific exercise therapy,but there is a lack of comparison of efficacy between different specific exercise therapy.This article compared the effectiveness of different specific exercise therapies to treat adolescent idiopathic scoliosis through a network meta-analysis. METHODS:Domestic and foreign electronic databases of relevant studies were searched for randomized controlled trials of specific exercise therapy for adolescent idiopathic scoliosis.Search time was from January 2000 to July 2023.The literature was screened by two reviewers using RevMan 5.4 and Stata 16.0 software to extract data and assess the bias risk of of inclusion studies. RESULTS:(1)This article includes 20 randomized controlled trials with 1 377 patients.Of them,12 studies involved Schroth therapy;2 studies involved BSPTS therapy,and 6 studies involved SEAS therapy.(2)The network meta-analysis indicated that in terms of improving Cobb angle and reducing trunk rotation angle in scoliosis patients,the BSPTS therapy group and Schroth therapy group were better than the conventional control group[WMD=-4.60,95%CI(-8.37,-0.82),P<0.05;WMD=-3.37,95%CI(-4.98,-1.75),P<0.05;WMD=-3.20,95%CI(-5.50,-0.90),P<0.05;WMD=-2.13,95%CI(-3.16,-1.09),P<0.05].The Schroth therapy group performed better than the conventional control group effective in improving the International Society for Scoliosis Research-22 Questionnaire quality of life score[WMD=1.41,95%CI(0.07,2.75),P<0.05]. CONCLUSION:Given the current evidence,BSPTS therapy group and Schroth therapy group were better than the conventional control group in improving Cobb angle and reducing trunk rotation angle.In the comparison of different specific exercise therapies,BSPTS therapy can be preferred to improve Cobb angle and reduce trunk rotation angle in adolescent idiopathic scoliosis patients.In addition,Schroth therapy may be the best treatment to improve the quality of life of adolescent idiopathic scoliosis patients.Limited by the quantity and quality of the included studies,the above conclusions should be interpreted with caution and need more high-quality studies to further validation.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.