BACKGROUND:Cellular senescence is closely related to the development and progression of osteoarthritis,but the specific targets and regulatory mechanisms are not yet clear. OBJECTIVE:To mine key genes in cellular senescence-mediated osteoarthritis by integrating bioinformatics and machine learning approaches and validate them via experiments to explore the role of cellular senescence in osteoarthritis. METHODS:The osteoarthritis gene expression profiles obtained from the GEO database were intersected with cellular senescence-related genes obtained from the CellAge database and the expression of the intersected genes was extracted for differential analysis,followed by GO and KEGG analysis of the differential genes.The key osteoarthritis cellular senescence genes were then screened by protein-protein interaction network analysis and machine learning,and in vitro cellular experiments were performed.Finally,the expression of the key genes was detected by qPCR. RESULTS AND CONCLUSION:A total of 31 osteoarthritis cell senescence differential genes were identified.GO analysis showed that these genes were mainly involved in the biological processes,such as regulation of leukocyte differentiation,monocyte differentiation,regulation of T cell differentiation and exerted roles in DNA transcription factor binding,histone deacetylase binding,chromatin DNA binding,and chemokine binding.KEGG analysis showed that osteoarthritis cell senescence differential genes were mainly activated in the JAK/STAT signaling pathway,PI3K/Akt signaling pathway and FoxO signaling pathway.MYC,a key gene for osteoarthritis cellular senescence,was identified by protein-protein interaction network topology analysis and machine learning methods.The results of the in vitro cellular assay showed that the mRNA expression of MYC was significantly lower in the experimental group(osteoarthritis group)than the control group(normal group)(P＜0.05).To conclude,MYC can be a key gene in the senescence of osteoarthritic cells and may be a new target in the prevention and treatment of osteoarthritis by mediating immune response,inflammatory response and transcriptional regulation.

Objective To investigate the value of monocyte to lymphocyte ratio(MLR)and neutrophil percentage to albumin ratio(NPAR)in predicting diabetic macular edema(DME).Methods One hundred and one diabetic retinopathy patients admitted to the Third Affiliated Hospital of Xinxiang Medical University from January 2018 to February 2023 were selected as the research subjects,and they were divided into DME group(n=56)and non-DME group(n=45)based on fun-dus examination results.The general data such as gender,age,course of diabetes and laboratory indicators were collected by consulting medical records.Fasting elbow venous blood was collected early in the morning of the next day after the diagnosis of DME in both groups,the monocytes(MONO)count,lymphocyte(LYM)count,white blood cell(WBC)count,percentage of neutrophils(NEUT),plasma albumin(ALB),glycosylated haemoglobin(HbA1c)were measured by full automatic blood routine analyzer,and MLR,NPAR were calculated.General information and laboratory indexes of patients in the two groups were compared,and risk factors for DME were analyzed by multivariate logistic regression,and receiver operator characteristic(ROC)curve was applied to evaluate the predictive value of MLR and NPAR for DME.Results The course of diabetes,MONO count,NEUT,MLR,NPAR,WBC count,and HbA1c level of patients between the DME group were significantly higher than those in the non-DME group(P＜0.05);there was no statistically significant difference in gender,age,LYM count,and ALB level of patients between the two groups(P＞0.05).Multivariate logistic regression analysis showed that increased levels of WBC,MLR,and NPAR were independent risk factors for the occurrence of DME(P＜0.05).The ROC curve showed that the best cut-off value of MLR was 0.192,and the area under the curve(AUC)for the prediction of DME was 0.729(95％confidence interval:0.631-0.826),with a sensitivity of 58.9％and a specificity of 82.2％;while the best cut-off value of NPAR was 1.404,and the AUC for predicting DME occurrence was 0.884(95％confidence interval:0.820-0.949),with a sensitivity of 75.0％and a specificity of 91.1％;the AUC of MLR and NPAP for predicting the occurrence of DME was 0.906(95％confidence interval:0.851-0.906),with a sensitivity of 69.6％and a specificity of 93.3％.With MLR＞0.192 as positive and NPAR＞1.404 as positive,the parallel test of MLR and NPAR predicted the occurrence of DME with a sensitivity of 87.5％,a specificity of 71.1％,and an accuracy of 80.2％;while the tandem test of MLR and NPAR predicted the occurrence of DME with a sensitivity of 46.4％,a specificity of 97.8％,and an accuracy of 69.3％.Conclusion Increased levels of MLR and NPAR are independent risk factors for the occurrence of DME and have certain predictive value for DME.The predictive value of combined MLR and NPAR test for DME is higher than that of separate test,and parallel experiment is more helpful for the early prediction of DME.

The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.

Lung cancer is one of the most common cancers in the world, and its treatment strategy is mainly surgery combined with radiotherapy and chemotherapy. However, long-term chemotherapy will result in drug resistance, which is also one of the difficulties in the treatment of lung cancer. Ferroptosis is an iron-dependent and lipid peroxidation-driven non-apoptotic cell death cascade, occurring when there is an imbalance of redox homeostasis in the cell. Nuclear factor erythroid 2-related factor 2 (Nrf2) is key for cellular antioxidant responses. Numerous studies suggest that Nrf2 assumes an extremely important role in regulation of ferroptosis, for its various functions in iron, lipid, and amino acid metabolism, and so on. In this review, a brief overview of the research progress of ferroptosis over the past decade will be presented. In particular, the mechanism of ferroptosis and the regulation of ferroptosis by Nrf2 will be discussed, as well as the role of the Nrf2 pathway and ferroptosis in tumor drug resistance, which will provide new research directions for the treatment of drug-resistant lung cancer patients.
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Humans ; Ferroptosis ; NF-E2-Related Factor 2/genetics* ; Lung Neoplasms/genetics* ; Drug Resistance, Neoplasm ; Iron

Objective: To systematically evaluate effectiveness of exercises on inflammatory response among obese adolescents. Methods: By searching CNKI, PubMed, Web of Science, EBSCOhost and other databases, randomized controlled trials (RCTs) on the influence of different exercises on inflammatory indicators in obese adolescents were collected according to the inclusion and exclusion criteria. Cochrane evaluation tools were conducted methodological studies on the included literature quality evaluation, and RevMan 5.3 analysis software was used for statistical analysis. Results: A total of 21 RCTs were included, involving 1 020 subjects. The results of Meta analysis showed that aerobic training (AT) and aerobic plus resistance training (AT+RT) could significantly reduce BMI, serum C reactive protein (CRP) and leptin levels in obese adolescents. In addition, the effects of AT+RT on pro inflammatory CRP ( MD=-0.52, 95%CI=-0.75--0.30, P <0.01), leptin ( MD=-7.20, 95%CI=-10.45--3.94, P <0.01) and anti inflammatory adiponectin ( MD=1.28, 95%CI=1.01-1.55, P <0.01) were stronger than AT. High intensity interval training (HIIT) was associated with BMI reduction ( MD=-1.14, 95%CI=-1.92--0.36, P <0.01) and increased adiponectin in obese adolescents ( MD=1.79, 95%CI=1.09-2.50, P <0.01), and HIIT was superior in improving adiponectin level in obese adolescents than AT and AT+RT. Conclusion Long term and regular AT, AT+RT and HIIT can reduce inflammation in obese adolescents. HIIT is a notable exercise method for obese adolescents to resist inflammation.

Under the background of high-quality development of public hospitals, the construction of digital hospitals plays an important role in improving hospital management and service quality. By analyzing the problems and experience of digital hospital construction, the authors identified such key paths of digital hospital construction in the " 14th Five-Year Plan" period as strengthening organizational leadership, increasing capital investment, consolidating talent teams and promoting data sharing, hence providing references to hospitals transformation to digital ones.

Digital reform serves as powerful driver for high-quality development of hospitals. Taking the problems existing in the decision-making mechanism of major issues as a breakthrough, a tertiary hospital used digital thinking to optimize the decision-making mechanism. The hospital took such means as optimizing the rules of procedure, strengthening the pre-decision assessment, clarifying the principle of " two initiatives" , improving the " No.1 issue" system, strengthening the linkage between the Party committee and meeting the president′s office meeting, and standardizing the supervision and implementation. By such means, the hospital successfully built a smart, efficient, coordinated, and closed-loop operation and management system, desirably strengthening the leadership and core role of the Party committee, enhancing the president′s overall management of business work, as well as improving the decision completion rate and feedback rate.

Objective:To analyze the abnormal vestibular function of Wernicke encephalopathy (WE) and to explore its diagnostic value.Methods:WE patients who visited the Vertigo Center of the Second Affiliated Hospital of Zhengzhou University from January 2018 to January 2021 were retrospectively collected. All patients were evaluated by clinical neurology. Before treatment, all patients completed video head impulse test (vHIT) and video nystagmusgraphy (VNG) in addition to cranial magnetic resonance and serum thiamine level examination.Results:All 12 patients had a history of eating defects, including 8 cases of alcoholism. All 12 patients had walking instability, 7 cases had dizziness and 8 cases had oscillopsia. Six cases had ophthalmoplegia. All 12 cases showed positive gaze nystagmus. The pathological saccades of bilateral horizontal semicircular canals were found in 12 patients by vHIT before treatment, but there was only 1 patient showing abnormality in vertical semicircular canals, the difference being statistically significant ( P<0.05). All patients could detect bilateral, horizontal, gaze-evoked nystagmus, including 3 cases with vertical nystagmus, 1 case with abnormal saccade test, 3 cases with abnormal smooth tracking test and 1 case with abnormal optokinetic test. There were abnormalities in the caloric test, including 6 cases of bilateral dysfunction and 2 cases of unilateral dysfunction. Conclusions:WE patients may have abnormal vHIT and bilateral, horizontal, gaze-evoked nystagmus, which is similar to the special abnormal signs of simultaneous damage of both peripheral and central vestibular dysfunction.Vestibular function test is valuable for diagnosis of WE, and it is suitable for patients with a history of nutritional disorders who have dizziness or walking instability and suspected WE.

The construction of high-quality public hospitals is the key to the construction of high-quality and efficient medical service system. The authors introduced the implementation of " 1+ 5″ engine-driven high-quality transformation development strategy in Zhejiang Provincial People′s Hospital, that is, adhering to the party building to lead the development of the hospital, and formulating measures to build a high-quality hospital from the five aspects of quality and safety, operational efficiency, brand influence, innovation driven and sustainable development, so as to provide some reference for other hospitals′ high-quality development.