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Background/purpose: Rho GTPase activating protein 11A (ARHGAP11A) can facilitate GTP hydrolysis in RhoA. The functions of ARHGAP11A in oral squamous cell carcinoma (OSCC) have not yet been explored. This study aimed to investigate the expression profile of ARHGAP11A in OSCC, its correlation with patient prognosis, its effect on cell-cycle progression, and the mechanisms by which it is dysregulated. Materials and methods: Bioinformatics analysis was conducted using data from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC). Lentiviruses carrying ARHGAP11A shRNAs were employed to determine the effects of ARHGAP11A knockdown on tumor cell proliferation and cell-cycle progression. Dual-luciferase reporter assays were utilized to examine how FOXM1 transcriptionally regulates ARHGAP11A expression. Results: ARHGAP11A upregulation was associated with unfavorable overall survival (OS) in patients with TSCC (HR: 2.142, 95%CI: 1.224–3.749, P = 0.007), but not in patients with OSCC of sites other than the tongue. ARHGAP11A knockdown inhibited the proliferation of TSCC cells in vitro and in vivo, and induced G1 phase arrest. ARHGAP11A knockdown increased GTP-RhoA but decreased p-RB levels, while it did not affect the total expression of RhoA and RB. ARHGAP11A knockdown increased p27 and decreased cyclin E1 expression. ARHGAP11A is transcriptionally activated by FOXM1 via multiple FOXM1 binding sites in the promoter regions in TSCC cells. Conclusion: This study revealed the oncogenic role of ARHGAP11A in TSCC, highlighting its impact on cell-cycle control and tumor proliferation. Furthermore, the regulatory relationship between FOXM1 and ARHGAP11A provides new insights into the transcriptional networks in TSCC.

Abstract Wind power DC collection system, as a crucial component of wind farms, plays a vital role in ensuring the safe and stable operation of the entire wind farm. This paper proposes a reliability assessment method for wind power DC collection systems based on MLFTA-SMC. Firstly, it analyzes the topology and key equipment of wind power DC collection systems. Secondly, based on the topology of different wind power DC collection systems, it constructs multi-level fault tree models to calculate the comprehensive importance of different events, thus providing data support for subsequent reliability assessment. Then, it utilizes the MLFTA-SMC method to assess and analyze the reliability of different wind power DC collection system topologies. Finally, taking a 100 MW wind farm in Northwest China as an example, the proposed reliability assessment method is verified through simulation. The results indicate that this method exhibits good effectiveness and superiority.

Abstract Aims Dipeptidyl peptidase-4 inhibitors (DPP-4i) served as oral antidiabetic agents for treatment of type 2 diabetes mellitus (T2DM). Although an action on glucose homeostasis was identified, no well-rounded illustration had been established on the changes of tumor necrosis factor alpha (TNF-alpha) levels during DPP-4i treatment. This study aimed to explore the anti-inflammatory effect of DPP-4i on TNF-alpha in patients with T2DM. Methods PubMed, Embase and Cochrane Library were systematically searched from inception to May 31, 2024. Randomized controlled trials exploring the impact of DPP-4i on TNF-alpha levels were identified. Risk of bias was assessed according to the Cochrane criteria. A fixed or random-effects model was selected to pool estimate on whether the heterogeneity was present. Subgroup analysis were performed to explore the potential factors that influenced heterogeneity. Related meta-analysis was conducted with the software of Revman 5.3 and STATA 12.0. Results Eleven trials involving 884 participants with T2DM were included. Pooled estimates suggested that DPP-4i did not significantly modulate TNF-alpha levels (WMD, − 0.70, 95% CI − 1.94 to 0.53, P = 0.26) in T2DM. DPP-4i produced a significant effect on TNF-alpha (WMD, − 4.50 pg/mL, 95% CI − 4.68 to − 4.32, P

Abstract Aims About 20–40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. Methods A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively. Results A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg’s and Egger’s tests. Conclusions Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. International Prospective Register for Systematic Review (PROSPERO) number CRD.42020144642.

Abstract Background Patients with type 2 diabetes mellitus (T2DM) are commonly at high risk for developing cognitive dysfunction. Antidiabetic agents might be repurposed for targeting cognitive dysfunction in addition to modulation on glucose homeostasis. This study aimed to evaluate the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on cognitive function in T2DM. Methods PubMed, Embase, Cochrane Library and Web of Science were systematically searched from inception to September 30, 2023. Weighted mean differences were calculated using the Mantel-Haenszel (M-H) fixed or random effects model based on the degree of heterogeneity among studies. Heterogeneity was evaluated using a Chi-squared test and quantified with Higgins I2. Sensitivity analysis was performed with the leave-one-out method, and publication bias was evaluated according to Begg’s and Egger’s tests. Results Six clinical trials involving 5,178 participants were included in the pooled analysis. Administration of DPP-4i generally correlated with an increase of Mini-Mental State Examination (MMSE) scores (1.09, 95% CI: 0.22 to 1.96). DPP-4i alleviated cognitive impairment in the copying skill subdomain of MMSE (0.26, 95% CI: 0.12 to 0.40). Treatment with DPP-4i also resulted in an increase of Instrumental Activities of Daily Living (IADL) scores (0.82, 95% CI: 0.30 to 1.34). However, DPP-4i produced no significant effects on Barthel Activities of Daily Living (BADL) scores (0.37, 95% CI: -1.26 to 1.99) or other test scores. Conclusions DPP-4i treatment favourably improved cognitive function in patients with T2DM. Further trials with larger samples should be performed to confirm these estimates and investigate the association of different DPP-4i with cognitive function among diabetic patients. Trial registration in PROSPERO CRD42023430873.

Abstract Background The mechanisms of age-dependent reproductive decline in men are largely overlooked. An age-dependent reduction in nicotinamide adenine dinucleotide (NAD+) levels has been reported in multiple somatic and female reproductive tissues, including oocytes and ovarian tissue. However, the relationship between NAD + levels and male reproduction has not yet been studied. In the current study, the association between sperm NAD + level and paternal age was investigated. In addition, we also investigated whether sperm NAD + levels were related to semen quality. Methods In this pilot observational cohort study, semen samples from 51 male subjects who visited a university-affiliated reproductive medical center for preconception consultation ( 40 years: n = 19) were recruited. Their anthropometric characteristics were recorded, and semen analysis was performed. Their sperm NAD + levels were evaluated spectrophotometrically. Results There were significant differences among the three age groups in the major parameters of semen quality. The sperm NAD + level was, however, similar among the three groups ( 40 years: 115.59 ± 16.55 nmol/106 sperm). Additionally, linear regression also revealed no correlation between sperm NAD + concentration and the age of the participants (r2 = 0.018, p = 0.35). Noticeably, a negative correlation was found between the sperm NAD + concentrations and the sperm quality parameters, including sperm concentration (r2 = 0.78, p

Abstract Background Primary central nervous system lymphoma (PCNSL) is a specific subtype of non-Hodgkin lymphoma that is highly invasive and confined to the central nervous system (CNS). The vast majority of PCNSLs are diffuse large B-cell lymphomas (DLBCLs). PCNSL is a highly heterogeneous disease, and its pathogenesis has not yet been fully elucidated. Further studies are needed to guide individualized therapy and improve the prognosis. Methods In this study, we detected 1) the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 by immunohistochemistry (IHC) and Western blotting, 2) the mRNA expression by real-time qPCR and 3) the deletion of PTEN gene by immunofluorescence in situ hybridization (FISH) in order to investigate the activation status of the PI3K/AKT/mTOR signaling pathway in PCNSL. Samples of reactive hyperplasia lymphnods were used as the control group. The correlations between the clinical characteristics and prognosis of PCNSL patients and the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 and the deletion of PTEN were assessed. Results The IHC results showed that the positive expression rates of p-AKT, p-mTOR, p-S6 and p-4E-BP1 in PCNSL were significantly higher in the PCNSL group than in the control group (P

Risk-taking is a key factor in corporate competitive advantage, and economic development. The type of strategic configuration that can drive high-level risk-taking is a problem worthy of attention. This study takes 2,219 listed firms in China as samples and performs a fuzzy set qualitative comparative analysis (fsQCA) to explore the linkage effect and path choice of strategic change, corporate social responsibility, innovation, diversification, and financialization with corporate risk-taking (CRT). It finds that: (a) a single strategy does not constitute a necessary condition for high-level CRT; (b) three types of adaptive schemes exist for high-level CRT, among which the risk-taking level is the highest under the path of “Innovation, diversification, and financialization”; and (c) the driving paths of CRT in different regions, industries, and ownership show obvious differences.

Abstract Background Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. Methods We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. Results Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0–44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). Conclusions These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.

Primary central nervous system lymphoma (PCNSL) remains a disease with poor outcome and high recurrence rate. We retrospectively analyzed the clinical data of 243 immunocompetent patients with PCNSL in Beijing Tiantan Hospital. The median age of PCNSL patients was 57 years (range 10-95 years). For induction therapy, 94.7% of patients received high-dose methotrexate (HD-MTX) containing regimens, and 59.3% received rituximab, which increased over time. The overall response rate was 72.8%, with 58.8% achieving complete response. With a median follow-up of 27.0 months (95% confidence interval 23.6-30.4), the median progression-free survival (PFS) time was 14.0 months (95% CI 9.45-18.55), and the 2-year PFS rate was 33.2%. The median overall survival (OS) was not reached (NR), with an estimated overall survival rate at 4 years of 61.6%. Among 95 patients who completed sequential consolidation chemotherapy with either pemetrexed or etoposide plus cytarabine, the median PFS was 28 months (95% CI 17.11-38.89), and the estimated overall survival at 4 years was 78.7%. In conclusion, HD-MTX based induction chemotherapy with non-myeloablative sequential consolidation chemotherapy is an alternative feasible treatment option.

The role of the CEO in an enterprise's management decisions renders their individual characteristics influential in decisions about mergers and acquisitions (M&As). Personal characteristics are based on many aspects, therefore, we provide a multi-angle insight into the personal characteristics of managers. Drawing on the upper echelons theory, we examine whether CEOs' proactive personality affects merger and acquisition decisions. The fuzzy-set qualitative comparative analysis (fsQCA) is performed using a sample of 64 listed firms in China for the period 2010–2019. There are three solutions for cross-industry mergers, and five for intra-industry mergers. The results suggest that: (a) proactive and overconfident CEOs are inclined toward cross-industry mergers; (b) non-proactive and low-educated CEOs are inclined toward intra-industry mergers; (c) emerging industry enterprises tend to choose intra-industry mergers; (d) overconfident CEOs are more likely to undertake cross-industry mergers in traditional industries.

Abstract Background Secondary central nervous system lymphoma (SCNSL) is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. It is considered a profoundly adverse complication with inferior clinical outcome. Parenchymal involvement in the CNS in aggressive B-cell lymphoma is not frequently seen and remains a diagnostic dilemma. Methods In our study, we retrospectively analyzed the clinical and magnetic resonance imaging (MRI) features of 26 parenchymal SCNSL patients. In addition, we compared MRI features of SCNSL and primary CNS lymphoma (PCNSL) patients after 1:1 propensity score matching. Also we presented two SCNSL cases with atypical MRI appearance. Results Among SCNSL patients, the median CNS relapse time was 3 months, and multiple lesions were found in 76.9% of the cases. In PCNSL, this percentage was 42.3% (p = 0.011). None of the SCNSL patients and 23.1% of the PCNSL patients had solitary infratentorial lesions (p = 0.003). Conclusions The majority of parenchymal involvement occurred within the first year of systemic lymphoma, in which mostly cases presenting with multiple and supratentorial locations, unlike what was found in PCNSL.

Abstract Background It has been indicated that abnormal glucose metabolism mediated by hypoxia‐inducible factor 1α (HIF‐1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL). Objective To investigate the protein levels of HIF‐1α, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in PCNSL and whether their levels are associated with prognostic factors. Methods Expression of HIF‐1α, GLUT1, and HK2 in 39 tumor tissues was evaluated by immunohistochemical stainning. The correlation of the expression of HIF‐1α with the protein level of GLUT1 and HK2 was investigated. In addition, the association between these protein expression levels and clinical parameters and prognosis was analyzed. Results In the tumor specimens of PCNSL, positive stainings of HIF‐1α, GLUT1, and HK2 were in 23 patients (58.97%), 25 patients (64.1%), and 26 patients (66.67%), respectively, which were associated with the expression level of lactic dehydrogenase (LDH), but not with age, gender, number of lesion, ECOG score, or deep structure. The expression of HIF‐1α was positively correlated with the expression of GLUT1 (p

Abstract Background Primary central nervous system lymphoma(PCNSL) is a rare kind of non-Hodgkin lymphoma. Rituximab combined with high-dose methotrexate, cytarabine and dexamethasone (R-MAD regimen) were reported effective for PCNSL patients. Rituximab can cause several side effects, including fever, chills and rigors. Case presentation In this case report, we demonstrate rituximab-induced interstitial pneumonitis in a PCNSL patient who has been treated with R-MAD regimen. The patient recovered after treatment and she remains complete remission after following consolidation chemotherapy. Conclusions Here is no report of potential fatal complications of Rituximab like interstitial pneumonitis nowadays in PCNSL patients. As Rituximab is widely used, physicians should raise their awareness of this rare complication and detect RTX-ILD in early stage.

To facilitate profiling mitochondrial transcriptomes, we developed a third-generation human mitochondria-focused cDNA microarray (hMitChip3) and its bioinformatic tools. hMitChip3 consists of the 37 mitochondrial DNA-encoded genes, 1098 nuclear DNA-encoded and mitochondria-related genes, and 225 controls, each in triplicate. The bioinformatic tools included data analysis procedures and customized database for interpretation of results. The database associated 645 molecular functions with 946 hMitChip3 genes, 612 biological processes with 930 genes, 172 cellular components with 869 genes, 107 biological chemistry pathways with 476 genes, 23 reactome events with 227 genes, 320 genetic disorders with 237 genes, and 87 drugs targets with 55 genes. To test these tools, hMitChip3 was used to compare expression profiles between human melanoma cell lines UACC903 (rapidly dividing) and UACC903(+6) (slowly dividing). Our results demonstrated internal geneset consistency (correlation R ≥ 0.980 ± 0.005) and interexperimental reproducibility (R ≥ 0.931 ± 0.013). Expression patterns of 16 genes, involved in DNA, RNA, or protein biosyntheses in mitochondrial and other organelles, were consistent with the proliferation rates of both cell lines, and the patterns of 6 tested genes were verified by quantitative reverse transcription PCR (RT-PCR). Thus, hMitChip3 and its bioinformatics software provide an integrated tool for profiling mitochondria-focused gene expression.