BACKGROUND:Complement Factor B (CFB) is a component of the alternative complement pathway with emerging roles in cancer biology. This study investigated the role of CFB in lung cancer progression and characterized its downstream molecular and immunological effects. METHODS:We performed transcriptomic analysis of CFB-silenced lung adenocarcinoma cells and validated findings in clinical specimens. CFB deficiency was assessed using in vitro functional assays, metabolite measurements, and T cell coculture systems. Immunomodulatory effects were evaluated in vivo using tumor models treated with an indoleamine 2,3-dioxygenase (IDO) inhibitor. RESULTS:CFB silencing activates a proto-oncogene C-Fos (FOS)-dependent upregulation of tryptophan metabolism enzymes. CFB expression inversely correlates with FOS and tryptophan metabolic enzymes in human lung cancer specimens, with stronger alterations in advanced disease. Mechanistically, CFB deficiency enhances tryptophan catabolism to kynurenine, promoting regulatory T cell activation through aryl hydrocarbon receptor (AhR) signaling while suppressing CD8 + T cell function. In vivo, CFB-knockdown tumors show accelerated growth, enhanced immune suppression, and increased tryptophan catabolism. These effects are reversed by IDO inhibitor treatment. CONCLUSION:We identify a CFB-FOS-IDO axis that regulates tryptophan metabolism and shapes the tumor immune microenvironment in lung cancer. CFB deficiency promotes tumor progression by enhancing tryptophan catabolism, resulting in an immunosuppressive microenvironment. These findings reveal potential therapeutic targets to overcome immune evasion in lung cancer.

Lung adenocarcinoma (LUAD) is the most common and highly aggressive subtype of non-small cell lung cancer, characterized by metabolic reprogramming with enhanced glycolysis. Upregulation of key glycolytic enzymes [hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA)] and lactate accumulation not only support tumor energy production and biosynthesis but also promote tumor progression and immune evasion through lactate-mediated immunosuppression and epigenetic regulation such as histone lactylation. Oncogenic signaling pathways, including phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), hypoxia-inducible factor-1α (HIF-1α), and MYC proto-oncogene (c-Myc), synergistically drive glycolytic activation, thereby reshaping the tumor immune microenvironment and influencing therapeutic responses. In recent years, glycolysis-related metabolic enzymes and imaging parameters have shown promising potential in the early diagnosis, prognostic evaluation, and treatment monitoring of LUAD, with multi-omics integration further facilitating their clinical translation. Collectively, glycolytic reprogramming is not only a hallmark metabolic feature of LUAD but also a critical nexus linking immunosuppression, therapeutic resistance, and precision medicine. This review summarizes the molecular mechanisms, associated biomarkers, and targeted strategies of glycolytic reprogramming, aiming to provide insights for early screening, risk stratification, and metabolism-targeted therapies in LUAD.

Distinguishing early-stage lung adenocarcinoma (LUAD) from benign pulmonary nodules remains challenging. This study aimed to identify plasma biomarkers and develop a non-invasive diagnostic model. Label-free quantitative proteomics screened tumor tissues and plasma, identifying LGALS3BP as a candidate. Validation involved RT-qPCR and ELISA in independent cohorts. A diagnostic model incorporating plasma LGALS3BP, CEA, family history, and nodule characteristics was developed (n = 138) and validated (n = 47). LGALS3BP was significantly upregulated in LUAD tissues and plasma. The combined model achieved an AUC of 0.893 in the training cohort, significantly outperforming the baseline model (NRI = 0.185, P = 0.019). Validation confirmed robust performance (AUC = 0.856). The model demonstrated high clinical utility, effectively stratifying risk with a positive predictive value of 91.3% in the intermediate-to-high risk group. In conclusion, plasma LGALS3BP is a novel biomarker for LUAD. The developed model integrating LGALS3BP with clinical factors provides a robust tool for differentiating malignant from benign nodules, potentially improving risk stratification and minimizing unnecessary invasive interventions.

Objectives Primary biliary cholangitis (PBC) is a chronic liver disease characterized by the progressive destruction of small intrahepatic bile ducts and cholestasis. This study aims to evaluate PBC-related blood markers to establish a digital nomogram model, providing an early diagnostic tool for patients with autoantibody-negative PBC. Methods In this study, laboratory data were collected from 614 patients at the First Affiliated Hospital of Kunming Medical University. Using stratified random sampling, the patients were divided into a training set (n = 429) and an internal validation set (n = 185) at a ratio of 7:3. Univariate and multivariate logistic regression analyses were performed on the training set data to identify independent risk factors for PBC and to construct a nomogram prediction model. Subsequently, external validation was conducted using data from 221 patients at the Second Affiliated Hospital of Kunming Medical University. The discrimination, calibration, and clinical net benefit of the model were evaluated using the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA), respectively. Results Independent risk factors for PBC included gender (OR = 2.847, 95% CI: 1.449–5.677), age (OR = 1.042, 95% CI: 1.023–1.062), total bilirubin (TBIL) (OR = 1.077, 95% CI: 1.024–1.136), direct bilirubin (DBIL) (OR = 0.915, 95% CI: 0.858–0.969), total bile acids (TBA) (OR = 1.007, 95% CI: 1.000-1.014), alkaline phosphatase (ALP) (OR = 1.01, 95% CI: 1.006–1.013), high-density lipoprotein (HDL) (OR = 2.107, 95% CI: 1.087–4.183), hemoglobin (HGB) (OR = 0.974, 95% CI: 0.959–0.988), and platelet count (PLT) (OR = 0.994, 95% CI: 0.990–0.997). Conclusions The PBC diagnostic model demonstrated excellent discriminative and calibration capabilities, along with strong clinical utility, making it a valuable reference tool for clinical decision-making.

Background:Yunnan Province remains a region with a high prevalence of human immunodeficiency virus (HIV) in China. Due to shared transmission routes, HIV/Hepatitis C virus (HCV) co-infection is common. This study aimed to analyze the prevalence and mutation patterns of HIV-1 drug resistance among HIV/HCV co-infected patients specifically following the virological failure of first-line highly active antiretroviral therapy (HAART) in Yunnan, and to compare these characteristics with HIV-1 mono-infected patients. Methods:A cross-sectional study was conducted among 104 HIV/HCV co-infected and 120 HIV-1 mono-infected patients who experienced virological failure (HIV-RNA\geq 1,000 copies/mL) after at least 6 months of ART. Genotypic drug resistance was tested using an in-house method and analyzed via the Stanford HIV drug resistance database. Multivariable logistic regression and stratified analysis were performed to adjust for confounders. Results:Among patients with treatment failure, the drug resistance rate in the HIV/HCV co-infection group (37.5%) was significantly lower than in the HIV-1 mono-infection group (55.0%, P = 0.009). Multivariable logistic regression showed that HIV/HCV co-infection was associated with a lower trend of resistance, although it did not reach formal statistical significance after adjusting for gender, treatment duration, and CD4 + Count (aOR = 0.49, P = 0.084). However, stratified analysis revealed that co-infection was significantly associated with lower resistance in patients with a treatment duration of 6-12 months (OR = 0.24, P = 0.001) and those with CD4 + Count ≤ 350 cells/μL (OR = 0.38, P = 0.001). The frequency of the NRTI-related mutation T69D/N/S was significantly lower in the co-infected group (P = 0.029). Conclusion:Among patients experiencing virological failure, HIV/HCV co-infection is associated with distinct genotypic resistance profiles, particularly in the early stages of treatment failure and among immunodeficient individuals. These findings suggest that co-infection status may influence the pathway to HIV drug resistance. Clinicians should prioritize prompt genotype resistance testing for co-infected patients failing ART to optimize second-line regimen adjustments.

Lung adenocarcinoma (LUAD) is highly prevalent in Xuanwei region, Yunnan, China, but little is known about the genetic basis of this regional cancer. In our study, by performing the transcriptome sequencing and exome sequencing of Xuanwei LUAD and expression quantitative trait loci (eQTL) analysis, ACSM5 c.1273 C> A variant was identified as the top polymorphism affecting the highest number of downstream genes in Xuanwei LUAD. While initial exome data suggested tumor-specific enrichment, expanded validation revealed comparable occurrence of this variant in tumors (15.0

Lung adenocarcinoma (LUAC) as the most common lung cancer, and its incidence is increasing. Complement factor B (CFB) is an important factor in the alternative complement pathway. CFB has been reported to be involved in the progression of many cancers, including in pancreatic cancer, cutaneous squamous cell carcinoma, and nasopharyngeal carcinoma, but the function and molecular mechanism of CFB in LUAC remains unclear. The present study aimed to explore the role of CFB in LUAC malignant progression. In our previous study, we found that CFB was downregulated expression in LUAC clinical samples. Here, we firstly detected the cell function in vitro. Cell proliferation and migration were increased, while cell apoptosis and cell cycle arrest were suppressed after CFB knockdown. Overexpression of CFB repressed the malignant progression of LUAC in vitro. Besides, in vivo experiments revealed that upregulation of CFB inhibited tumor growth and Ki67 expression. Additionally, our data indicated that CFB negatively regulated Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, upregulation of CFB inhibited the progression of LUAC was reversed by Ras/MAPK pathway activators (ML-098 or C16-PAF). Our study uncovered that CFB acts as a tumor suppressor repressed tumorigenesis of LUAC through inhibiting the Ras/MAPK pathway, suggesting that CFB may be a potential biomarker and therapeutic target for LUAC.

Butyric acid (BA) can potentially enhance the function of the intestinal barrier. However, the mechanisms by which BA protects the intestinal mucosal barrier remain to be elucidated. Given that the Ras homolog gene family, member A (RhoA)/Rho-associated kinase 2 (ROCK2)/Myosin light chain kinase (MLCK) signaling pathway is crucial for maintaining the permeability of the intestinal epithelium, we further investigated whether BA exerts a protective effect on epithelial barrier function by inhibiting this pathway in LPS-induced Caco2 cells. First, we aimed to identify the optimal treatment time and concentration for BA and Lipopolysaccharide (LPS) through a CCK-8 assay. We subsequently measured Trans-epithelial electrical resistance (TEER), FITC-Dextran 4 kDa (FD-4) flux, and the mRNA expression of ZO-1, Occludin, RhoA, ROCK2, and MLCK, along their protein expression levels, and average fluorescence intensity following immunofluorescence staining. We then applied the ROCK2 inhibitor Y-27632 and reevaluated the TEER, FD-4 flux, and mRNA, and protein expression of ZO-1, Occludin, RhoA, ROCK2, and MLCK, as well as their distribution in Caco2 cells. The optimal treatment conditions were determined to be 0.2 mmol/L BA and 5 μg/mL LPS for 24 hours. Compared with LPS treatment alone, BA significantly mitigated the reduction in the TEER, decreased FD-4 flux permeability, increased the mRNA expression of ZO-1 and Occludin, and normalized the distribution of ZO-1 and Occludin in Caco2 cells. Furthermore, BA inhibited the expression of RhoA, ROCK2, and MLCK, and normalized their localization within Caco2 cells. Following treatment with Y-27632, the epithelial barrier function, along with the mRNA and protein expression and distribution of ZO-1 and Occludin were further normalized upon inhibition of the pathway. These findings contribute to a deeper understanding of the potential mechanisms through which BA attenuates LPS-induced impairment of the intestinal epithelial barrier.

ObjectiveThis study aims to investigate the differences of clinical indices in HIV patients between three different first-line antiretroviral treatment strategies in Yunnan Province, China. Furthermore, the hematologic system, liver function, kidney function, blood lipid levels of HIV patients and its association with CD4+ count, CD8+ count, CD4/CD8 ratio and antiretroviral treatment were also assessed.MethodsThis retrospective cohort study included 81 participants who underwent highly active antiretroviral treatment from September 2009 to September 2019. Baseline sociodemographic and clinical characteristics were collected from each study participant. Routine blood tests, liver and renal function, lipid levels as well as lymphocyte subset counts were measured and recorded for evaluation before and 3, 6, 9, and 12 months after the treatment. Paired t-test was used to compare clinical indices changes after antiretroviral treatment. Univariate linear regression was performed to determine the association between clinical indices and CD4+ count, CD8+ count, CD4/CD8 ratio and antiretroviral treatment.ResultThere were no statistical differences in baseline demographic and clinical characteristics in either treatment group. Compared with the initiation of HARRT treatment, the CD4+ count(p < 0.001), CD4/CD8 ratio(p < 0.001) and PLT(p < 0.001) were increased in the three treatment groups. The TC(p < 0.01) and TG(p < 0.05) were increased in 3TC+AZT+EFV group after treatment. The ALT(p < 0.05), AST(p < 0.01) were decreased in 3TC+EFV+TDF group after treatment. The study indicated statistical differences in CD4+ count (p < 0.001), CD8+ count (p < 0.001), and CD4/CD8 ratio (p < 0.001) in the three treatment cohorts. Furthermore, a strong positive correlation was observed between WBC (p < 0.001), platelet (p < 0.001), Hb (p < 0.001), and CD4+ count in the three treatment cohorts. Moreover, ALT and AST were negatively associated with CD4+ count in the 3TC + AZT + EFV group. Whereas WBC were positively correlated with CD8+ count in the three treatment methods. In addition, platelet and TG were positively correlated with CD8+ count in the 3TC + EFV + TDF. The study also indicated that TC was positively associated with CD8+ count in the 3TC + AZT + NVP group. Furthermore, WBC was negatively related to CD4/CD8 ratio in the 3TC + EFV + TDF group. The platelet level analysis revealed a positive, while TG indicated a negative association with CD4/CD8 ratio in the 3TC + AZT + NVP group. Moreover, ALT and AST were negatively correlated with the CD4/CD8 ratio in the 3TC + AZT + EFV and 3TC + AZT + NVP groups.ConclusionThe results showed that HIV/AIDS patients treated with different first-line antiretroviral treatment strategies had different hematopoietic, liver, renal and immune system functions. Furthermore, some clinical indicators such as WBC, PLT, TC, TG, and ALT could predict the CD4+ count, CD8+ count, CD4/CD8 ratio levels and recuperation of HIV/AIDS patients, therefore, should be monitored by clinicians.

酰基辅酶A合成酶中链家族(Acyl-CoA Synthetase Medium Chains,ACSMs)是一类可以活化C6～C10脂肪酸,并参与中链脂肪酸的合成与分解的酶,对于细胞的存活具有重要意义.肿瘤发生时,由于肿瘤细胞增长快速,需要高出正常细胞所需的更多的能量供给,除外糖酵解途径,脂肪酸供能也是肿瘤细胞获取能量的重要途径.研究中链脂肪酸合成与代谢的关键酶ACSMs,对于深入探究肿瘤的发生发展及预后等方面均具有重要意义.主要介绍近年来ACSMs家族成员与肿瘤发生发展的研究进展.

目的 探讨丁酸对TNFα所致肠上皮屏障损伤的保护作用.方法 用CCK-8 细胞活力检测探索TNFα对Caco2 发挥损伤作用的最佳浓度和时间,并以此为基础探索在TNFα发挥损伤作用最佳作用时间附近丁酸对Caco2 细胞的保护情况,随后探索TNFα和丁酸共同作用于Caco2 细胞时的最佳时间和浓度,并检测Caco2 细胞单层上皮屏障的FITC-dextran渗透率,紧密连接ZO-1 和Occludin的mRNA表达情况及免疫荧光观察TNFα和丁酸共同作用后细胞的生长情况及ZO-1 和Occludin在Caco2 中的表达和分布.结果 100 ng/mL的TNFα刺激 48 h能明显降低Caco2 的细胞存活率(P<0.0001);丁酸作用于Caco2 细胞 48 h,0.2 mM/L的丁酸能明显提高Caco2 的细胞存活率(P<0.0001).当TNFα和丁酸共同作用时,与TNFα干预组相比,丁酸可以明显降低 TNFα所致的肠上皮单层屏障的 FITC-dextran渗透率(P<0.0001),提高 ZO-1(P<0.01)和Occludin(P<0.01)的表达及稳定其在Caco2 细胞中的分布.结论 丁酸可以减轻TNFα所致的肠上皮屏障损伤,为进一步明确丁酸在溃疡性结肠炎治疗中作用机制提供实验基础.

Abstract Bacground and Aim Butyric acid (BA), as a short-chain fatty acid, can improve intestinal barrier function, meanwhile intestinal mucosal epithelial injury is a common clinical phenomenon, especially in children. Moreover, RhoA/ROCK2/MLCK signaling pathway has been confirmed to play a vital role in the maintenance of intestinal epithelial permeability. However, the specific mechanism by which BA protects intestine mucosal barrier still needs to be clarified. This study intended to investigate the effect of BA in LPS-induced Caco2 cells, and determine whether BA protected epithelial barrier by inhibiting the RhoA/ROCK2/MLCK signaling pathway. Methods The optimal concentration and intervention time of the protective effect of BA on Caco2 were investigated by CCK-8 assay. On this basis of the above results, the damaged effect of LPS to Caco2 cells near the optimal time of BA protection was explored, then the optimal time and concentration were explored when BA and LPS were simultaneously administrated to Caco2 cells, the data were used to conduct further study. Then, cell growth status was observed, TEER and FD-4 permeability of monolayer barrier of Caco2 cells were detected, the mRNA expression of ZO-1 and Occludin, RhoA, ROCK2 and MLCK was detected by RT-qPCR. Moreover, immunofluorescence staning was adopted to observe the expression and distribution of ZO-1, Occludin, as well as RhoA, ROCK2 and MLCK in Caco2. After that, RhoA/ROCK2/MLCK pathway inhibitor Y-27632 was added to Caco2 cells, the cell growth status, TEER and FD-4 permeability of monolayers barrier, the expression level and distribution of ZO-1 and Occludin, RhoA, ROCK2 and MLCK in Caco2 cells were detected. Results The final concentration of 0.2mM BA action for 24 h had the greatest effect on the viability of Caco2 cells. After Caco2 cells exposure to LPS for 24 h, the final concentration of 5ug/ml LPS significantly decreased the viability of Caco2 cells. When combined with BA and LPS, compared with LPS alone, BA improved the growth state of Caco2 cells, restored the declined TEER, and reduced FD-4 permeability, as well as improved the mRNA expression of ZO-1, Occludin and inhibited the mRNA expression of RhoA, ROCK2 and MLCK, the expression and distribution of ZO-1, Occludin, RhoA, ROCK2 and MLCK were reversed in Caco2 cells. After treatment of Y-276432, the cell growth state and mucosal barrier function were further improved, the mRNA expression of ZO-1 and Occludin was further increased, the mRNA expression of RhoA, ROCK2 and MLCK was further decreased, and the expression and distribution of these proteins in Caco2 cells were further reversed. Conclusion This study provided complementary data for BA as a potential target for attenuating intestinal barrier injury induced by LPS through inhibiting the RhoA/ROCK2/MLCK signaling pathway, supporting a further research on BA protection intestinal barrier from damage and as a new therapeutic method.

Antibiotic resistance is a global threat. Antimicrobial peptides (AMPs) are highly desirable to treat multidrug-resistant pathogen infection. However, few AMPs are clinically available, due to high cost, instability, and poor selectivity. Here, ultrashort AMPs (2-3 residues with an N-terminal cysteine) are designed and assembled as gold nanoparticles. Au-S conjugation and ultrashort size restrict nonspecific reactions and peptide orientation, thus concentrating positively charged residues on the surface. The nanostructured assemblies enormously enhance antimicrobial abilities by 1000-6000-fold and stability. One representative (Au-Cys-Arg-NH2, Au_CR) shows selective antibacterial activity against Staphylococcus aureus with 10 nM minimal inhibitory concentration. Au_CR has comparable or better in vivo antimicrobial potency than vancomycin and methicillin, with low propensity to induce resistance, little side effects, and high stability (17.5 h plasma half-life). Au_CR acts by inducing collapse of membrane potential and rupture of the bacterial membrane. The report provides insights for developing AMP-metal nanohybrids, particularly tethering nonspecific reactions and AMP orientation on the metal surface.

Abstract Butyric acid (BA) could improve intestinal barrier function, meanwhile RhoA/ROCK2/MLCK signaling pathway has been confirmed vital in the maintenance of intestinal epithelial permeability. However, the specific mechanism by which BA protects intestine mucosal barrier still needs to be clarified. Here, the optimal time and concentration were explored. Then, cell growth status, TEER and FD-4 permeability, the mRNA expression of ZO-1 and Occludin, RhoA, ROCK2 and MLCK, and the expression and distribution of them in Caco2 were detected. After that, RhoA/ROCK2/MLCK pathway inhibitor Y-27632 was adopted. The final concentration of 0.2mM BA and 5ug/ml LPS treatment for 24 h was confirmed. Compared with LPS alone, BA improved the growth state of Caco2 cells, restored the declined TEER, reduced FD-4 permeability, improved the mRNA expression of ZO-1, Occludin and restored their distrbution, as well as inhibited the mRNA expression of RhoA, ROCK2 and MLCK, and the reversed their location. After treatment of Y-276432, the cell growth state and mucosal barrier function, the mRNA expression of ZO-1 and Occludin and their location were further improved, while the pathway was inhibitied. This study provided complementary data for BA as a potential target for attenuating LPS-induced intestinal barrier injury through inhibiting the RhoA/ROCK2/MLCKpathway.

Objective To investigate trends in clinical monitoring indices in HIV/AIDS patients receiving antiretroviral therapy (ART) at baseline and after treatment in Yunnan Province, China and to provide the basis for guiding clinical treatment to obtain superior clinical outcomes. Methods A total of 96 HIV/AIDS patients who had started and persisted in highly active ART treatment from September 2009 to September 2019 were selected. Of these, 54 had a CD4 cell count < 200 cells/μl while 42 had a CD4 cell count ≥ 200 cells/μl. Routine blood tests, liver and renal function, and lipid levels were measured before and 3, 6, 9, and 12 months after treatment. Lymphocyte subset counts and viral load were measured once per year, and recorded for analysis and evaluation. Three machine learning models (support vector machine [SVM], random forest [RF], and multi-layer perceptron [MLP]) were constructed that used the clinical indicators above as parameters. Baseline and follow-up results of routine blood and organ function tests were used to analyze and predict CD4+ T cell data after treatment during long-term follow-up. Predictions of the three models were preliminarily evaluated. Results There were no statistical differences in gender, age, or HIV transmission route in either patient group. Married individuals were substantially more likely to have <200 CD4+ cells/μl. There was a strong positive correlation between ALT and AST (r = 0.587) and a positive correlation between CD4 cell count and platelet count (r = 0.347). Platelet count was negatively correlated with ALT (r = -0.229), AST (r = -0.251), and positively correlated with WBCs (r = 0.280). Compared with the CD4 cell count < 200 cells/μl group, all three machine learning models exhibited a better predictive capability than for patients with a CD4 cell count ≥ 200 cells/μl. Of all indicators, the three models best predicted the CD4/CD8 ratio, with results that were highly consistent. In patients with a CD4 cell count < 200 cells/μl, the SVM model had the best performance for predicting the CD4/CD8 ratio, while the CD4/CD8 ratio was best predicted by the RF model in patients with a CD4 cell count ≥ 200 cells/μl. Conclusion By the incorporation of clinical indicators in SVM, RF, and MLP machine learning models, the immune function and recuperation of HIV/AIDS patients can be predicted and evaluated, thereby better guiding clinical treatment.

Complement factor B (CFB) serves a pivotal role in the alternative signaling pathway of the complement system and exerts a key role in the labelling of target particles, resulting from effective clearance of the target. The present study aimed to investigate the association between low expression levels of CFB and the clinical features and survival status of patients with lung adenocarcinoma (LUAD). Patient data were based on RNA-sequencing and clinical data from The Cancer Genome Atlas database. All patients were divided into two groups based on the median expression of CFB. Kaplan-Meier curve and univariate Cox regression analyses were used to investigate the association between CFB and survival status. Gene set enrichment analysis was used to examine the effects of CFB expression on signaling pathway impairment. Furthermore, reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to verify the relative expression levels of CFB in LUAD tissues. The data revealed that residual tumor classification, Karnofsky performance score and cancer stage were associated with overall survival, and that Karnofsky performance score and stage were associated with disease-free survival. The results demonstrated that high expression levels of CFB were associated with increased patient overall and disease-free survival according to both continuous and categorical models. The results of multivariate analysis identified that high expression levels of CFB were associated with increased overall and disease-free survival according to both the continuous model [hazard ratio (HR), 0.48; 95% confidence interval (95% CI), 0.25-0.93; P=0.029 for overall survival; HR, 0.29; 95% CI, 0.15-0.59; P=0.001 for disease-free survival] and the categorical model (HR, 0.46; 95% CI, 0.22-0.93; P=0.031 for overall survival; HR, 0.25; 95% CI, 0.12-0.55; P=0.001 for disease-free survival) after adjusting for corresponding covariates (residual tumour classification, Karnofsky performance score and stage). Furthermore, the results of both RT-qPCR and western blotting indicated that the relative mRNA and protein expression levels of CFB in lung tumor tissues were downregulated compared with those in adjacent non-tumor tissues. Collectively, the present results suggested that CFB expression was an independent predictor of overall and disease-free survival in patients with LUAD.

Background: Epilepsy is a debilitating brain disease with complex inheritance and frequent treatment resistance. However, the role of STX1B single nucleotide polymorphisms (SNPs) in epilepsy treatment remains unknown.Objective: This study aimed to explore the genetic association of STX1B SNPs with treatment response in patients with epilepsy in a Han Chinese population.Methods: We first examined the associations between STX1B SNPs and epilepsy in 1000 Han Chinese and the associations between STX1B SNPs and drug-resistant epilepsy in 450 subjects. Expression quantitative trait loci analysis was then conducted using 16 drug-resistant epileptic brain tissue samples and results from the BrainCloud database (http://eqtl.brainseq.org).Results: The allelic frequencies of rs140820592 were different between the epilepsy and control groups (p = 0.002) after Bonferroni correction. The rs140820592 was associated with significantly lower epilepsy risk among 1,000 subjects in the dominant model after adjusting for gender and age and Bonferroni correction (OR = 0.542, 95%CI = 0.358–0.819, p = 0.004). The rs140820592 also conferred significantly lower risk of drug-resistant epilepsy among 450 subjects using the same dominant model after adjusting for gender and age and Bonferroni correction (OR = 0.260, 95%CI = 0.103–0.653, p = 0.004). Expression quantitative trait loci analysis revealed that rs140820592 was associated with STX1B expression level in drug-resistant epileptic brain tissues (p = 0.012), and this result was further verified in the BrainCloud database (http://eqtl.brainseq.org) (p = 2.3214 × 10–5).Conclusion: The STX1B rs140820592 may influence the risks of epilepsy and drug-resistant epilepsy by regulating STX1B expression in brain tissues.

BackgroundEvidence from multiple studies suggests metabolic abnormalities play an important role in lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. The present study aimed to explore differences in the global metabolic response between male and female patients in LUAD and to identify the metabolic genes associated with lung cancer susceptibility.MethodsTranscriptome and clinical LUAD data were acquired from The Cancer Genome Atlas (TCGA) database. Information on metabolic genes and metabolic subsystems were collected from the Recon3D human metabolic model. Two validation datasets (GSE68465 and GSE72094) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis, gene set enrichment analysis and protein-protein interaction networks were used to identified key metabolic pathways and genes. Functional experiments were used to verify the effects of genes on proliferation, migration, and invasion in lung cancer cells in vitro.ResultsSamples of tumors and adjacent non-tumor tissue from both male and female patients exhibited distinct global patterns of gene expression. In addition, we found large differences in methionine and cysteine metabolism, pyruvate metabolism, cholesterol metabolism, nicotinamide adenine dinucleotide (NAD) metabolism, and nuclear transport between male and female LUAD patients. We identified 34 metabolic genes associated with lung cancer susceptibility in males and 15 in females. Most of the metabolic cancer-susceptibility genes had high prediction accuracy for lung cancer (AUC > 0.9). Furthermore, both bioinformatics analysis and experimental results showed that TAOK2 was down-regulated and ASAH1 was up-regulated in male tumor tissue and female tumor tissue in LUAD. Functional experiments showed that inhibiting ASAH1 suppressed the proliferation, migration, and invasion of lung cancer cells.ConclusionsMetabolic cancer-susceptibility genes may be used alone or in combination as diagnostic markers for LUAD. Further studies are required to elucidate the functions of these genes in LUAD.

BACKGROUND:Prior to being spread throughout broader China, multiple human immunodeficiency virus (HIV)-1 genotypes were originally discovered in the Yunnan Province. As the HIV-1 epidemic continues its spread in Yunnan, knowledge of the influence of gender, age, and ethnicity to instances of HIV reservoirs will benefit monitoring the spread of HIV.METHODS:The degree to which T cells are depleted during an HIV infection depends on the levels of immune activation. T-cell subsets were assessed in newly-diagnosed HIV/AIDS patients in Yunnan, and the influence of age, gender, and ethnicity were investigated. Patients that were newly diagnosed with the HIV-infection between the years 2015 and 2018 at the First Affiliated Hospital of Kunming Medical College were selected for this study (N = 408). The lymphocyte levels and T cell subsets were retrospectively measured in whole blood samples by FACS analysis.RESULTS:The median CD4 count was 224 ± 191 cells/μl. Significantly higher mean frequencies and absolute numbers were observed in CD3+, CD3+CD4+, CD3+CD8+, CD45+, and CD3+CD4+/CD45+ in females compared to males. Han patients showed a higher total number of CD3+T cells and the ratio of CD3+ /CD45+ cells compared to any other ethnic minority (P < 0.001). The numbers of CD3+ T-cells, CD3+CD8+ T cells, and CD45+ T cells were highest in the age group ≥ 60. Significant differences were observed in the counts of CD3+, CD3+CD8+, and CD45+ cells and the ratio of CD3+/CD45+ and CD3+CD4+/CD45+ cells between the ≤ 29 and 30-59 age groups.CONCLUSION:This study has revealed that low levels of CD4+ T cells can be observed in newly-diagnosed HIV/AIDS patients in the Yunnan province. It has also been demonstrated that gender, age, and ethnicity have a significant association with the ratio of T-cell subsets that may contribute to virus progression and disease prognosis in individuals belonging to certain subsets of the population. This study has highlighted the importance of HIV/AIDS screening in at-risk populations to ensure timely and adequate clinical management in Yunnan.