Role of Platelet/Lymphocyte, Neutrophil/Lymphocyte, and Interleukin-37/Interleukin-17 Ratios in the Occurrence and Treatment of Rheumatoid Arthritis.

This study was designed to investigate the correlation of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and interleukin (IL)-37/IL-17 ratio with the incidence/treatment of rheumatoid arthritis (RA). Firstly, fifty-eight patients with RA treated at the first affiliated hospital of Xinjiang Medical University from January 2018 to January 2019 were selected as the RA group; forty-nine healthy volunteers were enrolled in the control group. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs). Next, the NLR, PLR, IL-37, IL-17 and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) were deleted in two groups. Subsequently, Spearman correlation analysis was adopted for the correlations of various indicators before and after treatment in two groups. According to the analysis results, the levels of NLR, PLR, IL-37, and IL-17 before treatment in the RA group were higher than those in the control group (P < .05), but the difference in the IL-37/IL-17 level between the two groups was not significant (P > .05). After treatment, NLR, PLR, and IL-37/IL-17 levels were significantly reduced in RA patients (P < .05). NLR and PLR were significantly positively correlated with DAS28-ESR, ESR and C-reactive protein (CRP), of which represented the disease activity of RA. NLP was strongly correlated with IL-37/IL-17. Collectively, NLR, PLR, IL-37, and IL-17 are closely related to the occurrence of RA. In addition, NLR and IL-37/IL-17 are more suitable than PLR in reflecting the therapeutic effect. Therefore, IL-37/IL-17 can be considered as a new indicator for reflecting the treatment effectiveness of RA.

Comparison of morbidity and mortality after radical cystectomy between individuals older and younger than 80 years: a systematic review and meta-analysis.

OBJECTIVE: To compare outcomes related to survival and post-operative complications in individuals older and younger than 80 years with bladder cancer undergoing radical cystectomy (RC). METHODS: We conducted a systematic search using three large databases: PubMed, EMBASE, and Scopus. We included observational studies comparing outcomes between individuals older than 80 years and younger patients undergoing RC. The outcomes of interest included overall survival, disease-specific survival, progression-free survival, and risk of post-operative complications. We applied a random effects model for the analysis and reported pooled effect sizes as odds ratios (ORs) or hazards ratios (HRs) along with 95% confidence intervals. RESULTS: We analyzed 21 studies. Our results show that individuals older than 80 years had higher risks of mortality at 30 days (OR 2.82; 95% CI 1.97, 4.04), 90 days (OR 3.34; 95% CI 2.61, 4.27), 12 months (HR 3.03; 95% CI 2.64, 3.49), and 24 months (HR 3.54; 95% CI 2.27, 5.50) of the post-operative follow-up than younger individuals. In addition, individuals older than 80 years also had poor 5-year survivals (HR 2.17; 95% CI 1.64, 2.88), an increased risk of 5-year cancer-specific mortality (HR 1.58; 95% CI 1.24, 2.03), poor 5-year recurrence free survivals (HR 1.49; 95% CI 1.07, 2.08), and high complications risks (OR 1.20; 95% CI 1.02, 1.42) when compared to younger patients. CONCLUSION: Individuals older than 80 years undergoing RC are likely to have poor survival-related outcomes and increased complications risks. Pre-planned comprehensive geriatric assessments (CGAs) may be needed to offer better peri- and post-operative care to improve the outcomes in this patient population.

Wound infection in robotic-assisted radical prostatectomy compared with retropubic radical prostate surgery: A meta-analysis.

A meta-analysis investigation was executed to measure the wound infection (WI) in robotic-assisted radical prostatectomy (RRP) compared with retropubic radical prostate surgery (RRPS). A comprehensive literature investigation till February 2023 was applied, and 1197 interrelated investigations were reviewed. The 19 chosen investigations enclosed 107 153 individuals with prostate cancer (PC) at the starting point. 72 008 of them were utilising RRP, and 35 145 were utilising RRPS. Odds ratio (OR) in addition to 95% confidence intervals (CIs) was utilised to compute the value of the WI in RRP compared with RRPS by the dichotomous approaches and a fixed or random model. RRP had significantly lower surgical site wound infection (SSWI) (OR, 0.33; 95% CI, 0.21-0.52, P < .001) and infected lymphoceles (ILs) (OR, 0.45; 95% CI, 0.22-0.92, P = .03) compared with RRPS in individuals with PC. RRP had significantly lower SSWI and ILs compared with RRPS in individuals with PC. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.

Screening of renal clear cell carcinoma prognostic marker genes based on TCGA and GTEx chip data and construction of transcription factor-related regulatory networks.

This study aimed to identify prognostic marker genes for renal clear cell carcinoma (RCCC) and construct a regulatory network of transcription factors and prognostic marker genes. Three hundred eighty-six genes were significantly differentially expressed in RCCC, with functional enrichment analysis suggesting a relationship between these genes and kidney function and development. Cox and Lasso regression analyses revealed 10 prognostic marker genes (RNASET2, MSC, DPEP1, FGF1, ATP1A1, CLDN10, PLG, SLC44A1, PCSK1N, and LGI4) that accurately predicted RCCC patient prognosis. Upstream transcription factors of these genes were also identified, and in vitro experiments suggested that ATP1A1 may play a key role in RCCC patient prognosis. The findings of this study provide important insights into the molecular mechanisms of RCCC and may have implications for personalized treatment strategies.

Saussurea involucrata oral liquid regulates gut microbiota and serum metabolism during alleviation of collagen-induced arthritis in rats.

Saussurea involucrata oral liquid (SIOL) can clinically relieve symptoms, such as joint pain and swelling, and morning stiffness, in patients with rheumatoid arthritis (RA). However, the mechanism of action remains unclear. This study used a combination of gut microbiota and serum metabolomics analysis to investigate the effects and potential mechanisms of SIOL intervention on rats with RA induced by type II bovine collagen and Freund's complete adjuvant. Results showed that SIOL treatment consequently improved the degree of ankle joint swelling, joint histopathological changes, joint pathological score, and expression of serum-related inflammatory cytokines (interleukin (IL)-1ß, IL-4, IL-6, IL-10, and tumor necrosis factor-α) in RA model rats. 16 S rRNA sequencing results showed that SIOL increased the relative richness of the Lactobacillus and Bacteroides genus and decreased the relative richness of Romboutsia, Alloprevotella, Blautia, and Helicobacter genus. Serum nontargeted metabolomic results indicated that SIOL could regulate metabolites related to metabolic pathways, such as glycine, serine, threonine, galactose, cysteine, and methionine metabolism. Spearman correlation analysis showed that the regulatory effects of SIOL on the tricarboxylic acid (TCA) cycle, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism pathways were correlated with changes in the richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus in the gut microbiome. In conclusion, this study revealed the ameliorative effects of SIOL on RA and suggested that the therapeutic effects of SIOL on RA may be related to the regulation of the community richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus, thereby improving the TCA cycle; phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism-related pathways.

Understanding controversies in the α-ω and ω-ß phase transformations of zirconium from nonhydrostatic thermodynamics.

Significant debate has been noted in the α-ω and ω-ß phase transformations of zirconium. The initial pressure of the α-to-ω transformation at room temperature has been reported to vary from 0.25 to 7.0 GPa, while the hydrostatic transformation is believed to occur at approximately 2.2 GPa. Shear stress is commonly considered as a key factor leading to the discrepancy. However, the principal mechanisms previously proposed concluded that the phase transformation pressure would be decreased in the presence of shear stress. The experimental results of the α-ω transformation in zirconium are contrary to this conclusion. In the ω-ß phase diagram of zirconium, the dT/dP along the phase boundary near the α-ω-ß triple-point was reported to be either positive or negative, but no theoretical explanation, especially a quantitative one, has been proposed. This article aimed to quantitatively investigate and explain the controversies reported in the α-ω and ω-ß phase transformations of zirconium by applying a new nonhydrostatic thermodynamic formalism for solid medium, which has recently been proposed and is capable of quantitatively estimating the impact of shear stress on phase transformations in solids.

MiR-212-3p inhibits cell proliferation and promotes apoptosis by targeting nuclear factor IA in bladder cancer.

Accumulating evidence suggest that microRNAs play crucial roles in the development and progression of bladder cancer (BC). Here, we found that miR-212-3p was significantly down-regulated and negatively correlated with nuclear factor IA (NFIA) in human BC tissues. Bioinformatics analysis predicted that NFIA was a target gene of miR-212-3p. Then BC cell lines, T24 and J82 cells were transfected with miR-212-3p mimics or siNFIA to obtain miR-212-3p overexpression or NFIA knockdown cell lines, respectively. Quantitative real-time PCR was used to determine the expression of miR-212-3p and NFIA. Western blot analysis was utilized to detect NFIA expression. MTT assay showed either miR-212-3 overexpression or NFIA knockdown significantly inhibited the BC cell proliferation. Double staining with Annexin V-APC and 7-AAD showed the total number of apoptotic BC cells were remarkably increased after miR-212-3p overexpression or NFIA knockdown. Collectively, our results indicated that miR-212-3p targeting NFIA might serve as a promising target for BC.

Royleanone diterpenoid exhibits potent anticancer effects in LNCaP human prostate carcinoma cells by inducing mitochondrial mediated apoptosis, cell cycle arrest, suppression of cell migration and downregulation of mTOR/PI3K/AKT signalling pathway.

PURPOSE: Prostate cancer is a deadly malignancy and is responsible for significant cancer-related mortality in men. The incidence of prostate cancer is continuously increasing across the globe and the existing treatment options for this disease are limited and associated with a lot of side effects. Therefore there is an urgent need to identify novel and efficient therapeutic agents for the management of prostate cancer. In the current study we evaluated the anticancer activity of royleanone diterpenoid against prostate cancer LNCaP cell line. METHODS: The anticancer activity of royleanone was determined by CCK8 assay. Apoptosis was detected by acridine orange and ethidium bromide as well as by annexin V/ propidium iodide (PI) staining. Mitochondrial membrane potential (MMP) and cell cycle analysis were investigated by flow cytometry and protein expression by western blotting. RESULTS: The results showed that royleanone exerts potent anticancer activity on LNCaP prostate cancer cells with an IC50 of 12.5 µM at 48 hrs of incubation. The anticancer activity of royleanone was due to induction of cell cycle arrest and mitochondrial-mediated apoptosis. Moreover, royleanone could also suppress the cell migration potential and inhibited the mTOR/ PI3/AKT signalling pathway in LNCaP prostate cancer cells. CONCLUSIONS: Taken together, we propose that royleanone could prove to be an important anticancer lead molecule for the treatment and overall management of prostate cancer, provided further in vivo studies are carried out.

Phase I study of gemcitabine-cisplatin versus pemetrexed cisplatin for patients with advanced or metastatic bladder cancer.

PURPOSE: The present study aimed to compare the chemotherapeutic regimens of gemcitabine plus cisplatin (GC) vs pemetrexed plus cisplatin (PC) in bladder cancer (BC) with vascular invasion and/or distant metastasis. METHODS: From January 2010 to January 2017, 53 patients with advanced or metastatic BC were included and randomly divided into two groups. Patients in the GC group were administered 1,000 mg/m2 gemcitabine on day 1 and 15 and 70 mg/m2 cisplatin on day 1 as an IV infusion. Patients in the PC group were administered 500 mg/m2 pemetrexed on day 1 and 15 and 70 mg/m2 cisplatin on day 1 as an IV infusion. The two regimens were repeated every 28 days. Patients were treated for about 4-6 cycles until the occurrence of severe toxicity or patient refusal. RESULTS: The median overall survival (OS) and the median progression-free survival (PFS) in the GC group were significantly higher than that in the PC group (OS: p=0.033 and PFS: p=0.039, respectively). Besides, the response rates and disease control were obviously higher in the GC group (68% and 86%, respectively) compared to the PC group (44% and 56%, respectively), although without statistical significance. Regarding toxicity, higher rates of neutropenia and nausea in the PC group were noted, while thrombocytopenia was more frequent in the GC group. CONCLUSIONS: The gemcitabine plus cisplatin combination was more effective and well tolerated in patients with advanced or metastatic BC compared to the pemetrexed plus cisplatin regimen.

Identification of prognostic genes in kidney renal clear cell carcinoma by RNA­seq data analysis.

The present study aimed to analyze RNA-seq data of kidney renal clear cell carcinoma (KIRC) to identify prognostic genes. RNA­seq data were downloaded from The Cancer Genome Atlas. Feature genes with a coefficient of variation (CV) >0.5 were selected using the genefilter package in R. Gene co­expression networks were constructed with the WGCNA package. Cox regression analysis was performed using the survive package. Furthermore, a functional enrichment analysis was conducted using Database for Annotation, Visualization and Integrated Discovery tools. A total of 533 KIRC samples were collected, from which 6,758 feature genes with a CV >0.5 were obtained for further analysis. The KIRC samples were divided into two sets: The training set (n=319 samples) and the validation set (n=214 samples). Subsequently, gene co­expression networks were constructed for the two sets. A total of 12 modules were identified, and the green module was significantly associated with survival time. Genes from the green module were revealed to be implicated in the cell cycle and p53 signaling pathway. In addition, a total of 11 hub genes were revealed, and 10 of them (CCNA2, CDC20, CDCA8, GTSE1, KIF23, KIF2C, KIF4A, MELK, TOP2A and TPX2) were validated as possessing prognostic value, as determined by conducting a survival analysis on another gene expression dataset. In conclusion, a total of 10 prognostic genes were identified in KIRC. These findings may help to advance the understanding of this disease, and may also provide potential biomarkers for therapeutic development.

Trp358 is a key residue for the multiple catalytic activities of multifunctional amylase OPMA-N from Bacillus sp. ZW2531-1.

The oligosaccharide-producing multifunctional amylase-N (OPMA-N) is a novel multifunctional amylase and exhibits both hydrolytic and transglycosyl activities, but the molecular mechanism for its multiple catalytic activities is still unknown. Our research investigates the possible catalytic roles of a Trp residue in OPMA-N (Trp358) which is not only near the catalytic site Glu356 but also highly conserved in glycoside hydrolase subfamily 20 (the neopullulanase subfamily). Site-directed mutageneses at this site reveal that the size and charge of the occupying amino acid directly affect substrate binding, orientation of other crucial catalytic residues, the catalytic specificity, the oligomer formation, as well as the thermal stability of the enzyme. These findings may be useful in elucidating the different mechanisms of the multiple catalytic activities of multifunctional amylase OPMA-N and hence for developing an improved multifunctional amylase for the preparation of isomaltooligosaccharides.