A novel amino acid metabolism-related gene signature to predict the overall survival of esophageal squamous cell carcinoma patients.

Background: Esophageal squamous cell carcinoma (ESCC) has a poor early detection rate, prognosis, and survival rate. Effective prognostic markers are urgently needed to assist in the prediction of ESCC treatment outcomes. There is accumulating evidence of a strong relationship between cancer cell growth and amino acid metabolism. This study aims to determine the relationship between amino acid metabolism and ESCC prognosis. Methods: This study comprehensively evaluates the association between amino acid metabolism-related gene (AAMRG) expression profiles and the prognosis of ESCC patients based on data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify the expression of prognosis-related genes. Results: A univariate Cox regression analysis of TCGA data identified 18 prognosis-related AAMRGs. The gene expression profiles of 90 ESCC tumor and normal tissues were obtained from the GSE20347 and GSE67269 datasets. Two differently expressed genes (DEGs) were considered as ESCC prognosis-related genes; and they were branched-chain amino acid transaminase 1 (BCAT1) and methylmalonic aciduria and homocystinuria type C protein (MMACHC). These two AAMRGs were used to develop a novel AAMRG-related gene signature to predict 1- and 2-year prognostic risk in ESCC patients. Both BCAT1 and MMACHC expression were verified by RT-qPCR. A prognostic nomogram that incorporated clinical factors and BCAT1 and MMACHC gene expression was constructed, and the calibration plots showed that it had good prognostic performance. Conclusions: The AAMRG signature established in our study is efficient and could be used in clinical settings to predict the early prognosis of ESCC patients.

Clinical effect of anlotinib in combination with docetaxel in treating advanced non-small cell lung cancer.

This study aimed to explore the clinical performance of anlotinib in combination with docetaxel in treating advanced non-small cell lung cancer (NSCLC). One hundred advanced NSCLC patients admitted to our hospital from January 2019 to December 2022 were retrospectively chosen to be the study objects, and separated into observation group (OG, n=50) and control group (CG, n=50) based on the different drugs used. The CG was given docetaxel injection. The OG was treated with anlotinib hydrochloride capsule combined with docetaxel injection. The clinical effective rate, levels of serum tumor markers, quality of life and occurrence of adverse reactions in both groups were compared. The total clinical effective rate in the OG presented elevated relative to the CG (P<0.01). After treatment, CEA, CA125, SCC and CYFRA21-1 levels in both groups were decreased in both groups, and those in the OG presented lower relative to the CG (P<0.05). After treatment, KPS score in both groups was increased in both groups and that in the OG presented higher relative to the CG (P<0.05). No difference was seen in the occurrence of adverse reactions between 2 groups (P=0.35). In treating advanced NSCLC patients, anlotinib combined with docetaxel can promote efficacy to a certain extent, effectively regulate the level of serum tumor markers, promote the quality of life of patients, and will not significantly affect clinical safety.

miR­93­5p regulates the occurrence and development of esophageal carcinoma epithelial cells by targeting TGFßR2.

Emerging studies have indicated that the dysregulation of microRNAs (miRNAs or miRs) plays a vital role in the development and metastasis of tumors. However, the role of miR­93­5p in esophageal carcinoma (EC) has not been extensively reported. The present study thus focused on the role of miR­93­5p and its downstream target in the occurrence and development of EC. Firstly, miRNA expression profiles associated with EC were accessed from the TCGA_ESCA dataset and analyzed. Subsequently, the expression patterns of miR­93­5p and TGFßR2 were characterized in the human esophageal cell line, Het­1A, and the human EC cell lines, TE­1, Eca­109 and EC9706, by RT­qPCR and western blot analysis. WST­1 assay, flow cytometry, Transwell assay, wound healing assay and bioinformatics analysis were used to explore their functions in EC cells. Finally, a dual­luciferase reporter assay was employed to determine the targeted association between miR­93­5p and TGFßR2. The results revealed that the expression of miR­93­5p was markedly higher in EC cell lines compared with that in the normal cell line. The overexpression of miR­93­5p facilitated cell proliferation, migration and invasion, and inhibited cell apoptosis. Additionally, TGFßR2 was identified as a functional target of miR­93­5p in EC cells, as judged by a series of in vitro experiments. Furthermore, it was found that the simultaneous overexpression of miR­93­5p and TGFßR2 almost had no effect on the biological behaviors of EC cells. On the whole, the present study demonstrates that miR­93­5p promotes the proliferation, migration and invasion, and inhibits the apoptosis of EC cells by targeting TGFßR2.

Physicochemical Factors Affecting Microbiota Dynamics During Traditional Solid-State Fermentation of Chinese Strong-Flavor Baijiu.

Spontaneous solid-state fermentation (SSF) of Chinese Baijiu involves diverse microbes from Daqu and pit mud (PM). Given that the transfer of interphase microflora during the fermentation is a continuous and dynamic process, longitudinal studies are essential to provide ecological insights into community stability and response to consecutive disturbances in the process. In this context, this study aimed to generate a comprehensive longitudinal characterization of the microbiota during the fermentation processes of Chinese strong-flavor Baijiu (CSFB) differing in cellar ages with consideration for potential relation to physicochemical variables. The microecology variations observed during the 6-years cellar SSF (SCSSF) and 30-years cellar SSF (TCSSF) processes reveal that fungal composition contributes to a larger extent than bacterial composition to such variations. Orders of Lactobacillales, Anaerolineales, Enterobacteriales, Bacillales, Eurotiales, and Saccharomycetales dominated (average relative abundances >10%) the microbiota in both SCSSF and TCSSF processes but with a different percentage in the operational taxonomic unit (out) abundances. Compared with the SCSSF process, TCSSF possessed slower microbial succession rates, which were in accordance with the profile of physicochemical properties. From a network perspective, the microbial community structure observed in the TCSSF processes was more stable than that in the SCSSF. This may benefit from the milder physicochemical conditions of the TCSSF processes, especially the temperature, which is also more beneficial to the growth of some groups that have negative effects on fermentation, such as Staphylococcus, Pseudomonas, and Acinetobacter.

Isolation and diversity of sediment bacteria in the hypersaline aiding lake, China.

Halophiles are relatively unexplored as potential sources of novel species. However, little is known about the culturable bacterial diversity thrive in hypersaline lakes. In this work, a total of 343 bacteria from sediment samples of Aiding Lake, China, were isolated using nine different media supplemented with 5% or 15% (w/v) NaCl. The number of species and genera of bacteria recovered from the different media varied, indicating the need to optimize the isolation conditions. The results showed an unexpected level of bacterial diversity, with four phyla (Actinobacteria, Firmicutes, Proteobacteria, and Rhodothermaeota), fourteen orders (Actinopolysporales, Alteromonadales, Bacillales, Balneolales, Chromatiales, Glycomycetales, Jiangellales, Micrococcales, Micromonosporales, Oceanospirillales, Pseudonocardiales, Rhizobiales, Streptomycetales, and Streptosporangiales), including 17 families, 43 genera (including two novel genera), and 71 species (including four novel species). The predominant phyla included Actinobacteria and Firmicutes and the predominant genera included Actinopolyspora, Gracilibacillus, Halomonas, Nocardiopsis, and Streptomyces. To our knowledge, this is the first time that members of phylum Rhodothermaeota were identified in sediment samples from a salt lake.

Efficacy and safety of everolimus treatment on liver transplant recipients: A meta-analysis.

BACKGROUND: Everolimus is an effective immunosuppressant in organ transplantation without impaired renal function. The present study aimed to evaluate the efficacy and safety of everolimus therapy in liver transplant recipients. MATERIALS AND METHODS: A systematic literature search was conducted to identify the eligible studies. The quality of the included studies was assessed. The outcomes of interest were biopsy-proven acute rejection (BPAR), graft loss, death, renal function and adverse events. RESULTS: Eight trials involving 1570 participants were included. Compared to the standard exposure to calcineurin inhibitors (CNIs), the incidences of BPAR, graft loss and death were not increased in the everolimus combined with reduced CNIs group. The renal function was significantly improved after everolimus combined with reduced CNI therapy, and the glomerular filtration rate (GFR) was estimated to be elevated by 5.59 (95% CI: 2.17-9.01, P = .001) as compared to the standard exposure to CNIs. The risk of any adverse event was increased by everolimus combined with reduced CNI therapy (RR = 1.22, 95% CI: 1.04-1.42, P = .01) as compared to the standard exposure to CNIs. The likelihood of infection was not associated with the regimen. Any publication bias was not identified. CONCLUSIONS: Although everolimus combined with reduced CNI therapy significantly improved the renal function in liver transplant recipients, it did not influence the incidence of BPAR, graft loss and death. This regimen might be associated with an increased risk of adverse events, which needs to be elucidated further.

Accelerated and Severe Lupus Nephritis Benefits From M1, an Active Metabolite of Ginsenoside, by Regulating NLRP3 Inflammasome and T Cell Functions in Mice.

Chinese herbal medicines used in combination have long-term been shown to be mild remedies with "integrated effects." However, our study provides the first demonstration that M1, an active metabolite of ginsenoside, exerted its dramatic therapeutic effects on accelerated and severe lupus nephritis (ASLN) mice, featuring acute renal function impairment, heavy proteinuria, high serum levels of anti-dsDNA, and high-grade, diffuse proliferative renal lesions. In the present study, NZB/WF1 mice were given injections of lipopolysaccharide to induce the ASLN model. M1 (30 mg/kg) was then administered to the mice by gavage daily, and the mice were sacrificed on week 3 and week 5 after the induction of disease. To identify the potential mechanism of action for the pure compound, levels of NLRP3 inflammasome activation in bone marrow-derived dendritic cells (BMDCs), podocytes and macrophages, and antigen-specific T cell activation in BMDCs were determined in addition to mechanistic experiments in vivo. Treatment with M1 dramatically improved renal function, albuminuria and renal lesions and reduced serum levels of anti-dsDNA in the ASLN mice. These beneficial effects with M1 treatment involved the following cellular and molecular mechanistic events: [1] inhibition of NLRP3 inflammasome associated with autophagy induction, [2] modulation of T help cell activation, and [3] induction of regulatory T cell differentiation. M1 improved the ASLN mice by blunting NLRP3 inflammasome activation and differentially regulating T cell functions, and the results support M1 as a new therapeutic candidate for LN patients with a status of abrupt transformation of lower-grade (mesangial) to higher-grade (diffuse proliferative) nephritis.

Correlation between SNPs in CDH1 and gastric cancer in Chinese population.

BACKGROUND: Many recent studies revealed that the single nucleotide polymorphisms have considerable effects on the susceptibility of cancer, such as prostate cancer, lung cancer and gastric cancer. The E-cadherin, a calcium-dependent transmembrane glycoprotein encoded by CDH1 gene, is critical for epithelial construction, intercellular adhesion and cell migration. Some associations have been reported between single nucleotide polymorphisms and gastric cancer in the Chinese population. OBJECTIVE: To investigate whether the single nucleotide polymorphism in CDH1 gene is associated with the susceptibility of gastric cancer in the Chinese population. MATERIAL AND METHODS: The genotypes of 5 known single nucleotide polymorphisms (rs33935154, rs121964871, rs121964874, rs121964875, rs121964876) were determined in 359 gastric cancer patients and 368 healthy controls. High resolution melting curve detection and sequencing analysis were used in the present study. RESULTS: There is a statistical significance in the rs121964871 C>G polymorphism between gastric cancer patients and healthy controls (OR=1.769, 95%CI: 1.051-2.976). Elderly male individuals (>50 years of age) carrying this risk factor may be more susceptible to gastric cancer. CONCLUSIONS: The results indicated that the rs121964871 C>G polymorphism is associated with the susceptibility of gastric cancer in the Chinese population, with some age and sex-dependent tendencies observed.

Differences of plasma IL-1 and TNF-α in healthy Chinese Population.

Pleiotropic proinflammatory cytokines, interleukin- 1 (IL-1) and tumor necrosis factor-α (TNF-α), involved in the regulations of various immune responses, inflammatory processes and hematopoiesis. In the present study, the expression levels of IL-1 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). Following the cytokine blockade as a successful clinical therapy for autoimmune diseases such as rheumatoid arthritis, the patients are more susceptible to a variety of opportunistic infections. IL-1 and TNF-α may be useful predictive biomarkers of diseases and offer potential targets for therapeutic intervention of inflammatory diseases. However, our results showed that the plasma IL-1 level was significantly higher in women compared to men (69.5 ± 19.8 pg/ml in men and 80.1 ± 19.5 pg/ml in women, respectively); the plasma levels of TNF-α were higher in men than women (20.8 ± 4.9 pg/ml and 18.7 ± 7.1 pg/ml, respectively). The significant gender difference of plasma interleukin-1 (IL-1) and TNF-α levels present in healthy adults in Jiangsu Province, China (P=0.002 and P=0.015, respectively), and may be as a hint for sex differences of susceptibility to many diseases and elementary immune response.

Cryptosporidium andersoni as a novel predominant Cryptosporidium species in outpatients with diarrhea in Jiangsu Province, China.

BACKGROUND: Cryptosporidium hominis and C. parvum are usually considered to be the major pathogens responsible for human cryptosporidiosis. However, there have been few studies regarding the molecular epidemiology of Cryptosporidium in human infections in China. Here we investigated Cryptosporidium infection in patients with diarrhea, in Danyang Hospital of Jiangsu Province, China, at the genotype level. METHODS: A total of 232 stool specimens were collected from outpatients with diarrhea in Danyang Hospital of Jiangsu Province, China, from February 2012 to January 2013. Each specimen was stained from direct fecal smears and examined for Cryptosporidium using modified acid fast staining and microscopy. Moreover, genomic DNA of each fecal sample was screened for the presence of Cryptosporidium with nested PCR, which was genotyped by analyzing the DNA sequences of small subunit rRNA (SSU rRNA). RESULTS: The average infection rate of Cryptosporidium was 1.3% (3/232) by microscopy and subjected to PCR amplification of the SSU rRNA gene of Cryptosporidium, with 9.91% (23/232) being positive for Cryptosporidium with a significant peak in autumn. Based on the SSU rRNA gene, two Cryptosporidium spp. were identified, including C. andersoni (n =21) and C. hominis (n =2). Two types of C. andersoni, designated as A370 + and A370 - , were found in the SSU rRNA gene in our present study, which was 100% homologous to C. andersoni infections derived from dairy calves and goats, respectively. The clinical questionnaires showed no significant difference in age, gender and frequency of diarrhea, but duration of diarrhea was shorter for C. andersoni than that of C. hominis (mean, 2 vs. 4 days; p <0.01). CONCLUSIONS: C. andersoni is the dominant species in Danyang City of Jiangsu Province. The fact that SSU rRNA sequences of C. andersoni obtained from human stools exhibited 100% homologous to those derived from dairy calves and goats supported that C. andersoni infection might be attributable to animal origin. The difference in the duration of diarrhea of C. andersoni and C. hominis indicated that different Cryptosporidium species might cause different clinical manifestations.

Apo E gene polymorphism affects development of type 2 diabetic nephropathy in Asian populations, especially in East Asians: an updated meta-analysis.

BACKGROUND: Many studies have determined the correlation between the Apolipoprotein E (APO E) gene polymorphisms and diabetic nephropathy, but their results are inconclusive. MATERIAL/METHODS: With the aim to confirm this correlation, we performed a meta-analysis of 16 studies. The dichotomous data are presented as the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: The results of our study indicate that APO ε2 allele among the pooled Asian populations were more likely to show high risk of DN development (2 allele vs. ε3 allele: pooled OR =1.629, 95% CI=1.010-2.628, P=0.045). For further analysis, the APO e2 allele was associated with progress of DN in the group with duration >10 years, but not in the group with duration <10 years (ε2 allele vs. ε3 allele: pooled OR=1.920, 95% CI=1.338-2.754, P<0.001). The APO e2 polymorphism increased the susceptibility to DN in Asian population compared with healthy people (ε2 allele vs. ε3 allele: pooled OR=1.629, 95% CI=1.010-2.628, P=0.045). CONCLUSIONS: Development of DN is associated with APO E polymorphisms in Asian populations, especially in East Asians.