Restoring bone-fat equilibrium: Baicalin's impact on P38 MAPK pathway for treating diabetic osteoporosis.

Diabetes can lead to a disorder of bone-fat balance, a significant cause of osteoporosis due to changes in environmental factors. Baicalin (Bai), an active ingredient of Scutellaria baicalensis, has been confirmed to possess antioxidant, hypoglycemic, and anti-osteoporotic effects. However, a comprehensive understanding of Bai's influence on diabetic osteoporosis (DOP), including its effects and underlying mechanisms, remains elusive. This study investigated Bai's impact on the bone-fat equilibrium in rats with DOP. The results indicated that Bai alleviated bone damage in DOP by promoting osteogenesis and inhibiting adipogenesis. Concurrently, through bioinformatics analysis, it was suggested that Bai's mechanism of action might involve the P38-MAPK pathway. In vitro, Bai was found to enhance the development of bone marrow mesenchymal stem cells (BMSCs) towards osteogenic lineages while suppressing their differentiation towards adipogenic lineages. It was discovered that Bai's promotion of BMSC osteogenic differentiation depends on the P38-MAPK pathway. Additionally, the synergistic effect mediated by Bai and P38-MAPK inhibitor suppressed BMSC adipogenic differentiation. Our research indicates that the P38-MAPK pathway play a role in Bai's effects on the osteogenic-adipogenic differentiation of BMSCs, showcasing the potential for DOP treatment. This study highlights Bai's ability to regulate the equilibrium between bone and fat, presenting a novel approach to adressing DOP.

Characterization of a novel gammapartitivirus infecting the phytopathogenic fungus Pyricularia oryzae.

In this study, we identified a novel double-strand RNA (dsRNA) mycovirus in Pyricularia oryzae, designated "Magnaporthe oryzae partitivirus 4" (MoPV4). The genome of MoPV4 consists of a dsRNA-1 segment encoding an RNA-dependent RNA polymerase (RdRP) and a dsRNA-2 segment encoding a capsid protein (CP). Phylogenetic analysis indicated that MoPV4 belongs to the genus Gammapartitivirus within family Partitiviridae. The particles of MoPV4 are isometric with a diameter of about 32.4 nm. Three-dimensional structure predictions indicated that the RdRP of MoPV4 forms a classical right-handed conformation, while the CP has a reclining-V shape.

The anti-colorectal cancer effect and metabolites of Agrimonia pilosa Ledeb.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia pilosa Ledeb. (Rosaceae, A. pilosa) has been used in traditional medicine in China, Japan, Korea, and other Asian countries for treatment of acute and chronic enteritis and diarrhea. Secondary metabolites have been isolated and tested for biological activities. It remains unclear in terms of its potential components of anti-colorectal cancer properties. AIM OF THE STUDY: The study aimed to how extracts from A. pilosa and their components influenced tumor microenvironment and the colorectal tumor growth in vivo on AOM/DSS induced colorectal cancer mice, the metabolites of A. pilosa was also been studied. MATERIALS AND METHODS: Different methods have been used to extract different parts of A. pilosa. And the anti-proliferation effect of these extracts on colon cancer cells have been tested. The components of A. pilosa and its metabolites in vivo were analyzed by UPLC-QTOF-MS/MS. The anti-colorectal cancer (CRC) effects of A. pilosa and its components in vivo were studied on AOM/DSS induced CRC mice. The effects of constituents of A. pilosa on the composition of immune cells in tumor microenvironment (TME) were analyzed by flow cytometry. 16 S rDNA technology was used to analyze the effect of administration on the composition of intestinal microflora. Pathological section staining was used to compare the morphological changes and molecular expression of intestinal tissue in different groups. RESULTS: The constituent exists in root of A. pilosa showed the strongest anti-proliferation ability on colon cancer cells in vitro. The extract from the root of A. pilosa could attenuate the occurrence of colorectal tumors induced by AOM/DSS in a concentration-dependent manner. Administration of the extract from the root of A. pilosa could affect the proportion of γδT cells, tumor associated macrophages and myeloid derived suppressor cells in TME, increasing the proportion of anti-tumor immune cells and decrease the immunosuppressive cells in the TME to promote the anti-tumor immune response. The administration of the extract adjusted the composition of gut microbiota and its components Agrimoniin and Agrimonolide-6-o-glucoside showed the strongest anti-CRC effect in vivo with adjusting the gut microbiota differently. CONCLUSIONS: The extract from root of A. pilosa showed anti-colorectal cancer effects in vivo and in vitro, affecting the composition of gut microbiota and the anti-tumor immune response. Within all components of A. pilosa, Agrimoniin and Agrimonolide-6-o-glucoside showed remarkable anti-CRC efficiency in vivo and in vitro. Besides, the metabolites of extract from root of A. pilosa in gastrointestinal tract mainly composed of two parts: Agrimonolide-related metabolites and Urolithins. The extract from root of A. pilosa could contribute to potential drugs for assisting clinical anti-colon cancer therapy.

Genome characterization of a novel narnavirus infecting the plant-pathogenic fungus Ustilaginoidea virens.

Mycoviruses are viruses that infect fungi and oomycetes. They are widespread in all major groups of plant-pathogenic fungi and oomycetes. To date, only the full genome of dsRNA mycoviruses and the contigs of positive-sense single-stranded RNA (+ssRNA) mycoviruses have been reported in Ustilaginoidea virens, which is the notorious causal agent of rice false smut (RFS). Here, we report the molecular characterization of a novel +ssRNA mycovirus, Ustilaginoidea virens narnavirus 4 (UvNV4), isolated from U. virens strain Uv418. UvNV4 has a genome of 3,131 nucleotides (nt) and possesses an open reading frame (ORF) predicted to encode an RNA-dependent RNA polymerase (RdRp) of 1,017 amino acids (aa) sequence with a molecular mass of 116.6 kDa. BLASTp analysis revealed that the RdRp showed 50.34% aa sequence identity to that of the previously described Zhangzhou Narna tick virus 1. Phylogenetic analysis indicated that UvNV4 is closely related to members of the family Narnaviridae. Taken together, these results clearly demonstrate that UvNV4 is a novel +ssRNA virus infecting U. virens.

Prognostic impact of age in advanced non-small cell lung cancer patients undergoing first-line checkpoint inhibitor immunotherapy and chemotherapy treatment.

BACKGROUND: Research on the association between age and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy combined with chemotherapy as first-line setting is limited. The aim of study is to determine the influence of age on the progress-free survival (PFS) and overall survival (OS) in those patients after adjusting for potential confounders. METHODS: A total of 207 advanced NSCLC patients treated with immunotherapy combined with chemotherapy in the first-line treatment in Guangxi Medical University Cancer Hospital from March 10, 2019, to December 31, 2022, was retrospectively analyzed. χ2 (categorical variables) was used to analyze the differences among the different age groups. Cox regression and Kaplan-Meier analyses were used to assess the association between age and clinical outcomes. P values < 0.05 (two-sided) were considered statistically significant. RESULTS: The mean age of the cohort was 58.8 ± 10.3 years. The percentages of patients < 65, 65-69, 70-74, and ≥ 75 years were 66.7 %, 19.3 %, 9.2 % and 4.8 %, respectively. Compared to the aged < 65 years group, the HR for the risk of disease progression for each group are 0.67 (95 %CI = 0.40-1.12, P = 0.125), 0.66 (95 %CI = 0.31, 1.43, P = 0.298), and 2.27 (95 %CI = 0.80, 6.45, P = 0.124), respectively, with no significant differences in the results. And the HR for risk of death for the 65-69 years and 70-74 years groups was 1.16 (95 %CI = 0.64-2.08, P = 0.628) and 0.93 (95 %CI = 0.39-2.23, P = 0.879), respectively. The difference has no statistical significance. Whereas in patients aged ≥ 75, there is an increased risk of death after adjusted confounders with HR = 4.83 (95 %CI = 2.06-11.35). The difference was statistically significant (P < 0.001). Trend test indicates that with advancing age, the patient's risk of death increases (HR = 1.33, 95 % CI = 1.02-1.75, P = 0.034). CONCLUSION: Age may not be the primary factor influencing the efficacy of immunotherapy combined with chemotherapy, but particular attention should be given to the elderly population.

Computed tomography-guided microwave ablation for right middle lobe pulmonary nodules: a retrospective, single-center, case-control study.

PURPOSE: This retrospective, single-center, case-control study evaluated the safety and efficacy of Computed tomography (CT)-guided microwave ablation (MWA) for pulmonary nodules located in the right middle lobe (RML), a challenging location associated with a high frequency of complications. METHODS: Between May 2020 and April 2022, 71 patients with 71 RML pulmonary nodules underwent 71 MWA sessions. To comparison, 142 patients with 142 pulmonary nodules in non-RML were selected using propensity score matching. The technical success, technique efficacy, complications, and associated factors were analyzed. The duration of the procedure and post-ablation hospital stay were also recorded. RESULTS: Technical success was achieved in 100% of all patients. There were no significant differences in technique efficacy rates between the RML and non-RML groups (97.2% vs. 95.1%, p = 0.721). However, both major (47.9% vs. 19.7%, p < 0.001) and minor (26.8% vs. 11.3%, p = 0.004) pneumothorax were more common in the RML group than non-RML group. MWA for RML pulmonary nodules was identified as an independent risk factor for pneumothorax (p < 0.001). The duration of procedures (51.7 min vs. 35.3 min, p < 0.001) and post-ablation hospital stays (4.7 days vs. 2.8 days, p < 0.001) were longer in the RML group than non-RML group. CONCLUSIONS: CT-guided MWA for RML pulmonary nodules showed comparable efficacy compared with other lobes, but posed a higher risk of pneumothorax complications, necessitating longer MWA procedure times and extended hospital stays.

Estimation of 24-hour urinary sodium and potassium excretion among Chinese adults: a cross-sectional study from the China National Nutrition Survey.

BACKGROUND: High-sodium intake is one of the most important risk factors for hypertension and cardiovascular disease, yet reliable national estimates of sodium intake in Chinese adults have not been reported. OBJECTIVES: We estimated 24-h urinary sodium and potassium excretion and population daily sodium and potassium intake of Chinese adults for the first time at a national level. METHODS: A nationally representative cross-sectional survey was conducted to collect 24-h urine specimens from Chinese adults aged ≥18 y as part of the China National Nutrition Survey 2015. Finally, 10,114 participants (4932 males and 5182 females) with complete 24-h urine specimens were included in the analysis. Estimates of mean urinary electrolyte excretion and demographic, socioeconomic, and health characteristics were used with weighted coefficients that accounted for sample selection probabilities, poststratification weighting, and nonresponse rates. RESULTS: The estimation of overall weighted mean 24-h urinary sodium excretion was 4121 mg (95% confidence interval [CI]: 3993, 4250), 4155 mg (95% CI: 3993, 4317) in males and 4081 mg (95% CI: 3953, 4209) in females (P for sex difference = 0.36). Overall mean 24-h urinary potassium excretion was 1534 mg (95% CI: 1492, 1577), 1468 mg (95% CI: 1424, 1513) in males and 1614 mg (95% CI: 1569-1660) in females (P for sex difference <0.001). Mean 24-h urinary sodium excretion was significantly higher in rural adults (4350 mg; 95% CI: 4217, 4483) than in urban residents (3909 mg; 95% CI: 3739, 4080; P < 0.001), and in northern residents (4388 mg; 95% CI: 4237, 4539) than in southern residents (3998 mg; 95% CI: 3832, 4163; P = 0.002). CONCLUSIONS: The first nationwide survey with 24-h urine collection confirmed that mean sodium intake in Chinese adults was more than twice the upper limit, whereas mean potassium intake was <60% of the lower limit, recommended by the World Health Organization. Urgent measures should be taken to reduce sodium intake and increase potassium intake in China.

A universal mechanism on desiccation tolerance of Cronobacter based on intracellular trehalose accumulation regulated by EnvZ/OmpR.

Cronobacter (seven species) can survive in dry powdered infant formula for a long time, but the thorough molecular mechanism of resistance to desiccation remains elusive. Here we examine the regulation mechanism of Cronobacter's tolerance to desiccation by the typical two-component system (TCS) EnvZ/OmpR. When exposed to desiccation conditions, Cronobacter showed higher survival than other pathogens, as well as significantly up-regulated expression of ompR and otsAB genes with markedly decreased survival of their mutants, suggesting their relationship with desiccation tolerance. OmpR directly binds to the promoter of trehalose biosynthesis operon otsBA, significantly enhancing their expression, and boosting the trehalose levels. The ompR-deletion in other six species further confirmed its positive regulation in desiccation tolerance. Our data present a hypothesis that EnvZ/OmpR increases intracellular trehalose levels against damage to the cells, which prompts Cronobacter to survive in desiccation conditions. This study reveals a universal molecular mechanism for desiccation resistance in Cronobacter species.

Dry and wet experiments reveal diagnostic clustering and immune landscapes of cuproptosis patterns in patients with ankylosing spondylitis.

Cuproptosis is a new manner of mitochondrial cell death induced by copper. There is evidence that serum copper has a crucial impact on ankylosing spondylitis (AS) by copper-induced inflammatory response. However, the molecular mechanisms of cuproptosis modulators in AS remain unknown. We aimed to use a bioinformatics-based method to comprehensively investigate cuproptosis-related subtype identification and immune microenvironment infiltration of AS. Additionally, we further verified the results by in vitro experiments, in which peripheral blood and fibroblast cells from AS patients were used to evaluate the functions of significant cuproptosis modulators on AS. Finally, eight significant cuproptosis modulators were identified by analysis of differences between controls and AS cases from GSE73754 dataset. Eight prognostic cuproptosis modulators (LIPT1, DLD, PDHA1, PDHB, SLC31A1, ATP7A, MTF1, CDKN2A) were identified using a random forest model for prediction of AS risk. A nomogram model of the 8 prognostic cuproptosis modulators was then constructed; the model could be beneficial in clinical settings, as indicated by decision curve analysis. Consensus clustering analysis was used to divide AS patients into two cuproptosis subtypes (clusterA & B) according to significant cuproptosis modulators. The cuproptosis score of each sample was calculated by principal component analysis to quantify cuproptosis subtypes. The cuproptosis scores were higher in clusterB than in clusterA. Additionally, cases in clusterA were closely associated with the immunity of activated B cells, Activated CD4 T cell, Type17 T helper cell and Type2 T helper cell, while cases in clusterB were linked to Mast cell, Neutrophil, Plasmacytoid dendritic cell immunity, indicating that clusterB may be more correlated with AS. Notably, key cuproptosis genes including ATP7A, MTF1, SLC31A1 detected by RT-qPCR with peripheral blood exhibited significantly higher expression levels in AS cases than controls; LIPT1 showed the opposite results; High MTF1 expression is correlated with increased osteogenic capacity. In general, this study of cuproptosis patterns may provide promising biomarkers and immunotherapeutic strategies for future AS treatment.

Correlation of Hounsfield Units with Bone Mineral Density and T-Score in Chinese Adults.

OBJECTIVE: To examine the association between vertebral cancellous Hounsfield units (HUs), age, bone mineral density, and T-score in a sample of Chinese adults. METHODS: The study included a sample of 739 participants. Age, bone mineral density, and T-score of each participant were recorded, and HUs were measured in the L1-L4 vertebrae. RESULTS: Data analysis revealed that HUs of vertebral cancellous bone across the pedicle level decreased with age, with women having higher values than men up to age 50 and vice versa thereafter. Furthermore, a positive correlation was found between HUs of vertebral cancellous bone across the pedicle level and bone mineral density/T-score in the L1-L4 vertebrae, but with a weaker correlation in the L4 vertebrae. Additionally, HU values for participants with osteoporosis were significantly lower than HU values for participants with osteopenia and normal bone health. CONCLUSIONS: From the findings of this study, it can be concluded that HUs may be a potential predictor of bone health, with implications for presurgical assessment of the quality of bone-screw interfaces for spinal surgery.

Moraxella haemolytica sp. nov., isolated from a goat with respiratory disease.

An aerobic, haemolytic, Gram-negative and rod-shaped bacterial strain ZY171148T was isolated from the lung of a dead goat with respiratory disease in Southwest China. The strain grew at 24-39 °C, at pH 6.0-9.0 and in the presence of 0.5-2.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain belongs to the genus Moraxella. The nucleotide sequence similarity analysis of the 16S rRNA gene showed that the strain has the highest similarity of 98.1% to Moraxella (M.) caprae ATCC 700019 T. Phylogenomic analysis of 800 single-copy protein sequences indicated that the strain is a member of the genus Moraxella and forms a separated branch on the Moraxella phylogenetic tree. The strain exhibited the highest orthologous average nucleotide identity (OrthoANI) and average amino acid identity (AAI) values of 77.0 and 77.9% to M. nasibovis CCUG 75921T and M. ovis CCUG 354T, respectively. The strain shared the highest digital DNA-DNA hybridization (dDDH) value of 26.2% to M. osloensis CCUG 350T. The genome G + C content of strain ZY171148T was 42.6 mol%. The strain had C18:1 ω9c (41.7%), C18:0 (11.2%), C16:0 (14.1%) and C12:0 3OH (9.7%) as the predominant fatty acids and CoQ-8 as the major respiratory quinone. The strain contained phosphatidylglycerol, phosphatidylethanolamine, cardiolipin, dilysocardiolipin, monolysocardiolipin and phosphatidic acid as the major polar lipids. ß-haemolysis was observed on Columbia blood agar. All results confirmed that strain ZY171148T represents a novel species of the genus Moraxella, for which the name Moraxella haemolytica sp. nov. is proposed, with strain ZY171148T = CCTCC AB 2021471T = CCUG 75920T as the type strain.

Unravelling diagnostic clusters and immune landscapes of cuproptosis patterns in intervertebral disc degeneration through dry and wet experiments.

Cuproptosis is a manner of mitochondrial cell death induced by copper. However, cuproptosis modulators' molecular processes in intervertebral disc degeneration (IDD) are still unclear. To better understand the processes of cuproptosis regulators in IDD, a thorough analysis of cuproptosis regulators in the diagnostic biomarkers and subtype determination of IDD was conducted. Then we collected clinical IDD samples and successfully established IDD model in vivo and in vitro, and carried out real-time quantitative polymerase chain reaction (RT-qPCR) validation of significant cuproptosis modulators. Totally we identified 8 crucial cuproptosis regulators in the present research. Using a random forest model, we isolated 8 diagnostic cuproptosis modulators for the prediction of IDD risk. Then, based on our following decision curve analysis, we selected the five diagnostic cuproptosis regulators with importance scores greater than two and built a nomogram model. Using a consensus clustering method, we divided IDD patients into two cuproptosis clusters (clusterA and clusterB) based on the important cuproptosis regulators. Additionally, each sample's cuproptosis value was evaluated using principal component analysis in order to quantify the cuproptosis clusters. Patients in clusterB had higher cuproptosis scores than patients in clusterA. Moreover, we found that clusterB was involved in the immunity of natural killer cell, while clusterA was related to activated CD4 T cell, activated B cell, etc. Notably, cuproptosis modulators detected by RT-qPCR showed generally consistent expression levels with the bioinformatics results. To sum up, cuproptosis modulators play a crucial role in the pathogenic process of IDD, providing biomarkers and immunotherapeutic approaches for IDD.

Characterisation of strength and deformation characteristics of alkali-activated rice husk ash filler-assemblage perimeter rock.

In this study, the strength characteristics, deformation characteristics and damage characteristics of three kinds of specimens, namely, surrounding rock, cemented paste backfill (CPB) and a surrounding rock-CPB combination, were studied by uniaxial compression testing using rice husk ash and slag as cementing materials, and the mechanical properties of the combination specimens with different height ratios were also analyzed. The results showed that the surrounding rock specimens were the strongest, followed by the composite body, and the CPB was the weakest. The relationship between different height ratios of the assemblage and the cut line modulus was found according to the fitted curves. The CPB specimens and the surrounding rock specimens showed ductile damage, while the assemblage specimens showed brittle damage.

Sweroside plays a role in mitigating high glucose-induced damage in human renal tubular epithelial HK-2 cells by regulating the SIRT1/NF-κB signaling pathway.

Sweroside is a natural monoterpene derived from Swertia pseudochinensis Hara. Recently, studies have shown that sweroside exhibits a variety of biological activities, such as anti-inflammatory, antioxidant, and hypoglycemic effects. However, its role and mechanisms in high glucose (HG)-induced renal injury remain unclear. Herein, we established a renal injury model in vitro by inducing human renal tubular epithelial cell (HK-2 cells) injury by HG. Then, the effects of sweroside on HK-2 cell activity, inflammation, reactive oxygen species (ROS) production, and epithelial mesenchymal transition (EMT) were observed. As a result, sweroside treatment ameliorated the viability, inhibited the secretion of inflammatory cytokines (TNF-α, IL-1ß, and VCAM-1), reduced the generation of ROS, and inhibited EMT in HK-2 cells. Moreover, the protein expression of SIRT1 was increased and the acetylation of p65 NF-kB was decreased in HK-2 cells with sweroside treatment. More importantly, EX527, an inhibitor of SIRT1, that inactivated SIRT1, abolished the improvement effects of sweroside on HK-2 cells. Our findings suggested that sweroside may mitigate HG-caused injury in HK-2 cells by promoting SIRT1-mediated deacetylation of p65 NF-kB.

Plastrum testudinis Ameliorates Oxidative Stress in Nucleus Pulposus Cells via Downregulating the TNF-α Signaling Pathway.

BackgroundPlastrum testudinis (PT), a widely used traditional Chinese medicine, exerts protective effects against bone diseases such as intervertebral disc degeneration (IDD). Despite its effectiveness, the molecular mechanisms underlying the effects of PT on IDD remain unclear. Methods In this study, we used a comprehensive strategy combining bioinformatic analysis with experimental verification to investigate the possible molecular mechanisms of PT against IDD. We retrieved targets for PT and IDD, and then used their overlapped targets for protein-protein interaction (PPI) analysis. In addition, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to investigate the anti-IDD mechanisms of PT. Moreover, in vivo and in vitro experiment validations including hematoxylin-eosin (HE) and safranine O-green staining, senescence-associated ß-galactosidase (SA-ß-gal) assay, cell immunofluorescence staining, intracellular ROS measurement and Western blot analysis were performed to verify bioinformatics findings. Results We identified 342 and 872 PT- and IDD-related targets (32 overlapping targets). GO enrichment analysis yielded 450 terms related to oxidative stress and inflammatory response regulation. KEGG analysis identified 48 signaling pathways, 10 of which were significant; the TNF-α signaling pathway had the highest p-value, and prostaglandin G/H synthase 2 (PTGS2), endothelin-1 (EDN1), TNF-α, JUN and FOS were enriched in this pathway. Histopathological results and safranin O/green staining demonstrated that PT attenuated IDD, and SA-ß-gal assay showed that PT ameliorated nucleus pulposus cell (NPC) senescence. An ROS probe was adopted to confirm the protective effect of PT against oxidative stress. Western blot analyses confirmed that PT downregulated the protein expression of PTGS2, EDN1, TNF-α, JUN and FOS in the TNF-α signaling pathway as well as cellular senescence marker p16, proinflammatory cytokine interleukin-6 (IL6), while PT upregulated the expression of NPC-specific markers including COL2A1 and ACAN in a concentration-dependent manner. Conclusions To the best of our knowledge, this study is the first to report that PT alleviates IDD by downregulating the protein expression of PTGS2, EDN1, TNF-α, JUN and FOS in the TNF-α signaling pathway and upregulating that of COL2A1 and ACAN, thus suppressing inflammatory responses and oxidative stress in NPCs.

Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial.

AIM: To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. MATERIALS AND METHODS: In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. RESULTS: After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. CONCLUSIONS: Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.

Exploring the association between COVID-19 and male genital cancer risk in European population: evidence from mendelian randomization analysis.

BACKGROUND: Recently accumulated evidence indicates a potential association between COVID-19 and elevated susceptibility to cancer, including male genital cancer. However, the causal nature of this relationship remains unclear. METHODS: In this Mendelian randomization (MR) study, we investigated the potential causal relationship between COVID-19 and male genital cancer using genetic variants as instrumental variables. We utilized summary statistics from two large-scale genome-wide association studies of COVID-19 hospitalized Vs. controls, as well as data from a population-based male genital cancer database based on European ancestry. We applied stringent quality control measures to select instrumental variables, including checking for linkage disequilibrium, removing low-quality variants, and assessing the strength of the instruments using the F-statistic. We conducted the MR  analysis using the inverse-variance weighted method and several sensitivity analyses (including MR Egger and Weighted Median MR analysis) to test the robustness of our results. RESULTS: Our MR analysis revealed no causal associations between COVID-19 hospitalization and the incidence of male genital cancer. In the inverse-variance weighted analysis, no causal associations were observed between patients with COVID-19 hospitalization and the incidence of male genital cancer (odds ratio = 1.000 and 95% confidence interval = 0.998-1.001, p = 0.668). The estimated causal effect was consistent across all sensitivity analyses (including the Weighted Median, the MR Egger analysis, and the MR PROSSO analysis). The leave-one-out analysis showed that there was no any sing Single-nucleotide polymorphism significantly influencing our results. CONCLUSIONS: Our study provides evidence that there is no causal association between COVID-19 hospitalization and male genital cancer.

Deficiency of SR-B1 reduced the tumor load of colitis-induced or APCmin /+ -induced colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common tumors in the world. Cholesterol plays an important role in the pathogenesis of tumors. One of the cholesterol transporters, scavenger receptor class B type 1 (SR-B1), a multi-ligand membrane receptor protein, is expressed in the intestines which also highly expressed in various tumors. But the potential mechanism of SR-B1 in CRC development has not been reported. AIMS: This study aimed to clarify the importance of SR-B1 in the development and prognosis of CRC as much as possible to provide a possible strategy in CRC treatment. MATERIALS & METHODS: In this study, we used SR-B1 gene knockdown mice to study the effect of SR-B1 on colitis-induced or APCmin/+ -induced CRC. The expression of related molecules were detected through the immunohistochemistry and hematoxylin-eosin staining, western blot analysis, and Flow cytometry. The gene expression and microbiota in microenvironment of CRC mice were analyzed through eukaryotic mRNA sequencing and 16S rRNA high-throughput sequencing. RESULTS: The results showed that SR-B1 knockdown reduced the tumor load of colitis-induced or APCmin/+ -induced CRC. SR-B1 knockdown improved the immune microenvironment by affecting the level of tumor-associated macrophage (TAM), mononuclear myeloid-derived suppressor cells (M-MDSCs), granulocytic myeloid-derived suppressor cells (G-MDSCs), programmed cell death-ligand 1 (PD-L1), and human leukocyte antigen class I-B (HLA-B), and also reduced the level of low-density lipoprotein receptor (LDL-R), and increased the level of ATP binding cassette transporter A1 (ABCA1) to regulate the cholesterol metabolism, and regulated the expression of related genes and intestinal microbiota. SR-B1 knockdown can also trigger the anti-CRC effect of anti-PD 1 in colitis-induced CRC. DISCUSSION: SR-B1 deficiency significantly improved the immunity in tumor microenvironment of colitis-induced or APCmin/+ -induced CRC. In addition, the microbiota changes caused by SR-B1 deficiency favor improving the immune response to chemotherapeutic drugs and anti-PD1 therapy. The mechanism of action of SR-B1 deficiency on the development of CRC still needs further in-depth research. CONCLUSION: This study provides a new treatment strategy for treating CRC by affecting the expression of SR-B1 in intestine.

Significant response to transarterial chemoembolization combined with PD-1 inhibitor and apatinib for advanced intrahepatic cholangiocarcinoma: A case report and literature review.

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy rising from the biliary tree with poor prognosis. We report the feasibility and efficacy of transarterial chemoembolization (TACE) combined with PD-1 inhibitor and apatinib for the treatment of a patient with unresectable ICC. A 70-year-old female presented with intermittent right upper abdominal distension, abdominal pain, and vomiting after eating for more than one month. Enhanced computed tomography (CT) and magnetic resonance imaging (MRI) scan revealed multiple intrahepatic lesions, retroperitoneal lymph node, and left lung metastasis. Based on the patient's medical history and pathology, the diagnosis was confirmed as locally advanced unresectable ICC. Multimodal therapy was applied to the ICC. The therapy comprised TACE every three months, and a combination regimen of the PD-1 inhibitor camrelizumab and the antiangiogenic agent apatinib. The patient underwent microwave ablation for a lesion on the left lung that had not responded to systemic therapies. Enhanced CT scan after every 2-3 months was performed. After several sessions, the primary lesion reduced dramatically in size. At 20 months from diagnosis, the patient was alive, in good condition, and stable. The patient experienced no critical complications and toxicity associated with the administered therapies. This case suggests that treatment with TACE combined with systemic therapy of camrelizumab combined with apatinib may be a safe and effective treatment option for patients with inoperable ICC.

Transcriptomic analysis reveals novel desiccation tolerance mechanism of Cronobacter based on type VI secretion system inhibition.

Cronobacter malonaticus (C. malonaticus) is a food-borne pathogen inducing severe infections both in infants and adults, and it could survive in dry powdered infant formula (PIF) for a long time, implying its strong tolerance to desiccation. However, the thorough molecular mechanism of resistance to desiccation remains elusive. When C. malonaticus was exposed to desiccation conditions (7, 15, and 30 d), transcriptomic analysis provided a universal adaptation strategy to withstand desiccation with the increased compatible solutes accumulation, activated stress resistance-related regulators, suppressed protein export and bacterial secretion system, and reduced other unessential survival functions including adhesion, invasion, virulence, and flagellar motility. Importantly, type VI secretion system (T6SS) genes exhibited significantly downregulated expressions, as well as markedly increased survival and viability of their mutants after desiccation treatment, revealing the negative regulation of T6SS in desiccation tolerance. Meanwhile, the decreased expressions of T6SS structure genes in other six species further confirmed the vital role of T6SS in desiccation tolerance of Cronobacter spp. Thus, our studies present a novel hypothesis of desiccation resistance in Cronobacter based on type VI secretion system inhibition, causing the reduction of macromolecule secretion such as effectors and hyperosmolality development within the cytomembrane, which allow Cronobacter to survive in desiccation.