[3 + 2] Cycloaddition Reaction of Vinylsulfonium Salts with Hydrazonoyl Halides: Synthesis of Pyrazoles.

An efficient [3 + 2] cycloaddition reaction between in situ generated nitrile imines from hydrazonoyl halides and vinylsulfonium salts is developed. The nitrile imines are demonstrated to be a new class of reaction partner for vinylsulfonium salts to conduct the [3 + 2] cycloaddition reaction. The process provides a concise and efficient method for the construction of pyrazole derivatives under mild reaction conditions with broad substrate scope, good product yields, and high regioselectivity.

Molecular epidemiological characteristics of osteoarthritis-associated Brucella melitensis in China: evidence from whole-genome sequencing-based analysis.

BACKGROUND: Brucellosis, developing complications including arthritis, spondylitis, sacroiliitis, and osteomyelitis, is one of the most common zoonotic diseases in the current world which causes economic losses to the livestock industry and is a great public health concern. Brucella melitensis are the main pathogen of brucellosis epidemics in China, most of which are located in northern China. However, there is limited knowledge about the epidemiology of osteoarthritis-associated brucellosis. This study was aimed to reveal the prevalence of osteoarthritis-associated brucellosis in Inner Mongolia and also to investigate the molecular characteristics of B. melitensis isolates. METHODS AND RESULTS: In 2018, the osteoarthritis symptoms of brucellosis in the Brucellosis department of a hospital in Inner Mongolia were investigated. Twenty osteoarthritis-associated B. melitensis strains, isolated from the inpatients in Inner Mongolia during 2013-2017, were subjected to whole genome sequencing. The multilocus sequence type (MLST) and core genome SNP (cgSNP) analysis were conducted to detect molecular epidemiological characteristics. The incidence of brucellosis osteoarthritis symptoms in males (85/120, 70.8%) was significantly higher than that in females (35/120, 29.2%), and the age of patients was concentrated between 41 and 60 years old. In silico analyses indicated ST8 was the prevalent sequence type and the transmission of osteoarthritis-associated B. melitensis among different geographical areas. All strains carry virulence genes, including cgs, lpsA, manCoAg, pgm, pmm, virB4, wbdA and wboA. CONCLUSION: Our study showed the close epidemiologically connection of osteoarthritis-associated B. melitensis strains in northern China. And ST8 was the prevalent sequence type which need our attention.

Tiny Drosophila intestinal stem cells, big power.

The signaling pathways are highly conserved between Drosophila and mammals concerning intestinal development, regeneration, and disease. The powerful genetic tools of Drosophila make it a valuable and convenient alternative to answer basic biological questions that can not be addressed using mammalian models. In this review, we discuss recent advances in how we use fly midgut to answer the following key questions: (1) How intestine stem cell niches are established; (2) which factors control asymmetric division of stem cells; (3) how intestinal cells interact with environmental factors, such as tissue damage, microbiota, and diet; (4) how to screen aging/cancer-related factors or drugs by fly intestine stem cells.

Association between serum uric acid levels and the prevalence of heart failure due to acute coronary syndrome in Chinese hospitalized patients: A cross-sectional study.

BACKGROUND AND AIMS: Serum uric acid (SUA) may play a role in heart failure (HF). Our study was to find relationships between SUA and the prevalence of HF due to acute coronary syndrome (ACS), and the ethnic-specific relationship between them in an inpatient population. METHODS AND RESULTS: We analyzed 1075 Chinese ACS patients. SUA levels were cut to four groups as Q1 to Q4, according to quartiles. Binary logistic regression models were used to assess associations of SUA with HF due to ACS. Subgroup analysis was performed to find ethnic-specific association between SUA and HF due to ACS. We also performed univariate and multivariate logistic regression analyses taking into account an Italian's cut-off for SUA for HF prognosis stratification. After adjustment for all potential confounders, compared to the lowest quartile, quartiles 2, 3 and 4 had a prevalence OR of 0.69 (0.44-1.08), 1.06 (0.67-1.67) and 2.19 (1.35-3.56), respectively, for the HF due to ACS (p for trend <0.001). Subgroup analyses didn't reveal an ethnic-specific differences between SUA and HF due to ACS. In Han, the highest SUA level was significantly associated with the risk of HF due to ACS. OR with 95%CI for Q4 was 1.85 (1.02-3.37), Q1 as a reference. For Mongolians, the OR with 95%CI for Q4 was 6.82 (1.90-24.50), Q1 as a reference. CONCLUSION: We found positive associations between SUA and the prevalence of HF due to ACS among Chinese patients. No differences exist regarding ethnicity.

Corneal characteristics of Mongolian population with type 2 diabetic peripheral neuropathy in inner Mongolia, China: an assessment using corneal confocal microscopy.

OBJECTIVE: To quantify corneal nerve fiber parameters in a Mongolian population with diabetic peripheral neuropathy (DPN) by corneal confocal microscopy. METHODS: This study conducted a comprehensive evaluation of 114 participants from Hulunbuir between January 2020 and December 2021. The participants included healthy controls, Mongolian and Han patients with type 2 diabetes mellitus. Demographic, medical, and laboratory data were collected, and neuropathy was evaluated by confocal corneal microscopy. And compare various parameters between Han and Mongolian were performed using SPSS software. RESULTS: The average waist circumference of Mongolian diabetic patients was larger than that of Han diabetic patients (P < 0.05). The mean HbA1c of Mongolian was 9.30 (8.15, 10.30) %, and that of Han was 8.30 (7.20, 9.40) % (P = 0.023). The average values of Corneal Nerve Fiber Density (CNFD), Corneal Nerve Fiber Length (CNFL) and corneal nerve branch density (CNBD) in Mongolian diabetic patients were significantly lower than those in Han diabetic patients (P < 0.05). The correlation coefficient between CNFL and age was - 0.368. ROC results show that CNBD has a certain diagnostic value for DPN in Mongolian patients with type 2 diabetes and the optimal cut-off point value is 24.99(no./mm2), the sensitivity is 80.0%, and the specificity is 77.8%. CONCLUSION: The corneal confocal microscopy could possibly represent a promising adjuvant technique for the early diagnosis and assessment of PDN in Mongolian T2DM patients.

Association between serum 5-methyltetrahydrofolate and homocysteine in Chinese hypertensive participants with different MTHFR C677T polymorphisms: a cross-sectional study.

BACKGROUND AND AIMS: Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. METHODS: Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. RESULTS: There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: ß = - 0.50, P <  0.001; CC: ß = - 0.14, P = 0.087; CT: ß = - 0.20, P = 0.011; TT: ß = - 1.19, P <  0.001). Moreover, the decline in trend in genotype TT participants was stronger than in genotype CC participants (P for difference <  0.001) and genotype CT participants (P for difference <  0.001), while there was no significant difference between genotype CC and genotype CT participants (P for difference = 0.757). CONCLUSIONS: Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

Ferulic Acid Ameliorates Isoproterenol-Induced Heart Failure by Decreasing Oxidative Stress and Inhibiting Cardiocyte Apoptosis via Activating Nrf2 Signaling Pathway in Rats.

Ferulic acid (FA) has potential therapeutic effects in multiple diseases including cardiovascular diseases. However, the effect and molecular basis of FA in heart failure (HF) has not been thoroughly elucidated. Herein, we investigated the roles and mechanisms of FA in HF in isoproterenol (ISO)-induced HF rat model. Results found that FA ameliorated cardiac dysfunction, alleviated oxidative stress, reduced cell/myocardium injury-related enzyme plasma level, inhibited cardiocyte apoptosis in ISO-induced HF rat models. Moreover, FA reduced the co-localization of Keap1 and nuclear factor-E2-related factor 2 (Nrf2) in heart tissues of ISO-induced HF rats, and FA alleviated the inhibitory effects of ISO on expressions of p-Nrf2, heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1). Additionally, Nrf2 signaling pathway inhibitor ML385 showed adverse effects. FA weakened the effects of ML385 in ISO-induced HF rat models. Collectively, FA ameliorated HF by decreasing oxidative stress and inhibiting cardiocyte apoptosis via activating Nrf2 pathway in ISO-induced HF rats. Our data elucidated the underling molecular mechanism and provided a novel insight into the cardioprotective function of FA, thus suggested the therapeutic potential of FA in HF treatment.

Comparison of the efficacy and safety of Shanhuang Jiangzhi tablets and atorvastatin in the treatment of patients with hyperlipidaemia.

OBJECTIVES: To compare the efficacy and safety of Shanhuang Jiangzhi tablets and atorvastatin in reducing blood lipid levels. METHODS: Patients with hyperlipidaemia admitted to the cardiac centre between January 2019 and December 2020 were included in the study. A total of 1063 patients with hyperlipidaemia took either Shanhuang Jiangzhi tablets (n = 372) or atorvastatin (n = 691) and met the inclusion and exclusion criteria. Clinical data, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol, were retrospectively evaluated after propensity score matching (PSM) analysis. The adverse events were also recorded during the therapy process. RESULTS: Following PSM analysis, both groups were well matched across all parameters. Compared with the baseline, Shanhuang Jiangzhi tablets had greater effects on TC, TG and LDL-C, and the difference was statistically significant (p < 0.001). Furthermore, the results showed that Shanhuang Jiangzhi tablets are similar to atorvastatin in reducing TC and LDL-C, and all p-values were > 0.05. However, the decrease of TG was greater in the Shanhuang Jiangzhi group (p < 0.001). Clinical adverse reactions of Shanhuang Jiangzhi tablets are rare and have no statistical significance compared with atorvastatin (p = 0.682). CONCLUSIONS: Shanhuang Jiangzhi tablets have a higher hypotriglyceridaemic performance than atorvastatin and an equivalent ability to lower TC and LDL-C. In addition, Shanhuang Jiangzhi tablets are a low-risk option for lowering blood lipids.

A case report on digital preoperative design, clinical application and finite element analysis for a patient with ankylosing spondylitis kyphosis.

Objective: By assessing a case of ankylosing spondylitis (AS) after thoracic lumbar protrusion deformity in a digital model and verifying its effectiveness after surgery for orthopaedic surgery process simulation, a finite element model was established for biomechanical experiments. Method: A 56-year-old patient with AS underwent preoperative thoracic lumbar spine computed tomography. The data were reconstructed using MIMICS16.0 software and modelled to design and measure the nailing parameters. A three-dimensional model was established using ANSYS14.0 software, and the actual surgical procedure was simulated using biomechanical experiments. The model was verified by comparing the X-ray films obtained from patients during preoperative forward bending, stretching and lateral flexion, with the model further tested using the Hueter-Volkmann principle. Result: On comparing the measurements across three different load cases (forward bending, after stretching and lateral flexion) in patients with AS after thoracic lumbar protrusion deformity and the original X-ray images, no difference was found between the model of deformation and real patient movement displacement across the vertebral body. On simulating the stress distribution, the measured T10-L4 vertebral body stress values at every point in the injured vertebrae were, on the whole, directed at both the upper and lower ends and exhibited a decreasing trend, and the stress distribution gradually decreased from the injured vertebrae (T12 and L1) to the upper and lower ends. Conclusion: The accuracy of the research model is high, the geometric similarity is good and relevant applied anatomy can be undertaken using the model parameter measurement. This study provides a successful example of the application of digital technology in the field of spinal deformity and a novel idea for the treatment of AS-related kyphosis.

Explore the Role of the rs1801133-PPARG Pathway in the H-type Hypertension.

Both rs1801133 mutation on Methylenetetrahydrofolate reductase (MTHFR) gene and transcription factor peroxisome proliferator-activated gamma (PPARG) have been associated with plasma homocysteine (Hcy) levels and hypertension. However, their role in H-type hypertension remains unclear. In this study, we first tested the association between rs1801133 genotypes and Hcy level in H-type hypertension using clinical profiles collected from 203 patients before and after the treatment using enalapril maleate and folic acid tablets (EMFAT). Then, we constructed a literature-based pathway analysis to explore the role of the rs1801133-PPARG signaling pathway in H-type hypertension and its treatment. Although presented similar blood pressure, the patients with TT genotype of rs1801133 were much younger (p value <0.05) and significantly higher in Hcy levels (x 2 = 6.11 and p < 0.005) than that in the CC and CT genotype groups. Pathway analysis showed that T-allele of rs1801133 could inhibit the expression of PPARG through the downregulation of folate levels and upregulation of Hcy levels, which increased the risk of hypertension and hyperhomocysteinemia. Treatment using EMFAT led to similarly decreased Hcy levels for all patients with different genotypes (x 2 = 86.00; p < 0.36), which may occur partially through the activation of PPARG. Moreover, even after treatment, the patients with TT genotype still presented significantly higher Hcy levels (x 2 = 7.87 and p < 0.001). Our results supported that rs1801133 mutation could play a role in H-type hypertension, which might be partially through the downregulation of PPARG. Moreover, PPARG might also be involved in treating H-type hypertension using EMFAT.

GPNMB contributes to a vicious circle for chronic obstructive pulmonary disease.

Osteoporosis (OP) is significant and debilitating comorbidity of chronic obstructive pulmonary disease (COPD). We hypothesize that genetic variance identified with OP may also play roles in COPD. We have conducted a large-scale relation data analysis to explore the genes implicated with either OP or COPD, or both. Each gene linked to OP but not to COPD was further explored in a mega-analysis and partial mega-analysis of 15 independently collected COPD RNA expression datasets, followed by gene set enrichment analysis (GSEA) and literature-based pathway analysis to explore their functional linked to COPD. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in COPD. At the first step of the analysis, we have identified 918 genes associated with COPD, 581 with OP, and a significant overlap (P<2.30e-140; 210 overlapped genes). Partial mega-analysis showed that, one OP gene, GPNMB presented significantly increased expression in COPD patients (P-value = 0.0018; log fold change = 0.83). GPNMB was enriched in multiple COPD pathways and plays roles as a gene hub formulating multiple vicious COPD pathways included gene MMP9 and MYC. GPNMB could be a novel gene that plays roles in both COPD and OP. Partial mega-analysis is valuable in identify case-specific genes for COPD.

Spinal brucellosis in Hulunbuir, China, 2011-2016.

Purpose: To investigate the demographic, epidemiological, clinical, and laboratory characteristics; treatment options; and outcome of human brucellosis with spine involvement at a major hospital in Hulunbuir, a brucellosis epidemic region of China. Patients and methods: A total of 842 patients with human brucellosis treated in the Department of Brucellosis, Hulunbuir People's Hospital from January 2011 to December 2016 were included and analyzed in this study. The results of 67 brucellar spondylodiscitis (BS) cases were compared with those that were negative for spine involvements. Results: The mean age of spinal brucellosis patients was 50.5±10.2 years (43 males and 24 females; age range 29-70). The risk factors for transmission are direct contact with animals, such as working in the farm, and consumption of unpasteurized milk or daily products. Back pain (92.5%), fever (85.1%), sweating (62.7%), and fatigue (52.8%) were the most common symptoms. Magnetic resonance imaging (MRI) was performed in all the patients with spondylodiscitis. The sites of involvement were lumbar (81.2%), thoracic (8.7%), cervical (4.3%), thoracolumbar (2.9%), and lumbosacral (2.9%). All isolates from blood culture were identified as Brucella melitensis, with 61% biovar 3 and 39% biovar 1 isolates. The antimicrobial therapy for BS lasted for at least 3 months. In the presence of paravertebral or epidural abscess, longer treatment was conducted to avoid possible sequelae. Conclusion: In endemic areas such as Hulunbuir, BS should be considered in patients with back pain and fever. MRI is a highly sensitive imaging modality that can be used to differentiate BS from other spinal infections. This study will be helpful to establish strategies for prevention, surveillance, and management of spinal brucellosis in China.

Whole-Genome Sequence of Brucella melitensis Strain B7, Isolated from a Blood Sample of a Brucellosis Patient from Hulunbuir, Inner Mongolia, China.

We report here the draft genome sequence of Brucella melitensis strain B7, isolated from a blood sample of a brucellosis patient from Hulunbuir, Inner Mongolia, China. This report describes the genome sequence of a human B. melitensis isolate, which is endemic in this area of China.