Objective: To investigate the effect of Guangdong Shenqu (GSQ) on intestinal flora structure in mice with food stagnation through 16S rDNA sequencing. Methods: Mice were randomly assigned to control, model, GSQ low-dose (GSQL), GSQ medium-dose (GSQM), GSQ high-dose (GSQH), and lacidophilin tablets (LAB) groups, with each group containing 10 mice. A food stagnation and internal heat mouse model was established through intragastric administration of a mixture of beeswax and olive oil (1:15). The control group was administered normal saline, and the model group was administered beeswax and olive oil to maintain a state. The GSQL (2 g/kg), GSQM (4 g/kg), GSQH (8 g/kg), and LAB groups (0.625 g/kg) were administered corresponding drugs for 5 d. After administration, 16S rDNA sequencing was performed to assess gut microbiota in mouse fecal samples. Results: The model group exhibited significant intestinal flora changes. Following GSQ administration, the abundance and diversity index of the intestinal flora increased significantly, the number of bacterial species was regulated, and α and β diversity were improved. GSQ administration increased the abundance of probiotics, including Clostridia, Lachnospirales, and Lactobacillus, whereas the abundance of conditional pathogenic bacteria, such as Allobaculum, Erysipelotrichaceae, and Bacteroides decreased. Functional prediction analysis indicated that the pathogenesis of food stagnation and GSQ intervention were primarily associated with carbohydrate, lipid, and amino acid metabolism, among other metabolic pathways. Conclusion The digestive mechanism of GSQ may be attributed to its role in restoring diversity and abundance within the intestinal flora, thereby improving the composition and structure of the intestinal flora in mice and subsequently influencing the regulation of metabolic pathways.

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

In order to further strengthen the training and management of clinical teachers, broaden the career development channels of clinical teachers, and truly stimulate their teaching enthusiasm and initiative, this study further classifies clinical teachers according to the principle of the Snell model, focuses on the training of educational clinicians, and explores the training mechanism of teaching talents in line with the actual development needs of hospitals affiliated to universities from the aspects of selection, training, incentive, and assessment. The results of practice show that related practices have a good effect, and the mean number of teaching achievements was 1.98 for the 56 educational physicians, which was 3.9 times that for non-educational physicians. The per capita teaching achievements of educational physicians tended to increase every year compared with those of non-educational physicians. The training path for educational physicians provides useful experience for the construction of clinical teaching team and the high-quality development of education and teaching, and at the same time, it is necessary to further strengthen the dynamic adjustment of talent echelon, the improvement of operating mechanism, and the introduction of new technology.

Objective:To investigate the indication, effectiveness, tolerance, and safety of levosimendan in patients with acute heart failure (AHF) in 20 hospitals in Beijing, China.Methods:This prospective, observational, and multicenter study consecutively enrolled AHF patients who were treated with levosimendan at 20 hospitals in Beijing from April 2020 to March 2022. Baseline demographics, laboratory parameters, clinical presentation, concomitant diseases and medications were collected. After initiation of levosimendan, levosimendan administration, laboratory parameter pre- and post-administration, symptoms improvement, and adverse events were also collected.Results:Totally 800 AHF patients were included, 67% of whom were male, aged (65 ±17) years, 50% of whom had ischemic heart disease, and the left ventricular ejection fraction (LVEF) was (36±11)%. The dose of levosimendan was (11.84 ±2.11) mg and the mean infusion time was (1 450±307) min. Dyspnea was improved in 83.4% of AHF patients at 24 h after treatment. The level of B-type natriuretic peptide (BNP) significantly decreased from 689 (406-1509) pg/mL to 410 (156-697) pg/mL in all patients at 24-72 h after treatment ( P<0.001), and the level of N-terminal pro-brain natriuretic peptide (NT-pro BNP) decreased from 6910 (3 715-13 914) pg/mL to 2 851 (1 288-6 191) pg/mL ( P<0.001). Meanwhile, LVEF level also improved significantly [(40±11)% vs. (36±11)%, P<0.001]. During levosimendan administration, adverse events occurred in 74 (9.3%) patients, including hypotension (5.9%), arrhythmia (1.9%), and other symptoms (1.1%). Among them, 7 patients ( 2 patients with hypotension and 5 patients with ventricular tachycardia) interrupted levosimendan administration. Conclusions:The use of levosimendan is safe, and can improve symptoms reduce BNP or NT-pro BNP levels and increase LVEF level in AHF patients.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Background::The ideal blood pressure (BP) target for patients with atrial fibrillation (AF) is still unclear. The present study aimed to assess the effect of the baseline BP on all-cause mortality in patients with AF.Methods::This registry study included 20 emergency centers across China and consecutively enrolled patients with AF from 2008 to 2011. All participants were followed for 1 year ± 1 month. The primary endpoint was all-cause mortality.Results::During the follow-up, 276 (13.9%) all-cause deaths occurred. Kaplan-Meier curves showed that a systolic blood pressure (SBP) ≤110 mmHg or >160 mmHg was associated with a higher risk of all-cause mortality (log-rank test, P = 0.014), and a diastolic blood pressure (DBP) <70 mmHg was associated with the highest risk of all-cause mortality (log-rank test, P = 0.002). After adjusting for confounders, the multivariable Cox regression model suggested that the risk of all-cause mortality was increased in the group with SBP ≤110 mmHg (hazard ratio [HR], 1.963; 95% confidence interval [CI], 1.306-2.951), and DBP <70 mmHg (HR, 1.628; 95% CI, 1.163-2.281). In the restricted cubic splines, relations between baseline SBP or DBP and all-cause mortality showed J-shaped associations (non-linear P <0.001 and P = 0.010, respectively). The risk of all-cause mortality notably increased at a lower baseline SBP and DBP. Conclusions::Having a baseline SBP ≤110 mmHg or DBP <70 mmHg was associated with a significantly higher risk of all-cause mortality in patients with AF. An excessively low BP may not be an optimal target for patients with AF.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Background: Abnormal glucose metabolism is one of the malignant characteristics of tumors. LncRNA plays an important role in the process of aerobic glycolysis of tumors. Aims: To investigate the expression of LncRNA MEG3 in gastric cancer and its correlation with glycolysis. Methods: RT-qPCR was used to detect the mRNA expression of MEG3 in gastric cancer and paracancerous tissue. Immunohistochemical EnVision method was used to detect the protein expressions of PKM2, LDHA, mTOR, HIF-1α in gastric cancer and paracancerous tissue. Relationship between expressions of above-mentioned indices and clinicopathological features of gastric cancer were analyzed. The correlation between MEG3 and glycolysis level of gastric cancer was analyzed by Spearman correlation analysis, and its possible mechanism was explored. Results: The expression of MEG3 in gastric cancer tissue was significantly lower than that in paracancerous tissue (P< 0.05), and was correlated with lymph node metastasis (P<0.05). The positivity rates of expression of PKM2, LDHA, mTOR and HIF-1α in gastric cancer tissue were significantly higher than those in paracancerous tissue, and were correlated with the depth of tumor invasion, lymph node metastasis and pTNM stage (P<0.05). Spearman correlation analysis showed that the expression of MEG3 was negatively correlated with the expressions of PKM2, LDHA, mTOR and HIF-1α (r=-0.346，r= -0.306，r=-0.389, r=-0.338; P<0.05). The expression of MEG3 in HIF-1α

Objective:To investigate the baseline characteristics and 1-year follow-up prognosis of elderly (age ≥75 years) emergency department (ED) patients with atrial fibrillation (AF).Methods:From 2009 to 2011, patients with AF aged ≥75 years were continuously enrolled in the ED in 20 hospitals. The baseline characteristics and treatment status of the patients were collected and followed up for 1 year. The primary endpoint was all-cause death; Secondary endpoints were cardiovascular death, stroke, major bleeding and major adverse events. Uni- and multivariate Cox regression models were used to analyze the independent risk factors for the above events.Results:A total of 766 elderly ED patients with AF were enrolled, the average age was 80.76±4.66 years old, and 56.9% were female. The 1-year all-cause mortality was 24.3%, cardiovascular mortality was 12.8%, stroke rate was 10.6%, major adverse event rate was 33.6%, and the readmission rate was 32%. Multivariate Cox regression analysis showed that age ( HR1.073, 95% CI 1.042-1.105), heart rate ( HR1.008, 95% CI 1.002-1.013), history of dementia/cognitive impairment ( HR1.849, 95% CI 1.016) ~3.365), and history of chronic obstructive pulmonary disease ( HR1.824, 95% CI 1.303-2.551) were independent risk factors for death in elderly patients with AF in 1-year follow-up; female (HR1.664, 95% CI 1.036-2.675), and history of hypertension ( HR2.035, 95% CI 1.080-3.836), history of dementia/cognitive impairment ( HR2.773, 95% CI 1.220-6.302) were independent risk factors for 1-year stroke in elderly patients with AF. Conclusions:The prognosis of elderly ED patients with AF is poor. Age, heart rate, history of dementia/cognitive impairment, and history of chronic obstructive pulmonary disease are independent risk factors for 1-year all-cause death and major adverse events in elderly ED patients with AF. Female, history of hypertension, and history of dementia/ cognitive impairment are independent risk factors for stroke in elderly ED patients with AF.

Objective:To analyze the characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody type 1 (anti-LC1), in order to provide references for clinical and differential diagnosis.Methods:The clinical data of 23 832 inpatients and outpatients with positive anti-LC1 autoantibodies detected in routine autoantibody test from January 2010 to January 2020 were retrospectively analyzed, and their clinical and laboratory indexes were compared. Western blotting was used to detect anti-LC1, anti-soluble liver antigen antibody (anti-SLA), anti-glycoprotein 210 antibodies and anti-nucleosome 100 antibodies. Indirect immunofluorescence assay was used to detect anti-nuclear antibody (ANA), anti-mitochondrial antibody, anti-Smooth muscle antibody (ASMA), anti-liver and kidney microsomal antibody (anti-LKM) and other autoantibodies. Normally distributed measurement data between the two groups were compared by independent-sample t-test, and the multiple groups comparison were compared by one-way analysis of variance. Non-normally distributed measurement data were compared by non-parametric rank sum test.Results:38 anti-LC1 positive patients were detected in 23832 autoantibody tests. The age of initial diagnosis ranged from 11.0 to 84.0 (50.6 ± 16.0) years. There were 8 males (21.1%) and 30 females (78.9%). A total of 31 cases (81.6%) were positive for anti-LC1 and ANA, and the dominant karyotype was speckled pattern, accounting for 54.8%. Five cases (13.2%) were positive for ASMA, and no simultaneous positive with anti-LKM or anti-SLA. Among the 38 anti-LC1 positive patients, 9 were diagnosed with autoimmune hepatitis (AIH), 6 with possible AIH, 6 with primary biliary cholangitis (PBC), 8 with hepatitis B, 2 with hepatitis C, 1 with alcoholic liver disease, 2 with non-alcoholic fatty liver disease, 1 with drug-induced liver injury, 1 with hepatolenticular degeneration, and 2 with tumor. Confirmed and probable AIH cases accounted for 39.5% (15/38) of anti-LC1 positive cases. Among anti-LC1 positive patients, 47.4% (18/38) had entered the stage of liver cirrhosis. AIH group globulin level was higher than HBV group ( P = 0.006) and other disease groups ( P = 0.001). AIH group IgG level was higher than PBC group ( P = 0.027), HBV group ( P = 0.009) and other disease groups ( P = 0.004). the of the PBC group IgM level was higher than AIH group ( P = 0.003), HBV group ( P = 0.003) and other disease groups ( P = 0.006). Conclusion:Anti-LC1 is not only detected in AIH, but also observed in patients with primary biliary cholangitis, hepatitis B and C, alcoholic and non-alcoholic liver disease, drug-induced liver injury, hereditary metabolic liver disease and tumor. In addition, it is mainly female gender dominance and nearly half of ANA-positive young, middle-aged and elderly patients develop liver cirrhosis. For the diagnosis of type 2 autoimmune hepatitis, whether anti-LC1 is a specific antibody needs further research, but if AIH is highly suspected, this antibody can be used as a substitute.