Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Objective:To investigate the incidence and risk factors of deep vein thrombosis(DVT)in patients with rheumatoid arthritis(RA).Methods:The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed,including demographic characteristics,concomitant diseases,laboratory examinations(blood routine,biochemistry,coagulation,inflammatory markers,rheumatoid factor,antiphospholipid antibodies and lupus anticoagulant,etc.)and treatment regimens.The patients were compared according to the presence or absence of DVT,and the t test,Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT,followed by Logistic regres-sion analysis to determine risk factors for DVT in patients with RA.Results:The incidence of DVT in the RA patients was 9.6％(31/322);the median age of RA in DVT group was significantly older than that in non-DVT group[64(54,71)years vs.50(25,75)years,P＜0.001];the level of disease activity score using 28 joints(DAS28)-erythrocyte sedimentation rate(ESR)in DVT group was higher than that in non-DVT group[5.2(4.5,6.7)vs.4.5(4.5,5.0),P＜0.001];the incidence of hypertension,chronic kidney disease,fracture or surgery history within 3 months,and varicose veins of the lower ex-tremities in DVT group was higher than that in non-DVT group(P＜0.001).The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group(P=0.009,P=0.004),while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group(P＜0.001).The use rate of glucocorticoid in DVT group was higher than that in non-DVT group(P=0.009).Logistic regression analysis showed that the age(OR=1.093,P＜0.001),chronic kidney disease(OR=7.955,P=0.005),fracture or surgery history with-in 3 months(OR=34.658,P=0.002),DAS28-ESR(OR=1.475,P=0.009),and the use of glu-cocorticoid(OR=5.916,P=0.003)were independent risk factors for DVT in RA patients.Conclu-sion:The incidence of DVT in hospitalized RA patients was significantly increased,in addition to tradi-tional factors,such as age and chronic kidney disease,increased DAS28-ESR level and the use of glu-cocorticoid were also independent risk factors for DVT.

Objective:To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique; To explore the possibility of its treatment for cough variant asthma.Methods:The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot.Results:Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased ( P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased ( P<0.05). Conclusion:Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.

Objective:To analyze the effect of modified Banxia Baizhu Tianma Decoction combined with Nimodipine on cognitive dysfunction and changes on cerebral blood flows of the patients with chronic cerebral insufficiency (CCCI).Methods:A total of 91 patients with CCCI who received treatment in our hospital from March 2019 to March 2020 were selected and divided into the treatment group ( n=46) and the control group ( n=45), according to random number table method. The control group was treated with Nimodipine oral treatment, and the treatment group was treated with modified Banxia Baizhu Tianma Decoction on the basis of the control group treatment. Both groups were treated for 2 weeks. The Traditional Chinese Medicine (TCM) syndrome scores were performed before and after treatment, and transcranial Doppler ultrasound was used to detect the average blood flow of bilateral vertebral arteries (VA), basilar arteries (BA), internal carotid arteries (ICA) and middle cerebral arteries (MCA). The whole blood viscosity high shear (HS), whole blood low shear (LS), plasma viscosity (PV), fibrinogen (FIB) and hematocrit (HCT) were detected by automatic blood rheometerusing. The Montreal Cognitive Assessment Scale (MoCA) was used to assess the degree of cognitive impairment and evaluate the clinical efficacy. Results:The total effective rate was 91.3% (42/46) in the treatment group and 73.3% (33/45) in the control group, with a statistically significant difference between the two groups ( χ2=5.07, P=0.024). The scores of dizziness, headache, forgetfulness, insomnia and total scores in the treatment group were significantly lower than those in the control group after treatment ( t values were 8.59, 7.79, 3.92, 4.11, 5.01, all Ps<0.01), and the MoCA score (25.13±2.16 vs. 23.88±2.70; t=2.44, P=0.017) in the treatment group significantly higher than that in the control group. After treatment, VA [(35.49±4.08) cm/s vs. (32.17±4.25) cm/s, t=3.80], BA [(36.99±3.79) cm/s vs. (33.76±4.12) cm/s, t=3.89], ICA [(62.49±5.07) cm/s vs. (58.91±5.31) cm/s, t=3.29], MCA [(70.09±5.04) cm/s vs. (67.12±5.85) cm/s, t=2.60] in the treatment group was significantly higher than those in the control group ( P<0.01). After treatment, the levels of HS, LS, PV, Fg, and HCT in the treatment group were significantly lower than those in the control group ( t values were 2.37, 4.35, 2.23, 2.42, 2.20, P<0.05 or P<0.01). Conclusion:Modified Banxia Baizhu Tianma Decoction combined with Nimodipine tablets can relieve the clinical symptoms of CCCI patients, improve blood flow velocity, blood rheology level and cognitive function, and improve clinical efficacy.

Background Evidence on the association between greenness and adiposity in children and adolescents is inconsistent and mostly from developed countries. Relatively limited evidence is from China. Objective To assess the association between greenness and adiposity in children and adolescents based on satellite remote sensing data. Methods From 2016 to 2018, a cross-sectional study was conducted among 52316 children and adolescents aged 5-18 years in three cities in the Pearl River Delta region of China. Basic sociological and demographic characteristics of the population and adiposity levels were collected through questionnaires. Land Remote-Sensing Satellite (Landsat) data and moderate-resolution imaging spectroradiometer (MODIS) products were used to quantify the greenness around the schools and homes, including normalized difference vegetation index (NDVI), vegetation continuous field (VCF), soil-adjusted vegetation index (SAVI), and enhanced vegetation index (EVI) calculated within 500 m and 1000 m buffers centered around the participants' homes or schools. A restricted cubic spline function was used to assess the exposure-response relationship. After categorizing greenness levels into quartiles with the first quartile as the reference, two-level generalized linear models were applied to assess the change in body mass index z-scores (zBMI) and the risk of overweight of children and adolescents in higher quartiles relative to the lowest quartile. In addition, counterfactual framework modelling was applied to assess the potential mediation effects of PM_2.5 and NO₂, and physical activity levels on the associations between greenness and adiposity levels. Results Of the 52316 children included, 8406 (16.1%) were overweight. A non-linear negative association of the level of greenness around the homes or schools and zBMI was found, with a significant lower zBMI in children and adolescents when a certain level of greenness was reached. After adjusting for confounders, the participants in the highest quartile had a significantly lower level of zBMI and a significantly lower risk of overweight compared with those in the lowest quartile of NDVI_{500 m} and VCF_{500 m}. The estimate change (\begin{document}$b$\end{document}) for zBMI was −0.07 (95%CI: −0.10-−0.04) and the odds ratio (OR) for overweight was 0.92 (95%CI: 0.85-0.99) for the students in the highest NDVI_{500 m} quartile based on home address compared to those in the lowest quartile. Significant negative associations were also observed when 1000 m buffer, SAVI, and EVI were used. The mediation analysis showed that PM_2.5 and NO₂ partially mediated the negative association of NDVI_{500 m} with zBMI , and the proportions of mediation were 50% (95%CI: 20%-80%) and 90% (95%CI: 50%-160%), respectively while no significant mediation effect was observed for physical activity level. Conclusion Higher levels of greenness surrounding homes or schools may be associated with a reduced risk of overweight and decreased zBMI in children and adolescents, and such associations may be partially mediated by reducing air pollutant concentrations.

Amyloid fibrils are found in systemic amyloidosis diseases such as Alzheimer's disease, Parkinson's disease, and type II diabetes. Currently, these diseases are diagnosed by observation of fibrils or plaques, which is an ineffective method for early diagnosis and treatment of disease. The goal of this study was to develop a simple and quick method to predict the possibility and speed of fibril formation before its occurrence. Oligomers generated from seven representative peptide segments were first isolated and detected by ion-mobility mass spectrometry (IM-MS). Then, their assemblies were disrupted using formic acid (FA). Interestingly, oligomers that showed small ion intensity changes upon FA addition had rapid fibril formation. By contrast, oligomers that had large ion intensity changes generated fibrils slowly. Two control peptides (aggregation/no fibrils and no aggregation/no fibrils) did not show changes in their ion intensities, which confirmed the ability of this method to predict amyloid formation. In summary, the developed method correlated MS intensity ratio changes of peptide oligomers on FA addition with their amyloid propensities. This method will be useful for monitoring peptide/protein aggregation behavior and essential for their mechanism studies.

BACKGROUND/OBJECTIVES: The association between tea consumption and risk of coronary heart disease (CHD) remains controversial. This study aimed to determine whether tea consumption has an effect on CHD risk in Chinese adults. SUBJECTS/METHODS: In this hospital-based case-control study, 267 cases of CHD and 235 non-CHD controls were enrolled. Blood samples from all cases were examined. Cardiac function indices (left ventricular ejection fraction, left ventricular end-diastolic dimension, lactate dehydrogenase, and creatine kinase of the muscle or brain type), blood lipid index (high-density lipoprotein cholesterol), and blood coagulation function indices (fibrinogen and activated partial thromboplastin time) were recorded. Tea consumption of study participants was assessed by a specifically designed questionnaire. The baseline characteristics of the study populations were recorded, and CHD-related biomarkers were detected. Differences in baseline characteristics of the study participants were examined using t-tests for continuous variables and chi-squared tests for categorical variables. Unconditional logistic regression was used to measure the association between tea and CHD. RESULTS: There were significant differences in cardiac function indices, blood lipid index, and blood coagulation indices between CHD cases and controls (P < 0.05). We found tea consumption reduced CHD risk in female participants (adjusted odds ratio (OR) = 0.484, 95% CI: 0.242–0.968, P = 0.0403). Regarding the type of tea consumed, the risk of CHD was reduced in women who drank partially fermented tea (adjusted OR = 0.210, 95% CI: 0.084–0.522, P = 0.0008). Analytic results for the amount of tea consumed per unit time showed CHD risk was reduced in women who consumed 1–2 cups of tea per day (adjusted OR = 0.291, 95% CI: 0.131–0.643, P = 0.0023). A tea-drinking frequency of > 6 days/week was beneficial for CHD prevention (adjusted OR = 0.183, 95% CI: 0.049–0.679, P = 0.0112). When analyzed according to the duration of tea consumption, the risk of CHD was reduced in participants who had been drinking tea for 10–20 years (adjusted OR = 0.360, 95% CI: 0.137–0.946, P = 0.0382). CONCLUSIONS: Tea consumption is associated with a reduced risk of CHD in female but not male populations in Guangzhou.

L-arginine (L-Arg) is an alkaline amino acid that possesses various function groups and acts as an important precursor for useful chemical synthesis. L-Arg derivatives are widely applied in pharmaceutical, food and cosmetic industries. Environment friendly and cost-effective production of L-Arg derivatives by enzymatic catalysis provides significant advantages over chemical synthesis and microbial fermentation. In this article, several typical L-Arg derivatives and their enzymatic production processes are highlighted. Furthermore, prospect is also addressed about enzymatic production of L-Arg derivatives.

Practice teaching and supervision has become an important part of hospital social work practice, and the handling and response to internship dilemma is the problem that every institution supervisor needs to think a-bout. Based on qualitative interview and text analysis, starting from the needs of intern, this paper found that students of social work major mainly faced the following dilemma in the process of hospital practice: role adapta-tion, the dilemma of professional practice, the dilemma of ethical relationship and practice burnout and so on. Combined with their own supervision experience, this paper put forward coping methods.

Objective: To investigate the relationship between the erythrocyte membrane protein gene mutations and the clinical severity of hereditary spherocytosis (HS). Methods: Targeted sequencings were performed on 25 HS patients, correlation between HS mutations and patients’ clinical characteristics were evaluated. Results: A total of 25 HS patients were enrolled, including 13 males and 12 females with median age of 20 (4-55) years, including 9 compensatory hemolysis patients, 9 patients with mild anemia, 3 patients with moderate anemia and 4 patients with severe anemia. Of them, 18 patients (72%) harbored HS-related mutations, including ANK1 mutation in 6 cases, SLC4A1 mutation in 6 cases, SPTB mutation in 5 cases and 1 case with EPB41 mutation. Seven patients (28%) didn’t carry common HS mutations. SPTB and SLC4A1 mutations mainly affected male patients. There was no significant difference between the age of diagnosis (P=0.130) and HGB level (P=0.585) in patients with HS mutation and those without mutation, however, the EMA binding fluorescence intensity (P=0.015), AGLT50 (P=0.032) and EOF minimal hemolytic concentration (P=0.027) were significantly different in these two groups of HS patients. Conclusion To screen erythrocyte membrane protein coding gene mutations could favor the diagnosis of HS, and patients without mutations have mild clinical phenotype.