ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis （CAG） through regulating the Golgi protein 73 （GP73）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway and modulating endoplasmic reticulum stress （ERS）. MethodA mouse model of CAG was induced by multiple factors， including ranitidine， N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and irregular feeding. The CAG mice were randomized into five groups： model， Morodan （2.0 g·kg^-1）， and high-dose， medium-dose， and low-dose （7.6， 3.8， 1.9 g·kg^-1， respectively） Xianglian Huazhuo prescription， with 10 mice in each group. At the same time， 10 mice in normal group were set up. The mice in the Morodan group and the high-dose， medium-dose， and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage， and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration， the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin （HE） staining and transmission electron microscopy （TEM） were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， gastrin-17 （G-17）， and GP73 were determined by enzyme-linked immunosorbent assay （ELISA）. The pepsinogen ratio （PGR， PGⅠ/PGⅡ） was calculated. The protein levels of GP73， PERK， phosphorylated （p）-PERK， glucose-regulated protein 78 （GRP78）， ATF4， CCAAT enhancer-binding protein homologous protein （CHOP）， cysteinyl aspartate-specific protease-12 （Caspase-12）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence （IF） assay， and the location of Bcl-2 and Bax by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands， declined serum levels of PGI， PGR， G-17， and GP73 （P<0.01）. downregulated protein levels of GP73， p-PERK， ATF4， GRP78， CHOP， Caspase-12， and Bax in the gastric tissue， and upregulated protein level of Bcl-2 （P<0.01）. Compared with the model group， the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds， alleviated pathological damage， swelling endoplasmic reticulum， elevated serum levels of PGI， G-17， and GP73 （P<0.05， P<0.01）， and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue （P<0.05， P<0.01）. The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR （P<0.05， P<0.01） and upregulated protein levels of GP73， p-PERK， ATF4， GRP78， and CHOP in the gastric tissue （P<0.05， P<0.01）. ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa， thereby demonstrating a protective effect against CAG in mice.

ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis （CAG） through regulating the Golgi protein 73 （GP73）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway and modulating endoplasmic reticulum stress （ERS）. MethodA mouse model of CAG was induced by multiple factors， including ranitidine， N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and irregular feeding. The CAG mice were randomized into five groups： model， Morodan （2.0 g·kg^-1）， and high-dose， medium-dose， and low-dose （7.6， 3.8， 1.9 g·kg^-1， respectively） Xianglian Huazhuo prescription， with 10 mice in each group. At the same time， 10 mice in normal group were set up. The mice in the Morodan group and the high-dose， medium-dose， and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage， and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration， the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin （HE） staining and transmission electron microscopy （TEM） were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， gastrin-17 （G-17）， and GP73 were determined by enzyme-linked immunosorbent assay （ELISA）. The pepsinogen ratio （PGR， PGⅠ/PGⅡ） was calculated. The protein levels of GP73， PERK， phosphorylated （p）-PERK， glucose-regulated protein 78 （GRP78）， ATF4， CCAAT enhancer-binding protein homologous protein （CHOP）， cysteinyl aspartate-specific protease-12 （Caspase-12）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence （IF） assay， and the location of Bcl-2 and Bax by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands， declined serum levels of PGI， PGR， G-17， and GP73 （P<0.01）. downregulated protein levels of GP73， p-PERK， ATF4， GRP78， CHOP， Caspase-12， and Bax in the gastric tissue， and upregulated protein level of Bcl-2 （P<0.01）. Compared with the model group， the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds， alleviated pathological damage， swelling endoplasmic reticulum， elevated serum levels of PGI， G-17， and GP73 （P<0.05， P<0.01）， and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue （P<0.05， P<0.01）. The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR （P<0.05， P<0.01） and upregulated protein levels of GP73， p-PERK， ATF4， GRP78， and CHOP in the gastric tissue （P<0.05， P<0.01）. ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa， thereby demonstrating a protective effect against CAG in mice.

Objective To investigate the therapeutic effect of Sheng Mai San mixed Jiawei Sheng Xian Tang on patients with heart failure with reduced ejection fraction(HFrEF)of Qi deficiency blood stasis type,and its impact on the immune inflammatory response of patients.Methods Ninety patients with HFrEF of Qi deficiency blood stasis type were selected and divided into two groups according to the treatment plan.Patients of the conventional group(42 cases)took sacubitril/valsartan sodium tablets orally.Patients of the combined group(48 cases)were treated with Sheng Mai San combined with Jiawei Sheng Xian Tang on the basis of the conventional group,one dose per day,and divided it in two servings used in the morning and evening.The symptoms of the patients were evaluated by using traditional Chinese medicine(TCM)syndrome score before and after the treatment respectively.Echocardiography technology was used to measure the left ventricular end-diastolic diameter(LVEDD)and left ventricular ejection fraction(LVEF).Enzyme-linked immunosorbent assay was used to detect pentaggrin 3(PTX3),tumor necrosis factor-α(TNF-α),galectin-3(Gal-3),interleukin(IL)-8,IL-6,IL-33 and angiotensin Ⅱ(Ang Ⅱ).N-terminal pro-brain natriuretic peptide(NT-proBNP)was detected by immunofluorescence analysis.The therapeutic effect was evaluated based on the symptoms and the New York Heart Association(NYHA)cardiac function classification in the United States.Results After treatment,the levels of TCM syndrome scores,LVEDD,TNF-α,PTX3,IL-8,IL-6,IL-33,NT-proBNP,Gal-3 and AngⅡ decreased in both groups,and those in the combined group were lower than those in the conventional group(P＜0.05).The LVEF increased,and which were higher in the combined group than those of the conventional group(P＜0.05).After the treatment,the total effective rate of the combined group was higher than that of the conventional group(P＜0.05).Conclusion The Sheng Mai San mixed Jiawei Sheng Xian Tang as adjuvant therapy can effectively reduce the levels of immune inflammatory cytokines in HFrEF patients of Qi deficiency blood stasis type,improve their clinical symptoms and enhance therapeutic effect.

Objective To investigate the therapeutic effect of Sheng Mai San mixed Jiawei Sheng Xian Tang on patients with heart failure with reduced ejection fraction(HFrEF)of Qi deficiency blood stasis type,and its impact on the immune inflammatory response of patients.Methods Ninety patients with HFrEF of Qi deficiency blood stasis type were selected and divided into two groups according to the treatment plan.Patients of the conventional group(42 cases)took sacubitril/valsartan sodium tablets orally.Patients of the combined group(48 cases)were treated with Sheng Mai San combined with Jiawei Sheng Xian Tang on the basis of the conventional group,one dose per day,and divided it in two servings used in the morning and evening.The symptoms of the patients were evaluated by using traditional Chinese medicine(TCM)syndrome score before and after the treatment respectively.Echocardiography technology was used to measure the left ventricular end-diastolic diameter(LVEDD)and left ventricular ejection fraction(LVEF).Enzyme-linked immunosorbent assay was used to detect pentaggrin 3(PTX3),tumor necrosis factor-α(TNF-α),galectin-3(Gal-3),interleukin(IL)-8,IL-6,IL-33 and angiotensin Ⅱ(Ang Ⅱ).N-terminal pro-brain natriuretic peptide(NT-proBNP)was detected by immunofluorescence analysis.The therapeutic effect was evaluated based on the symptoms and the New York Heart Association(NYHA)cardiac function classification in the United States.Results After treatment,the levels of TCM syndrome scores,LVEDD,TNF-α,PTX3,IL-8,IL-6,IL-33,NT-proBNP,Gal-3 and AngⅡ decreased in both groups,and those in the combined group were lower than those in the conventional group(P＜0.05).The LVEF increased,and which were higher in the combined group than those of the conventional group(P＜0.05).After the treatment,the total effective rate of the combined group was higher than that of the conventional group(P＜0.05).Conclusion The Sheng Mai San mixed Jiawei Sheng Xian Tang as adjuvant therapy can effectively reduce the levels of immune inflammatory cytokines in HFrEF patients of Qi deficiency blood stasis type,improve their clinical symptoms and enhance therapeutic effect.

This study explored whether Astragalus polysaccharide(APS)can regulate the VEGF/VEGFR signaling pathway to affect the proliferative activity of rat intestinal mucosal microvascu-lar endothelial cells(RIMMVECs).RIMMVECs were isolated from newborn rats,then purified and treated with APS at concentrations of 0.1,1.0,10.0,100.0,1 000.0,and 10 000.0 mg/L.MTT was used to determine the effect of APS on RIMMVECs proliferation and screen for the optimal concentration of APS.Subsequently,flow cytometry was used to detect the changes in cell cycle to evaluate the stage of action of APS on the cell cycle in RIMMVECs.Then,the ELISA was used to detect the changes of VEGFA in cell supernatant to evaluate the potential of cell proliferation and angiogenesis.The changes in fluorescence intensity of Fluo-8AM was observed using fluorescence microscopy to evaluate intracellular Ca2+levels.Finally,Western blot was used to detect the ex-pression of PERK in RIMMVECs to analyze the possible mechanism of APS.The results showed that 100 mg/L APS significantly enhanced the proliferative activity of RIMMVECs,increased the content of VEGFA in the cell supernatant,the intracellular Ca2+levels,and the expression of PERK protein,indicating that APS promotes the proliferation of RIMMVECs,which may be a-chieved by promoting the expression of VEGFA and activating the ERK pathway.

This study explored whether Astragalus polysaccharide(APS)can regulate the VEGF/VEGFR signaling pathway to affect the proliferative activity of rat intestinal mucosal microvascu-lar endothelial cells(RIMMVECs).RIMMVECs were isolated from newborn rats,then purified and treated with APS at concentrations of 0.1,1.0,10.0,100.0,1 000.0,and 10 000.0 mg/L.MTT was used to determine the effect of APS on RIMMVECs proliferation and screen for the optimal concentration of APS.Subsequently,flow cytometry was used to detect the changes in cell cycle to evaluate the stage of action of APS on the cell cycle in RIMMVECs.Then,the ELISA was used to detect the changes of VEGFA in cell supernatant to evaluate the potential of cell proliferation and angiogenesis.The changes in fluorescence intensity of Fluo-8AM was observed using fluorescence microscopy to evaluate intracellular Ca2+levels.Finally,Western blot was used to detect the ex-pression of PERK in RIMMVECs to analyze the possible mechanism of APS.The results showed that 100 mg/L APS significantly enhanced the proliferative activity of RIMMVECs,increased the content of VEGFA in the cell supernatant,the intracellular Ca2+levels,and the expression of PERK protein,indicating that APS promotes the proliferation of RIMMVECs,which may be a-chieved by promoting the expression of VEGFA and activating the ERK pathway.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.

Data analysis models may assist the transmission of traditional Chinese medicine （TCM） experience and clinical diagnosis and treatment， and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis， and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases， syndrome elements， evolution of pathogenesis， and syndrome differentiation protocols； knowledge-driven is to make use of data and information to promote decision-making and action processes， and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy， and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research， we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state， and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile， the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained， and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored， so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal circulation technique that provides circulatory and oxygenation support, and it is currently used in the treatment of cardiogenic shock (CS), pulmonary embolism, cardiac arrest (CA), and other diseases. However, this technology is still associated with high complications and mortality. The use of predictive scores for risk stratification before VA-ECMO will be helpful to screen the optimal benefiting population, make optimal clinical decisions, and allocate medical resources reasonably. At present, there are few reports about predictive scores for VA-ECMO. This article systematically reviewed the predictive performance of various scoring tools [the survival after venoarterial ECMO (SAVE) score, prediction of cardiogenic shock outcome for acute myocardial infarction (AMI) patients salvaged by VA-ECMO (ENCOURAGE) score, model for end-stage liver disease (MELD-Ⅺ) score, post-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) score, the predicting mortality in patients undergoing VA-ECMO after coronary artery bypass grafting (REMEMBER) score, predictors of mortality with VA-ECMO for acute massive pulmonary embolism, extracorporeal cardiopulmonary resuscitation (ECPR) score, the hypothermia outcome prediction after extracorporeal life support (HOPE) score] for patients receiving VA-ECMO to provide reference for clinical treatment.

Objective:To study the relationship between serum osteopontin and osteopontin and type 2 diabetes mellitus (T2DM) complicated with coronary heart disease, and to evaluate the correlation between the levels of serum osteopontin and osteopontin with the severity of coronary artery lesions in T2DM patients.Methods:A total of 100 T2DM patients who were suspected to have stable coronary heart disease and underwent coronary angiography from November 2019 to December 2020 were selected from the Affiliated Hospital of Chengde Medical College, according to coronary angiography results, 60 patients with confirmed coronary heart disease were classified as the case group and 40 patients with non-coronary heart disease were classified as the control group for retrospective analysis. The clinical data and biochemical indicators of all patients were recorded, and Gensini score was calculated. The concentration of osteopontin and osteopontin in serum was quantitatively determined by double-antibody enzyme linked immunosorbent assay method. Independent sample t-test was used to compare the mean of normal distribution measurement data between the two groups. The non normal distribution data are represented by M ( Q1, Q3), and Mann Whitney U test is used for comparison between groups. Composition comparison between count data groups χ 2 inspection. Spearman correlation analysis was used to analyze the correlation between serum osteopontin and osteopontin and Gensini score in patients with T2DM. Results:Univariate analysis showed that serum osteopontin and osteopontin were (13.076(8.433, 23.552) μg/L) and (0.437(0.300, 0.630) μg/L) significantly higher in the case group than in the control group (6.367(4.605, 9.048) μg/L) and (0.299(0.196, 0.399) μg/L) respectively, with statistically significant differences ( Z=5.12, 3.28, all P<0.001). Multi-factor logistic regression analysis showed that osteoprotegerin ( OR=2.887, 95% CI:1.850-8.515, P=0.024) and osteopontin ( OR=13.109, 95%CI: 2.557-67.204, P=0.002) were associated with T2DM combined with coronary heart disease, and the risk of T2DM combined with coronary heart disease increased with higher levels of osteoprotegerin and osteopontin. Spearman correlation analysis showed that serum osteopontin and osteoprotegerin were positively correlated with Gensini score in T2DM patients ( r=0.591, 0.467; all P<0.05). Conclusion:Serum osteopontin and osteoprotegerin are associated with T2DM combined with coronary heart disease, and high serum osteopontin and osteoprotegerin are risk factors for T2DM combined with coronary heart disease; serum osteopontin and osteoprotegerin are positively correlated with the degree of coronary artery disease in T2DM patients.