ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.

Objective To investigate the correlation between TCM syndrome types and solar term of onset in patients with gastric cancer.Methods A total of 359 patients with gastric cancer admitted to the Cancer Center of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to August 2023 were included in this study,and the frequency distribution method was used to analyze their information such as sex,age,solar term of onset,differentiation,metastasis and TCM syndrome type.The solar term of onset corresponding to the onset date was calculated,and then the association between solar term of onset and TCM syndrome type in gastric cancer was analyzed.The circular distribution method was used to explore the peak of solar term of onset and TCM syndrome type.Results Among the 359 patients with gastric cancer included in this study,male patients were more than female patients(1.69∶1).The age of onset was mainly between 60 and 70 years old(117 cases,32.6%),and male patients(85 cases,72.6%)were more than female patients(32 cases,27.3%)in this age group.The most common TCM syndromes were qi and blood deficiency syndrome(160 cases,44.6%)and phlegm damp condensation syndrome(94 cases,26.2%).The onset of the disease mainly occurred in winter(132 cases,36.8%),and the peaks were light snow(31 cases,23.5%),major cold(25 cases,18.9%),heavy snow(23 cases,17.4%)and the start of winter(22 cases,16.7%).Qi and blood deficiency syndrome and phlegm damp condensation syndrome in patients with gastric cancer were correlated with solar terms and seasons(P<0.05).The 285 patients with gastric cancer were mainly poorly differentiated gastric cancer(175 cases,61.4%),mainly concentrated in winter(66 cases,37.7%).The main route of gastric cancer metastasis is lymph node metastasis,followed by liver and abdominal cavity metastasis.Conclusion Qi and blood deficiency syndrome and phlegm dampness condensation syndrome are common in patients with gastric cancer.The onset time of gastric cancer is mostly in winter,and the syndrome type is significantly correlated with the onset solar term and differentiation degree.

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role. The cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674S knock-in mice (SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. In addition, suppressing the IRE1α/XBP1s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2a, SERCA2b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1α/XBP1s pathway and SERCA2 might be potential targets for PH therapy.

Pulmonary arterial hypertension (PAH) is a clinical hemodynamic syndrome characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance leading to right heart failure and death. Vascular remodeling is the most prominent histopathological feature of PAH, which is regulated by many factors. Endoplasmic reticulum stress, calcium disorder and mitochondrial dysfunction are involved in the vascular cell proliferation and apoptosis by regulating intracellular calcium homeostasis and cellular metabolism. Epigenetic phenomenon such as DNA damage and abnormal expression of miRNA are also involved in the regulation of abnormal proliferation of vascular cells. Vascular cell phenotype switching including endothelial-mesenchymal transition and smooth muscle cell phenotype switching play an important role in abnormal proliferation of vascular cells. Vascular remodeling is produced by a variety of cells and molecular pathways, and aiming at multiple targets which is expected to find a new breakthrough in the treatment of PAH,and to improve abnormal vascular remodeling, delay or even reverse the progression of PAH.
Cell Proliferation ; Cells, Cultured ; Humans ; Hypertension, Pulmonary ; physiopathology ; MicroRNAs ; genetics ; Myocytes, Smooth Muscle ; pathology ; Pulmonary Artery ; pathology ; Vascular Remodeling ; genetics

Objective To investigate the predictive value of D-dimer for early neurological deteriora- tion (END) in patients with acute ischemic stroke. Methods Patients with acute ischemic stroke admitted to the Department of Neurology, the Second People ' s Hospital of Shenzhen between January 2015 and December 2017 were enrolled retrospectively. END was defined as an increase ≥2 in the National Institutes of Health Stroke Scale (NIHSS) score or an increase ≥1 in the motor function score within 7 days after admission compared with the baseline score. Demographics, baseline clinical data, and primary treatment options during hospitalization were compared between the END group and the non-END groups. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of D-dimer for END. Results A total of 625 patients were enrolled in the study, including 40 in the END group (including 3 deaths) and 585 in the non-END group. The mean hospital stay, international normalized ratio, D-dimer, uric acid, NIHSS score and modified Rankin Scale (mRS) score at admission, and the proportion of patients with complete anterior circulation infarction, large atherosclerotic stroke, and pulmonary infection were significantly higher than those in the non-END group (all P < 0. 05). There was no significant difference in the proportion of patients receiving thrombolysis, antiplatelet,anticoagulation, and statins between the two groups. ROC curve analysis showed that the area under the curve of D-dimer predicting END was 0. 810 (95％ confidence interval [CI] 0. 736-0. 884; P < 0. 001); the optimal cut-off value was 2. 35 mg/L, and the sensitivity and specificity were 54. 74％ and 96. 13％ respectively. Multivariate logistic regression analysis showed that large atherosclerotic stroke (odds ratio [OR] 1. 115, 95％ CI 1. 005-1. 390; P = 0. 003 ), D-dimer ≥2. 35 mg/L (OR 1. 055,95％ CI 1. 012-1. 150; P = 0. 001 ), NIHSS score at admission (OR 1. 191, 95％ CI 1. 006-1. 410; P <0. 001), mRS score > 1 at admission (OR 1. 755, 95％ CI 1. 139-3. 656; P = 0. 037 ), and pulmonary infection (OR 2. 598, 95％ CI 1. 132-3. 081; P = 0. 012) were the independent risk factors for END in patients with acute ischemic stroke. Conclusion D-dimer ≥2. 35 mg/L at admission has higher predictive value for END in patients with acute ischemic stroke.

Objective To evaluate the predictive value of HEART and GRACE scores for risk stratification and 30-day major adverse cardiovascular events (MACE) in patients with acute chest pain in emergency department.Methods This is a prospective observational study.Patients with acute chest pain aged 18 years or older who were first diagnosed in our emergency department were enrolled from January 1,2016 to September 1,2017.The clinical data were collected,and HEART and GRACE scores were calculated.All causes of MACE in each patient were followed up for 30 days.Results This study included 1004 patients with acute chest pain for analysis.Finally this study enrolled 600 patients with an age range of 20-98 years (mean 63.28±15.47 years),351 males (58.5％) and 249 females (41.5％).The age,past history (smoking,coronary heart disease and diabetes),GRACE score and HEART score in MACE patients were significantly higher than those in non-MACE patients (P＜0.05).The area under the ROC curve of HEART and GRACE scores were 0.817 (95％ CI 0.771-0.863) and 0.739 (95％ CI:0.687-0.791),respectively.The percent of patients with 30-day MACE with GRACE score and HEART score were 6.2％ vs 4.1％ in low-risk stratification,19.7％ vs 15.1％ in medium-risk stratification,and 35.1％ vs 56.5％ in high-risk stratification,respectively.Conclusions The HEART score is superior to the GRACE score in predicting 30-day MACE in patients with acute chest pain in emergency department.

Objective: To investigate the feasibility and efficacy of transcatheter closure of anastomotic leakage after aortic surgery using Amplatzer Vascular Plug Ⅲ (AVP Ⅲ). Methods: A retrospective analysis was performed in 5 patients with anastomotic leakage after aortic surgery, who underwent transcatheter closure in our hospital from January to June 2017 using AVP Ⅲ. Surgeries were performed in 3 cases of Standford type A dissection, 1 case of ascending aortic aneurysm and 1 case of persistent truncus.There were 3 males,and age was (43.8±13.1) years old. Anastomotic leakages located at the ascending aorta in 4 patients, and the other one located between the aortic arch and the stent-graft.Three of them had aorta-right atrium fistula and patients suffered from progressive heart failure. False aneurysm between aorta and pulmonary artery was formed in 1 patient, and patent aortic false lumenwas found in the other patient. All the AVP Ⅲ were deployed based on a femoral arteriosus loop. Patients were followed up after transcatheter closure to observe the clinical results. Results: Six AVP Ⅲ were successfully implanted in the 5 patients. Trivial residual shunt was seen in 1 patient after closure. The patients were followed up 6 (1, 6) months. The cardiac function improved from NYHA class Ⅱ-Ⅳ to class Ⅰ-Ⅱ after the procedure in 3 congestive heart failure patients.The right atrium systolic pressure was significantly reduced after the procedure((8.7±1.8) mmHg (1 mmHg=0.133 kPa) vs. (24.3±2.3) mmHg, P=0.03). The diameter of the false aneurysm reduced in 1 patient after the procedure. Complete thrombosis formation of the thoracic false lumen was observed in 1 patient. Conclusion Transcatheter closure of anastomotic leakage after aortic surgery using AVP Ⅲ is feasible and effective according to our primary experience.

Objective To evaluate the long-term outcome of fully covered self-expandable metal stents(FCSEMS)for the treatment of benign biliary strictures(BBS). Methods Between June 2008 and September 2013, 68 patients with BBS receiving endoscopic retrograde cholangiopancreatography and FCSEMS placement were retrospectively enrolled. Data of endoscopic treatment, stricture resolution and recurrence were collected, and related risk factors were analyzed. Results FCSEMSs were successfully placed in all patients and removed in 93.4%(57/61). The median stent duration was 9.0(range 0.2-37.1)months. Stricture resolution occurred in 74.2%(46/62)patients. During median follow-up of 54.0 (range 2.5-96.0)months,stricture recurrences were seen in 16.7%(6/36)patients. Multivariate analysis revealed that distance between stricture and hepatic bifurcation of less than 1.5 cm(P=0.034,OR=6.395, 95%CI:1.153-35.464), and stent migration(P= 0.024, OR= 0.153, 95%CI:0.030-0.782)were significant risk factors for stricture resolution. Meanwhile, the stricture length longer than 1.0 cm(P=0.028, HR = 6.766, 95% CI:1.233-37.122)was a significant risk factor for stricture recurrence. Conclusion Endoscopic treatment combined with FCSEMS can achieve excellent efficacy in resolving BBS with low recurrence rate. However, location and length of BBS, as well as stent migration may impair its effectiveness.

Objective: To investigate the clinical efficacy and safety of acupuncture and moxibustion in the adjuvant treatment of internet addiction disorder. Methods: From January 2013 to April 2015, a total of 38 patients with internet addiction disorder were randomly selected and divided into study group(19 cases) and control group(19 cases) according to the odd and even order of hospitalize.The control group received psychological therapy, antianxiety therapy and antidepression therapy.The study group received acupuncture and moxibustion in addition to all therapies of the control group.The patients were treated for 8 weeks.Chiese Internet Addiction Scale(CIAS), Family Assessment Device(FAD), HAMD, HAMA were used to determine the internet addiction severity and social function of the two groups at baseline and the 8th weekend of treatment, and TESS at the 8th weekend of treatment. Results: At the 8th weekend of treatment, the scores of CIAS, FAD, HAMA+ HAMD in the two groups were all significantly lower than baseline[(86.8±13.6)points vs.(38.3±11.5)points, t=11.872, (85.6±12.3)points vs.(54.6±18.2)points, t=7.123; (185.8±31.5)points vs.(80.6±29.4)points, t=10.643, (182.7±12.7)points vs.(110.5±32.3)points, t=9.068; (53.4±7.6)points vs.(21.7±9.7)points, t=11.215, (55.2±8.3)points vs.(35.2±8.3)points, t=7.428)](all P<0.05). At the 8th weekend of treatment, the scores of CIAS, FAD, HAMA+ HAMD in the study group were significantly lower than those in the control group(t=3.301, 2.985, 10.825, all P<0.05). There was no statistically significant difference in the incidence rate of side effects between the two groups(all P>0.05). Conclusion Acupuncture and moxibustion is effective and safe in the treatment of patients with internet addiction disorder.