We have designed and carried out problem based learning (PBL) pedagogy since 2004. According to clinical eases, students learnt the pathophysiology of heart failure knowledge by themselves. Each group recommen-ded one student to make an oral presentation and wrote a review about heart failure. Preparing clinical cases and group discussions are very important. At the same time we should pay attention to the change in role of the teacher in PBL and cooperation with other disciplines.

Objective: To study the protective effect of enteral nutrition with Salvia miltiorrhiza on injuries multiple organs in rabbits. Method: Forty-four rabbits were randomly divided into four groups: Normal control group (N) 8 rabbits, Endotoxin group (LPS), Enteral nutrition group (LPS+EN) and Enteral nutrition with Salvia miltiorrhiza group (LPS+DS),each 12 rabbits. Three days before given endotoxin, LPS+DS group was fed enteral nutrition fluid with Sallvia miltiorrhiza 80 ml/kg bw (15g salvia per 100 ml fluid) and LPS+ EN group was fed enteral nutrition only.N group was fed the same quantity of normal saline. At the end of 10 d, the rabbits were killed and serum SOD, MDA, endotoxin and intestinal mucus SIgA contents were determined. Small intestine, liver, lung, kidney and heart were taken for pathological examination. Results: Serum MDA of LPS+DS group was much lower than LPS group, endotoxin level also lower , but intestinal SIgA content higher LPS group . The pathological examination showed that the intestinal villi were shortend, injured , and necrotic in LPS group; liver was hemorrhagic at portal area with cytoplasmic vacuolization, lung and kidney were also injuried pathologically. These pathological features were comparatively mild in LPS+EN group and much better in LPS+ DS group. Conclusion: Enteral nutrition with Salvia miltiorrhiza may reduce the oxidative damages of multiple organs induced by endotoxin as shown by increased SIgA of small intestine, maintenance of intestinal mucosa integrity and alleviation of pathological changes of multiply organs in rabbits.

Objective To investigate the effects of Sini decoction on function of hypothalamic-pituitary-adrenal axis in patients with sepsis.Methods A prospective single-blind randomized controlled trial was conducted.60 septic patients were divided into three groups with the method of random number table,20 cases in the control group,20 in the Chinese herb group,and 20 in corticoid group.All of them received routine treatment.Patients in Chinese herb group were given Sini decoction in addition (decoction of monkshood 15 g,dried ginger 15 g,honey-fried licorice 10 g) 100 mL/d orally or by nasal feeding,while patients in corticoid group were given hydrocortisone 200 mg/d intravenously instead,both for 7 days.Before the treatment,3 days and 14 days after treatment,blood was collected to determine the levels of adrenocorticotropic hormone (ACTH) and cortisol,and the result of ACTH stimulating test was observed.At the same time,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was recorded,and 3-day shock recovery rate and 28-day death rate were also compared among these groups.Results None of the three groups showed different result in ACTH stimulating test (x2=1.101,P=0.605).ACTH in three groups was gradually decreased.Compared with that before treatment,ACTH in Chinese herb group and corticoid groups began to decrease obviously on day 3 (ng/L:29.90 ± 3.31 vs.33.10 ±.3.31,28.20 ±.2.45 vs.33.30 ± 3.84,both P＜0.01),while in control group declined ACTH appeared later (on day 14) compared with before treatment (ng/L:29.40 ±5.63 vs.33.50 ±4.89,P＜0.05).No obvious difference in ACTH level was showed between the Chinese herb group and the cortical group (both P＞0.05).Cortisol level in both Chinese herb and cortical groups showed a raise-fall biphase trend while there was no change in the control.The cortical levels on day 3 in Chinese herb and cortical groups were much higher than that before treatment (μg/L:343.04 ± 31.20 vs.294.70 ±42.10,331.25 ±42.80 vs.280.36 ± 38.10,both P＜0.01) and that of control group (μg/L:291.61 ± 41.50,both P＜0.01),though no significant statistical difference was observed between two groups (both P＞0.05).APACHE Ⅱ score on day 14 in control,Chinese herb and cortical groups was significantly lower than that before treatment (16.8 ± 5.1 vs.20.1 ± 4.3,13.4 ± 3.2 vs.18.3 ± 3.8,15.1 ± 2.5 vs.19.5 ± 4.0,all P＜0.01),and the score was much lower in Chinese herb group comparing with that of control group (P＜0.05).No statistical difference was observed among control,Chinese herb and cortical groups in lowering 28-day death rate [35.0％ (7/20),25.0％ (5/20),20.0％ (4/20)] and improving 3-day shock recovery rate [40.0％ (8/20),70.0％ (14/20),60.0％ (12/20),all P＞0.05].Conclusions Sini decoction could elevate cortisol while lower ACTH at the early stage of sepsis.Sini decoction could also effectively improve symptoms and hypothalamic-pituitary-adrenal axis function in septic patients without affecting death rate.

Objective To evaluate the imaging diagnosis of anomalous origin of coronary artery from the pulmonary artery(ACAPA).Methods A total of 11 cases with ACAPA were included in the present study.Chest films,echocardiography,cardioangiography,and electron beam computed tomography (EBCT) were employed as diagnostic modalities.Macroscopic anatomy at operation was referred. Results Ten cases were classified as anomalous origin of left coronary artery from the pulmonary artery(ALCAPA) and 1 case as anomalous origin of right coronary artery from the pulmonary artery(ARCAPA).They could not be diagnosed by chest films,but could be diagnosed by echocardiography in 3 cases,by EBCT in 1 case,and by cardioangiography in all cases.In ALCAPA,cardioangiography showed that the left coronary arteries arising from the posterior sinus or posterior wall of the pulmonary artery were perfused retrogradely via the collaterals from the dilated right coronary artery.In ARCAPA,the right coronary artery originated from the right sinus of the pulmonary artery.Gross anatomy at operation showed that the sites of the anomalous origins were the same as that of cardioangiography.Ischemic fibrosis of the anterior papillary muscles,mitral valve annulus enlargement,and prolapse of mitral valve,which led to mitral valve insufficiency,were found in 3 cases.Conclusion Chest film has limitation in the diagnosis and echocardiography should be further improved.Cardioangiography remains the “gold standard” of the preoperative diagnosis.

Objective:To investigate the expression of B lymphocyte induced maturation protein 1 (Blimp-1) in peripheral blood CD4 + T cells, CD19 + B cells and labial glands of patients with primary Sj?gren′s syndrome (pSS) and the correlation of Blimp-1 with clinical features. Methods:Expression of PRDM1 at mRNA level in CD4 + T cells, CD19 + B cells and labial gland tissues were detected by RT-PCR. Immunohistochemistry (IHC) was used to observe the distribution of Blimp-1. Correlation of PRDM1 expression at mRNA level with clinical indicators was analyzed. Results:PRDM1 expression at mRNA level in CD4 + T and CD19 + B cells were significantly higher in pSS group than in healthy control (HC) group ( P<0.01). Based on European League Against Rheumatism Sj?gren′s Syndrome Disease Activity Index (ESSDAI), the patients were classified into two groups: active group (ESSDAI≥5) and inactive group (ESSDAI<5). PRDM1 expression at mRNA level in CD4 + T and CD19 + B cells were also higher in the active group than in inactive group ( P<0.05). Blimp-1 protein accumulated around the acinus and duct of labial gland and in the germinal center in pSS patients. PRDM1 expression at mRNA level in labial gland tissues of pSS patients was positively correlated with lymphocyte infiltration ( r=0.781, P<0.001). Conclusions:pSS displayed high expression of Blimp-1. Blimp-1 might affect pSS disease activity and have clinical significance in pSS treatment.

Clopidogrel is one of the anti-platelet drugs, which is widely used in the world.It plays an important role in the treatment of patients with acute coronary syndrome and those undergoing percutaneous coronary intervention.Clopidogrel is effective in inhibiting the activity of platelets, decreasing the incidence of thrombosis in the stent, and then reducing the risk of adverse cardiovascular events in affected individuals. However, some patients still have coronary thrombosis after taking clopidogrel.This phenomenon is known as clopidogrel resistance or clopidogrel non-response or low response. Identification of clopidogrel resistance is of great significance in preventing the occurrence of adverse cardiovascular events.This paper provides guidance for the clinical treatment of clopidogrel resistance by discussing the definition, mechanisms and laboratory evaluation of clopidogrel resistance.

Objective:To summarize and elucidate the impact of ambient air pollution on biological aging among middle-aged and older adults.Methods:"Air pollution""Biological age""Epigenetic age""Biological aging"and"Epigenetic aging", as well as specific names of air pollutants and biological age were used as search keywords. This study searched the databases of PubMed and Web of Science for eligible English articles and CNKI, CQVIP, Wanfang, CBM, CSTP and other Chinese databases for eligible Chinese articles from inception until June 30, 2023. The language was limited to Chinese and English.Results:Among the 14 included articles, five studies investigated the impact of air pollution on DNA methylation age using different algorithms, while six studies explored the relationship between air pollutants and telomere length. Six studies focused on frailty as an outcome, and an additional study revealed the relationship between fine particulate matter (PM 2.5) and its components with composite indicator age (KDM age). The results indicated that, although different forms of biological ages were susceptible to different ambient air pollutants at different degrees, previous studies had consistently found that the increased levels of PM 2.5 and one of its major components, black carbon (BC), could significantly accelerate the biological aging of middle-aged and older adults. Similar trends were observed with nitrogen oxides (NO x) and ozone (O 3) but with relatively limited evidence. Conclusion:Major air pollutants could accelerate the biological aging of middle-aged and older adults.

Objective To investigate the mutation characteristics and influencing factors of ethambutol(EMB)resistance gene of Mycobacterium tuberculosis in Guangxi Zhuang Autonomous region,and to provide evidence for molecular diagnosis and clinical treatment of tuberculosis.Methods A total of 655 strains of Myco-bacterium tuberculosis(52 ethambutol resistant strains and 603 ethambutol sensitive strains)were collected continuously from 30 TB drug resistance monitoring sites in Guangxi in 2018-2019,and the mutation characteristics and influencing factors of ethambutol resistant genes were analyzed by whole genome sequencing.Results Among 655 strains of Mycobacterium tuberculosis,54 strains had ethambutol drug resistance gene mutation,the mutation rate was 8.24%(54/655).Among 52 EMB-resistant strains detected by proportional method,21 had gene mutation,the mutation rate was 40.38%(21/52),and 33 of 603 EMB-sensitive strains had gene mutation,the mutation rate was 5.47%(33/603).The gene mutation rate in drug-resistant strains was higher than that in sensitive strains(χ2 = 77.133,P = 0.000).The coincidence rate of EMB drug resistance phenotype and gene mutation was 40.38%(21/52),and the results of the two tests were not highly consistent(Kappa = 0.343,P<0.001).The mutant genes of 54 strains were embA,embB and embC,and there were 20 mutant forms,among which 29 were mutated at unit point,accounting for 53.70%(29/54),and 25 were mutated at joint site,accounting for 46.30%(25/54).Among the unit point mutations,embB306(35.19%)had the highest mutation proportion,followed by embB497(5.56%)and embB406(3.70%).Among the joint site mutations,embC270+embB378 had the highest mutation proportion(22.22%),The second was embB306+embA-12(3.70%).Gender,anti-tuberculosis treatment history,genotype and MDR might be related to EMB gene mutation(χ2 = 9.388,P = 0.004;χ2 = 27.084,P = 0.000;χ2 = 6.671,P = 0.010;χ2 = 68.826,P = 0.000).Multivariate logistic regression analysis showed that male(OR = 6.150),retreatment(OR = 2.636)and multidrug resistance(OR = 7.333)may be risk factors for EMB resistance gene mutation,and Beijing genotype may be a protective factor for EMB resistance gene mutation(OR = 0.511).Conclusion EMB resistance of Mycobacterium tuberculosis is related to embA,embB and embC gene mutations,and the incidence of EMB resistance phenotype is not high.For male,retreatable,MDR-resistant,and non-Beijing genotype TB patients,attention should be paid to the mutation of the EMB resistance gene.

Objective:To summarize and elucidate the impact of ambient air pollution on biological aging among middle-aged and older adults.Methods:"Air pollution""Biological age""Epigenetic age""Biological aging"and"Epigenetic aging", as well as specific names of air pollutants and biological age were used as search keywords. This study searched the databases of PubMed and Web of Science for eligible English articles and CNKI, CQVIP, Wanfang, CBM, CSTP and other Chinese databases for eligible Chinese articles from inception until June 30, 2023. The language was limited to Chinese and English.Results:Among the 14 included articles, five studies investigated the impact of air pollution on DNA methylation age using different algorithms, while six studies explored the relationship between air pollutants and telomere length. Six studies focused on frailty as an outcome, and an additional study revealed the relationship between fine particulate matter (PM 2.5) and its components with composite indicator age (KDM age). The results indicated that, although different forms of biological ages were susceptible to different ambient air pollutants at different degrees, previous studies had consistently found that the increased levels of PM 2.5 and one of its major components, black carbon (BC), could significantly accelerate the biological aging of middle-aged and older adults. Similar trends were observed with nitrogen oxides (NO x) and ozone (O 3) but with relatively limited evidence. Conclusion:Major air pollutants could accelerate the biological aging of middle-aged and older adults.

ObjectiveTo explore the potential molecular mechanism of Qizhu Kang'ai Formula （芪术抗癌方， QZKAF） for the treatment of colorectal cancer （CRC）. MethodsNetwork pharmacology was used to analyze the active ingredients and targets of QZKAF for CRC， and analyze the key targets of QZKAF for the treatment of CRC by gene function annotation （GO） and Kyoto Encyclopedia of Genomes （KEGG） pathway enrichment analysis. Molecular docking was applied to predict the binding activity of the core active ingredients to the key targets. A orthotopic transplantation tumor mice model of CRC was established to validate the key targets of QZKAF for CRC obtained from network pharmacology analysis. Forty-eight mice were randomly divided into the sham operation group， the model group， the 5-fluorouracil （5-Fu） group， and the QZKAF low-， medium-， and high-dose groups， with 8 mice in each group. Except for the sham operation group， the remaining groups underwent colon cancer orthotopic transplantation tumor modeling. The 5-Fu group was given 30 mg/kg of 5-Fu by intraperitoneal injection once every 3 days on the alternate day after modeling， while the QZKAF low-， medium-， and high-dose groups were given 2.925， 5.85， and 11.7 g/（kg·d） of QZKAF by gastric gavage， respectively， and the sham-operation group and the model group were gavaged with 0.1 ml/10 g of normal saline every day， all for 21 days. The in situ tumors mass and the number of liver metastases were compared between the groups. The pathological changes of colon tumor tissues were observed by HE staining， and the protein expression of protein tyrosine phosphatase nonreceptor type 1 （PTPN1）， vinculin， integrin subunit αν， integrin subunit β3， and E-cadherin were detected in colon tumor tissues by Western blot. ResultsNetwork pharmacology screening yielded that the top six core active ingredients of QZKAF intervening in CRC were quercetin， kaempferol， apigenin， luteolin， baicalein and ursolic acid. There were 212 targets of action， and the ranked top three were prostaglandin endoperoxide synthase 1 （PTGS1）， prostaglandin endoperoxide synthase 2 （PTGS2）， and PTPN1， which may be the key targets of QZKAF in the treatment of CRC. These key targets were significantly enriched mainly in phosphatidylinositol 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， focal adhesion and adhesion junction. Molecular docking results： except for PTGS1 with better binding activity to quercetin， kaempferol， and apigenin （binding energy ≥-7.0 kcal/mol）， PTGS1 showed strong binding activity to lignans， baicalein， ursolic acid， as well as PTGS2 and PTPN1 to the six core active ingredients （binding energy ＜-7.0 kcal/mol）. Experimental validation results： the protein expression of PTPN1， vinculin， integrin subunit αν， integrin subunit β3 in the colon tumor tissues of mice in the model group significantly increased， and the expression of E-cadherin significantly decreased compared to those in the sham operation group （P＜0.05）. Compared to those in the model group， the mass of the in situ tumors was reduced， and the number of hepatic metastasis nodules decreased in the high- and medium-dose QZKAF groups （P＜0.05）； the expression levels of PTNP1， vinculin， integrin subunit αν， integrin subunit β3 and E-cadherin in all QZKAF groups and 5-Fu group showed different degrees of retracement， and the changes of the indicators in all QZKAF groups showed a certain degree of dose-dependence （P＜0.05）. HE staining showed that the nuclei of tumor cells in the model group were mostly schizophrenic， and there were different degrees of nuclear fragmentation of tumor cells in all QZKAF groups with more in the medium- and high-dose groups. ConclusionQZKAF could inhibit the growth of in situ tumors and liver metastasis of CRC. Its mechanism might be related to the regulation of tumor cell-cell and tumor cell-extracellular matrix adhesion by PTPN1.