Research on Teaching Reform of Basic Medical Courses in Comprehensive Universities Oriented Towards“Clinical Competency”

Through this study,we aim to construct a teaching model for basic medical courses that enhances“clinical competency.”We explore the optimal methods and pathways for the organic integration of exam-oriented teaching and professional teaching,optimize teaching efficiency,improve teaching quality and educational effectiveness,and provide theoretical support for the cultivation of clinical medical talents in China.The goal is to establish a talent cultivation objective oriented towards“clinical competency,”promote the teaching reform of basic medical courses in comprehensive universities,facilitate the transition of basic medical course teaching from“teacher knowledge presentation”to“student knowledge construction,”and cultivate high-quality medical talents with clinical competency.

Surviving the shift: College student satisfaction with emergency online learning during COVID-19 pandemic

BACKGROUND The coronavirus disease 2019(COVID-19)epidemic disrupted education systems by forcing systems to shift to emergency online leaning.Online learning satisfaction affects academic achievement.Many factors affect online learning satisfaction.However there is little study focused on personal characteristics,mental status,and coping style when college students participated in emergency online courses.regression analyses were performed to identify factors that affected online learning satisfaction.RESULTS Descriptive findings indicated that 62.9%(994/1580)of students were satisfied with online learning.Factors that had significant positive effects on online learning satisfaction were online learning at scheduled times,strong exercise intensity,good health,regular schedule,focusing on the epidemic less than one hour a day,and maintaining emotional stability.Positive coping styles were protective factors of online learning satisfaction.Risk factors for poor satisfaction were depression,neurasthenia,and negative coping style.CONCLUSION College students with different personal characteristics,mental status,and coping style exhibited different degrees of online learning satisfaction.Our findings provide reference for educators,psychologists,and school adminis-trators to conduct health education intervention of college students during emergency online learning.

Artificial intelligence for disease diagnostics still has a long way to go

Artificial intelligence(AI)can sometimes resolve difficulties that other advanced technologies and humans cannot.In medical diagnostics,AI has the advantage of processing figure recognition,especially for images with similar characteristics that are difficult to distinguish with the naked eye.However,the mechanisms of this advanced technique should be well-addressed to elucidate clinical issues.In this letter,regarding an original study presented by Takayama et al,we suggest that the authors should effectively illustrate the mechanism and detailed procedure that artificial intelligence techniques processing the acquired images,including the recognition of non-obvious difference between the normal parts and pathological ones,which were impossible to be distinguished by naked eyes,such as the basic constitutional elements of pixels and grayscale,special molecules or even some metal ions which involved into the diseases occurrence.

Mendelian randomization analysis:the causal relationship between statins and eye diseases

Background:The specific role of statins in the field of ophthalmology is not clear.Statins have the advantages of pleiotropic,relatively safety and low cost,and are a promising choice for the prevention and management of eye diseases.Nevertheless,there is a divergence of findings regarding the correlation between statin treatment and ocular conditions.Hence,our intention is to investigate the impact of statins on eye conditions through the utilization of Mendelian randomization(MR).Methods:The UK Biobank provided data on five statins,while the FinnGen database provided data on six eye diseases,including age-related macular degeneration,glaucoma,diabetic retinopathy,senile cataract,drug-induced cataract,and other cataracts.Causality exploration involved the utilization of various methods including inverse variance weighted(IVW),weighted median,weighted multivariate(weighted mode),and MR-Egger regression.To assess the reliability of the findings,funnel analysis,MR-Egger regression,leave-one-out method,and Cochran’s Q test were employed.Additionally,reverse MR analysis was performed to evaluate the potential for reverse causality between statin use and eye diseases.Results:Based on IVW analysis,there were three pairs of positive results with significant(P<0.05)causal relationship,including atorvastatin and drug-induced cataract(odds ratio(OR)=1.65E-05,95%confidence interval(CI):2.24E-09–0.12;P_(IVW)=0.02),rosuvastatin and drug-induced cataract(OR=2.77E-18,95%CI:7.53E-35–0.1;P_(IVW)=0.04)and fluvastatin with senile cataract(OR=0.5,95%CI:0.25–0.99;P_(IVW)=0.05).No significant causal relationship was observed between other types of statins and eye diseases.Sensitivity analysis found that the results were robust.Reverse MR analysis indicated no evidence of reverse causality between statin use and the examined eye diseases.Conclusion:Our study finally verified the strong causal relationship between three drugs and two diseases(atorvastatin and rosuvastatin and drug cataract,fluvastatin and senile cataract).This study confirms that statins may reduce the risk of certain eye diseases and provides new insights into the prevention and treatment of eye diseases.Furthermore,the lack of reverse causality reinforces the reliability of these associations.

Analysis of the Effect of GINS4 Regarding the Proliferation and Invasion of Breast Cancer Cells

Objective: To analyze the role and influence of the GINS4 gene in breast cancer progression and to explore its expression in triple-negative and non-triple-negative breast cancer cell lines. Methods: Single-gene analysis of GINS4 was performed by breast cancer RNA transcriptome data from The Cancer Genome Atlas (TCGA). Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of GINS4 in triple-negative and non-triple-negative breast cancer cell lines. The knockdown effects of GINS4 in MDA-MB-231 and MCF-7 cell lines on the proliferation and invasion of breast cancer cells were examined by cell counting kit 8 (CCK8) and Transwell assays. Results: Bioinformatics analysis showed that the expression of GINS4 in breast cancer was significantly higher than that in normal breast tissues (P > 0.05). At the same time, cell experiments confirmed that GINS4 was highly expressed in human breast cancer cell lines with normal breast cells as reference and in MDA-MB-231 and MCF-7 cell lines as reference, where the ability of proliferation and invasion of MDA-MB-231 and MCF-7 cells decreased after GINS4 knockdown. Conclusion: GINS4 is a gene associated with breast cancer malignancy, which can act as a novel tumor marker and has the potential as a new therapeutic target for breast cancer.

Basic fibroblast growth factor improves learning and memory deficits in a mouse model of vascular dementia: Associated with the role of free radicals clearance?

BACKGROUND： Basic fibroblast growth factor （bFGF） exhibits neuroprotective functions, but the possible mechanisms of bFGF on vascular dementia remain unclear. OBJECTIVE： To explore the neuroprotective effects of bFGF on a mouse model of vascular dementia, with focus on oxidative damage. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Medical College of Beihua University from March to December 2008. MATERIALS： bFGF was purchased from Peprotech, USA. METHODS： A total of 80 healthy, Kunming mice were randomly assigned to control, sham-surgery, model, and bFGF groups. The model and bFGF groups were used to establish vascular dementia models by repetitive cerebral ischemia-reperfusion in a conscious state. In addition, bFGF group mice were intraperitoneally injected with bFGF （100 pg/kg） following model establishment, once a day for 7 consecutive days. MAIN OUTCOME MEASURES： The Morris water maze was used to determine the influence of bFGF on learning and memory abilities in vascular dementia mice. The pathomorphological changes in hippocampal CA1 neurons were observed by Nissl staining. Superoxide dismutase and malondialdehyde changes were analyzed using biochemical analysis methods. Annexin V-FITC/PI-double-labeled flow cytometry was used to detect neuronal apoptosis. RESULTS： Learning and memory functions in model mice significantly decreased, as characterized by prolonged latency and reduced time and number of platform crossings （P 〈 0.01, P 〈 0.05）. Superoxide dismutase activity was significantly reduced, malondialdehyde content was significantly increased （P 〈 0.01）, and hippocampal neuronal apoptosis was increased （P 〈 0.01） following vascular dementia, bFGF increased superoxide dismutase activity, decreased malondialdehyde content, and reduced hippocampal neuronal apoptosis （P 〈 0.01）, which resulted in improved learning and memory in mice with vascular dementia. CONCLUSION： bFGF improved learning and memory deficits in mice with vascular dementia by reducing free radical injury and inhibiting hippocampal neuronal apoptosis.

Basic fibroblast growth factor improves learning and memory functions in chronic stress mice

Four weeks of uncertain stress was used to establish an animal model of chronic stress. Basic fibroblast growth factor was injected daily for 15 days following stress induction. Cell morphology in the hippocampal CA3 region of chronic stress mice revealed cell damage. Nitric oxide content and calcium concentration were significantly increased in the hippocampus, and learning and memory functions were significantly decreased. After basic fibroblast growth factor intervention, Ca2~ overload was decreased and neuronal damage was relieved in hippocampal neurons, which improved learning and memory functions in chronic stress mice. Latency was prolonged and the number of errors was decreased in a passive avoidance test.

Influence of ganglioside combined with methylprednisolone sodium succinate on efficacy and neurological function in patients with acute myelitis

BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.

Predicting visual acuity with machine learning in treated ocular trauma patients

AIM:To predict best-corrected visual acuity(BCVA)by machine learning in patients with ocular trauma who were treated for at least 6mo.METHODS:The internal dataset consisted of 850 patients with 1589 eyes and an average age of 44.29y.The initial visual acuity was 0.99 log MAR.The test dataset consisted of 60 patients with 100 eyes collected while the model was optimized.Four different machine-learning algorithms(Extreme Gradient Boosting,support vector regression,Bayesian ridge,and random forest regressor)were used to predict BCVA,and four algorithms(Extreme Gradient Boosting,support vector machine,logistic regression,and random forest classifier)were used to classify BCVA in patients with ocular trauma after treatment for 6mo or longer.Clinical features were obtained from outpatient records,and ocular parameters were extracted from optical coherence tomography images and fundus photographs.These features were put into different machine-learning models,and the obtained predicted values were compared with the actual BCVA values.The best-performing model and the best variable selected were further evaluated in the test dataset.RESULTS:There was a significant correlation between the predicted and actual values[all Pearson correlation coefficient(PCC)>0.6].Considering only the data from the traumatic group(group A)into account,the lowest mean absolute error(MAE)and root mean square error(RMSE)were 0.30 and 0.40 log MAR,respectively.In the traumatic and healthy groups(group B),the lowest MAE and RMSE were 0.20 and 0.33 log MAR,respectively.The sensitivity was always higher than the specificity in group A,in contrast to the results in group B.The classification accuracy and precision were above 0.80 in both groups.The MAE,RMSE,and PCC of the test dataset were 0.20,0.29,and 0.96,respectively.The sensitivity,precision,specificity,and accuracy of the test dataset were 0.83,0.92,0.95,and 0.90,respectively.CONCLUSION:Predicting BCVA using machine-learning models in patients with treated ocular trauma is accurate and helpful in the identification of visual dysfunction.

Bioinformatics screening of breast cancer-related genes and potential drug research

Objective:To search the the differentially expressed genes between breast cell carcinoma tissues and normal tissues by using bioinformatics technology,and the potential therapeutic drugs for breast cancer were identified,which can provide reference for clinical immune targeted therapy and drug therapy of breast cancer in the future.Methods:"Breast cancer"was searched by using Gene Expression Omnibus(GEO),and GSE79586 chip data was downloaded.The differentially expressed genes in the control group and the breast cancer model group were screened by using bio-communication technology and subjected to GO function analysis,KEGG pathway analysis,differential gene characteristic expression analysis and protein-protein interaction network(PPI)analysis,and the analysis results were further visualized.Prognosis analysis,related function prediction and immune infiltration analysis were performed using the GEPIA,GeneMANIA,and Timer2.0 databases,respectively.Finally,the compounds with potential therapeutic effects on breast cancer are identified through Connectivity Map(CMap).Western blotting and real-time PCR(RT-PCR)were used to verify the core genes and potential therapeutic agents with the highest correlation in vitro.Results:A total of 3916 differentially expressed genes including 1786 up-regulated genes and 2130 down-regulated genes were screened.GO analysis showed that the differential genes were mainly involved in the positive regulation of phosphorylation,secretory vesicles,racemase and epimerase activities.KEGG analysis showed that differential genes were involved in systemic lupus erythematosus,alcoholism,sticky spots,amoebic dysentery Ras signal pathways and other disease pathways.The characteristic expression analysis of differential genes showed that MEK inhibitors,HSP90 inhibitors and signal transduction pathway kinase inhibitors were drugs similar to the differential genes.PPI results showed that H2AFJ,TFF1,GATA3,FOXA1,and CDH1 were core genes related to breast cancer.Two core genes of H2AFJ and TFF1 with the highest correlation were further selected for GEPIA analysis.The results of the analysis showed that the mRNA expression levels of H2AFJ and TFF1 in breast cancer cells were significantly higher than those in normal tissues,and there was a significant correlation with the pathological staging,overall survival rate and disease-free survival rate of breast cancer patients.H2AFJ and TFF1 may be potential prognostic biomarkers for survival of breast cancer patients.The functions of differentially expressed H2AFJ and TFF1 are mainly related to hormone receptor binding,epithelial structure maintenance and epigenetic negative regulation of genes,chromatin tissue involved in negative regulation of transcription,etc.The results of immune infiltration showed that the expressions of H2AFJ and TFF1 had a significant correlation with the infiltration of macrophages,neutrophils,monocytes,CD4+T,CD8+T,B lymphocytes and other immune cells.CMap results showed that compounds such as Gefitinib,Alpelisib,Sorafenib,and Sunitinib had potential therapeutic effects on breast cancer.Western blot and RT-PCR results showed that H2AFJ and TFF1 were significantly overexpressed in breast cancer cells.Gefitinib significantly inhibited the expression of H2AFJ and TFF1 in breast cancer cells(P<0.05,P<0.01).Conclusion:In this study,differentially expressed genes between breast cell carcinoma tissues and normal tissues were screened out by bioinformatics means to further identify key genes and compounds with potential therapeutic effects in the onset process of breast cancer and to further verify the effectiveness of the screened drugs on breast cancer through experiments.It will provide reference for clinical research and development of new drugs against breast cancer in the future in order to develop more effective treatment options.

Systematic evaluation and meta-analysis of the efficacy and safety of cinobufagin injection combined with western medicine in the treatment of liver cancer

Objective:To evaluate the clinical efficacy and safety of cinobufagin injection in the treatment of liver cancer.Methods:PubMed database,Embase database and Cochrane Library database,CNKI,Wanfang database,VIP database and Sinomed database were used to search for the randomized controlled trials of cinobufagin injection combined with Western medicine in the treatment of primary liver cancer.The retrieval time was from the establishment to December 15,2020.Two independent researchers conducted systematic screening,literature inclusion and quality assessment of the articles according to the inclusion criteria,respectively.Meta-analysis of the data was performed using RevMan 5.4 software.Results:A total of 30 studies with a total of 2355 patients were included.Compared with conventional western medicine treatment,the clinical effective rate of Hububutin injection combined with western medicine was significantly higher[RR=1.16,95%CI=(1.11,1.22),P<0.00001].It could effectively reduce the tumor size[RR=1.33,95%CI=(1.17,1.51),P<0.00001],prolong the survival time of patients[RR=1.41,95%CI=(1.31,1.52),P<0.00001],improve the quality of life[RR=1.37,95%CI=(1.19,1.57),P<0.00001],improve the liver function of patients[RR=-14.52,95%CI=(-16.15,-12.88),P<0.00001],and reduce the occurrence of adverse reactions[RR=0.94,95%CI=(0.85,1.42),P=0.25]such as bone marrow suppression[RR=0.44,95%CI=(0.31,0.62),P<0.00001].Conclusion:Cinobufagin injection combined with western medicine therapy can effectively improve the clinical symptoms of primary liver cancer,and the safety is good.However,the methodological quality of the included literature is low,which affects the objectivity of the outcome,and it still needs to be verified by multi-sample,multi-center,randomized double-blind controlled trial.

Prognostic significance of identification of traditional Chinese medicine syndromes in colorectal cancer

Background:Traditional Chinese medicine(TCM)syndrome is the basic unit of TCM treatment,which help clinicians assess the disease progression and treatment preoperative of tumor patients.However,the prognostic significance of TCM syndrome is still unclear.This study aims to detect the differences in overall survival between different TCM syndrome and further develop a new nomogram with TCM syndrome for predicting overall survival in colorectal cancer.Methods:A total of 324 patients with colorectal cancer were enrolled and categorized into three groups based on TCM syndrome:deficiency,excess,and deficiency-excess.The prognosis of colorectal cancer patients with different TCM syndromes was evaluated using Kaplan-Meier analysis and Cox regression analysis.Results:The proportion of advanced stage and lymph metastasis in the patients with deficiency syndrome was higher,and the overall survival was shorter than other syndromes.Meanwhile,the TCM syndrome(P<0.001),tumor invasion depth(P<0.001),lymph metastasis(P=0.018),organic metastasis(P=0.005)and tumor node metastasis(TNM)stage(P=0.029)were the independent prognostic factor.Then,a new nomogram with TCM syndrome was established and assessed.324 colorectal cancer patients were randomly divided into training(n=215)and validation cohorts(n=109).A nomogram incorporating preoperative TCM syndrome,gender,age,T,N,and M status was developed,which had good discrimination and calibration.Conclusion:Taken together,our results indicated that TCM syndrome could assess the prognosis of colorectal cancer.The nomogram incorporating TCM syndromes and tumor information is helpful for risk stratification and prognostic predictions in colorectal cancer preoperatively.

实验性NIDDM模型胰岛素抵抗的评估

目的 用糖耐量曲线下面积 (SBG)、胰岛素释放曲线下面积 (SIns)、胰岛素敏感指数 ,这些临床糖尿病常用的指标对非胰岛素依赖型糖尿病 (non insulin- dependentdiabetes mellitus,NIDDM)模型胰岛素抵抗评估。方法 大鼠尾静脉注射小剂量链尿佐菌素 ,使大鼠糖耐量异常 ,然后加喂高热量食物 ,引起动物肥胖 ,饲养 8wk,可形成类似 NIDDM的肥胖大鼠模型 ,并设置对照组 ,同时测定了大鼠糖耐量试验过程中血清葡萄糖 (BG)、胰岛素 (Ins) ,并计算了 SBG、SIns、胰岛素敏感指数。结果 1模型组糖耐量试验 ,血清 BG糖耐量下降 ,Ins在糖负荷后 2 h明显升高 (P<0 .0 1) ;2 Ins敏感指数较对照组明显降低 (P<0 .0 1) ;3SBG明显上升 (P<0 .0 1) ;SIns无明显变化 ,SIns/ SBG下降 (P<0 .0 1)。结论 SBG、SIns、胰岛素敏感指数可较好反映 Ins作用 ,B细胞储备功能及 Ins敏感性 ,可广泛用于实验性糖尿病基础研究和作为临床正确评价 IR的指标。

A case-control study of risk factors for severe hand-foot-mouth disease in Yuxi, China, 2010–2012

Dear Editor,Here,we report the risk factors for severe hand-foot-mouth disease(HFMD)determined by our case-controlstudy.Our findings could help disease prevention and in-tervention initiatives.Patients with severe HFMD displayfatal clinical manifestations with sequelae,requiring≥7days of hospitalization.A tota1 of 249 severe cases treat-ed at Yuxi Children’s Hospital were included in the

Expression and significance of homeodomain protein Cdx2 in gastric carcinoma and precancerous lesions

AIM： To investigate the expression and significance of caudal-related homeobox transcription factor （Cdx2） in gastric carcinoma （GC） and precancerous lesions. METHODS： The expression of Cdx2 in GC, precancer- ous lesions and normal gastric mucosa were detected using immunohistochemical method. Hematoxylin and eosin staining, alcian blue/periodic acid-schiff and high iron diamine/alcian blue staining were used to classify intestinal metaplasia （IM） and GC. RESULTS： Cdx2 was not detected in normal gas- tric mucosa. Cdx2 expression was detected in 87.1% （101/116） of IM, 50% （36/72） of dysplasia and 48.2% （41/85） of GC. The Cdx2-expressing cells in IM were more prevalent than in dysplasia and carcinoma （P 〈 0.05）. There was no relationship between Cdx2 ex- pression and the classification of IM or the degree of dysplasia. Expression of Cdx2 was significantly higher in intestinal-type carcinoma than in diffuse and mixed- type carcinoma （P 〈 0.05）. Positive expression of Cdx2was mainly found in moderately to well differentiated GC. There was a negative association between nuclear Cdx2 expression and lymph node metastasis and tumor, nodes, metastasis stage of GC （P 〈 0.05）. The patients with Cdx2-positive expression showed a higher survival rate than those with Cdx2-negative expression （P = 0.038）. Multivariate analysis revealed that the expres- sion of Cdx2 and lymph node metastasis were indepen- dent prognostic indicators of GC （P 〈 0.05）.

Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis in vitro and in vivo: From biological characteristics to therapeutic mechanisms

Liver fibrosis is a wound-healing response to chronic injuries, characterized by the excessive accumulation of extracellular matrix or scar tissue within the liver;in addition, its formation is associated with multiple cytokines as well as several cell types and a variety of signaling pathways. When liver fibrosis is not well controlled, it can progress to liver cirrhosis, but it is reversible in principle. Thus far, no efficient therapy is available for treatment of liver fibrosis. Although liver transplantation is the preferred strategy, there are many challenges remaining in this approach, such as shortage of donor organs, immunological rejection, and surgical complications. Hence, there is a great need for an alternative therapeutic strategy. Currently, mesenchymal stem cell (MSC) therapy is considered a promising therapeutic strategy for the treatment of liver fibrosis;advantageously, the characteristics of MSCs are continuous self-renewal, proliferation, multipotent differentiation, and immunomodulatory activities. The human umbilical cord-derived (hUC)-MSCs possess not only the common attributes of MSCs but also more stable biological characteristics, relatively easy accessibility, abundant source, and no ethical issues (e.g., bone marrow being the adult source), making hUC-MSCs a good choice for treatment of liver fibrosis. In this review, we summarize the biological characteristics of hUC-MSCs and their paracrine effects, exerted by secretion of various cytokines, which ultimately promote liver repair through several signaling pathways. Additionally, we discuss the capacity of hUC-MSCs to differentiate into hepatocyte-like cells for compensating the function of existing hepatocytes, which may aid in amelioration of liver fibrosis. Finally, we discuss the current status of the research field and its future prospects.

New progress in roles of nitric oxide during hepatic ischemia reperfusion injury

Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1 alpha-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

AIM： To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS： Fifty SD rats were divided into control group （n=20） and model group （n=30）. Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole （1 000：250：3）. Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid （HA）, type IV collagen （COW） and laminin （LN） were determined by radioimmunoassay. Liver tissue was fixed in formalin （10%） and 6-μm thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polydonal antibody against LN and ColⅣ. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. RESULTS： The diameter （2.207 ± 0.096 vs 1.528±0.054 mm, P〈0.01） and pressure （11.014±0.395 vs 8.533±0.274 mmHg, P〈0.01） of portal vein were significantly higher in model group than those in the control group. Plasma HA （129.97±16.10 vs 73.09±2.38 ng/mL, P〈0.01）, ColⅣ （210.49±4.36 vs 89.65±4.42 ng/mL, P〈0.01） and LN （105.00±7.29 vs 55.70±4.32 ng/mL, P〈0.01） were upregulated in model group. Abundant collagen deposited around the central vein of Iobules, hepatic sinusoids and hepatocytes in model group. ColⅠ and ColⅢ increased remarkably and perisinusoids were almost surrounded by ColⅢ. Immunohistochemical staining showed that ColⅣ protein level （0.130±0.007 vs 0.032±0.004, P〈0.01） and LN protein level （0.152±0.005 vs 0.029±0.005, P〈0.01） were up-regulated remarkably in model group. MMP-2 protein expression （2.306±1.089 vs 0.612±0.081, P〈0.01） and TIMP-1 protein expression （3.015±1.364 vs 0.446±0.009, P〈0.01） in freshly isolated hepatic nonparenchymal cells were up-regulated in model group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression （2.669±0.170 vs 1.695±0.008, P〈0.05）. CONCLUSION： Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are responsible for alcoholinduced portal hypertension in rats,

Inhibitory effect of Tong Xie-Yao Fang formula on colonic contraction in rats

AIM:To investigate the pharmacological effect ofTong Xie-Yao Fang(TXYF)formula and its underlying mechanisms.METHODS:A neonatal maternal separation plus restraint stress(NMS+RS)model of diarrheapredominant irritable bowel syndrome was developed by subjecting male Sprague-Dawley rats to daily maternal separation from postnatal days 2 to 21 plus restraint stress from days 50 to 59.Rats were randomly divided into two groups(NMS+RS and TXYF formula),and rats with no handling or separation were used as normal controls.Starting from postnatal day 60,rats were administered TXYF formula(9.84 g/100 g body weight)orally twice daily for 14 consecutive days,while the normal and NMS+RS groups were given distilled water.The distinctions of movement index(MI,area under the curve of contraction intensity/min,mg/min)and contraction frequency(CF,number of contractions/min,times/min)of isolated colonic longitudinal smooth muscle strips(CLSMs)in the three groups before and after treatment were observed with a Power Lab system.Different inhibitors were applied,and then 10-4mol/L acetylcholine chloride(Ach)was added to CLSMs to induce muscle contraction.RESULTS:Before treatment,the MI of CLSMs in the NMS+RS and TXYF formula groups was similar and both higher than that in the normal group(545.49±73.66 mg/min vs 245.76±34.44 mg/min and551.09±54.29 mg/min vs 245.76±34.44 mg/min,P<0.01,respectively).After treatment,the MI in the TXYF formula group was lower than that in the NMS+RS group(261.39±38.59 mg/min vs 533.9±61.63 mg/min,P<0.01).In the same way,the CF of CLSMs in the NMS+RS and TXYF formula groups was similar and both higher than that in the normal group(3.42±0.25 times/min and 3.31±0.21 vs1.1±0.17 times/min,P<0.01)before treatment.After treatment,the CF in the TXYF formula group was lower than that in the NMS+RS group(1.42±0.87 times/min vs 3.11±0.82 times/min,P<0.01)and similar to that in the normal group(1.42±0.87 times/min vs 1.09±0.13 times/min).When8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride and 4-aminopyridine were added to the bath and equilibrated for 30 min,respectively,and10-4 mol/L Ach was added to CLSMs to induce muscle contraction,MI of the CLSMs in the TXYF formula group was lower than that in the normal group(666±36.32 mg/min vs 747.77±49.47 mg/min,and 686.53±39.17 mg/min vs 750.45±29.39 mg/min;P<0.01,respectively).The MI of CLSMs in the TXYF formula group was lower than that in the normal group after treatment with nifedipine(689.48±30.84 mg/min vs741.65±32.41 mg/min;P<0.05).CONCLUSION:TXYF formula inhibits colon contraction in rats.This may be related to activation of specific potassium channels and inhibition of extracellular calcium internal flow.

Mesenteric lymph reperfusion may exacerbate brain injury in a rat model of superior mesenteric artery occlusion shock

BACKGROUND：The intestinal lymphatic pathway and intestinal ischemia/reperfusion are mainly involved in mesenteric lymph duct ligation or drainage; moreover,intervention by reducing the lymph liquid reflux might relieve lung and other organ dysfunction induced by intestinal ischemia/reperfusion; however,research addressing mesenteric lymph reperfusion （MLR） and brain injury has not yet to be reported.OBJECTIVE：To observe the effect of MLR on brain tissue in a rat model of superior mesenteric artery occlusion （SMAO） shock,and to explore the molecular mechanism of MLR.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment at a neuro-pathophysiology level was performed at the Institute of Microcirculation,Hebei North University; Department of Pathophysiology,Basic Medical College; Department of Pathology,the First Hospital of Hebei North University between December 2007 and March 2009.MATERIALS：Adenosine triphosphate （ATP） standard was provided by the National Institute for the Control of Pharmaceutical and Biological Products; lactic acid （LA）,superoxide dismutase （SOD）,malonaldehyde （MDA）,nitrogen monoxidum （NO）,nitric oxide synthase （NOS）,myeloperoxidase （MPO） and ATPase assay kits were provided by Nanjing Jiancheng Bioengineering Institute,China.METHODS：A total of 24 male Wistar rats were randomly divided into four groups.In the sham-surgery group （n = 6）,both the mesenteric lymph duct and the superior mesenteric artery were not blocked; in the MLR group （n = 6）,the mesenteric lymph duct was occluded for 1 hour followed by 2-hour reperfusion; in the SMAO group （n = 6）,the superior mesenteric artery was occluded for 1 hour followed by 2-hour reperfusion; in the MLR ＋ SMAO group （n = 6）,both the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour followed by 2-hour reperfusion.MAIN OUTCOME MEASURES：Mean arterial blood pressure prior to and following ischemia/reperfusion; brain tissue morphology levels of LA,MDA,SOD,NO,NOS,MPO,ATPase and ATP following reperfusion.RESULTS：MLR did not cause changes in mean arterial blood pressure,brain tissue morphology,LA,MDA,NO,ATP,SOD,NOS,MPO and ATPase.However,SMAO caused a rapid decrease and gradual increase of mean arterial blood pressure.Neuronal necrosis,degeneration and swelling were observed in brain tissue.Contents of MDA,NO,LA and ATP as well as activities of NOS and MPO were significantly increased （P〈 0.05）,but activities of SOD and Na＋-K＋-ATPase were significantly decreased （P 〈 0.05）.MLR aggravated neuronal damage in a rat model of SMAO shock.Following MLR,mean arterial blood pressure was significantly decreased （P 〈 0.05）,contents of MDA and NO as well as activities of NOS and MPO were significantly increased （P 〈0.05）,but activities of Ca2＋-ATPase,Mg2＋-ATPase and Ca2＋-Mg2＋-ATPase as well as ATP content were significantly decreased （P〈 0.05）.CONCLUSION：MLR aggravates brain injury in a rat model of SMAO shock,which correlates with oxygen-derived free radical injury,NO synthesis and release,sequestration of neutrophilic granulocytes,decreasing activity of cell membrane pumps and energy metabolism dysfunction.Pathogenesis of the intestinal lymphatic pathway should be thoroughly investigated to prevent ischemia/reperfusion injury.