Objective To investigate the protective effects of emulsified isoflurane(8% v/v) on myocardial cells after hypoxia/reoxygenation(H/R) in cultured myocardial cells from neonatal rats.Methods Myocardial hypoxia/reoxygenation model was established by culturing myocardial cells primarily isolated from neonatal rats.The myocardial cells were divided into 4 groups,the normal group,model group,fat milk treatment group,and mulsified isoflurane treatment group(0.28 mmol/L).Cellular morphologic changes and pulsation frequency were observed under inverted microscope.Cell activity was determined by XTT assay.The activities of plasma superoxide dismutase(SOD) was measured by xanthine oxidase method and the contents of serum malonicaldehyde(MDA) by thiobarbituric acid method.The activities of lactate dehydrogenase(LDH) in the culture medium after H/R injury was measured.Western blot analysis was used to detect caspase-3 protein expression in every group.Results Compared with normal group,SOD activity was decreased,and MDA content,LDH activity and the expression of caspase-3 protein were increased in model group(P

Objective To investigate the effects of emulsified isoflurane on myocardial apoptosis, and the expressions of Bcl-2 and Bax after hypoxia/reoxygenation in cultured myocardial cells of neonatal rats. Methods Myocardial hypoxia/reoxygenation model was established on cultured primary myocardial cells of neonatal rat. The myocardial cells were divided into four groups: the normal group, model group, fat milk group, and emulsified isoflurane group. The cellular morphologic changes and pulsatile frequency of each group were observed under inverted microscope and the ultrastructure of myocardial cells was observed under transmission electron microscope. The apoptotic rate of myocardial cells was determined by flow cytometry, the expression of bcl-2 mRNA and bax mRNA were detected by RT-PCR and the protein expressions of Bcl-2/Bax were observed by Western blot. Results The apoptotic rate were significantly decreased in both emulsified isoflurane and fat milk groups (P0.05). Conclusion Emulsified isoflurane and one of its components, fat milk,can inhibit myocardial apoptosis induced by hypoxia/reoxygenation in cultured myocardial cells. Emulsified isoflurane exerts its anti-apoptosis effect maybe through up-regulating Bcl-2 expressions and down-regulating Bax expressions.

This study was aimed to observe the effect ofIllicium verum water extract on excess-cold syndrome in rats. The intragastric administration of the decoction of gypsum, gentian, phellodendron andrhizoma anemarrhenae (2:1.2:1:1.5) was used to establish the excess-cold rat model. Effects ofI. verum water extract on general body signs of excess-cold syndrome rats were observed. The detection was made on the contents of LD, PA, TG, TSH, T4 in the serum and LD, PA, glycogen in liver tissues. The vitality of the LDH, SDH and ATPas was also detected. The results showed thatI. verum water extract can improve the general body signs of excess-cold syndrome rats. It reduced the content of TG; increased the content of PA, T4, TSH; reduced the content of LD, glycogen, and the vitality of LDH;increased the vitality of LDH, Ca2+-Mg2+-ATPase in liver tissues. It was concluded thatI. verum water extract can improve some general body signs of excess-cold syndrome rats, improve the substance and energy metabolism, and regulate the thyroid axis function, in order to achieve the warmingyang for dispelling cold effect.

Objective:To discuss the effect of azathioprine(AZA)on ferroptosis in spermatocytes of the mice induced by reduced glutathione(GSH)peroxidase 4 inhibitor RSL3,and to clarify the potential mechanism.Methods:The spermatogonia GC-2 cells of the mice were randomly divided into control group(no treatment),RSL3 group(treated with 10 nmol·L-1 RSL3 for 24 h),RSL3+ferroptosis inhibitor(Ferrostatin-1,Fer-1)group(treated with 10 nmol·L-1 RSL3 for 24 h+2 μmol·L-1 Fer-1 for 12 h),RSL3+low dose of AZA group(treated with 10 nmol·L-1 RSL3 for 24 h+5 μmol·L-1 AZA for 12 h),RSL3+medium dose of AZA group(treated with 10 nmol·L-1 RSL3 for 24 h+10 μmol·L-1 AZA for 12 h),and RSL3+high dose of AZA group(treated with 10 nmol L-1 RSL3 for 24 h+20 μmol·L-1 AZA for 12 h).The MTT method was used to detect the activities of the GC-2 cells in various groups after treated with different concentrations of AZA and RSL3;the GSH and GSSG levels in the GC-2 cells were detected by GSH and oxidized glutathione(GSSG)detection kits;the malondialdehyde(MDA)levels in the GC-2 cells in various groups were detected by MDA detection kit;Western blotting method was used to detect the expression levels of long-chain acyl-CoA synthetase 4(ACSL4),heme oxygenase-1(HO-1),and glutathione peroxidase 4(GPX4)proteins in the cells in various groups;immunofluorescence staining was used to detect the expressions of ACSL4 protein in the cells in various groups.Results:Compared with control group,the differences in activities of the GC-2 cells in 5,10,and 20 μmol·L-1 AZA groups had no significant differences(P＞0.05),while the activities of the GC-2 cells in 30 and 40 μmol·L-1 AZA groups were significantly decreased(P＜0.01);therefore,the AZA concentration was selected to be within 20 μmol·L-1.Compared with control group,the differences of the activities of the GC-2 cells in 1,5,and 10 nmol·L-1 RSL3 groups had no significant differences(P＞0.05),while the activities of the GC-2 cells in 50,100,500,and 1 000 nmol·L-1 RSL3 groups were significantly decreased(P＜0.05 or P＜0.01);therefore,the RSL3 concentration was set to be within 10 nmol·L-1.The GSH and MDA detection kits results showed that compared with control group,the levels of GSSG and MDA in the GC-2 cells in RSL3 group were significantly increased(P＜0.05),while the GSH levels were significantly decreased(P＜0.05);compared with RSL3 group,the levels of GSSG and MDA in the GC-2 cells in RSL3+Fer-1 group and RSL3+AZA group were significantly decreased(P＜0.01),while the GSH levels were significantly increased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of ACSL4 and HO-1 proteins in the GC-2 cells in RSL3 group were significantly increased(P＜0.05),while the expression level of GPX4 protein was significantly decreased(P＜0.01);compared with RSL3 group,the expression levels of GPX4 protein in the GC-2 cells in RSL3+Fer-1 group and RSL3+AZA group were significantly increased(P＜0.05),while the expression levels of ACSL4 and HO-1 proteins were significantly decreased(P＜0.01).The immunofluorescence staining results showed that compared with control group,the expression amount of ACSL4 protein in the GC-2 cells in RSL3 group was significantly increased,and compared with RSL3 group,the expression amounts of ACSL4 protein in the cells in RSL3+Fer-1 group and RSL3+AZA group were significantly decreased.Conclusion:AZA can alleviate the ferroptosis-induced by RSL3 in spermatocytes of the mice.

Medical ethics has a long history and rich connotations.It has developed from the simple "medical morality" of ancient times to the modem medical ethics.The basic principles of medical ethics include autonomy,non-maleficence,beneficence,justice,and so on.Researchers often conduct clinical researches in the balance between achievements and ethical norms.Clinical researchers of surgery should have a deep understanding of medical ethical principles and strictly abide by medical ethics.Ethics committee should strictly perform their duties and play the role of inspection and supervision.Modem medical knowledges should be popularized throughout the society to make clinical research correctly understood.Adhering principles of ethics first,people orientation and cooperation practice,with patients' benefit as evaluation criteria,balance of surgical "Dao" and "Shu" can be achieved.

ObjectiveTo review the ancient and modern literature of Huanglian Ejiaotang and learn about the historical evolution and clinical application， thereby providing a theoretical basis for the modern application of the classical prescription. MethodLiterature in the Chinese Medical Classics Database was retrieved with "Huanglian Ejiaotang" as the keyword. In China National Knowledge Infrastructure （CNKI） and PubMed， "Huanglian Ejiaotang" in Chinese and English was used as the keyword to retrieve literature. The items and modern clinical application studies related to the prescription， medicine， dosage， syndrome， and treatment of Huanglian Ejiaotang were selected and recorded. The inclusion and exclusion criteria were used to screen out literature. The information about the dynasty， book title， function， and indication was integrated to understand the history， evolution， and clinical application of Huanglian Ejiaotang. ResultFinally， 89 ancient books were included with 111 items. Huanglian Ejiaotang was initially recorded in ZHANG Zhongjing's Treatise on Cold Damage and Miscellaneous Diseases in the Han dynasty. It was composed of five herbs， namely Coptidis Rhizoma， Scutellariae Radix， Paeoniae Radix Alba， Asini Corii Colla， and egg yolk. With the change of historical dynasties， the composition， origin basis， dosage， and preparation method of Huanglian Ejiaotang all changed， but the changes in the processing were not obvious， which was basically consistent with Treatise on Cold Damage and Miscellaneous Diseases. In addition， 48 studies were included to analyze the clinical application of Huanglian Ejiaotang， which was mainly used for insomnia， anxiety， depression， diabetes， and so on. ConclusionAccording to the ancient and modern literature， the origin basis， dosage， processing， decoction， administration， and other content of Huanglian Ejiaotang are consistent with Treatise on Cold Damage and Miscellaneous Diseases. The present clinical application has expanded the usage scale of the ancient record， which promotes the innovation and development of the classic prescription and provides references for later research， development， and accurate application.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.