基于培养卓越医生的生物化学课程思政的探索与实践

近年来，课程思政受到党、国家和教育界的普遍关注，如何将思政元素融合到专业课程的教学中并达到协同效应，是一个值得深思的问题。基于卓越医生教育培养计划，根据医学教育的规律和医学生的培养目标，结合生物化学教学内容的特点，着重挖掘生物化学课程的思政元素，建立思政元素资料库；并进一步探讨生物化学课程思政的实施策略，将课程思政有机融入生物化学教学中，为医学专业的课程思政教学改革提供参考。     

二妙散对类风湿关节炎调控基因Toll样受体4和重组牛磷酸肌醇3激酶A表达的影响

目的研究二妙散对类风湿关节炎(RA)调控基因Toll样受体(TLR4)和重组牛磷酸肌醇3激酶A(PI3KA)表达的影响。方法通过构建Wistar大鼠胶原诱导性关节炎(CIA)模型,不同浓度二妙散灌胃治疗,酶联免疫吸附试验(ELISA)检测血清中炎症因子的表达,苏木精-伊红(HE)染色进行病理学分析,实时荧光定量聚合酶链反应(qRT-PCR)分析TLR4和PI3KA的表达特性。结果二妙散组与CIA模型组相比,脾脏指数差异无统计学意义(P>0.05);CIA模型组与对照组相比,脾脏指数显著降低,差异有统计学意义(P<0.05);二妙散组滑膜组织炎性细胞较少;较正常组白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α表达量极显著降低,差异有统计学意义(P<0.01,P<0.05),较模型组显著降低,差异有统计学意义(P<0.05);随二妙散浓度增加IL-37表达量显著增加,差异有统计学意义(P<0.05,P<0.01)。模型组大鼠关节中IL-6、TLR4和PI3KA mRNA水平表达量极显著高于对照组和甲氨蝶呤组,差异有统计学意义(P<0.01)。结论本实验成功构建CIA大鼠模型,TLR4和PI3KA在不同实验组大鼠关节组织中均有不同程度的表达,说明TLR4和PI3KA参与CIA大鼠炎性反应的形成,介导RA炎性因子的形成和发展,二妙散对于减少炎症因子和增加抑炎因子的表达具有重要作用,具体作用机制需进一步研究证实。     

远志叶绿体基因组序列特征与系统发育分析

目的 解析远志Polygalatenuifolia叶绿体基因组信息序列特征和确定其在远志属的系统位置。方法 获得远志叶绿体基因组序列,借助Ge Seq、Chloroplot、MISA、REPute、Tandem repeats finder、CodonW、Geneious、IRscope、MAFFT7和IQtree2.0.5等生物信息学工具进行序列分析、密码子偏好分析、远志属基因组比较分析和系统发育研究。结果 远志的叶绿体基因组全长165 423 bp,为典型的环状四段式结构;包括1个大单拷贝区（large single copy,LSC;83 699 bp）,1个小单拷贝区（small single copy,SSC;8044 bp）和1对反向重复区（inverted repeats,IRs;36 840 bp）,该基因组共注释到135个基因,包括8个rRNA基因、38个tRNA基因和89个蛋白编码基因。该基因组中共检测到161个SSR位点,223条散在重复序列,90条串联重复序列;亮氨酸（Leu）是远志叶绿体基因组中使用次数最高的氨基酸（10.21%）,同义密码子相对使用频次（RS...     

Chinese Herbal Formula Ermiao Powder (二妙散) Regulates Cholinergic Anti-inflammatory Pathway in Rats with Rheumatoid Arthritis

Objective: To investigate the effect of Chinese herbal formula Ermiao Powder (二妙散, EMP) on the expression of cholinergic anti-inflammatory pathway in rats with rheumatoid arthritis (RA). Methods: Seventy two rats were randomly ivided into 6 groups according to body weight, including normal control group, collagen induced arthritis (CIA) group, three doses EMP groups, and methotrexate (MTX) group (n=12 per group). All of the rats except for those in the normal control group were given multipoint subcutaneous injection of bovine type Ⅱ collagen to establish a CIA model. Three EMP groups received a high- (4.5 g/kg), medium- (3.0 g/kg), and low- (1.5 g/kg) doses of EMP by intragavage, respectively. MTX group was injected intraperitoneally MTX at 0.9 mg/kg once a week as the positive control. The administration was 3 consecutive weeks. Joint swelling, arthritis index, and body weight changes in different experimental groups of rats were tested. The joint damage was evaluated by masson staining. Quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry (IHC) were performed to evaluate the expression of CHRNA7, encoding α 7 nicotinic acetylcholine receptor in the cholinergic anti-inflammatory pathway, in different tissues and their localization in the spleen and joints. Results: CHRNA7 expression levels were significantly higher in the joints and spleens of CIA group than those in normal control group (both P<0.05). Moreover, the CHRNA7 mRNA and protein levels in the spleen and joints of MTX and three doses of EMP groups were significantly lower than CIA group (all P<0.05). Compared with the MTX group, treatment with low-dose EMP resulted in significant reduction of CHRNA7 mRNA and protein expression levels (P<0.05 or P<0.01). IHC showed positive signals of CHRNA7 in the white pulp and red pulp of the spleens of rats; CHRNA7 was expressed on fibroblast-like synoviocytes, macrophages, and endothelial cells in the joints of rats, and the expression in the joints of low-dose EMP group was significantly lower than that in the CIA group (P<0.01). Conclusion: Cholinergic anti-inflammatory pathway was involved in the generation of the inflammatory reaction in CIA rats, and EMP exerted therapeutic effect on RA through cholinergic anti-inflammatory pathway.     

经典名方驻景丸的历史沿革与方证信息分析

驻景丸是2023年《古代经典名方目录（第二批）》汉族医药的第40首,出自北宋《太平圣惠方》,由菟丝子、车前子、熟地黄3味药组成,功用补益肝肾、清热明目,主治肝肾亏虚之眼病,为中医眼科临床常用名方。采用文献统计学方法,搜集分析驻景丸的古今文献,共筛选有效古籍数据63条,涉及47部中医古籍。从驻景丸的方源方名、组成剂量、药物基原与炮制、制法用法、主治功效等方面进行系统梳理,总结其方证关键信息。研究发现,驻景丸中菟丝子、车前子、熟地黄的配比为5∶3∶3是采用《太平惠民和剂局方》所载剂量;《黎居士简易方论》首载加减驻景丸,该方的主治范围与原方相仿,但药效更全面有力,历代应用更加频繁;现代医家继续对驻景丸进行化裁,提出驻景丸加减方、通络驻景丸等衍生方,广泛应用于眼科临床,取得良好效果。驻景诸方以滋补肝肾为本,或兼宁心安神,或兼清热利湿,或兼化瘀通络,然其对应的病机根本在于肝肾虚损,导致目力不足、障翳昏花。驻景诸方在老年性眼病、其他老年退行性改变及青少年近视防治方面均有良好的应用前景,后续可开展相关药理研究和制剂研发。     

Expression and localization analyses of the cholinergic anti-inflammatory pathway and α7nAchR in different tissues of rats with rheumatoid arthritis

Rheumatoid arthritis (RA) is a complicated chronic multisystem autoimmune disease, wherein the inflammatory cascade leads to vasospasm and osteoclastogenesis, which ultimately results in bone and cartilage destruction. In this study, we investigated the expression and localization of the alpha-7 nicotinic receptor (α7nAchR) gene CHRNA7 in the heart, liver, spleen, lung, kidney, and joints of the collagen-induced arthritis (CIA) rat model. The CHRNA7 mRNA and protein expression levels in these tissues of rats from CIA and normal groups were analyzed via real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. The cellular localization of CHRNA7 protein was determined via immunohistochemistry (IHC) assays. CHRNA7 was expressed at varying levels in different tissues of rats from the groups, among which joints showed significantly higher CHRNA7 expression levels than other tissues (P < 0.05). CIA rats had significantly higher CHRNA7 expression levels in the spleen and joints than the control group rats (P < 0.05). Positive expression signals for CHRNA7 were detected in various tissues of CIA and control group rats, among which strong positive signals were detected in joint fibroblast-like synoviocytes (FLSs), endothelial cells, stromal cells, and macrophages. Our results further confirmed the involvement of the CAP in the onset and development of inflammatory responses in RA, suggesting that CHRNA7 may be a new therapeutic target for RA. This study is of great clinical and theoretical significance for understanding the differential expression of CHRNA7 in various tissues and cholinergic anti-inflammatory pathway (CAP)-targeted treatment of RA.     

PRSS2 regulates EMT and metastasis via MMP-9 in gastric cancer

Serine protease 2 (PRSS2) is upregulated in gastric cancer tissues, correlates with poor prognosis and promotes migration and invasion of gastric cancer cells. However, the exact mechanism by which PRSS2 promotes metastasis in gastric cancer is unclear. We examined serum PRSS2 levels in healthy controls and gastric cancer patients by enzyme linked immunosorbent assay (ELISA) and analyzed the correlation between PRSS2 serum level with the clinicopathological characteristics of gastric cancer patients and matrix metalloproteinase-9 (MMP-9) expression. A lentiviral MMP-9 overexpression vector was constructed and used to transfect gastric cancer cells with stable silencing of PRSS2, and migration, invasion and epithelial-mesenchymal transition (EMT) of gastric cancer cells were examined. High serum PRSS2 levels were detected in gastric cancer patients and associated with lymphatic metastasis and TNM stage. Serum PRSS2 was positively correlated with serum MMP-9 level. PRSS2 silencing inhibited EMT, and knock-down of PRSS2 partially abrogated cell metastasis and EMT caused by overexpression of MMP-9. These results suggest that PRSS2 promotes the migration and invasion of gastric cancer cells through EMT induction by MMP-9. Our findings suggest that PRSS2 may be a potential early diagnostic marker and therapeutic target of gastric cancer.     

Protective effect of cordycepin-enriched Cordyceps militaris on alcoholic hepatotoxicity in Sprague–Dawley rats

This study was to investigate the protective effect of cordycepin-enriched Cordyceps militaris against alcohol-induced hepatotoxicity in Sprague–Dawley rats. Alcohol-feeding rats were fed diets with Paecilomyces japonica as CPJ group, C. militaris as CCM group, cordycepin-enriched C. militaris as CCMα group at the 3% (w/w) level and silymarin at the 0.1% (w/w) level for 4 weeks. Alcohol administration resulted in a significant increase in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and the levels of blood alcohol and acetaldehyde in serum. However, CCMα group markedly prevented from alcohol-induced elevation of these parameters in serum. CCMα group showed the increased both hepatic activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). Unlike the action of alcohol treatment on alcoholic fatty liver, CCMα group was also attenuated lipid droplet accumulation in the hepatocytes. Present study was also confirmed the beneficial roles of silymarin (hepatoprotective agent) against alcohol-induced liver injury in rats. Therefore, cordycepin-enriched C. militaris can be a promising candidate to prevent from alcohol-induced hepatotoxicity.     

Dihydroartemisinin inhibited interleukin-18 expression by decreasing YAP1 in hepatocellular carcinoma cells

BackgroundYes-associated protein 1 (YAP1) is highly expressed in liver cancer and has been used as an independent prognostic marker for hepatocellular carcinoma (HCC), while inhibition of YAP1 slows down the progression of HCC. Interleukin-18 (IL-18) also tends to be highly expressed in liver cancer. Previous research has proved that dihydroartemisinin (DHA) plays an important role in HCC treatment by reducing YAP1 expression. However, the relationship between YAP1 and IL-18 has not been reported in HCC, especially during DHA therapy.ObjectiveThe purpose of this study was to clarify the relationship between YAP1 and IL-18 in HCC cells, and to explicit the role of IL-18 in the treatment of HCC by DHA.Methods and resultsWe found that YAP1 and IL-18 were highly expressed in patients with hepatocellular carcinoma by bioinformatics analysis. Moreover, YAP1 was positively correlated with IL18 in liver cancer. YAP1 and IL18 correlated with immune cell infiltration, notably T cell exhaustion. YAP1 knockdown decreased IL-18 expression, while YAP1 overexpression increased the IL-18 expression in HCC cells. DHA reduced IL-18 expression through YAP1 in HCC cells. Further, DHA reduced the growth of Hepa1–6 cells subcutaneous xenograft tumors by inhibiting the expression of YAP1 and IL-18. However, DHA improved IL-18 in serum and adjacent tissues from DEN/TCPOBOP-induced liver tumor model in C57BL/6 mice.ConclusionYAP1 was positively correlated with IL-18 in HCC. DHA reduced the expression of IL-18 by inhibiting YAP1 and plays a role in the treatment of HCC. Our study suggested that IL-18 is a potential target for the treatment of HCC, and DHA is a promising drug for HCC therapy.Data availabilityThe dataset that supports the findings of this study is available from the corresponding author upon reasonable request.     

Resveratrol as an antitumor agent for glioblastoma multiforme: Targeting resistance and promoting apoptotic cell deaths

Glioblastoma multiforme (GBM) is one of the most aggressive brain and spinal cord tumors. Despite the significant development in application of antitumor drugs, no significant increases have been observed in the survival rates of patients with GBM, as GBM cells acquire resistance to conventional anticancer therapeutic agents. Multiple studies have revealed that PI3K/Akt, MAPK, Nanog, STAT 3, and Wnt signaling pathways are involved in GBM progression and invasion. Besides, biological processes such as anti-apoptosis, autophagy, angiogenesis, and stemness promote GBM malignancy. Resveratrol (RESV) is a non-flavonoid polyphenol with high antitumor activity, the potential of which, regulating signaling pathways involved in cancer malignancy, have been demonstrated by many studies. Herein, we present the potential of RESV in both single and combination therapy- targeting various signaling pathways- which induce apoptotic cell death, re-sensitize cancer cells to radiotherapy, and induce chemo-sensitizing effects to eventually inhibit GBM progression.