Explore Mechanism of Modified Si Junzitang in Improving Acidic Microenvironment and Reversing Gastric Precancerous Lesions Based on MCT4/CD147 / 中国实验方剂学杂志

Objective:To observe the effect of modified Si Junzitang on the level of lactic acid in gastric mucosa and the expression of Carboxylic acid transporter 1（MCT1）， monocarboxylic acid transporter 4（MCT4）， and extracellular matrix metalloproteinase inducer （CD147）in rats with gastric precancerous lesions（GPL）. Method:Seventy-four SD male rats were randomly divided into normal group （12 rats） and model group （62 rats）. <italic>N</italic>-methyl-<italic>N'</italic>-nitro-<italic>N</italic>-nitrosoguanidine（MNNG）-ammonia compound method was used to establish GPL rat models， and at the 9^th week， the model rats were randomly divided into model group， folic acid group（2.7 mg·kg^-1）， modified Si Junzitang high， medium and low dose groups（12.6， 6.3， 3.15 g·kg^-1）， with 12 rats in each group. After intragastric administration for 12 weeks， the general conditions of the rats were observed. Hematoxylin-eosin（HE）staining was used to observe the histopathological changes of gastric mucosa in rats， chemical colorimetry was used to detect the content of lactic acid in gastric mucosa； immunohistochemistry and real-time polymerase chain reaction（Real-time PCR）were used to detect MCT1， MCT4， CD147 protein and mRNA expression in gastric mucosal tissues. Result:Modified Si Junzitang significantly improved the pathological manifestations in GPL rats such as gastric mucosal epithelial gland structure， disorder of arrangement and cell atypia. Compared with the normal group， the lactic acid content of the gastric mucosa tissue in the model group increased significantly（<italic>P</italic><0.01）， and the protein and mRNA expressions of MCT1， MCT4， CD147 significantly increased（<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the lactic acid content in each dose group of modified Si Junzitang was significantly reduced（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expression levels of MCT4 and CD147 were also significantly reduced in each dose group of modified Si Junzitang（<italic>P</italic><0.05， <italic>P</italic><0.01）. The mRNA expression of MCT4 was significantly reduced in the middle and high dose groups（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the mRNA expression of CD147 was significantly reduced in the high dose group（<italic>P</italic><0.05）. Modified Si Junzitang showed no significant regulatory effect on MCT1. Conclusion:Modified Si Junzitang can significantly improve the abnormal histopathology of gastric mucosal epithelium in GPL model rats. Its mechanism may be related to down-regulating the overexpression of MCT4 and CD147， inhibiting lactic acid outflow， and improving the acidic microenvironment of gastric mucosal epithelium.

Large- scale prospective clinical study on prophylactic intervention of COVID-19 in community population using Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules / 中国中药杂志

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.

Effect of Shenqi Compound on Islet β-cell Function in Type 2 Diabetic GK Rats / 中国实验方剂学杂志

Objective:To explore the effect of Shenqi compound on islet β-cell function in type 2 diabetic GK rats. The whole genome expression profile chip technology is used to explore the molecular mechanism of Shenqi compound regulating pancreatic islet cell function and provide theoretical basis for the prevention and treatment of type 2 diabetes with traditional Chinese medicine. Method:GK rats were fed with high-fat diet daily for 4 weeks. Rats were randomly selected from GK rats to detect random blood glucose and verified the success of type 2 diabetes model. Rats were divided into 4 groups， Wistar group， model group， Shenqi compound（1.44 g∙kg-1） group and west glenn（16 mg∙kg-1） group. After 8 weeks of gavage， the serum insulin（INS） levels were detected by enzyme-linked immunosorbent assay（ELISA）. The apoptosis of islet β cells was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling（TUNEL）fluorescence method. Differential gene detection uses whole-genome expression profiling chip technology in each group of rat pancreatic tissues， the mRNA transcription level of key differential genes is detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with blank group， before gavage， 4 weeks， 8 weeks， GK rats have higher blood sugar in each group （P<0.01）.Gavage for 4 weeks and gavage for 8 weeks， compared with model group， the blood sugar of rats in each drug intervention group was lower （P<0.01）. Gavage for 8 weeks， compared with blank group， the INS level of model group was lower （P<0.01）. Compared with model group， the Shenqi compound group had a higher INS level， and the sitagliptin group had a higher INS level （P<0.01）. After gavage for 8 weeks， compared with the blank group， the number of pancreatic islet β-cell apoptosis in the model group was higher （P<0.05）. Compared with model group， the number of pancreatic islet β cell apoptosis in the Shenqi compound group and sitagliptin group was lower （P<0.05，P<0.01）. Gene chip and Real-time PCR tests both showed that phosphatidylinositol 3-kinase receptor 1（PIK3R1） was up-regulated in the Shenqi compound group/model group， and down-regulated in the sitagliptin group/model group， model group/blank group. Protein kinase B1（Akt1） was expressed in the Shenqi compound group/model The expression was up-regulated in the group， sitagliptin group/model group， and down-regulated in the model group/blank group. Conclusion:Shenqi compound which has the function of supplenmenting Qi and Yin and promoting the blood circulation， can inhibit the islet β cell apoptosis， improve islet β cell function， regulate insulin secretion， and prevent T2DM by up-regulating the expression of genes PIK3R1 and Akt1.