In recent year, one of the hot topics in esophageal carcinoma research is the impaired gene expression resulted from hypermethylation within the promoter regions of rumor suppressor genes. Many studies suggested that DNA methylation plays an important role in the initiation, invasion, and metastasis of esophageal carcinoma. DNA methylation spectrum in peripheral blood may be used as markers for early diagnose, prognosis prediction and follow up in esophageal cancer patients. De-methylation of tumor suppressor genes may become a target of esophageal carcinoma therapy.

OBJECTIVE: To study the pathogenic spectrum and the clinical characteristics of viral diarrhea in children.METHODS: The study was conducted in 400 children with viral diarrhea hospitalized in Children's Hospital from January to December in 2016. The stool specimens(about 5 mL)were collected for detection from the children on the day of hospitalization. The ELISA method and PCR method were used to detect the genotypes of HUCV,HADV,HAsta V and HRV in stool specimens,and the clinical data of children were collected at the same time. RESULTS: In 2016,the total positive rate of HRV,HUCV,EAd V and HAst V in the stool specimens of children with viral diarrhea was 59%(236 cases). The positive detection rates of the four viruses were 178 cases(75.42%),68 cases(28.81%),12 cases(5.08%)and 5 cases(2.12%)respectively,of which 11.42% were double mixed infection and 41% were of unknown pathogens. The HRVG6(93.63%,147 cases)and P3(91.08%)as well as G6[P3](90.45%)combination were the popular superior type in 2016,and about 11.79%couldn't be typed. Norovirus accounted for 92.65% of the calicivirus viruses,and GⅡ accounted for 98.41%. About 81.79%of the children(193 cases)hospitalized for viral diarrhea were less than 24 months old. Pathogens were different at different peak age. The peak season of onset was fromJanuary to March and December. The main clinical manifestations were diarrhea,vomiting and fever. CONCLUSION: It is essential to determine the unknown pathogens and improve the pathogenic spectrum in children with viral diarrhea. Viral diarrhea is often accompanied by extraintestinal clinical manifestations.

Objective Voxel-based morphological analysis was used to explore the changes of gray matter volume in patients with first-episode untreated depression，and to explore the structural changes of brain regions in patients with depression，so as to provide new ideas for in-depth understanding of the pathogenesis of depression.Methods 30 patients with first-episode untreated depression and 22 healthy volunteers were included. Used the PHILPS 3.0T MRI scanner for sagittal three-dimensionl brain structre scans，the brain structure images of the two groups were studied by the VBM method to explore the changes of gray matter volume in patients with first-episode untreated depression.Results Compared to healthy controls，the volume of gray matter in left middle tempral gyrus，right inslar lobe，left supeior occiptal gyrus and right dorsolteral supeior frontal gyrus were decresed in the first-episode untreated depression group（P<0.05，cluster size>45，AlphaSim correction），no region increased.Conclusion The brain regions with decreased gray matter volume in patients with first-episode untreated depression are mainly located in frontal lobe，temporal lobe，occipital lobe and insular lobe，indicating that the occurrence and development of depression is related to multiple brain regions.

OBJECTIVE： To investigate the effects of Hericium erinaceus polysaccharide on the content of short-chain fatty acids （SCFAs） in the intestine of ulcerative colitis model rats. METHODS： A total of 40 SD rats were randomly divided into blank group， model group and H. erinaceus polysaccharide low-dose and high-dose groups （0.5， 1.0 g/kg）， with 10 rats in each group. Except for blank group， other groups were given acetic acid enema to induce ulcerative colitis model. The next day after modeling， H. erinaceus polysaccharide groups were given relevant medicine solution intragastrically； blank group and model group were given relevant volume of water intragastrically， for 10 consecutive days. Colon tissue was collected， and pathological changes of colon tissue were observed by HE staining. The pathological changes of colon in rats were observed with naked eyes and scored so as to evaluate the therapeutic efficacy. The contents of 6 kinds of SCFAs （acetic acid，propionic acid，butyric acid，isobutyric acid，pentanoic acid and isovaleric acid） in intestine of rats were determined by GC-MS. RESULTS： Compared with blank group， inflammatory lesions of colonic mucosal epithelium in model group rats were obvious； colonic mucosal ulcer score increased significantly （P＜0.01）； the contents of 5 kinds of SCFAs and the total amount of SCFAs in colon except for propionic acid were decreased significantly （P＜0.01）. Compared with model group， the degree of colonic histopathological damage in H. erinaceus polysaccharide groups was significantly reduced； colonic mucosal ulcer scores were significantly reduced （P＜0.05 or P＜0.01）； the contents of 5 kinds of SCFAs and the total amount of SCFAs in colon except for propionic acid were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： H. erinaceus polysaccharide can effectively improve the pathological condition of ulcerative colitis model rats； its regulation of intestinal SCFAs （especially acetic acid and butyric acid） may be an important mechanism of its anti-ulcerative colitis.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

ObjectiveTo investigate the mechanism of action and main active components of Xiaoyaosan in the treatment of diabetic mellitus-induced erectile dysfunction （DMED）. MethodStreptozotocin （STZ） was used to induce a diabetic rat model. The therapeutic efficacy of Xiaoyaosan was evaluated by measuring intracavernous pressure/mean arterial pressure （ICP/MAP） and using Masson's trichrome staining. The main active components， key targets， and potential signaling pathways of Xiaoyaosan for the treatment of DMED were predicted by network pharmacology and molecular docking. The predicted results were then validated by in vitro and in vivo experiments. ResultThe ICP/MAP measurements and Masson's staining results showed that compared with the results in the control group， the erectile function of rats in the model group was significantly reduced （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly reduced （P<0.01）. After treatment with Xiaoyaosan， compared with the results in the model group， the ICP/MAP value of the diabetic rats was significantly elevated （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly higher （P<0.01）. The results of network pharmacology showed that Xiaoyaosan acted on key targets such as albumin （ALB）， protein kinase B1 （Akt1）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF） through its main active components， including quercetin， kaempferol， β-sitosterol， and stigmasterol. These components were involved in the regulation of the advanced glycation end-products/receptor for advanced glycation end-products （AGE/RAGE） signaling pathway and the phosphoinositide 3-kinases（PI3K）/Akt signaling pathway in diabetic complications. The results of molecular docking showed that the key components of Xiaoyaosan had good binding capabilities with core targets， with β-sitosterol showing the strongest binding affinity with ALB. In vivo experiments demonstrated that Xiaoyaosan could significantly increase the protein and mRNA expression of ALB and Akt1 in serum， and inhibit the expression of IL-6 and TNF-α. It also significantly upregulated the expression of protein and mRNA of phosphorylation（p）-PI3K and p-Akt， and inhibited the RAGE expression. The results of cellular thermal shift assay （CETSA） showed that β-sitosterol could significantly inhibit the degradation of ALB protein. ConclusionXiaoyaosan may restore erectile function in diabetic rats by modulating targets such as ALB， Akt1， IL-6， and TNF， and through the RAGE/PI3K/Akt signaling pathway， and its main active component is likely β-sitosterol.

Objective:To investigate the protective effect of Wutou Chishizhi Wan on myocardial ischemia reperfusion injury （MIRI） in rats， and observe its effect on such mechanisms as coagulation function， vascular endothelial cells and oxidative stress in rats. Method:A total of 40 SD rats were randomly divided into normal group， model group， positive drug group （Urokinase group） and Wutou Chishizhi Wan group， with 10 rats in each group. Except for the normal group， rat myocardial ischemia-reperfusion injury models were established. The changes of heart rate （HR） at 10 min before ischemia， 30 min after ischemia and 30， 60， 120 min （T₀，T₁，T₂，T₃，T₄）， and the change of electrocardiogram （ECG） J point after modeling in rats were observed. The pathological changes of rat myocardial tissue were observed by hematoxylin-eosin （HE） staining. The changes of four indexes of coagulation ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， fibrinogen content decreased significantly （FIB）］ in rats were observed. The contents of endothelin-1 （ET-1）， thromboxane A₂ （TXA₂） and prostacyclin （PGI₂） in serum and myocardium levels of superoxide dismutase （SOD）， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） of MIRI rats were observed. Western blot assay was used for the detection of oxidative stress protein Keap1 and transcription factor-E2-related factor （Nrf2） expression levels in rat myocardial tissue. Result:Compared with the normal group， the ECG of MIRI rats showed significant myocardial ischemic injury-like changes， ST segment was significantly elevated， J point was significantly increased， and the incidences of HR in T₁， T₂， T₃ and T₄ were significantly reduced （P<0.05， P<0.01）. Compared with the model group， Wutou Chishizhi Wan significantly reduced ECG J-point changes in MIRI rats， while increased the incidence of HR in T₁， T₂， T₃ and T₄ （P<0.05， P<0.01）. Compared with the normal group， PT， APTT and TT in the model group were significantly shortened （P<0.01）， FIB content was significantly increased （P<0.01）， and the serum PGI₂ level decreased and TXA₂ and ET-1 levels increased significantly in the model group （P<0.01）. SOD content and GSH-Px activities of myocardial tissue in the model group were significantly reduced （P<0.01）， whereas the MDA content was increased （P<0.01）. Compared with the model group， PT of the Wutou Chishizhi Wan group was prolonged （P<0.05） and APTT slightly prolonged， TT significantly prolonged （P<0.01）， FIB content decreased （P<0.05）， serum PGI₂ increased （P<0.05）， TXA₂ and ET-1 decreased significantly in the Wutou Chishizhi Wan group （P<0.01）， myocardial MDA content decreased， and SOD content and GSP-Px activity increased significantly （P<0.01）. Meanwhile， the Wutou Chishizhi Wan group was able to activate the Keap1/Nrf2 signaling pathway， which significantly increased Nrf2 expression and significantly decreased Keap1 expression （P<0.01）. Conclusion:Wutou Chishizhi Wan group can protect myocardial injury in MIRI rats. The specific mechanism is to protect MIRI by regulating vascular endothelial cell homeostasis and oxidative stress levels and activating Keap1/Nrf2 signaling pathway.