ObjectiveTo explore the biological foundation of colorectal adenoma in damp-heat accumulation syndrome and the possible anti-tumor mechanism of Shenbai Jiedu prescription. MethodEight patients with colorectal adenoma in damp-heat accumulation syndrome， 11 patients with non-damp-heat accumulation syndrome， and 10 patients with colorectal cancer recruited by Jiangsu Provincial Hospital of Traditional Chinese Medicine from February 2019 to December 2020 meeting the inclusion criteria were clinically obtained， and the tissue of the three groups of patients was subjected to transcriptome sequencing to screen for the differentially expressed genes between the syndrome and the diseases. The intersection of the differentially expressed genes between the syndrome and the disease was taken for further screening of the differentially expressed genes sequentially increasing or sequentially decreasing in patients with non-damp-heat accumulation syndrome， damp-heat accumulation syndrome， and colorectal cancer， and functional enrichment analysis and signaling pathway enrichment analysis were carried out. Real-time polymerase chain reaction （Real-time PCR） was used to detect the effect of Shenbai Jiedu prescription on the expression of the above key differential genes. ResultBy comparing the damp-heat accumulation syndrome and non-damp-heat accumulation syndrome， a total of 384 differentially expressed genes were screened， of which 203 were up-regulated genes， and 181 were down-regulated genes. By comparing the colorectal adenoma of colorectal cancer and damp-heat accumulation syndrome， a total of 2 965 differentially expressed genes were screened， of which 2 460 were up-regulated genes， and 505 were down-regulated genes. The intersection of differentially expressed genes of the two groups was taken， and a total of 58 differentially expressed genes with the same changes were screened. The gene ontology functions were mainly enriched in UDP-galactose： β-N-acetylglucosamine beta-1，3-galactosyltransferase activity， N-acetyllactosaminide beta-1，3-N-acetylglucosaminyltransferase activity， and poly-N-acetyllactosamine biosynthetic process. Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways were mainly enriched in glycosphingolipid biosynthesis-globo and isoglobo series， glycosphingolipid biosynthesis-lacto and neolacto series， and IL-17 signaling pathway. Shenbai Jiedu prescription significantly inhibited the expression of key genes involved in the enrichment， such as FOSB and B3GALT5， in a dose-dependent manner （P<0.05）. ConclusionGlycolipid metabolism may be the biological foundation of colorectal adenoma in damp-heat accumulation syndrome， and Shenbai Jiedu prescription may inhibit colorectal adenoma carcinogenesis by down-regulating the expression of FOSB and B3GALT5.

ObjectiveTo observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets. MethodA total of 21 patients diagnosed with colorectal adenoma were enrolled in this study. Following a four-week administration of Shenbai Jiedu prescription， their clinical symptoms were observed， and fecal samples of patients before and after treatment were collected. Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry （LC-MS） were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients. ResultThe total scores of traditional Chinese medicine （TCM） syndromes of patients after drug administration decreased significantly （P<0.01）. The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration， and a total of 106 differential metabolites were screened out （P<0.05）. The Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis revealed that arginine-proline metabolism， ferroptosis， glycine， and serine and threonine metabolism were significantly enriched metabolic pathways （P<0.05）. Notably， L-4-hydroxyglutamate semialdehyde， glutathione， isopentenyl pyrophosphate， creatinine， 4-acetamido-2-aminobutanoic acid， and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways. Furthermore， the association between these metabolites and different intestinal flora was analyzed， and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium， Eggerthella， and Dialister （P<0.05）. ConclusionShenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria， reducing the abundance of harmful bacteria， and regulating metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma. This study may provide some research ideas and directions for Shenbai Jiedu prescription to interfere with colorectal adenoma recurrence and carcinogenesis.

Colorectal adenoma is a benign tumor originating from the mucosal glandular epithelium of the colorectum and belongs to the category of intraepithelial neoplasia. Its etiology and pathogenesis are not completely clear， and some patients have genetic factors. In recent years， with the improvement in living standards， the incidence of colorectal adenoma has gradually increased due to high-fat diets， intestinal flora disorder， and emotional disturbance. As one of the precancerous lesions of colorectal cancer， colorectal adenoma is increasingly threatening human health. Surgical resection is the most direct and effective method for the treatment of colorectal adenoma， but some patients with colorectal adenoma have the possibility of recurrence after resection. At present， there is still a lack of effective prevention and treatment measures for the recurrence of colorectal adenoma. Traditional Chinese medicine （TCM） plays a unique advantage in improving the clinical symptoms of patients with colorectal adenoma and preventing postoperative recurrence and carcinogenesis. Therefore， this review summarized the clinical research and mechanism of TCM compounds in the prevention and treatment of colorectal adenoma in recent years. The clinical study on the prevention and treatment of colorectal adenoma by TCM compounds can be divided into internal treatment， external treatment， and internal and external combined treatment. The internal treatment mainly focuses on strengthening the spleen， and the external treatment includes retention enema， acupoint application， and other methods. The internal and external combined treatment is mainly based on the internal administration of TCM compounds combined with acupuncture， retention enema， and acupoint stimulation. The study on the mechanism of TCM compounds in preventing and treating colorectal adenoma was mainly explored from the aspects of regulating intestinal flora， regulating cell proliferation immune function， and achieving anti-inflammation. This review summarized the research progress of TCM compounds in the prevention and treatment of colorectal adenoma in recent years and provided a reference for future treatment with TCM.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

OBJECTIVE: To investigate the protective effect of serine hydroxymethyl transferase 2 (SHMT2) against hepatic ischemia-reperfusion injury in mice. METHODS: Sixty C57BL/6 mice were divided equally into sham-operated group, saline adeno-associated virus group (AVV-GFP), and adeno-associated virus silencing group (AAV-SHMT2). The adeno-associated virus and normal saline were injected into the tail vein of the mice 2 weeks before establishment of a 70% ischemia-reperfusion model in the liver. qPCR, Western blotting, immunofluorescence and immunohistochemistry were used to detect the changes of AST/ALT concentration, SHMT2, JNK, NF-κB, caspase-3 and downstream inflammatory factors in the mice, and HE staining was used to observe the pathological damage of the liver tissue in each group; the cell apoptosis in the liver was detected using TUNEL assay. RESULTS: The expression of SHMT2 increased with time after hepatic ischemia-reperfusion and reached the highest level at 24 h (the relative expression was 1.5, < 0.05). At 24 h after hepatic ischemia-reperfusion, the levels of AST/ALT in AAV-SHMT2 group (588/416 U/L) were significantly higher than those in the control group (416/345 U/L) and the empty vector group (387/321 U/L) ( < 0.05). Compared with those in the control group and the empty vector group, the level of SHMT2 was significantly decreased in AAV-SHMT2 group (with a relative expression of 0.24, < 0.05), the levels of p-JNK and p-p65 were significantly increased (relative expression of 0.80 and 0.97, respectively, < 0.05), and the levels TNF-α and IL-1β were consistently elevated (relative expression levels of 1.6 and 1.2, respectively, < 0.05). No significant differences were found in these parameters between the empty vector group and the control group (>0.05). CONCLUSIONS SHMT2 may alleviate liver cell apoptosis in mice with hepatic ischemia-reperfusion injury by inhibiting the activation of JNK pathway and excessive activation of NF-κB pathway to reduce hepatic damage.
Animals ; Apoptosis ; Liver ; Methyltransferases ; Mice ; Mice, Inbred C57BL ; NF-kappa B ; Reperfusion Injury ; Serine

Objective: To analyze the prognostic factors of adult nonclear cell renal cell carcinoma (nccRCC). Methods: The clinical data of 286 patients with pathologically diagnosed one specific type of nccRCC after radical nephrectomy and nephron sparing surgery(NSS) in the affiliated hospital of Qingdao university followed up from January 2012 to January 2019 were retrospectively analyzed.There were 159 males and 127 females. Their age ranged from 17 to 81 years old, with an average age of 53. Based on the AJCC combination stage, 218 cases were in stage Ⅰ, 56 cases were in stage Ⅱ, 9 cases were in stage Ⅲ, 3 cases were in stage Ⅳ. Assay indicators were collected, including lymphocyte percentage(LY%)(31.5±10.5), neutrophil-lymphocyte ratio(NLR)(2.6±2.8), albumin(40.9±4.7)g/L, prealbumin(255.0±74.3)mg/L, lactate dehydrogenase (LDH)(201.0±174.0)U/L, creatine kinase isoenzyme (CK-MB)(20.0±62.1)U/L, total cholesterol(4.9±1.0)mmol/L, blood urea nitrogen/creatinine (BUN/Cr)(12.9±9.9), blood glucose(5.4±1.3)mmol/L, triglyceride(1.4±1.1)mmol/L, low-density lipoprotein cholesterol (LDL-C)(2.9±0.8)mmol/L. The optimal cut-off value of the above indexes were obtained by the receiver operating characteristic curve(ROC) in the SPSS software, and difference between high cut-off and low cut-off divided basing on the optimal cut-off value were evaluated respectively. The prognostic factors of adult nccRCC were evaluated by univariate and multivariate Cox proportional hazards regression analysis. Kaplan-Meier survival curve was used to study the survival relationship. The log-rank test were used to compare survival rate in two groups. The prognostic factors of nccRCC were analyzed after the results above were presented. Prognostic factors in renal chromophobe cell carcinoma and papillary cell carcinoma were analyzed by the same method. Results: The 286patients were followed up from 1 to 87 months, with an average of 43.9 months. The 3-year and 5-year survival rates were 93.8% and 89.3%, respectively. Results of univariate and multivariate Cox regression model revealed that AJCC combined staging (HR=2.38, 95%CI1.48-3.83), LDH(HR=2.99, 95%CI1.16-7.69), blood glucose (HR=4.13, 95%CI 1.74-9.78), CK-MB (HR=3.85, 95%CI1.63-9.08) were independent prognostic factors of nccRCC. NLR(HR=8.28, 95%CI1.66-41.35) and LDH(HR=9.82, 95%CI2.94-32.82) were the independent prognostic factor in the renal chromophobe cell carcinoma subgroup and the papillary renal cell carcinoma subgroup, separately. Conclusions AJCC combination stage, LDH, blood glucose and CK-MB are independent prognostic factors of adult nccRCC. Patients with low LDH, hypoglycemia, CK-MB and early AJCC stage have better prognosis. NLR is an independent predictor of renal chromophobe cell carcinoma, and the low NLR group has a better prognosis and higher survival rate. LDH is an independent predictor of papillary renal cell carcinoma and low LDH is beneficial to patients' prognosis. NLR and LDH can be used as a prognostic indicator for clinical evaluation in renal chromophobe cell carcinoma and papillary renal cell carcinoma, respectively.

OBJECTIVETo investigate the role of miR-520a in regulation ErbB4 expression and the biological behavior of esophageal squamous cell carcinoma (ESCC).

METHODSThe role of miR-520a in regulating the expression of ErbB4 was investigated by Western blotting and luciferase reporter assay system. The effect of miR-520a on the proliferation and invasion of ESCC cells was detected by MTT and Transwell invasion assay, respectively.

RESULTSWestern blotting and luciferase reporter assay revealed that miR-520a down-regulated the expression of ErbB4 in vitro. miR-520a significantly inhibited the proliferation and suppressed the invasion of ESCC cell line Eca109.

CONCLUSIONmiR-520a regulates the expression of ErbB4 and suppresses the proliferation and invasion of ESCC cells in vitro, suggesting its role as a tumor suppressor.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Esophageal Neoplasms ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; metabolism ; Receptor, ErbB-4 ; metabolism

Objective To design and synthesize a series of new type four hydrogen quinoline-benzyl/benzimidazole amine derivatives as a potential new inhibitor targeting auxiliary receptor CXCR 4, and determine their inhibitory activities to HIV-1.Methods Based on HIV-1 receptor CXCR4 inhibitors containing three nitrogen structure-activity motif and CCR5 partial hydrophobic pharmacophore , a series of new compounds were designed , synthesized and characterized by 1 HNMR and MS.The inhibitory activities of these compounds were determined using HIV-1 IIIB virus.Results and Conclusion Ten target compounds are synthesized .Four hydrogen quinoline-benzimidazole amine derivatives exhibit good anti-HIV activity(IC50 <1 μmol/L), but four hydrogen quinoline-benzyl amine compounds are less active ((IC50 >8 μmol/L).

Objective To investigate the role of miR-520a in regulation ErbB4 expression and the biological behavior of esophageal squamous cell carcinoma (ESCC). Methods The role of miR-520a in regulating the expression of ErbB4 was investigated by Western blotting and luciferase reporter assay system. The effect of miR-520a on the proliferation and invasion of ESCC cells was detected by MTT and Transwell invasion assay, respectively. Results Western blotting and luciferase reporter assay revealed that miR-520a down-regulated the expression of ErbB4 in vitro. miR-520a significantly inhibited the proliferation and suppressed the invasion of ESCC cell line Eca109. Conclusion miR-520a regulates the expression of ErbB4 and suppresses the proliferation and invasion of ESCC cells in vitro, suggesting its role as a tumor suppressor.

Objective To investigate the role of miR-520a in regulation ErbB4 expression and the biological behavior of esophageal squamous cell carcinoma (ESCC). Methods The role of miR-520a in regulating the expression of ErbB4 was investigated by Western blotting and luciferase reporter assay system. The effect of miR-520a on the proliferation and invasion of ESCC cells was detected by MTT and Transwell invasion assay, respectively. Results Western blotting and luciferase reporter assay revealed that miR-520a down-regulated the expression of ErbB4 in vitro. miR-520a significantly inhibited the proliferation and suppressed the invasion of ESCC cell line Eca109. Conclusion miR-520a regulates the expression of ErbB4 and suppresses the proliferation and invasion of ESCC cells in vitro, suggesting its role as a tumor suppressor.