As a classic work of Japanese Chinese medicine, Huang Han Yi Xue, with its ancient prescription school theories and Western medical principles, influenced the formation of Hu Xishu's academic thinking on cold-induced disease. This article combined Huang Han Yi Xue with the recordings and manuscripts of Hu's existing lectures to show another perspective on the flow of Hu's academic thought on cold-induced disease. It is considered that the influence of Huang Han Yi Xue made Hu different from the traditional typhoid scholars. Hu abandoned the annotations of Huang Di Nei Jing, emphasized the relativity of prescriptions and syndrome, focused on the state of Mingxuan reaction, paid attention to food, water and blood stasis, explained the essence of disease with physiological and anatomical knowledge, innovated the cognition of the six meridians and the eight compendiums, and formed a new theoretical system.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Objective To compare the clinical effects and safety of treating newly diagnosed type 2 diabetes patients by combining Glargine insulin with Metformin or/and Acarbose. Methods 84 patients with newly diagnosed type 2 diabetes ,who have a history of weight loss, body mass index( BMI )23 ～ 28kg/m2 and poorly controlled blood glucose in Metformin at least a month ,were randomly divided into three groups. Glargine insulin plus Mefformin were used in group A. Glargine insulin plus Acarbose(without mefformin)were used in group B, Glargine insulin, Acarbos and metformin were used in Group C. All three groups were given a 12-week follow-up. Results FBG,2hBG and HbA1c levels were lower in the patients after treatment( P ＜0. 05 ). HbA1c of patients was partly up to the standard in group A and group B,but HbA1c of patients was all up to the standard in group C. The effects in group C were better than those in group A and group B. It had the shortest time to achieve the target and the smallest dose of insulin in group C. BMI in group A and B did not change but decreased in group C(P＞0.05).The incidence of low blood sugar in all three groups was low and no significant difference observed among three groups (P＞0.05). And in all three groups no severe hypoglycemia occurred. Conclusion The method of combining Glargine insulin with Mefformin or/and Acarbose could effectively control blood sugar had little impact on body weight of the newly diagnosed type 2 diabetes patients, and moreover, the incidence of low blood sugar in the newly diagnosed type 2 diabetes patients was lower. It would be the ideal method to treat newly diagnosed type 2 diabetes patients considering the general safety and effectiveness and convenience.