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ObjectiveTo explore the mechanism of Shaoyaotang （SYT） in the treatment of ulcerative colitis （UC） based on network pharmacology and experimental verification. MethodThe core components， target genes， and main pathways of SYT were predicted based on network pharmacology， and UC-related components， target genes， and pathways were screened. Dextran sodium sulfate （DSS） was used to induce the UC model in mice， and the effect of SYT on UC mice was observed， followed by mechanism verification. ResultNetwork pharmacology indicated that 174 active components and corresponding 159 target genes of SYT were screened， and the related pathways were those mediated by 5-hydroxytryptamine （5-HT） degredation and 5-HT receptor 3. The results of animal experiments showed that compared with the model group， the SYT group showed increased body weight and colon length（P<0.01）， reduced disease activity index （DAI） score （P<0.01）， improved histopathological manifestations， reduced concentrations of 5-HT in the colonic tissues and serum （P<0.05， P<0.01）， and increased mRNA expression of monoamine oxidase A （MAOA）， monoamine oxidase B （MAOB）， sodium-dependent serotonin transporter （SLC6A4）， and 5-HT receptor 3A （5-HTR3A） related to 5-HT metabolism in the colon （P<0.01）. ConclusionSYT can alleviate the local inflammatory response of the intestinal tract in UC by regulating 5-HT degredation pathways.
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METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
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Animals , Mice , Methylation , Chromatin , Histones/metabolism , RNA, Messenger/genetics , Methyltransferases/metabolism , RNA/metabolismABSTRACT
Background Keratoconus is a progressive corneal thinning and protrusion disease that develop in the age of puberty,resulting in a certain extent impairment of visual function.Corneal collagen cross-linking (CXL) increases the stiffness of the cornea through the photooxidation of ultraviolet A (UVA) and riboflavin,with the aim to postpone and prevent the progression of keratoectasia.Objective This study was to evaluate the safety and efficacy of transepithelial CXL in the treatment of pediatric keratoconus.Methods Ten eyes of 9 pediatric patients with keratoconus undergoing transepithelial CXL were enrolled from February 2010 to March 2013 in Affiliated Eye Hospital of Wenzhou Medical University,with the mean age was (15± 1) years (range from 13 years to 17 years).After topical anesthesia (0.1％ tetracaine) for 15 minutes,0.5％ riboflavin was applied until it was saturated in the anterior chamber,then UVA with the intensity of 3 mW/cm2 was performed on the cornea for 30 minutes.The uncorrected distance visual acuity (UDVA),corrected distance visual acuity (CDVA),refractive error,topography,corneal thinnest thickness were measured 7 days,1 month,3 months,6 months and 1 year after operation.Endothelium cell density (ECD) was measured 7 days afier operative.Results The mean corneal reepithelization time was (1.4±0.8) days.The UDVA and CDVA were significantly improved from preoperative 1.02±0.16 and 0.34±0.20 to postoperative 0.77±0.18 and 0.25 ±0.15,respectively (t =4.251,3.750;both at P＜0.05).The refractive sphere and spherical equivalent significantly changed from preoperative (-7.15±3.00)D and (-9.26±3.23)D to postoperative (-5.28±2.05) D and (-7.05±2.08) D 1 year,respectively (t =-2.515,-2.597;both at P＜0.05).Maximum Kvalue (Kmax) was significantly decreased from preoperative (64.1 ± 11.9) D to postoperative (61.8 ± 10.4) D (t =2.304,P＜0.05).The refractive cylinder,corneal thinnest thickness and ECD showed no significant differences between preoperation and postoperation (t =-1.331,0.328,1.205;all at P＞0.05).Stromal opacity was observed in 2 eyes 3 months and 6 months after operation,respectively.Conclusions Transepithelial CXL is safe and effective in prolonging or halting progression in adolescent keratoconus.
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Objective To investigate the effect of intrathecal injection of ropivacaine in the treatment of carpal tunnel syndrome with nervi medianus entrapment syndrome. Methods 164 patients with carpal tunnel syndrome were selected and divided into two groups, 82 cases in the control group were given intrathecal injection of lidocaine + methylprednisolone + vitamin B1, 82 cases in the experimental group received injection of ropivacaine + methylprednisolone + vitamin B1, the symptom score, nerve electrophysiological examination index, high frequency ultrasound quantitative parameters, the clinical effect and total recurrence rate were compared after treatment. Results The effective rate in the control group(74.39%)was lower than the experimental group(87.81%)(P<0.05); compared with the control group, the visual analogue scale (VAS), global symptom score (GSS), fatigue severity scale (FSS) and Levine carpal tunnel syndrome questionnaire score were lower in the experimental group after treatment, the nervi medianus distal motor latency (DML) level was lower, sensory nerve action potential (SNAP) and sensory conduction velocity (SCV) levels were higher after treatment, the diameter of the nervi medianus, the transverse diameter (a), anteroposterior diameter (b) of nervi medianus and cross sectional area (CSA) were lower after treatment, with significant difference (P<0.05); the total recurrence rate in the control group(53.66%)was higher than the experimental group(37.80%), with significant difference (P<0.05). Conclusion The clinical effect of intrathecal injection of ropivacaine in the treatment of carpal tunnel syndrome with nervi medianus entrapment syndrome was obvious, can effectively alleviate pain, improve the symptoms of nervi medianus entrapment, restore the nervi medianus conduction velocity and function, and reduce the recurrence rate.
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Objective To explore the clinical features and treatment of upper gastrointestinal bleeding with rare etiologies.Methods A total of 45 cases with rare etiologies was selected from a group of 1200 patients with upper gastrointestinal bleeding admitted from January 2012 to December 2015.Results The incidence of gastric stromal tumor (24.4％) and Dieulafoy's lesion (20.0％) was the highest.Among rare etiologies of upper gastrointestinal bleeding were Mallory-Weiss syndrome (17.8％) and stomal ulcer and hemorrhage of efferent loops after subtotal gastrectomy (17.8％),as well as left-side portal hypertension (6.7％),liver cirrhosis complicated with variceal bleeding in the descending part of the duodenum (2.1％),esophageal hematoma (2.1％),esophageal mucosa avulsion (2.1％),P-J syndrome (2.1％),duodenal adenocarcinoma (2.1％),and cutaneous malignant melanoma with duodenal metastasis (2.1％).Conclusions Gastroscopy in early stages played a role in etiologies identification,while etiological treatments could substantially reduce recurrent bleeding rate,thus enhanced cure rate.Analysis on rare etiologies promoted the medical understanding,with clinical diagnosis and treatment improved.
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<p><b>OBJECTIVE</b>To construct a small interfering RNA (siRNA) vector targeting p63 and observe its effect on the proliferation and invasiveness of human cholangiocarcinoma cells in vitro.</p><p><b>METHODS</b>Real-time PCR was used to examine the expression of p63 in human cholangiocarcinoma QBC939 cells. The recombinant lentivirus shRNA-p63 vector was constructed and transfected into QBC939 cells via Lipofectamine 2000 to establish a cholangiocarcinoma cell line with stable expression of siRNA-p63. The interfering efficiency of the siRNA targeting p63 was assessed using Western blotting. MTT and soft agar colony formation assays were used to evaluate the changes in the cell proliferation, and Boyden test was employed to observe the cell invasiveness after the transfection.</p><p><b>RESULTS</b>QBC939 cells showed a high expression of p63. The recombinant lentivirus shRNA-p63 vector was successfully constructed as verified by sequencing. Transfection with the vector significantly suppressed the proliferation and invasiveness of QBC939 cells.</p><p><b>CONCLUSION</b>Down-regulation of p63 can inhibit the proliferation and invasiveness of human cholangiocarcinoma QBC939 cells in vitro.</p>