Objective To assess the effects of low-dose esketamine on the median effective dose(ED50)of ciprofol for anesthesia induction in painless gastrointestinal endoscopy.Methods Fifty-nine pa-tients underwent elective painless gastrointestinal endoscopy,26 males and 33 females,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups by random number table method:esketamine combined with ciprofol group(group EC,n = 29)and ciprofol group(group C,n = 30).Group EC received intravenous injection of esketamine 0.3 mg/kg and group C received the same amount of normal saline 2 minutes before administration of ciprofol.The initial anesthesia induction dose of ciprofol was 0.4 mg/kg.If a positive reaction occurs during the examination,the next patient will receive an increase dose of propofol 0.04 mg/kg,otherwise will decrease by propofol 0.04 mg/kg.The positive reaction was defined that the patient's BIS can not be decreased to 60 2 minutes after anesthesia induction,or the cough or body movement reaction occur at level 2 or above when entering the mirror.The dosage of ciprofol,recovery time,discharge time,the occurrence of intraoperative and postoperative adverse reactions were recorded.The ED50,95%effective dose(ED95)and 95%confidence interval(CI)of the two groups were calculated by Probit probability regression analysis.Results Compared with group C,the dosage of ciprofol,the incidence of hypotension and frequency of administration of vasoactive drugs during the exami-nation process in group EC were significantly reduced(P＜0.05).The ED50 of ciprofol for anesthesia in-duction in painless gastrointestinal endoscopy in group EC was 0.21 mg/kg(95%CI 0.12-0.25 mg/kg)and the ED95 was 0.32 mg/kg(95%CI 0.26-0.39 mg/kg).The ED50 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group C was 0.37 mg/kg(95%CI 0.32-0.40 mg/kg)and the ED95 was 0.48 mg/kg(95%CI 0.43-0.54 mg/kg).The ED50 and ED95 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group EC was significantly lower than that in group C(P＜0.05).There was no significant difference in other frequency of adverse events between the two groups.Conclusion Esketamine 0.3 mg/kg can reduce the ED50 of ciprofol in painless gastrointestinal endoscopy and reduce the dosage of ciprofol during the examination process,which is safe for painless gastrointestinal endoscopy with stable intraoperative circulation.

Pelvic inflammatory disease （PID） is an infection of women's reproductive organs， which lasts a long time and features frequent recurrence. It is mainly caused by apoptosis， low immunity， abnormal metabolism and blood rheology indexes， and bacterial imbalance. The pathological manifestations are tissue adhesion， fibrosis， and chronic inflammation， and inflammatory response occurs in the whole process of this disease. Therefore， interfering with the inflammatory response tends to be a solution. A few therapies are available in western medicine and antibiotics are commonly used. However， antibiotic resistance is still a bottleneck in the treatment and thus the symptoms of patients fail to be obviously relieved， with pelvic tissue adhesions remained. In the treatment of inflammation， traditional Chinese medicine has remarkable effect and internal-use and external-use medicines are both used， such as oral Chinese medicinal decoction， Chinese medicine enema， Chinese medicine iontophoresis， and acupuncture. They exert therapeutic effect by regulating the conduction of related signaling pathways and influencing the expression of inflammatory cytokines. At the moment， most articles focus on the efficacy of traditional Chinese medicine in the treatment of PID， and there is a lack of summary on traditional Chinese medicine regulation of relevant signaling pathways and the pathogenesis of PID. Therefore， by summarizing relevant research， this review proposed five signaling pathways related to the occurrence of this disease， namely， transforming growth factor-β/Smads protein （TGF-β/Smads） signaling pathway， Janus kinase/signal transducer and transcription activator （JAK/STAT） signaling pathway， nuclear factor-κB （NF-κB） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and Hippo signaling pathway， and described the pathogenesis of this disease. Thereby， this study is expected to provide effective targets and ideas for the treatment of this disease.

OBJECTIVE To investigate the effects of Compound troxerutin and poreine cerebroside injection on the activity of cytochrome P450 （CYP450） enzyme in vivo and in vitro. METHODS Human liver microsomes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） and the specific probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 for 30 min. The production of corresponding metabolites was detected by ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and the half inhibitory concentration （IC50） was calculated. The relative mRNA expression （i.e. induction multiple） of CYP450 enzyme was determined by real-time fluorescence quantitative PCR after human primary hepatocytes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） or 3 positive inducers of CYP1A2， CYP2B6， CYP3A4 for 48 hours. Male SD rats were randomly divided into control group （normal saline+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10， 10， 8 mg/kg） and experimental group （Compound troxerutin and poreine cerebroside injection 0.9 mL/kg+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10，10， 8 mg/kg）， with 6 rats in each group. The pharmacokinetic parameters of probe substrates were detected by UPLC-MS/MS and Cocktail probe drug method. RESULTS After the lzqpharm@126.com treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the activities of CYP2B6， CYP2C8 and CYP2C19 in human liver microsomes had no significant change， and IC50 could not be fitted； IC50 of CYP1A2， CYP2C9， CYP2D6 and CYP3A4 were 419.90%， 97.78%， 176.00%， 19.42%， respectively. After the treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the average induction multiple of CYP3A4 mRNA in human primary hepatocytes （No. MHK） was 4.88 （and the average induction multiples of 2 concentration points were higher than 2）. After the treatment of Compound troxerutin and poreine cerebroside injection， AUC0－t and AUC0－∞ of CYP2C8， CYP2C9 and CYP2C19 substrates were increased significantly， CL of CYP2C8 and CYP2C19 substrates were decreased significantly， while t1/2 of CYP2C9 substrate was prolonged significantly （P＜0.05）. CONCLUSIONS Compound troxerutin and poreine cerebroside injection has no obvious inhibitory effect on CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 in human liver microsomes in vitro， but can induce the mRNA expression of CYP3A4 in human primary hepatocytes in vitro， and can inhibit the activities of CYP2C8， CYP2C9 and CYP2C19 in rats in vivo.

Objective:To explore the effectiveness of situational simulation teaching in the clinical clerkship education of endodontics.Methods:Stomatology students from Batch 2015 of Xinjiang Medical University were selected and randomly divided into two groups, experimental group ( n=28), taking situational simulation teaching and control group ( n=27), taking traditional teaching. The SEGUE scale was used to evaluate the effectiveness of the teaching methods. SPSS 21.0 software was used for independent samples t-test. Results:The theoretical results of the experimental group [(91.31±3.37) points] were higher than those of the control group [(87.93±4.28) points], with significant differences ( P < 0.05). According to the scores of SEGUE scale, the communication ability scores before and after teaching in the experimental group were (9.07±3.37) points and (21.86±2.47) points, respectively, and the difference was statistically significant ( P < 0.05); the control group were (8.85±3.43) points and (15.67±2.87) points, respectively; the teaching effect of the experimental group was significantly better than that of the control group, and the difference was statistically significant ( P < 0.05). Conclusion:The application of situational simulation teaching can effectively improve doctor-patient communication skills of medical students, thereby promoting the combination of theory and practice, and has a positive impact on improving students' clinical practice communication skills in the future.

OBJECTIVETo investigate the clinical efficacy and safety of modified stapled transanal rectal resection (STARR) combined with perioperative pelvic floor biofeedback therapy (POPFBFT) in treating obstructed defecation syndrome (ODS).

METHODSThirty female ODS patients underwent modified STARR (resection and suture was performed in rectocele with one staple) combined with POPFBFT in Department of Colorectal and Anal Surgery, The First Hospital of Jilin university from October 2013 to March 2015. Before the modified STARR, patients received a course of POPFBFT (20 min/time, 2 times/d, 10 times as a course), and another 2 courses were carried out in clinic after discharge. Efficacy evaluation included general conditions of patients, morbidity of postoperative complication, overall subjective satisfaction (excellent: without any symptoms; good: 1 to 2 times of laxatives per month and without the need of any other auxiliary defecation; fairly good: more than 3 times of laxatives per month ; poor: with no improvement; excellent, good, fairly good are defined as effective), Longo ODS score (range 0 to 40 points, the higher the score, the more severe the symptoms), gastrointestinal quality of life index(GIQLI)(range 0 to 144 points, the lower the score, the more severe the symptoms), anorectal manometry and defecography examination. The follow-up lasted 12 months after operation (ended at April 2016).

RESULTSAverage age of 30 patients was 57(46 to 72) years and Longo ODS score of every patient was ≥9 before operation. The modified STARR was completed successfully in all the 30 patients with average operation time of 25 (18 to 34) min and average hospital stay of 6(4 to 9) d. Postoperative complications included pain(20%, 6/30), urinary retention (16.7%, 5/30), anorectal heaviness (6.7%, 2/30), and fecal urgency(26.7%, 8/30). Anaorectal heaviness and fecal urgency disappeared within 3 months. No severe complications, such as postoperative bleeding, infection, rectovaginal fistula, anastomotic dehiscence and anal incontinence were observed. The effective rate of overall subjective satisfaction was 93.3%(28/30) during the follow-up of 12 months. There was no significant difference in Longo ODS score between pre- POPFBFT and pre-operation (pre- POPFBFT: 32.95±3.22, pre-operation: 32.85±3.62, t=1.472, P=0.163). Compared with pre-POPFBFT, Longo ODS score at 1 week after operation decreased (t=4.306, P=0.000), moreover, score at 1 month after operation was lower than that at 1 week (13.05±7.49 vs. 15.00±7.17, t=7.322, P=0.000), while no significant differences were found among 1, 3, 6, 12 months after operation (F=2.111, P=0.107). Likewise, there was no significant difference in GIQLI score between pre-POPFBFT and pre-operation (pre-POPFBFT: 79.39±17.14, pre-operation: 76.65±17.56, t=1.735, P=0.096). Compared with the pre-POPFBFT, GIQLI score at 1 week after operation increased (t=4.714, P=0.000), moreover, GIQLI score at 1 month after operation was higher than that at 1 week (102.26±19.24 vs 91.31±21.35, t=5.628, P=0.000), while no significant differences were found among 1, 3, 6, 12 months after operation(F=1.211, P=0.313). In comparison with pre- POPFBFT, parameters of defecography examination at 12 months after operation showed obvious improvement: the rectocele decreased from (34.1±0.4) mm to (3.1±0.3) mm (t=6.847, P=0.000), anorectal angle during defecation increased from (123.8±6.7)degree to (134.7±8.5)degree, enlargement of anorectal angle during defecation increased from (29.1±3.5)degree to (37.1±5.3)degree, while no significant differences in descend of perineum, anorectal angles at rest as well as parameters of anorectal manometry were found (all P>0.05).

CONCLUSIONModified STARR combined with POPFBFT is safe and effective for ODS patients.

Aged ; Anal Canal ; surgery ; Biofeedback, Psychology ; physiology ; Constipation ; rehabilitation ; surgery ; Defecation ; Defecography ; Digestive System Surgical Procedures ; methods ; rehabilitation ; Female ; Humans ; Length of Stay ; Middle Aged ; Operative Time ; Pain, Postoperative ; etiology ; Pelvic Floor ; physiology ; Postoperative Complications ; Quality of Life ; Rectocele ; Surgical Stapling ; Suture Techniques ; Treatment Outcome ; Urinary Retention ; etiology

The inhibitory effect of NACOS on dyslipidemia and potential molecular mechanisms by in vitro and in vivo experiments were investigated. For in vitro study, four experimental groups were designed by using HepG2 cells, including the control group, palmitic acid (PA) treatment alone group, NACOS treatment alone group and NACOS + PA treatment group. For in vivo study, male C57BL/6 mice were divided into four groups (n=5) at random including the normal control group (NCD), high fat diet (HFD) group, NACOS treatment alone group, NACOS+HFD group, which were treated for 20 weeks. The used methods in this study were as follows: the observation of lipid droplet deposition in HepG2 cells by oil red O staining, the detection of mRNA levels of lipid metabolism-related regulators and inflammatory cytokine by RT-PCR method, the monitoring of MAPKs and PI3K/Akt pathway activation by Western blotting method. The in vitro study shows that, NACOS had no toxicity on the viability of HepG2 cells at 25-100 μg/mL and significantly reduced the deposition of lipid droplet. Also, based on both in vitro and in vivo investigation, NACOS evidently down-regulated the expression of lipid metabolism-related regulators (PGC1α, Cox5b, Mcad) and inflammatory cytokine (IL-1β) at mRNA level (P<0.05 or 0.01), and suppressed the activation of p38, ERK1/2 and Akt in HepG2 cells and lever tissues from HFD-fed mice (P<0.05 or 0.01). Based on the above, NACOS may inhibit the oxidation of liver mitochondrial fatty acid and the lipid biosynthesis, block the inflammatory responses and prevent the HepG2 cells and C57BL/6 mice from lipidemia.

Aim To investigate the role of miR-125 b and its DNA methylation in homocysteine ( Hcy )-in-duced vascular smooth muscle cells( VSMCs) prolifera-tion. Methods VSMCs were stimulated with 0,50, 100, 200, 500 μmol · L-1 Hcy respectively. Then qRT-PCR was used to detect the mRNA levels of miR-125b,and nested-touchdown methylation-specific PCR ( ntMS-PCR) was used to detect the methylation levels of miR-125b. VSMCs were transfected with miR-125b precursor or the inhibitor of miR-125b ,then 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide ( MTT ) assay was used to reflect the proliferation of VSMCs. The distribution of CpG islands of miR-125b promoter region was analyzed by bioinformatics meth-ods. VSMCs were stimulated with 100 μmol·L-1 Hcy and transfected with or without DNA methylation inhib-itors 5-nitrogen impurity cytidine ( AZC) , then the ex-pression of miR-125b was detected by qRT-PCR. Re-sults The mRNA levels of miR-125 b were decreased in 100,200,500 μmol·L-1 Hcy group compared with 0 μmol·L-1 Hcy group. The precursor of miR-125b could inhibit the proliferation activity and the inhibitor of miR-125 b could increase the proliferation activity of VSMCs cells. Bioinformatics analysis indicated that MiR-125 b promoter region had a CpG island whose length was 792 bp ( 1881-2672 ) . The miR-125 b pro-moter region methylation levels increased after Hcy in-tervention ( P <0. 01 ) . The expression level of miR-125 b increased after AZC intervention ( P <0. 05 ) . Conclusions ① Hcy promotes vascular smooth mus-cle cell proliferation maybe by down-regulating the ex-pression of miR-125b. ② Hcy down-regulates the ex-pression of miR-125 maybe by up-regulating the methy-lation levels of miR-125b promoter region.

Aim To investigate the possible mecha-nisms of the levels of NO decrease induced apoptosis in human placental trophoblast cells. Methods Human placental trophoblast cells ( HTR-8 ) were cultured in 5 ml DMEM-F12 culture medium with 37℃ 5% CO2 . Then, the old culture medium was discarded and re-placed with 10,100,500,1 000 μmol·L-1 L-NAME, and the group without L-NAME was set as the control group, cultured for 48h. The effects of L-NAME on the survival of cells were detected by methylthiazolyldiphe-nyl tetrazolium bromide ( MTT); the content of NO in cells was tested by nitrate reductive enzymatic;trans-mission electron microscopy, flow cytometry analysis and Annexin-V FITC dyeing were used to test the effects of L-NAME on apoptosis in HTR-8 cells;restore Fe3+ colorimetric assay was applied for detection of to-tal antioxidant capacity ( T-AOC ) , xanthine oxidase for detection of superoxide dismutase ( SOD) activity, and thiobarbituric acid colorimetry for determination of content of MDA. Results Compared with the control group, the survival rate of HTR-8 cells and the levels of NO in 100,500,1 000 μmol·L-1 L-NAME group were significantly reduced(P<0.05,P<0.01). Flow analysis and Annexin-V FITC staining showed that L-NAME could induce cell apoptosis in a dose-dependent manner. The number of cell apoptosis was negatively correlated with the content of NO ( r = -0.5210 ) in HTR-8 cells. Transmission electron microscopy results showed that compared with the control group, the ex-perimental group's cell nucleus shape was irregular, nuclear pyknosis in irregular shape, the chromatin ag-glutination or side the collection, mitochondrial swell-ing or enrichment, crest fracture or dissolved, even vanished, forming the vacuole, especially in 100 μmol ·L-1 L-NAME group, the apoptotic bodies obviously appeared. At the same time, T-AOC, SOD levels in HTR-8 cells decreased ( P <0.05 ) , and the MDA content increased ( P<0.05 ) . The number of cell ap-optosis was negatively correlated with the level of T-AOC ( r= -0.3212 ) , SOD ( r= -0.2779 ) in HTR-8 cells , while positively correlated with the content of MDA(r=0.2807). Conclusion Oxidative stress may play an important role in the levels of NO decrease in-duced apoptosis in human placental trophoblast cells.

Aim To explore the role of ERO1 αand its DNA methylation in homocysteine (Hcy)-induced in-hibition of hepatocytes proliferation.Methods The hepatocytes stimulated with 0 μmol·L -1 Hcy were set as the normal group (NC group)and the hepatocytes stimulated with 1 00 μmol·L -1 Hcy as the experimen-tal group (Hcy group).Methyl thiazolyl tetrazolium (MTT)reduction assay was used to reflect the prolifer-ation of the hepatocytes;qRT-PCR and Western blot were used to detect the mRNA and protein levels of ERO1 α;the expression of green fluorescence protein was observed in hepatocytes after the recombinant plas-mid of ERO1 α was constructed,which was used to confirm if the recombinant plasmid into hepatocytes was successful,then the mRNA and protein levels of ERO1 αwere assayed and the proliferation of the hepa-tocytes was also detected;ntMSP was used to detect the change of ERO1 αDNA methylation.Results The mRNA and protein levels of ERO1 αwere decreased in Hcy group compared with NC group,and the prolifera-tion activity of hepatocytes in Hcy group was de-creased.Sequencing result showed that the recombi-nant plasmid of ERO1 αwas constructed successfully. QRT-PCR and Western blot revealed that ERO1 αwas overexpressed. The result of MTT suggested that ERO1 αoverexpression restored hepatocyte proliferation inhibited by Hcy.Hcy caused ERO1 αDNA hyperm-ethylation.Conclusions Hcy inhibits hepatocyte pro-liferation by downregulating the expression of ERO1 α, and methylation of ERO1 αpromoter may play a role in this process.