Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.

基于网络药理学探析远志散治疗痴呆的分子生物机制研究（英文）

目的采用网络药理学技术预测远志散治疗老年痴呆的主要活性成分、潜在靶点及分子作用机制。方法通过数据库及文献构建远志散的化学成分库,进行反向分子对接预测潜在靶点,构建成分-靶标网络;通过与AD的靶标网络进行映射、分析,获得"有效成分-AD靶标"网络;通过网络分析筛选出关键靶点;通过与已知文献报道的靶点进行对比,分析预测靶点的合理性。结果远志散各味中药共有180种化学成分作用于AD靶标,其作用靶标包括三个关键靶标(环氧酶-2、毒蕈碱型乙酰胆碱受体M1、毒蕈碱型乙酰胆碱受体M2)及一个重要靶标(乙酰胆碱酯酶)。可能通过调节乙酰胆碱受体活性及与β-淀粉样蛋白结合从而治疗阿兹海默症,其生物过程可能集中于乙酰胆碱受体信号通路、突触传递的负调节等。结论远志散治疗老年痴呆符合中药多成分-多靶点-多途径的特点,网络分析所获得的重要靶点在文献研究中占有很大比例,具有一定的合理性。

Using HyperCoal to prepare metallurgical coal briquettes via hot-pressing

HyperCoal was prepared from low-rank coal via high-temperature solvent extraction with N-methylpyrrolidone as an extraction solvent and a liquid-to-solid ratio of 50 mL/g in a high-temperature and high-pressure reactor. When HyperCoal was used as a binder and pulverized coal was used as the raw material, the compressive strength of the hot-pressed briquettes(each with a diameter of 20 mm and mass of 5 g) under different conditions was studied using a hot-pressing mold and a high-temperature furnace. The compressive strength of the hot-pressed briquettes was substantially improved and reached 436 N when the holding time period was 15 min, the hot-pressing temperature was 673 K, and the HyperCoal content, was 15 wt%. Changes in the carbonaceous structure, as reflected by the intensity ratio between the Raman G-and D-bands(IG/ID), strongly affected the compressive strength of hot-pressed briquettes prepared at different hot-pressing temperatures. Compared with cold-pressed briquettes, hot-pressed briquettes have many advantages, including high compressive strength, low ash content, high moisture resistance, and good thermal stability; thus, we expect that hot-pressed briquettes will have broad application prospects.

Effect of titanium dioxide nanoparticles on zebrafish embryos and developing retina

AIM: To investigate the impact of titanium dioxide nanoparticles(Ti O2NPs) on embryonic development and retinal neurogenesis.METHODS: The agglomeration and sedimentation of Ti O2 NPs solutions at different dilutions were observed,and the ultraviolet-visible spectra of their supernatants were measured. Zebrafish embryos were experimentally exposed to Ti O2 NPs until 72 h postfertilization(hpf). The retinal neurogenesis and distribution of the microglia were analyzed by immunohistochemistry and whole mount in situ hybridization.RESULTS: The 1 mg/L was determined to be an appropriate exposure dose. Embryos exposed to Ti O2 NPs had a normal phenotype. The neurogenesis was initiated on time, and ganglion cells, cones and rods were well differentiated at 72 hpf. The expression of fms m RNA and the 4C4 antibody, which were specific to microglia in the central nervous system(CNS), closely resembled their endogenous profile.CONCLUSION: These data demonstrate that short-term exposure to Ti O2 NPs at a low dose does not lead to delayed embryonic development or retinal neurotoxicity.

Effect of BRM S1 expression on proliferation, migration and adhesion of mouse forestomach carcinoma

Objective: To discuss the ef ect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma(MFC). Methods: The constructed p CMV-myc-BRMS1 recombinant plasmid and blank plasmid were transfected into mouse forestomach carcinoma. MTT method was employed to measure the activity of gastric cancer cell; the scratch assay and Transwell assay to measure the migration and invasion of gastric cancer cell; the adhesion assay to measure the adhesion of gastric cancer cell; while the Western blot assay to measure the expression of The NF-毷B signal pathway, downstream matrix metalloproteinase(MMP-2), MMP-9 and osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted animal model of gastric cancer in mice was constructed to measure the size of tumor xenograft. Results: Results of MTT assay showed that, compared with the empty vector control group, the activity of gastric cancer cell was not af ected in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit the adhesion, migration and invasion of gastric cancer cell(P<0.01). Besides, compared with the empty vector control group, the phosphorylation of NF-毷B p65 and I毷Bα was reduced in the BRMS1 transfection group, with the decreased expression of MMP 2, MMP 9 and osteopontin and the increased expression of E-cadherin(P<0.01). Results of animal experiment also showed that the expression of BRMS1 did not af ect the transplanted tumor. Conclusions: The expression of BRMS1 can signii cantly inhibit the adhesion, migration, invasion and metastasis of MCF gastric cancer cell, which is related to The NF-毷B signal pathway.

Correlation between photoreceptor injury-regeneration and behavior in a zebrafish model

Direct exposure to intensive visible light can lead to solar retinopathy, including macular injury. The signs and symptoms include central scotoma, metamorphopsia, and decreased vision. However, there have been few studies examining retinal injury due to intensive light stimulation at the cellular level. Neural network arrangements and gene expression patterns in zebrafish photoreceptors are similar to those observed in humans, and photoreceptor injury in zebrafish can induce stem cell-based cellular regeneration. Therefore, the zebrafish retina is considered a useful model for studying photoreceptor injury in humans. In the current study, the central retinal photoreceptors of zebrafish were selectively ablated by stimulation with high-intensity light. Retinal injury, cell proliferation and regeneration of cones and rods were assessed at 1, 3 and 7 days post lesion with immunohistochemistry and in situ hybridization. Additionally, a light/dark box test was used to assess zebrafish behavior. The results revealed that photoreceptors were regenerated by 7 days after the light-induced injury. However, the regenerated cells showed a disrupted arrangement at the lesion site. During the injury-regeneration process, the zebrafish exhibited reduced locomotor capacity, weakened phototaxis and increased movement angular velocity. These behaviors matched the morphological changes of retinal injury and regeneration in a number of ways. This study demonstrates that the zebrafish retina has a robust capacity for regeneration. Visual impairment and stress responses following high-intensity light stimulation appear to contribute to the alteration of behaviors.

Application of"balancing digestive functions by regulating pivot"in chronic atrophic gastritis and professor Wei Wei's clinical experience

Chronic atrophic gastritis(CAG)has attracted wide attention in clinic due to its high incidence rate and high canceration rate.At present,modern medicine lacks an effective treatment scheme for CAG.Traditional Chinese medicine can improve clinical symptoms,laboratory indexes,pathological examination results and patients'quality of life for patients of CAG.Professor Wei used the method of"Balancing Digestive Functions by Regulating Pivot"to treat CAG in clinical practice.With flexible addition and subtraction on the basic prescription Banxia Xiexin decoction and coordination with various external treatment methods and psychological construction,professor Wei has achieved satisfactory clinical effects with the pungent-opening and bitter-descending method and dispersing liver and promoting blood circulation method.

Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naive chronic hepatitis B patients: a prospective and randomized controlled trial

Background:The efficacy of entecavir(ETV)add-on peg-interferon therapy compared with ETV monotherapy in treatment-naive hepatitis B virus(HBV)patients remains controversial.We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.Methods:All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital(China).Eligible HBV patients(n=144)were randomly divided(1:1)to receive either ETV monotherapy(n=70)or peg-interferon add-on therapy from week 26 to 52(«=74).Patients were followed-up for at least 2 years.Indexes including hepatitis B surface antigen(HBsAg)and hepatitis B e antigen(HBeAg)seroconversion rate,sustained virologic response,transient elastography value,and histological scores were evaluated every 3 months until the end of the study.The rate of patients with HBsAg loss was defined as the primary endpoint criteria.Results:At week 26,no patient achieved HBsAg seroconversion in either group.At week 52,one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group.The monotherapy group showed significantly better liver function recovery results than the combination therapy group.At week 78,one patient in the combination group had HBsAg seroconverted.At week 104,only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy.The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline.Both groups showed a favorable decrease in alpha-fetoprotein(monotherapy:4.5[2.8,7.1]vs.2.2[1.8,3.1]ng/mL,P<0.001;combination therapy:5.7[3.0,18.8]vs.3.2[2.0,4.3]ng/mL,P<0.001)and an improved result of liver biopsy examination scores.The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 6.6[4.9,9.8]vs.7.8[5.4,11.1]kPa,P=0.028).But there was no significant difference in HBsAg conversion rate(1.8%[1/56]i^s.4.1%[3/73],P=0.809)and HBeAg conversion rate(12.5%[7/56]i/s.11.0%[8/73],P=0.787),as well as HBV-DNA,sustained virologic response(93.2%vs.98.5%,P=0.150)between the two groups.Conclusions:Both therapies supported liver function recovery and histology improvement.Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy.However,combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.Trial registration:ClinicalTrials.gov:NCT02849132;https://clinicaltrials.gov/ct2/show/NCT02849132.

Clinical prognosis of optimal medical therapy after percutaneous coronary intervention in patients with coronary heart disease

To the Editor:Revascularization,regardless of whether it is percutaneous coronary intervention(PCI)or coronary artery bypass grafting(CABG),is still the dominant treatment of severe coronary heart disease(CHD).The long-term clinical outcome of revascularization is unpredictable because of the progression of atherosclerosis continuing after surgery.[1]Many studies and trials have proven that optimal medical therapy(OMT)with or without revascularization is critical for decreasing the incidence of adverse events and improving quality of life.In recent years,patients from China with higher adherence to medical therapy have shown a lower incidence of adverse events at 1 year after PCI.[2]However,there have been no large clinical trials or observational studies for accurate understanding of maintenance of medical strategies in patients with CHD in China.

Gonorrhea in China, 2018

Objective:Gonorrhea is a globally widespread sexually transmitted infection caused by Neisseria gonorrhoeae.This study is aimed to analyze the epidemiological characteristics of gonorrhea cases reported in China in 2018 and provide evidence for strategies making in the gonorrhea prevention and control programme.Methods:Gonorrhea cases were extracted from National Notifiable Disease Report System (NNDRS) covering 31 provinces,autonomous regions,arnd municipalities in the mainland of China.The overall incidence rate was calculated,as were rate per province,sex,age group,and occupation group.ResultS:in 2018,133,156 new cases of gonorrhea were reported in China,corresponding to an incidence rate of 9.59 cases per 100,000 population and having a 36.03% increase from 2014 (7.05 cases per 100,000 population).Zhejiang,Hainan,Guangdong,Fujian provinces,and Shanghai city had a higher reported rate (14.05-28.00 per 100,000 population).Hebei,Tianjin,Tibet,Heilongjiang,and Jilin provinces had a lower rerted rate (1.56-5.19 per 100,000 population).The males had a much higher incidence than the females (15.81 per 100,000 vs.3.08 per 100,000) and a faster rising rate (38.32% vs.27.27%).The highest rate was detected in the aged 25-29 years both of male and female (46.37 and 6.60 per 100,000,respectively),followed by those aged 30-34 years (41.12 and 6.39 per 100,000,respectively).The largest proportion of gonorrhea cases was among the farmers accounting for 27.74%,followed by the unemployed persons (24.67%),business persons (17.02%) and industrial workers (9.50%).Conclusion:In general,gonorrhea has an increasing trend from 2014 and remains a common notifiable disease in China in 2018.Young males who are sexually active are high risk populations for gonococ~ infection.The southeast coastal areas with developed economy have a higher rate of gonorrhea reported.Corresponding strategies on disease prevention and control should be performed on the high risk populations and regions.

Gasification reactivity and kinetic parameters of coal chars for non-isothermal steam gasification

The gasification reactivity and kinetic parameters of coal chars for non-isothermal steam gasification were investigated.One kind of lignite and three kinds of bituminous coals were used as the samples,and their coal ranks follow the ascending order:XB<KL<ZJ<GD.As characterized by the comprehensive gasification index,the gasification reactivity of coal chars follows the descending order:XB>KL>ZJ>GD.Through systematically analyzing factors affecting gasification reactivity,it was ascertained that the gasification reactivity is mostly determined by the carbonaceous structure.The gasification reactivity is inversely proportional to the coal rank,and the higher the coal rank,the lower the gasification reactivity.A new kinetic model was proposed to calculate the kinetic parameters,in which the reaction order was considered as an unknown kinetic parameter.The reaction order n follows the ascending order:XB<KL<ZJ<GD,which are n=1.00,n=1.34,n=1.83,and n=2.63,respectively.It is proved that the reaction order is proportional to the coal rank,and the higher the coal rank,the higher the reaction order.

Temporal trends in gonorrhoea incidence in China,1991 to 2016: a joinpoint regression analysis

Objective To study the temporal trends in gonorrhoea incidence in China between 1991 and 2016.Methods We obtained gonorrhoea surveillance data from the National Center for STD Control and population data from the National Bureau of Statistics in China.Joinpoint regression was performed to assess temporal trends of gonorrhoea incidence stratified by age and gender.Results Male-to-female incidence ratios of gonoeehoea have been increasing during the study period,ranging from 1.60 to 5.08.After the earlier increases,gonorrhoea incidence rates were found to have declined from the early 2000s.However,stalls or reversals of declining trends were observed in sexually active age groups in recent years,particularly a sharp increase (18.5％ per year) among males aged between 15 and 19 years.Conclusions Gonnorrhoea incidence increased sharply from 1991 to 1999 and then declined significantly until 2012.Further observations are needed for slight and nonsignificant increases of incidence in recent years,and more effective interventions targeting adolescents or other high risk populations are needed for disease control and prevention.