Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Effects of Kangfuxin Solution (康复新液) Combined with Low-level Laser on Cytokines and Immune Function in Patients with Radiation-induced Oral Mucositis

Objective:To investigate the effect of Kangfuxin Solution(康复新液)combined with low-level laser therapy(LLLT)on cytokines and immune function in patients with radiation-induced oral mucositis.Methods:There were 84 nasopharyngeal carcinoma patients with oral mucositis after intensity-modulated radiation therapy(IMRT)were randomly divided into the control group(CG)and the observation group(OG),with 42 cases in each group.The CG was given LLLT,and the OG was treated with Kangfuxin Solution in addition to LLLT for 10 consecutive days.The healing time of oral mucosa,mucositis grading,oral pain scores,cytokines(interleukin-6,interleukin-1βand tumor necrosis factor-α)and T lymphocyte subsets were compared between the 2 groups before and after treatment.Results:The healing time of oral mucosa in the OG was(6.8±1.4)d,which was significantly shorter than(8.6±1.9)d in the CG(t=4.943,P<0.01).After treatment,the grading of oral mucositis in the OG was better than that in the CG,with a statistically significant difference(Z=2.942,P<0.05).The oral pain scores of the OG was lower than that in the CG at different time points after treatment,and the difference was statistically significant(t=8.207,11.017,P<0.01).After treatment,the levels of IL-6,IL-1βand TNF-αin peripheral blood of the OG were significantly lower than those in the CG(t=5.217,2.775,4.053,P<0.01).There were statistically significant differences in CD4+,CD8+and CD4+/CD8+between the OG and the CG after treatment(t=5.692,6.093,3.658,P<0.01).Conclusion:Kangfuxin Solution combined with LLLT can significantly shorten the healing time of oral mucosal,reduce the grading of oral mucositis,relieve oral pain,reduce inflammatory response and improve the immune function of patients.

Development of Better-Quality Assay Method for the Citric Acid and Sodium Citrate in Ophthalmic/Oral Solutions and Their Application to Deformulation Studies

There were several techniques determined for the analysis of citrate and citric acid mixtures in the pharmaceutical dosage forms. Titration methods, photometric and ion chromatographic methods were used for their determination. These methods will restrict too many factors where the accurate quantification of citrate and citric acid is extremely challenging. Citric acid is the natural flavor used as a preservative for many pharmaceutical applications. Deformulation techniques used for the manufacturing of generic drugs require authentic data for their regulatory submissions. Simple accurate and reproducible validated method developed for the determination of citric acid and sodium citrate by titration followed by HPLC analysis. Free citric acid was determined by the titration method and total citric acid was determined by HPLC analysis. After subtracting the free citric acid from total citric acid content, citric acid present in the sodium citrate content was determined. Sodium citrate content was determined by applying sodium correction factor to the subtracted value of the citric acid. The results met all the validation parameters and the method was successfully measured the amount of citric acid and sodium citrate in the marketed ophthalmic/oral solutions.

Near-Infrared Spectroscopy Combined with Absorbance Upper Optimization Partial Least Squares Applied to Rapid Analysis of Polysaccharide for Proprietary Chinese Medicine Oral Solution

Near-infrared (NIR) spectroscopy was applied to reagent-free quantitative analysis of polysaccharide of a brand product of proprietary Chinese medicine (PCM) oral solution samples. A novel method, called absorbance upper optimization partial least squares (AUO-PLS), was proposed and successfully applied to the wavelength selection. Based on varied partitioning of the calibration and prediction sample sets, the parameter optimization was performed to achieve stability. On the basis of the AUO-PLS method, the selected upper bound of appropriate absorbance was 1.53 and the corresponding wavebands combination was 400 - 1880 & 2088 - 2346 nm. With the use of random validation samples excluded from the modeling process, the root-mean-square error and correlation coefficient of prediction for polysaccharide were 27.09 mg·L-1 and 0.888, respectively. The results indicate that the NIR prediction values are close to those of the measured values. NIR spectroscopy combined with AUO-PLS method provided a promising tool for quantification of the polysaccharide for PCM oral solution and this technique is rapid and simple when compared with conventional methods.

Drug-Excipient Interaction of Methylphenidate with Glycerin in Methylphenidate Oral Solution and Identification of its Transesterification Products by UPLC-MS/MS

Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. In the present paper transesterification reaction of methylphenidate with glycerin to form different structural isomeric products was described. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. Stability samples were analyzed and observed that about ~0.6% of the Methylphenidate content was transformed into methylphenidate-glycerin isomers within 3 Months at 40&deg;C/75% RH and 18 Months at 25&deg;C/60% RH conditions. Analysis of two lots of marketed preparations having expiry dates in 2012 and 2013 showed content of the Methylphenidate esters corresponding to ~0.6% of the declared Methylphenidate content. The samples of this impurity were investigated by HPLC, UPLC-MS/MS to generate the mechanism of the impurity formation.

Correspondence: Newer oral rehydration solution OS-1 for emesis gravidarum

Though nausea and vomiting are quite common in pregnancy, hyperemesis is found in only 1 - 2 patients per 100. Appropriate oral fluid and electrolyte replacement is the initial treatment regimen for patients with mild to moderate emesis to avoid hyperemesis gravidarum defined as dehydration, electrolyte unbalance and ketosis. A newer oral rehydration solution OS-1 therapy may be safe and feasible in the mild to moderate emesis gravidarum population. Physicians are encouraged to use this practice to maintain the amount of water in the body and electrolytes and to improve the patient’s comfort.

Safety and Feasibility of Oral Rehydration Solution Prior to Endoscopic Retrograde Cholangiopancreatography

Purpose: The safety of oral rehydration therapy before endoscopic screening with respect to vital signs and complications after the screening procedure was assessed in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Methods: A total of 107 patients scheduled for ERCP were assigned to either the intravenous drip injection (DIV) group during fasting (56 patients) or ORS group given oral rehydration solution (51 patients) prior to endoscopy. Vital signs after ERCP, including blood pressure and temperature, blood biochemical data and the incidence of post-ERCP complications were compared between the groups. Results: No cases of aspiration pneumonia were detected in either groups. Moreover, there were no statistically significant differences between the DIV group and ORS group in terms of the biochemical data and vital signs after ERCP. The intergroup difference in the development of pancreatitis after ERCP was 2.3% [95% CI: ?5.7, 10.3], which was not statistically significant. Conclusions: The safety of oral rehydration therapy was found to be equivalent to that of the customary practice of infusion as a method for managing hydration and replenishing electrolytes in patients receiving ERCP. Oral rehydration therapy may be easily utilized as rehydration therapy prior to endoscopic screening for ERCP and other procedures.

Randomized Study Comparing Pre-Operative Glycemic Profile in Pediatric Cardiac Surgical Patients Administered Oral Carbohydrate Solution Preoperatively versus Those Kept Fasting

Objectives: Hypoglycemia is a recognized danger in pediatric patients. Extended period of preoperative fasting in this subset of patients is not well tolerated with metabolic derangements. The oral carbohydrate loading preoperatively can ameliorate many adverse effects. The aim of this study was to compare the glycemic profile in pediatric cardiac surgical patients kept fasting preoperatively with those fed oral clear solutions of carbohydrate half hour prior to induction of anaesthesia. Also we tried to establish a correlation with other factors contributing to preoperative hypoglycemia. Methodology: We planned a randomized controlled study. Group A included patients who were kept fasting according to the ASA guidelines preoperatively and Group B included patients who received 2 ml per kg of body weight of 10% Dextrose water as oral feeds half hour before the expected time of start of anaesthesia. Results: The mean (SD) preoperative BG concentrations were higher in group B (102.5 ±16.97) as compared to group A (64.08 ± 25.37) (p value -0.86 and -0.67) (pvalue Conclusion: Preoperative oral carbohydrate preloading can develop as the easiest and cheapest path to better perioperative blood glucose concentration management in congenital cardiac disease children.

Effect of adjuvant therapy of transfer factor oral solution on the infection process of children with Mycoplasma pneumonia

Objective:To explore the effect of adjuvant transfer factor oral solution therapy on the infection process of children with mycoplasma pneumonia.Methods:A total of 164 children with mycoplasma pneumonia who were treated in our hospital between January 2017 and January 2018 were selected as the research subjects and divided into control group (n=82) and transfer factor oral solution group (n=82) by random number table method. Control group received clinical routine therapy for children with mycoplasma pneumonia, transfer factor oral solution group received both routine therapy and transfer factor oral solution therapy, and both groups were treated for consecutive 1 week. The differences in infection-related index levels were compared between the two groups before and after treatment.Results:Before treatment, the differences in serum levels of inflammatory factors, coagulation indexes and immunoglobulins were not statistically significant between the two groups. After 1 week of treatment, serum inflammatory factors IL-2, IL-13 and IL-18 contents of transfer factor oral solution group were lower than those of control group;serum coagulation index FIB level was lower than that of control group whereas PT and APTT levels were higher than those of control group;serum immunoglobulins IgG, IgA and IgM contents were lower than those of control group.Conclusion: Adjuvant transfer factor oral solution therapy can effectively relieve the systemic inflammatory response and reduce the coagulation system and humoral immune system function damage in children with mycoplasma pneumonia.

Comparative efficacy of oral glucose solution versus non-nutritive sucking for pain relief in neonates during nociceptive procedures： a systematic review

背景和目的：葡萄糖溶液与非营养性吸吮对新生儿疼痛缓解的比较效果仍存在争议。因此，我们进行了系统评价以客观地研究在新生儿伤害感受过程中新生儿口服葡萄糖溶液与非营养性吸吮相关的镇痛作用。方法：在PubMed，Web of Science，EMBASE和Cochrane Library中搜索所有潜在记录，以获取2017年1月前比较葡萄糖溶液与非营养性吸吮在新生儿疼痛评分方面的随机对照试验。两名独立研究人员筛选出已鉴定的文章，提取数据，并评估纳入研究的方法学质量。使用Review Manager（RevMan）版本5．3．0完成所有统计分析。结果：本研究对248例新生儿进行 项统计分析。葡萄糖溶液与非营养性吸吮相比在减少疼痛评分方面没有检测到统计学差异（4项试验；MD=0．75；95％CI，-0．77-2．27；P=0．33）。结论：葡萄糖溶液与非营养性吸吮均可降低接受乙型肝炎疫苗接种和静脉穿刺的新生儿的疼痛评分，但非营养性吮吸在一定程度上比葡萄糖溶液更方便。考虑到证据的有限性，有必要进行更多随机对照试验，以及高质量、大规模和适当的测量时间，以进一步确定这两种方案的效果比较。

Effect of xiaoer feire kechuan oral solution on extrapulmonary injury induced by mycoplasma pneumoniae in infant wistar rats

目的:观察小儿肺热咳喘口服液对肺炎支原体感染致幼龄Wistar大鼠肺外损伤的影响。方法:采用肺炎支原体滴鼻感染幼龄Wistar大鼠,每日1次,连续4天,各给药组感染当天给予小儿肺热咳喘口服液,每天1次,连续4天。第5天取血,检测血常规和血液生化指标;称取脑、心、肝、肾的重量,计算脏器指数;采用Elisa法检测脑组织中GM1、GALC-Ab含量;采用HE染色对脑、心、肝、肾、小脑组织进行病理学观察。结果:肺炎支原体感染大鼠后,模型组及小儿肺热咳喘口服液三个剂量组大鼠血常规指标均在正常范围内波动;小儿肺热咳喘口服液三个剂量组可明显降低大鼠血清中LDH、CK、CRE含量,与模型对照组比较具有显著性差异(P<0.01,P<0.05);模型对照组大鼠脑指数有增高趋势;模型对照组脑组织中GALC-Ab含量有明显增高趋势,小儿肺热咳喘口服液三个剂量组可明显降低大鼠脑组织中GALC-Ab含量,其中低剂量组与模型对照组比较有显著性差异(P<0.05);模型组心、肾、肝组织均出现轻度的病理改变,小儿肺热咳喘口服液三个剂量组均可改善不同组织的病理损伤。结论:小儿肺热咳喘口服液对肺炎支原体感染幼龄大鼠所致的肺外损伤具有明显的抑制作用。

Effect of L-carnitine on Cardiomyocyte Apoptosis and Cardiac Function in Patients Undergoing Heart Valve Replacement Operation

Summary： The effects of L-carnitine, as an ingredient of cardioplegia solution, on cardiac function and cardiomyocyte apoptosis in patients undergoing heart valve replacement operation were investigated. Twenty-three cases undergoing heart valve replacement with cardiopulmonary bypass （CPB） were randomly allocated into two groups： L-carnitine group （n=12, 12 g/L L-carnitine was put in the ST. Thomas cardioplegia） and control group （n=11, identical to the L-carnitine group except that normal saline was administered instead of L-carnitine）. Serum cardial troponin I （cTnI） levels, the left ventricular ejection fraction （LVEF）, and cardiac index （CI） were measured perioperatively. A bit of myocardial tissue obtained from right atria was taken before CPB and by the end of intracardiac procedure to undergo electron microscopy examination and estimate apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. From the end of CPB to 3 days after operation, the serum levels of cTnI in the L-carnitine group was significantly lower than that in the control group （P〈0.05）. Heart color ultrasonogram showed that the CI index and LVEF at 7th day postoperatively in the L-carnitine group were significantly higher than in the control group （P〈0.05）. Compared to the control group, L-carnitine significantly alleviated the morphologic changes of cardiac muscle cells （electron microscopy examination） and decreased the amounts of apoptotic cardiac muscle cells （TUNEL）. Furthermore, the dosage of vasoactive drugs used after operation was significantly less in the L-carnitine group （P〈0.01）. It was concluded that L-carnitine cardioplegia solution could improve cardiac function in patients undergoing heart valve replacement operation and alleviate CPB-mediated apoptosis of cardiac muscle cells.

基于滋水涵木法联合导入不同浓度的氨甲环酸溶液治疗女性黄褐斑疗效评价

目的观察基于“滋水涵木法”指导下的杞黄口服液联合导入不同浓度的氨甲环酸溶液治疗黄褐斑的有效性和安全性。方法选取河南科技大学第二附属医院皮肤科门诊2021年1月至2022年12月就诊的120例黄褐斑志愿者,随机分为3组,每组40例。C组口服维生素C片、维生素E软胶囊、杞黄口服液;B组在C组基础上同时用滚针导入5%氨甲环酸溶液,2次/月;A组在C组基础上同时导入10%氨甲环酸溶液,2次/月;3组疗程均为3个月。治疗前后进行黄褐斑面积及严重程度评分(melasma area severity index,MASI)、皮肤图像检测评分、氧化应激指标[血清丙二醛(Maleic dialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)]水平。结果A组有效率为87.5%,B组有效率为67.5%,C组有效率为52.5%,3组比较差异有统计学意义(P<0.05);3组治疗后,MASI评分、皮肤图像检测评分、MDA水平均下降,GSH-Px、SOD水平升高(P<0.05),组间比较,A组优于B组,B组优于C组(P<0.05)。结论导入高、低浓度氨甲环酸溶液组、杞黄口服液组均可治疗黄褐斑,但导入10%氨甲环酸溶液组能更有效地治疗黄褐斑,提高GSH-Px、SOD,降低MDA,改善MASI,在皮肤图像检测中,肉眼可见斑点、紫外线斑、红区均能改善,安全性较高。

通天口服液治疗脑梗死有效性及安全性的meta分析

目的系统评价通天口服液治疗脑梗死的有效性和安全性。方法全面检索中国知网、万方、维普等数据库,搜索通天口服液治疗脑梗死的临床研究,只纳入随机对照试验(RCT)。检索时间从建库至2023年4月。由2名研究者独立完成筛选文献、数据提取及偏倚风险评估。meta分析使用RevMan 5.3软件完成。结果共纳入9个RCT,共计1148例患者。meta分析结果显示,通天口服液治疗脑梗死的总有效率高于对照组,差异有统计学意义(OR=2.18,95%CI:1.53~3.12,P<0.0001);通天口服液治疗急性脑梗死的美国国立卫生研究院卒中量表(NIHSS)评分低于对照组,差异有统计学意义(MD=-1.63,95%CI:-2.20~-1.07,P<0.00001);两组不良事件发生率比较,差异无统计学意义(P>0.05)。结论循证医学分析表明通天口服液治疗脑梗死有效性和安全性较好。

大黄三味片治疗抗精神病药药物性便秘临床观察

目的探讨大黄三味片治疗抗精神病药药物性便秘的有效性和安全性。方法收集2020年7月至2022年12月沈阳市精神科卫生中心精神科病房符合抗精神病药药物性便秘诊断标准的120例患者,按照随机数字法分为治疗组和对照组,每组60例,治疗组予大黄三味片治疗,对照组予乳果糖口服溶液。观察两组患者治疗前后便秘症状积分,排便时间,腹痛评分(VAS),大便性状改善时间、停药7 d内排便次数及生活质量评分。结果两组治疗有效率对比无统计学差异(P>0.05);治疗组大便性状改善时间短于对照组、停药7 d的排便次数多于对照组(均P<0.05);治疗后,治疗组便秘症状评分、腹痛评分、排便时间低于对照组,生活质量评分高于对照组(均P<0.05)。结论大黄三味片治疗抗精神病药药物性便秘临床疗效确切,有效减轻患者痛苦,停药后疗效持久,两组患者均未见不良反应,安全有效。

羧甲司坦口服溶液联合重组人干扰素α1b治疗小儿急性喘息性支气管炎的效果

目的分析急性喘息性支气管炎患儿接受重组人干扰素α1b单药与联合羧甲司坦口服溶液治疗的效果。方法回顾性分析2021年6月至2023年6月医院收治的100例急性喘息性支气管炎患儿资料,按不同治疗方案分为对照组、观察组,各50例。对照组接受重组人干扰素α1b治疗,观察组接受羧甲司坦口服溶液联合重组人干扰素α1b治疗。比较两组临床疗效、主要症状缓解时间、气道炎症相关因子[趋化因子配体3(CCL3)、高迁移率族蛋白B1(HMGB1)、α1-酸性糖蛋白(α1-AG)]、T淋巴细胞(CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+))及不良反应。结果观察组临床总有效率高于对照组(P<0.05)。治疗后观察组气促、喘息、咳嗽、肺部音等症状缓解时间降低(P<0.05)。治疗4、7 d后,两组CCL3、HMGB1、α1-AG较治疗前下降,且观察组低于对照组(P<0.05);两组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)较治疗前升高,且观察组高于对照组(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论羧甲司坦口服溶液联合重组人干扰素α1b治疗急性喘息性支气管炎,可抑制气道炎症,调节机体免疫,促进症状缓解,疗效确切,且安全性高。

精浆肉碱测定在男性生育力评估和弱精子症疗效监测中的应用

目的比较正常男性与弱精子症男性精浆中肉碱含量,评估精浆肉碱水平与前向运动精子百分率(PR)之间的一致性,并外源性补充肉碱对弱精子症患者的影响。方法收集511例正常可育男性及弱精子症患者精液样本,采用精浆肉碱检测试剂盒(固定时间法)测定精浆肉碱,比较两组水平差异及与PR的一致性。另选77例弱精子症患者给予左卡尼汀(1 g/次,3次/日,30日/疗程)治疗,监测服药前后精浆肉碱及PR变化。结果弱精子症患者组精浆肉碱含量[(194.34±65.41)μmol/L]显著低于正常可育男性组[(405.43±72.12)μmol/L](P<0.01);以精浆肉碱≥325μmol/L为阈值,Kappa值为0.81,诊断符合率达93.74%;给予左卡尼汀治疗后,弱精子症组精浆肉碱浓度[(356.03±84.87)μmol/L]较之前[(183.61±79.54)μmol/L]明显上升,PR[(32.69±8.35)%]较之前[(16.56±7.74)%]显著升高(P均<0.01)。结论精浆肉碱检测试剂盒能准确高效检测大量临床样本,可用于弱精子症诊断及疗效评估。外源性补充肉碱可提高弱精子症患者精浆肉碱水平和精子活力,有助于改善其生育能力。

物理抗菌网液在儿童低温等离子扁桃体切除术后康复中的应用效果

目的 探讨物理抗菌网液在儿童低温等离子扁桃体切除术后康复中的应用效果。方法 便利抽样法选取2022年6月至2023年6月温州医科大学附属第二医院耳鼻咽喉科接受治疗的180例儿童扁桃体切除术患儿,按照随机数字表法将其分为对照组和观察组,各90例。对照组术后采用常规护理措施,观察组在常规护理的基础上采用物理抗菌网液。比较两组患儿术后并发症总发生率、住院时间、切口愈合时间及临床疗效。结果 观察组术后并发症总发生率低于对照组(P<0.05)。观察组住院时间、切口愈合时间短于对照组(P<0.05)。两组临床疗效比较,差异无统计学意义(P>0.05)。结论 物理抗菌网液在儿童低温等离子扁桃体切除术后口腔管理中的应用效果显著,有助于降低患儿术后并发症的发生,促进手术切口的早期恢复,值得临床推广应用。

化瘀清热汤联合西帕依固龈液对口腔扁平苔藓患者复发情况的影响

目的探究化瘀清热汤联合西帕依固龈液对口腔扁平苔藓患者复发情况的影响。方法选取2021年7月~2023年8月收治的口腔扁平苔藓患者100例,按照随机数字法分为对照组(n=50)和观察组(n=50),其中对照组采用西帕依固龈液治疗,观察组采用化瘀清热汤联合西帕依固龈液治疗。比较两组口腔黏膜症状面积、炎症因子水平、血液流变学指标、疼痛程度及复发率,评估两组患者的临床疗效。结果观察组的总有效率高于对照组(P<0.05);治疗后观察组的口腔黏膜症状面积均小于对照组(P<0.05);治疗后观察组的炎症因子水平及血液流变学指标低于对照组(P<0.05);治疗后观察组的疼痛程度评分为(0.65±0.13)分,明显低于对照组的(0.97±0.24)分,差异有统计学意义(P<0.001);随访1年后,观察组的复发率为6.00%,明显低于对照组的22.00%,差异有统计学意义(P=0.021)。结论口腔扁平苔藓患者采用化瘀清热汤联合西帕依固龈液治疗具有相对较佳的效果,可改善患者的血液流变学和炎症反应,降低患者的复发率和疼痛程度。

Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.