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.

Effect of Shuanghuanglian Oral Solution on Liver Function in a Mouse Model of Non-alcoholic Steatohepatitis

[Objectives]To observe the effect of Shuanghuanglian oral solution on liver function in BABL/cJ mice in non-alcoholic steatohepatitis(NASH)model.[Methods]The BABL/cJ mice were randomly divided into three groups:a control group,a model group,and an experimental group.The experimental group was administered with 10%Shuanghuanglian oral solution at a dose of 0.1 mL/(10 g·d),while the control group and experimental group received an equivalent dosage of normal saline.All three groups were treated for a period of 28 d.The liver function of the mice in each group was examined after the treatment.[Results]The body mass,liver index,triacylglycerol(TG),total cholesterol(TC),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels were all significantly reduced compared to the model group(P<0.05).[Conclusions]Shuanghuanglian oral solution has a beneficial effect on liver function in BABL/cJ mice.

Identification of Qishen Oral Solution with TLC and HPLC

[Objective] This study aimed to establish the standards for quality control of Qishen oral solution. [Method] Astragalus membranaceus, Atractylodes macro- cephala Koidz. and Glycyrrhiza uralensis in the preparation were identified by using thin layer chromatography （TLC）, and Codonopsis pilosula was identified by using high-performance liquid chromatography （HPLC）. [Result] By using the developed TLC system, experimental solution and reference solution showed clear spots, while negative control presented no interference. By using the developed HPLC system, the chromatographic peak of Iobetyolin was detected in experimental solution. [Con- clusion] The developed TLC and HPLC systems presented high specificity and good repeatability for identification of these four components and could be used in the quality control of Qishen oral solution.

Determination of Astragaloside IV in Yupingfeng Oral Solution by HPLC-ELSD Method

[Objective] This study aimed to establish a method for determining the content of Astragaloside IV in Yupingfeng oral solution.[Method] The HPLC-ELSD method was adopted.The chromatographic column was Venusil MP（4.6 mm × 150 mm,5 μm）.The mobile phase was acetonitrile-water（35∶65）.The ELSD evaporator tube temperature was 65 ℃.N2 was used as the carrier gas（pressure,30 psi）.[Result] When the content of Astragaloside IV ranged from 0.5 to 5.0 μg,the Astragaloside IV content showed a good linear relationship with peak area（r=0.999,n=6）.The average recovery was 96.36%,and the RSD was 2.46%.[Conclusion] This method is accurate and reliable,and can be applied in the quality control of Yupingfeng oral solution.

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.

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

Objective To observe the effect of Xiaoer Feire Kechuan oral solution on the extrapulmonary injury induced by Mycoplasma pneumoniae in infant Wistar rats. Methods Infant Wistar rats were infected intranasally with M. pneumoniae once a day for four days. In the treatment groups, Xiaoer Feire Kechuan oral solution was administered daily for four days beginning from the day of infection. On day 5, blood of the rats was collected, and blood routine and biochemistry indexes were measured. All rats were sacrificed, and the weight of brain, heart, liver, and kidney was measured to calculate the organ indexes. The GM1 and GALC-Ab content in brain tissue was determined by ELISA. Pathological changes in the brain, heart, liver, kidney, and cerebellum were observed by HE staining. Results Blood routine indexes fluctuated within the normal range in the infection control group and in three of the Xiaoer Feire Kechuan oral solution groups. The serum LDH, CK, and CRE in all three Xiaoer Feire Kechuan oral solution groups were distinctly lower than those in the infection control group (P < 0.01, P < 0.05). Rat brain index and GALC-Ab content in the brain tissue showed an increase in infection control group. In the Xiaoer Feire Kechuan oral solution groups, the GALC-Ab content in brain tissue was decreased significantly. The heart, liver, and kidney tissues showed mild pathological changes in the infection group, which were reversed by Xiaoer Feire Kechuan oral solution treatment. Conclusions The extrapulmonary injury induced by M. pneumoniae in infant Wistar rats was significantly inhibited by Xiaoer Feire Kechuan oral solution.

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

Background and aims： The comparative efficacy of glucose solution （GS） versus non-nutritive sucking （NNS） for pain re- lief in neonate remains controversial. This systematic review was consequently performed to objectively investigate the analgesic effect of Oral GS related to NNS in newborns during nociceptive procedures. Methods： All potential records were searched in PubMed, Web of Science, EMBASE, and the Cochrane Library to capture the randomized controlled trials comparing GS with NNS in terms of pain scores in neonates through January 2017. Two independent investigators screened the identified articles, extracted the data, and assessed the methodological quality of the included studies. All statistical analyses were completed by using Review Manager （RevMan） version 5.3.0. Results： Four studies, involving 248 neonates, were incorporated into these statistical analyses. For reducing pain scores, no statistical difference was detected when GS compared to NNS （4 trials; mean difference [MD], 0.75; 95% confidence interval [CI], -0.77 to 2.27; P = 0.33）. Conclusion： Both the GS and NNS reduced the pain scores in neonates who undergoing Hepatitis B vaccination and venipuncture, but the NNS is more convenience than GS to some extent. Considered the limited evidences, more randomized controlled trials with high-quality, large-scale and appropriate measures time are warranted to further establish the comparative efficacy of these two options.

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.

Stability Indicating RP-UPLC Method for Quantification of Glycopyrrolate, Methylparaben and Propylparaben Assay in Liquid Oral Formulation

Stability indicating RP-UPLC technique was developed for the simultaneous quantification of glycopyrrolate, methylparaben, and propylparaben in glycopyrrolate oral solution. The method was established by using gradient UPLC and a Waters Acquity UPLC BEH C18, 100 mm 2.1 mm, i.d 1.7 μm particle size column with a gradient program of mobile phase A and mobile phase B with a flow rate of 0.25 mL/minute, UV wavelength detection at 222 nm, column temperature of 40°C, injection volume of 2 μL, mobile phase A contains 0.05% trifluoro acetic acid in water and Acetonitrile (90:10) v/v and mobile phase-B contains 0.05% trifluoro acetic acid in water and Acetonitrile (10:90) v/v. The current research describes a single UPLC method for developing an assay method for Glycopyrrolate Oral solution that includes Glycopyrrolate (Active), Methylparaben (Preservative), and Propylparaben (Preservative). The assay method was validated in accordance with ICH guidelines. The retention times of glycopyrrolate, methyl paraben and propylparaben were 6.051 min, 3.458 min and 8.095 min, respectively. Linearity range of glycopyrrolate, methyl paraben and propylparaben were in the range of 4 - 32 μg per mL, 35 - 290 μg per mL and 4 - 32 μg per mL, respectively. Recovery of glycopyrrolate, methylparaben and propylparaben ranged from 100.1% to 98.9%, 100.2% - 100.8%, and 100.2% - 100.8%. Validation of analytical method demonstrated that the method is suitable, specific, linear, accurate, precise, rugged and stability indicating for estimating three components in the pharmaceutical dosage form.

Impact of Yupingfengsan Oral Liquid on the Expression of IL-4, IFN-<i>γ</i>and NF-<i>κ</i>B of Allergic Rhinitis Mice

To observe the impact of Yupingfengsan Oral Liquid on the expression of IL-4 and IFN-γ in AR mice’s serum and expression level of nuclear factor—κB (NF-κB) protein and gene in nasal mucosa. Method: Forty BALB/c mice were randomly divided into the normal group, model group, Yupingfengsan Oral Liquid group (6 g/kg) and Loratadine group, with 10 mice per group. AR mice model was established by OVA, and IL-4 and IFN-γ contents can be measured with ELISA. The morphological changes of nasal mucosa were observed by hematoxylin eosin (HE) staining and NF-κB expression in the nasal mucosa of mice was tested with Real-Time PCR and Western blot. Results: Compared with the model group, the nasal symptoms in the Yupingfengsan Oral Liquid group and Loratadine group were obviously relieved. HE staining showed that there was a little inflammatory cell infiltration in the nasal mucosa of Yupingfengsan Oral Liquid group and Loratadine group and it was significantly reduced when compared with the model group. IL-4 level in the serum and expression of NF-κB protein and gene in the nasal mucosa was consistent and it was decreased when compared with the model group (P < 0.01), but the IFN-γ level in the serum was increased (P < 0.01). Conclusion: Yupingfengsan Oral Liquid can improve the clinical symptoms and histopathological manifestations of AR mice sensitized by OVA, inhibit the NF-κB expression, balance the percentage of Th1/Th2 cells, increase the IFN-γ level in the serum and decrease the IL-4 level.

Diarrhea in neonatal intensive care unit

AIM:To investigate the frequency,etiology,and current management strategies for diarrhea in newborn.METHODS:Retrospective,nationwide study involving 5801 subjects observed in neonatal intensive care units during 3 years.The main anamnesis and demographic characteristics,etiology and characteristics of diarrhea,nutritional and therapeutic management,clinical outcomes were evaluated.RESULTS:Thirty-nine cases of diarrhea(36 acute,3 chronic) were identified.The occurrence rate of diarrhea was 6.72 per 1000 hospitalized newborn.Etiology was defined in 29 of 39 newborn(74.3%):food allergy(20.5%),gastrointestinal infections(17.9%),antibiotic-associated diarrhea(12.8%),congenital defects of ion transport(5.1%),withdrawal syndrome(5.1%),Hirschsprung's disease(2.5%),parenteral diarrhea(2.5%),cystic fibrosis(2.5%),and metabolic disorders(2.5%).Three patients died due to complications related to diarrhea(7.7%).In 19 of 39 patients(48.7%),rehydration was performed exclusively by the enteral route.CONCLUSION:Diarrhea in neonates is a challenging clinical condition due to the possible heterogeneous etiologies and severe outcomes.Specific guidelines are advocated in order to optimize management of diarrhea in this particular setting.

Calcium-sensing receptor: A new target for therapy of diarrhea

Management of acute diarrhea remains a global challenge, particularly in resource-limiting countries. Oral rehydration solution (ORS), a passive rehydrating therapy developed approximately 40 years ago, remains the mainstay treatment. Although ORS is effective for hydration, since it does not inhibit enterotoxin-mediated excessive secretion, reduced absorption and compromised barrier function - the primary mechanisms of diarrhea, ORS does not offer a rapid relief of diarrhea symptom. There are a few alternative therapies available, yet the use of these drugs is limited by their expense, lack of availability and/or safety concerns. Novel anti-diarrheal therapeutic approaches, particularly those simple affordable therapies, are needed. This article explores intestinal calcium-sensing receptor (CaSR), a newly uncovered target for therapy of diarrhea. Unlike others, targeting this host antidiarrheal receptor system appears &#x0201c;all-inclusive&#x0201d;: it is anti-secretory, pro-absorptive, anti-motility, and anti-inflammatory. Thus, activating CaSR reverses changes of both secretory and inflammatory diarrheas. Considering its unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators, it is possible that through targeting of CaSR with a combination of specific nutrients, novel oral rehydrating solutions that are inexpensive and practical to use in all countries may be developed.

Health Emergency and Disaster Risk Management (Health-EDRM) in Remote Ethnic Minority Areas of Rural China:The Case of a Flood-Prone Village in Sichuan

Remote,rural ethnic-minority communities face greater disaster-related public health risks due to their lack of resources and limited access to health care.The Ethnic Minority Health Project(EMHP) was initiated in 2009 to work with remote,disaster-prone ethnic-minority villages that live in extreme poverty.One of the project's aims is to develop and evaluate bottom-up health risk reduction efforts in emergency and disaster risk management(HealthEDRM).This article shares project updates and describes field intervention results from the Yi ethnic community of Hongyan village in China's Sichuan Province,an area that experiences recurrent floods.It was found that 64% of the village respondents had never considered any form of disaster preparation,even with the recurrent flood risks.Health intervention participants showed sustained knowledge retention and were nine times more likely to know the correct composition of oral rehydration solution(ORS) after the intervention.Participants also retained the improved knowledge on ORS and disaster preparedness kit ownership12 months after the intervention.

Clinical and Experimental Study on Zhixie Buye Mixture (止泻补液合剂) in Treating Infantile Diarrhea Complicated with Dehydration

Objective: To observe the therapeutic effect of Zhixie Buye mixture (止泻补液合剂, ZXBYM) on infantile diarrhea patients with mild or middle degree of dehydration. Methods: Controlled observation method was adopted in the clinical and experimental study. Results: There was no significant difference in the treatment of dehydration between the ZXBYM group and oral rehydration solution (ORS) group (P>0.05), at the same time it was more effective for ZXBYM to eliminate such symptoms as vomiting and abdominal distension (P<0.01). In addition, it was confirmed that the ion concentration of sodium, potassium, chlorine, glucose and osmotic pressure in the mixture was similar to those in ORS. Animal experiment showed that ZXBYM has the effect of rat intestine peristalsis suppression and water absorption promotion in colon. And there was statistical difference in antidiarrhea effect between the mixture and ORS (P<0.01). Conclusion: ZXBYM is an effective mixture in the treatment of diarrhea with dehydration. It has a good prospect for the development and application.