Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Clinical efficacy of Baijin pills in the treatment of generalized tonicclonic seizure epilepsy with cognitive impairment

BACKGROUND The generalized tonic-clonic seizure(GTCS)is the most usual variety of epileptic seizure.It is mainly characterized by strong body muscle rigidity,loss of consciousness,a disorder of plant neurofunction,and significant damage to cognitive function.The effect of antiepileptic drugs on cognition should also be considered.At present,there is no effective treatment for patients with epilepsy,but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should,therefore,be considered for the therapy means of epilepsy with cognitive dysfunction.AIM To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment.METHODS This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups(experimental and control)using random number table method.The control group was treated with sodium valproate,and the experimental group was Baijin pills and sodium valproate for three months.The frequency and duration of each seizure,the Montreal Cognitive Assessment Scale(MoCA),and the Quality of Life Rating Scale(QOLIE-31)were recorded before and after treatment.RESULTS There were 85 patients included(42 in the control group and 43 in the experimental group).After treatment,the seizure frequency in the experimental group was significantly reduced(P<0.05),and seizure duration was shortened(P<0.01).The total MoCA score in the experimental group significantly increased compared to before treatment(P<0.01),and the sub-item scores,except naming and abstract generalization ability,significantly increased(P<0.05),whereas the total MoCA score in the control group significantly decreased after treatment(P<0.05).The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment(P<0.01).CONCLUSION Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.

Effect of dietary with Zhibai dihuang pills and gonadotropinreleasing-hormone-analogue on girls with precocious and rapidly progressive puberty

BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.

Mechanism of action of Wuzi Yanzong pill in the treatment of oligoasthenozoospermia in rats determined via serum metabolomics

Objective:To investigate the mechanism of action of Wuzi Yanzong pill(WYP)in rats with oligoasthenozoospermia(OAZ)via metabolomics and to provide a possible basis for improving this WYP-based treatment.Methods:A rat model of OAZ was established by treating male SpragueeDawley rats with glucosides from Tripterygium wilfordii Hook.F.Seventy-two rats were randomly divided into six groups:control,L-carnitine(positive control),model,and low-,medium-,and high-dose WYP groups.Rats in the experimental groups were treated with WYP for 4 weeks.At the end of the treatment period,sperm cell quality(density,motility,and viability)was assessed using a semen analysis system,mitochondrial membrane potential(MMP)was assessed using flow cytometry,and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ.Further,serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment.Results:A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group.WYP-M and WYP-H treatments significantly improved sperm cell density,motility,and viability compared with those in the model group(all P<.05).Compared with the model group,both WYP-M and WYP-H treatments increased MMP values(P=.006 and P=.021 respectively),while there was no significant difference in the L-carnitine group.L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group.Further,44 differential metabolites and four metabolic pathways,especially autophagy pathway,related to OAZ were identified via metabolomics.Conclusions:WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation.These findings can be employed to improve the efficacy of WYP in humans.

Coating Process of Paeonol Sustained Release Pills

[Objectives] To study the coating process of paeonol sustained release pills by extrusion-spheronization method taking ethyl cellulose as the coating material. [Methods] Paeonol pills were made by Auari AW-95 Full Automatic Pill Making Machine. Coating of paeonol sustained release pills was prepared by Auari Mini Pill Polishing Machine. The prescription and process factors of paeonol sustained release pills coating were investigated by single factor experiment and orthogonal experiment. The release of paeonol sustained release pills was determined according to the cumulative release curve of paeonol. [Results] The prepared paeonol sustained release pills released slowly within 24 h, and the release rate reached 80% in 12 h. [Conclusions] The prepared paeonol sustained release pills basically meet the 24 h sustained release standard, and can be further developed and applied.

Clinical Study on the Combination of Dingjing Pills and Risperidone in the Treatment of Patients with Schizophrenia Accompanied by Risky Behaviors

[Objectives]To observe the clinical efficacy of Dingjing Pills on patients with schizophrenia accompanied by risky behaviors.[Methods]Two hundred patients diagnosed with schizophrenia and risky behaviors were divided into two groups based on the random and double-blinded principle:the treatment group(100 cases)treated with Dingjing Pills combined with risperidone,and the control group(100 cases)treated with risperidone alone.The observation course was 6 weeks.The clinical efficacy was compared using brief psychiatric rating scale(BPRS),modified overt aggression scale(revised edition)(MAOS),treatment emergent symptom scale(TESS),and blood routine,liver function,kidney function,and electrocardiogram examinations were conducted.[Results]After treatment,Dingjing Pills significantly reduced the scores of brief psychiatric rating scale,modified overt aggression scale and treatment emergent symptom scale in patients with schizophrenia and dangerous behaviors,and had no significant toxic or side effects.The total effective rate in the treatment group was 88.8%,while the total effective rate in the control group was 77.1%.There was a significant difference in therapeutic efficacy between the two groups(P<0.05).[Conclusions]Dingjing Pills has an intervention and therapeutic effect on high-risk behaviors of schizophrenia,with minimal side effects and easy acceptance by patients.

Antidepressant Effect of Mongolian Pharmaceutical Betel Shisanwei Ingredient Pills and Its Improvement Effect on Depressive Syndromes

[Objectives]To analyze the effect of Mongolian pharmaceutical Betel Shisanwei Ingredient Pills in the clinical treatment of patients with depression.[Methods]From June 2020 to May 2021,64 patients with depression who received treatment in Inner Mongolia Minzu University were selected to participate in this study.These patients were randomly numbered from 1 to 64,and then divided into two groups according to the principle of odd or even number.Patients with odd number were regarded as the reference group,and treated by western medicine fluoxetine;patients with even number were regarded as the study group,and treated by Mongolian pharmaceutical Betel Shisanwei Ingredient Pills.The therapeutic effects of the two groups of patients were compared.[Results]Before treatment,there was no significant difference in the scores of patients'depressive syndromes between the two groups(P>0.05).After treatment,there were two significant changes in comprehensive score of depressive symptoms in both groups.Compared with before treatment,the data of the same group after treatment decreased significantly.Comparison between the two groups showed that the score of patients'depressive syndromes in the study group(13.28±5.49)was significantly lower than that in the reference group(18.46±6.51),and the overall response rate of treatment in the study group(96.88%,31/32)was obviously higher than that in the reference group(75.00%,24/32),showing statistically significant differences(P<0.05).[Conclusions]In the treatment of depression,Mongolian medicine therapy can significantly improve the depressive syndromes in patients,with more prominent curative effects,and is worthy of promotion and application.

Packed with pills-obstructing duodenal web in the setting of intestinal malrotation:A case report

BACKGROUND The incidence of intestinal malrotation in adults has been reported to only be about 0.2%.Duodenal web as a cause of intestinal obstruction is rare,with an incidence of about 1:20000-1:40000.Furthermore,when described,these conditions are usually seen in early life and very infrequently in adulthood.CASE SUMMARY We report a case of a middle-aged woman with intestinal malrotation who presented with a three-month history of right-sided abdominal pain,early satiety,and a 22-pound weight loss.Patient underwent an esophagogastroduodenoscopy,which demonstrated numerous retained pills in a deformed first portion of the duodenum,concerning for a partial gastric outlet obstruction.An upper gastrointestinal series showed marked distention of the proximal duodenum with retained debris and the presence of a windsock sign,increasing the suspicion of a duodenal web.The patient subsequently underwent surgical intervention where a duodenal web with two lumens was noted and resected,opening the duodenum.There were over 150 pill capsules that were removed.The patient is doing well after this intervention.CONCLUSION Both intestinal malrotation and duodenal webs are infrequently encountered in the adult population.These pathologies can also present with nonspecific abdominal symptoms such as chronic abdominal pain and nausea.Hence,providers might not consider these pathologies in the differential for patients who present with vague symptoms which can lead to delay in management and increased mortality and morbidity.

A Review of Studies about Mongolian Patent Medicine Huhegaridi-9 (Qinggan Jiuwei Pills)

It has been applied for many diseases such as plague fever, cold cough, sore throat and so on. In order to better study Huhegaridi-9, this paper started from the production process of Mongolian Patent Medicine Huhegaridi-9. It analyzed and discussed the clinical application, chemical components and pharmacological research of Huhegaridi-9. It is expected to provide a reference for relevant researchers and workers.

The Effect of Ginkgo Biloba Leaf Dropping Pill Combined with Butylphthalide Capsule on Cognitive Dysfunction in Patients after Acute Ischemic Stroke and Its Impact on Serum Cytokines

Objective: To investigate the therapeutic effect of Ginkgo biloba extract dropping pills combined with butylphthalide capsules on cognitive dysfunction in patients after acute ischemic stroke (AIS) and its impact on serum cytokines CRP, IL-6, and Hcy. Methods: This study selected 76 patients with cognitive dysfunction after ischemic stroke who were hospitalized at Zhuji People’s Hospital from January 2023 to January 2024. The patients were divided into two groups. The control group was treated with butylphthalide capsules, while the combination group received Ginkgo biloba extract dropping pills in addition to the treatment given to the control group. The neurological function, cognitive function, activities of daily living, and levels of serum cytokines CRP, IL-6, and Hcy were compared between the two groups after 1 month and 3 months of treatment. Results: The NIHSS scores, MMSE scores, ADL scores, and levels of CRP, IL-6, and Hcy in both groups showed statistically significant differences compared to before treatment (P Conclusion: The combination of Ginkgo biloba extract dropping pills and butylphthalide capsules has a better therapeutic effect on cognitive dysfunction in patients after ischemic stroke. It can improve the neurological function and cognitive function of patients, enhance their ability to perform daily activities, and reduce inflammatory responses.

Exploring the molecular mechanism of Suoquan pill in the treatment of diabetic kidney disease based on network pharmacology,molecular docking,in vitro experiment

Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.

Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia

Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.

Application of Guizhi Fuling Pill in Gynecology

This paper reviews the research progress of Guizhi Fuling Pill in the clinical application of gynecology,such as the treatment of uterine leiomyoma,ovarian cyst,infertility and dysmenorrhea,in order to provide further research ideas for clinical researchers.

Effects of Fufang Biejia Ruangan Pills on hepatic fibrosis in vivo and in vitro

AIM:To explore the protective effect and the relevant mechanisms of Fufang Biejia Ruangan Pills(FFBJRGP)on hepatic fibrosis in vivo and in vitro.METHODS:Hepatic fibrosis was induced by carbon tetrachloride composite factors.Adult Wistar rats were randomly divided into four groups:normal control group;hepatic fibrosis model group;FFBJRGP-treated group at a daily dose of 0.55 g/kg;and colchicinetreated group at a daily dose of 0.1 g/kg.The effects of FFBJRGP on liver function,serum levels of hyaluronic acid(HA),typeⅣcollagen(CⅣ),typeⅢprocollagen(PCⅢ),laminin(LN),histopathology,and expression of transforming growth factor(TGF-β1)and Smad3 in hepatic fibrosis were evaluated in vivo.The effects of FFBJRGP on survival rate,hydroxyproline content and cell cycle distribution were further detected in vitro.RESULTS:Compared with the hepatic fibrosis model group,rats treated with FFBJRGP showed a reduction in hepatic collagen deposition and improvement in hepatic lesions.Compared with those of the model group,the activities of alanine aminotransferase(62.0±23.7 U/L)and aspartate aminotransferase(98.8±40.0 U/L)in the FFBJRGP-treated group were decreased(50.02±3.7 U/L and 57.2±30.0 U/L,respectively,P<0.01).Compared with those in the model group,the levels of PCⅢ(35.73±17.90 g/mL),HA(563.82±335.54 ng/mL),LN(89.57±7.59 ng/mL)and CⅣ(29.20±6.17ng/mL)were decreased to 30.18±9.41,456.18±410.83,85.46±7.51 and 28.02±9.45 ng/mL,respectively.Reverse-transcriptase polymerase chain reaction and Western blotting also revealed that expression of TGF-β1 and Smad3 were down-regulated in vivo.Cell proliferation was inhibited,the level of hydroxyproline was decreased compared with the control group(P<0.01),and the cell cycle was redistributed when exposed to FFBJRGP in vitro.CONCLUSION:FFBJRGP inhibits hepatic fibrosis in vivo and in vitro,which is probably associated with downregulation of fibrogenic signal transduction of the TGF-β-Smad pathway.

Clinical and experimental study of therapeutic effect of Weixibaonizhuan pills on gastric precancerous lesions

IMS To observe the therapeutic effect of Weixibaonizhuan pills on gastric precancerous lesions.METHODS Thirty patients with gastric precancerous lesions were treated with Weixibaonizhuan pills for 3 months. Of the 36 cases, 13 (361%) were mild atrophic gastritis, 14 (389%) moderate atrophic gastritis and 9 (250%) severe atrophic gastritis; among them 22 (611%) and 27 cases (750%) were accompanied with intestinal metaplasia (IM) and dysplasia (DYS) respectively. Of the 36 patients, 20 were men and 16 women, aged from 30-60 years and those aged 30-59 years accounted for 611%. The course of disease ranged from 3 months to 21 years, and 20 (556%) of them had a course of 5-10 years. The clinical manifestations were fullness of the abdomen (31 cases), abdominalgia (27 cases), anorexia (30 cases), gas eructation (26 cases), acid regurgitation (6 cases) and loose stool (9 cases). When treatment ended, the improvement of patients′ clinical symptoms, atrophy of gastric mucosa, IM and DYS were analysed.RESULTS After 3 months′ treatment with Weixibaonizhuan pills, 7 cases recovered, 11 cases were much improved, 13 cases showed some improvement, and 5 cases were ineffective; the total rate of symptomatic improvement was 861%. Of the 13 cases with mild atrophic gastritis, 11 cases changed into superficial gastritis, and 2 cases had no changes. Of the 14 cases of moderate atrophic gastritis, 4 cases changed into superficial gastritis, 7 cases changed into mild atrophic gastritis, and 3 cases had no changes. Five of 9 cases of severe atrophic gastritis were reduced to moderate atrophic gastritis, and 4 cases had no changes. The total effective rate was 778% in chronic atrophic gastritis. Of the 9 cases with mild IM, IM disappeared in 6 cases and 3 showed no change. Of the 10 cases with moderate IM, it disappeared in 2 cases, 5 cases changed to mild IM, and 3 cases had no change. One of the 4 cases of severe IM changed to moderate IM and 3 had no change. The total effective rate was 636% in IM. Of the 16 cases of mild DYS, 11 cases showed disappearance of DYS and 5 had no change. In 9 cases of moderate DYS, 2 showed disappearance, 5 changed to mild DYS and 2 had no change. Two cases of severe DYS, both showed no change. The total effective rate was 667% in DYS. Before treatment, the Ⅰ, Ⅱ, Ⅲ and Ⅳ degree positive expressions of CEA were present in 13, 12, 9 and 2 cases, respectively, whereas after treatment, the positive expressions were present in 25, 7, 3 and 1, respectively. Before treatment, the Ⅰ, Ⅱ, Ⅲ and Ⅳ degree positive expressions of PCNA were present in 16, 11, 10 and 4 respectively, but after treatment, they were present in 21, 9, 5 and 1 respectively. In short, the positive expressions of CEA and PCNA of gastric mucosa were significantly decreased after treatment (P<001).CONCLUSION Weixibaonizhuan pill has a therapeutic effect in gastric precancerous lesions..

Herbal cardiotonic pills prevent gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically

AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.

Zuogui pills for myelinolysis in a rat model of experimental autoimmune encephalomyelitis

Zuogui pills have been shown to attenuate the inflammatory reaction in a rat model of experimental autoimmune encephalomyelitis （EAE）. The present study attempted to investigate the pathology underlying the influence of Zuogui pills on myelinolysis in EAE rats. Hematoxylin-eosin and Luxol fast blue staining showed that the myelinolysis foci in the cerebrum, cerebellum, brain stem, and the spinal cord of EAE rats were significantly decreased, along with serum myelin basic protein content following treatment with Zuogui pills.

Effect of Shoutai Pills on Th1/Th2 Cytokines in Serum and Endometrium of Rats with Stimulated Ovulation

In our previous study,we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen,progesterone and estrogen receptor in rats with stimulated ovulation.However,the mechanism is not clear.This study was designed to investigate the effect of Shoutai pills on the levels of Th1 and Th2 cytokines in rats with stimulated ovulation and the mechanism.The rat model of stimulated ovulation was established by combined injection of pregnant mare serum gonadotropin(PMSG)and human chorionic gonadotropin(HCG).Then the rats were randomly divided into model group(M),Shoutai pills group(S),progesterone group(P)and normal group(N).All the pregnant rats were treated from the first day.The S and P groups were administrated with gavage of Shoutai pills and injection of progesterone respectively,and N and M groups were given the same volume of normal saline and distilled water respectively.After treatment for 7 days,the animals were executed for serum and uterine tissues.The ELISA method was adopted to detect the contents of Thl cytokines[interferon-γ(INF-γ),interleukin-2(IL-2)]and Th2 cytokines(IL-4,IL-6,IL-10).The expression of leukemia inhibitory factor(L1F)and leukemia inhibitory factor receptor(LIFR)was detected by Western blotting and real-time PCR.As compared with N group,the expression levels of IFN-y and IL-2 in M group were significantly increased,and those of IL-4,IL-6,IL-10.LIF and LIFR were significantly decreased(P<0.05).As compared with M group,the levels of IL-4,IL-6,IL-10,LIF and LIFR in S group were significantly increased(P<0.05),and those of IFN-γand IL-2 were significantly decreased(P<0.05).It was suggested that Shoutai pills can increase the levels of IL-4.1L-6,IL-10,LIF and LIFR as well as reduce the levels of INF-γand IL-2 in rats with stimulated ovulation.The Shoutai pills may improve endometrial receptivity and promote embryo implantation by maintaining the balanee of Th1/Th2 cytokines.

Shuyu pills inhibit immune escape and enhance chemosensitization in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is characterized by dysregulation of the immune microenvironment and the development of chemoresistance.Specifically,expression of the programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1)axis,an immune checkpoint,may lead to tumour immune escape,resulting in disease progression.The latest research shows that tumour immune escape may be caused by the upregulation of PD-L1 mediated by hypoxia-inducible factor-1 alpha(HIF-1α),and simultaneous inhibition of HIF-1αand PD-L1 has the potential to enhance the host’s antitumour immunity.Moreover,inhibition of the PD-1/PD-L1 axis may mitigate tumour chemoresistance.Shuyu pills(SYPs)contain immunity-enhancing and antitumour components,making them a potential HCC treatment.AIM To investigate the efficacy of SYPs for HCC treatment via simultaneous HIF-1α and PD-L1 inhibition and the mechanism involved.METHODS A subcutaneous xenograft tumour model was first established in BALB/c nude mice by the subcutaneous injection of 1×107 SMMC-7721 cells.Male mice(male,5 weeks old;n=24)were then randomly divided into the following four groups(n=6):Control(0.9%normal saline),SYP(200 mg/kg),SYP+cisplatin(DDP)(200 mg/kg+5 mg/kg DDP weekly via intraperitoneal injection),and DDP(5 mg/kg cisplatin weekly via intraperitoneal injection).The dose of saline or SYPs for the indicated mouse groups was 0.2 mL/d via intragastric administration.The tumour volumes and body weights of the mice were measured every 2 d.The mice were euthanized by cervical dislocation after 14 d of continuous treatment,and the xenograft tissues were excised and weighed.Western blot assays were used to measure the protein expression of HIF-1α,PD1,PD-L1,CD4+T cells,and CD8+T cells in HCC tumours from mice.Quantitative reverse transcription polymerase chain reaction was used for real-time quantitative detection of PD-1,PD-L1,and HIF-1α mRNA expression.An immunofluorescence assay was conducted to examine the expression of CD4+T cells and CD8+T cells.RESULTS Compared to mice in the control group,those in the SYP and SYP+DDP groups exhibited reduced tumour volumes and tumour weights.Moreover,the protein and mRNA expression levels of the oncogene HIF1α and that of the negative immunomodulatory factors PD-1 and PD-L1 were decreased in both the SYP and SYP+DDP groups,with the decrease effects being more prominent in the SYP+DDP group than in the SYP group(HIF-1α protein:Control vs SYP,P=0.0129;control vs SYP+DDP,P=0.0004;control vs DDP,P=0.0152,SYP+DDP vs DDP,P=0.0448;HIF-1αmRNA:control vs SYP,P=0.0009;control vs SYP+DDP,P<0.0001;control vs DDP,P=0.0003,SYP vs SYP+DDP,P=0.0192.PD-1 protein:Control vs SYP,P=0.0099;control vs SYP+DDP,P<0.0001,SPY vs SYP+DDP,P=0.0009;SYP+DDP vs DDP,P<0.0001;PD-1 mRNA:control vs SYP,P=0.0002;control vs SYP+DDP,P<0.0001;control vs DDP,P=0.0003,SPY vs SYP+DDP,P=0.0003;SYP+DDP vs DDP,P=0.0002.PD-L1 protein:control vs SYP,P<0.0001;control vs SYP+DDP,P<0.0001;control vs DDP,P<0.0001,SPY vs SYP+DDP,P=0.0040;SYP+DDP vs DDP,P=0.0010;PD-L1 mRNA:Control vs SYP,P<0.0001;control vs SYP+DDP,P<0.0001;control vs DDP,P<0.0001,SPY vs SYP+DDP,P<0.0001;SYP+DDP vs DDP,P=0.0014).Additionally,the quantitative and protein expression levels of CD4+T cells and CD8+T cells were simultaneously upregulated in the SYP+DDP group,whereas only the expression of CD4+T cells was upregulated in the SYP group.(CD4+T cell quantitative:Control vs SYP+DDP,P<0.0001,SYP vs SYP+DDP,P=0.0005;SYP+DDP vs DDP,P=0.0002.CD4+T cell protein:Control vs SYP,P=0.0033;Control vs SYP+DDP,P<0.0001;Control vs DDP,P=0.0021,SYP vs SYP+DDP,P=0.0004;SYP+DDP vs DDP,P=0.0006.Quantitative CD8+T cells:Control vs SYP+DDP,P=0.0013;SYP vs SYP+DDP,P=0.0347;SYP+DDP vs DDP,P=0.0043.CD8+T cell protein:Control vs SYP+DDP,P<0.0001;SYP vs SYP+DDP,P<0.0001;SYP+DDP vs DDP,P<0.0001).Finally,expression of HIF-1αwas positively correlated with that of PD-1/PD-L1 and negatively correlated with the expression of CD4+T cells and CD8+T cells.CONCLUSION SYPs inhibit immune escape and enhance chemosensitization in HCC via simultaneous inhibition of HIF-1α and PD-L1,thus inhibiting the growth of subcutaneous xenograft HCC tumours.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation

BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.