Epigastric pain syndrome: What can traditional Chinese medicine do? A randomized controlled trial of Biling Weitong Granules

BACKGROUND Recent research suggests that although prokinetic agents,acid suppressors,and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia(FD),a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions.Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases.The present study was designed to verify the efficacy of Biling Weitong Granules(BLWTG),a traditional Chinese medicinal herbal compound formula,in alleviating epigastric pain syndrome(EPS)in FD patients,in an attempt to provide an effective prescription for the clinical treatment of this disease.AIM To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD.METHODS In this multicenter,stratified,randomized,double-blind,placebo-controlled,parallel group clinical trial,eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk.Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared.RESULTS The baseline demographic data and clinical characteristics,such as epigastric pain symptoms,pain intensity,and frequency of attacks,were matched between the two groups before randomization.After 6 wk of treatment and after the center effect was eliminated,the epigastric pain was significantly improved in 28.33%and 85.59%of the patients in the placebo and BLWTG groups,respectively(P<0.05).At 6 wk,the resolution rate of epigastric pain was 15%and 69.49%in the placebo and BLWTG groups,respectively(P<0.05).The differences of total FD clinical score between these two groups were significant(P<0.05)at 2,4,and 6 wk(P<0.05).The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated(P<0.05).There was no significant difference in the incidence of adverse events between the two groups,and no serious adverse event was noted during the observation.CONCLUSION Compared with placebo,BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.

International expert consensus on clinical application of traditional Chinese medicine formula granules

Guided by the theory of traditional Chinese medicine(TCM),TCM formula granules are made through the optimal process of extraction,concentration,drying,and granulation by combining modern new preparation technologies and pharmaceutical technologies.TCM formula granules are stable,safe,convenient,and effective.Compared with TCM decoction pieces,TCM formula granules can achieve the full process control of its industry chain from field to workshop and standardize the management of the origin of medicinal materials,processing of decoction pieces,processing technology,quality inspection,sales,and products distribution.TCM formula granules can partially replace Chinese patent medicines.Only available for around 800 common varieties of TCM,TCM formula granules cannot replace decoction pieces for many types which are not commonly used in clinical practice.A large number of formula granules are used in clinical and animal studies so that investigators no longer need to extract and control the quality of TCM decoction pieces.How to improve the production process,establish the quality standard,perfect the regulatory system,and expand the clinical application are the problems we need to solve as soon as possible for the better development of formula granules.

Efficacy and Safety of Traditional Chinese Patent Medicine Qizhi Weitong Granules(气滞胃痛颗粒)in Irritable Bowel Syndrome with Predominant Constipation:A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Objective:To systematically review the efficacy and clinical safety of Qizhi Weitong Granules(气滞胃痛颗粒)(QZWT)in the treatment of irritable bowel syndrome with predominant constipation(IBS-C).Methods:Randomized controlled trials(RCTs)of QZWT in patients with IBS-C were retrieved from Pub Med,EMBASE,Cochrane Library,China National Knowledge Infrastructure(CNKI),Wanfang,Chinese Scientific Journals Database(VIP),and Chinese Biological Medical Database(CBM)from inception to December 3,2022.Conventional meta-analysis with random-effects model or fixed-effects model and trial sequential analysis(TSA)were performed by Review Manager 5.4,Stata and TSA software.Results:A total of 4 RCTs and 368 patients with IBS-C were included in this study.The findings of the meta-analysis indicated that the cure and efficacy rate of the experimental group was significantly higher than that of the control group[RR=2.19;(95%CI,1.35–3.55),P<0.01;RR=1.14;(95%CI,1.03–1.27),P<0.05],while the result of Bristol Score was negative.The funnel plot was probably symmetry,and the P value was>0.05 in the Egger test,which confirmed the nonexistence of significant publication bias in this outcome.TSA showed the cumulative z-value crossed the traditional threshold and TSA threshold,while it didn't get to the required information size.Finally,2 studies reported adverse events after QZWT treatment,including 3 cases of diarrhea.No serious adverse events were reported.Conclusion:QZWT was an effective and safe complementary therapy in the treatment of IBS-C with no obvious adverse reactions.TSA analysis confirmed our meta-analysis results.Therefore,QZWT may be a potential candidate for the treatment of IBS-C.However,due to the limited quality of current studies,more long-term,randomized,double-blinded clinical trials are needed in future studies.

Research of Quality Standards for Stachydrine Hydrochloride in Chinese Medicine TJF Granule

A high-performance liquid chromatographic method was applied to the determination of stachydrine hydrochloride concentration in TJF granule (Chinese name: Tiao-Jing-Fang), using a mobile phase of methanol-acetonitrile (50:50, v/v) by the Agilent Kromasi NH2 column (250 mm × 4.6 mm, 5 μm, S/N: 22N25110). Detection wavelength was 201 nm. The result revealed good linearity of stachydrine hydrochloride and was obtained within the range of 0.20 - 1.98 μg/mL (R = 0.9995). The average recovery was 97.01%;the relative standard deviation (RSD) was 0.19%. To the best of our knowledge, this is the first report dedicated to the determination of stachydrine hydrochloride by the evaporative light scattering detector-high-performance liquid chromatographic (ELSD-HPLC) method.

Clinical Research on the Treatment of Simple Obesity by Oral Chinese Medicine Combined with Health Education to Improve Phlegm Dampness Constitution

OBJECTIVE: To observe the clinical effect of oral traditional Chinese medicine granules combined with health education to regulate phlegm constitution and treat simple obesity. METHODS: According to the method of constitution evaluation in TCM Constitution Classification and Evaluation(Chinese Association of Chinese Medicine), the TCM classification of Chinese medicine was performed on patients who came to the outpatient department of the Traditional Chinese Medicine Hospital of Pinggu District of Beijing and met the diagnostic criteria of simple obesity. One hundred patients with phlegm constitution were selected and those in accordance with the standards, were randomly divided into group with oral TCM granules combined with health education(refer to as treatment group) and health education group(refer to as control group) according to 1:1 ratio. The control group was given health education including diet and exercise instruction. Treatment group:(1) Health education includes diet and exercise instruction.(2) Oral Chinese medicine granules: ingredients: atractylodes rhizome 15g, raw barley 30g, Folium Nelumbinis 10g, Chinese hawthorn fruit 10g, Chinese waxgourd peel 15g, milk-vetch root;15g, kudzuvine root 15g, danshen root10g, 2 times/d. The two groups were intervened for 12 weeks each time, and obesity evaluation indicators such as body weight, body fat, waist circumference, hip circumference, weight index, and score table of TCM constitutional were observed before and after the intervention. Statistical software was used for statistical analysis. RESULTS: The total curative effect of the treatment group was better than that of the control group(P<0.001). The weight index, body weight, waist and hip circumference decreased significantly after treatment(P <0.01). Compared with the two groups, the treatment group is better than the control group in terms of dampness constitution improvement, weight and fat losing and waist and hip circumference reducing.(P<0.01). CONCLUSION: Oral Chinese medicine granules Jiangzhuo Fang(combined with health education) and simple health education can improve phlegm constitution, and improve the body weight, body fat percentage and other indicators of the patients, but oral granules combined with health education to improve the physical fitness of phlegm is better than simple health education. The thoughts and methods of Chinese medicine granules combined with health education to regulate phlegm constitution is effective for weight losing and is worthy of further research and promotion.

Efficacy and safety of Yangxue Qingnao Granules in treatment of migraine:A systematic review and meta-analysis

BACKGROUND Yangxue Qingnao Granules(YXQN)is a Chinese patent medicine that has been commonly used in the clinical treatment of migraine.AIM To assess the efficacy and safety of YXQN alone for the treatment of migraine.METHODS We searched 10 databases to identify relevant randomized controlled trials(RCTs)published before September 2022.Two review authors independently searched and screened the literature,extracted the data,and assessed the methodological quality of the studies using criteria from ROB 2.0,and analyzed the data using Review Manager 5.4 software.RESULTS A total of 12 RCTs including 767 participants with migraine met the selection criteria.We divided these studies into comparisons of YXQN with placebo,routine treatment drugs,and other Chinese patent medicines.The meta-analysis showed the following:(1)Efficacy:The YXQN group outperformed the placebo group[relative risk(RR)=0.29,95%confidence interval(95%CI):0.15–0.43,P<0.00001],routine treatment group(RR=0.18,95%CI:0.09–0.27,P<0.0001),and Chinese patent medicine group(RR=0.27,95%CI:0.13–0.41,P<0.001);(2)frequency of headache:There was a significant difference between YXQN vs placebo[mean difference(MD)=-1.25,95%CI:-1.60 to-0.90,P<0.00001],routine treatment drugs(MD=-0.85,95%CI:-1.15 to-0.56,P<0.00001),and Chinese patent medicine(MD=-0.91,95%CI:-1.35 to-0.46,P<0.0001);(3)headache duration:We found great heterogeneity between studies,with no differences between YXQN and placebo(MD=-0.61,95%CI:-1.53 to-0.31,P=0.19)and routine treatment drugs(MD=-0.22,95%CI:-0.89 to 0.46,P<0.53).YXQN was more effective than other Chinese patent medicines in reducing headache duration(MD=-1.24,95%CI:-1.70 to-0.77,P<0.00001);and(4)headache severity:There was no significant difference between YXQN vs placebo(MD=-1.67,95%CI:-3.52 to 0.19,P=0.08),routine treatment drugs(MD=-0.53,95%CI:-2.02 to 0.96,P=0.68),and other Chinese patent medicines(MD=-0.49,95%CI:-2.83 to 1.85,P=0.68).Mild gastrointestinal adverse reactions were reported in three cases.CONCLUSION This study revealed that YXQN is effective and safe for treatment of migraine.

Yiwei Xiaoyu granules for treatment of chronic atrophic gastritis with deficiency syndrome of the spleen and stomach

BACKGROUND The Correa sequence,initiated by Helicobacter pylori(H.pylori),commonly progresses to gastric cancer through the stage of chronic atrophic gastritis(CAG).Although eradication of H.pylori only reduces the risk of gastric cancer,it does not eliminate the risk for neoplastic progression.Yiwei Xiaoyu granules(YWXY)are a commonly used composite preparation in Chinese clinics.However,the pursuit of excellence in clinical trials and the establishment of standardized animal experiments are still needed to contribute to full understanding and application of traditional Chinese medicine in the treatment of CAG.AIM To demonstrate the effectiveness of YWXY in patients with CAG and spleenstomach deficiency syndrome(DSSS),by alleviating histological scores,improving response rates for pathological lesions,and achieving clinical efficacy in relieving DSSS symptoms.METHODS We designed a double-blind,randomized,controlled trial.The study enrolled seventy-two H.pylori-negative patients(mean age,52.3 years;38 men)who were randomly allocated to either the treatment group or control group in a 1:1 ratio,and treated with 15 g YWXY or 0.36 g Weifuchun(WFC)tablet combined with the respective dummy for 24 wk.The pre-randomization phase resulted in the exclusion of 72 patients:50 participants did not meet the inclusion criteria,12 participants declined to participate,and 10 participants were excluded for various other reasons.Seven visits were conducted during the study,and histopathological examination with target endoscopic biopsy of narrow-band imaging was requested before the first and seventh visits.We also evaluated endoscopic performance scores,total symptom scores,serum pepsinogen and gastrin-17.RESULTS Six patients did not complete the trial procedures.Treatment with YWXY improved the Operative Link on Gastric Intestinal Metaplasia Assessment(OLGIM)stage,compared with WFC(P<0.05).YWXY provided better relief from symptoms of DSSS and better improvement in serum gastric function,compared with WFC(P<0.05).CONCLUSION YWXY compared with WFC significantly reduced the risk of mild or moderate atrophic disease,according to OLGIM stage,significantly relieved symptoms of DSSS,and improved serum gastric function.

Traditional Chinese medicine compound ShengJinRunZaoYangXue granules for treatment of primary Sjogren＇s syndrome： a randomized, double-blind, placebo-controlled clinical trial

Background Traditional Chinese medical treatment of primary Sj（o）gren＇s syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions.This study was a multicenter,randomized,doubleblind,placebo-controlled clinical trial of the efficacy and safety of ShengJinRunZaoYangXue granules for the treatment of primary Sj（o）gren＇s syndrome,including the symptoms of dry mouth and dry eye.Methods We undertook a 6-week,double-blind,randomized trial involving 240 patients with primary Sj（o）gren＇s syndrome at five centers in East China.A computer-generated randomization schedule assigned patients at a 2∶1 ratio to receive either ShengJinRunZaoYangXue granules or placebo once daily.Patients and investigators were blinded to treatment allocation.The primary endpoints were the salivary flow rate,Schirmer test results,and sugar test results.Intention-to-treat and per-protocol analyses were performed.Results All 240 patients were randomly allocated to either the treatment group （n=160,ShengJinRunZaoYangXue granules） or placebo group （n=80） and were included in the intention-to-treat analysis.After program violation and loss to follow-up,a total of 199 patients were included in the per-protocol analysis.At six week,intention-to-treat and per-protocol analyses of the left-eye Schirmer I test results showed an improved difference of 1.36 mm/5 min （95% CI：0.03 to 2.69 mm/5 min） and 1.35 mm/5 min （95% CI：0.04 to 2.73 mm/5 min）,respectively,and those of the right-eye Schirmer I test results showed an improved difference of 1.12 mm/5 min （95% CI：0.02 to 2.22 mm/5 min） and 1.12 mm/5 min （95% CI：-0.02 to 2.27 mm/5 min）,respectively.There was no significant difference between the two groups before treatment.After treatment,the between-group and within-group before-and-after paired comparison results were statistically significant （P 〈0.05）.Intention-to-treat and per-protocol analyses showed an improved salivary flow rate by 0.04 ml/15 min （95% CI：-0.49 to 0.58 ml/15 min） and 0.04 ml/15 min （95% CI：-0.52 to 0.60 ml/15 min）,respectively,but the differences were not significant.Intention-to-treat and per-protocol analyses showed that the sugar test results were improved by 1.77 minutes （95% CI：0.11 to 3.44 minutes） and 1.84 minutes （95% CI：0.12 to 3.55 minutes）,respectively,but the differences were not significant.For the secondary endpoint,intention-to-treat and per-protocol analyses showed significant improvement in the integrated evaluation of treated patients with dry eye and dry mouth after six weeks of treatment.The incidence of adverse events was 15.6% in the treatment group and 10.0% in the placebo group.Most （94%） adverse events were mild to moderate in the two groups,and only two cases of serious adverse events occurred in the treatment group; both were caused by autoimmune liver disease.Conclusions Six-week treatment with ShengJinRunZaoYangXue granules for primary Sj（o）gren＇s syndrome in this large-scale study improved the symptoms of dry mouth,dry eyes,and low tear flow rate with minimal adverse events.

Biomechanical analysis of optic nerve injury treated by compound light granules and ciliary neurotrophic factor

In this study, rabbit models of optic nerve injury were reproduced by the clamp method. After modeling, rabbit models were given one injection of 50 ng recombinant human ciliary neurotrophic factor into the vitreous body and/or intragastric injection of 4 g/kg compound light granules containing Radix Angelicae Sinensis and Raidix Paeoniae Alba at 4 days after modeling, once per day for 30 consecutive days. After administration, the animals were sacrificed and the intraorbital optic nerve was harvested. Hematoxylin-eosin staining revealed that the injured optic nerve was thinner and optic nerve fibers were irregular. After treatment with recombinant human ciliary neurotrophic factor, the arrangement of optic nerve fibers was disordered but they were not markedly thinner. After treatment with compound light granules, the arrangement of optic nerve fibers was slightly disordered and their structure was intact. After combined treatment with recombinant human ciliary neurotrophic factor and compound light granules, the arrangement of optic nerve fibers was slightly disordered and the degree of injury was less than after either treatment alone. Results of tensile mechanical testing of the optic nerve showed that the tensile elastic limit strain, elastic limit stress, maximum stress and maximum strain of the injured optic nerve were significantly lower than the normal optic nerve. After treatment with recombinant human ciliary neurotrophic factor and/or compound light granules, the tensile elastic limit strain, elastic limit stress, maximum stress and maximum strain of the injured optic nerve were significantly increased, especially after the combined treatment. These experimental findings indicate that compound light granules and ciliary neurotrophic factor can alleviate optic nerve injury at the histological and biochemical levels, and the combined treatment is more effective than either treatment alone.

Zishenpingchan granules for the treatment of Parkinson＇s disease：a randomized,double-blind,placebo-controlled clinical trial

Levodopa preparations remain the preferred drug for Parkinson＇s disease.However,long-term use of levodopa may lead to a series of motor complications.Previous studies have shown that the combination of levodopa and Zishenpingchan granules（consisting of Radix Rehmanniae preparata,Lycium barbarum,Herba Taxilli,Rhizoma Gastrodiae,Stiff Silkorm,Curcuma phaeocaulis,Radix Paeoniae Alba,Rhizoma Arisaematis,Scorpio and Centipede） can markedly improve dyskinesia and delay the progression of Parkinson＇s disease,with especially dramatic improvements of non-motor symptoms.However,the efficacy of this combination has not been confirmed by randomized controlled trials.The current study was approved by the Hospital Ethics Committee and was registered in the Chinese Clinical Trial Register（registration number：Chi CTR-INR-1701194）.From December 2014 to December 2016,128 patients（72 males and 56 females,mean age of 65.78 ± 6.34 years） with Parkinson＇s disease were recruited from the Department of Neurology of Longhua Hospital and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine in China.Patients were equally allocated into treatment and control groups.In addition to treatment with dopamine,patients in treatment and control groups were given Zishenpingchan granules or placebo,respectively,for 24 weeks.Therapeutic efficacy was assessed using the Unified Parkinson＇s Disease Rating Scale,on-off phenomenon,Hoehn-Yahr grade,Scales for Outcomes in Parkinson＇s disease–Autonomic,Parkinson＇s disease sleep scale,Hamilton Anxiety Scale,Hamilton Depression Scale,Mini-Mental State Examination,and the Parkinson＇s Disease Quality of Life Questionnaire.Artificial neural networks were used to determine weights at which to scale these parameters.Our results demonstrated that Zishenpingchan granules significantly reduced the occurrence of motor complications,and were useful for mitigating dyskinesia and non-motor symptoms of Parkinson＇s disease.This combination of Chinese and Western medicine has the potential to reduce levodopa dosages,and no obvious side effects were found.These findings indicate that Zishenpingchan granules can mitigate symptoms of Parkinson＇s disease,reduce toxic side effects of dopaminergic agents,and exert synergistic and detoxifying effects.

Anticancer effect of Jinlongshe granules on in situ-transplanted human MKN-45 gastric cancer in nude mice and xenografted sarcoma 180 in Kunming mice and its mechanism

AIM： To study the antitumor effect of Chinese compound Jinlongshe （JLS） granules on sarcoma 180 and MKN-45 human gastric cancer cell lines in vivo and its mechanism. METHODS： After establishment of S180 sarcoma （S180） and MKN-45 gastric cancer model of nude mice, the tumor-bearing mice were divided into 5 groups at random. Three experimental groups were respectively given the aqueous extract of JLS granules at doses of 120 g, 60 g and 20 g/（kg per 6/wk,i.g） for 3 wk in S180 and 6 wk in nude mice model. Positive control was given cyclophosphamide （Cy） at a dose of 50 mg/（kg per 3/wk, i.g） for 3 wk in S180 models and 5-Fluorouracil （5-FU） 20 mg/（kg per 3/wk, i.g） for 3 wk in nude mice model. Negative control was given normal saline （NS） at a dose of 0.18 g/（kg per 6/wk, i.g） respectively. After 3 wk in mice bearing S180 tumor and 6 wk in nude mice model, the experimental animals were sacrificed and the masses of tumor were weighed, and the rates of tumor inhibition of each treated group were calculated respectively. To determine the antitumor mechanisms, the morphological changes, cell cycle and apoptosis were observed in MKN-45 nude mice model. Annexin V-FITC/PI double staining FCM assay was used to further determine the live cells, apoptotic cells, necrotic cells and debris. RESULTS： The inhibitory rates of JLS granules at the doses of 20 g/kg, 60 g/kg and 120 g/kg were 50.31%, 55.94% and 68.13% （P 〈 0.01） in nude mice models and 40.90%, 50.32% and 58.46% （P 〈 0.01） in S180 model. The inhibitory rate of Cy was 85.22% in S180 models and the inhibitory rate of 5-FU was 53.43% in nude mice model （P 〈 0.01）. Nuclear chromatin and margination were observed under a transmission electron microscope （TEM）. The G0/G1 phase was arrested, typical apoptotic peak appeared, the apoptotic rate was 22.81%-38.54% in three JLS granule-treated groups. Annexin V-FITC/PI double staining FCM assay showed that the apoptotic cells were 4.36%, 3.08% and 7.08% in three dosages, most cells were localized in the low right quadrant. CONCLUSION：Jinlongshe granules possess anti-tumor effects on experimental tumor models in vivo, and apoptosis induction is one of its anti-tumor mechanisms.

Network Pharmacology and in vitro Experimental Veriflcation on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer

Objective: To explore the potential mechanism of Yishen Qutong Granules(YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research. Methods: The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry(HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified. Results: Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B(NF-κB) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF-κB was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF-κB, the main therapeutic target. Conclusion: YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Treating Alzheimer's disease with Yizhijiannao granules by regulating expression of multiple proteins in temporal lobe

Yizhijiannao granules have been shown to improve cognitive function in Alzheimer＇s disease patients. The present study sought to explore the mechanisms involved in the cognitive enhancing effects of Yizhijiannao granule. Senescence-accelerated mouse prone 8 mice with learning and memory disorders were intragastrically treated with Yizhijiannao granule for 8 weeks. Mice intragastrically treated with double distilled water for 8 weeks were considered as the control group. 2D gel electrophoresis was used to isolate total protein from the temporal lobe of senescence-accelerated mouse prone 8 mice, and differential protein spots were obtained by mass spectrometry. Thirty-seven differential protein spots were found in the temporal lobe area of both groups. Ten protein spots were identified： high mobility group box 1, dimethylarginine dimethylaminohydrolase-1, nenroglobin, hemoglobin beta adult major chain, peroxiredoxin-6, cofilin-1, flotiUin 1, peptidylprolyl isomerase A, voltage-dependent anion channel-2 and chaperonin containing TCP1, and subunit 2. Among other functions, these proteins are separately involved in the regulation of amyloid beta production, oxidative stress, neuroinflammation, regulation of tau phosphorylation, and regulation of neuronal apoptosis. Our results revealed that Yizhijiannao granule can regulate the expression of various proteins in the temporal lobe of senescence-accelerated mouse prone 8 mice, and may be therapeutically beneficial for the treatment of Alzheimer＇s disease.

Chinese Medicine Yishen Jiangu Granules(益肾健骨颗粒)on Aromatase Inhibitor-Associated Musculoskeletal Symptoms

Objective： To assess the effectiveness of Yishen Jiangu Granules（益肾健骨颗粒, YSJGG） on aromatase inhibitor-associated musculoskeletal symptoms（AIMSS）. Methods： A single-arm, open-label study was conducted in 34 postmenopausal women with breast cancer who experienced AIMSS. Patients were treated with YSJGG for 12 weeks（12.4 g orally twice daily）. The primary outcome was a change in the mean worst pain score of Brief Pain Inventory-Short Form（BPI-SF） over 12 weeks, and the second outcomes included changes in pain severity and pain-related interference of BPI-SF and Western Ontario and McMaster Universities Osteoarthritis Index（WOMAC）, Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands（M-SACRAH）, the Functional Assessment of Cancer Therapy-Breast（FACT-B）, bone mineral density（BMD） and blood indices such as calcium（Ca）, phosphate（P）, and alkaline phosphatase（ALP）. Results： Of 37 women recruited, 30 initiated the therapy and 24 were evaluable at 12 weeks. The primary outcome（BPI-SF worst pain scores） achieved a 2.17-point reduction compared with baseline（5.75±1.87 vs 3.58±2.15, P〈0.01）. There were reductions in pain severity（decreased 1.65, P〈0.01） and pain-related interference（decreased 2.55, P〈0.01）. The changes in WOMAC and M-SACRAH scores were similar to BPI-SF（P〈0.05）. In the FACT-B, only physical wel-being and functional wel-being were improved compared with baseline（P〈0.05）. No clinical differences were found in BMD, Ca, P and ALP. Conclusion： YSJGG is an effective and wel-tolerated agent to reduce AIMSS.

Xiangbinfang granules enhance gastric antrum motility via intramuscular interstitial cells of Cajal in mice

BACKGROUND Interdigestive migrating motor complexes(MMC)produce periodic contractions in the gastrointestinal tract,but the exact mechanism of action still remains unclear.Intramuscular interstitial cells of Cajal(ICC-IM)participate in gastrointestinal hormone and neuromodulation,but the correlation between ICCIM and MMC is also unclear.We found that xiangbinfang granules(XBF)mediated the phase III contraction of MMC.Here,the effects of XBF on gastric antrum motility in W/Wv mice and the effects of ICC-IM on gastric antrum MMC are reported.AIM To observe the effects of ICC-IM on gastric antrum motility and to establish the mechanism of XBF in promoting gastric antrum motility.METHODS The density of c-kit-positive ICC myenteric plexus(ICC-MP)and ICC-IM in the antral muscularis of W/Wv and wild-type(WT)mice was examined by confocal microscopy.The effects of XBF on gastric antrum slow waves in W/Wv and WT mice were recorded by intracellular amplification recording.Micro-strain-gauge force transducers were implanted into the gastric antrum to monitor the MMC and the effect of XBF on gastric antrum motility in conscious W/Wv and WT mice.RESULTS In the gastric antrum of W/Wv mice,c-kit immunoreactivity was significantly reduced,and no ICC-IM network was observed.Spontaneous rhythmic slow waves also appeared in the antrum of W/Wv mice,but the amplitude of the antrum slow wave decreased significantly in W/Wv mice(22.62±2.23 mV vs 2.92±0.52 mV,P<0.0001).MMCs were found in 7 of the 8 WT mice but no complete MMC cycle was found in W/Wv mice.The contractile frequency and amplitude index of the gastric antrum were significantly increased in conscious WT compared to W/Wv mice(frequency,3.53±0.18 cpm vs 1.28±0.12 cpm;amplitude index,23014.26±1798.65 mV·20 min vs 3782.16±407.13 mV·20 min;P<0.0001).XBF depolarized smooth muscle cells of the gastric antrum in WT and W/Wv mice in a dose-dependent manner.Similarly,the gastric antrum motility in WT mice was significantly increased after treatment with XBF 5 mg(P<0.05).Atropine(0.1 mg/kg)blocked the enhancement of XBF in WT and W/Wv mice completely,while tetrodotoxin(0.05 mg/kg)partially inhibited the enhancement by XBF.CONCLUSION ICC-IM participates in the regulation of gastric antrum MMC in mice.XBF induces MMC III-like contractions that enhance gastric antrum motility via ICCIM in mice.

Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic receptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Effects of Qidi Tangshen granules and their separate prescriptions on podocytes in mice with diabetic nephropathy

Objective:Previous studies have found that Qidi Tangshen granules(QDTS),a combination therapy of supplementing essence(Tianjing,TJ)and unblocking the collaterals(Tongluo,TL),can reduce kidney damage in db/db mice.This study aimed to explore the effect of QDTS and their separate prescriptions on podocytes in mice with diabetic nephropathy.Methods:The db/db mice were used in this experiment as an animal model,while wild-type C57BL/6J mice were used as normal controls.At the age of 12 weeks,the db/db mice were randomly divided into 5 groups(db/db,db/dbþvalsartan,db/dbþQDTS,db/dbþTJ and db/dbþTL).The urine albumin excretion ratio(UAE)was measured by enzyme-linked immunosorbent assay before and after the intervention.The ultrastructure of the kidney podocytes was observed by transmission electron microscopy.The protein expression levels of nephrin and desmin were detected by immunohistochemistry.Results:QDTS and their separate prescriptions significantly decreased the UAE and attenuated the renal pathological injury.QDTS and their separate prescriptions also reduced the fusion rate of the foot processes and increased the expression of nephrin protein.In contrast,QDTS and their separate prescriptions(TJ and TL)reduced the expression level of desmin protein.Conclusion:QDTS and their separate prescriptions might reduce diabetes-induced renal injury by reducing podocyte damage.The therapeutic effect of QDTS was more pronounced than TJ and TL.

Network Pharmacology-based Analysis on Determining the Mechanisms of Yishen Qutong Granules(益肾祛痛颗粒)in Alleviating Cancer-related Fatigue

Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)have achieved good curative effects in the treatment of CRA.However,the mechanism of whether it can alleviate CRF needs further confirmation.We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription.Through the analysis and research in this paper,we obtained 76 effective compounds and 76 drug-disease intersection targets to construct a network,indicating that quercetin,luteolin,baicalein,β-sitosterol and stigmasterol were possibly the most important compounds in YSQTG.The key targets of YSQTG for CRF were mainly enriched in IL-17 and TNF pathways.816 GO entries and 113 pathways were obtained by GO and KEGG enrichment,respectively,which proved that YSQTG might have a comprehensive therapeutic effect on CRF mainly through regulating IL-17,TNF,MAPK,NF-κB and chemokines,as well as cholinergic synapse and 5-HT synapse pathways.The results of molecular docking showed thatβ-sitosterol and stigmasterol could form PI-Alkyl or Alkyl hydrophobic interactions with CXCL8 and ESR1 at residues LEU25,ARG26,PHE65,ALA69 and LEU346,ALA350,LEU391,PHE404,LEU525,VAL533,respectively.In conclusion,the therapeutic effect of YSQTG on CRF is based on the comprehensive pharmacological effect of multicomponent,multitarget,and multichannel pathways.This study provides a theoretical basis for further experimental research.

Comparable effects of Jiedu Granule, a compound Chinese herbal medicine, and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study

Objective:Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma(HCC),and Chinese herbal medicine has also been used to manage advanced HCC.The present work evaluates the effectiveness and safety of Jiedu(JD)Granule,a compound of traditional Chinese herbal medicine,side-by-side with sorafenib for the treatment of advance HCC.Methods:Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS)and safety.Propensity score matching(PSM)analysis was used to control for possible selection bias from the study group allocation process.Results:Of the 325 patients included,161 received JD Granule and 164 received sorafenib.No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib(P>0.05).Median OS of the two study groups was 6.83 months(95%confidence interval[CI]:5.83–9.47)in the group receiving JD Granule and 8 months(95%CI:6.67–9.80)in the group receiving sorafenib,with half-,1-and 2-year survival rates of 53.6%,31.2%and 13.2%vs 60.1%,35.5%and 14.2%,respectively.Even after PSM,the median survival time did not differ between the JD Granule group(9.03 months;95%CI:6.37–14.2)and the sorafenib group(7.93 months;95%CI:6.5–9.97),with comparable half-,1-and 2-year survival rates.The most common adverse events(AEs)were diarrhea(13.7%)and fatigue(5.6%)in the JD Granule group,and hand-foot skin reaction(46.3%)and diarrhea(36.6%)in the sorafenib group.The JD Granule was more cost-effective than sorafenib treatment for advanced HCC.Conclusion:Compared to sorafenib,JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial

Objective:To evaluate the efficacy and safety of Chinese medicine(CM)improving pregnancy outcomes after surgery for endometriosis-associated infertility.Methods:A multicenter,randomized,doubleblind placebo parallel controlled clinical trial was designed.A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017,101 patients in each group.The two groups received continuous intervention at 1–5 days after surgery,for 6 menstrual cycles.Before ovulation,the CM group was treated Huoxue Xiaoyi Granule(活血消异颗粒);after ovulation,Bushen Zhuyun Granule(补肾助孕颗粒)was involved.The control group was treated with placebo.Transvaginal ultrasonography was performed every menstrual cycle during the treatment,and female hormone levels in the follicular and luteal phases were measured during the 1 st,3 rd and 6 th menstrual cycles.The analysis was continued until pregnancy.The primary outcomes were clinical pregnancy rate and pregnancy outcome,and the secondary outcomes were follicular development and endometrial receptivity.Safety evaluations were performed before and after treatment.Results:(1)Clinical pregnancy and live birth rates:the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group[44.6%(45/101)vs.29.7%(30/101),34.7%(35/101)vs.20.8%(21/101),both P<0.05].(2)Follicle development:the incidence of dominant follicles,rate of cumulative cycle ovulation,and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group[93.8%(350/373)vs.89.5%(341/381),80.4%(275/342)vs.69.1%(253/366),65.8%(181/275)vs 56.1%(142/253),P<0.05 or P<0.01]).The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group[11.7%(40/342)vs.17.8%(65/366),P<0.05).(3)Endometrial receptivity:after treatment,both endometrial types and endometrial blood flow types in the CM group were mainly types A and B,while those in the placebo group were mainly types B and C,with a significant difference between the two groups(both P<0.05).(4)Adverse events:the incidence of adverse events between the two groups was not significantly different(P>0.05).Conclusion:Strategies for activating blood circulation-regulating Gan(Liver)-tonifying Shen(Kidney)sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy,improve follicular development,promote ovulation,improve endometrial receptivity,while being a safe treatment option.(Trial registration No.NCT02676713).