Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules form...Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.展开更多
Osteosarcoma(OS)is the most frequent primary bone sarcomas with high recurrence and poor prognosis.Emerging evidence indicates that membraneless organelles stress granules(SGs),whose assemblies are driven by scaffold ...Osteosarcoma(OS)is the most frequent primary bone sarcomas with high recurrence and poor prognosis.Emerging evidence indicates that membraneless organelles stress granules(SGs),whose assemblies are driven by scaffold protein G3BP1,are extensively involved in tumor,especially in OS.However,how SGs behave and communicate with organelles,particularly nucleoli and mitochondria,during drug challenges remain unknown.This study revealed that chemotherapeutic drugs activated the cysteine protease asparagine endopeptidase(AEP)to specifically cleave the SG core protein G3BP1 at N258/N309 in OS and malignant glioma.tG3BP1-Ns modulated SG dynamics by competitively binding to full-length G3BP1.Strikingly,tG3BP1-Cs,containing a conserved RNA recognition motif CCUBSCUS,sequestered mRNAs of ribosomal proteins and oxidative phosphorylation genes in the nucleoli and mitochondria to repress translation and oxidative stress.Moreover,the inhibition of AEP promoted the tumor-suppressing effect of chemotherapeutic drugs,whereas AEP-cleaved G3BP1 rescue reversed the effect in both OS and glioma models.Cancerous tissues exhibited high levels of AEP and G3BP1 truncations,which were strongly associated with poor prognosis.展开更多
OBJECTIVE:To assess the efficacy and safety of the Qingyanyin formulated granules(轻燕饮配方颗粒,QYY),press needles(PN),and their combined application in addressing abdominal obesity(AO).This trial aims to offer a mor...OBJECTIVE:To assess the efficacy and safety of the Qingyanyin formulated granules(轻燕饮配方颗粒,QYY),press needles(PN),and their combined application in addressing abdominal obesity(AO).This trial aims to offer a more scientifically grounded therapeutic regimen for clinical interventions.METHODS:From March 2021 to July 2021,a multicenter,triple-blind,randomized 2×2 factorial design clinical trial was conducted across 7 centers in 4 major cities within China's mainland.The trial participants were patients diagnosed with AO.The trial followed a 1∶1∶1∶1 random allocation ratio,assigning participants to one of four groups:QYY placebo plus simulated press needles(SPN)(placebo+SPN),QYY plus SPN(QYY+SPN),QYY placebo plus PN(placebo+PN),and QYY plus PN(QYY+PN).The trial participants received treatment for 12 weeks.Observe the changes in waist circumference,body weight,body mass index(BMI),Beck Depression Inventory(BDI),Beck Anxiety Inventory(BAI)scores,and Pittsburgh Sleep Quality Index(PSQI)before and after treatment.RESULTS:The QYY+PN group exhibited significant improvements in waist circumference compared to placebo+PN[Difference=-1.59,95%CI(-3.03,-0.16)]and placebo+SPN groups[Difference=-2.01,95%CI(-3.46,-0.57)].QYY+PN demonstrated a significant advantage over placebo+SPN[Difference=-2.01,95%CI(-3.46,-0.57)],and no statistically significant interaction was observed between the two interventions(P>0.05).In terms of weight and BMI improvements,the QYY+PN,QYY+SPN,and the PN+placebo groups all experienced trending greater reductions in weight compared to the placebo group.In terms of the total scores of PSQI,BAI,and BDI,all four groups exhibited improvements compared to the baseline.Specifically,concerning the change in total PSQI scores,the QYY+PN group exhibited a greater reduction;Regarding the change in total BAI scores,the PN+placebo group demonstrated a greater decrease;As for the change in total BDI scores,the QYY+SPN group displayed a greater reduction.CONCLUSION:This study confirmed that QYY+PN can effectively reduce the waist circumference of patients with AO.Furthermore,the combined approach offers greater benefits than either treatment alone,all without any reported serious adverse events.展开更多
Objective:To explore the clinical efficacy and safety of Naomaili granules in the treatment of acute ischemic stroke.Methods:Eighty-eight patients were randomly divided into a treatment group and a control group,with ...Objective:To explore the clinical efficacy and safety of Naomaili granules in the treatment of acute ischemic stroke.Methods:Eighty-eight patients were randomly divided into a treatment group and a control group,with 44 patients in each group.The control group received conventional Western medicine treatment,while the treatment group was additionally administered Naomaili granules at 10g per time,3 times per day,for 20 days.Neurological function(NIHSS),activities of daily living(BI),inflammatory factors(hs-CRP,IL-6)levels,and adverse reactions were observed before and after treatment.Results:After 20 days of treatment,the NIHSS score of the treatment group decreased from(9.20±2.10)to(5.12±1.30),the BI index increased from(52.30±8.50)to(78.60±9.20),and hs-CRP and IL-6 decreased to(3.12±1.10)mg/L and(18.20±4.20)pg/mL,respectively,all significantly better than the control group(P<0.01).The incidence of adverse reactions in the treatment group was 4.55%,lower than the 15.91%in the control group(P<0.05).Conclusion:Naomaili granules can improve neurological function and living ability,reduce inflammatory response,and have good safety in patients with acute ischemic stroke.展开更多
BACKGROUND Prediabetes mellitus(PDM)is receiving increasing attention as a precursor to type 2 diabetes mellitus.Lifestyle and traditional Chinese medicine(TCM)inter-ventions are effective for PDM prevention and treat...BACKGROUND Prediabetes mellitus(PDM)is receiving increasing attention as a precursor to type 2 diabetes mellitus.Lifestyle and traditional Chinese medicine(TCM)inter-ventions are effective for PDM prevention and treatment.Therefore,we con-ducted a preliminary investigation and an exploratory randomised controlled trial to assess the effects of a combined lifestyle and TCM intervention on PDM indicators.AIM To study the effectiveness of Xiaokeqing granules(XQG)and lifestyle inter-ventions in PDM participants while using metabolomics to identify potential markers.METHODS Forty PDM participants with yin deficiency syndrome with excessive heat were recruited and randomly allocated to the control(Con)group or the XQG group(20 per group).The Con group underwent lifestyle interventions,whereas the XQG group underwent lifestyle and XQG interventions.The follow-up duration was 2 months.Fasting blood glucose,2-hour postprandial glucose(2hPG),gly-cated haemoglobin A1c,fasting insulin,homeostasis model assessment-insulin resistance levels,and serum metabolomics characteristics were compared via liquid chromatography-tandem mass spectrometry analysis.RESULTS There were significant differences in 2hPG between the two groups(P<0.05)in the intention-to-treat analysis and per-protocol analysis.The intervention method used in this study was safe(P>0.05).Groenlandicine,kaempferol,isomangiferin,etc.,are the XQG constituents absorbed in the blood.N-Nervonoyl methionine and 5-hydroxy-L-tryptophan are core potential metabolomic biomarkers for the effectiveness of XQG and lifestyle interventions.HTR1A,HTR2C,SLC6A4,etc.,are the core targets of XQG and lifestyle interventions,as well as the reason for their clinical efficacy.Possible mechanistic pathways include tryptophan metabolism,pantothenate and certificate of analysis biosynthesis,lysine degradation and biosynthesis of cofactors.CONCLUSION This pilot study provides evidence that a combined XQG and lifestyle intervention can improve 2hPG in par-ticipants with PDM.The mechanism of action is related to multiple constituents,targets and pathways.展开更多
Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-bli...Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-blind,placebo-controlled trial was conducted at the Third Central Hospital of Tianjin,China from March to December 2023.A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days.Efficacy was assessed through measures such as the total melasma area,reduced melasma area,reduction rate of melasma area,melasma color score,Melasma Area and Severity Index(MASI)score,and traditional Chinese medicine(TCM)symptom score scale.Safety assessments included routine blood and biochemical tests.Results:Participants in both groups were aged 52-63 years,with no significant differences.After the 2-month intervention,the total melasma area decreased in both groups;however,a greater reduction was observed in the test group[462.50 mm^(2)(12.81%)vs.100.00 mm2(3.11%),P<.001].Moreover,LDBG treatment significantly reduced the MASI and melasma color scores in the test group(P<.05).The total TCM symptom evaluation score significantly decreased(test group:6.00 vs.placebo group:7.00,P=.001),with significant relief in symptoms such as improvement in dark lips,nails,and waist soreness in the test group,compared with that in the placebo group(P<.05).Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group(P<.05).Conclusion:LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.展开更多
BACKGROUND Injury to the glomerular filtration barrier causes diabetic kidney disease(DKD),and glomerular endothelial-mesenchymal transition damages the filtration barrier of glomerular endothelial cells.Shenfushu gra...BACKGROUND Injury to the glomerular filtration barrier causes diabetic kidney disease(DKD),and glomerular endothelial-mesenchymal transition damages the filtration barrier of glomerular endothelial cells.Shenfushu granules(SFSGs)can treat chronic renal failure;however,their role and mechanism in DKD remain unclear.AIM To investigate the role of SFSGs in delaying DKD progression and their underlying mechanism in a streptozotocin-induced DKD mouse model.METHODS The microalbumin content in the urine and the blood glucose,creatinine,and blood urea nitrogen levels in the serum were measured.The expression and distribution ofα-smooth muscle actin(α-SMA),heparan sulfate(HS)and cluster of differentiation(CD)31 were observed through immunofluorescence or immunohistochemistry.Western blotting was conducted to measure the expression of CD31,α-SMA,PIK3R1,protein kinase B(AKT),phospho-PIK3R1,phospho-AKT,and heparanase-1.Network pharmacology was conducted to screen and identify the core components and targets of SFSGs.Molecular docking and dynamic simulations were performed to evaluate the binding ability of the core components of SFSGs to their core targets.RESULTS Compared with those in the model group,the 24-hour microalbuminuria(188.2±20.1 and 140.4±24.7 vs 323.2±44.4),serum creatinine(79.4±2.6 and 68.7±6.0 vs 110.2±4.8),blood urea nitrogen(14.4±1.1 and 13.1±0.5 vs 19.5±1.1),and renal index(20.3±1.0 and 19.6±0.8 vs 25.3±1.7)were significantly lower in the SFSGs(2.08 and 4.16 g/kg/day extract)-treated DKD mice.SFSGs inhibited the down regulation of CD31 and the upregulation ofα-SMA in the glomerular endothelial cells of DKD mice.Additionally,SFSGs suppressed the decrease in glycocalyx thickness and the expression of its component HS.Network pharmacology revealed that PIK3R1 was the core target of SFSGs.SFSGs markedly downregulate the expression of phospho-PIK3R1,phospho-AKT,and heparanase-1.However,the PIK3R1 agonist abolished the regulatory effect of SFSGs on the expression of CD31,α-SMA,and heparanase-1.CONCLUSION Collectively,these results suggest that SFSGs can significantly delay DKD progression and inhibit injury to the glycocalyx and the endothelial-mesenchymal transition of glomerular endothelial cells.This mechanism is related to PIK3R1/AKT/heparanase-1 signaling pathway regulation.展开更多
Dear Editor,Stress granules(SGs)are dynamic membraneless RNAprotein aggregates or organelles that are formed in response to various cellular stresses and disassemble rapidly with the decay of stresses[1].Under stressf...Dear Editor,Stress granules(SGs)are dynamic membraneless RNAprotein aggregates or organelles that are formed in response to various cellular stresses and disassemble rapidly with the decay of stresses[1].Under stressful conditions,protein translation is often inhibited suddenly.The resulting untranslated messenger ribonucleoproteins interact with the so-called"nucleator proteins"(such as G3BP1/2 and TIA1)to form the core structure of SGs,which then grow or merge into mature SGs by sequestering untranslated mRNAs and misfolded proteins[2,3].展开更多
With the advancement of the modernization of traditional Chinese medicine(TCM),TCM granules have emerged and garnered widespread attention.This study provides a comprehensive review of the development of TCM granules,...With the advancement of the modernization of traditional Chinese medicine(TCM),TCM granules have emerged and garnered widespread attention.This study provides a comprehensive review of the development of TCM granules,analyzing their characteristics in terms of ease of use,quality stability,and pharmacodynamic advantages.It also explores their broad application prospects in clinical TCM treatment and preventive healthcare.Through an integrative analysis of relevant research literature,the study highlights the significant value and vast development potential of TCM granules in modern medicine.The article aims to offer valuable references for the modernization and internationalization of TCM while promoting the continuous development and innovative application of TCM granules in the field of traditional Chinese medicine.展开更多
Jing Fang granules(JFG)are a modern Chinese medicinal formulation derived from Jing Fang Defeating Toxin San(JFDS).JFG primarily contains bioactive compounds such as flavonoids/flavonoid glycosides,coumarins and other...Jing Fang granules(JFG)are a modern Chinese medicinal formulation derived from Jing Fang Defeating Toxin San(JFDS).JFG primarily contains bioactive compounds such as flavonoids/flavonoid glycosides,coumarins and other components,which have various activities:anti-inflammatory,immune system regulation,antiviral,anti-aging,detoxification,and protection of the liver,lungs,and kidneys.JFG has broad potential therapeutic applications.The mechanisms of JFG’s actions are primarily associated with signaling pathways such as TLR4/NF-κB,PI3K/AKT,and MAPK.This article reviews the research progress on JFG,including chemical composition,pharmacologic effects,mechanism of action,safety,clinical application,etc.,serving as a foundation for future research and clinical applications.展开更多
Background:Fufang Muji Granules is a traditional Chinese medicine of the Manchu ethnic group and is thought to treat hepatitis and liver injury by inhibiting the elevation of alpha-fetoprotein.Methods:In this investig...Background:Fufang Muji Granules is a traditional Chinese medicine of the Manchu ethnic group and is thought to treat hepatitis and liver injury by inhibiting the elevation of alpha-fetoprotein.Methods:In this investigation,tandem mass tag(TMT)-based quantitative proteomics was performed to figure out the therapeutic mechanisms of Fufang Muji Granules on liver injury caused by carbon tetrachloride(CCl_(4))in rats.Results:Biochemical analyses(alanine aminotransferase;glutamate aminotransferase;aspartate aminotransferase)and histologic analyses(hematoxylin-eosin)demonstrated that FMG was effective in ameliorating liver injury.A sum of 6,208 proteins were identified and 2,475 proteins were determined as differential abundance proteins(DAPs)in rat liver treated with Fufang Muji Granules which compared to the model group.Bioinformatics analysis indicated that the DAPs are primarily enriched in multiple pathways such as rno00280(valine,leucine,and isoleucine degradation),rno00640(Propanoate metabolism),and rno00380(Tryptophan metabolism).Western blot was employed to validate the findings from the proteomic analysis.Conclusion:This study not only provides useful information on the mechanism of Fufang Muji Granules in the treatment of liver injury but also serves as a basis for further study of Fufang Muji Granules in vivo.展开更多
[Objectives]This study aims to establish the quality standard of Fuzheng Wangan granules.[Methods]The qualitative identification of Radix Bupleuri and Radix Paeoniae Alba was carried out by the thin layer chromatograp...[Objectives]This study aims to establish the quality standard of Fuzheng Wangan granules.[Methods]The qualitative identification of Radix Bupleuri and Radix Paeoniae Alba was carried out by the thin layer chromatography(TLC).The content of ginsenosides Rg1,Re and Rb was determined by the high performance liquid chromatography(HPLC).[Results]The spots of Radix Bupleuri and Radix Paeoniae Alba were clear,and the negative control had no interference.The total content of ginsenoside Rg1,Re and Rb ranged from 0.0762 to 0.0739 mg/g.[Conclusions]The method for the quality control of Fuzheng Wangan granules established in this study is stable and feasible.展开更多
BACKGROUND Owing to the absence of specific symptoms in early-stage gastric cancer,most patients are diagnosed at intermediate or advanced stages.As a result,treatment often shifts from surgery to other therapies,with...BACKGROUND Owing to the absence of specific symptoms in early-stage gastric cancer,most patients are diagnosed at intermediate or advanced stages.As a result,treatment often shifts from surgery to other therapies,with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment.A total of 116 patients with advanced gastric cancer,admitted from January 2021 to December 2023,were selected and divided into two groups of 58 each using the random number table method.The control group received FOLFOX4 chemothe-rapy(oxaliplatin+calcium+folinate+5-fluorouracil)combined with intravenous sindilizumab.The observation group received the same treatment as the control group,supplemented by oral administration of Senqi Shiyiwei granules.Both groups underwent treatment cycles of 3 weeks,with a minimum of two cycles.The therapeutic efficacy,immune mechanisms,and treatment-related toxicity and side effects were compared between the groups.The objective remission rate in the observation group(55.17%)was higher than that of the control group(36.21%)(P<0.05).After two treatment cycle,CD3+,CD4+,and CD4+/CD8+levels were higher in the observation group compared to the control group,while CD8+,regulatory T cells,and natural killer cells were lower(P<0.05).Additionally,the incidence of leukopenia,nausea,and vomiting was lower in observed group(P<0.05).No significant differences were observed in the incidence of other adverse reactions(P>0.05).CONCLUSION Adjuvant therapy with Shenqixian granules may enhance the efficacy of simudizumab combined with FOLFOX4 chemotherapy in advanced gastric cancer and the immune function by increasing immune cell counts,making it a valuable option in clinical treatment.展开更多
BACKGROUND Tic disorders(TDs)are a type of neurological and psychiatric disorder characterized by vocal or motor tics in the head,body,or limbs.Clinical studies have shown that Changmaxifeng granules(CG)can treat TDs....BACKGROUND Tic disorders(TDs)are a type of neurological and psychiatric disorder characterized by vocal or motor tics in the head,body,or limbs.Clinical studies have shown that Changmaxifeng granules(CG)can treat TDs.However,the pharmaceutical substances and mechanism of action of CG remain unclear.AIM To investigate the pharmaceutical substances and action mechanisms of CG against TDs,this study employs serum medicinal chemistry,network pharmacology,and molecular docking analysis.METHODS Ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry was used to identify the blood-absorbed constituents of CG;Network pharmacology was then used to integrate these compounds with disease targets,followed by protein-protein interaction(PPI)networks analysis to pinpoint key proteins.Finally,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses combined with molecular docking elucidated the underlying mechanism of action.RESULTS Overall,187 chemical components,including terpenoids,sugars,phenolic acids,and flavonoids,were identified in vitro.In addition,75 components,namely 49 prototype components and 26 metabolites,were identified in vivo.The PPI results revealed 225 overlapping targets,with TNF,IL-6,FOS,VEGFA,and ESR1 being the major targets.GO and KEGG analyses were performed to identify key signaling pathways and biological processes.Paeonol,evofolin B,aspalathin,and paeoniflorin were identified as potential pharmacodynamic substances based on the results of the“compound-target”network.The maximum binding energy between the core target and the active ingredient was less than-4.7 kcal/mol,indicating that the pharmacophore exhibited a strong affinity toward the core ingredient.CONCLUSION This study elucidated the in vitro and in vivo chemical components of CG and outlined their potential targets and action mechanisms.This study provides a basis for further research into the action mechanism and clinical application of CG.展开更多
A universal quantitative model was developed to determine the azithromycin content in granules using near infrared （NIR） diffuse reflectance spectroscopy. The diffuse reflection spectra were recorded with the integr...A universal quantitative model was developed to determine the azithromycin content in granules using near infrared （NIR） diffuse reflectance spectroscopy. The diffuse reflection spectra were recorded with the integrating sphere at 8 cm-1 resolution in 4000–12 000 cm-1 spectral range. During each measurement, 32 co-added scans were performed. This quantitative model was constructed with 103 batches of azithromycin granules from 21 different manufacturers. The azithromycin content ranges from 3.0% to 24.5%. The root mean square error of prediction （RMSEP） of model was 0.613. In addition, the quantitative model was evaluated in terms of specificity, linearity, accuracy, and precision according to ICH guidelines. In conclusion, it is feasible to construct a universal quantitative model for azithromycin granules by choosing suitable training set samples and selecting an appropriate wavelength range. The quantitative model could be applied in the quick assay of azithromycin granules produced by domestic manufacturers （content： 3.0%–24.5%）.展开更多
High strength aluminum alloy plate has a low elongation at room temperature, which leads to the forming of its components need a high temperature. Liquid or gas is used as the pressure-transfer medium in the existing ...High strength aluminum alloy plate has a low elongation at room temperature, which leads to the forming of its components need a high temperature. Liquid or gas is used as the pressure-transfer medium in the existing flexible mould forming process, the heat resistance of the medium and pressurizing device makes the application of aluminum alloy plate thermoforming restricted. To solve this problem, the existing medium is replaced by the heat-resisting solid granules and the general pressure equipments are applied. Based on the pressure-transfer performance test of the solid granules medium, the feasibility that the assumption of the extended Drucker-Prager linear model can be used in the finite element analysis is proved. The constitutive equation, the yield function and the theoretical forming limit diagram（FLD） of AA7075 sheet are established. Through the finite element numerical simulation of hot granules medium pressure forming（HGMF） process, not only the influence laws of the process parameters, such as forming temperature, the blank-holder gap and the diameter of the slab, on sheet metal forming performance are discussed, but also the broken area of the forming process is analyzed and predicted, which are coincided with the technological test. The conical part whose half cone angle is 15° and relative height H/d0 is 0.57, is formed in one process at 250℃. The HGMF process solves the problems of loading and seal in the existing flexible mould forming process and provides a novel technology for thermoforming of light alloy plate, such as magnesium alloy, aluminium alloy and titanium alloy.展开更多
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 proportio...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.展开更多
OBJECTIVE： This study aims to evaluate the bioactivity of five components of the traditional Chinese medicine complex prescription Jiangzhi granules against hepatocellular steatosis. METHODS： The five major componen...OBJECTIVE： This study aims to evaluate the bioactivity of five components of the traditional Chinese medicine complex prescription Jiangzhi granules against hepatocellular steatosis. METHODS： The five major components, including protopanaxadiol, tanshinone IIA, emodin, chlorogenic acid, and nuciferine, were extracted from Jiangzhi granules. Their cytotoxicity was assessed to determine the safe dose of each component for HepG2 cells. HepG2 cellular steatosis was induced using 1 mmol/L of free fatty acids （FFAs） for 24 h, and then treated with each component at high, intermediate, and low doses （500, 50, and 5 μmol/L）, respectively for another 24 h. The effects on HepG2 steatosis were observed directly under optical phase microscopy, or through oil red O staining and Nile red assays. In addition, the levels of reactive oxygen species （ROS） in the steatotic HepG2 cells with and without high-dose protopanaxadiol treatment were measured using fluorescent dye 2＇,7＇-dichlorodihydrofluorescein diacetate staining. RESULTS： No obvious cytotoxicity was observed in the HepG2 cells incubated with each of the five components at up to 500μmol/L. At 24 h after incubation with FFAs, the HepG2 cells swelled and many lipid droplets accumulated. The lipid content was attenuated after 24 h of incubation with protopanaxadiol, tanshinone IIA, and emodin at 500 or 50 μmol/L （P 〈 0.05）, especially with 500 μmol/L protopanaxadiol （P 〈 0.01）. In addition, the ROS level was elevated in steatotic cells, but decreased after intervention with 500μmol/L protopanaxadiol （P 〈 0.05）. CONCLUSION： Protopanaxadiol, tanshinone IIA, and emodin alleviate hepatocellular steatosis in a dose-dependent manner, and oxidative stress regulation may partially contribute to the effects of protopanaxadiol. ：展开更多
OBJECTIVE: To investigate the protective effects of Jiayan Kangtai(JYKT) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis(AIT), and the possible underlying mechanism.METHODS: Female Le...OBJECTIVE: To investigate the protective effects of Jiayan Kangtai(JYKT) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis(AIT), and the possible underlying mechanism.METHODS: Female Lewis rats(6-8 weeks) were randomly apportioned to 5 groups of 10, including a normal control. AIT was induced in the untreated AIT-model group, and rats treated subsequently with daily low, medium, or high dose JYKT granules. After 12 weeks, plasma levels of thyroid autoantibodies and morphological changes in the thyroid were detected by enzyme-linked immunosorbent assay and histological examination, respectively. The presence of interleukin(IL)-6,IL23 p19, and IL-2 in thyroid tissue was assessed by immunohistochemical staining. The percentages of T helper(Th)17 cells and regulatory T cells(Tregs) in the peripheral blood were analyzed by flow cytometry. Relevant levels of cytokines and proteins were examined via bead-based multiplex flow cytometry and ELISA, respectively. Expressions of genes and proteins regulated by Th17 cells and Tregs were shown by real-time PCR and Western blot.RESULTS: Compared to the control, AIT-model rats had higher plasma concentrations of thyroid autoantibodies. The high-dose JYKT rats showed significantly lower levels of thyroid autoantibodies compared with the AIT model group. Rats in the AIT-JYKT groups also had fewer thyroid lesions and less lymphocytic infiltration, a lower percentage of Th17 cells, and a higher percentage of Tregs, compared with the AIT-model. Rats given high-dose JYKT had a significantly lower Th17/Treg ratio compared with the AIT model. Differences in plasma cytokine concentrations and relevant gene and protein expressions in the spleens of JYKT-treated rats and the AIT group suggested an association between JYKT treatment and lower Th17 cell percentage and higher Treg activity.CONCLUSION: JYKT treatment appeared to be protective against AIT in rats, possibly via the regulation of the Th17 cell/Treg imbalance in AIT.展开更多
基金supported by a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center(to PKS)the Rutgers University Startup Fund(to PKS).
文摘Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.
基金supported by the National Key R&D Program of China(grant number 2023ZD0502206,2024YFB3213200,Topic No.2024YFB3213204)National Natural Science Foundation of China(nos.82273278,82373514,82373202,82272728,82002630,81772654)+5 种基金the National Key Research and Development Program of China(grant number 2022YFC2404602)Shanghai Hospital Development Center Foundation(grant number SHDC12023108)Scientific and Technological Innovation Action Plan of Shanghai Science and Technology Committee(grant number 22Y31900103)Beijing Science and Technology Innovation Medical Development Foundation(grant number KC2021-JX-0170-9)the Shanghai Association for Science and Technology(nos.201409003000,201409002400,20YF1426200)Shanghai Science and Technology Innovation Action Plan(grant number 23Y41900100).
文摘Osteosarcoma(OS)is the most frequent primary bone sarcomas with high recurrence and poor prognosis.Emerging evidence indicates that membraneless organelles stress granules(SGs),whose assemblies are driven by scaffold protein G3BP1,are extensively involved in tumor,especially in OS.However,how SGs behave and communicate with organelles,particularly nucleoli and mitochondria,during drug challenges remain unknown.This study revealed that chemotherapeutic drugs activated the cysteine protease asparagine endopeptidase(AEP)to specifically cleave the SG core protein G3BP1 at N258/N309 in OS and malignant glioma.tG3BP1-Ns modulated SG dynamics by competitively binding to full-length G3BP1.Strikingly,tG3BP1-Cs,containing a conserved RNA recognition motif CCUBSCUS,sequestered mRNAs of ribosomal proteins and oxidative phosphorylation genes in the nucleoli and mitochondria to repress translation and oxidative stress.Moreover,the inhibition of AEP promoted the tumor-suppressing effect of chemotherapeutic drugs,whereas AEP-cleaved G3BP1 rescue reversed the effect in both OS and glioma models.Cancerous tissues exhibited high levels of AEP and G3BP1 truncations,which were strongly associated with poor prognosis.
基金National Key Research and Development Project:Clinical Evaluation of the Interventional Techniques for Abdominal Obesity(No.2019YFC1710102)。
文摘OBJECTIVE:To assess the efficacy and safety of the Qingyanyin formulated granules(轻燕饮配方颗粒,QYY),press needles(PN),and their combined application in addressing abdominal obesity(AO).This trial aims to offer a more scientifically grounded therapeutic regimen for clinical interventions.METHODS:From March 2021 to July 2021,a multicenter,triple-blind,randomized 2×2 factorial design clinical trial was conducted across 7 centers in 4 major cities within China's mainland.The trial participants were patients diagnosed with AO.The trial followed a 1∶1∶1∶1 random allocation ratio,assigning participants to one of four groups:QYY placebo plus simulated press needles(SPN)(placebo+SPN),QYY plus SPN(QYY+SPN),QYY placebo plus PN(placebo+PN),and QYY plus PN(QYY+PN).The trial participants received treatment for 12 weeks.Observe the changes in waist circumference,body weight,body mass index(BMI),Beck Depression Inventory(BDI),Beck Anxiety Inventory(BAI)scores,and Pittsburgh Sleep Quality Index(PSQI)before and after treatment.RESULTS:The QYY+PN group exhibited significant improvements in waist circumference compared to placebo+PN[Difference=-1.59,95%CI(-3.03,-0.16)]and placebo+SPN groups[Difference=-2.01,95%CI(-3.46,-0.57)].QYY+PN demonstrated a significant advantage over placebo+SPN[Difference=-2.01,95%CI(-3.46,-0.57)],and no statistically significant interaction was observed between the two interventions(P>0.05).In terms of weight and BMI improvements,the QYY+PN,QYY+SPN,and the PN+placebo groups all experienced trending greater reductions in weight compared to the placebo group.In terms of the total scores of PSQI,BAI,and BDI,all four groups exhibited improvements compared to the baseline.Specifically,concerning the change in total PSQI scores,the QYY+PN group exhibited a greater reduction;Regarding the change in total BAI scores,the PN+placebo group demonstrated a greater decrease;As for the change in total BDI scores,the QYY+SPN group displayed a greater reduction.CONCLUSION:This study confirmed that QYY+PN can effectively reduce the waist circumference of patients with AO.Furthermore,the combined approach offers greater benefits than either treatment alone,all without any reported serious adverse events.
文摘Objective:To explore the clinical efficacy and safety of Naomaili granules in the treatment of acute ischemic stroke.Methods:Eighty-eight patients were randomly divided into a treatment group and a control group,with 44 patients in each group.The control group received conventional Western medicine treatment,while the treatment group was additionally administered Naomaili granules at 10g per time,3 times per day,for 20 days.Neurological function(NIHSS),activities of daily living(BI),inflammatory factors(hs-CRP,IL-6)levels,and adverse reactions were observed before and after treatment.Results:After 20 days of treatment,the NIHSS score of the treatment group decreased from(9.20±2.10)to(5.12±1.30),the BI index increased from(52.30±8.50)to(78.60±9.20),and hs-CRP and IL-6 decreased to(3.12±1.10)mg/L and(18.20±4.20)pg/mL,respectively,all significantly better than the control group(P<0.01).The incidence of adverse reactions in the treatment group was 4.55%,lower than the 15.91%in the control group(P<0.05).Conclusion:Naomaili granules can improve neurological function and living ability,reduce inflammatory response,and have good safety in patients with acute ischemic stroke.
基金Supported by the Open Bidding for Selecting the Best Candidates for Xin’an Medicine and the Modernization of Traditional Chinese Medicine of IHM,No.2023CXMMTCM024 and No.2023CXMMTCM003the Anhui University Collaborative Innovation Project,No.GXXT-2020-025+2 种基金the Scientific Research Project of Health and Wellness in Anhui Province,No.AHWJ2023BAc10002the Anhui Province New Era Education Quality Project,No.2023gjxslt014and the Clinical and Translational Research Project of Anhui Province,No.202427b10020046.
文摘BACKGROUND Prediabetes mellitus(PDM)is receiving increasing attention as a precursor to type 2 diabetes mellitus.Lifestyle and traditional Chinese medicine(TCM)inter-ventions are effective for PDM prevention and treatment.Therefore,we con-ducted a preliminary investigation and an exploratory randomised controlled trial to assess the effects of a combined lifestyle and TCM intervention on PDM indicators.AIM To study the effectiveness of Xiaokeqing granules(XQG)and lifestyle inter-ventions in PDM participants while using metabolomics to identify potential markers.METHODS Forty PDM participants with yin deficiency syndrome with excessive heat were recruited and randomly allocated to the control(Con)group or the XQG group(20 per group).The Con group underwent lifestyle interventions,whereas the XQG group underwent lifestyle and XQG interventions.The follow-up duration was 2 months.Fasting blood glucose,2-hour postprandial glucose(2hPG),gly-cated haemoglobin A1c,fasting insulin,homeostasis model assessment-insulin resistance levels,and serum metabolomics characteristics were compared via liquid chromatography-tandem mass spectrometry analysis.RESULTS There were significant differences in 2hPG between the two groups(P<0.05)in the intention-to-treat analysis and per-protocol analysis.The intervention method used in this study was safe(P>0.05).Groenlandicine,kaempferol,isomangiferin,etc.,are the XQG constituents absorbed in the blood.N-Nervonoyl methionine and 5-hydroxy-L-tryptophan are core potential metabolomic biomarkers for the effectiveness of XQG and lifestyle interventions.HTR1A,HTR2C,SLC6A4,etc.,are the core targets of XQG and lifestyle interventions,as well as the reason for their clinical efficacy.Possible mechanistic pathways include tryptophan metabolism,pantothenate and certificate of analysis biosynthesis,lysine degradation and biosynthesis of cofactors.CONCLUSION This pilot study provides evidence that a combined XQG and lifestyle intervention can improve 2hPG in par-ticipants with PDM.The mechanism of action is related to multiple constituents,targets and pathways.
基金funded by the National Key Research and Development Plan of the Traditional Chinese Medicine Modernization Research Key Project(2018YFC1706800).
文摘Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-blind,placebo-controlled trial was conducted at the Third Central Hospital of Tianjin,China from March to December 2023.A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days.Efficacy was assessed through measures such as the total melasma area,reduced melasma area,reduction rate of melasma area,melasma color score,Melasma Area and Severity Index(MASI)score,and traditional Chinese medicine(TCM)symptom score scale.Safety assessments included routine blood and biochemical tests.Results:Participants in both groups were aged 52-63 years,with no significant differences.After the 2-month intervention,the total melasma area decreased in both groups;however,a greater reduction was observed in the test group[462.50 mm^(2)(12.81%)vs.100.00 mm2(3.11%),P<.001].Moreover,LDBG treatment significantly reduced the MASI and melasma color scores in the test group(P<.05).The total TCM symptom evaluation score significantly decreased(test group:6.00 vs.placebo group:7.00,P=.001),with significant relief in symptoms such as improvement in dark lips,nails,and waist soreness in the test group,compared with that in the placebo group(P<.05).Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group(P<.05).Conclusion:LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.
基金Supported by the Changsha Science and Technology Major Project,No.kh2205035the Hunan Traditional Chinese Medicine Science and Technology Project,No.2021061the Natural Science Foundation of Hunan Province,No.2025JJ80080。
文摘BACKGROUND Injury to the glomerular filtration barrier causes diabetic kidney disease(DKD),and glomerular endothelial-mesenchymal transition damages the filtration barrier of glomerular endothelial cells.Shenfushu granules(SFSGs)can treat chronic renal failure;however,their role and mechanism in DKD remain unclear.AIM To investigate the role of SFSGs in delaying DKD progression and their underlying mechanism in a streptozotocin-induced DKD mouse model.METHODS The microalbumin content in the urine and the blood glucose,creatinine,and blood urea nitrogen levels in the serum were measured.The expression and distribution ofα-smooth muscle actin(α-SMA),heparan sulfate(HS)and cluster of differentiation(CD)31 were observed through immunofluorescence or immunohistochemistry.Western blotting was conducted to measure the expression of CD31,α-SMA,PIK3R1,protein kinase B(AKT),phospho-PIK3R1,phospho-AKT,and heparanase-1.Network pharmacology was conducted to screen and identify the core components and targets of SFSGs.Molecular docking and dynamic simulations were performed to evaluate the binding ability of the core components of SFSGs to their core targets.RESULTS Compared with those in the model group,the 24-hour microalbuminuria(188.2±20.1 and 140.4±24.7 vs 323.2±44.4),serum creatinine(79.4±2.6 and 68.7±6.0 vs 110.2±4.8),blood urea nitrogen(14.4±1.1 and 13.1±0.5 vs 19.5±1.1),and renal index(20.3±1.0 and 19.6±0.8 vs 25.3±1.7)were significantly lower in the SFSGs(2.08 and 4.16 g/kg/day extract)-treated DKD mice.SFSGs inhibited the down regulation of CD31 and the upregulation ofα-SMA in the glomerular endothelial cells of DKD mice.Additionally,SFSGs suppressed the decrease in glycocalyx thickness and the expression of its component HS.Network pharmacology revealed that PIK3R1 was the core target of SFSGs.SFSGs markedly downregulate the expression of phospho-PIK3R1,phospho-AKT,and heparanase-1.However,the PIK3R1 agonist abolished the regulatory effect of SFSGs on the expression of CD31,α-SMA,and heparanase-1.CONCLUSION Collectively,these results suggest that SFSGs can significantly delay DKD progression and inhibit injury to the glycocalyx and the endothelial-mesenchymal transition of glomerular endothelial cells.This mechanism is related to PIK3R1/AKT/heparanase-1 signaling pathway regulation.
基金supported by the National Natural Science Foundation of China(32394032 and 82371402)Postdoctoral Fellowship Program of China(GZC20242295)+1 种基金the Natural Science Foundation of Shaanxi Province(2025SF-YBXM-393)the Military Medical Promoting Project of FMMU(2021JSTS27).
文摘Dear Editor,Stress granules(SGs)are dynamic membraneless RNAprotein aggregates or organelles that are formed in response to various cellular stresses and disassemble rapidly with the decay of stresses[1].Under stressful conditions,protein translation is often inhibited suddenly.The resulting untranslated messenger ribonucleoproteins interact with the so-called"nucleator proteins"(such as G3BP1/2 and TIA1)to form the core structure of SGs,which then grow or merge into mature SGs by sequestering untranslated mRNAs and misfolded proteins[2,3].
文摘With the advancement of the modernization of traditional Chinese medicine(TCM),TCM granules have emerged and garnered widespread attention.This study provides a comprehensive review of the development of TCM granules,analyzing their characteristics in terms of ease of use,quality stability,and pharmacodynamic advantages.It also explores their broad application prospects in clinical TCM treatment and preventive healthcare.Through an integrative analysis of relevant research literature,the study highlights the significant value and vast development potential of TCM granules in modern medicine.The article aims to offer valuable references for the modernization and internationalization of TCM while promoting the continuous development and innovative application of TCM granules in the field of traditional Chinese medicine.
基金supported by the Key R&D Program of Shandong Province,China(No.2024TZXD067,2022SFGC0105)Natural Science Foundation of Shandong Province(No.ZR2023QB021)+2 种基金Young Taishan Scholarship to Xuekui Xia(No.tsqn202103100)Jinan Talent Project for Universities(No.2021GXRC062,202228088)Key innovation Project and Science,Education and Industry Integration Innovation Pilot Project of Qilu University of Technology(Shandong Academy of Sciences)(No.2022JBZ01-06,2024ZDZX03,2023RCKY214).
文摘Jing Fang granules(JFG)are a modern Chinese medicinal formulation derived from Jing Fang Defeating Toxin San(JFDS).JFG primarily contains bioactive compounds such as flavonoids/flavonoid glycosides,coumarins and other components,which have various activities:anti-inflammatory,immune system regulation,antiviral,anti-aging,detoxification,and protection of the liver,lungs,and kidneys.JFG has broad potential therapeutic applications.The mechanisms of JFG’s actions are primarily associated with signaling pathways such as TLR4/NF-κB,PI3K/AKT,and MAPK.This article reviews the research progress on JFG,including chemical composition,pharmacologic effects,mechanism of action,safety,clinical application,etc.,serving as a foundation for future research and clinical applications.
基金National Natural Science Foundation of China(82104532 and 82173913)Joint Program(Applied Basic Research Project)of Liaoning Provincial Science and Technology Program(2023JH2/101700074)+1 种基金High-level Talent Innovation Support Program of Dalian(2021RD10)Fundamental Research Funds for the Central Universities(2023-SWGC-0101)。
文摘Background:Fufang Muji Granules is a traditional Chinese medicine of the Manchu ethnic group and is thought to treat hepatitis and liver injury by inhibiting the elevation of alpha-fetoprotein.Methods:In this investigation,tandem mass tag(TMT)-based quantitative proteomics was performed to figure out the therapeutic mechanisms of Fufang Muji Granules on liver injury caused by carbon tetrachloride(CCl_(4))in rats.Results:Biochemical analyses(alanine aminotransferase;glutamate aminotransferase;aspartate aminotransferase)and histologic analyses(hematoxylin-eosin)demonstrated that FMG was effective in ameliorating liver injury.A sum of 6,208 proteins were identified and 2,475 proteins were determined as differential abundance proteins(DAPs)in rat liver treated with Fufang Muji Granules which compared to the model group.Bioinformatics analysis indicated that the DAPs are primarily enriched in multiple pathways such as rno00280(valine,leucine,and isoleucine degradation),rno00640(Propanoate metabolism),and rno00380(Tryptophan metabolism).Western blot was employed to validate the findings from the proteomic analysis.Conclusion:This study not only provides useful information on the mechanism of Fufang Muji Granules in the treatment of liver injury but also serves as a basis for further study of Fufang Muji Granules in vivo.
基金Supported by the Project for the Development and Promotion of Appropriate Technology of Traditional Chinese Medicine in Guangxi(GZSY2024017).
文摘[Objectives]This study aims to establish the quality standard of Fuzheng Wangan granules.[Methods]The qualitative identification of Radix Bupleuri and Radix Paeoniae Alba was carried out by the thin layer chromatography(TLC).The content of ginsenosides Rg1,Re and Rb was determined by the high performance liquid chromatography(HPLC).[Results]The spots of Radix Bupleuri and Radix Paeoniae Alba were clear,and the negative control had no interference.The total content of ginsenoside Rg1,Re and Rb ranged from 0.0762 to 0.0739 mg/g.[Conclusions]The method for the quality control of Fuzheng Wangan granules established in this study is stable and feasible.
文摘BACKGROUND Owing to the absence of specific symptoms in early-stage gastric cancer,most patients are diagnosed at intermediate or advanced stages.As a result,treatment often shifts from surgery to other therapies,with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment.A total of 116 patients with advanced gastric cancer,admitted from January 2021 to December 2023,were selected and divided into two groups of 58 each using the random number table method.The control group received FOLFOX4 chemothe-rapy(oxaliplatin+calcium+folinate+5-fluorouracil)combined with intravenous sindilizumab.The observation group received the same treatment as the control group,supplemented by oral administration of Senqi Shiyiwei granules.Both groups underwent treatment cycles of 3 weeks,with a minimum of two cycles.The therapeutic efficacy,immune mechanisms,and treatment-related toxicity and side effects were compared between the groups.The objective remission rate in the observation group(55.17%)was higher than that of the control group(36.21%)(P<0.05).After two treatment cycle,CD3+,CD4+,and CD4+/CD8+levels were higher in the observation group compared to the control group,while CD8+,regulatory T cells,and natural killer cells were lower(P<0.05).Additionally,the incidence of leukopenia,nausea,and vomiting was lower in observed group(P<0.05).No significant differences were observed in the incidence of other adverse reactions(P>0.05).CONCLUSION Adjuvant therapy with Shenqixian granules may enhance the efficacy of simudizumab combined with FOLFOX4 chemotherapy in advanced gastric cancer and the immune function by increasing immune cell counts,making it a valuable option in clinical treatment.
基金Supported by Key Research and Development Plan Project of Heilongjiang Province,No.2022ZX02C08Heilongjiang Science and Technology Talent Spring Swallow Support Program Project,No.CYCX240092025 Graduate Innovation Research Funding Project of Harbin University of Commerce,No.YJSCX2025-833HSD。
文摘BACKGROUND Tic disorders(TDs)are a type of neurological and psychiatric disorder characterized by vocal or motor tics in the head,body,or limbs.Clinical studies have shown that Changmaxifeng granules(CG)can treat TDs.However,the pharmaceutical substances and mechanism of action of CG remain unclear.AIM To investigate the pharmaceutical substances and action mechanisms of CG against TDs,this study employs serum medicinal chemistry,network pharmacology,and molecular docking analysis.METHODS Ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry was used to identify the blood-absorbed constituents of CG;Network pharmacology was then used to integrate these compounds with disease targets,followed by protein-protein interaction(PPI)networks analysis to pinpoint key proteins.Finally,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses combined with molecular docking elucidated the underlying mechanism of action.RESULTS Overall,187 chemical components,including terpenoids,sugars,phenolic acids,and flavonoids,were identified in vitro.In addition,75 components,namely 49 prototype components and 26 metabolites,were identified in vivo.The PPI results revealed 225 overlapping targets,with TNF,IL-6,FOS,VEGFA,and ESR1 being the major targets.GO and KEGG analyses were performed to identify key signaling pathways and biological processes.Paeonol,evofolin B,aspalathin,and paeoniflorin were identified as potential pharmacodynamic substances based on the results of the“compound-target”network.The maximum binding energy between the core target and the active ingredient was less than-4.7 kcal/mol,indicating that the pharmacophore exhibited a strong affinity toward the core ingredient.CONCLUSION This study elucidated the in vitro and in vivo chemical components of CG and outlined their potential targets and action mechanisms.This study provides a basis for further research into the action mechanism and clinical application of CG.
基金National Science and Technology Major Project of the Ministry of Science and Technology of China (Grant No.2010ZX09401-403)
文摘A universal quantitative model was developed to determine the azithromycin content in granules using near infrared （NIR） diffuse reflectance spectroscopy. The diffuse reflection spectra were recorded with the integrating sphere at 8 cm-1 resolution in 4000–12 000 cm-1 spectral range. During each measurement, 32 co-added scans were performed. This quantitative model was constructed with 103 batches of azithromycin granules from 21 different manufacturers. The azithromycin content ranges from 3.0% to 24.5%. The root mean square error of prediction （RMSEP） of model was 0.613. In addition, the quantitative model was evaluated in terms of specificity, linearity, accuracy, and precision according to ICH guidelines. In conclusion, it is feasible to construct a universal quantitative model for azithromycin granules by choosing suitable training set samples and selecting an appropriate wavelength range. The quantitative model could be applied in the quick assay of azithromycin granules produced by domestic manufacturers （content： 3.0%–24.5%）.
基金Supported by National Natural Science Foundation of China(Grant Nos.51305386,51305385)Hebei Provincial Natural Science Foundation of China(Grant No.E2013203093)
文摘High strength aluminum alloy plate has a low elongation at room temperature, which leads to the forming of its components need a high temperature. Liquid or gas is used as the pressure-transfer medium in the existing flexible mould forming process, the heat resistance of the medium and pressurizing device makes the application of aluminum alloy plate thermoforming restricted. To solve this problem, the existing medium is replaced by the heat-resisting solid granules and the general pressure equipments are applied. Based on the pressure-transfer performance test of the solid granules medium, the feasibility that the assumption of the extended Drucker-Prager linear model can be used in the finite element analysis is proved. The constitutive equation, the yield function and the theoretical forming limit diagram（FLD） of AA7075 sheet are established. Through the finite element numerical simulation of hot granules medium pressure forming（HGMF） process, not only the influence laws of the process parameters, such as forming temperature, the blank-holder gap and the diameter of the slab, on sheet metal forming performance are discussed, but also the broken area of the forming process is analyzed and predicted, which are coincided with the technological test. The conical part whose half cone angle is 15° and relative height H/d0 is 0.57, is formed in one process at 250℃. The HGMF process solves the problems of loading and seal in the existing flexible mould forming process and provides a novel technology for thermoforming of light alloy plate, such as magnesium alloy, aluminium alloy and titanium alloy.
基金National New Drug Innovation Program,No.2017ZX09304003Special Research on Modernization of Traditional Chinese Medicine in the National Key Research and Development Program in the 13th Five-Year Plan Demonstrative Research,No.2017YFC1703703.Institutional review board statement:This study was approved by the IRB of Xiyuan Hospital of China Academy of Chinese Medical Sciences(No.2016XL011).
文摘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.
基金supported by Natural Science Foundation of Shanghai (No. 11ZR1436900)Leading Academic Discipline Project, Shanghai Municipal Education Commission (No. J50305 & E03008)+1 种基金Innovation Program of Shanghai Municipal Education Commission(No. 12ZZ119)Budget Research Program of Shanghai Municipal Education Commission (No. 2010JW35)
文摘OBJECTIVE： This study aims to evaluate the bioactivity of five components of the traditional Chinese medicine complex prescription Jiangzhi granules against hepatocellular steatosis. METHODS： The five major components, including protopanaxadiol, tanshinone IIA, emodin, chlorogenic acid, and nuciferine, were extracted from Jiangzhi granules. Their cytotoxicity was assessed to determine the safe dose of each component for HepG2 cells. HepG2 cellular steatosis was induced using 1 mmol/L of free fatty acids （FFAs） for 24 h, and then treated with each component at high, intermediate, and low doses （500, 50, and 5 μmol/L）, respectively for another 24 h. The effects on HepG2 steatosis were observed directly under optical phase microscopy, or through oil red O staining and Nile red assays. In addition, the levels of reactive oxygen species （ROS） in the steatotic HepG2 cells with and without high-dose protopanaxadiol treatment were measured using fluorescent dye 2＇,7＇-dichlorodihydrofluorescein diacetate staining. RESULTS： No obvious cytotoxicity was observed in the HepG2 cells incubated with each of the five components at up to 500μmol/L. At 24 h after incubation with FFAs, the HepG2 cells swelled and many lipid droplets accumulated. The lipid content was attenuated after 24 h of incubation with protopanaxadiol, tanshinone IIA, and emodin at 500 or 50 μmol/L （P 〈 0.05）, especially with 500 μmol/L protopanaxadiol （P 〈 0.01）. In addition, the ROS level was elevated in steatotic cells, but decreased after intervention with 500μmol/L protopanaxadiol （P 〈 0.05）. CONCLUSION： Protopanaxadiol, tanshinone IIA, and emodin alleviate hepatocellular steatosis in a dose-dependent manner, and oxidative stress regulation may partially contribute to the effects of protopanaxadiol. ：
基金Supported by the International Science and Technology Cooperation Project(No.2015DFA309010):Screening technology and formula optimization on traditional Chinese medicine intervention in Hashimoto's thyroiditis
文摘OBJECTIVE: To investigate the protective effects of Jiayan Kangtai(JYKT) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis(AIT), and the possible underlying mechanism.METHODS: Female Lewis rats(6-8 weeks) were randomly apportioned to 5 groups of 10, including a normal control. AIT was induced in the untreated AIT-model group, and rats treated subsequently with daily low, medium, or high dose JYKT granules. After 12 weeks, plasma levels of thyroid autoantibodies and morphological changes in the thyroid were detected by enzyme-linked immunosorbent assay and histological examination, respectively. The presence of interleukin(IL)-6,IL23 p19, and IL-2 in thyroid tissue was assessed by immunohistochemical staining. The percentages of T helper(Th)17 cells and regulatory T cells(Tregs) in the peripheral blood were analyzed by flow cytometry. Relevant levels of cytokines and proteins were examined via bead-based multiplex flow cytometry and ELISA, respectively. Expressions of genes and proteins regulated by Th17 cells and Tregs were shown by real-time PCR and Western blot.RESULTS: Compared to the control, AIT-model rats had higher plasma concentrations of thyroid autoantibodies. The high-dose JYKT rats showed significantly lower levels of thyroid autoantibodies compared with the AIT model group. Rats in the AIT-JYKT groups also had fewer thyroid lesions and less lymphocytic infiltration, a lower percentage of Th17 cells, and a higher percentage of Tregs, compared with the AIT-model. Rats given high-dose JYKT had a significantly lower Th17/Treg ratio compared with the AIT model. Differences in plasma cytokine concentrations and relevant gene and protein expressions in the spleens of JYKT-treated rats and the AIT group suggested an association between JYKT treatment and lower Th17 cell percentage and higher Treg activity.CONCLUSION: JYKT treatment appeared to be protective against AIT in rats, possibly via the regulation of the Th17 cell/Treg imbalance in AIT.
