Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

Thin Layer Identification of Jiedu Shengxue Granules and Determination of Notoginsenoside R1 Content

[Objectives]To establish the quality standard of hospital preparation Jiedu Shengxue granules.[Methods]Scleromitrion diffusum and Prunella vulgaris in Jiedu Shengxue granules were qualitatively identified by thin layer chromatography(TLC).A high performance liquid chromatography(HPLC)was established to determine the content of notoginsenoside R1 in the granule.[Results]The traditional Chinese medicinal materials in Jiedu Shengxue granules could be identified by TLC,and the characteristic spots were stable and clear.Notoginsenoside R1 had a good linear relationship in the range of 10.45-104.5μg/mL,with an average recovery of 98.52%and RSD=2.36%.[Conclusions]TLC and HPLC,as the quality control methods of Jiedu Shengxue granules,have high accuracy and good repeatability,which lays a foundation for the quality control of this mixture.

Effect of Jianpi Wenshen Granules on the Nutritional Control Status Score in Elderly Patients Undergoing Maintenance Hemodialysis

Objective:To explore the effect of Jianpi Wenshen Granules on the Controlling Nutritional Status(CONUT)score in elderly patients undergoing maintenance hemodialysis.Methods:Seventy elderly outpatients undergoing maintenance hemodialysis from January 2023 to January 2024 at the Blood Purification Centers of Taizhou Traditional Chinese Medicine Hospital and Taizhou Second People’s Hospital were selected as the study subjects.The patients were randomly divided into two groups:the study group and the control group,with 35 patients in each group.Both groups received maintenance hemodialysis,while the control group received only conventional Western medicine treatment,and the study group was additionally treated with Jianpi Wenshen Granules.The changes in biochemical and inflammatory markers before and after treatment were compared between the two groups.The nutritional status of the patients was assessed using the Controlling Nutritional Status(CONUT)score,and detailed statistics were gathered on anemia and albumin levels in both groups.Results:After treatment,the CONUT score in the study group significantly decreased compared to the control group,showing a significant correlation(P<0.05).Albumin and hemoglobin levels significantly increased,with a notable difference(P<0.05).There were no significant differences in alanine aminotransferase and aspartate aminotransferase levels between the two groups before and after treatment(P>0.05).Conclusion:In elderly patients undergoing maintenance hemodialysis,Jianpi Wenshen Granules improve the CONUT score and enhance nutritional status,demonstrating potential for clinical application and promotion.

Analysis of the Effectiveness of Biling Weitong Granules Combined with Trimethoprim and Vonoprazan in The Treatment of Reflux Esophagitis

Objective:To analyze the effectiveness of Biling Weitong Granules(BLWTG)combined with trimethoprim and vonoprazan in treating reflux esophagitis.Methods:Sixty patients with reflux esophagitis admitted to our hospital from March 2020 to March 2023 were selected as study subjects and randomly divided into a control group and an experimental group,with 30 cases in each group.The control group received only the combination treatment of trimethoprim and vonoprazan,while the experimental group was treated with BLWTG based on the control group.The acid reflux and heartburn symptom scores,quality-of-life scores,clinical efficacy,Chinese medicine symptom incidences,and the occurrence of adverse reactions before and after treatment in the two groups were compared.Results:After treatment,the acid reflux and heartburn symptom scores of patients in the experimental group were lower than those of the treatment control group,and the quality-of-life scores were higher than those of the treatment control group(P<0.05).The total clinical efficacy of the experimental group was 96.66%,which was significantly higher than that of the control group(73.33%,P<0.05).After treatment,the incidence of Chinese medicine symptoms,such as nausea and vomiting,abdominal distension and abdominal pain,and loss of appetite of the patients in the experimental group were significantly lower than those of the control group(P<0.05).During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,which indicated that the safety of the two treatments was comparable(P>0.05).Conclusion:BLWTG combined with trimethoprim and vonoprazan was safe and reliable in treating reflux esophagitis,effectively relieving the symptoms and improving its clinical efficacy.This treatment is worthy of popularization.

The Therapeutic Effect of Biling Weitong Granules Combined with Oryz-Aspergillus Enzyme and Pancreatin Tablet on Reflux Esophagitis with Functional Dyspepsia

Objective:To investigate the therapeutic effect of Biling Weitong Granules combined with oryz-aspergillus enzyme and pancreatin tablets on patients with reflux esophagitis with functional dyspepsia.Methods:Sixty patients diagnosed with reflux esophagitis with functional dyspepsia who were admitted to the Affiliated Hospital of Hebei University between June 2020 and June 2023 were selected and divided into two groups:the control group and the observation group,each consisting of 30 cases.The control group received oryz-aspergillus enzyme and pancreatin tablets only,while the observation group received Biling Weitong Granules in addition to the tablets.The clinical efficacy,Chinese medicine syndrome points,esophageal kinetic indexes,gastrointestinal hormone levels,and therapeutic safety of both groups were evaluated.Results:The total efficiency of the observation group reached 93.33%,significantly higher than the 73.33%of the control group(P<0.05).After treatment,patients in the observation group exhibited significantly lower scores for Chinese medicine symptoms such as early satiety,belching,abdominal distension,abdominal pain,and loss of appetite compared to the control group(P<0.05).Furthermore,the observation group showed significantly higher upper esophageal sphincter pressure,lower esophageal sphincter pressure,and distal esophageal contraction scores compared to the control group(P<0.05).Additionally,levels of gastric motility hormone,vasoactive intestinal peptide,and gastrin were significantly higher in the observation group compared to the control group(P<0.05).Throughout the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,indicating comparable safety of the two treatment modalities(P>0.05).Conclusion:The combination of Biling Weitong Granules with oryz-aspergillus enzyme and pancreatin tablets demonstrates significant efficacy in the treatment of reflux esophagitis with functional dyspepsia,with a better safety profile.This finding warrants further clinical promotion.

Hepatocellular carcinoma:An analysis of the expression status of stress granules and their prognostic value

BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in HCC.METHODS The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical information.Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,respectively.The prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software package.Nomogram models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction accuracy.RESULTS We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score model.The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort.Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological processes.CONCLUSION Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

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.

To explore the mechanism of Fuyang Jiebiao granules against viral pneumonia based on network pharmacology and pharmacodynamics

Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.

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.

Network pharmacology investigation of the mechanism underlying the therapeutic action of Shikang granules in retinal ischemia-reperfusion injuries

Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations commonly used in clinical practice for treating optic atrophy.Methods:Despite decades of clinical use,the precise mechanism of action(MoA)of SKG remains elusive.Here,we employ a network pharmacological approach to elucidate its MoA by identifying active ingredients and relevant targets using the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform.Targets associated with retinal I/R injury were sourced from GeneCards,Online Mendelian Inheritance in Man,and DisGeNET.Venny software facilitated the identification of intersecting targets,which were then subjected to gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.To validate the protective effect and explore the MoA of SKG in retinal I/R injuries,we conducted experiments using rat models.Results:Our animal experiments demonstrated that SKG mitigated apoptosis following retinal I/R injury by upregulating the expression of the anti-apoptotic protein Bcl-2 and downregulating the expression of BAX,Caspase-9,Caspase-3,PARP,and cytochrome C.Additionally,SKG was found to increase the expression of PI3K and AKT.Conclusions:SKG may exert its protective effects by inhibiting apoptosis through modulation of pro-apoptotic and anti-apoptotic protein expression,as well as activation of the PI3K/AKT pathway.

Multicenter Clinical Randomized Controlled Trial and Network Pharmacology Analysis of Zhenzhu Qingyuan Granules for the Treatment of Gastroesophageal Reflux Disease

Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network pharmacology.Methods Patients with gastroesophageal reflux disease(GERD)of liver–stomach stagnant heat pattern who met the inclusion and exclusion criteria were randomly divided into the control group and the observation group.The control group received oral rabeprazole,whereas the observation group were given Zhenzhu Qingyuan Granules in addition to the rabeprazole.The treatment duration was 8 weeks.Clinical efficacy was observed in both groups after 8 weeks.Network pharmacology was used to analyze the action targets of ZhenzhuQingyuanGranules and the genes related to GERD,and core targets were inferred.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential mechanisms of this formula.Results The clinical research results showed that the total effective rate in the treatment group was 92.68%,compared with 70.00%in the control group,with a statistically significant difference(p<0.05).After treatment,both Chinese medicine syndrome score and endoscopic score improved in both groups compared with before treatment(p<0.05),and the treatment group showed greater improvement than the control group(p<0.05).Network pharmacology identified effective components of Zhenzhu Qingyuan Granules for treating GERD,including quercetin,luteolin,andβ-sitosterol,with potential action targets such as tumor protein 53(TP53),protein kinase B(AKT1),and tumor necrosis factor.Conclusion Zhenzhu Qingyuan Granules can significantly improve clinical symptoms in patients with GERD of liver–stomach stagnated heat pattern,enhance clinical efficacy,and have high safety.This formula may exert therapeutic effects through multiple targets and pathways.

Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Quality Standard of Fuyang Wenshen Granules

[Objectives]To establish the quality standard of Fuyang Wenshen Granules and carry out the routine examination of granule type.[Methods]The particle size,water content,solubility,loading difference and microbial limit of Fuyang Wenshen Granules were examined,and TLC was used for qualitative identification of Astmgali Radix and Notoginseng Radix Et Rhizoma.[Results]The particle size,water content,solubility,loading difference,and microbial limit of Fuyang Wenshen Granules complied with the relevant provisions of the Pharmacopoeia of the People's Republic of China(2020).The TLC spots of Astmgali Radix and Notoginseng Radix Et Rhizoma were clearly colored,and negative had no interference.[Conclusions]The method was simple,accurate,reliable,specific and reproducible,and can effectively control the quality of Fuyang Wenshen Granules.

Quality Standard Research of Shenqi Qiangjing Granules

[Objectives]The paper was to establish the quality standard of Shenqi Qiangjing granules and to conduct routine inspection of granular dosage forms.[Methods]The particle size,moisture,loss on drying,dissolubility,content uniformity and microbial limit of Shenqi Qiangjing granules were detected.Radix Astragali,Herba Epimedii,Radix Dipsaci and Fructus Schisandrae Chinensis were qualitatively identified by thin layer chromatography(TLC).[Results]The particle size,moisture,loss on drying,dissolubility,content uniformity and microbial limit of Shenqi Qiangjing granules were all in line with the relevant regulations of Pharmacopoeia of the People's Republic of China(2020 edition).Radix Astragali,Herba Epimedii,Radix Dipsaci and Fructus Schisandrae Chinensis had clear fluorescent spots in TLC assay,and no such spots were found in negative control.[Conclusions]The method has the advantages of simple operation,accurate and reliable results,strong specificity and good repeatability,and can effectively control the quality of Shenqi Qiangjing granules.

Determination of Total Lignanoids in Tangjiangshenkang Granules by Two-Wavelength Ultraviolet Spectrophotometry

[Objectives] To establish a determination method for the content of total lignanoids in Tangjiangshenkang granules. [Methods] Two-wavelength ultraviolet spectrophotometry (TWBS) was used to scan arctiin control solution, chlorogenic acid control solution and Tangjiangshenkang granule test solution in the range of 200-400 nm. In the ultraviolet scanning diagram of arctiin reference solution, the maximum absorption wavelength of 280 nm was determined as the determination wavelength λ 1, the detection wavelength in the ultraviolet scanning diagram of chlorogenic acid reference solution ( λ 1=280 nm) was determined, and 350 nm was the reference wavelength λ 2;the content of total lignosides in Tangjiangshenkang granules was determined with arctiin as the reference substance. [Results] The precision, accuracy, and durability of this method were fine. The concentration of arctiin was linearly correlated with the absorbance difference in the range of 0.007 95-0.071 55 mg/mL ( r =0. 999 9). The average recovery of arctiin was 100.8%, and the RSD value was 1.04% ( n =6). Calculated as arctiin, three batches of Tangjiangshenkang granules contain no less than 20% of total lignosides. [Conclusions] The method has the advantages of simple operation, good accuracy, precision and reliable stability. It can be used as the content determination and quality control method of total lignosides in Tangjiangshenkang granules.

基于SAT的GRANULE算法不可能差分分析

基于布尔可满足性问题(SAT)的自动化搜索方法可以直接刻画与、或、非、异或等逻辑运算,从而建立更高效的搜索模型。为更高效地评估GRANULE算法抵抗不可能差分攻击的能力,首先,基于S盒差分分布表性质优化S盒差分性质刻画的SAT模型;其次,对GRANULE算法建立基于比特的不可能差分区分器的SAT模型,通过求解模型得到多条10轮GRANULE算法的不可能差分区分器;再次,针对不可能差分区分器,给出改进的SAT自动化验证方法并验证;最后,将得到的区分器往前和往后各扩展3轮,对GRANULE-64/80算法发起16轮的不可能差分攻击,通过该攻击可以恢复80比特主密钥,时间复杂度为251.8次16轮加密,数据复杂度为241.8个选择明文。与表现次优的对GRANULE算法不可能差分分析的方法相比,所得到的区分器轮数和密钥恢复攻击轮数都提高了3轮,且时间复杂度、数据复杂度都进一步下降。

Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure

BACKGROUND Stress granules(SGs)could be formed under different stimulation to inhibit cell injury.AIM To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure(ALF)by reducing endoplasmic reticulum stress(ERS)mediated apoptosis.METHODS The agonist of SGs,arsenite(Ars)was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models.Further,the siRNA of activating transcription factor 4(ATF4)and SGs inhibitor anisomycin was then used to intervene in cell models.RESULTS With the increase of hypoxia time from 4 h to 12 h,the levels of HIF-1α,ERS and apoptosis gradually increased,and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased.Compared with the hypoxia cell model group and ALF mice model,the levels of HIF-1α,apoptosis and ERS were increased in the Ars intervention group.After siRNA-ATF4 intervention,the level of SGs in cells increased,and the levels of HIF-1α,ERS and apoptosis decreased.Compared with the siRNA-ATF4 group,the levels of G3BP1 in the siRNAATF4+anisomycin group were decreased,and the levels of HIF-1α,ERS and apoptosis were increased.Moreover,compared with the ALF group,the degree of liver injury and liver function,the levels of HIF-1α,ERS and apoptosis in the Ars intervention group were decreased,the level of SGs was increased.CONCLUSION SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERSmediated apoptosis.

Possible mechanisms associated with immune escape and apoptosis on anti-hepatocellular carcinoma effect of Mu Ji Fang granules

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common digestive system cancers with high mortality rates worldwide.The main ingredients in Mu Ji Fang Granules(MJF)are alkaloids,flavonoids,and polysaccharides.MJF has been used in the clinical treatment of hepatitis,cirrhosis and HCC for more than 30 years.Few previous studies have focused on the mechanism of MJF on tumor immunology in the treatment of HCC.AIM To explore the mechanism of action of MJF on tumor immunology in the treatment of HCC.METHODS The absorbable ingredients of MJF were identified using Molecule Network related to High Performance Liquid Chromatography-Electron Spray Ionization-Time of Flight-Mass Spectrometry,and hub potential anti-HCC targets were screened using network pharmacology and pathway enrichment analysis.Forty male mice were randomly divided into the Blank,Model,and MJF groups(1.8,5.4,and 10.8 g/kg/d)following 7 d of oral administration.Average body weight gain,spleen and thymus indices were calculated,tumor tissues were stained with hematoxylin and eosin,and Interferon gamma(IFN-γ),Tumor necrosis factorα(TNF-α),Interleukin-2,aspartate aminotransferase,alanine aminotransferase,alpha-fetoprotein(AFP),Fas,and FasL were measured by Enzyme-linked Immunosorbent Assay.Relevant mRNA expression of Bax and Bcl2 was evaluated by Real Time Quantitative PCR(RTqPCR)and protein expression of Transforming growth factorβ1(TGF-β1)and Mothers against decapentaplegic homolog(SMAD)4 was assessed by Western blotting.The HepG2 cell line was treated with 10 mg/mL,20 mg/mL,30 mg/mL,40 mg/mL of MJF,and another 3 groups were treated with TGF-β1 inhibitor(LY364947)and different doses of MJF.Relevant mRNA expression of TNF-α,IFN-γ,Bax and Bcl2 was evaluated by RT-qPCR and protein expression of TGF-β1,SMAD2,p-SMAD2,SMAD4,and SMAD7 was assessed by Western blotting.RESULTS It was shown that MJF improved body weight gain and tumor inhibition rate in H22 tumorbearing mice,protected immune organs and liver function,reduced the HCC indicator AFP,affected immunity and apoptosis,and up-regulated the TGF-β1/SMAD signaling pathway,by increasing the relative expression of TGF-β1,SMAD2,p-SMAD2 and SMAD4 and decreasing SMAD7,reducing immune factors TNF-αand IFN-γ,decreasing apoptosis cytokines Fas,FasL and Bcl2/Bax,and inhibiting the effect of LY364947 in HepG2 cells.CONCLUSION MJF inhibits HCC by activating the TGF-β1/SMAD signaling pathway,and affecting immune and apoptotic cytokines,which may be due to MJF adjusting immune escape and apoptosis.

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.

Bufei Yishen granules suppress oxidative stress in rats with chronic obstructive pulmonary disease via Nrf2 signaling

OBJECTIVE To explore the antioxidant effect of Bufei Yishen granules on chronic obstructive pulmo⁃nary disease(COPD)and investigate its underlying mechanism.METHODS Forty-eight rats were randomly divided into normal,model,Bufei Yishen granules(BY)and N-acetylcysteine(NAC)groups,12 rats in each group.The stable COPD rat model was duplicated by using repeated cigarette smoke exposure combined with Klebsiella bacterial infection for 12 weeks(week 1-12),and the corresponding drugs were administered for the next 8 weeks(week 13-20).Minute volume(MV),tidal volume(TV)and peak expiratory flow(PEF)were measured by whole body plethysmography(WBP)system every 4 weeks.Before sacrificed,forced vital capacity(FVC)and forced expiratory volume 0.1(FEV0.1)were measured byPFT system.The pathological changes of lung tissue were observed by pathological techniques.Heme oxygenase 1(HO-1),superoxide dismutase 1(SOD1)and Nrf2 in lung tissue were measured by immunohisto-hemical method.The total anti oxidizing capability(T-AOC),lipid peroxide(LPO)in rat serum were measured.The expression of Nrf2,HO-1 andγ-glutamyl cysteine synthetase(γ-GCS)mRNA in lung tissue was detected by quantitative polymerase chain reac⁃tion(qPCR).The protein expression of Keap1,Nrf2 and HO-1 in lung tissue were detected by Western blotting.RESULTS①Lung function:compared with normal group,the MV in model group was significantly decreased at week 8(P<0.01),the TV and PEF were significantly decreased at week 4(P<0.01).At week 20,compared with model group,MV,TV,and PEF in the BY and NAC groups were significantly increased(P<0.01);compared with the NAC group,MV,TV,and PEF in BY group were significantly increased(P<0.01).At the end of week 20,the FVC and FEV0.1 in model group were significantly lower than that in normal group(P<0.01).Compared with model group,the FVC and FEV0.1 in the BY and NAC groups were significantly increased(P<0.05).②Oxidative indexes:Compared with Normal group,T-AOCin serum was significantly decreased in Model group,while LPO was significantly increased(P<0.01).Compared with the Model,T-AOC in BY and NAC groups was significantly increased(P<0.01),and the LPO was significantly decreased(P<0.05,P<0.01).There were no difference between the BTG and NAC.③Nrf2 signaling:Nrf2 and HO-1 in lung tissue were mainly expressed in the cytoplasm and part of the nucleus of alveolar epithelial cells.SOD1 protein was mainly distributed in bronchial epithelial cells and alveolar septa.Compared with normal group,the expression of Nrf2 in the model group was increased(P<0.01),and HO-1 and SOD1 were decreased(P<0.01).Compared with the model,the expression of Nrf2 in the BY group was significantly increased(P<0.05),and HO-1 and SOD1 in BY and NAC groups were both increased(P<0.01).Compared with the NAC group,the expression of HO-1 in BY group was increased(P<0.01).Compared with normal group,the Nrf2 mRNA expression of lung tissue in the model was significantly increased(P<0.01),the HO-1 andγ-GCS mRNA was decreased(P<0.01).Compared with model group,the Nrf2,HO-1,andγ-GCS mRNA in the BY group were increased(P<0.01),the HO-1,andγ-GCS mRNA in NAC group were increased(P<0.01).Compared with normal group,the Nrf2 protein expression of lung tissue in the model group was significantly increased(P<0.01),and HO-1 protein expression was significantly decreased(P<0.01).Compared with the model,the Nrf2 and HO-1 protein in NAC and BY groups was significantly increased(P<0.01).CONCLUSION Bufei Yishen gran⁃ules has beneficial curative effect in COPD rats,and has the same antioxidation effect as NAC,the mechanism may be involved in upregulating Nrf2 signaling.