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.

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.

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.

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。

Preparation of Ephedra houttuynia Granule and Its Therapeutic Mechanism of Anti-Mycoplasma gallisepticum Infection Based on Network Pharmacology

The use of Chinese herbal medicines can replace antibiotics that cause drug-resistance problems,which are currently necessary for disease control.In this paper,a traditional Chinese medicine compound named Ephedra houttuynia granule for the treatment of Mycoplasma galliscepticum(MG)infection was prepared.Furthermore,its action mechanism was explored through network pharmacology.The optimal extraction and granulation processes of the compound were determined by high performance liquid chromatography(HPLC)method and L9 orthogonal test,and in the treatment experiment,Ephedra houttuynia granule showed a significant therapeutic effect on MG infection.In the study of network pharmacology,the results showed that the core targets of Ephedra houttuynia granule against MG infection were vascular endothelial growth factor(VEGFA),fos proto-oncogene(FOS),prepro-coagulation factor II(F2),etc.,the gene ontology/kyoto encyclopedia of genes and genomes(GO/KEGG)analysis results indicated that the signaling pathways of neuroactive ligand receptor interaction,cAMP,IL-17,T cell receptor,and tumor necrosis factor(TNF)might involve in anti-MG infection.In conclusion,this study would provide a new idea for elucidating the action mechanism of other diseases in veterinary clinic,which had a certain guiding significance.

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.

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.

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.

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.

Study on compound Duzhong Jiangu granule in the treatment of knee osteoarthritis based on transcriptome analysis strategy

Duzhong Jiangu Granule in the treatment of primary osteoarthritis(POA)model of postmenopausal kidney deficiency type in Hartley female guinea pigs after ovariectomy,and the correlation between gene expression of bone marrow tissue,cartilage tissue,and knee osteoarthritis.Methods:383-months-old Hartley female guinea pigs after one week of adaptive feeding were weighed about 400 g±20 g,numbered,and sorted by ear tag.Six of them were selected as normal groups by looking up random number tables.The remainder were removed from the bilateral ovaries to construct the postmenopausal kidney deficiency model,and castrated guinea pigs were used to construct the postmenopausal kidney deficiency POA model.After the modeling cycle,a guinea pig from the blank group and a guinea pig from the model group were sacrificed and the right knee was observed.The model was established and the experiments continued.There were five guinea pigs in the blank group,and the remaining model guinea pigs were randomly divided into model control group,high-dose group of compound Duzhong Jiangu granules,middle-dose group of compound Duzhong Jiangu granules,low-dose group of compound Duzhong Jiangu granules and design group,with 5 guinea pigs in each group.Blanks and model groups were given a cellulose sodium solution by gavage.The guinea pigs were sacrificed after 30 days of intragastric administration.The left knee cartilage and bone marrow of the blank group,model group,middle dose group,and high dose group of compound Duzhong Jiangu granule were collected and applied to transcriptome sequencing,and the sequencing data were analyzed,including differential gene expression analysis,functional enrichment analysis of database established by Gene Ontology federation(GO)and Kyoto Encyclopedia of Gene and Genome(KEGG)pathway enrichment analysis.The complete specimens of the right knee joint were collected,and the morphological changes of the cartilage of the right knee joint in each group were observed by saffron rapid green staining,and the subchondral bone was quantitatively analyzed by Micro CT so that the expression of TRAF6,MIP-1βand IL-1βprotein in NF-kappa B signaling pathway was detected by Western Blot technique(WB).Results:The results of Safranin Fast Green staining showed that Compound Duzhong Jiangu Granules could effectively reduce the degree of morphological damage of articular cartilage in guinea pigs with the POA model.According to the analysis results of the subchondral bone structure under Micro CT,Compound Duzhong Jiangu Granules can improve the bone condition of the POA model,thus delaying the process of degenerative changes of the knee joint.From the results of transcriptome analysis,Compound Duzhong Jiangu Granules can inhibit the expression of related genes in POA model guinea pigs.According to the results of Wester Bolt verification,Compound Duzhong Jiangu Granules can effectively improve knee osteoarthritis.Conclusions:The effect of Compound Duzhong Jiangu Granules on OA is obvious,and its mechanism may be related to the expression of genes GZMK,Jchain,igkc,IGHV3-74,IGHV3-11,IGHV4-1,CCL5,and IGKV1–39.

Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism

BACKGROUND Liver fibrosis is a formidable global medical challenge,with no effective clinical treatment currently available.Yinhuang granule(YHG)is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos.It is frequently used for upper respiratory tract infections,pharyngitis,as well as acute and chronic tonsillitis.AIM To investigate the potential of YHG in alleviating carbon tetrachloride(CCl4)-induced liver fibrosis in mice.METHODS To induce a hepatic fibrosis model in mice,this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk.Meanwhile,liver fibrosis mice in the low dose of YHG(0.4 g/kg)and high dose of YHG(0.8 g/kg)groups were orally administered YHG once a day for 4 wk.Serum alanine/aspartate aminotransferase(ALT/AST)activity and liver hydroxyproline content were detected.Sirius red and Masson's trichrome staining assay were conducted.Realtime polymerase chain reaction,western-blot and enzyme-linked immunosorbent assay were conducted.Liver glutathione content,superoxide dismutase activity level,reactive oxygen species and protein carbonylation amount were detected.RESULTS The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice,as reflected by decreased serum ALT/AST activity and improved liver histological evaluation.YHG also attenuated liver fibrosis,evident through reduced liver hydroxyproline content,improvements in Sirius red and Masson's trichrome staining,and lowered serum hyaluronic acid levels.Furthermore,YHG hindered the activation of hepatic stellate cells(HSCs)and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice.YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2(Nrf2)and upregulated the expression of Nrf2-dependent downstream antioxidant genes.In addition,YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice,as demonstrated by increased liver adenosine triphosphate content,mitochondrial DNA levels,and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1.CONCLUSION YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs,reducing inflammation,alleviating liver oxidative stress damage through Nrf2 activation,and promoting liver mitochondrial biogenesis.

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.

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.

GRANULE算法的截断不可能差分分析

GRANULE是Feistel结构的轻量级分组密码算法,分组长度为64比特,密钥长度为80比特和128比特,算法根据密钥长度分别记为GRANULE-80和GRANULE-128.首先构造了两条新的7轮不可能差分链;其次,研究了GRANULE密钥编排计划的冗余性得到了轮密钥之间的一些线性关系;第三,在一条7轮不可能差分链的前后各扩展3轮,得到了13轮GRANULE-80的不可能差分分析攻击路径,执行此攻击需要的数据复杂度为2^(62.06)个选择明文,时间复杂度为2^(62.15)次13轮GRANULE-80加密,存储复杂度为2^(46.06)个64-比特数据块;最后,基于另一条7轮不可能差分链构造了14轮GRANULE-128的不可能差分分析攻击路径,恢复128比特主密钥需要的数据、时间和存储复杂度分别为2^(62.57)个选择明文、2^(101.84)次14轮GRANULE-128加密和2^(74.57)个64-比特数据块.与之前的结果相比,GRANULE-80的攻击轮数提高了2轮,同时还对GRANULE-128的安全边界进行了评估.

SLC6A9对结直肠癌细胞生长和对5-FU药物敏感性的影响

目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结肠癌组织、正常结肠细胞系(NCM460)和结直肠癌细胞系(SW620、HCT116、HT29、Lovo和SW480)中的表达。将SCL6A9过表达质粒及阴性对照(SLC6A9 OE、Vector)转染HT29细胞,将SCL6A9小干扰RNA及阴性对照(SLC6A9 siRNA1#、siRNA2#和Scramble)转染SW620细胞。划痕愈合实验和Transwell实验检测各组细胞的迁移、侵袭能力。Western blot和细胞免疫荧光检测EMT相关蛋白E-cadherin、Vimentin的表达水平。利用CCK-8法和构建裸鼠移植瘤模型检测SLC6A9过表达对结直肠癌细胞5-FU药物敏感性的影响。结果:与正常结肠组织和NCM460细胞相比,SLC6A9在结肠癌组织和结直肠癌细胞系中低表达(均P<0.05)。SLC6A9过表达引起E-cadherin蛋白表达增加,Vimentin蛋白水平降低,抑制结直肠癌细胞的迁移、侵袭(P<0.05)。SLC6A9低表达引起E-cadherin蛋白表达降低,Vimentin蛋白水平增加,促进结直肠癌细胞的迁移、侵袭能力(P<0.05)。SLC6A9过表达提高了5-FU的药物敏感性,并使肿瘤生长缓慢,质量减轻(P<0.05)。而SLC6A9低表达降低了5-FU的药物敏感性(P<0.05)。结论:SLC6A9过表达能够抑制结直肠癌细胞的迁移、侵袭和EMT进程,并增强5-FU对结直肠癌细胞的药物敏感性。

薏苡仁油联合5-FU对结肠癌HCT-116细胞株增殖、凋亡的影响

目的:分析薏苡仁油联合5-氟尿嘧啶(5-fluorouracil,5-FU)对结肠癌HCT-116细胞株增殖、凋亡的影响及其作用机制。方法:采用四甲基偶氮唑盐(methyl thiazolyl tetrazdium,MTT)法测定不同浓度薏苡仁油、5-FU以及薏苡仁油+5-FU对人结肠癌HCT-116细胞株的生长抑制效应;采用流式细胞术检测细胞凋亡情况;采用逆转录聚合酶链反应(RT-PCR)检测生存蛋白(Survivin)mRNA表达水平。结果:薏苡仁油、5-FU、5-FU+薏苡仁油均对人结肠癌HCT-116细胞增殖产生一定抑制作用,且薏苡仁油浓度越高,作用时间越长,细胞增殖抑制率越高,3组比较差异有统计学意义(P<0.05);与薏苡仁油组及5-FU组相比,5-FU+薏苡仁油组细胞增殖抑制率更高,差异有统计学意义(P<0.05)。薏苡仁油组、5-FU组、5-FU+薏苡仁油组的细胞凋亡率均高于空白对照组,差异有统计学意义(P<0.05);薏苡仁油浓度越高,细胞凋亡率也越高,差异有统计学意义(P<0.05);5-FU+薏苡仁油组细胞凋亡率高于5-FU组及薏苡仁油组,差异有统计学意义(P<0.05)。与空白对照组相比,不同浓度薏苡仁油组Survivin mRNA表达降低,差异有统计学意义(P<0.05);5-FU组Survivin mRNA表达升高,差异有统计学意义(P<0.05);5-FU+薏苡仁油组Survivin mRNA表达较5-FU组降低,差异有统计学意义(P<0.05)。结论:薏苡仁油能抑制结肠癌HCT-116细胞增殖,诱导细胞凋亡,与5-FU联合应用能发挥药物协同作用,其作用机制可能与调控Survivin mRNA表达有关。

ONECUT2高表达介导胃癌复发患者5-FU化疗耐药

目的:探究One cut结构域家族成员2(ONECUT2)是否可以作为对5-FU耐药的胃癌复发患者的治疗靶点。方法:利用癌症基因组图谱(TCGA)数据库分析ONECUT2基因在胃癌患者及胃癌复发患者的表达情况。利用基因集富集分析(GSEA)评估TCGA数据库中ONECUT2表达量与药物代谢相关生物学过程的相关性。利用CCK-8细胞毒性实验评估胃癌细胞敲低或过表达ONECUT2对5-FU的耐药情况。分析30例胃癌术后复发患者ONECUT2表达量与5-FU治疗效果的相关性。结果:TCGA数据库分析显示,在经受过化疗且复发的胃癌患者中,ONECUT2高表达的患者无病间隔期(disease-free interval,DFI)更短。GSEA分析结果表明,ONECUT2高表达与异生药物代谢通路呈正相关,这提示可能与胃癌患者的耐药相关。体外实验中,敲低ONECUT2降低胃癌细胞对5-FU的半数抑制浓度(IC_(50))值;反之,过表达ONECUT2增加细胞对5-FU的IC_(50)值。30例胃癌复发患者对5-FU的药物敏感性与ONECUT2表达量相关。结论:胃癌复发患者的ONECUT2表达量更高,ONECUT2高表达与胃癌复发患者的5-FU耐药相关,可能是潜在的治疗靶点。

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.