1. Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking
Yan-Min HOU ; Li-Juan ZHANG ; Yu-Yao LI ; Wen-Xin ZHOU ; Hang-Yu WANG ; Jin-Hui WANG ; Ke ZHANG ; Mei XU ; Dong LIU ; Jin-Hui WANG
Chinese Pharmacological Bulletin 2024;40(2):363-371
Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I
2.Ethylene oxide residue detection method based on multi-component medical devices
Ruo-Jin LIU ; Zi-Meng WANG ; Hui LI ; Wen-Liang SHAO ; Bao-Yu LIU ; Yi FENG
Chinese Medical Equipment Journal 2024;45(1):56-61
Objective To establish a stable and reliable method for the determination of ethylene oxide residue,and to analyze ethylene oxide residue in multi components made of different materials involved in some medical devices,so as to provide references for sample selection and ethylene oxide residue detection of multi-component medical device kits.Methods A method for the determination of ethylene oxide residue of multi-component medical devices was developed using headspace-gas chromatography and DB-WAX column under the conditions of headspace extraction with equilibration at 80℃ for 20 min,and the weighing mass,linearity,limit of detection,limit of quantification,precision and recovery of the method were determined.Trials of the method were carried out on the items undergoing ethylene oxide sterilization,including disposable perineal care kit,disposable gynecological examination kit,disposable suture dressing kit,disposable debridement kit and the components contacting human body in the disposable dialysis kit,and the abilities of different materials of the components were analyzed in absorbing,retaining and releasing ethylene oxide.Results The method showed high linearity(r=0.999 8)in the range of ethylene oxide mass concentration from 0.4 to 16.0 μg/mL with a weighing mass of 1.00 g,which had the limit of detection being 0.11 μg/mL,the limit of quantification being 0.37 μg/mL and the relative standard deviations(RSDs)for the precision from 0.35%to 1.52%.The average recoveries of different spiked amounts of ethylene oxide in the three blank matrices ranged from 92.68%to 101.42%with the relative standard deviations(RSDs)from 2.46%to 7.59%,which all satisfied the detection requirements.The components made of rubber and acrylonitrile-butadiene-styrene copolymer(ABS)in multi-component medical device kits had the highest ethylene oxide residues,followed by the components made of wood,degreased cotton,polypropylene and polystyrene.Conclusion The method proposed gains advantages in easy operation and high specificity,quantification and reproducibility,which can be used for the determination of ethylene oxide residue in the multi-component medical device kit undergoing ethylene oxide sterilization.References are provided for sample selection of multi-component medical devices.[Chinese Medical Equipment Journal,2024,45(1):56-61]
3.Simultaneous content determination of twelve constituents in Bushen Huoxue Sanjie Capsules by HPLC
Ji-Yao YIN ; Jing HU ; Xia SHEN ; Xiao-Min CUI ; Hui REN ; Tong QU ; Ning LI ; Wen-Jin LU ; Zhi-Yong CHEN ; Kai QU
Chinese Traditional Patent Medicine 2024;46(1):1-6
AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.
4.Clinical effects of Supplemented Buzhong Yiqi Decoction on patients with HP-positive chronic atrophic gastritis of Spleen-Stomach Deficiency Pattern
Hui-Hu GAN ; Lian-Ning JIN ; Hong-Gen HUANG ; Wen-Bo ZHOU
Chinese Traditional Patent Medicine 2024;46(2):469-473
AIM To explore the clinical effects of Supplemented Buzhong Yiqi Decoction on patients with HP-positive chronic atrophic gastritis of Spleen-Stomach Deficiency Pattern.METHODS One hundred and thirty-two patients were randomly assigned into control group(66 cases)for 12-week intervention of conventional treatment,and observation group(66 cases)for 12-week intervention of both Supplemented Buzhong Yiqi Decoction and conventional treatment.The changes in clinical effects,HP clearance rate,miR-32,TGF-β1,IL-6,PGⅠ,PGⅡ,EGF,somatostatin,gastrin,motilin,gastroscopy pathological score and TCM symptom score were detected.RESULTS The observation group demonstrated higher total effective rate and HP clearance rate than the control group(P<0.05).After the treatment,the two groups displayed decreased miR-32,TGF-β1,IL-6,gastroscopy pathological score,TCM symptom score(P<0.05),and increased PGⅠ,PGⅡ,EGF,somatostatin,gastrin,motilin(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with HP-positive chronic atrophic gastritis of Spleen-Stomach Deficiency Pattern,Supplemented Buzhong Yiqi Decoction can alleviate inflammation,regulate gastrointestinal hormone levels,improve symptoms,and enhance efficacy.
5.Ten kinds of antipyretic-antidotal traditional Chinese medicine extracts against extensively drug-resistant Acinetobacter baumannii infection
Yan YANG ; Jian-Wen FENG ; Bo JI ; Jin YUAN ; Yan WANG ; Jian LI ; Xue-Jiu CAI ; Zhi-Hui JIANG
Chinese Journal of Infection Control 2024;23(3):271-276
Objective To study the activity of ten kinds of antipyretic-antidotal traditional Chinese medicine(TCM),including radix tinosporae.herb of blin conyza and turmeric,against extensively drug-resistant Acineto-bacter baumannii(XDR-AB)infection,screen out the extracts of antipyretic-antidotal TCM which have in vivo anti-infection activity,provide a research basis for the discovery of novel antimicrobials against XD-RAB infection.Methods Ten antipyretic-antidotal TCM were extracted with water,50%ethanol and 95%ethanol respectively,and TCM extracts with different concentrations were prepared,which were co-incubated with the model of XDR-AB-infected Caenorhabditis elegans previously optimized by the research group.The in vivo activity of antipyretic-antidotal TCM against XDR-AB infection was judged through the survival rate of Caenorhabditis elegans.Results With the increase of concentration of turmeric and cortex pseudolaricis extracts,the survival rate of XDR-AB-infec-ted nematodes continued to improve.The water extract,50%ethanol extract,and 95%ethanol extract of turmeric at a concentration of 1 000 μg/mL could increase the survival rates of XDR-AB-infected Caenorhabditis elegans to 54.2%(compared to the negative control group,P<0.001),18.8%,and 13.3%,respectively.The water ex-tract,50%ethanol extract,and 95%ethanol extract of cortex pseudolaricis at a concentration of 1 000 μg/mL could increase the survival rates of XDR-AB-infected Caenorhabditis elegans to 47.4%(compared to the negative control group,P<0.001),23.8%,and 15.8%,respectively.Conclusion The water extracts of turmeric and cortex pseudolaricis have good activity against XDR-AB infection,and their main chemical components can be tested for in vitro antimicrobial efficacy to discover novel antimicrobial agents against XDR-AB infection.
6.Effect of paeoniflorin on aerobic glycolysis of macrophages induced by resiquimod
Ying-Ying JIN ; Le SHI ; Yong-Xi HAO ; Fan TANG ; Wen-Hui JIANG ; Tao LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):683-687
Objective To investigate the effect of paeoniflorin on aerobic glycolysis of macrophages induced by resiquimod.Methods THP-1 cells were treated with phorbol ester(PM A)to differentiate into macrophages.The cells were divided into control group,model group and low,medium,high dose experimental group.The cells in the control group were cultured normally;in the model group,2 μg·mL-1 resiquimod was used to stimulate macrophages for 24 h to induce aerobic glycolysis.The low,medium and high dose experimental groups were treated with 1,10 and 100 μmol·L-1 paeoniflorin for 24 h on the basis of the model group.Cell activity was detected by cell counting kit-8(CCK-8)method.Lactate and glucose determination kit were used to detect lactate secretion and glucose consumption of cells in each group.The protein and mRNA expression levels of(PKM2)and(LDHA)were detected by Western blot and real-time fluorescence quantitative polynucleotide chain reaction(q-PCR)respectively.Immunofluorescence method was used to compare the fluorescence intensity of PKM2 in each group.Results After 24 h stimulation of THP-1 cells with 2 μg·mL-1 resiquimod,the glucose contents in cell culture supernatants of control group,model group and low,medium and high dose experimental groups were(14.70±0.44),(9.83±0.43),(10.68±0.29),(11.79±0.33)and(13.63±0.74)mmol·L-1;the lactate secreted by cells were(6.17±0.48),(11.94±0.55),(9.08±0.55),(7.79±0.66)and(6.50±0.55)mmol·L-1;the protein expression levels of PKM2 in cells were 1.00±0.00,1.33±0.18,1.02±0.17,0.74±0.17 and 0.73±0.18;the protein expression levels of LDHA were 1.00±0.00,1.20±0.09,0.90±0.14,0.76±0.12 and 0.78±0.17;the PKM2 mRNA levels were 1.00±0.09,2.11±0.23,1.98±0.31,1.38±0.25 and 0.93±0.32;the LDHA mRNA levels were 1.00±0.13,1.85±0.25,1.44±0.21,0.91±0.24 and 0.96±0.14;the average fluorescence intensities of PKM2 were 136.41±33.63,217.94±5.33,210.27±1.03,204.14±3.27 and 186.79±14.03.Compared with control group,the above indicators in model group showed statistically significant differences(P<0.05,P<0.01);compared with model group,the differences in the above indicators in medium and high dose experimental group were all statistically significant(P<0.05,P<0.01).Conclusion Paeoniflorin can inhibit the aerobic glycolysis of macrophages induced by resiquimod.
7.Research progress on drug resistance mechanism of sorafenib in radioiodine refractory differentiated thyroid cancer
En-Tao ZHANG ; Hao-Nan ZHU ; Zheng-Ze WEN ; Cen-Hui ZHANG ; Yi-Huan ZHAO ; Ying-Jie MAO ; Jun-Pu WU ; Yu-Cheng JIN ; Xin JIN
The Chinese Journal of Clinical Pharmacology 2024;40(13):1986-1990
Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.
8.Pharmacokinetics of JS026 and JS026-JS016 for single intravenous administration in healthy volunteers
Yan TIAN ; Hui-Jing YE ; Jing-Jing WANG ; Nan-Yang LI ; Juan MA ; Xi TAN ; Fan WU ; Jie WANG ; Shu-Yan YU ; Xiao-Jie WU ; Jin-Jie HE ; Jing ZHANG ; Wen-Hong ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2251-2255
Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.
9.Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis
Fei Wen GU ; Xia SHI ; Xin MA ; Lei Jun YU ; Chuan Jin XU ; Cheng Cheng QIAN ; Dong Zhi HU ; Hui ZHANG
Biomedical and Environmental Sciences 2024;37(2):170-177
Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB). Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115 patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,GeneXpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS). Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%. Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.
10.Identification and expression analysis of AP2/ERF gene family in Artemisia argyi
Xue-xue YUE ; Chuang XIAO ; Qian-wen ZHANG ; Sai-nan PENG ; Chang-jie CHEN ; Jia ZHOU ; Jin-xin LI ; Yu-kun LI ; Yu-huan MIAO ; Da-hui LIU
Acta Pharmaceutica Sinica 2024;59(9):2634-2647
italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of

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