1.Study of honey-processed Hedysari Radix on the protection of intestinal mucosal barrier in rats with spleen deficiency
Mao-Mao WANG ; Qin-Jie SONG ; Zhe WANG ; Ding-Cai MA ; Yu-Gui ZHANG ; Ting LIU ; Zhuan-Hong ZHANG ; Fei-Yun GAO ; Yan-Jun WANG ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(15):2231-2235
Objective To explore the protective mechanism of honey-processed Hedysari Radix in regulating intestinal mucosal injury in rats with spleen qi deficiency.Methods The three-factor composite modeling method of bitter cold diarrhea,overwork and hunger and satiety disorder was used to construct a spleen qi deficiency model rats.After the model was successfully made,they were randomly divided into model group,honey-processed Hedysari Radix group and probiotic group,with 15 animals in each group.Another 15 normal rats were taken as the blank group.The honey-processed Hedysari Radix group was given 12.6 g·kg-1 water decoction of honey-processed Hedysari Radix by gavage,the probiotics group was given Bifidobacterium Lactobacillus triple viable tablets suspension at a dose of 0.625 g·kg-1,and the blank group and the model group were given the same dose of distilled water.The rats in the four groups were administered once a day for 15 days.Enzyme-linked immunosorbent assay was used to detect diamine oxidase(DAO)in serum,D-lactic acid(D-LA),secretory immunoglobulin A factor,and Western blotting was used to detect the expression levels of AMP-activated protein kinase(AMPK),zonula occludens-1(ZO-1)and occludin in colon tissues.Results The serum levels of DAO in the blank group,model group,honey-processed Hedysari Radix group and probiotic group were(138.93±9.78),(187.95±12.90),(147.21±6.92)and(166.47±3.37)pg·mL-1;the contents of D-LA were(892.23±49.17),(1 099.84±137.64),(956.56±86.04)and(989.61±51.75)μg·L-1;the contents of SIgA in colon tissues were(14.04±1.42),(11.47±2.39),(11.84±1.49)and(12.93±1.65)μg·mL-1;the relative expression levels of ZO-1 protein in colon tissues were 1.18±0.11,0.42±0.04,0.77±0.05 and 0.95±0.07;the relative expression levels of occludin protein were 1.35±0.31,0.61±0.17,1.19±0.19 and 0.88±0.13;the relative expression levels of AMPK protein were 0.91±0.02,0.35±0.09,0.74±0.08 and 0.59±0.11.Compared with the model group,there were significant differences in the serum content of DAO and D-LA,SIgA content in colon,and the content of ZO-1,occludin and AMPK protein in the honey-processed Hedysari Radix group(P<0.01,P<0.05).Conclusion Honey-processed Hedysari Radix can enhance the protective effect on the intestinal mucosa of rats with spleen qi deficiency by regulating the expression of related inflammatory cytokines,intestinal mucosal upper cell enzymes and tight junction proteins in rats with spleen qi deficiency.
2.Research status on the mechanism of action of Astragaloside Ⅳ on cardiovascular diseases
Er-Dan XIN ; Yu-Gui ZHANG ; Tian-Tian BIAN ; Ding-Cai MA ; Zhe WANG ; Mao-Mao WANG ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(17):2580-2585
Asragaloside Ⅳ(AS-Ⅳ)is one of the active ingredients of Astragalus membranaceus,and AS-Ⅳ can play a protective role in cardiovascular diseases by inhibiting inflammatory response,inhibiting cardiomyocyte apoptosis,improving myocardial ischemia reperfusion injury,regulating lipid metabolism,promoting cardiac vascular regeneration,inhibiting myocardial fibrosis,and improving myocardial hypertrophy.In this paper,we reviewed the relevant literature on the prevention and treatment of cardiovascular diseases of AS-Ⅳ,and summarized and analyzed its role and mechanism,in order to provide a reference for the in depth research on cardiovascular diseases and the development and application of drugs.
3.Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study
Ding-Hua CHEN ; Chao-Fan LI ; Yue NIU ; Li ZHANG ; Yong WANG ; Zhe FENG ; Han-Yu ZHU ; Jian-Hui ZHOU ; Zhe-Yi DONG ; Shu-Wei DUAN ; Hong WANG ; Meng-Jie HUANG ; Yuan-Da WANG ; Shuo-Yuan CONG ; Sai PAN ; Jing ZHOU ; Xue-Feng SUN ; Guang-Yan CAI ; Ping LI ; Xiang-Mei CHEN
Chinese Journal of Infection Control 2024;23(3):257-264
Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P<0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P>0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P>0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
4.Clinical comprehensive evaluation of recombinant Mycobacterium tuberculosis fusion protein
Xiaofeng NI ; Sha DIAO ; Siyi HE ; Xuefeng JIAO ; Xiao CHENG ; Zhe CHEN ; Zheng LIU ; Linan ZENG ; Deying KANG ; Bin WU ; Chaomin WAN ; Binwu YING ; Hui ZHANG ; Rongsheng ZHAO ; Liyan MIAO ; Zhuo WANG ; Xiaoyu LI ; Maobai LIU ; Benzhi CAI ; Feng QIU ; Feng SUN ; Naihui CHU ; Minggui LIN ; Wei SHA ; Lingli ZHANG
China Pharmacy 2023;34(4):391-396
OBJECTIVE To evaluate the effectiveness, safety, economy, innovation, suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein (EC), and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin (TB-PPD) were analyzed by the method of systematic review. Cost minimization analysis, cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD, and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation, suitability and accessibility were determined by systematic review and improved Delphi expert consultation, and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness, safety, economy, innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent, while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight, the scores of effectiveness, safety, economy, innovation, suitability, accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD, EC performs better in all dimensions of effectiveness, safety, economy, innovation, suitability and accessibility. However, it is worth noting that EC should further improve its availability in the dimension of accessibility.
5.Correlation between PAFAH1B3 Expression Level and Risk of Disease Progression After Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients.
Zhe-Yun GU ; Jian TAO ; Yi-Feng CAI ; Ling WANG
Journal of Experimental Hematology 2023;31(2):448-454
OBJECTIVE:
To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138+ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years.
METHODS:
147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis.
RESULTS:
At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ2=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor.
CONCLUSION
The expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.
Humans
;
Disease Progression
;
Hematopoietic Stem Cell Transplantation
;
Multiple Myeloma/drug therapy*
;
Prognosis
;
Retrospective Studies
;
Transplantation, Autologous
;
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics*
6.Research progress of powder modification of TCM based on particle design theory
Wei-feng ZHU ; Fu-cai CHEN ; Wen-jun LIU ; Liang-shan MING ; Yong-mei GUAN ; Li-hua CHEN ; Zhe LI
Acta Pharmaceutica Sinica 2022;57(6):1781-1791
Particle design, based on the concept of "quality by design", combines the elements of microbiology, formulation science, heat and mass transfer, solid state physics, powder science, and nanotechnology. It is widely used to develop particles with excellent functional properties. Without affecting the active ingredients, the modification technology of traditional Chinese medicine (TCM) powder based on particle design theory, could improve the flowability, tabletability, disintegration and dissolution behavior, hygroscopicity, wettability, and other functional properties at the physical structure level. This greatly promotes the development of solid preparations of TCM. The present review aims to summarize and discuss the research progress of powder modification of TCM from the perspective of the theory of particle design, powder modification technology, equipment used for powder modification, application in TCM and modification mechanism mainly based on researches published in recent ten years. This review could provide ideas and theory basis for the development of particle design.
7.Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China.
Bi-Jun SHI ; Ying LI ; Fan WU ; Zhou-Shan FENG ; Qi-Liang CUI ; Chuan-Zhong YANG ; Xiao-Tong YE ; Yi-Heng DAI ; Wei-Yi LIANG ; Xiu-Zhen YE ; Jing MO ; Lu DING ; Ben-Qing WU ; Hong-Xiang CHEN ; Chi-Wang LI ; Zhe ZHANG ; Xiao RONG ; Wei SHEN ; Wei-Min HUANG ; Bing-Yan YANG ; Jun-Feng LYU ; Hui-Wen HUANG ; Le-Ying HUO ; Hong-Ping RAO ; Wen-Kang YAN ; Xue-Jun REN ; Yong YANG ; Fang-Fang WANG ; Dong LIU ; Shi-Guang DIAO ; Xiao-Yan LIU ; Qiong MENG ; Yu WANG ; Bin WANG ; Li-Juan ZHANG ; Yu-Ge HUANG ; Dang AO ; Wei-Zhong LI ; Jie-Ling CHEN ; Yan-Ling CHEN ; Wei LI ; Zhi-Feng CHEN ; Yue-Qin DING ; Xiao-Yu LI ; Yue-Fang HUANG ; Ni-Yang LIN ; Yang-Fan CAI ; Sha-Sha HAN ; Ya JIN ; Guo-Sheng LIU ; Zhong-He WAN ; Yi BAN ; Bo BAI ; Guang-Hong LI ; Yue-Xiu YAN
Chinese Journal of Contemporary Pediatrics 2022;24(1):33-40
OBJECTIVES:
To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.
METHODS:
A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.
RESULTS:
Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).
CONCLUSIONS
There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology*
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Female
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Gestational Age
;
Humans
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Infant
;
Infant, Extremely Premature
;
Infant, Newborn
;
Pregnancy
;
Respiratory Distress Syndrome, Newborn/epidemiology*
;
Retrospective Studies
;
Treatment Outcome
8.Study on time-toxicity relationship and mechanism of Gardeniae Fructus extract on hepatoxicity in rats based on proteomics.
Feng ZHOU ; Kai ZHANG ; Zhi-Wei CAI ; Yin-Fang CHEN ; Xiao-Bo ZENG ; Xi-Zhe HE ; Xiao-Die HU ; Qing WEN ; Ri-Yue YU ; Li-Ping HUANG
China Journal of Chinese Materia Medica 2021;46(1):162-170
To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats. Rats were randomly divided into C group(0 day), D5 group(5 days), D12 group(12 days), D19 group(19 days), and D26 group(7 days recovery after 19 days of administration). The rats in normal group received normal saline through intragastric administration, and the rats in other groups received 10 g·kg~(-1 )Gardeniae Fructus extract through intragastric administration. After the final administration, the livers were collected. Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue. Total liver proteins were extracted for proteomic analysis, detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software. SIEVE software was used for relative quantitative and qualitative analysis of proteins. The protein-protein interaction network was constructed based on STRING. Cytoscape software was used for cluster analysis of differential proteins. Kyoto encyclopedia of genes and genomes(KEGG) database was used to perform enrichment signal pathway analysis. Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score. The results showed that the severity of liver injury in D5, D12 and D19 groups was significantly higher than that in group C. The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups, with no significant difference between group D26 and group C. Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters, involving in drug metabolism pathways, retinol metabolism pathways, proteasomes, amino acid biosynthesis pathways, and glycolysis/gluconeogenesis pathways. The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree. The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal. The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.
Animals
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Drugs, Chinese Herbal/toxicity*
;
Fruit
;
Gardenia
;
Liver
;
Proteomics
;
Rats
;
Signal Transduction
9.Deep vein thrombosis after closed fracture of lower extremity and blood types ABO
Shuhao LI ; Kun ZHANG ; Zhe SONG ; Wei FAN ; Xiaolong WANG ; Chen WANG ; Dongxu FENG ; Lisong HENG ; Fan XU ; Xiao CAI ; Pengfei WANG ; Yangjun ZHU
Chinese Journal of Orthopaedic Trauma 2021;23(1):81-87
Objective:To investigate the differences in incidence of deep vein thrombosis (DVT) after closed fracture of lower extremity between patients with different blood types ABO.Methods:A retrospective study was conducted in the 1, 951 patients who had been admitted to Department of Orthopaedics Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University for lower extremity fractures from August 2014 to June 2018. They were 924 males and 1,027 females with a mean age of 63 (46, 78) years (range, from 16 to 102 years). Of them, 572 were type O, 564 type A, 609 type B and 206 type AB. Venous ultrasonography was performed on both lower extremities within 12 hours after admission. The incidences of DVT after fracture were compared between different blood types in all the patients, patients with proximal fracture of the knee, peri-knee fracture and distal fracture of the knee, and patients<60 years old and ≥60 years old.Results:The incidences of DVT were, respectively, 26.75% (153/572), 28.72% (162/564), 34.32% (209/609) and 29.61% (61/206) for patients with blood type O, type A, type B and type AB. The DVT incidence for type B was significantly higher than that for type O ( P< 0.008). The incidences of DVT were, respectively, 28.74% (98/341), 28.99% (100/345), 39.45% (144/365) and 30.97% (35/113) for blood type O, type A, type B and type AB in the patients with proximal fracture of the knee. The DVT incidence for blood type B was significantly higher than those for blood type O and blood type A ( P< 0.008). There were no significant differences in the DVT incidence between different blood types ABO in the patients with peri-knee fracture, distal fracture of the knee,<60 years old or ≥60 years old( P>0.05). The incidences of DVT were, respectively, 30.99% (97/313), 33.33% (108/324), 45.22% (156/345), 34.74% (33/95) for blood type O, type A, type B and type AB in the patients ≥60 years old. The DVT incidence for blood type B was significantly higher than those for blood type O and blood type A ( P< 0.008). Conclusions:The incidence of DVT varied with different blood types ABO after lower extremity fracture. The highest DVT incidence was found in patients with blood type B. The impact of blood type on the DVT incidence after lower extremity fracture was mainly observed in the patients with proximal fracture of the knee or an age of ≥ 60 years old.
10.Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3.
Tian LU ; Yong LI ; Wenchao LU ; Twgm SPITTERS ; Xueyu FANG ; Jun WANG ; Simian CAI ; Jing GAO ; Yanting ZHOU ; Zhe DUAN ; Huan XIONG ; Liping LIU ; Qi LI ; Hualiang JIANG ; Kaixian CHEN ; Hu ZHOU ; Hua LIN ; Huijin FENG ; Bing ZHOU ; Christopher L ANTOS ; Cheng LUO
Acta Pharmaceutica Sinica B 2021;11(10):3206-3219
The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

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