1.Improvement effects of 3,5,6,7,8,3′,4′-heptamethoxyflavone of Fructus Aurantii on rats with damp blockage of the middle energizer
Wenhui GONG ; Yating XIE ; Li XIN ; Shihao YAN ; Beibei ZHAO ; Yuqing ZHENG ; Jingying GUO ; Jie SHANG ; Peng ZHENG ; Jinlian ZHANG
China Pharmacy 2024;35(7):819-824
OBJECTIVE To investigate the improvement effects of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group, model group, positive control group (Raceanisodamine tablet, 1 mg/kg), HMF low-dose, medium-dose and high-dose groups (0.3, 0.6, 0.9 mg/kg), with 7 rats in each group. Except for the normal group, the other groups were modeled by internal and external composite factors. After successful modeling, the rats in each group were given the corresponding drug or normal saline, once a day, for 14 days. The general behavioral states such as dietary intake, water intake and mental state of the rats were observed, and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin (HE) staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected, and the expression of aquaporins (AQP3) in the gastric tissue of rats was determined. RESULTS Compared with the normal group, the dietary intake and water intake of the model group rats were significantly decreased (P<0.01), the fecal water content rate, salivary flow rate, plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly (P<0.01). Gastric tissue injury invaded the mucosal muscle layer, resulting in mucosal muscle layer rupture; pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group, the dietary intake and water intake of rats were increased in HMF groups; fecal water content rate, salivary flow rate, plasma content of aldosterone, the expression of AQP3 in gastric tissue were decreased, most of the above differences were statistically significant (P<0.05 or P<0.01). The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer, the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.
2.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
3.Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction
Qi Yan NAN ; Shang Guo PIAO ; Ji Zhe JIN ; Byung Ha CHUNG ; Chul Woo YANG ; Can LI
Kidney Research and Clinical Practice 2024;43(5):586-599
Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.
4.Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction
Qi Yan NAN ; Shang Guo PIAO ; Ji Zhe JIN ; Byung Ha CHUNG ; Chul Woo YANG ; Can LI
Kidney Research and Clinical Practice 2024;43(5):586-599
Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.
5.Cinnamomi Ramulus-Alismatis Rhizoma in Treatment of External-contraction Diseases from Traditional Chinese Medicine and Modern Pharmacy: A Review
Yuqing CAO ; Yang GUO ; Xiyu SHANG ; Zihan JIA ; Yibai XIONG ; Renbo CHEN ; Lei ZHANG ; Lin TONG ; Huamin ZHANG ; Yan MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):279-288
Cinnamomi Ramulus and Alismatis Rhizoma are commonly used in the treatment of external-contraction diseases. Cinnamomi Ramulus is pungent, sweet, and warm, with the effects of ventilating lung and dispersing cold, warming Yang and transforming Qi, and promoting water and liquid flow from Taiyang meridian to remove dampness. Alismatis Rhizoma is sweet and cold, with the effects of draining dampness and promoting urination, regulating the waterway, removing water retention in lung, and promoting urination to remove dampness and heat. Herbal pairs are extracted from the accumulated experience of medical practitioners over the ages in the use of medicines and have been proved by clinical application to be composed of simple and effective combinations for specific diseases. The herb pair Cinnamomi Ramulus-Alismatis Rhizoma is an important part in ancient classic formulas such as Wulingsan. Both herbs play a role in draining dampness and promoting urination, warming Yang and transforming Qi, being a representative herb pair used for treating external-contraction exterior syndrome and water retention inside. The review of ancient medical publications revealed that there were a large number of compound formulas containing Cinnamomi Ramulus-Alismatis Rhizoma for dispersing cold and removing dampness, which were widely used for thousands of years in clinical practice. Modern pharmacological studies have shown that the active pharmacological components of Cinnamomi Ramulus (cinnamaldehyde and cinnamic acid) and Alismatis Rhizoma (alisol A and 23-acetate alisol B) have anti-inflammatory, antiviral, and immunoregulatory effects and high safety. Qingfei Paidu decoction containing this herbal pair played an important role in fighting against COVID-19. Despite the extensive pharmacological studies on Cinnamomi Ramulus and Alismatis Rhizoma, few studies have been carried out regarding this herb pair. This paper summarizes the traditional Chinese medicine knowledge about Cinnamomi Ramulus and Alismatis Rhizoma in the treatment of external-contraction diseases and summarizes the chemical composition, pharmacological effects, toxicology and other aspects of the two herbs before and after compatibility, aiming to provide a reference for further research and clinical application.
6.Discussion on medication law of Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair based on data mining of ancient prescriptions and Chinese patent medicine
Yuqing CAO ; Xiyu SHANG ; Guangkun CHEN ; Yibai XIONG ; Yang GUO ; Yipin FAN ; Xinyu JI ; Zhaoyuan GONG ; Lei ZHANG ; Lin TONG ; Yan MA
International Journal of Traditional Chinese Medicine 2024;46(9):1212-1218
Objective:To explore the compatibility and medication law of Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair in ancient and modern prescriptions.Methods:Ancient prescriptions and Chinese patent medicines containing Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were retrieved from the database of ancient classic famous prescriptions 1.0 and the database of listed Chinese patent medicines 1.0 developed by the Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences. Excel 2019 was used to establish a database. The ancient and modern medical record cloud platform V2.3.5 and SPSS Modeler 18.0 software were used to perform frequency statistics, association rule analysis, clustering analysis, etc. on the data.Results:Totally 79 ancient articles with Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were obtained, including 76 ancient prescriptions, involving 250 kinds of Chinese materia medica; 25 kinds of Chinese patent medicine were obtained, involving 186 kinds of Chinese materia medica. The drug properties of ancient prescriptions and modern TCM patent medicines were both mainly warm, cold and neutral. The main tastes of ancient prescriptions and modern Chinese patent medicines were pungent, sweet and bitter. And the drugs mainly belong to spleen, lung, liver and kidney meridians. Correlation analysis suggested the same high-frequency association compatibility of ancient and modern prescriptions, Poria-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Macrocephalae Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma. Both clinical symptoms and diseases associated with medicinal compatibility of ancient prescriptions were intestinal flora, edema and vomiting. The syndrome types included bladder impoundment, dampness trapped in the guardian surface, internal retention of phlegm and morbid fluid. The clinical symptoms associated with medicinal compatibility of modern TCM patent medicine were limb joints pain and edema. The diseases included rheumatic arthritis (RA) and kidney disease. The syndrome types included wind-cold-dampness RA, stagnation of collaterals and kidney yang deficiency. High frequency drug clustering yielded 4 clustered squares.Conclusion:The core indications treated by Cinnamomi Ramulus-Alismatis Rhizoma are exogenous diseases with dampness caused by syndrome types including internal storage of water-dampness, cold-dampness obstruction and so on, which can provide reference for further in-depth research and guidance on clinical medication.
7.Effects of Yiqi-Huoxue formula on autophagy and PI3K/Akt/mTOR sig-naling pathway in rats with cerebral ischemia-reperfusion injury
Tiantian ZHANG ; Jinxi WANG ; Guo MAO ; Yan SHANG ; Li LI ; Piao HE ; Ting ZHANG ; Liang OU ; Guoheng HU
Chinese Journal of Pathophysiology 2024;40(11):1993-2004
AIM:To explore the possible mechanism of Yiqi-Huoxue formula(YQHXF)in treating cerebral ischemia-reperfusion injury.METHODS:Male SD rats were randomly divided into six groups,namely,the sham,mod-el,nimodipine,and low-,middle-and high-dose YQHXF groups.The middle cerebral artery occlusion/reperfusion(MCAO/R)model was established in all groups except the sham group.After successful modeling,the YQHXF low-,me-dium-,and high-dose groups were given 3.8,7.5,and 15 g?kg-1?d-1 of YQHXF,respectively,by gavage,while the ni-modipine group was given 12 mg?kg-1?d-1 of nimodipine tablets by gavage.The sham and model groups were given 10 mL?kg-1?d-1 of distilled water by gavage.After 14 days of drug intervention,the rats were euthanized and the neurological func-tion was evaluated.The infarct volume was assessed using 2,3,5-triphenyltetrazolium chloride(TTC)staining and brain histopathological changes were determined by hematoxylin-eosin(HE)staining.Transmission electron microscopy was used to investigate changes in autophagosomes,with immunofluorescence used to assess expression of microtubule-associ-ated protein 1 light chain 3(LC3)protein in the cerebral cortex,Western blot was used to measure protein levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,LC3B,p62,beclin-1,and Atg5,and RT-qPCR was used to determined LC3 and P62 mRNA expression.RESULTS:Compared with the sham group,the neural function scores of rats in the model group rats were significantly increased,and TTC staining revealed large areas of white cerebral infarction.There was severe pathological damage to the cerebral tissue in the ischemic cortical area,and large numbers of autophagosomes were seen inside the cells.Immunofluorescence staining showed significant numbers of LC3B-positive cells(P<0.01).Protein expression of beclin-1,Atg5,and LC3-Ⅱ/LC3-Ⅰ was significantly upregulated(P<0.01),while that of p62 was markedly downregulated(P<0.01).The expression of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR proteins was also significantly reduced(P<0.01).In addition,the mRNA expression of LC3 was significantly upregulated(P<0.01),with downregulation of P62 mRNA levels(P<0.01).Compared with the model group,both the YQHXF medium-and high-dose groups showed upregulated LC3-Ⅱ/LC3-Ⅰ values after 12 h of reperfusion(P<0.01),followed by downregulation of the ratios(P<0.05)after 3,7,and 14 days of reperfusion.Furthermore,after 14 days of reperfusion,compared with the model group,the middle-and high-dose YQHXF groups and the nimodipine group showed reduced neurological function scores(P<0.01),reduced cerebral infarction volumes(P<0.01),improvements in the pathological damage to cortical tis-sue,and reduced autophagosome formation to varying degrees.At the same time,the number of LC3B-positive cells was reduced(P<0.01).Protein expression of beclin-1,Atg5,and LC3-Ⅱ/LC3-Ⅰ was significantly downregulated,while that of p62 was upregulated(P<0.01).The mRNA expression of LC3 and p62 was consistent with the protein levels(P<0.01).In addition,the expression of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR proteins was upregulated(P<0.01).CONCLUSION:YQHXF can dynamically regulate autophagy in ischemic brain tissue,with inhibition of excess autophagy by activation of the PI3K/Akt/mTOR signaling pathway,thus reducing the infarct volume,alleviating brain dam-age,and promoting the recovery of neurological function.
8.Genetic correlations among Brucella melitensis isolates from sheep in four provinces of northwest China
Xiao-An CAO ; Zhi-Jie LIU ; Ping LIU ; Jin-Yan WU ; You-Jun SHANG ; Ji-Jun HE ; Zhi-Guo LIU ; Zhen-Jun LI
Chinese Journal of Zoonoses 2024;40(10):922-927
Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90%(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87%of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.
9.Survival and Prognosis of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes Transformed from Myelodysplastic Syndrome
Li-Mei SHANG ; Hui-Juan CHEN ; Yue LIU ; Yang CAO ; Feng LI ; Yan-Ting GUO ; Wei-Min DONG ; Yan LIN ; Wei-Ying GU
Journal of Experimental Hematology 2024;32(2):347-354
Objective:To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes(AML-MRC)transformed from myelodysplastic syndrome(MDS).Methods:The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed.The demographic data and laboratory parameters,cytogenetic karyotypes,target genes of AML detected by next generation sequence,risk stratification,treatment regimen,therapeutic efficacy and survival outcome were documented.Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy.The effects of clinical parameters,risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis.Results:The median overall survival(OS)of the AML-MRC patients was 4.5 months,the 1-year OS rate was 28.3%,and the complete remission(CR)rate after treatment was 33.3%.The univariate analysis showed that age≥60 years,leukocytosis,severe thrombocytopenia,poor-risk group and only accepted hypomethylating agents(HMAs)or supportive therapy were the risk factors affecting OS.COX multivariate analysis showed that thrombocytopenia(HR=4.46),HMAs therapy(compared to transplantation,HR=10.47),supportive therapy(compared to transplantation,HR=25.80)and poor-risk group(compared to medium-risk group,HR=13.86)were independent hazard factors for median OS of patients with AML-MRC.The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age ≥ 60 years,thrombocytopenia,time of transformation from MDS to AML(TTA)≥3 months,fibrinogen-albumin ratio index(FARI)≥ 0.07,CONUT score≥5,poor-risk group and supportive therapy.Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age ≥ 60 years(HR=11.23),thrombocytopenia(HR=8.71),FARI ≥ 0.07(HR=5.19)and poor-risk group(HR=14.00).The risk factors affecting CR of AML-MRC patients in univariate analysis were age ≥ 60 years,thrombocytopenia,FARI ≥ 0.1,CONUT score ≥ 5,poor-risk group and supportive therapy,while binary logistic regression analysis showed that age ≥ 60 years(HR=7.35),CONUT score ≥ 5(HR=9.60),thrombocytopenia(HR=12.05)and poor-risk group(HR=32.5)were independent risk factors affecting CR of the patients.Conclusion:The OS of AML-MRC patients is poor,old age(≥ 60 years old),supportive therapy,HMA therapy,poor-risk,thrombocytopenia,FARI ≥ 0.07 and CONUT score ≥ 5 may be associated with poor prognosis.
10.Effect of Collagen Peptides on Function of Mouse T Lymphocytes under Simulated Microgravity
Shao-Yan SI ; Ya-Ya QIN ; Ying-Ying WU ; Xiao-Yu MA ; Ying SHANG ; Shu-Jun SONG ; Yan-Chuan GUO
Journal of Experimental Hematology 2024;32(4):1258-1263
Objective:To understand the effect of collagen peptides on the function of mouse lymphocytes under simulated microgravity.Methods:The splenocytes of mice were isolated,and the rotary cell culture system was used to simulate the microgravity.The T lymphocytes were stimulated with mitotic agents,concanavalin A(ConA),and the cells were treated with different concentrations of collagen peptides.The proliferation of lymphocytes and the levels of cytokines in the supernatant were detected.Results:Simulated microgravity could inhibit the proliferation of spleen T lymphocytes and decrease the level of cytokines in the supernatant.Collagen peptides could promote the lymphocyte proliferation and cytokine production in cells cultured under simulated microgravity.Conclusion:Collagen peptides may attenuate the inhibitory effect of simulated microgravity on T lymphocytes by regulating the cell proliferation and the secretion of cytokines.

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