1.Clinical Application and Pharmacological Mechanism of Sishenwan in Treatment of Ulcerative Colitis: A Review
Keqiu YAN ; Xiaoyu ZHANG ; Sifeng JIA ; Yuyu DUAN ; Zixing QIAN ; Yifan CAI ; Junyi SHEN ; Wenjie XIAO ; Xinkun BAO ; Guangjun SUN ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):261-270
Ulcerative colitis (UC), a chronic, non-specific inflammatory bowel disease with typical symptoms such as abdominal pain, diarrhea, and bloody stools, demonstrates a high relapse rate and difficulty in curing. Sishenwan, first recorded in Internal Medicine Abstract (Nei Ke Zhai Yao), are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney, and astringing the intestine and stopping diarrhea. In recent years, Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors, including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term, its side effects, high relapse rate, and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan, used alone or in combination with Western medicine or other Chinese medicine compound prescriptions, significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus, pus, and blood in stools, and persistent abdominal pain, reduce Mayo scores and the relapse rate, and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen, isopsoralen, and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level, Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future, a full-chain system covering syndrome differentiation, targeting, and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics, providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.
2.Clinical Application and Pharmacological Mechanism of Sishenwan in Treatment of Ulcerative Colitis: A Review
Keqiu YAN ; Xiaoyu ZHANG ; Sifeng JIA ; Yuyu DUAN ; Zixing QIAN ; Yifan CAI ; Junyi SHEN ; Wenjie XIAO ; Xinkun BAO ; Guangjun SUN ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):261-270
Ulcerative colitis (UC), a chronic, non-specific inflammatory bowel disease with typical symptoms such as abdominal pain, diarrhea, and bloody stools, demonstrates a high relapse rate and difficulty in curing. Sishenwan, first recorded in Internal Medicine Abstract (Nei Ke Zhai Yao), are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney, and astringing the intestine and stopping diarrhea. In recent years, Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors, including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term, its side effects, high relapse rate, and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan, used alone or in combination with Western medicine or other Chinese medicine compound prescriptions, significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus, pus, and blood in stools, and persistent abdominal pain, reduce Mayo scores and the relapse rate, and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen, isopsoralen, and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level, Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future, a full-chain system covering syndrome differentiation, targeting, and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics, providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.
3.Exploration of mechanism of polydatin in learning and cognitive impairment in aging mice based on Keap1/Nrf2/HO-1 pathway
Xiao-Xuan MA ; Yi LIU ; Yu CAI ; Chun-Chao YAN ; Yun-Zhong CHEN
Chinese Pharmacological Bulletin 2024;40(7):1287-1295
Aim To study the regulatory effect of poly-datin on D-galactose-induced aging model mice.Methods Fifty-six ICR mice(half male and half fe-male)were divided into normal group,model group,positive group,low,medium and high polydatin treat-ment groups.Aging model was established by subcuta-neous injection of D-galactose(500 mg·kg-1)into the back of neck every day.During the modeling peri-od,the positive group was given donepezil hydrochlo-ride tablets(0.75 mg·kg-1)by gavage,the treat-ment group was given polydatin(40,70,100 mg·kg1)by gavage,and the normal group was given the same amount of normal saline.The learning and cogni-tive ability of mice was evaluated by nesting experi-ment,new object recognition experiment and Morris water maze experiment.The heart,liver,spleen,kid-ney and thymus of mice were taken to calculate the or-gan index.The pathological changes of whole brain tis-sue in mice were observed by hematoxylin-eosin(HE)staining.The levels of T-SOD,MDA,GSH-Px and AchE in serum and whole brain tissue of mice were de-tected by ELISA.The protein expression levels of Keap1,Nrf2 and HO-1 in hippocampus of mice were detected by Western blot.Results Compared with the model group,the nesting ability,the ability to recog-nize new objects and the ability to find platforms under-water of the mice in the positive group and the low,medium and high dose groups of polydatin were im-proved.The organ index increased.The neuronal dam-age in the cerebral cortex and hippocampus was signifi-cantly ameliorated.The activities of T-SOD and GSH-Px in serum and brain tissue increased and the activi-ties of MDA and AchE decreased.The expression lev-els of Nrf2 and HO-1 protein in hippocampus in-creased,and the expression level of Keap1 protein de-creased.Conclusions Polydatin can ameliorate the learning and cognitive impairment in D-galactose-in-duced aging model mice,and its mechanism may be related to the Keap1/Nrf2/HO-1 pathway.
4.Study on detection of bacterial endotoxin by micro kinetic chromogenic method
Chen-Xue ZHANG ; Tong CAI ; Chen CHEN ; Xiao-Yan ZHAO ; Yu-Sheng PEI
Chinese Pharmacological Bulletin 2024;40(7):1392-1398
Aim To determine whether the micro kinetic chro-mogenic method can meet the requirements of Chinese Pharma-copoeia,as a supplement to the existing bacterial endotoxin test method.Methods Using micro kinetic chromogenic horseshoe crab reagent,the sample volume per well was 25 μL,the detec-tion wavelength was 405 nm,the preset OD value was 0.05,and the detection was carried out by half-well enzyme plate.In accordance with the provisions of"9101 Guiding Principles for Validation of Drug Quality Analysis Methods"in the fourth part of the 2020 edition of the People's Republic of China Pharmaco-poeia,the methodological verification of 7 items of specificity,accuracy,precision,limit of quantification,linearity,range and durability was carried out according to the specific requirements of the"quantitative"item in the"Determination of Impurities".The variety suitability study was conducted on 74 batches of samples from 48 drug varieties,and 143 batches of samples from 76 drug varieties(including 133 batches of negative samples and 10 batches of positive samples)were tested daily,and the re-sults were compared with the results of traditional color rendering method.Results The method of microdynamic color develop-ment met the requirements of the Pharmacopoeia of the People's Republic of China for quantitative methods.The results of varie-tal applicability and consistency comparison showed that the mi-crodynamic color development method had better equivalence compared with the traditional color development method.Con-clusion The micro kinetic chromogenic method can be promo-ted as a supplementary alternative to the existing bacterial endo-toxin methods.
5.Application of electrocardiogram in predicting culprit vessels in acute inferior myocardial infarction
Feng LIU ; Hua-Kang LI ; Yan-Xiu CHEN ; Xiao-Lian CAI
Journal of Regional Anatomy and Operative Surgery 2024;33(5):440-444
Objective To explore the value of electrocardiogram in predicting culprit vessels in acute inferior myocardial infarction.Methods The clinical data of 129 patients with acute inferior myocardial infarction admitted to First Affiliated Hospital of Army Medical University from January 2015 to December 2021 were retrospectively analyzed.Patients were received coronary intervention treatment,and the culprit vessels were identified by coronary angiography.The culprit vessels during surgery were recorded.The preoperative electrocardio-gram of patients were analyzed,a new method for predicting culprit vessels in acute inferior myocardial infarction was established based on the previous researches,and the accuracies of the Fiol method,Tiala method,Huang's algorithm and new method in predicting the culprit vessels in acute inferior myocardial infarction were also counted.The predictive abilities of various methods on culprit vessels were evaluated using receiver operating characteristic(ROC)curve and the area under the curve(AUC)was calculated.Results The culprit vessels of 109 patients were the right coronary artery,16 cases were the left circumflex artery,and 4 cases were the anterior descending artery.A total of 52 patients developed clinical complications,of which the culprit vessels of 47 cases were right coronary artery and 5 cases were circumflex artery.The accuracies of the Fiol method,Tierala method,Huang's algorithm,and new method in predicting culprit vessels were 83.7%,81.4%,82.9%,and 85.3%,respectively.The ROC curve analysis showed that the Fiol method(AUC=0.941),Tierrala method(AUC= 0.945),Huang's algorithm(AUC=0.945),and new method(AUC=0.964)all had strong predictive ability for culprit vessels.Conclusion For patients with acute inferior myocardial infarction,the Fiol method,Tierala method,Huang's algorithm,and new method all have high predictive value for culprit vessels in analyzing the preoperative electrocardiogram,and the new method has a higher predictive value.
6.Effects of climate change on scrub typhus in Xiamen
Xue-Mei KE ; Jiao-Na CHEN ; Shan-Shan MA ; Si-Han WU ; Chun-Xiang CAI ; Xiao-Yan WANG ; Shi-Jie HUANG
Chinese Journal of Zoonoses 2024;40(10):965-970
This study was aimed at examining the influence of meteorological factors on scrub typhus in Xiamen.Scrub ty-phus monitoring data and meteorological factors were collected in Xiamen from 2005 to 2023.Spearman correlation analysis and nonlinear regression were used to analyze the correlation between scrub typhus incidence and meteorological factors.The inci-dence of scrub typhus first increased and subsequently decreased in Xiamen from 2005 to 2023.The highest incidence was be-tween 2014 and 2016,and the peak incidence was from June to October.The monthly incidence of scrub typhus positively cor-related with daily minimum temperature(r=0.637,P<0.001,daily average temperature(r=0.627,P<0.001),daily maxi-mum temperature(r=0.612,P<0.001),sunshine duration(r=0.405,P<0.001),average relative humidity(r=0.346,P<0.001),and daily rainfall(r=0.207,P=0.002),and negatively correlated with average atmospheric pressure(r=-0.549,P<0.001),whereas no correlation was observed with the average wind speed in Xiamen.The regression equation of scrub ty-phus monthly incidence and meteorological parameters was y=-433.869-11.503x1+0.381x1 2+9.150x2-0.197x2 2+3.936 x3-0.132x3 2+0.881x4+0.035x4 2-1.048x5+0.009x5 2+0.186x6-0.023x6 2+0.421x7+6.210×10-5x8-1.051 × 10-10x8 2 in Xiamen,and the R2 was 0.473,thus indicating good model fit.Scrub typhus incidence correlated with the daily minimum av-erage temperature,average temperature,daily maximum tem-perature,sunshine duration,daily rainfall,relative humidity,and average atmospheric pressure in Xiamen.Various meteoro-logical factors had differing effects on scrub typhus.
7.Protective Effects of Astrocyte-derived Exosomes on Mitochondrial Functional Damage after Oxygen-glucose Deprivation/Reoxygenation
Xiao GAO ; Zheng-Wei WANG ; Na CAI ; Zhi TANG ; Chang-Xue WU ; Xiao-Lan QI ; Zhi-Zhong GUAN ; Yan XIAO
Chinese Journal of Biochemistry and Molecular Biology 2024;40(6):827-837
Exosomes can ameliorate neuronal cell injury induced by hypoxia-ischemia,but the relation-ship between astrocyte-derived exosomes(As-exo)and mitochondrial function,mitochondrial associated ER membrane(MAM)function and whether mitochondrial autophagy is relevant is currently unclear.The aim of this study was to investigate the role of astrocyte-derived exosomes in the regulation of mito-chondrial function,MAM and mitochondrial autophagy in PC 12 cells after oxygen and glucose depriva-tion/reoxygenation(OGD/R).Exosomes were extracted from the supernatant of the astrocyte culture me-dium by ultracentrifugation.Using the live cell imaging system,we observed that fluorescently labeled exosomes could show obvious enrichment in PC 12 cells at 24 h.Meanwhile,co-localization of exosomes with mitochondria could be observed under the laser confocal scanning microscope;mitochondrial pres-sure changes were detected using the Seahorse cellular energy metabolism fractionation instrument.The result showed that basal respiration in the OGD/R group,compared with that in the control group,proton leakage,maximal respiration and ATP-related respiration were significantly reduced(P<0.05 or P<0.01),and all four indexes were elevated and statistically significant in the OGD/R+exo group compared with the control group(P<0.05 or P<0.01).The results of the co-localization of the mitochondria and ER showed that the structure of the MAM was harmed by oxygen-sugar deprivation and then reoxygen-ation,and the structure of As-exo and the mitochondria appeared to have a distance-reduced polymeriza-tion phenomenon,while the mitochondria and ER co-localized.The co-localization results of mitochondri-a and ER showed that the structure of MAM was damaged by oxygen deprivation and reoxygenation,and the aggregation phenomenon of MAM was weakened by the treatment of As-exo;the flow-through results showed that As-exo could restore the decrease of the mitochondrial membrane potential and the elevation of the ROS by oxygen deprivation to a certain degree.Western blotting showed that As-exo could signifi-cantly inhibit the mitochondrial autophagy-associated tension protein homologue induced hypothetical ki-nase 1(PTEN induced kinase 1(PINK1)and Parkin protein(parkin RBR E3 ubiquitin protein ligase(Parkin))were elevated,and the addition of As-exo decreased LC3 Ⅱ/LC3 Ⅰ protein expression,ele-vated P62 protein expression,and reduced OGD/R-induced mitochondrial autophagy.The results showed that OGD/R treatment can cause mitochondrial dysfunction,MAM structural changes and increased mito-chondrial autophagy in PC12 cells,and As-exo treatment can improve mitochondrial function,attenuate the formation of MAM,and reduce mitochondrial autophagy in PC 12 cells,which can have the potential of preventing the reperfusion injury in ischemic stroke.
8.Signalling Pathways and Mechanisms of Linamarin in the Intervention of Disease
Xue-Ru YAN ; En-Peng HE ; Xiao-Di CAI
Chinese Journal of Biochemistry and Molecular Biology 2024;40(8):1057-1064
In recent years,the growing public awareness of personal health has sparked a surge in inter-est in the beneficial effects of polyphenols on the human organism.Extensive research by domestic and international scholars has established that polyphenols,due to their unique chemical properties,exhibit remarkable anti-inflammatory and antioxidant properties,leading to improvements in various diseases,in-cluding cancer,diabetes,and colitis.Notably,China stands as one of the world's largest producers and consumers of flax,a crop rich in lignans,a subclass of polyphenols.These flax lignans possess significant effects on the body,demonstrating immense potential for therapeutic applications.This paper delves into the origins,metabolic processes,and health benefits of flax lignans in China.It offers a comprehensive review of the mechanisms underlying flax lignans role in disease intervention,focusing on their interac-tions with relevant signalling pathways.Our findings suggest that flaxseed lignans can promote organismic health by either directly modulating gene expression or indirectly regulating signalling pathways.Further-more,flaxseed lignans can exhibit diverse effects depending on specific physiological conditions.
9.Effect of UVRAG Gene on Ferroptosis Induced by Sorafenib in K562 Cells
Yan-Min MA ; Yan WANG ; Min YANG ; Ze-Min CAI ; Xiao-Cheng YIN
Journal of Experimental Hematology 2024;32(3):653-657
Objective:To explore the effect of UV radiation resistance-associated gene(UVRAG)on ferroptosis induced by sorafenib in leukemia K562 cells.Methods:K562 cells were treated with 0,0.625,1.25,2.5,5,10,and 20μmol/L sorafenib for 24 or 48 hours,and the cell viability was detected by CCK-8 assay.Flow cytometry technology was used to detect the changes of reactive oxygen species(ROS)in K562 cells treated with 0,5,and 10 μmol/L sorafenib for 24 hours.Western blot was used to detect the protein expression of GPX4 in K562 cells treated with 0,5,and 10μmol/L sorafenib and pretreatment with ferroptosis inhibitor.A recombinant lentiviral vector was used to construct UVRAG overexpression cell line in K562 cells.qPCR and Western blot were used to verify UVRAG gene overexpression,and Western blot detected the effect of UVRAG on the protein expression of GPX4 and HMGB1 after treatment with sorafenib.Results:Different concentrations of sorafenib could significantly inhibit the proliferation of K562 cells,and the cell viability gradually decreased with the increase of concentration(r24h=-0.9841,r48 h=-0.9970).The level of ROS was increased(When the concentration was 10 μmol/L,P<0.00 1),while the expression of GPX4 protein was decreased in the process of 0,5,10 μmol/L sorafenib-induced K562 cell death(P<0.05),and the decrease in GPX4 protein could be partially reversed by pretreatment with ferroptosis inhibitor(P<0.05).Compared with NC group and NC-Sorafenib group,the expression of GPX4 protein was significantly decreased(both P<0.05),while HMGB1 protein was significantly increased(both P<0.05).Conclusion:Sorafenib can induce ferroptosis in K562 cells,and this process can be promoted by UVRAG.
10.Horseshoe kidney transplantation: a report of 2 cases
Qiong CHEN ; Yehong YAN ; Zeyu CAI ; Jialiang HAN ; Xingjian ZHANG ; Qi XIAO
Chinese Journal of Organ Transplantation 2024;45(11):807-810
To explore the feasibility and experience of kidney transplantation with horseshoe kidney as donor kidney. The horseshoe kidney donated by a brain dead donor was obtained by in-situ perfusion and whole piece incision. After methylene blue staining was injected into the inferior pole artery of the kidney and separated from the isthmus along the edge of the stained site, two kidney donors were divided into two recipients with successful implantation. After renal transplantation, the blood supply of the two donor kidneys was good. During the perioperative period, there was no bleeding or urine leakage. Postoperative ureteral obstruction occurred in one recipient. After the double J-tube drainage was ineffective, autologous ureter was anastomoted with the renal pelvis of the transplanted kidney. Up to now, the renal function of two recipients remained stable. According to literature analysis, kidney transplantation with well-functioning horseshoe kidney as donor kidney is safe and feasible, but its postoperative complication rate is higher than that of conventional kidney transplantation.

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