1.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
2.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
3.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
4.Mechanism and research progress of S100A8/A9 in the microenvironment before high-risk tumor metastasis
Hai-Xia MING ; Zhao-Hua LIU ; Yan-Jun WANG ; Ming SHEN ; Yan-Wen CHEN ; Yang LI ; Ling-Ling YANG ; Qian-Kun LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1991-1995
S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.
5.Effects of hypericin on bone metabolism,biomechanics and mechanism of osteoporosis in rats with chronic obstructive pulmonary disease
Ming-Xia SHEN ; Wen-Jun DING ; Hai-Bin XIE ; Yun ZHANG ; Xing-Xing YANG ; Yong-Rui GAO
The Chinese Journal of Clinical Pharmacology 2024;40(20):3003-3007
Objective To investigate the effect and mechanism of hypericin on osteoporosis(OP)in rats with chronic obstructive pulmonary disease(COPD).Methods COPD combined with OP rat model was established by cigarette combined with bacteria.The rats were randomly divided into control group,model group(COPD combined with OP model was constructed),experimental-L group(50 mg·kg-1 hypericin was given by intragastric administration after constructing COPD combined with OP model),experimental-H group(100 mg·kg-1 hypericin was given intragastric administration after constructing COPD combined with OP model),positive group(subcutaneous injection of 16 U·kg-1 salmon calcitonin after constructing COPD combined with OP model);each group was given 12 rats for 90 days.The lung function of rats was detected by pulmonary function apparatus;bone mineral density(BMD)was detected by micro-computed tomography(CT);serum bone metabolism and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA);Western blot assay was used to detect the relevant indicators of the pathway.Results The levels of forced vital capacity(FVC)in control group,model group,experimental-H group and positive group were(10.42±1.40),(4.10±0.60),(6.75±0.37),(4.18±0.33)mL,respectively;BMD levels were(0.31±0.04),(0.12±0.02),(0.28±0.03),(0.29±0.04)g·mm-3,respectively;bone alkaline phosphatase(BALP)levels were(200.04±20.03),(80.80±6.00),(148.16±14.23),(173.97±23.55)U·L1,respectively;interleukin-1β(IL-1β)levels were(122.60±8.70),(695.59±74.84),(422.41±44.86),(527.90±39.36)pg·mL-1,respectively;phosphorylated p38 mitogen-activated protein kinase(p-P38)protein expression levels were 0.99±0.11,0.36±0.05,0.79±0.08,0.36±0.04,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P<0.05);the above indexes in experimental-H group were significantly different from those in model group(all P<0.05).Conclusion Hypericin can inhibit inflammatory response,improve bone metabolism and biomechanics.
6.Effects of propranolol on femoral fracture healing in mice via miR-92a-3p
Jin ZHANG ; Zhi-Wei CHEN ; Sheng-Zhong XUE ; Wen-Jie ZHOU ; Jiu-Xia WANG ; Jian-Jun SHEN
The Chinese Journal of Clinical Pharmacology 2024;40(20):3028-3032
Objective To explore the effect of propranolol on femoral fracture healing in mice through regulation of microRNA-92a-3p(miR-92a-3p)and its mechanism.Methods C57BL/6J male mice were randomly divided into sham group(equal amount of 0.9%NaCl),model group(equal amount of 0.9%NaCl),experimental group(50 mg·kg-1 propranolol administration),inhibitor group(mice were injected with 100 mg·kg-1 miR-92a-3p inhibitor via tail vein on the basis of the experimental group).Femur was severed and molded in all mice except sham operation group.X-ray was used to observe bone healing.Quantitative real time polymerase chain reaction was used to detect the expression of miR-92a-3p in femur tissues.The expression level of bone formation and bone metabolism markers was detected by enzyme linked immunosorbent assay.Western blot was used to detect the expression of pathway-related proteins.Results The X-ray scores of femur in sham group,model group and experimental group were 11.20±2.60,4.70±1.50 and 9.60±2.40,respectively;the relative expression levels of miR-92a-3p in sham operation group,model group,experimental group and inhibitor group were 1.00±0.09,0.73±0.06,0.90±0.07 and 0.78±0.06;alkaline phosphatase levels were(35.21±2.63),(43.16±3.29),(67.58±5.37)and(49.62±4.05)U·L-1,respectively;crosslaps levels were(4.57±0.52),(8.41±0.91),(4.26±0.67)and(5.73±0.84)ng·mL-1,respectively;the relative expression levels of brain derived neurotrophic factor were 1.00±0.14,0.58±0.05,0.83±0.09 and 0.71±0.06,respectively;the relative expression levels of phospho-tyrosine kinase receptor B were 1.00±0.12,0.62±0.05,0.89±0.08 and 0.76±0.07,respectively;the relative expression levels of phospho-extracellular regulated protein kinases were 1.00±0.11,0.54±0.04,0.78±0.07 and 0.65±0.05,respectively.The above indexes in the model group were compared with those in the sham group,those in the experimental group were compared with those in the model group,and those in the inhibitor group were compared with those in the experimental group,and the differences were statistically significant(P<0.05,P<0.001).Conclusion Propranolol can promote femoral fracture healing in mice,which may be achieved by up-regulating miR-92a-3p activation of brain derived neurotrophic factor/tyrosine kinase receptor B/extracellular regulated protein kinases signaling pathway.
7.Biomarkers Screening and Mechanisms Analysis of the Restraint Stress-Induced Myocardial Injury in Hyperlipidemia ApoE-/-Mice
Shang-Heng CHEN ; Sheng-Zhong DONG ; Zhi-Min WANG ; Guang-Hui HONG ; Xing YE ; Zi-Jie LIN ; Jun-Yi LIN ; Jie-Qing JIANG ; Shou-Yu WANG ; Han-Cheng LIN ; Yi-Wen SHEN
Journal of Forensic Medicine 2024;40(2):172-178
Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.
8.Comparison of the posterior hemipelvectomy of the greater trochanter approach with the standard Kocher-Langen-beck approach in the treatment of posterior acetabulum wall fractures
Jin ZHANG ; Jian-Jun SHEN ; Xiang HAI ; Chuan-Yuan LIU ; Wen-Jie ZHOU ; Zhi-Wei CHEN
China Journal of Orthopaedics and Traumatology 2024;37(8):786-792
Objective To compare the clinical efficacy of the posterior hemipelvectomy of the greater trochanter approach with the standard Kocher-Langenbeck(K-L)approach in the treatment of posterior acetabulum wall fractures and to explore a more optimal approach for the treatment of posterior acetabulum wall fractures.Methods Total of 26 patients with posterior ac-etabulum wall fractures were retrospectively analysed and divided into two groups:the posterior hemipelvectomy of the greater trochanter group(test group)and the standard K-L approach group(control group).In the test group,there were 24 patients including 16 males and 8 females with an average age of(42.00±4.52)years old,the time of injury to surgery was(6.75±1.15)d.In the control group,there were 23 patients including 16 males and 7 females with an average age of(41.00±5.82)years old,the time of injury to surgery was(7.09±1.20)days.The total hospital stay,length of incision,operation time,intraoperative bleeding,postoperative drainage,discharge,fracture reduction quality(Matta criteria),hip abduction muscle strength,hip func-tion(Merle d'Aubigne-Postel score),postoperative complications and the incidence of ectopic ossification were compared.Results All cases were followed up for 6 months.There was no significant difference in incision length,intraoperative bleeding and postoperative drainage between two groups(P>0.05).However,the operation time of the test group was shorter than that of the control group(P<0.05).There was no statistically significant difference in fracture reduction and hip function between two groups(P>0.05).The hip abduction muscle strength of test group was better than that of control group(P<0.05).In addition,there was no significant difference in the incidence of postoperative complications and heterotopic ossification between two groups(P>0.05).Conclusion Compared with the standard K-L approach,the posterior hemipelvectomy of the greater trochanter approach can shorten the operative time,has better recovery of the postoperative hip abduction muscle strength,ex-poses the view of the fracture involving the more comminuted posterior acetabulum wall or the fracture of the roof of the socket,improved the rate of fracture anatomical repositioning,provides a new idea for the clinical treatment of posterior acetabulum wall fractures,and allows patients to perform functional exercises at an early stage.
9.Risk factors for adenocarcinoma of duodenal papilla
Zhan ZHAN ; Kun LIU ; Wen LI ; Song ZHANG ; Bei TANG ; Wei CAI ; Qi LI ; Jun CHEN ; Lei WANG ; Shanshan SHEN
Chinese Journal of Digestive Endoscopy 2024;41(5):379-383
Objective:To explore the risk factors for duodenal papillary adenocarcinoma by comparing the differences in clinical and endoscopic features between patients with duodenal papillary adenomas and adenocarcinomas.Methods:This study retrospectively included patients diagnosed as having duodenal papillary adenocarcinoma and adenoma from January 1st 2018 to June 1st 2023 at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. Demographic, clinical manifestations, laboratory tests, imaging, endoscopic and pathological characteristics of patients with adenomas and adenocarcinomas were collected and compared. Multivariable logistic regression analysis was employed to identify high-risk factors for duodenal papillary adenocarcinoma.Results:A total of 119 cases of adenocarcinoma and 171 cases of adenoma were included. There were statistically significant differences between the two groups in terms of patient age, body mass index (BMI), clinical symptoms, family history of malignant tumors, bile duct dilation, pancreatic duct dilation, lesion size, adenoma site classification, stage assessed by EUS, and involvement of the bile and pancreatic ducts ( P<0.05). Univariate logistic regression analysis revealed that non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, involvement of the bile and pancreatic ducts assessed by EUS, age ≥60 years, lesion size ≥1.5 cm, clinical symptoms, family history of malignant tumors, bile duct dilation, and pancreatic duct dilation were risk factors for duodenal papillary adenocarcinoma. Multivariate logistic regression analysis showed that non-ampullary lesions ( OR=7.00, 95% CI:1.44-34.15, P=0.016), involvement not limited to the major duodenal papilla assessed by EUS ( OR=13.77, 95% CI: 4.69-40.45, P<0.001), age ≥60 years ( OR=2.52, 95% CI: 1.23-5.18, P=0.011), bile duct dilation ( OR=2.58, 95% CI: 1.12-5.94, P=0.026), and lesion size ≥1.5 cm ( OR=2.76, 95% CI:1.36-5.59, P=0.005) were independent risk factors for duodenal papillary adenocarcinoma. Conclusion:This study shows the independent risk factors for duodenal papillary adenocarcinoma, which include non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, age ≥60 years, bile duct dilation, and lesion size ≥1.5 cm.
10. Study on the protective effect of salidroside on memory impairment in mice under high altitude hypoxia
Ning-Ning QIN ; Yi-Ke SHEN ; Jun-Fei CHENG ; Rong WANG ; Ning-Ning QIN ; Yi-Ke SHEN ; Jun-Fei CHENG ; Xiao-Jing ZHANG ; Wen-Bin LI ; Rong WANG
Chinese Pharmacological Bulletin 2023;39(1):65-70
Aim To explore the effect of salidroside on the learning and memory ability of mice under high altitude hypoxia. Methods Forty-eight C57BL/6J male mice were randomly divided into plain control group, plateau model group and salidroside group according to their body weight, with 16 mice in each group. The animals in each group were given prophylactic doses for three days and then rushed to a plateau with an altitude of 4 010 m. After one day of hypoxia exposure, Morris water maze was performed to test the learning and memory ability of mice; malondialdehyde(MDA), hydrogen peroxide(H

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