1.Mechanism of action of Qingre huatan huoxue decoction against atherosclerosis based on macrophage polarization
Huaping ZHONG ; Qicheng ZHU ; Zhengwei ZOU ; Zhengyi HE ; Heping XIE ; Xu CHEN ; Zhisheng DUAN ; Tian XIAO
China Pharmacy 2026;37(4):438-443
OBJECTIVE To explore the mechanism of action of Qingre huatan huoxue decoction against atherosclerosis (AS)based on macrophage polarization. METHODS Using atorvastatin served as the positive control, the drug-containing serum of the Qingre huatan huoxue decoction was prepared to treat RAW264.7 macrophages. Macrophage viability, apoptosis rate, and the fluorescence intensities of CD86 and CD206 were measured, along with the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Apolipoprotei n E-deficient (ApoE -/- ) mice (AS model mice) fed with a high-fat diet were randomly assigned to model group, atorvastatin group (2.6 mg/kg), and low-, medium- and high-dose groups of Qingre huatan huoxue decoction (90, 180, 360 mg/kg), respectively. C57BL/6J mice fed with a standard diet served as the normal control group, with 10 mice per group. The treatment group mice were administered the corresponding drugs intragastrically, once daily, for 8 consecutive weeks. Serum levels of TNF-α and IL-1β were measured in all groups. Lipid deposition in the aorta (assessed by the percentage of plaque in the entire aorta and aortic root) and morphological changes in the aortic root were observed. Expression levels of CD86 and CD206 in aortic tissue, as well as the protein expression levels of inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), AMP-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), and peroxisome proliferator-activated receptor γ (PPAR-γ) in aortic tissues were all detected. RESULTS Cell experiment results showed that, at concentrations of 5-100 μg/mL, the drug-containing serum of the Qingre huatan huoxue decoction significantly increased RAW264.7 cell viability ( P <0.05). The drug-containing serum of the Qingre huatan huoxue decoction at concentrations of 10, 50, and 100 μg/mL, along with atorvastatin, significantly reduced apoptosis rates, CD86 fluorescence intensity, and TNF-α and IL-1β levels in RAW264.7 cells, while markedly enhancing CD206 fluorescence intensity ( P <0.05). Animal experiment results showed that, compared with the model group, all dosage groups of Qingre huatan huoxue decoction and the atorvastatin group showed significantly reduced/down-regulated levels of TNF-α and IL-1β in serum, along with decreased aortic total and root plaque percentages, CD86 expression, and iNOS protein expression. CD206 expression and Arg-1, p-AMPK/AMPK, PPAR-γ protein expression were significantly up-regulated ( P <0.05). Pathological morphology of the aorta showed varying degrees of improvement. CONCLUSIONS The formula of Qingre huatan huoxue decoction exerts its anti-AS effects by regulating macrophage polarization, increasing the proportion of M2 macrophages, thereby effectively inhibiting AS plaque formation and reducing inflammatory responses.
2.AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing.
Kaiyi WANG ; Xinhai CHEN ; Nan LI ; Huimin FENG ; Xiaoyi LIU ; Yifei WANG ; Yanfei WU ; Yufeng GUO ; Shuoshuo XU ; Lu YAO ; Zhaohua ZHANG ; Jun JIA ; Zhishu TANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2025;15(8):4193-4209
The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.
3.Role of Iron-lipid Disorder in Nonalcoholic Fatty Liver Disease and Research Progress of Traditional Chinese Medicine Intervention: A Review
Yanxu CHEN ; Lei ZHANG ; Zhisheng JIN ; Qinyuan ZHANG ; Xiaoxue JIANG ; Changqing XU ; Pengcheng DOU ; Cong SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):281-290
Nonalcoholic fatty liver disease (NAFLD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Cell death caused by iron-lipid disorder is a new mode of regulating programmed cell death, which is characterized by lipid peroxidation induced by the accumulation of lipid reactive oxygen species and excessive accumulation of iron ions induced by iron metabolism disorders. Among them, iron homeostasis disorder and metabolic pathway disorder are the main causes of iron-lipid disorder, which play an important role in a variety of pathological processes related to cell death. Because the liver is an important organ for iron storage and lipid metabolism, iron-lipid disorder is an ideal target for liver disease, and inhibition of iron-lipid disorder may become a new strategy for the treatment of NAFLD. However, the pathogenic relationship and mechanism between NAFLD and iron-lipid disorder have not been fully elucidated. Based on the complex molecular regulation mechanism of iron-lipid disorder, by expounding the role of iron-lipid disorder in NAFLD and its related mechanism, this paper summarizes the research status of traditional Chinese medicine on the target treatment of NAFLD in recent years, so as to provide a new perspective and point out a new direction for the treatment of NAFLD in the future.
4.Correlation Between TyG Index,MHR and Coronary Lesions,Myocardial Ischemia in Patients with Coronary Heart Disease,and the Value of Combined Detection
Shuangshuang XU ; Wei ZHAO ; Lei JIANG ; Huajiang LIU ; Fang WANG ; Zhisheng TAN ; Likun ZHOU
Journal of Kunming Medical University 2024;45(3):65-71
Objective To investigate the correlation of triacylglycerol glucose(TyG)index,monocyte to high-density lipoprotein cholesterol ratio(MHR)with coronary artery disease and myocardial ischemia degree in coronary heart disease(CHD),and to analyze the two Predictive value of coronary artery disease and myocardial ischemia degree.Methods CHD patients from the 920th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from January 2019 to January 2022 were selected as the study group(n = 150),and healthy physical examination subjects from the same period were selected as the control group(n = 75).The TyG index and MHR of the two groups were compared and analyzed.The extent of coronary artery disease was evaluated based on the Gensini score,and the TyG index and MHR of patients with different coronary lesions and myocardial ischemia were compared,and their correlation with Gensini score and myocardial ischemia was analyzed.The predictive value of TyG index,MHR,and the combined detection of both for coronary lesions and myocardial ischemia was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).Results The TyG index and MHR of the study group were(4.12±0.35)and(0.26±0.08)×109,respectively,which were higher than those of the control group(4.94±0.55)and(0.43±0.12)×109,and the TyG index and MHR of severe coronary artery disease>moderate coronary artery disease>mild coronary artery disease,acute myocardial infarction TyG index,MHR>unstable angina pectoris>stable angina pectoris(P<0.05);TyG index and MHR were positively correlated with Gensini score(r = 0.621,0.635,P<0.05),and positively correlated with the severity of myocardial ischemia(r = 0.617,0.642,P<0.05).The AUC of TyG index and MHR for the joint identification of mild coronary artery disease and moderate coronary artery disease was 0.917,which was greater than the AUCs of 0.749 and 0.832 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of mild to moderate coronary artery disease and severe coronary artery disease was 0.935,which was greater than the AUCs of 0.770 and 0.767 for the two conditions individually(P<0.05).The AUC of TyG index and MHR for the joint identification of stable angina pectoris and unstable angina pectoris was 0.922,which was greater than the AUCs of 0.812 and 0.824 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of stable angina pectoris,unstable angina pectoris,and acute myocardial infarction was 0.913,which was greater than the AUCs of 0.708 and 0.714 for the two conditions individually(P<0.05).Conclusions TyG index and MHR are positively correlated with Gensini score and myocardial ischemia degree.The combined detection of the two has a higher application value in the evaluation of coronary artery disease and myocardial ischemia degree.
5.3D printing precise positioning guided ulnar groove plasty for treatment of cubital tunnel syndrome
Hanqing DONG ; Xing WU ; Pengcheng XU ; Qingwen WANG ; Zhisheng ZHANG ; Jianyong ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(18):2825-2829
BACKGROUND:With the increase of patients with cubital tunnel syndrome,ulnar groove plasty does not affect the normal anatomical structure and distribution of the ulnar nerve,which is one of the main surgical procedures for the treatment of cubital tunnel syndrome.3D printing combined with ulnar groove plasty can more accurately position the expansion depth and width of the ulnar groove to avoid some surgical complications. OBJECTIVE:To investigate the effect of 3D printing technology combined with ulnar groove plasty on nerve electrophysiology and prognosis in patients with cubital tunnel syndrome. METHODS:A total of 70 patients with moderate and severe cubital tunnel syndrome who were treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into two groups,with 35 cases in each group.The control group underwent traditional ulnar groove plasty.The observation group underwent 3D printing technology combined with ulnar groove plasty.The patients were followed up for 3 months.The clinical efficacy,latency,amplitude of compound muscle action potential of abductor pollicis brevis of the affected limb and ulnar nerve motor conduction velocity,grip strength on the affected side,pinch strength of the middle and thumb fingers,S-W monofilament of the little finger,two-point discrimination of the little finger,and Disabilities of the Arm,Shoulder and Hand Questionnaire score were compared between the two groups. RESULTS AND CONCLUSION:(1)Compared with the control group(74%),the excellent and good rate was significantly higher in the observation group(91%)(P<0.05).(2)Compared with pre-treatment,the latency of compound muscle action potential of abductor pollicis brevis of affected limb was significantly shorter and the wave amplitude and ulnar nerve motor conduction velocity were significantly higher in the two groups after treatment.The latency was significantly shorter and the wave amplitude and ulnar nerve motor conduction velocity were significantly higher in the observation group than those in the control group(P<0.05).(3)Compared with pre-treatment,the grip strength,middle finger and thumb pinch strength of the affected side,S-W monofilament of the little finger and two-point discrimination of the little finger were significantly decreased in the two groups after treatment.The grip strength,middle finger and thumb pinch strength on the affected side were greater,S-W monofilament of the little finger and two-point discrimination of the little finger were significantly smaller in the observation group than those in the control group(P<0.05).(4)Compared with pre-treatment,the Disabilities of the Arm,Shoulder and Hand Questionnaire scores of the two groups were significantly reduced after treatment,and the Disabilities of the Arm,Shoulder and Hand Questionnaire scores of the observation group were significantly lower than those of the control group(P<0.05).(5)It is concluded that 3D printing technology combined with ulnar groove plasty in the treatment of cubital tunnel syndrome can effectively improve its clinical efficacy,promote the neurophysiological recovery of patients,and enhance the function of fingers and upper limbs,which has high clinical application value.
6.Effect of Intraoperative Shaping,Screw Distribution,and Postoperative Healing on Plate Biomechanics
Wang ZHOU ; Jianqing XU ; Siyuan HE ; Shu ZHANG ; Junwen WANG ; Jing JIAO ; Bobin MI ; Guohui LIU ; Weiwei ZHU ; Zhisheng HE ; Liuyun ZHANG ; Mengxing LIU
Journal of Medical Biomechanics 2024;39(4):644-650
Objective To analyze the influence of shaping on the bending strength of bone plates and the influence of different locking nail distributions on plate force to provide biomechanical references for shaping plates and selecting different locking nail distributions.Methods Finite element simulation analysis of the four-point bending strength of a plate was performed according to the YY/T 0342-2020 standard.Theoretical analysis and finite element simulation method were used to analyze the force on prosthesis models with different lock-nail distributions.Results At 30° bending,the 3.7 mm-thick plate had 28%higher equivalent plastic strain than the 2.7 mm-thick plate.The 3.7 and 2.7 mm-thick plates had ultimate bending angles of 55° and 67°,respectively.The crease had little impact on the plate stress.The four-point bending strength and equivalent bending stiffness of the unshapeed structure were 2.64 N·m and 1.12 N·m2,respectively.The four-point bending strength and equivalent bending stiffness with the crease were 2.63 N·m and 1.10 N·m2,respectively.After forward and backward bending,the four-point bending strength of the plate decreased from 2.64 to 2.45 N·m by approximately 7.72%,and the equivalent bending stiffness decreased from 1.12 to 0.98 N·m2 by approximately 12%.The impact was obvious.After implantation of tamponade screws,the four-point bending strength of the single-hole plate improved significantly from 2.64 to 3.15 N·m,by approximately 19.32%and the equivalent bending stiffness increased from 1.12 to 1.14 N·m2,by approximately 2.1%.At least two locking holes were reserved on both sides of the fracture line.Not inserting the locking screw reduced the stress by approximately 50%compared with the full insertion of the locking screw.During 15-week postoperative walking without bone callus formation,the material stress of TC4 reached 852.7 MPa and yielding occurred.Conclusions In a clinical scenario where larger shaping is required,it is not suitable for plates with larger thicknesses and plate fractures are more likely to occur after large-thickness shaping.This can guide the clinical selection of plates with appropriate thickness based on the shaping angle,and tamponade screws can be implanted in extreme cases.Fixing locking screws clinically is recommended;however,a method of fixing the locking screws with full screws is not recommended.The biomechanical effect is best when two locking holes at both ends of the fracture line are maintained without fixing the locking screws.
7.Fibroblast growth factor-2 inhibits vascular smooth muscle cell apoptosis and pro-motes its proliferation by suppressing the TET2/UQCRH expression
Ruiyan XU ; Wen LI ; Xinyuan LIU ; Tong YAO ; Shunlin QU ; Dangheng WEI ; Zuo WANG ; Zhisheng JIANG ; Guohua LI
Chinese Journal of Arteriosclerosis 2024;32(10):843-849
Aim To explore the role of the ten-eleven translocation 2(TET2)/ubiquinol-cytochrome C reductase hinge protein(UQCRH)axis in the inhibition of vascular smooth muscle cell(VSMC)apoptosis by fibroblast growth fac-tor-2(FGF-2).Methods Cultured VSMCs were divided into control group,FGF-2 group,and FGF-2+fibroblast growth factor receptor(FGFR)pan-inhibitor LY2874455 group.VSMCs overexpressing TET2(OETET2)or UQCRH(OEUQCRH)were divided into control group,FGF-2 group,and OETET2+FGF-2 or OEUQCRH+FGF-2 group.Ho-echst33342 and PI staining were used to detect cell apoptosis,CCK-8 assay was employed to measure cell proliferation,and Western blot was used to examine the expression levels of apoptosis-related proteins pro-Caspase-3,cleaved Caspase-3,Bax,Bcl-2,as well as TET2 and UQCRH.The NCBI and methprimer websites were utilized for predicting and analyzing CpG island sites in the UQCRH gene promoter.Results FGF-2 could inhibit VSMC apoptosis,promote proliferation,downregulate apoptosis-related proteins cleaved Caspase-3,Bax,TET2,and UQCRH expression,and upregulate anti-ap-optotic protein Bcl-2 expression(compared with control group,P<0.05).However,it did not affect pro-Caspase-3 ex-pression(compared with control group,P>0.05).LY2874455 could counteract the effects of FGF-2(compared with FGF-2 group,P<0.05).Overexpression of TET2 or UQCRH could reverse the anti-apoptotic and pro-proliferative effects of FGF-2 on VSMC,with upregulation of apoptosis-related protein expression and downregulation of anti-apoptotic protein expression(compared with FGF-2 group,P<0.05).The UQCRH gene promoter region contained three CpG islands.Overexpression of TET2 could upregulate UQCRH expression in VSMC treated with FGF-2(compared with FGF-2 group,P<0.05).Conclusion FGF-2,by inhibiting TET2 expression and UQCRH expression,reduces VSMC apoptosis and promotes its proliferation.
8.New insights into the mechanisms of atherosclerosis
Chinese Journal of Arteriosclerosis 2024;32(11):921-931
Atherosclerosis is a chronic vascular disease primarily affecting large and medium-sized arteries,involving multiple complex pathogenic factors.In recent years,numerous research trends in atherosclerosis,such as in-flammation,gut microbiota,pyroptosis,ferroptosis,autophagy,cuproptosis,exosome and non-coding RNA have emerged.This article aims to review the recent advancements in these research directions,with the hope of opening new avenues for the mechanism of atherosclerosis and the treatment of diseases related to atherosclerosis.
9.Mechanism of Hedysari Radix Polysaccharide on Diabetic Nephropathy in db/db Mice Based on JAK2/STAT3 Signaling Pathway
Yanxu CHEN ; Zhisheng JIN ; Xiaoxue JIANG ; Boling ZHANG ; Yaoqin FU ; Caiyun JIN ; Qinyuan ZHANG ; Changqing XU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):65-71
ObjectiveTo observe the effect of Hedysari Radix polysaccharide (HRP) on the Janus kinase 2 (JAK2)/signal transducer and activator of transcription protein 3 (STAT3) signaling pathway in diabetic nephropathy db/db mice. MethodFifty db/db mice were randomly divided into model group, irbesartan group (irbesartan suspension, 22.75 mg·kg-1), and high-, medium-, and low-dose HRP groups (HRP suspension, 200, 100, 50 mg·kg-1) according to the body weight, with 10 mice in each group. Another 10 C57BL/6 mice were assigned to the normal group. The mice were treated with corresponding drugs by gavage, while those in the normal group and the model group received distilled water at 5 mL·kg-1. The mice in the six groups were administered once a day by gavage for 12 consecutive weeks. The uric acid (UA), triglycerides (TG), and total cholesterol (TC) were detected. Periodic acid-Schiff (PAS) staining and Masson staining were used to observe the pathological changes in kidney tissues. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect the protein and mRNA expression levels of JAK2, STAT3, suppressor of cytokine signaling 3 (SOCS3), and tumor necrosis factor-α (TNF-α) in the kidney. ResultAfter 12 weeks of treatment, compared with the normal group, the model group showed significant pathological ultrastructural changes in kidney tissues and increased UA, TG, and TC levels (P<0.01). Compared with the model group, the high- and medium-dose HRP groups and the irbesartan group showed improvement in pathological ultrastructure of kidney tissues and reduced UA, TG, and TC levels (P<0.05, P<0.01). Compared with the normal group, the model group showed a decrease in SOCS3 protein and mRNA expression levels and an increase in JAK2, STAT3, and TNF-α protein and mRNA expression levels (P<0.01). Compared with the model group, the high- and medium-dose HRP groups and the irbesartan group showed an increase in SOCS3 protein and mRNA expression levels and a decrease in JAK2, STAT3, and TNF-α protein and mRNA expression levels (P<0.05, P<0.01). ConclusionHRP can alleviate renal damage in diabetic nephropathy to a certain extent, and its mechanism may be related to the inhibition of the activation of the JAK2/STAT3 signaling pathway.
10.Advances in the levels of neurotransmitters associated with attention deficit hyperactivity disorder in children with tic disorders
Wanbing XU ; Dan SUN ; Zhisheng LIU
International Journal of Pediatrics 2023;50(7):482-486
Tic disorders(TD)including Tourette syndrome are childhood-onset neurodevelopmental disorders characterized by motor and/or vocal tics that commonly affect children′s physical and mental health.More than half of TD patients also have attention deficit hyperactivity disorder(ADHD). The pathogenesis of TD is not clear, and it is believed to be related to the abnormal level of neurotransmitters caused by the dysfunction of the cortical-striatal-thalamic-cortical circuitry, and the disorder of neurotransmitters is also related to the pathogenesis of ADHD, but the current research results on the level of neurotransmitters in TD with comorbid ADHD are controversial, and even some neurotransmitters show completely opposite changes in the two diseases.This paper reviews the research progress of neurotransmitters in children with TD co-suffering from ADHD in recent years, in order to provide ideas for exploring its pathogenesis.

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