1.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
2.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
3.Mechanism of Dangui Shaoyaosan in Alleviating Inflammatory Responses in Diabetic Kidney Disease by Modulating Macrophage Polarization in Kidneys of db/db Mice
Luyu HOU ; Linlin ZHENG ; Wenjing SHI ; Zixuan WANG ; Shilong GUO ; Zhe LYU ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):1-10
ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease (DKD), and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group, and forty db/db mice were randomly divided into a model group, low-, medium-, and high-dose Danggui Shaoyaosan groups (8.39, 16.77, 33.54 g·kg-1), and an irbesartan group (0.025 g·kg-1). All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention, 24-h urine samples were collected using metabolic cages, after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein (GSP), serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), and triglycerides (TG). The urinary albumin-to-creatinine ratio (UACR) was measured. Renal pathological changes were observed using hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and monocyte chemoattractant protein-1 (MCP-1) levels. Immunofluorescence (IF) was performed to detect F4/80 expression in renal tissue, and immunohistochemistry (IHC) was used to assess CD206 expression. Real-time quantitative polymerase chain reaction (Real-time PCR) was employed to measure the mRNA expression of TNF-α, IL-10, inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1). Western blot analysis was used to detect the protein expression of iNOS, Arg-1, CD86, and CD206 in renal tissue. ResultsCompared with the normal group, the model group showed increased levels of GSP, UACR, SCr, BUN, TC, and TG, elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1, and decreased IL-10 levels (P<0.01). Pathological examination revealed glomerular hypertrophy, mesangial cell proliferation with marked mesangial expansion, inflammatory cell infiltration, vacuolar degeneration of renal tubular epithelial cells, prominent glycogen deposition, and increased collagen fiber deposition. In addition, relative F4/80 fluorescence intensity was enhanced, CD206 expression in the glomeruli and renal interstitium was reduced, and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased, iNOS and CD86 protein expression was increased, and Arg-1 and CD206 protein expression was decreased (P<0.05, P<0.01). Compared with the model group, the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP, UACR, SCr, BUN, TC, and TG, reduced serum TNF-α and MCP-1 levels, and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced, CD206 expression in the glomeruli and renal interstitium was increased, and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased, iNOS and CD86 protein expression was reduced, and Arg-1 and CD206 protein expression was increased (P<0.05, P<0.01). ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization, promoting M2 anti-inflammatory macrophage polarization, reducing inflammatory responses, delaying the progression of renal fibrosis, improving renal pathological injury, and thereby exerting renal protective effects.
4.Mechanism of Danggui Shaoyaosan in Improving Inflammatory Response in Mice with Diabetic Kidney Disease Based on TLR4/p65/NLRP3 Signaling Pathway
Shilong GUO ; Ruijia LI ; Zixuan WANG ; Xinai WANG ; Luyu HOU ; Wenjing SHI ; Mengyuan TIAN ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):19-27
ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 (TLR4/NF-κB p65/NLRP3) signaling pathway in the renal tissues of db/db mice with spontaneous diabetes, and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease (DKD). MethodsThirty db/db mice were divided into five groups: A model group, Danggui Shaoyaosan low- (16.77 g·kg-1·d-1), medium- (33.54 g·kg-1·d-1), and high-dose (67.08 g·kg-1·d-1) intervention groups, as well as an irbesartan group (0.025 g·kg-1·d-1) by the random number table method, with 6 mice in each group. Additionally, 6 db/m mice were assigned to the normal group. After 8 weeks of intervention, the following parameters were determined by corresponding methods: body weight, fasting blood glucose (FBG), 24-hour urinary protein (24 h-UTP), and serum creatinine (SCr) levels, renal histopathological analysis by hematoxylin-eosin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining, the protein and mRNA expression levels of TLR4, NF-κB p65, NLRP3, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-18 (IL-18) by Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR), as well as TLR4, NF-κB p65, and NLRP3 protein expression in renal tissues by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group exhibited increased body weight, FBG, 24 h-UTP, and SCr levels (P<0.05); disordered renal structure, thickened basement membrane, and interstitial inflammatory cell infiltration, elevated TLR4, NF-κB p65, NLRP3, TNF-α, IL-1β, IL-6, and IL-18 expression; as well as decreased IL-10 expression (P<0.05). Compared with the model group, these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees (P<0.05). ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.
5.Research advances in mitochondrial dysfunction in the pathogenesis of hepatic fibrosis
Yudie HONG ; Jinchen GUO ; Weibing SHI ; Yujie SUN ; Jiamin WANG ; Tiantian GAO
Journal of Clinical Hepatology 2026;42(1):190-196
Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors, and it may progress to liver cirrhosis, portal hypertension, and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury, inflammatory cell infiltration with the release of inflammatory mediators, hepatic stellate cell activation, and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression, including the molecular pathways for hepatic fibrosis driven by metabolic disorders, energy deficiency, oxidative stress, mitochondrial dynamic imbalance, and autophagic dysfunction, all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis, in order to provide new therapeutic strategies for clinical management.
6.Status of anemia and iron deficiency among primary and secondary school students in Rural Nutrition Improvement Program areas of Guizhou Province in 2023
ZHU Shu, GUO Hua, LI Hongbo, SHI Zhu, WU Shengnan, HUANG Yiyanwen, SUN Yan, LIU Yiya
Chinese Journal of School Health 2026;47(2):178-182
:
To analyze the prevalence of anemia and iron deficiency among primary and secondary school students in Rural Nutrition Improvement Program areas of Guizhou Province in 2023, and to explore the related factors, so as to provide evidence for Rural Nutrition Improvement Program optimization.
Methods:
In September 2023, a stratified random cluster sampling strategy was used to select 40 rural compulsory education schools with rural nutrition improvement program in five counties of Guizhou Province. School level questionnaire was employed to collect information of basic characteristics and school meal implementation. A total of 7 826 primary and secondary school students aged 6-16 underwent anthropometry and hemoglobin (Hb) determination; serum ferritin (SF) was additionally measured in a random subsample of 1 795 pupils. Students in Grade 3 and above also completed a questionnaire covering demographic characteristics, dietary behaviours and nutrition knowledge. Group comparisons were conducted by Chi square test or Fisher s exact test, and multivariable Logistic regression models were constructed to identify factors associated with anemia and iron deficiency.
Results:
The overall Hb level was (133.21±12.95)g/L, with an anemia prevalence of 7.17%. The overall SF level was (69.58±59.01)μg/L, with an iron deficiency prevalence of 2.73%. Multivariable analysis showed that stunting ( OR =1.88), school menus without nutrient calculation ( OR =1.61) and absence of menu planning software in the current semester ( OR =2.34) independently increased anemia risk, whereas obesity reduced it ( OR =0.54) (all P <0.05). Girls ( OR =4.16) and Grades 7-9 ( OR =5.93) increased iron deficiency risk (both P <0.05). Compared with rarely eating fresh vegetables, students with consuming <3 kinds per day ( OR =0.08) or exactly 3 kinds per day ( OR =0.06) had lower iron deficiency risks (both P <0.05).
Conclusions
Anemia and iron deficiency are prevalent among primary and secondary school students in Guizhou. Targeted intervention measures should be implemented for key populations to enhance the effectiveness of nutrition improvement program.
7.Association of 24 hour physical activity index with screening myopia and obesity in school aged children
ZHOU Keyi, LIU Su, MAIHELIYAKEZI Tuersunniyazi, GUO Manyu, YU Hongjie, SHI Huijing
Chinese Journal of School Health 2026;47(2):203-207
Objective:
To develop a 24 hour physical activity index for school aged children, and to analyze the association of 24 hour physical activity index with screening myopia and obesity, so as to provide a more effective assessment tool for student health risk screening.
Methods:
From April to June 2024, a total of 451 students in Grades 3-4 from two monitored primary schools in Shanghai were selected using stratified cluster random sampling method. Data on eight core indicators, including daily moderate to vigorous physical activity time, total physical activity time, outdoor activity time, screen time, sleep duration, sleep efficiency, social jetlag and daytime sleepiness, were collected through questionnaires and accelerometer monitoring. Each indicator was standardized and synthesized into a 0-80 point school aged children s 24 hour physical activity index. Spearman correlation analysis and t-test were used to assess consistency between questionnaire and accelerometer derived indices. Multivariate Logistic regression was applied to analyze the association of strength of the composite index with single behavior indicators in screening myopia and overweight/obesity.
Results:
The compliance rates were higher for moderate to vigorous physical activity time and screen time (50.8%, 98.7%), while the compliance rate for outdoor activity time was only 42.6%, and that for sufficient sleep duration was merely 10.2%. There was no significant difference between the total scores derived from the questionnaire and accelerometer methods (45.13±5.83, 45.05±6.87, t=0.29, P >0.05), but they showed a strong positive correlation ( r=0.58, P <0.01). Multivariate Logistic regression revealed that adjusting for individual behaviors such as grade, gender and both parents being myopic, among single behavior indicators of 24 hour physical activity index, only insufficient outdoor activity time was significantly associated with screening myopia among school aged children ( OR=1.50, 95%CI =1.01-2.21); the detection risk of screening myopia and obesity in the low index group were higher than those in the high index group ( OR=2.47, 95%CI =1.02-5.96; OR=16.63,95%CI = 5.99- 46.20) (all P <0.05).
Conclusion
The developed 24 hour physical activity index for school aged children demonstrates good measurement accuracy and shows stronger associations with screening myopia and obesity than single behavior indicator.
8.Effect of remote ischemic preconditioning on preoperative heart rate variability in patients undergoing heart valve surgery: A randomized controlled trial
Zhipeng GUO ; Jian ZHANG ; Qiaoli WAN ; Fengyan SHI ; Rui LI ; Zongtao YIN ; Jinsong HAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(04):592-596
Objective To explore the effect of remote ischemic preconditioning (RIPC) on preoperative heart rate variability in patients with heart valves. Methods Patients scheduled to undergo on-pump cardiac valve surgery in the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, between January and July 2022 were initially enrolled. Eligible patients were randomly assigned at a 1 : 1 ratio to either the RIPC group or the control group. Relevant indicators of heart rate variability [standard deviation of NN interval (SDNN), standard deviation of mean value of NN interval in every five minutes (SDANN), mean square root of difference between consecutive NN intervals (RMSSD), percentage of adjacent RR interval>50 ms (PNN50), low frequency (LF) component, high frequency (HF) component and LF/HF] at 8 hours in the morning on the surgical day between two groups were compared. Results A total of 118 patients were initially assessed. After screening, 58 patients were excluded, and 60 patients provided written informed consent and were enrolled in the trial, with 30 allocated to the RIPC group and 30 to the control group. Seven patients in the control group and 5 patients in the RIPC group were subsequently excluded due to missing heart rate variability data resulting from cancelled operations. Finally, 23 patients in the control group and 25 patients in the RIPC group were included in the analysis. There was no statistical difference in baseline characteristics between the two groups, and there was no significant difference in heart rate variability 24 hours before intervention (P>0.05). After the intervention measures were taken, the comparison of the results of heart rate variability at 8 hours on the day of operation showed that SDNN and SDANN of patients in the RIPC group were higher than those in the control group, with statistical differences (P<0.05). Conclusion RIPC can stabilize the preoperative heart rate variability of patients undergoing cardiac valve surgery.
9.Wen-Shen-Tong-Du Decoction promoting spinal cord injury repair in mice
Ruihua ZHAO ; Sixian CHEN ; Yang GUO ; Lei SHI ; Chengjie WU ; Mao WU ; Guanglu YANG ; Haoheng ZHANG ; Yong MA
Chinese Journal of Tissue Engineering Research 2025;29(6):1118-1126
BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P<0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P<0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P<0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P<0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P<0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P<0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P<0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P<0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P<0.05),as well as a significant increase in Bax protein expression(P<0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P<0.05),as well as a significant decrease in Bax protein expression(P<0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.
10.The multi-center mid-term clinical outcomes of combined complete preservation of chordal structure mitral valve replacement with total anatomic complete arterial myocardial revascularization for coronary patients with moderate-to-severe or severe ischemic mitral regurgitation
Ke GUO ; Xujun CHEN ; Baoshi ZHENG ; Chao SHI ; Keli HUANG ; Yong CAO ; Chengquan LIAO ; Jingwei CHEN ; Yu LIN ; Chengxin LIU ; Quansheng CAO ; Lin SHEN ; Zhendong WANG
Chinese Journal of Surgery 2025;63(1):58-67
Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.


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