1.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
2.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
3.Effect of modified Dingke Decoction in patient with post infectious cough: a retrospective real-world study
An'an WANG ; Yanlan LI ; Chengyong MA ; Jing SUN ; Weirong PAN ; Zherui WANG ; Tiansong ZHANG
International Journal of Traditional Chinese Medicine 2024;46(8):980-985
Objective:To explore the curative efficacy of Dingke Decoction in the treatment of post infectious cough based on the the real-world clinical data.Methods:Retrospective cohort study was conducted. 245 patients with cough after infection in the hospital of Jingan Chinese Medical Hospital from July 2021 to July 2022 were set as study objects. The fact that whether the patients with Dingke Decoction or not were divided into control group (90 cases, without Dingke Decoction) and treatment group (155 cases, with Dingke Decoction). By using propensity nearest neighbor 1:1 matching to balance the confounding factors before treatment, 56 cases were successfully matched in both groups. The control group was treated symptomatically according to the actual clinical situation, while the treatment group was treated with modified Dingke Decoction on the basis of symptomatic treatment in the control group. The treatment for both groups lasted for 2 weeks. TCM symptom scores and cough severity score were evaluated using the Leicester Cough Quality of Life Questionnaire (LCQ) before and after treatment. Levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were detected through ELISA; adverse reactions during the treatment were recorded, and the clinical efficacy was evaluated.Results:The total effective rate of the treatment group was 91.07% (51/56), while that of the control group was 76.79% (43/56), with a statistically significant difference between the two groups ( χ2=4.24, P=0.040). The daytime cough symptom score (1.03 ± 0.67 vs. 1.20 ± 0.66, t=7.40) and nighttime cough symptom score (0.74 ± 0.62 vs. 1.26 ± 0.54, t=6.27) in the treatment group were lower than those in the control group after treatment ( P<0.001). After treatment, the LCQ physiological (5.30 ± 0.79 vs. 4.78 ± 1.09, t=-2.44), psychological (5.33 ± 0.92 vs. 4.70 ± 1.12, t=-2.39), and social (5.23 ± 0.94 vs. 4.60 ± 0.81, t=-2.86) scores in the treatment group were higher than those in the control group ( P<0.05). After treatment, he treatment group serum IL-6 [(14.29 ± 3.94) ng/L vs. (19.99 ± 5.17) ng/L, t=4.80] and TNF-α [(36.23 ± 7.83) ng/L vs. (42.44 ± 7.63) ng/L, t=3.11] were lower than those in the control group ( P<0.01). The incidence of adverse reactions in the control group was 8.92% (5/56) and 5.36% (3/56), respectively, without statistical significance ( χ2=0.54, P=0.716). Conclusion:Based on the real-world research method, medicine Dingke Decoction can improve the clinical efficacy and the quality life of post infectious cough patients, and the mechanism may be related to reducing airway inflammation response.
4.Application progress of mesh in the environment of potential contaminated and contaminated abdominal hernia repair
Kun YU ; Yunfeng LI ; Binjie SUN ; Weirong JIANG ; Yongjiang YU
International Journal of Surgery 2022;49(1):62-66
Abdominal hernia repair is a challenging surgery with high complication rate and recurrence rate, especially in potentially contaminated or contaminated abdominal wall hernias. The application of hernia mesh has significantly reduced the recurrence rate. However, different types of meshes have their own advantages and disadvantages. There are still controversies regarding the selection of mesh in the environment of potential contaminated and contaminated abdominal hernia repair. The biological mesh, which was once considered that have anti-infection advantages and was widely used, has not been found to reduce the infection rate in recent studies, but instead leads to a higher recurrence rate and expensive medical costs. On the contrary, synthetic mesh represented by monofilament and large mesh polypropylene mesh have achieved good results in potentially contaminated or contaminated hernia repairs recently. The emergence of new types of meshes such as absorbable synthetic mesh may be a better choice for potentially contaminated or contaminated abdominal hernia repair. This article reviews the application progress of mesh in the environment of potential contaminated and contaminated abdominal hernia repair, aiming to provide reliable evidence for the selection of mesh for these patients.
5.Evolution and research progress of mesh fixation in laparoscopic trans-abdominal preperitoneal hernia repair
Weirong JIANG ; Kun YU ; Yunfeng LI ; Binjie SUN ; Yongjiang YU
International Journal of Surgery 2022;49(4):267-272
Since the development of tension-free hernia repair, the choice of mesh type and fixation mode has become a problem that surgeons must consider in operation. The selection of appropriate mesh fixation mode is of great significance to the prognosis of patients. In recent years, with the development of laparoscopic technology and hernia repair materials, new mesh types and mesh fixation techniques have been popularized in clinical practice, tack fixation and suture fixation have been less used in trans-abdominal preperitoneal hernia repair, and medical glue and self-gripping mesh have become the mainstream choice. Some scholars believe that in addition to large direct hernia, vacuum suction fixation is also a safe and effective fixation method. The best method of mesh fixation is still controversial, and the choice of intraoperative fixation methods is also to reach a unified standard. This paper reviews the advantages and disadvantages of different mesh fixation methods in trans-abdominal preperitoneal hernia repair, as well as the selection of intraoperative fixation methods, in order to provide basis for clinicians' intraoperative selection.
6.Progress in the diagnosis and treatment of chronic postoperative inguinal pain
Binjie SUN ; Yunfeng LI ; Kun YU ; Weirong JIANG ; Yongjiang YU
International Journal of Surgery 2021;48(7):493-499
Inguinal hernia is one of the most common diseases in general surgery. Surgery is the only treatment. In recent years, with the emergence and popularization of tension-free hernia repair, the recurrence rate has been lower than before. Chronic Postoperative Inguinal Pain (CPIP) has gradually become the focus of research. CPIP has now become one of the important efficacy indicators for inguinal hernia surgery. The etiology of CPIP is more complicated, mainly including neuropathic pain, non-neuropathic pain, somatic pain and visceral pain. Female, young, obese, low pain control, preoperative anxiety, preoperative pain, high pain sensitivity and other patient factors, and experience of the surgeon, open hernia repair, weight patch, patch fixation, surgery Surgical factors such as post-acute pain are risk factors for CPIP. CPIP is not only a product of neuropathic and nociceptive pain, but is also affected by various factors such as psychology, emotion, cognition, and genetics. Therefore, detailed medical history, physical examination, and correct pain and quality of life assessment tools are essential for the diagnosis of CPIP is very necessary. The treatment of CPIP should follow certain steps. The first choice is anticipatory treatment, drug treatment, psychological and behavioral treatment, physical therapy and other conservative treatments and interventional treatments, If the pain relief is not obvious after 6 months to 1 year by the above methods, surgical treatment is considered. So far, preventive analgesia and standardized surgery are the most important means to improve the prognosis of patients.
7.Advance in abdominal hernia repair based on enhanced recovery after surgery
Yunfeng LI ; Yongjiang YU ; Binjie SUN ; Weirong JIANG ; Kun YU
International Journal of Surgery 2021;48(10):695-699
Enhanced recovery after surgery (ERAS) is a systematic approach to care that optimizes perioperative management, improves clinical outcomes, and reduces healthcare costs. ERAS has been introduced into abdominal hernia repair in recent years. Preoperative management was optimized through health education, smoking cessation, weight control, blood glucose and pain management, infection and thrombosis prophylaxis. And prevention of hypothermia, standardized anesthesia management, fluid replacement control, minimally invasive operation, controlled catheter placement and other intraoperative management optimization measures. And multi-mode analgesia, early postoperative activity, recovery of gastrointestinal function and control of blood glucose and other postoperative management optimization measures effectively reduced the incidence of complications such as surgical site infection, alleviated the pain of patients, and shortened the hospital stay. ERAS factors such as perioperative pain management, early postoperative activity, and recovery of gastrointestinal function are the key to shorten hospital stay and improve prognosis during abdominal wall hernia repair. ERAS can be used safely and effectively for abdominal hernia repair.
8.Retrospective analysis of the predictive value of immunoglobulin and complement combined leukocyte levels on the outcome of severe COVID-19
Yong ZHAO ; Weirong ZENG ; Fuan YU ; Youtao HU ; Li XU ; Junfeng ZENG ; Kunyun JIA ; Jianbin SUN ; Jiancheng TU
Chinese Journal of Experimental and Clinical Virology 2021;35(1):1-6
Objective:To retrospectively analyze the blood leukocytes (WBC), lymphocytes (LYM), lymphocyte% (LYM%), and serum total immunoglobulin (IGA, IGG, IGM) and complement (C3, C4) index levels to explore its predictive value for the outcome of COVID-19 severe pneumonia.Methods:Eighty-five COVID-19 patients with severe pneumonia diagnosed in our hospital were randomly selected and were divided into good outcome group (50 cases) and poor outcome group (35 cases). WBC, LYM, LYM%, IGA, IGG, IGM, and C3, C4 level data, and analyze the differences between the two groups, the correlation of each indicator, and ROC curves of single and joint detection to explore relationship between indicators and outcomes, and the predictive efficacy of indicators on outcomes.Results:Differences in WBC, LYM, LYM%, IGG, and IGA levels were significant between the two groups ( P=0.000, 0.015, 0.000, 0.000, 0.001), among them with significant differences, LYM and LYM% were significantly positively correlated ( r=0.669, P=0.000), while WBC and LYM% levels were significantly negatively correlated ( r=-0.600, P=0.000), WBC and IGA levels were significantly positively correlated ( r=0.283, P=0.009) and IGG and IGA levels were also significantly positively correlated ( r=0.0.442, P=0.000); After logistic regression analysis, WBC, LYM, LYM%, IGG, and IGA are all important influencing factors ( P=0.001, 0.022, 0.000, 0.000, 0.003); but only the levels of WBC, IGG, and LYM% are Independent risk factors ( P=0.034, 0.004, 0.001), the ROC curve of the single detection and joint detection of their predicted outcome performance, respectively, and the max AUC (AUC=0.890, P=0.000) at the time of joint testing of WBC, LYM% and IGG, index YI=0.657, it has the greatest predictive power for adverse outcomes, with a sensitivity of 77.10% and a specificity of 88.00%. IGM, C3, C4, IGG/IGM, and C3/C4 levels were not significantly different( P=0.066, 0.204, 0.076, 0.310, 0.156). Conclusions:The levels of WBC, LYM, LYM%, IGG, and IGA in the early admission of COVID-19 infected patients with severe pneumonia have important predictive value for the outcome of them. WBC, LYM% and IGG levels are independent risks and joint detection of the three indexes have the best predictive performance.
9.Outcomes of allogeneic hematopoietic stem cell transplantation for 18 patients with paroxysmal nocturnal haemoglobinuria.
Feng CHEN ; Depei WU ; Xiaowen TANG ; Miao MIAO ; Chengcheng FU ; Huiying QIU ; Zhengming JIN ; Shengli XUE ; Xiao MA ; Aining SUN ; Weirong CHANG ; Changgeng RUAN
Chinese Journal of Hematology 2015;36(12):1005-1010
OBJECTIVETo evaluate the outcomes of allogeneic hematopoietic stem cell transplantation(allo-HSCT)for paroxysmal nocturnal haemoglobinuria(PNH)and aplastic anemia(AA)- PNH syndrome.
METHODSThe clinical data of 18 PNH or AA-PNH patients, including 4 classic PNH and 14 AA-PNH, received allo-HSCT from Dec 2007 to Feb 2015 were analyzed retrospectively. Nine patients received HLA-haploidentical donor HSCT(1 patient received salvage HLA-haploidentical donor HSCT after the graft failure of double cord blood transplantation), 7 patients received HLA-identical sibling donor HSCT, and 2 HLA-identical unrelated donor HSCT. The conditioning regimens were as follow: 13 patients received modified BU/CY- based regimens, 5 non- myeloablative regimens [fludarabine (Flu) + antithymocyte globulin(ATG)+ cyclophosphamide(CY)or busulfan(BU)]. Prophylaxis for graft- versushost disease(GVHD): the patients with HLA-identical sibling donor received cyclosporine(CsA)plus short-term methotrexate(MTX), the patients with HLA -haploidentical donor or HLA-identical unrelated donor received CsA or tacrolimus(FK506)+ mycophenolate mofetil(MMF)+ short- term methotrexate (MTX).
RESULTSAll patients were engrafted successfully(1 patient engrafted by haploidentical donor after the graft failure of double cord blood transplantation). The median days of neutrophils(ANC)above 0.5 × 109/L and platelets (PLT) more than 20 × 10⁹/L were 11(10- 26)days and 15(11- 120)days, respectively. Three patients(17.6%)developed acute GVHD(aGVHD), 2 for grade Ⅱ aGVHD, 1 for grade Ⅳ aGVHD. Of 16 patients, 2 occurred limited chronic GVHD(cGVHD). After a median follow-up of 14.6(2.0-86.7)months, 3 patients(17.6%)died, out of which one died of severe aGVHD, one died of severe pulmonary infection, one pulmonary infection with transplant- associated thrombotic microangiopathy. The 5- year estimated disease free survival was(80.5 ± 10.2)%. No patient relapsed.
CONCLUSIONAllo-HSCT is an effective and curable therapy for PNH or AA-PNH with improved prognosis, and offers a valid therapeutic option for these patients before humanized monoclonal antibody against C5 are widely used clinically.
Anemia, Aplastic ; therapy ; Antilymphocyte Serum ; Busulfan ; Cyclophosphamide ; Cyclosporine ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hemoglobinuria, Paroxysmal ; therapy ; Humans ; Methotrexate ; Mycophenolic Acid ; analogs & derivatives ; Retrospective Studies ; Siblings ; Tacrolimus ; Transplantation Conditioning ; Treatment Outcome ; Unrelated Donors ; Vidarabine ; analogs & derivatives
10.Lumbar Intervertebral Discs Degeneration:A Quantitative Evaluation by Using T2 Mapping
Xiaobo ZHANG ; Weirong SUN ; Xiao ZHANG ; Peng DU ; Xiaofeng HE ; Xin ZHANG ; Yueyong XIAO
Chinese Journal of Medical Imaging 2015;(7):544-548
PurposePifrrmann scoring based on T2WI can only evaluate intervertebral disc qualitatively and is easily affected by the surrounding environment and imaging parameters. The present study attempted to make a quantificational study on lumbar intervertebral disc degeneration by using MR T2 mapping sequence so as to improve its diagnosis.Materials and Methods Sagittal T1FSE, sagittal and axial T2FSE, sagittal T2 mapping sequence were performed on 265 lumbar intervertebral discs from 53 subjects. The MR imaging was analyzed and all the discs were classified according to Pifrrmann scoring. T2 relaxation time of the discs was calculated and statistical analysis was conducted on its correlation.Results Among the 265 discs, 5 (1.9%) were scored as Pfirrmann I, 153 (57.7%) were scored as Pfirrmann II, 86 (32.3%) were scored as Pfirrmann III, 20 (7.5%) were scored as Pfirrmann IV, 1 (0.38%) were scored as Pifrrmann V. The average anterior annulus T2 values showed no difference between every Pfirrmann grade (P>0.05), while the difference of average posterior annulus T2 values was significant between groups (P<0.05). The relaxation time of anterior annulus was signiifcantly shorter than that of posterior annulus in the discs of Pifrrmann II-IV, whilst the reverse occurred in the discs of Pifrrmann I (P<0.05). The differences of the relaxation time of nucleus pulposus T2 values were signiifcant between groups of Pifrrmann grade I to IV (P<0.05). The T2 relaxation time of each partition of nucleus pulposus (ROI2/ROI3, ROI3/ROI4, ROI2/ROI4) was signiifcantly correlated (r=0.86, 0.76 and 0.63,P<0.05), the T2 relaxation time of anterior annulus and posterior annulus had no correlation (r=0.09, P<0.05), and the nucleus pulposus T2 values and Pfirrmann grade were negatively correlated (r=-0.78,P<0.05).Conclusion MR T2 mapping can quantitatively evaluate the T2 relaxation time of lumbar intervertebral discs, and is signiifcantly correlated with Pifrrmann grades.

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