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.Analysis on health-related quality of life of migrant workers with pneumoconiosis in Hunan Province
Zhilin YU ; Xiaoli LIU ; Dan YU ; Lehua YANG ; Xiongbin XIAO ; Zhongchun ZHAN ; Weirong DAI ; Li LI
China Occupational Medicine 2023;50(3):301-304
Objective To understand the health-related quality of life (HRQOL) of migrant workers with pneumoconiosis who received basic medical treatment in Hunan Province. Methods A total of 613 migrant workers with pneumoconiosis who received basic medical treatment and assistance in Hunan Province was selected as the study subjects using stratified random sampling method. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to assess their HRQOL. Results The abnormality of the five dimensions of the EQ-5D health description system, from high to low, were as follows: daily activities, mobility, pain/discomfort, anxiety/depression, and self-care, with the abnormal rates of 50.9%, 46.8%, 41.1%, 21.0%, and 14.5%, respectively. The visual analogue scale (VAS) score of EQ-5D was (63.5±18.6) points. Patients with stage Ⅲ pneumoconiosis had high abnormality in mobility, daily activities, and pain/discomfort compared with those with stage Ⅰ and Ⅱ disease (all P<0.02). Patients in stage Ⅱ and Ⅲ of pneumoconiosis had higher incidence of anxiety/depression compared with those with stage I disease (all P<0.02). Patients with complications in addition to pneumoconiosis had higher abnormality in mobility, self-care, and pain/discomfort compared to those with simple pneumoconiosis or those eligible for lung lavage treatment (all P<0.02). Patients with simple pneumoconiosis had a higher incidence of anxiety/depression compared with those eligible for lung lavage treatment (P<0.02). Patients with stage Ⅲ pneumoconiosis had lower average VAS scores compared with stage Ⅰ and Ⅱ patients (all P<0.02). Patients with simple pneumoconiosis or those with complications had lower average VAS scores compared with those eligible for lung lavage treatment (all P<0.05). Conclusion The HRQOL of pneumoconiosis patients among migrant workers needs improvement, especially for patients with stage Ⅲ disease and those with complications. This study indicates the need of optimizing policies, raising the hospitalization expense limit for critically ill patients with stage Ⅲ pneumoconiosis or with complications, and improving their HRQOL.
4.Probe the syndrome differentiation system of six meridians of circular motion
Xianbin DENG ; Lujun CHEN ; Fang YAN ; Xing LIU ; Qiang ZHANG ; Weirong CHEN ; Jiansong ZHANG ; Wenjing CHEN ; Jiaona HE ; Yu LIAO
International Journal of Traditional Chinese Medicine 2022;44(10):1086-1091
The internal organs and meridians were associated with Yin and Yang, five elements, six qi, and time and space, based on the holistic view of heaven, earth and human, according to Huangdi Neijing. The syndrome differentiation system of six meridians and Zang Fu meridians were established by Shanghan Zabing Lun, on the basis of the three Yin, three Yang, six meridians, and five Zang system in Huangdi Neijing. We put forward the concept of the six meridians syndrome differentiation system of circular motion, considering that the six meridians syndrome differentiation system actually implies the theory of circular motion. The syndrome differentiation system was constructed with the circular model of one qi circulating around the road, rising left and falling right, corresponding up and down, and maintaining conservation in the middle as the core, integrating Yin and Yang, five elements, six qi, Zang Fu and meridians, qi, blood and body fluid, and the integration of heaven, earth and human, focusing on "disease location and disease nature", taking classical prescriptions as the main treatments, and cooperating with external treatments such as acupuncture and moxibustion. We organically combined the circular motion with the syndrome differentiation of the six meridians, systematically interpreted the physiological bases, pathological changes, progressive patterns, and the treatments, based on syndrome differentiation, by inheriting the classical thinking mode of Hetu, Luoshu,Zhouyi, Huangdi Neijing, ShennongHerbal Classic, and Shanghan Zabing Lun.
5.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.
6.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.
7.Analysis of risk factors of chronic postoperative inguinal pain after laparoscopic trans-abdominal preperitoneal hernia repair and construction of a nomogram prediction model
Weirong JIANG ; Xiaobei ZHANG ; Weigang WANG ; Dong CAO ; Baoshun YANG ; Yongjiang YU
International Journal of Surgery 2022;49(8):509-515,C1
Objective:To explore the risk factors of chronic postoperative inguinal pain for laparoscopic trans-abdominal preperitoneal hernia repair and establish a nomogram prediction model for it.Methods:The clinical data of 576 patients who underwent laparoscopic trans-abdominal preperitoneal hernia repair for inguinal pain at the First Hospital of Lanzhou University from January 2015 to December 2020 were analyzed retrospectively. According to different postoperative outcomes, patients were divided into chronic pain group ( n=54) and non-chronic pain group ( n=522), compared two groups of patients in the material, including gender, age, BMI, smoking history, history of drinking, hypertension, diabetes, chronic bronchitis, abdominal surgery history, history of inguinal hernia, hernia type, the hernial sac size, prophylactic use of antibiotics, VAS score, mesh fixation techniques, operation time, length of stay. Measurement data with normal distribution were expressed as ( ± s) and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M( Q1, Q3), and the Mann-Whitney U test was used for comparision between groups. Chi-square test was used to compare the measurement data of counting data.Multivariate logistic regression was used to analyze the independent risk factors for chronic postoperative inguinal pain. R software was used to establish the drawing of the nomogram prediction model, and the consistency index, calibration chart and area under the receiver operating characteristic curve was used to evaluate the predictive ability of the nomogram prediction model. Results:According to the results of the Logistic regression analysis, age≤45 years ( OR=2.202, 95% CI: 1.080-4.491), BMI≥24 kg/m 2 ( OR=2.231, 95% CI: 1.204-4.134), hernial sac≤5 cm ( OR=2.623, 95% CI: 1.309-5.257), recurrent hernia ( OR=2.769, 95% CI: 1.118-6.860), preoperative pain ( OR=4.121, 95% CI: 2.004-8.476), suture fixation ( OR=2.204, 95% CI: 1.151-4.219)and Postoperative acute pain (VAS>3) ( OR=5.814, 95% CI: 2.532-13.350) were independent risk factors for chronic postoperative inguinal pain ( P<0.05). Based upon the above independent risk factors, the nomogram prediction model was established and verified. The area under the curve of the nomogram prediction model was 0.779 (95% CI: 0.718-0.840, P<0.01). After internal verification, the concordance index value of the prediction model was 0.779. Conclusion:age≤45 years, BMI ≥24 kg/m 2, hernial sac≤5 cm, recurrent hernia, preoperative pain, suture fixation and Postoperative acute pain (VAS>3) are independent risk factors for chronic postoperative inguinal pain for laparoscopic trans-abdominal preperitoneal hernia repair, the nomogram prediction model has a good accuracy and discrimination with a high value of clinical application.
8.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.
9.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.
10.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.

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