1.Prognosis and influencing factors analysis of patients with initially resectable gastric cancer liver metastasis who were treated by different modalities: a nationwide, multicenter clinical study
Li LI ; Yunhe GAO ; Liang SHANG ; Zhaoqing TANG ; Kan XUE ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Bin KE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Hongqing XI ; Yun TANG ; Zhi QIAO ; Han LIANG ; Jiafu JI ; Lin CHEN
Chinese Journal of Digestive Surgery 2024;23(1):114-124
Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.
2.Safety and efficacy of domestic Kangduo endoscopic robotic surgical system in lapa-roscopic partial nephrectomy
Mingxin DIAO ; Bing WANG ; Yaming GU ; Yingzhi DIAO ; Zhongyuan ZHANG ; Cheng SHEN ; Xuesong LI ; Zheng ZHANG
Journal of Modern Urology 2024;29(7):622-626
Objective To investigate the safety and efficacy of domestic Kangduo endoscopic robotic surgical system(SR1500)in laparoscopic partial nephrectomy via abdominal approach.Methods Perioperative data of 5 patients with renal tumors undergoing transabdominal partial nephrectomy with SR1500 at Miyun Hospital during Jul.and Aug.2023 were prospectively collected.The surgical procedure,operation time,pathological margins,intraoperative bleeding,hospital stay,and catheter removal time were recorded.Results The average tumor diameter was 1.92 cm,staged as T1a in TNM classification,with an average R.E.N.A.L score of 5.80.The mean docking time of equipment was 3.00 min,robotic arm operating time 97.20 min,and renal warm ischemia time 19.80 min.Postoperative pathology revealed negative surgical margins in all patients.No high-grade perioperative complications or device-related adverse events occurred.Conclusion Laparoscopic partial nephrectomy using the Kangduo endoscopic robotic surgical system(SR1500)via abdominal approach is safe and effective in the treatment of T1a renal tumors.
3.Pathogenesis and Treatment of Recurrent Granulomatous Mastitis Based on "Deficiency, Toxin and Blood Stasis"
Aijing CHU ; Yuezhu WANG ; Jieying ZHENG ; Zhongyuan XIA
Journal of Traditional Chinese Medicine 2024;65(12):1287-1291
To explore the pathogenesis and treatment of recurrent granulomatous mastitis based on "deficiency, toxin and blood stasis". It is believed that the main pathogenesis of recurrent granulomatous mastitis is spleen and stomach deficiency due to chronic illness, and at the same time, the persistent or intermittent presence of various causes makes the residual toxin unclear, which leads to the stagnation of local meridians and collaterals in the breast, accumulation of lumps, and then suppuration. Deficiency of qi and blood in zang-fu organs is the main cause of this disease, and residual toxin is the key factor of this disease. The treatment should focus on promoting therapy, promoting with dispersing, expelling with supplementing, supplementing with warming and dredging, dissolving toxins and releasing stasis, and the prescription is based on modified Tuoli Xiaodu Powder (托里消毒散) or self-prescribed Jiangru No.2 Formula (浆乳2号方). Overall, the treatment should combine deficiency, toxin and blood stasis with different syndrome differentiation and treatment, reinforce healthy qi and express toxin, and activate blood circulation and dredge collaterals with flexibly modification, to promote disease healing.
4.Treatment of Cardiovascular Diseases in Diabetes Mellitus with Traditional Chinese Medicine: A Review
Yu ZHANG ; Yu LI ; Zhongyuan ZHENG ; Yan LIANG ; Chengcheng LIU ; Yue DAI ; Luqi WANG ; Tuo LIU ; Lina CHEN ; Yujie LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):327-337
The complex pathophysiological mechanisms between diabetes mellitus and cardiovascular diseases have not yet been fully elucidated, becoming one of the challenges in clinical care. Glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium glucose cotransporter-2 inhibitors (SGLT2) are clinically used to reduce the cardiovascular risk of patients with diabetes mellitus. Traditional Chinese medicine has diverse biological activities and unique advantages in the treatment of chronic complex diseases due to its multi-component and multi-target effects. Based on recent reports, this paper reviewed the common risk factors of diabetes mellitus and cardiovascular diseases (e.g., hyperglycemia, insulin resistance, and inflammation), related targets such as apolipoprotein C-Ⅲ (APOC3), S100 calcium-binding protein A8/A9 (S100A8/A9), growth/differentiation factor-15 (GDF-15), and NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), advanced glycation end products, insulin resistance, endothelial dysfunction, endoplasmic reticulum stress, mitochondrial dysfunction, and intestinal flora disorder. In addition, this paper summarized the research progress in the treatment of cardiovascular diseases in diabetes mellitus with the active ingredients (e.g., baicalein, puerarin, curcumin, notoginsenoside, and tanshinone ⅡA), single herbal medicines (e.g., Astragali Radix, Ginseng Radix et Rhizoma, Sophorae Flavescentis Radix, Cinnamomi Cortex, and Corni Fructus), and compound formulas (e.g., Buzang Tongluo Fang, Yiqi Yangyin Huoxue Fang, Shenqi Fang, Huangqisan, Danggui Buxue Tang, and Liuwei Dihuang Wan) of traditional Chinese medicine. Traditional Chinese medicine mainly treats cardiovascular diseases in diabetes mellitus by reducing inflammation and oxidative stress, ameliorating dyslipidemia and insulin resistance, protecting islet β cell function, repairing endothelial damage, inhibiting smooth muscle cell proliferation, foam cell formation, macrophage polarization, and cardiac hypertrophy and fibrosis, and regulating intestinal flora disorder. These processes involve insulin receptor substrate/ phosphatidylinositol 3-kinase/protein kinase B (IRS/PI3K/Akt), peroxisome proliferator-activated receptor α/γ (PPAR α/γ), nuclear factor-kappa B (NF-κB), adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), hypoxia-inducible factor-1-BCH domain-containing protein (HIF-1-BNIP), vascular endothelial growth factor/hypoxia-inducible factor-1α (VEGF/HIF-1α) and other signaling pathways. This review is expected to provide a theoretical basis and reference for the treatment of cardiovascular diseases in diabetes mellitus with traditional Chinese medicine.
5.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
6.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
7.Optimized CRISPR/Cas9 System in Brain Science and Application Prospects in Field of Traditional Chinese Medicine
Shuoqiu DENG ; Shuiqing QU ; Yu ZHANG ; Yuanmin YANG ; Zhongyuan ZHENG ; Tuo LIU ; Lina CHEN ; Yujie LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):169-180
Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR associated nuclease 9 (CRISPR/Cas9) is a self-defense system found in bacteria and archaea that enables targeted gene editing based on the principle. Due to its universality, efficiency, and simplicity, CRISPR/Cas9 has been applied in the pathological mechanism and prevention and treatment of diseases in many fields. Cerebrovascular diseases and central nervous system diseases seriously endanger human health. Stroke is related to genetics, unhealthy living habits, chronic diseases, and other factors. The brain tissue structure is complex and the cell types are diverse. It is difficult for a universal gene editing platform to study target genes safely, specifically, and efficiently. Scholars have continuously improved and optimized gene editing technology, explored the potential and research methods of gene editing technology, and promoted the research process of brain science. After a brief introduction to the mechanism of CRISPR/Cas9, this paper mainly summarized the optimization of the system in the fields of cerebral science including delivery methods, adeno-associated virus assembly, and new nanomaterials. Its application in cerebrovascular research including vascular homeostasis, microglial homeostasis, angiogenesis, blood-brain barrier, and drug screening was also summarized. Finally, this paper prospected the development of CRISPR/Cas9 in traditional Chinese medicine, hoping to provide references for related research design.
8.Influences and mechanism of berberine on wound healing of full-thickness skin defects in diabetic mice
Liming ZHENG ; Zhongyuan LIU ; Hongyu YAN ; Hengfei LI ; Zhiwen ZHANG
Chinese Journal of Burns 2023;39(11):1072-1082
Objective:To investigate the influences and mechanism of berberine on wound healing of full-thickness skin defects in diabetic mice.Methods:The experimental research method was adopted. Mouse dermal fibroblasts (MDF) conventional-glucose complete medium (hereinafter referred to as conventional medium) were prepared with final mass concentrations of berberine of 0 (no berberine), 1.25, 2.50, 5.00, 10.00, 20.00, 40.00, 80.00, and 160.00 μg/mL, respectively. Primary MDF were cultured using conventional medium and MDF high-glucose (30 mmol/L glucose) complete medium (hereinafter referred to as high-glucose medium), and the 3 rd to 6 th passage cells were collected for the following experiments. Cells cultured in conventional medium were taken and subjected to starvation treatment for 12 hours, and then cultured in conventional media containing different concentrations of berberine for 48 hours to screen out the optimal working concentration of berberine using the cell counting kit 8 (CCK-8), the sample number was 6, and the selected optimal berberine concentration was used for subsequent cell culture experiments. Cells cultured in 2 media were taken, of which the cells cultured in conventional medium were included to the normal control group; cells cultured in high-glucose medium were divided into high-glucose alone group and high-glucose+berberine group according to the random number table (the same grouping method below). After 48 h of cultivation, cell viability was detected by CCK-8, cell migration capacity was evaluated by scratch test and Transwell assays, and mRNA and protein expression levels of platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-β 1 (TGF-β 1), matrix metalloproteinase 9 (MMP-9), and cysteine aspartic acid specific protease (caspase-3) in the cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction and Western blotting, respectively, and the sample numbers of the aforementioned experiments were 6, 3, 9, 3, and 6, respectively. Fifteen 8-week-old male BALB/c mice were used to establish diabetic mouse model, then full-thickness skin defect wounds on their backs were made and divided into diabetes alone group, diabetes+low-concentration berberine group (25 μg/mL), and diabetes+high-concentration berberine group (75 μg/mL) for corresponding treatments, with 5 mice in each group. The wound areas were measured using ImageJ software on post injury day (PID) 0 (immediately), 3, 7, 14, and 21. On PID 21, histological changes and collagen formation in the wound tissue were detected by hematoxylin-eosin and Masson staining, respectively, protein expression and mRNA levels of MMP-9, PDGF, TGF-β 1, VEGF, CD31, and caspase-3 in the wound tissue were detected by immunohistochemistry and real-time fluorescence quantitative reverse transcription polymerase chain reaction, respectively, the sample number of animal experiments was all 5. Data were statistically analyzed with one-way analysis of variance, independent sample t-test, Tukey's test, and factorial design analysis of variance. Results:After 48 hours of cultivation, the cell viability was the highest when the mass concentration of berberine was 20.00 μg/mL. After 48 h of cultivation, compared with that in normal control group, cell viability in both high-glucose alone group and high-glucose+berberine group reduced significantly ( P<0.05); compared with that in high-glucose alone group, the cell viability in high-glucose+berberine group was significantly enhanced ( P<0.05). After 48 h of cultivation, scratch test results showed that, the cell migration rates in 24 h in both high-glucose alone group and high-glucose+berberine group were significantly decreased than that in normal control group ( P<0.05); compared with that in high-glucose alone group, the cell migration rate in 24 h in high-glucose+berberine group was significantly enhanced ( P<0.05). After 48 h of cultivation, the results of Transwell experiments showed that, compared with (141±7) of cells migrating in 24 h in normal control group, the number of cells migrating in 24 h in high-glucose alone group and high-glucose+berberine group were 28±3 and 86±6, respectively, which were significantly decreased ( P<0.05); compared with that in high-glucose alone group, the number of cells migration in 24 h in high-glucose+berberine group was significantly increased ( P<0.05). After 48 h of cultivation, compared with those in normal control group, the mRNA levels of PDGF, VEGF, TGF-β 1, and MMP-9 of cells in high-glucose alone group and high-glucose+berberine group were significantly decreased ( P<0.05), the mRNA levels of caspase-3 were significantly increased ( P<0.05); compared with those in high-glucose alone group, the mRNA levels of PDGF, VEGF, TGF-β 1, and MMP-9 of cells in high-glucose+berberine group were significantly increased ( P<0.05), the mRNA expression level of caspase-3 was significantly decreased ( P<0.05). After 48 h of cultivation, compared with those in normal control group, the protein expression levels of PDGF, VEGF, TGF-β 1, and MMP-9 of cells in high-glucose group and high-glucose+berberine group were significantly decreased ( P<0.05), the protein expression levels of caspase-3 were significantly increased ( P<0.05); compared with those in high-glucose alone group, the protein expression levels of PDGF, VEGF, TGF-β 1, and MMP-9 of cells in high-glucose+berberine group were significantly increased ( P<0.05), and the protein expression level of caspase-3 was significantly decreased ( P<0.05). Compared with those in diabetes alone group, the wound areas of mice in diabetes+low-concentration berberine group on PID 14 and 21 and in diabetes+high-concentration berberine group on PID 3, 7, 14, and 21 were significantly decreased ( P<0.05); compared with that in diabetes+low-concentration berberine group, the wound area in diabetes+high-concentration berberine group was significantly decreased on PID 3, 7, 14, and 21 ( P<0.05). On PID 21, the wound of mice in diabetes alone group was not epithelialized with a large number of inflammatory cells and granulation tissue in the dermis; most of the wound tissue of mice in diabetes+low-concentration berberine group was already epithelialized, although there was a large number of inflammatory cells in the dermis; and most of the wound tissue of mice in diabetes+high-concentration berberine group had completed epithelialization with a small number of hair follicles and inflammatory cells in the dermis. On PID 21, compared with that in diabetes alone group, the collagen area of wound of mice in diabetes+low-concentration berberine group and diabetes+high-concentration berberine group was significantly increased ( P<0.05); compared with that in diabetes+low-concentration berberine group, the collagen area of wound of mice in diabetes+high-concentration berberine group was significantly increased ( P<0.05). On PID 21, compared with those in diabetes alone group, the protein expression levels of MMP-9, PDGF, TGF-β 1, VEGF, and CD31 in wound tissue of mice in diabetes+low-concentration berberine group and diabetes+high-concentration berberine group were significantly increased ( P<0.05), the protein expression levels of caspase-3 were significantly decreased ( P<0.05); compared with those in diabetes+low-concentration berberine group, the protein expression levels of MMP-9, PDGF, TGF-β 1, VEGF, and CD31 in wound tissue of mice in diabetes+high-concentration berberine group were significantly increased ( P<0.05), the protein expression level of caspase-3 was significantly decreased ( P<0.05). On PID 21, compared with those in diabetes alone group, the mRNA levels of MMP-9, PDGF, TGF-β 1, VEGF, and CD31 in wound tissue of mice in diabetes+low-concentration berberine group and diabetes+high-concentration berberine group were significantly increased ( P<0.05), the mRNA levels of caspase-3 were significantly decreased ( P<0.05); compared with those in diabetes+low-concentration berberine group, the mRNA levels of MMP-9, PDGF, TGF-β 1, VEGF, and CD31 in wound tissue of mice in diabetes+high-concentration berberine group were significantly increased ( P<0.05), the mRNA level of caspase-3 was significantly decreased ( P<0.05). Conclusions:Berberine can promote the proliferation and migration of MDF and the healing of full-thickness skin defect wounds of mice in diabetic mice by up-regulating the expression of biofactors including MMP-9, PDGF, TGF-β 1, and VEGF, and down-regulating the expression of caspase-3, a pro-apoptotic factor in wound tissue of mice.
9.Effect of Mitochondrial Autophagy in Clinical Diseases and Intervention by Chinese Medicine: A Review
Hongyue MA ; Lin SONG ; Zhongyuan PIAO ; Xiaolei BAI ; Wei CHU ; Yuanwu ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(19):250-257
Mitochondrial autophagy is a process to clear dysfunctional mitochondria in the cytoplasm to maintain the integrity of mitochondrial function and cell homeostasis. Mitochondrial autophagy is a complex physiological process, which can maintain the balance of mitochondrial quality and quantity, cell survival under starvation and harsh conditions, and the stability of the intracellular environment. Its molecular mechanism involves a variety of proteins. Many factors can induce mitochondrial autophagy, such as starvation, oxidative stress, hypoxia, depolarization, and other stresses. The accumulation of unfolded proteins can also induce mitochondrial autophagy. In recent years, as a research hotspot, the abnormality of mitochondrial morphology and function is closely related to the occurrence of a variety of diseases. The research on mitochondrial autophagy and the pathogenesis of clinical diseases has attracted more attention, such as tumors, cardiovascular diseases, liver diseases, nervous system diseases, and glucose metabolism disorders. It has been found that regulating mitochondrial autophagy may inspire the treatment of some diseases. Meanwhile, clinical researchers have paid more attention to traditional Chinese medicine (TCM). As revealed by in-depth research, Chinese medicine has a certain value in regulating mitochondrial autophagy. The research on the pathogenesis of mitochondrial autophagy in related diseases and the intervention of Chinese medicine has found that there are many reports on the regulation of mitochondrial autophagy by Chinese medicine in tumors, cardiovascular diseases, and nervous system diseases. However, the mechanism of mitochondrial autophagy, the balance of mitochondrial autophagy, and the difference in the activation or inhibition of mitochondrial autophagy by Chinese medicine remain unclear. The regulation of mitochondrial autophagy has become a new research target strategy of Chinese medicine in the prevention and treatment of diseases. This paper reviewed the available literature in recent years to provide reference materials for the regulation of mitochondrial autophagy by Chinese medicine and ideas for the follow-up research of Chinese medicine in mitochondrial autophagy.
10.Protective Effect of Shenlian Prescription on Acute Lung Injury Induced by Particulate Matter Exposure in Rats
Yuanmin YANG ; Shuiqing QU ; Lina CHEN ; Shuoqiu DENG ; Yu ZHANG ; Zhongyuan ZHENG ; Xiaoxin ZHU ; Yuxiang LI ; Yujie LI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(20):37-44
ObjectiveTo observe the protective effect of Shenlian prescription on acute lung injury induced by particulate matter (PM) exposure in rats and explore the mechanism. MethodFifty male SD rats were randomly divided into the control group, model group, Shenlian low-dose group (4.32 g·kg-1), Shenlian high-dose group (8.64 g·kg-1), and roflumilast group (3.46 mg·kg-1), with 10 in each group. Pre-administration with drugs by gavage was performed for one week. On the 8th and 11th days, the control group was instilled with normal saline in the trachea and the other groups with PM suspension to establish a rat model of acute lung injury induced by PM exposure. After modeling, drugs were given continuously until the end of the experiment. Forty-eight hours after the last exposure, the lung function of rats was detected. Then the rats were sacrificed and the lung morphological changes and pathological changes by hematoxylin-eosin (HE) staining were observed. CD68 expression in lung was detected by immunohistochemistry, and the levels of lung injury markers surfactant protein A (SP-A) and Clara cell protein16 (CC16) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of interleukin-1α (IL-1α), IL-6, IL-18, and monocyte chemoattractant protein-1 (MCP-1) in lung tissue was measured by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with those in the control group, the rats in the model group had decreased lung function and obvious structural damage of lung tissue, PM deposition, and infiltration of CD68 positive cells. The expressions of IL-1α, IL-6, IL-18, and MCP-1 in lung tissue were increased (P<0.01). Compared with the model group, Shenlian prescription low and high doses restored the rats' lung function injury(P<0.05,P<0.01), improved lung morphological and pathological structure, and reduced PM deposition. Infiltration of CD68 positive cells in lung was not significantly decreased. The levels of inflammatory factors IL-1α, IL -6, IL-18, and MCP-1 in lung were lowered (P<0.01). ConclusionShenlian prescription could protect the rats' lung injury caused by PM exposure, improve lung morphology, and reduce PM deposition and inflammatory factor expression.

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