1.Liuwei Dihuangwan Promote Mitophagy to Modulate Neuroinflammation and Behavioral Impairments in Rat Model of Autism Spectrum Disorder (ASD)
Pengjue HUANG ; Mingyue JIANG ; Ji WU ; Niya YIN ; Lei OUYANG ; Qinquan ZHU ; Di ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):52-60
ObjectiveTo observe the effect of Liuwei Dihuangwan on behavioral impairments in the rat model of autism spectrum disorder (ASD) and explore the mechanism of action. MethodsTwelve SD pregnant rats were intraperitoneally injected with valproic acid (VPA) (10 rats) or normal saline (2 rats), and male offspring were selected to establish the model of ASD and the control rats. Rats were randomly assigned into model, low-dose (0.75 g·kg-1) and high-dose (1.5 g·kg-1) Liuwei Dihuangwan, vitamin D (positive drug, 3.7×10-5 g·kg-1), and blank groups. Each group was administrated with the corresponding concentration of drugs or the same volume of normal saline by gavage for 2 weeks. After the intervention, the three-chamber social test was conducted to evaluate social interaction and social preference. The open field test was carried out to observe spontaneous behavior and anxiety state. Hematoxylin-eosin staining (HE) was used to observe the pathological changes of the prefrontal tissue. Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in prefrontal neurons. Immunofluorescence was used to detect the expression of ionized calcium-binding adapter molecule-1 (Iba-1) in the prefrontal tissue. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Western blot was employed to assess the expression differences of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), adenosine monophosphate-activated protein kinase (AMPK), phosphorylated Unc-51-like autophagy-activating kinase 1 (p-ULK1), Unc-51-like autophagy-activating kinase 1 (ULK1), and FUN14 domain-containing protein 1 (FUNDC1). ResultsCompared with the blank group, the model group spent less time sniffing stranger 1 and stranger 2 in the three-chamber social test (P<0.01) and showed reductions in the total distance traveled, average speed, distance traveled in the central area, and time spent in the central area in the open field test (P<0.01). In addition, the model group showed extensive apoptosis of neurons, with shrunken nuclei and red-stained cytoplasm, and extensive necrosis of neurons in the prefrontal tissue, mitochondrial swelling, decreased matrix density, disrupted cristae, and autophagic lysosomes in neurons, increases in the rate of Iba-1 positive cells in the prefrontal area (P<0.01) and the levels of TNF-α and IL-6 (P<0.01), and down-regulation in the expression of p-AMPK/AMPK, p-ULK1/ULK1, and FUNDC1 (P<0.01). Compared with the model group, low-dose and high-dose Liuwei Dihuangwan and the vitamin D prolonged the time spent sniffing stranger 1 and stranger 2 in the three-chamber social test (P<0.05, P<0.01), increased the total distance traveled, average speed, distance traveled in the central area, and time spent in the central area in the open field test (P<0.05, P<0.01), restored the morphology of neurons in the prefrontal tissue, decreased the number of apoptotic cells, alleviated the swelling of mitochondria in neurons, increased the matrix density, mitigated the fragmentation and disorder of cristae, and increased the number of autophagosomes. Moreover, the drugs decreased the rate of Iba-1 positive cells in the prefrontal area (P<0.01), lowered the levels of TNF-α and IL-6 (P<0.01), and up-regulated the expression of p-AMPK/AMPK, p-ULK1/ULK1, and FUNDC1 (P<0.01). ConclusionLiuwei Dihuangwan ameliorate autism-like behaviors and reduce neuronal apoptosis and neuroinflammatory damage in the rat model of ASD by promoting mitophagy mediated by the AMPK/ULK1/FUNDC1 pathway.
2.Risk factors of benign anastomostic strictures after esophagectomy with cervical reconstruction.
Sheng ZHONG ; Qinquan WU ; Su'an SUN ; Biao GU ; Ming ZHAO ; Qiyou CHEN
Chinese Journal of Gastrointestinal Surgery 2014;17(9):877-880
OBJECTIVETo identify the risk factors of benign cervical anastomotic strictures after esophagectomy.
METHODSClinical data of 946 esophageal cancer patients undergoing esophagectomy with cervical anastomosis between 2003 and 2012 were analyzed retrospectively. Benign stricture was defined as dysphagia for which endoscopic dilation of the anastomosis was needed. Histologically proven malignant stricture was not regarded as benign stricture. χ(2) test and logistic regression model were used for univariate and multivariate analysis respectively.
RESULTSA total of 146 patients(16.5%) developed benign stricture during follow-up. Univariate analysis showed that the patients with cardiovascular disease (P=0.001), diabetes mellitus(P=0.041), gastric tube reconstruction(P=0.050), end-to-end anastomosis (P=0.013), or postoperative anastomotic leakage(P=0.008) had higher stricture rate. Multivariate analysis revealed that cardiovascular disease(P=0.004), gastric tube reconstruction (P=0.026), end-to-end anastomosis(P=0.043), and postoperative anastomotic leakage(P=0.001) were independently predictive factors for development of benign stricture.
CONCLUSIONSThe benign cervical stricture rate after esophagetomy with cervical gastric anastomosis is quite high. In order to prevent benign stricture formation, end-to-end anastomosis should be avoid. Blood pressure should be controlled for those with cardiovascular disease. Endoscopic dilation in an earlier stage postoperatively should be considered for those who develop anastomotic leakage.
Anastomosis, Surgical ; adverse effects ; Anastomotic Leak ; Constriction, Pathologic ; etiology ; Deglutition Disorders ; etiology ; Esophageal Neoplasms ; complications ; surgery ; Esophageal Stenosis ; etiology ; Esophagectomy ; adverse effects ; Follow-Up Studies ; Humans ; Postoperative Complications ; etiology ; Reconstructive Surgical Procedures ; adverse effects ; Retrospective Studies ; Risk Factors
3.Risk factors of benign anastomostic strictures after esophagectomy with cervical reconstruction
Sheng ZHONG ; Qinquan WU ; Su′an SUN ; Biao GU ; Ming ZHAO ; Qiyou CHEN
Chinese Journal of Gastrointestinal Surgery 2014;(9):877-880
Objective To identify the risk factors of benign cervical anastomotic strictures after esophagectomy. Methods Clinical data of 946 esophageal cancer patients undergoing esophagectomy with cervical anastomosis between 2003 and 2012 were analyzed retrospectively. Benign stricture was defined as dysphagia for which endoscopic dilation of the anastomosis was needed. Histologically proven malignant stricture was not regarded as benign stricture. χ2 test and logistic regression model were used for univariate and multivariate analysis respectively. Results A total of 146 patients(16.5%) developed benign stricture during follow-up. Univariate analysis showed that the patients with cardiovascular disease (P=0.001), diabetes mellitus(P=0.041), gastric tube reconstruction(P=0.050), end-to-end anastomosis (P=0.013), or postoperative anastomotic leakage (P=0.008) had higher stricture rate. Multivariate analysis revealed that cardiovascular disease (P=0.004), gastric tube reconstruction (P=0.026), end-to-end anastomosis (P=0.043), and postoperative anastomotic leakage (P=0.001) were independently predictive factors for development of benign stricture. Conclusions The benign cervical stricture rate after esophagetomy with cervical gastric anastomosis is quite high. In order to prevent benign stricture formation, end-to-end anastomosis should be avoid. Blood pressure should be controlled for those with cardiovascular disease. Endoscopic dilation in an earlier stage postoperatively should be considered for those who develop anastomotic leakage.
4.Risk factors of benign anastomostic strictures after esophagectomy with cervical reconstruction
Sheng ZHONG ; Qinquan WU ; Su′an SUN ; Biao GU ; Ming ZHAO ; Qiyou CHEN
Chinese Journal of Gastrointestinal Surgery 2014;(9):877-880
Objective To identify the risk factors of benign cervical anastomotic strictures after esophagectomy. Methods Clinical data of 946 esophageal cancer patients undergoing esophagectomy with cervical anastomosis between 2003 and 2012 were analyzed retrospectively. Benign stricture was defined as dysphagia for which endoscopic dilation of the anastomosis was needed. Histologically proven malignant stricture was not regarded as benign stricture. χ2 test and logistic regression model were used for univariate and multivariate analysis respectively. Results A total of 146 patients(16.5%) developed benign stricture during follow-up. Univariate analysis showed that the patients with cardiovascular disease (P=0.001), diabetes mellitus(P=0.041), gastric tube reconstruction(P=0.050), end-to-end anastomosis (P=0.013), or postoperative anastomotic leakage (P=0.008) had higher stricture rate. Multivariate analysis revealed that cardiovascular disease (P=0.004), gastric tube reconstruction (P=0.026), end-to-end anastomosis (P=0.043), and postoperative anastomotic leakage (P=0.001) were independently predictive factors for development of benign stricture. Conclusions The benign cervical stricture rate after esophagetomy with cervical gastric anastomosis is quite high. In order to prevent benign stricture formation, end-to-end anastomosis should be avoid. Blood pressure should be controlled for those with cardiovascular disease. Endoscopic dilation in an earlier stage postoperatively should be considered for those who develop anastomotic leakage.
5.Effects of different anesthetic techniques on perioperative changes in T-lymphocyte subsets in patients with esophageal carcinoma
Qinqing HU ; Hongqing LI ; Xiaojia ZHANG ; Minru DENG ; Qinquan JI ; Lijuan WU
Chinese Journal of Primary Medicine and Pharmacy 2008;15(4):538-539
Objective To determine the effects of different anesthetic techniques on T-lymphocyte subsets in patients with esophageal carcinoma. Methods Forty patients were randomly assigned into general anesthesia group (group Ⅰ),or combined generae anesthesia with epidural anesthesia group(group Ⅱ). Peripheral blood CD3, CD4,CD8 were measured before induction ( T1 ), after anesthesia ( T2 ), end of operation ( T3 ), 1d ( T4 ), 3d ( T5 ) after surgery. Resolts CD3,CD4,CD8,CD4/CD8 decreased at T2 in the two groups. In group Ⅱ ,CD3,CD4,CD8,CD4/CD8 ratio almost returned to the baseline values at T4 ,while group Ⅰ did not. Conclusion Epidural anesthesia combined with general anesthesia can reduce depression of T-lymphocyte subsets induced by surgical trauma and anesthesia, and is the anesthetic tecnique of choice for cancer patients undergoing major operation.

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