1.Effects of leptin on brain injury and long-term cognitive function in rats undergoing orthotopic liver transplantation
Hongjie LYU ; Lijuan DONG ; Hongjun LI
Chinese Journal of Anesthesiology 2019;39(3):327-330
Objective To evaluate the effects of leptin on brain injury and long-term cognitive function in rats undergoing orthotopic liver transplantation. Methods Ninety clean-grade male Sprague-Dawley rats, aged 3 months, weighing 200-250 g, were divided into 3 groups by a random number table method: sham operation group ( S group) , liver ischemia-reperfusion ( I∕R) group ( I∕R group) and lep-tin group ( L group) , with 18 rats in each group. Orthotopic liver transplantation was performed to estab-lish the model of liver I∕R injury in I∕R and L groups. Leptin 1 mg∕kg was intraperitoneally injected at the onset of ischemia in L group, and the equal volume of normal saline was given instead of leptin in S and I∕R groups. Twelve rats in each group were sacrificed at 3 days after operation, and brains were removed for ex-amination of the pathological changes in hippocampal CA1 region ( with a light microscope) and for determi-nation of apoptosis in hippocampal neurons ( by TUNEL assay) and expression of aquaporin 4 ( AQP4) and protein kinase C ( PKC) in the hippocampus ( by Western blot) . The apoptosis rate was calculated. The remaining 6 rats in each group underwent a Morris water maze test at 30 days after surgery to evaluate long-term cognitive function. Results Compared with S group, the apoptosis rate of hippocampal neurons was significantly increased, the expression of AQP4 and PKC was up-regulated, the escape latency was pro-longed, and the time of staying at the platform quadrant was shortened in I∕R and L groups (P<0. 05). Compared with I∕R group, the apoptosis rate of hippocampal neurons was significantly decreased, the ex-pression of AQP4 and PKC was down-regulated, the escape latency was shortened, and the time of staying at the platform quadrant was prolonged in L group (P<0. 05). Conclusion Leptin can reduce the brain damage in rats undergoing orthotopic liver transplantation, the mechanism may be related to down-regulating the expression of PKC and AQP4, and leptin can also improve long-term cognitive function after orthotopic liver transplantation in rats.
2.Effects of dexmedetomidine on brain injury and long -term cognitive dysfunction in rats after orthotopic liver transplantation ischemia/reperfusion
Hongjie LYU ; Lijuan DONG ; Hongjun LI
Chinese Journal of Neuromedicine 2019;18(2):122-126
Objective To investigate the effect of dexmedetomidine (DEX) on brain injury and long-term cognitive dysfunction in rats after orthotopic liver transplantation ischemia/reperfusion and its mechanism. Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into sham-operated group (n=18), orthotopic liver transplantation ischemia/reperfusion group (I/R group, n=18) and DEX pre-administration group (DEX group, n=18). The orthotopic liver transplantation ischemia/reperfusion models were established in I/R group and DEX group. Rats of the DEX group were intraperitoneally injected with DEX 100 μg/kg 30 min before the incision, and an equal volume of normal saline was injected into rats of the sham-operated group and I/R group at the same time. Twelve rats in each group were sacrificed 3 d after operation and brain tissues were taken. The pathological changes of the hippocampus were observed under light microscope. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to detect neuronal apoptosis index of the hippocampus. Western blotting was used to detect the protein levels of aquaporin 4 (AQP4) and protein kinase C (PKC) in the hippocampus. The remaining 6 rats accepted Morris water maze test to evaluate the long-term cognitive function 30 d after surgery. Results As compared with those in the sham-operated group, rats in the I/R group and DEX group had hippocampus edema and disordered cell arrangement; as compared with sham-operated group, I/R group and DEX group had significantly increased neuronal apoptosis index, significantly increased protein levels of AQP4 and PKC, significantly shorter quadrant retention time of the platform, and statistically longer escape latency (P<0.05). As compared with those in the I/R group, the pathological damage of hippocampal neurons was significantly alleviated, the neuronal apoptosis index was significantly decreased, the protein levels of AQP4 and PKC were statistically decreased, and the residence time of the quadrant in the platform was significantly prolonged, and the escape latency was statistically shorter in DEX group (P<0.05). Conclusion Pre-administration of DEX may reduce the brain damage and improve long-term cognitive dysfunction in rats after orthotopic liver transplantation ischemia/reperfusion, which may be related to down-regulating the AQP4 and PKC expression levels and reducing neuronal apoptosis.
3.Comparision of the effect between Mammotome assisted minimally invasive atherectomy and traditional surgery in treatment of youth giant breast fibroadenoma
Yuejun QIAN ; Jin LYU ; Yingxu YANG ; Hongjun HAO
Chinese Journal of Endocrine Surgery 2018;12(2):124-127
Objective To compare the effect between Mammotome minimally invasive surgery and traditional surgery in resection of youth giant breast fibroadenoma (YGBF).Methods We randomly selected 73 patients who had YGBF and already accepted surgical treatment in our hospital from Jul.2009 to Jan.2016.The 75 patients recruited from screening programmes were alloted to either treatment according to their choice (37 cases in MS and 38 cases in traditional surgery).The median follow-up was 18 months (from 6 to 36 months).Comparative analysis was done between the two groups in operation time,incision healing time,incision length,intraoperative bleeding,wound infection,subcutaneous hematoma,residual tumor,breast deformation,scar size,and patient satisfaction degree.Results There was no statisticaly significant difference betwen these two groups in operation time,intraoperative blood loss,incision infection,subcutaneous hematoma,or residual tumor (P>0.05),however,MS group was superior to traditional surgery group in the incision healing time,incision length,breast deformation,scar size and postoperative satisfaction degree,and the difference was statistically significant(P< 0.05).Conclusion The advantage of Mammotome minimally invasive operation auxiliary for YGBF is obvious,such as fast wound healing,small incision,infection rate,small breast without deformation and scar etc.,also higher satisfaction degree to the treatment,which is regarded as the preferred surgical treatment for YGBF patients.
4.Effect of dexmedetomidine on mammalian target of rapamyein signaling pathway in hippocampus of mice with postoperative cognitive dysfunction
Lijuan DONG ; Guanghui YANG ; Hongjie LYU ; Hongjun LI
Chinese Journal of Neuromedicine 2018;17(10):987-993
Objective To investigate the effect of dexmedetomidine (DEX) on mammalian target of rapamyein (mTOR) signaling pathway in the hippocampus of mice with postoperative cognitive dysfunction (POCD).Methods A total of 64 specific pathogen free (SPF) adult C57BL/6J mice were randomly divided into four groups (n=16):sham-operated group,POCD group,DEX-L group (giving low dose of DEX) and DEX-H group (giving high dose of DEX).Mice only received anesthesia but not partial hepatectomy surgery in sham-operated group;mouse models of POCD in POCD group were established by partial hepatectomy surgery under anesthesia;DEX (25 μg/kg or 50 μg/kg) was given by intraperitoneal injection 30 min prior to partial hepatectomy surgery,and then,the mouse models of POCD were established in DEX-L group and DEX-H group;normal saline of the same volume was injected intraperitoneally prior to partial hepatectomy surgery in sham-operated group and POCD group.Behavioral test was performed via Fear Conditioning Test (FCS) one d before surgery and 3 d after surgery for training and behavioral testing,and the percentage of freezing time was recorded.Enzyme linked immunosorbent assay (ELISA) was used to detect the protein levels of beta amyloid protein 42 (Aβ-42) and phosphorylated(p)-tau-181 in cerebrospinal fluid of mice 3 d after surgery.The hippocampus tissues of mice were collected 3 d after surgery,and the mRNA expressions of mTOR,Tau,nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) in hippocampal tissues were tested by reverse transcription-polymerase chain reaction (RT-PCR).The protein expressions ofmTOR,p-tau (pS396 Tau protein),NF-κB and TNF-α in hippocampal tissues were tested by Westem blotting.Results (1) As compared with that in sham-operated group,the percentage of freezing time in conditioning FCS in POCD group was statistically lower (P<0.05);as compared with that in POCD group,the percentage of freezing time in conditioning FCS in DEX-L group and DEX-H group was significantly higher (P<0.05).(2) The protein levels of Aβ-42 and p-tau-181 in cerebrospinal fluid of POCD group,DEX-L group and DEX-H group were significantly higher than those in sham-operated group (P<0.05);the protein levels of Aβ-42 and p-tau-181 in cerebrospinal fluid of DEX-L group and DEX-H group were significantly lower as compared with those in POCD group (P<0.05);DEX-H group had significantly lower protein levels of Aβ-42 and p-tau-181 in cerebrospinal fluid as compared with DEX-L group (P<0.05).(3) The mRNA and protein expressions of mTOR,NF-κB p65 and TNF-α,Tau mRNA expression,and pS396 Tau protein expression in the hippocampus of the POCD group were significantly higher as compared with those in the sham-operated group (P<0.05);the mRNA and protein expressions ofmTOR,NF-κB p65 and TNF-α,Tau mRNA expression,and pS396 tau protein expression in the hippocampus of the DEX-L group and DEX-H group were significantly lower as compared with those in the POCD group (P<0.05);those in the DEX-H group were significantly lower than those in the DEX-L group (P<0.05).Conclusion DEX can improve early POCD in mice,and the mechanism may be related to down-regulation of mTOR signaling pathway.
5.Effect of dexmedetomidine on platelet activating factor levels in plasma and hippocampus of mice with postoperative cognitive dysfunction
Lijuan DONG ; Guanghui YANG ; Hongjie LYU ; Hongjun LI
Chinese Journal of Neuromedicine 2018;17(3):277-281
Objective To investigate the effect of dexmedetomidine (DEX) on platelet activating factor (PAF) levels in the plasma and hippocampus of mice with postoperative cognitive dysfunction (POCD).Methods A total of 30 specific pathogen free C57BL/6J mice were randomly divided into three groups (n=10):sham-operated group,POCD group and DEX intervention group.Mice in sham-operated group only received anesthesia but not partial hepatectomy surgery;the POCD models of POCD group and DEX intervention group were established by partial hepatectomy surgery under anesthesia;DEX (25 μg/kg) was given to mice from the DEX intervention group by intraperitoneal injection 30 min prior to partial hepatectomy surgery;normal saline of the same volume was injected intraperitoneally prior to partial hepatectomy surgery in sham-operated group and POCD group.Behavioral test was performed via fear conditioning tests (FCS),and the percentage of freezing time was recorded on the 3rd d of POCD modeling.The PAF levels in the blood and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA).Results (1) As compared with the sham-operated group,POCD group had significantly lower percentage of freezing time in audible alerts on FCS (57.3%±9.1% vs.30.0%±5.4%,P<0.05);as compared with the POCD group,DEX intervention group had significantly higher percentage of freezing time in audible alerts on FCS (30.0%±5.4% vs.46.5%±6.6%,P<0.05).(2) The PAF levels in the plasma and hippocampus of POCD group were significantly increased as compared with those in the sham-operated group ([0.5±0.3] ng/mL vs.[22.5±2.2] ng/mL;[5.7±1.0]ng/mL vs.[9.8±1.4] ng/mL],P<0.05);the PAF levels in the plasma and hippocampus of DEX intervention group were significantly increased as compared with those in the POCD group ([22.5±2.2] ng/mL vs.[14.6±1.6] ng/mL;[9.8±1.4] ng/mL vs.[7.4±1.2] ng/mL,P<0.05).Conclusion DEX can improve early POCD in mice after partial hepatectomy surgery by reducing PAF levels in the plasma and hippocampus.
6.Study on Molecular Mechanism of Xiaochaihu Decoction for Sepsis Based on TCMIP Platform
Qingxin YANG ; Hongjun LYU ; Xiaobo WANG ; Jinsong REN ; Nan ZENG
China Pharmacy 2019;30(11):1506-1512
OBJECTIVE: To investigate the substance basis and mechanism of Xiaochaihu decoction in treatment of sepsis, and to provide reference for clinical application and R&D of the decoction. METHODS: Based on TCM integrative pharmacology platform (TCMIP), chemical component analysis of Xiaochaihu decoction, disease target prediction, gene function and pathway enrichment analysis were all performed. The multi-dimensional network relationship of “TCM-chemical components-core targets-key pathways” was established, and the mechanism of Xiaochaihu decoction in treatment of sepsis was investigated. RESULTS: A total of 224 predicted chemical ingredients of Xiaochaihu decoction (including saikoside, ginsenoside, glycyrrhizin, etc.) interacted with 118 key targets about sepsis, including PF4, MYD88, TLR4, CD14, NOS3, etc. Its anti-sepsis mechanism involved nervous system, endocrine system, immune response and energy metabolism, etc. CONCLUSIONS: Based on “neuronal- endocrine-immune-metabolism”, Xiaochaihu decoction achieved its role in regulating sepsis by multi-level, multi-channel and multi-channel. This research may reveal the potential mechanism of Xiaochaihu decoction for sepsis, and the prescription provide theoretical basis for further experimental research of pharmacodynamic substance basis and mechanism of action.
7. Risk factors for central neck lymph node metastases of papillary thyroid carcinoma
Yushi SUN ; Hongjun LYU ; Yanru ZHAO ; Shaoqiang ZHANG ; Yanxia BAI ; Bingyin SHI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2017;52(6):421-425
Objective:
To investigate the impact factors for central neck lymph node metastases(CLNM) of papillary thyroid carcinoma(PTC).
Methods:
A total of 498 patients with PTC who underwent total or hemi-thyroidectomy plus central neck lymph node dissection between January 2014 and July 2016 were included. Univariate and multivariate analyses were performed to identify clinicopathological characteristics, thyroid function parameters and US findings that associated with CLNM of PTC. A nomogram was developed to predict the probability of CLNM. The receiver operating characteristic curve(ROC) was used to estimate the efficiency of the nomogram.
Results:
Among 498 patients, 284 patients were affected by CNLM. The sensitivity and specificity of US in predicting PTC metastasis in the central neck were 31.3% and 88.3%, respectively. Univariate and multivariate analyses showed that gender, age, number and size of suspicious malignant nodules in thyroid, and suspicious lymph node metastasis detected by ultrasonography were independently correlated with CLNM. The ROC showed that the AUC was 0.748, with sensitivity of 80.8%, and specificity of 59.8%.
Conclusions
Gender, age, number and size of suspicious malignant nodules in thyroid, suspicious lymph node metastasis were predictive factors for CLNM in patients with PTC. The nomogram developed based on related factors with CLNM is more sensitive than sonographic central neck lymph node features in predicting the probability of CLNM.