1.The mechanism of Belamcanda chinensis in the treatment of glioma based on network pharmacology and molecular simulation
Yang ZHOU ; Dongjing JIANG ; Songbai LIU ; Haifeng LU ; Feng ZENG ; Qixin ZHONG ; Xiaorong DAI
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(5):769-778
【Objective】 To explore the potential molecular biological mechanism of Belamcanda chinensis in the treatment of glioma based on network pharmacology, molecular docking technology and in vitro cell experiments. 【Methods】 ① The active components, targets of Belamcanda chinensis and targets of glioma were obtained by database search. String database was used to analyze protein-protein interaction relationship, R project was used to analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Cytoscape software was used to build "compound-target-disease" network and PPI network, and AutoDock software was used to verify molecular docking. ② Western blotting, qRT-PCT and apoptosis assay were used to verify the enrichment results of network pharmacology targets and protein pathway. 【Results】 ① We screened out 32 types of active components, 484 types of targets and 464 types of glioma targets, and obtained 62 kinds of therapeutic targets after mapping. We obtained 12 kinds of key pharmacodynamic molecules such as Isoiridogermanal, Iridobelamal A and Rhamnazinand and other key pharmacodynamic molecules, as well as AKT1, STAT3, HRAS and other core targets by network topology analysis. Enrichment analysis results demonstrated that they were mainly involved in biological processes such as peptide serine phosphorylation, protein kinase B signal transduction, peptide serine modification, and pathways including PI3K/AKT signal pathway and Rap1 signal pathway. The results of molecular docking verified the good binding activity of the key pharmacodynamic molecules with the core targets. ② The results of Western blotting showed that the protein expressions of VEGF and MMP9 of Belamcanda chinensis extracts in 8 mg/mL and 16 mg/mL groups were significantly lower than those in the blank control group (P<0.01 or P<0.001). Compared with the blank control group, the early apoptosis rate of Belamcanda chinensis extracts at 8 mg/mL and 16 mg/mL were significantly decreased (P<0.001 or P<0.000 1). qRT-PCR results showed that the mRNA expression levels of VEGF and MMP9 in Belamcanda chinensis extracts at 8 mg/mL and 16 mg/mL were significantly decreased (P<0.001 or P<0.0001). 【Conclusion】 The treatment of glioma with Belamcanda chinensis is the result of multi-component, multi-target and multi-channel interactions. The results of cell experiments confirmed that Belamcanda chinensis extracts can affect the expressions of related target proteins of PI3K/AKT signal pathway and VEGF and MMP9, which verified the results of network pharmacology. The results provide a theoretical basis for the clinical application of Belamcanda chinensis and studies on glioma.
2.Clinical guideline for surgical treatment of symptomatic chronic osteoporotic vertebral fractures
Bohua CHEN ; Qixin CHEN ; Liming CHENG ; Tongwei CHU ; Zhongliang DENG ; Jian DONG ; Haoyu FENG ; Shiqing FENG ; Shunwu FAN ; Yanzheng GAO ; Zhong GUAN ; Yong HAI ; Dingjun HAO ; Baorong HE ; Dianming JIANG ; Jianyuan JIANG ; Chunde LI ; Fang LI ; Feng LI ; Li LI ; Weishi LI ; Zhongshi LI ; Qi LIAO ; Bin LIU ; Guodong LIU ; Xiaoguang LIU ; Zhongjun LIU ; Shibao LU ; Xinlong MA ; Limin RONG ; Huiyong SHEN ; Yong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Jiwei TIAN ; Huan WANG ; Hong XIA ; Jianzhong XU ; Zhengwei XU ; Huilin YANG ; Jie ZHAO ; Yue ZHOU ; Yue ZHU
Chinese Journal of Trauma 2020;36(7):577-586
According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.
3.Feasibility analysis on 3D laparoscopic surgery via transrectal extraction of specimens without abdominal incision in the treatment of slow transit constipation.
Bing LU ; Chuangang FU ; Zhuqing ZHOU ; Junyi HAN ; Tao DU ; Zhe ZHU ; Wei GAO ; Qixin JIANG ; Fang JI ; Zhenyu ZHANG
Chinese Journal of Gastrointestinal Surgery 2018;21(8):901-907
OBJECTIVETo investigate the safety and feasibility of 3D laparoscopic surgery via transrectal extraction of specimens without abdominal incision in the treatment of slow transit constipation (STC).
METHODSFrom May 2015 to January 2017, 8 STC patients (6 females and 2 males) with informed consent were selected to receive subtotal colectomy with 3D laparoscopy as the no-incision incision group, in which the initial part of ascending colon and rectum were end-to-end anastomosed directly after extraction of the specimen through the rectum. Twelve STC patients (9 females and 3 males) undergoing traditional subtotal colectomy with 3D laparoscopy were selected as the traditional group by case matching method (gender, age, BMI, the difference of receiving operation time less than 12 months, same surgeon team). Perioperative parameters (operation duration, intraoperative blood loss, exhausting time, postoperative hospital stay, complications, postoperative pain score and additional pain management), inflammation index at postoperative day 1 and day 3 (leukocyte, procalcitonin, interleukin 6, C-reactive protein), postoperative peritoneal infection, wound healing, short-term and long-term efficacy, patient satisfaction evaluation (subjective hundred-mark system) at postoperative one year were compared between two groups.
RESULTSThere were no significant differences between two groups in operation duration, intraoperative blood loss, exhausting time, postoperative hospital stay and morbidity of complication (all P>0.05). Significantly lower pain scores at postoperative 6-hour (median 3.0 vs. 4.5, U=23.0, P=0.042), lower ratio of additional analgesic at postoperative day 1(1/8 vs. 7/12, P=0.040) were found in the no-incision group. Leukocyte level at postoperative day 1 was significantly lower in the no-incision group [(11.0±3.5)×10/L vs. (14.7±3.6)×10/L, t=-2.281, P=0.035]. C-reactive protein concentration at postoperative day 3 was not significantly different between two groups but with different trend [median 78.1(0.1 to 154.0) mg/L vs. 22.0 (7.0 to 55.9) mg/L,U=33.0, P=0.047]. There were no significant differences of interleukin-6 and procalcitonin between two groups(all P>0.05). All the patients had follow-up for 14-31 months. Subjective effectiveness score was 90±9 in the no-incision group and 94±6 in the traditional group without significant difference(t=-1.099, P=0.286). No long-term complications associated with abdominal infection was observed in the no-incision group.
CONCLUSION3D laparoscopic subtotal colectomy via transrectal extraction of specimens without abdominal incision in the treatment of STC has similar short-term and long-term efficacies compared with traditional laparoscopic assisted surgery, and does not increase the probability of abdominal contamination.
Colectomy ; methods ; Constipation ; surgery ; Female ; Humans ; Laparoscopy ; Length of Stay ; Male ; Operative Time ; Rectum ; Treatment Outcome
4.Protective measures in laparoscopic resection for upper or mid rectal cancer and sigmoid colon cancer with transrectal specimen extraction surgery.
Chuangang FU ; Zhuqing ZHOU ; Junyi HAN ; Bin LU ; Wei GAO ; Zhe ZHU ; Qixin JIANG ; Fang JI ; Tao DU
Chinese Journal of Gastrointestinal Surgery 2017;20(10):1151-1155
OBJECTIVETo introduce the use of a self-made specimen protective sleeve in laparoscopic resection for upper or mid rectal cancer and sigmoid colon cancer with transrectal specimen extraction surgery and the improvement of implantation method, so as to avoid and reduce bacterial contamination and tumor cell dissemination in abdominal cavity.
METHODSDuring June 2015 and May 2017, 48 cases of high located rectal or sigmoid colon cancer were operated laparoscopically with natural orifices specimen extraction surgery (NOSES) using a self-made specimen protecting sleeve. Operation indication: (1) Rectum and sigmoid colon cancer with the distance of more than 6 cm from tumor inferior margin to dentate line. (2) The maximum diameter of intestine together with mesangial and tumor <7 cm by intraoperative judgment. (3) No anal and distal rectal surgery, no anorectal stenosis or lack of expansion capacity caused by trauma. (4) No ulcerative colitis, Crohn's disease or radiation proctitis. After transecting the rectum, the specimen protective sleeve was inserted through the right lower 12 mm main Trocar (This sleeve was tailored from the laparoscopic protective sleeve produced by China 3L Corporation, which was intercepted with 25-35 cm from one end of the sleeve according to the length of distal rectal retention. One end was ligated and the other was open with a ligature band. About 5 ml paraffin oil was used to rinse and lubricate during the operation). The rectal stump retained 7-8 cm in abdominal cavity. The transanal ligation part of the protective sleeve was cut off, then the stapler nail seat was inserted and specimen was pull out through the sleeve and rectum.
RESULTSThere were 30 males and 18 females. The average age was (64.5±14.1) years, the BMI was (25.4±3.9) kg/m, the tumor diameter was (3.3±1.1) cm, the maximum diameter of specimen was (5.4±1.5) cm and the length of specimen was (18.6±4.3) cm. Among these 48 cases, specimens of 36 patients were pulled out through inside of the sleeve easily, while specimens of 12 patients were quite difficult with resistance. Of 12 cases, 7 needed the help of transverse forceps, 4 needed to make 1 cm incision in pull-through bowel and insert a suction to decrease the volume of large specimens with gathering of gas and fluid, and 1 received small abdominal incision to remove specimen and perform intestinal reconstruction due to big specimen (the diameter of tumor and mesentery was 7.5 cm). Specimen tears of 6 patients didn't result in dissemination thanks to the specimen protecting sleeve. The operation time was (113.2±76.1) min, the bleeding amount was (38.5±17.3) ml, the time to first oral intake was (47.9±4.4) h, and the postoperative hospitalization length was (8.5±1.7) d. Anastomotic leakage occurred in 1 case (2.1%). No intra-abdominal and trocar infection, and obstruction were found.
CONCLUSIONThe use of protective sleeve and the improvement of the method of intraperitoneal implantation can effectively reduce the abdominal contamination during the specimen extraction. It can be applied to big specimens as well.
5.Improvement of NET and 5-HTT expression involved in the anti-depressive effect of valproate
Huizhi FEI ; Xiaoya HU ; Hongmei QIU ; Dan LIU ; Qixin ZHOU
Journal of China Pharmaceutical University 2016;47(4):474-478
This study aimed at investigating the correlations between antidepressive effect of valproate and improvements of NET and 5-HTT expression in depressive rats leaded by chronic mild unpredicted stress(CUMS)with solitary condition. Sixty male SD rats were divided into normal group(NG), model group(MG), valproate treated-normal group(VNG), and valproate treated-model group(VMG), randomly. The changes of depressive behaviors were evaluated by the open-field test and force swimming test. The contents of MDA, activities of SOD and CAT in serum, the mRNA and protein expression of NET, 5-HTT in hippocampus were determined by biochemical methods, Real-time PCR and Western Blot, respectively. Results showed that CUMS can significantly decrease the activities in open-field test, SOD and CAT activities in serum, expression of 5-HTT in hippocampus, and obviously increase the immobility time in force swimming test, the level of MDA and expression of NET. The treatment of valproate obviously improved the changes induced by CUMS. However, the treatment of valproate had no significant influences on behaviors of NG rats. So, it revealed that improvements of the mRNA and protein expression of NET, 5-HTT may be involved in the antidepressive effect of valproate.
6.Optimization of initial antibacterial drug regimens for treating common staphylococcal infection in ICU
Xinkai YAO ; Yaling WU ; Ren LIU ; Qixin ZHOU ; Changqing LI
Chongqing Medicine 2015;(10):1300-1304
Objective To optimize the antibacterial drug regimen in ICU common staphylococcal infection.Methods The pharmacokinetic and pharmacodynamic parameters of antibacterial drugs were collected in combination with the hospital ICU anti-microbial drug resistance monitoring reports from the national antimicrobial resistance investigation net (Mohnarin)of the Ministry of Health and the performance standards for antimicrobial susceptibility testing (2013)issued by the clinical and laboratory stand-ards institute (CLSI),the minimum inhibitory concentration (MIC)of staphylococci was set by using the discrete uniform distribu-tion method and 16 kinds of administration regimens with 6 antimicrobial agents were worked out.The best initially antimicrobial regimen was optimized by using the pharmacokinetic and pharmacodynamic models and Monte Carlo simulations of cumulative frac-tion of response (CFR)from 5 000 patients.Results The alternative initially drug regimens to the infectious bacteria were:linezolid 0.40 g twice daily and vancomycin 0.75 g twice daily for staphylococcus aureus;amikacin 0.60 g once daily and linezolid 0.40 g twice daily,and vancomycin 0.75 g twice daily for hemolytic staphylococci and staphylococcus epidermidis;linezolid 0.40 g twice daily and vancomycin 0.75 g twice daily for methicillin-resistant Staphylococcus aureus;ampicillin/sulbactam 1.50 g 4 times daily, cefuroxime 0.75 g 4 times daily,amikacin 0.60 g once daily,moxifloxacin 0.40 g once daily for methicillin-sensitive staphylococcus aureus.Conclusion In the Staphylococcus aureus infection occurred in ICU,if which being methicillin-sensitive could be deter-mined,ampicillin/sulbactam,cefuroxime,amikacin and moxifloxacin could be selected for treatment,and linezolid or vancomycin could be selected for treating possible methicillin-resistant Staphylococcus aureus infection or undetermined whether being methicil-lin-resistant Staphylococcus aureus infection.
7.Down-regulation of monoamine neurotransmitter synthetase expression involved in CUS-induced depression of rats
Lijia WANG ; Hongmei QIU ; Xinhui JIANG ; Dan LIU ; Huizhi FEI ; Xiaoya HU ; Qixin ZHOU
Chinese Pharmacological Bulletin 2015;(4):527-531
Aim To investigate whether chronically un-predictable stress (CUS)-induced depression-like be-haviors of rats is associated with the variant expression of tryptophan hydroxylase (TPH)and tyrosine hydrox-ylase (TH).Methods 30 male SD rats were ran-domly divided into depression model group(MG)and control group (CG),the former was established using CUS plus solitary condition for 28 d,whereas the latter was fed normally as five rats per cage without CUS. The open field test(OFT)and the sucrose preference test were used to evaluate depressive behaviors.Both mRNA and protein expressions of TPH and TH in hip-pocampus and forebrain cortex were determined by re-al-time fluorescent quantitative PCR and western blot (WB),respectively.Results MG rats showed obvi-ous depressive behaviors with much lower locomotive activity and sucrose preference than CG.Meanwhile, the mRNA and protein expressions of TPH and TH also significantly decreased in MG rats,compared with CG rats.Conclusion The depression behaviors of rats in-duced by CUS may be associated with down-regulation of TPH and TH expression.
8.Improving oxidative stress response and reversing abnormal expression of hippocampus NET and 5-HTT involved in anti-depressive effect of venlafaxine
Xiaoya HU ; Huizhi FEI ; Xinhui JIANG ; Dan LIU ; Hongmei QIU ; Qixin ZHOU
Chinese Pharmacological Bulletin 2014;(6):848-852
Aim To investigate if anti-depressive effect of venlafaxine was associated with improving oxi-dative stress and expression of hippocampus NET and 5-HTT in rat model induced by CUS. MethodsEighty SD male rats were randomly divided into four groups:model group(MG),normal group(NG), ven-lafaxine-treated normal group ( VNG ) , and venlafax-ine-treated model group ( VMG) . VNG and VMG were given venlafaxine (23. 4 mg·kg-1 ·d-1 ) once daily;NG and MG were given the same volume solvent. Soli-tary condition with chronic unpredicted stress ( CUS ) was taken to establish rat depression model. The force swimming test was used to evaluate the behavior chan-ges of experimental rats. The malondialdehyde ( MDA) level and activity of superoxide dismutase ( SOD ) in serum were determined by biochemical methods. The mRNA and protein expressions of NET and 5-HTT in
hippocampus were determined by Real-Time Reverse transcription polymerase chain reaction ( real-time RT-PCR) and Western blot ( WB) , respectively. Results Compared with NG rats, obviously increasing immo-bile time of rats in force swimming test and serum MDA level, as well as significantly decreasing SOD activity in serum was observed with clearly decreasing 5-HTT expression and elevating NET expression in hippocam-pus of MG rats. The treatment of venlafaxine distinctly suppressed changes above from CUS-induced rats. However, significant changes failed to be found in VNG rats. Conclusion The anti-depressive effect of venlafaxine may at least partly involve in improving ox-idative stress/anti-oxidative stress balance and revers-ing abnormal expression of NET and 5-HTT.
9.Study on the role of COX-2 in BMP9 induced osteogenic differentiation in mesenchymal stem cells
Jun HUANG ; Yingzi LIU ; Shuangxue YUAN ; Qiuxiang WU ; Dongxu WANG ; Qixin ZHOU ; Baicheng HE
Chinese Pharmacological Bulletin 2014;(7):1006-1011
Aim To investigate the role of COX-2 in BMP9 induced osteogenic differentiation,and the pos-sible mechanism underlying this function of COX-2. Methods We introduced real-time PCR, Western blot, and immunocytochemical staing to detect the effect of BMP9 on COX-2 expression.We employed chemiluminescence technique to assay ALP activities, RT-PCR to detect the expression of Smad6 and Smad7 , and Western blot to measure the expression of Runx2, Dlx-5,total Smad1/5/8,and phosphorylated Smad1/5/8.Finally,BMPR-Smad luciferase reporter assay was applied to measure the activation of BMPs/Smads signaling.Results BMP9 could induce the expression of COX-2 in C3H10T1/2 cells.Either inhibiting enzy-matic activity of COX-2 or knockdown of the expression of COX-2 reduced the BMP9 induced ALP activities in C3H10T1/2 cells,and COX-2 knockdown also inhibited the ectopic bone formation induced by BMP9 in C3H10T1/2 cells.Moreover,COX-2 knockdown inhibi-ted BMPR-Smad reporter activities and the phosphoryl-ation of Smad1/5/8,so did the expression of Smad6 and Smad7 .Conclusion COX-2 may play an impor-tant role in BMP9 induced osteogenic differentiation in MSCs by regulating the BMPs/Smads signaling trans-duction.
10.Study on effect of berberine on modulating lipid and CPT I A gene expression.
Hong WANG ; Lingyun SHI ; Huafeng YIN ; Qixin ZHOU
China Journal of Chinese Materia Medica 2011;36(19):2715-2718
OBJECTIVETo investigate the modulating effect on lipid and gene expressions of CPT I A caused by berberine (Ber) in experimental hyperlipidemia rats.
METHODMale SD rats were randomly divided into 5 groups according to the blood lipid values: normal group, hyperlipidemia group, 300 mg x kg(-1) x d(-1) Ber-treated group, 60 mg x kg(-1) x d(-1) Ber-treated group, and 7.2 mg x kg(-1) x d(-1) lovastatin-treated group. Normal group were fed with base diet and other groups were fed with high fat and cholesterol diet. 12 weeks after drugs were given the TC, TG, LDL-C, and HDL-C from rat blood samples were tested by automatic biochemistry analyzer. Gene expressions of CPT I A and PPARalpha were evaluated by RT-PCR and Western blot, respectively.
RESULTIt was shown that Ber significantly decreased TC and LDL-C, but increased HDL-C in dose-dependent manner, elevated expressions of CPT I A mRNA and protein without influence on PPARalpha expression. Similar effects from lovastatin on lipidemia were observed except the Ber effect on CPT I A gene expression.
CONCLUSIONBer has modulating effect on the lipid metabolism, the mechanism of which may be by promoting the CPT I A gene expression.
Animals ; Berberine ; administration & dosage ; Carnitine O-Palmitoyltransferase ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Gene Expression ; drug effects ; Humans ; Hyperlipidemias ; drug therapy ; enzymology ; genetics ; metabolism ; Lipid Metabolism ; drug effects ; Male ; PPAR gamma ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar

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