1.Comparison of endoscopic variceal ligation and pericardial devascularization in treatment of portal hypertension
Lan BAI ; Xiaozhong GUO ; Hongyu LI
Journal of Clinical Hepatology 2014;30(12):1283-1286
Objective To compare the clinical efficacy of endoscopic variceal ligation versus pericardial devascularization in the treatment of portal hypertension.Methods The clinical data of 101 cirrhotic patients with gastroesophageal varices and variceal hemorrhage from January 2010 to January 2012 were analyzed.Fifty-three patients received endoscopic variceal ligation,and forty-eight patients received pericardial devascularization.Postoperative changes in liver function and hypersplenism were compared between the two groups.The rate of rehaemorrhagia and incidence of postoperative complications after surgery were compared as well.Continuous data were expressed as mean ±SD,and categori-cal data were expressed as number of cases or percentage.Comparison of continuous data between the two groups was made by independent-samples t test,and comparison of categorical data was made by chi-square test.Results After surgery,the variceal ligation group showed no significant changes in liver reserve function,while the albumin level was significantly decreased in the pericardial devascularization group (t=2.512,P<0.05).There were no significant changes in the counts of white blood cells and platelets in the endoscopic variceal ligation group after surgery (P>0.05),but significant increases in the counts of white blood cells and platelets were detected in the pericardial devascular-ization group (P<0.05).The rates of postoperative haemorrhage in the two groups were:3 months,7.5%vs 6.2%(χ2 =0.066,P>0.05), 6 months,7.5%vs 8.3%(χ2 =0.021,P>0.05),and 1 year,9.4%vs 8.3%(χ2 =0.038,P>0.05).The incidence rates of postopera-tive complications in the two groups were 24.5%and 50%,respectively (χ2 =7.040,P<0.05).Conclusion Compared with pericardial devascularization,endoscopic variceal ligation causes fewer microlesions,preserves liver function,and leads to a lower incidence of postopera-tive complications.However,if hypersplenism is observed in the cirrhotic patients with gastroesophageal varices and variceal hemorrhage,peri-cardial devascularization can be used to control the hypersplenism and prevent esophageal hemorrhage.
2.Cloning and functional characterization of a cDNA encoding isopentenyl diphosphate isomerase involved in taxol biosynthesis in Taxus media.
Tian SHEN ; Fei QIU ; Min CHEN ; Xiaozhong LAN ; Zhihua LIAO
Acta Pharmaceutica Sinica 2015;50(5):621-6
Taxol is one of the most potent anti-cancer agents, which is extracted from the plants of Taxus species. Isopentenyl diphosphate isomerase (IPI) catalyzes the reversible transformation between IPP and DMAPP, both of which are the general 5-carbon precursors for taxol biosynthesis. In the present study, a new gene encoding IPI was cloned from Taxus media (namely TmIPI with the GenBank Accession Number KP970677) for the first time. The full-length cDNA of TmIPI was 1 232 bps encoding a polypeptide with 233 amino acids, in which the conserved domain Nudix was found. Bioinformatic analysis indicated that the sequence of TmIPI was highly similar to those of other plant IPI proteins, and the phylogenetic analysis showed that there were two clades of plant IPI proteins, including IPIs of angiosperm plants and IPIs of gymnosperm plants. TmIPI belonged to the clade of gymnosperm plant IPIs, and this was consistent with the fact that Taxus media is a plant species of gymnosperm. Southern blotting analysis demonstrated that there was a gene family of IPI in Taxus media. Finally, functional verification was applied to identify the function of TmIPI. The results showed that biosynthesis of β-carotenoid was enhanced by overexpressing TmIPI in the engineered E. coli strain, and this suggested that TmIPI might be a key gene involved in isoprenoid/terpenoid biosynthesis.
3.Enhancement of tropane alkaloids production in transgenic hair roots of Atropa belladonna by overexpressing endogenous genes AbPMT and AbH6H.
Shiping LONG ; Yan LU ; Yaxiong WANG ; Chunxian YANG ; Xiaozhong LAN ; Zhihua LIAO
Acta Pharmaceutica Sinica 2013;48(2):243-9
Atropa belladonna L. is the officially medicinal plant species and the main commercial source of scopolamine and hyoscyamine in China. In this study, we reported the simultaneous overexpression of two functional genes involved in biosynthesis of scopolamine, which respectively encoded the upstream key enzyme putrescine N-methyltransferase (PMT; EC 2.1.1.53) and the downstream key enzyme hyoscyamine 6beta-hydroxylase (H6H; EC 1.14.11.11) in transgenic hair root cultures of Atropa belladonna L. HPLC results suggested that four transgenic hair root lines produced higher content of scopolamine at different levels compared with nontransgenic hair root cultures. And scopolamine content increased to 8.2 fold in transgenic line PH2 compared with that of control line; and the other four transgenic lines showed an increase of scopolamine compared with the control. Two of the transgenic hair root lines produced higher levels of tropane alkaloids, and the content increased to 2.7 fold in transgenic line PH2 compared with the control. The gene expression profile indicated that both PMT and H6H expressed at a different levels in different transgenic hair root lines, which would be helpful for biosynthesis of scopolamine. Our studies suggested that overexpression of A. belladonna endogenous genes PMT and H6H could enhance tropane alkaloid biosynthesis.
4.Design, synthesis and anti-hBV evaluation of adefovir mono-L-amino acid ester, mono non-steroidal anti-inflammatory drugs carboxylic ester prodrugs.
Xiaozhong FU ; Yonglin WANG ; Yanyu LAN ; Aimin WANG ; Yu OU ; Chun LUO ; Yan LI
Acta Pharmaceutica Sinica 2010;45(8):1017-24
A series of adefovir mono-L-amino acid esters, mono non-steroidal anti-inflammatory drugs carboxylic ester prodrugs with more potent anti-HBV activity and lower nephrotoxicity were designed and synthesized. Adefovir bis (L-amino acid) ester was used as lead compound, according to pathological and pharmacological findings that non-steroidal anti-inflammatory drugs can effectively inhibit the organic anion transporter 1 (hOAT1)-mediated adefovir phosphonic acid pairs of anion transport across tubular basement membrane thereby reducing the nephrotoxicity of adefovir. Flatten design principle was used to introducing non-steroidal anti-inflammatory drugs structural fragments to design and synthesize target adefovir mixture ester prodrugs. HepG2 2.2.15 cell line was used as in vitro anti-HBV activity evaluation model. Five compounds exhibited antiviral activity, and compound 18 showed the most potent anti-HBV activity and relatively high selective index (EC50 3.92 micromol L(-1), SI 9.97). HK-2 cell line was used as in vitro model to evaluate nephrotoxicity. Results suggested the target compounds have lower cytotoxicity than the positive control. Moreover, by analyzing the primary structure and activity relationship of these compounds, it could suggest that mono-L-amino acid ester, mono non-steroidal anti-inflammatory drugs carboxylic ester prodrugs strategy has significant potential in the acyclic nucleoside phosphonates prodrug design.
5.Clinical effect analysis in the treatment of acute limb arterial critical ischemia
Guanhua XUE ; Changning HAO ; Lei LYU ; Hui XIE ; Xiangjiang GUO ; Xiaozhong HUANG ; Meng YE ; Lan ZHANG
International Journal of Surgery 2016;43(12):814-817
Objective To discuss the therapeutic effect in the treatment of the acute limb arterial critical ischemia.Methods Collect thirty-nine cases of acute limb arterial critical ischemia in Renji Hospital from Janary 2014 to July 2016.According to the patients' manifestation,these operations were porfermed including thrombectomy,cathetery-directed thrombolysis,mechanical suction bolt,percutaneous angioplasty and stenting.The effect and complications were observed.Results The eighteen patients in 39 cases (46.2%) were dead,including 5 cases without operation,13 operation.The eight cases were amputated during 34 cases of operations.In the 21 out-patients safely,2 cases were not followed up.The time of follow-up was from 3 to 27 months,on average 14.3 months.During the 21 patients,5 cases died from heart cerebrovascular or tumor diseases,3 cases with footdrop,2 cases with toe amputations,3 cases with distal leg and foot anesthesias.Conclusions The patiens with acute limb arteries critical ischemia must be treated as early as,and reinforced the management of multiple organ function,which may improve the diseases' therapeutic effect.
6.Percutaneous endovascular treatment of below-the-knee arterial bifurcation lesions with coronary bifurcation stenting techniques
Meng YE ; Biao HONG ; Xiaozhong HUANG ; Hui XIE ; Zezheng YAN ; Lan ZHANG
Chinese Journal of General Surgery 2015;30(11):870-874
Objective To report the preliminary results of drug eluting stents (DES) in infrapopliteal bifurcation lesions after failed angioplasty.Methods From April 2011 to December 2013, 21 patients with critical limb ischemia and infrapopliteal atherosclerotic disease underwent DES placement in tibial bifurcation using 4 techniques: balloon and stent (single stent), T-shape double-stent, Crush double-stent and Culotte double-stent.Clinical and angiographic end points included: Amputation-free survival, target lesion revascularization (TLR)-free survival, target vessel revascularization (TVR)-free survival.Angiographic primary and secondary patency of DES, 2-vessel primary patency (2VPP), and 1-vessel primary patency (1VPP).Results Technical success was achieved in all patients (100%) without major intraoperative complications.ABI increased from 0.23 ± 0.07 to 0.67 ± 0.24 (P < 0.05) after 1 week.The mean follow-up intervals were 23 ± 7 months;amputation-free survival, TLR-free survival and TVR-free survival were 100%, 90.5% and 79.1%, respectively, at 1 year.8 patients underwent angiography reevaluation.The angiographic primary and secondary patency of DES were 62.5%, 87.5%, respectively.The primary patency of 2VVP and 1VVP were 28.6%, 57.1%, respectively at 1 year.Conclusions Bifurcation stenting techniques utilized in coronary arteries can be used in the infrapopliteal arteries.Although provisional stenting in the origin of tibial bifurcation cannot inhibit restenosis in distal lesions treated with balloon angioplasty, clinical outcomes and limb salvage rates are acceptable for these techniques.
7.Design, synthesis and anti-oxidative evaluation of L-amino acid prodrugs of scutellarein.
Xiaozhong FU ; Wei ZHANG ; Yonglin WANG ; Yanyu LAN ; Aimin WANG ; Wen ZHOU ; Yong HUANG ; Jing LI ; Fengjing XING ; Ying LIU
Acta Pharmaceutica Sinica 2011;46(5):548-55
To design and synthesize a series of novel scutellarein 4'-L-amino acid prodrugs with more potent anti-oxidative activity and improved physicochemical properties. Scutellarein was used as lead compound, according to successful experience of improving bioavailability of oral administration drugs by active transport mechanism, principle of hybridization was used to introducing L-amino acid structural fragments at 4'-position of scutellarein to design and synthesize target scutellarein 4'-L-amino acid prodrugs. The synthetic compounds were tested on their physicochemical properties and in vitro anti-oxidative activity against H202 induced oxidative damage in PC12 cells. Five compounds were found to have more potent anti-oxidative activity than positive control VE. Moreover the physicochemical properties of synthesized compounds were evaluated, and the results revealed that L-amino acid ether derivatives are more stable (t1/2 9-92 h) than their corresponding ester derivatives (t1/2 0.5 h). Water solubility of scutellarein 4'-L-amino acid ester and ether derivatives were 1 796-4 100 microg.mL-1 and 27.7-81.1 microg.mL-1 respectively, in comparison with scutellarin, the solubility of compounds 18, 19 and 22, 24-27 increased about 120-280 fold and 2-6 fold respectively. All these results suggested that L-amino acid prodrug strategy has significant potential in scutellarein prodrug design.
8.Reasons for clinical failure after endovascular treatment of chronic iliac vein occlusions
Meng YE ; Xiaozhong HUANG ; Guanhua XUE ; Changning HAO ; Lan ZHANG
Chinese Journal of General Surgery 2017;32(10):868-871
Objective To discuss the risk factors of iliaofemoral vein restenosis after percutaneous recanalization of post-thrombotic occlusion.Method From March 2006 to December 2014,44 limbs in 41 patients with chronic post-thrombotic iliaofemoral vein occlusion underwent endovascular treatment in our hospital.Post-operative patency was evaluated by ultrasonography and anterograde veinography.Results Initial technical success was 90.2% (37/41).During the follow-up,5 cases of reobstruction were determined,2 were caused by insufficient stent extension into the inferior vena cave.Failure in two cases of intra-stent thrombosis were found due to arbitrary discontinuity of oral anticoagulative therapy.Moreover,2 of 9 cases with venous ulcers in lower extremities were exacerbated after failure of endovascular treatment,we therefore performed surgical ligation and endovenous laser treatment of circumambient perforating veins.Conclusion Insufficient lesion cover,not enough extension to interior vena cave and unreasonable post-operative anticoagulation discontinuity are major causes of intra-stent reobstruction in iliaofemoral venous occlusion.
9.Molecular insights into AabZIP1-mediated regulation on artemisinin biosynthesis and drought tolerance in Artemisia annua.
Guoping SHU ; Yueli TANG ; Mingyuan YUAN ; Ning WEI ; Fangyuan ZHANG ; Chunxian YANG ; Xiaozhong LAN ; Min CHEN ; Kexuan TANG ; Lien XIANG ; Zhihua LIAO
Acta Pharmaceutica Sinica B 2022;12(3):1500-1513
Artemisia annua is the main natural source of artemisinin production. In A. annua, extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid (ABA) treatment can increase artemisinin biosynthesis. ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes. Here, we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1, which AabZIP1 does not directly activate. Subsequently, it was found that AabZIP1 up-regulates AaMYC2 expression through direct binding to its promoter, and that AaMYC2 binds to the promoter of AaALDH1 to activate its transcription. In addition, AabZIP1 directly transactivates wax biosynthesis genes AaCER1 and AaCYP86A1. The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression, whereas they were significantly decreased in RNAi-AabZIP1 plants. Collectively, we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis, which may have general implications. We have also identified AabZIP1 as a promising candidate gene for the development of A. annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding.