1.Specific inhibition of NLRP3 expression in GABAergic neurons in CA1 area of the hippocampus improves cognitive dysfunction in mice after traumatic brain injury
Huitao MIAO ; Rongxin SONG ; Jingjing SHAO ; Shiyan JIA ; Wenguang LI ; Dongxue ZHANG ; Jianyong ZHAO ; Xiaoming LI ; Limin ZHANG
Chinese Journal of Neuromedicine 2024;23(2):119-130
Objective:To explore the effect of NOD-like receptor thermal protein 3 ( NLRP3) knockout in γ-aminobutyric acid (GABA)-ergic neurons in the hippocampal CA1 area on improving cognitive dysfunction in mice after traumatic brain injury (TBI). Methods:Forty-eight healthy male NLRP3 flox/flox mice weighing 25-28 g were randomly divided into 4 groups ( n=12): sham-operated+control virus group (SV group), sham-operated+ NLRP3 specific knockout group (SG group), TBI+control virus group (TV group), TBI+ NLRP3 specific knockout group (TG group). TBI in the TV and TG groups was established by free-fall method, while surgical procedures such as scalp incision and cranial window opening without impact were given to the SV and SG groups. Adenovirus was injected into the hippocampal CA1 area of SG and TG groups 21 d before TBI to induce NLRP3 specific knockout in GABA-ergic neurons in the hippocampal CA1 area; empty virus was injected into the CA1 area of SV and TV groups. Cognitive function was evaluated using novel object recognition test 30 and 31 d after TBI, and learning and memory functions were assessed using Morris water maze test 32-36 d after TBI. Field potentials in the hippocampal CA1 area were recorded during novel object recognition 31 d after TBI. After behavioral tests, these mice were sacrificed. Immunofluorescent staining was used to detect the fluorescent intensity of microtubule-associated protein2 (MAP2), glutamic acid decarboxylase 67 (GAD67), and postsynaptic density protein 95 (PSD95) in the hippocampal CA1 area, as well as percentage of pyroptosis-associated inflammatory factor interleukin-18 (IL-18)/GAD67 double-positive neurons in total GAD67 positive neurons. Results:Compared with the SV and SG groups, the TV and TG groups had decreased novel object recognition index, decreased number of platform crossings during the experimental period, increased escape latency on day 3 and day 4 of the training period in Morris water maze test, decreased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, decreased fluorescent intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, increased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Compared with the TV group, the TG group had increased novel object recognition index, increased number of platform crossings in Morris water maze test, decreased escape latency during the training period, increased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, increased fluorescence intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, decreased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Conclusion:Specific inhibition of NLRP3 expression in GABA-ergic neurons in the hippocampal CA1 area can improve cognitive dysfunction in mice after TBI, whose mechanism may be related to inhibited GABA-ergic neuronal pyroptosis in the hippocampal CA1 area.
2.Correlation of polymorphisms at the matrix metalloproteinase-3-1612 position of the promoter region with the inflammatory response and oxidative stress in elderly patients with cerebral ischemic stroke
Cheng MIAO ; Zhiyong WANG ; Hongling ZHAO ; Xuanzhao GAO ; Lianping MA ; Jing YANG ; Wenguang CHANG
Chinese Journal of Geriatrics 2023;42(10):1174-1179
Objective:To investigate the association of polymorphisms at the matrix metalloproteinase(MMP)-3-1612 position of the promotor region with the inflammatory response and oxidative stress in elderly patients with cerebral ischemic stroke.Methods:In this retrospective study, 129 elderly patients with cerebral infarction diagnosed and treated in our hospital between March 2019 and March 2021 were enrolled as the study group, and 110 healthy subjects were selected as the control group.Polymorphisms of the MMP-3-1612 position in the promotor region, the inflammatory response and oxidative stress were examined using appropriate parameters and the associations between them were analyzed. Results:Compared with the control group, the proportions of patients with hypertension, diabetes, and smoking history in the study group were significantly higher( χ2=16.05, 17.19, 14.19, all P<0.05), and the levels of fasting blood glucose, low-density lipoprotein, and homocysteine were also significantly higher( t=6.22, 3.64, 2.69, all P<0.05).Meanwhile, compared with patients carrying the MMP-3-5A/6A or the MMP-3-6A/6A genotype, the levels of serum inflammatory markers such as high mobility group box-1 protein(HMGB1), fractalkine(FKN), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β)and interleukin-17(IL-17)in patients carrying the MMP-3 gene 5A/5A genotype were significantly higher(all P<0.05).In addition, the expression of serum oxidative stress-related molecules Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid-2 related factor2(Nrf2), antioxidant response element(ARE), quinone oxidoreductase 1(NQO1), and heme oxygenase-1(HO-1)was also significantly increased(all P<0.05), but there was no difference in these markers between patients carrying the MMP-3-5A/6A genotype and patients carrying the MMP-3-6A/6A genotype( P>0.05).Patients carrying the 5A/5A genotype and the 6A/6A genotype exhibited only one 97 bp band and one 120 bp band, respectively, while the patients carrying the 5A/6A genotype exhibited two 97 bp bands and two 120 bp bands.There was no statistical difference in the number of patients carrying the 5A/6A genotype in the cerebral infarction group compared with the control group( P>0.05), and the number of patients carrying the 5A/5A genotype in the cerebral infarction group was higher than that in the control group(69% or 53.49% vs.35% or 31.82%, χ2=11.34, P<0.05).Polymorphisms of the MMP-3 gene had a positive correlation with the risk of stroke( r=0.25, P<0.05). MMP-3-1612 gene polymorphism( OR=7.21, 95% CI: 1.13-1.83, P=0.01), elevated blood glucose( OR=1.27, 95% CI: 1.18-2.06, P<0.001), high homocysteine( OR=1.05, 95% CI: 1.08-1.58, P<0.01), hypertension( OR=5.414, 95% CI: 1.140-4.46, P<0.01), elevated low-density lipoprotein( OR=4.03, 95% CI: 1.03-2.35, P=0.02), coronary heart disease( OR=1.17, 95% CI: 1.47-3.19, P<0.01)and diabetes( OR=8.52, 95% CI: 1.32-4.71, P<0.01)were risk factors for cerebral infarction. Conclusions:In elderly patients with cerebral infarction, polymorphisms of the MMP-3-1612 position in the promotor region is closely related to the risk of cerebral ischemic stroke, the inflammatory response and oxidative stress.MMP-3 gene polymorphisms are risk factors for stroke.
3.A study of pleural effusion in genomic detection of lung adenocarcinoma
Guodong WU ; Wenguang GU ; Mingming YUAN ; Jun ZHAO ; Sheng LI
Chinese Journal of Oncology 2022;44(8):873-876
Objective:To investigate the reliability of gene detection results using pleural effusion from patients with lung adenocarcinoma, and evaluate the clinical application value of pleural effusion supernatant in gene detection of lung adenocarcinoma.Methods:A total of 145 patients with lung adenocarcinoma pathologically confirmed from February 2015 to December 2019 were included, including 129 patients from Peking University Cancer Hospital & Institute and 16 patients from the First Hospital of Fangshan District. In this study, 55 pleural effusion supernatant samples, 52 plasma samples, and 48 tumor tissue samples were selected to targeted next-generation sequencing (NGS) of 1, 021 cancer-related genes, and the ability of gene detection of pleural effusion supernatant, tumor tissue, and plasma were compared.Results:The mutation rate of pleural effusion supernatant was 100.00%, the median maximum somatic allele frequency (MSAF) was 16.40%, and the chromosomal copy number detection (CNV) was 45.45%, showed no statistically significant difference compared with the tumor tissue samples (95.56%, 26.55% and 45.83%, respectively, P>0.05); However, it showed many advantages compared with plasma samples (90.38%, 2.50% and 9.62%). Among the drug-related driver genes, the percentage of EGFR mutation carrier in pleural effusion supernatant, tumor tissue and plasma were 61.82%, 58.33% and 38.46% respectively, the percentagein pleural effusion was higher than that in plasma ( P<0.05), but had no statistical difference compared with the tissue ( P>0.05). Conclusions:Pleural effusion supernatant has high reliability and effectiveness in detecting gene mutation. When lung adenocarcinoma patients are difficult to obtain tumor tissue clinically, it can be used as a substitute sample for genetic testing.
4.A study of pleural effusion in genomic detection of lung adenocarcinoma
Guodong WU ; Wenguang GU ; Mingming YUAN ; Jun ZHAO ; Sheng LI
Chinese Journal of Oncology 2022;44(8):873-876
Objective:To investigate the reliability of gene detection results using pleural effusion from patients with lung adenocarcinoma, and evaluate the clinical application value of pleural effusion supernatant in gene detection of lung adenocarcinoma.Methods:A total of 145 patients with lung adenocarcinoma pathologically confirmed from February 2015 to December 2019 were included, including 129 patients from Peking University Cancer Hospital & Institute and 16 patients from the First Hospital of Fangshan District. In this study, 55 pleural effusion supernatant samples, 52 plasma samples, and 48 tumor tissue samples were selected to targeted next-generation sequencing (NGS) of 1, 021 cancer-related genes, and the ability of gene detection of pleural effusion supernatant, tumor tissue, and plasma were compared.Results:The mutation rate of pleural effusion supernatant was 100.00%, the median maximum somatic allele frequency (MSAF) was 16.40%, and the chromosomal copy number detection (CNV) was 45.45%, showed no statistically significant difference compared with the tumor tissue samples (95.56%, 26.55% and 45.83%, respectively, P>0.05); However, it showed many advantages compared with plasma samples (90.38%, 2.50% and 9.62%). Among the drug-related driver genes, the percentage of EGFR mutation carrier in pleural effusion supernatant, tumor tissue and plasma were 61.82%, 58.33% and 38.46% respectively, the percentagein pleural effusion was higher than that in plasma ( P<0.05), but had no statistical difference compared with the tissue ( P>0.05). Conclusions:Pleural effusion supernatant has high reliability and effectiveness in detecting gene mutation. When lung adenocarcinoma patients are difficult to obtain tumor tissue clinically, it can be used as a substitute sample for genetic testing.
5.Clinicalefficiencyofendovascularinterventionaltherapyforthesolitarykidneywithrenalaneurysm
Fangzheng LI ; Jianzhuang REN ; Wenguang ZHANG ; Xuhua DUAN ; Jiaxing WANG ; Li WAN ; Linhui XU ; Guorui ZHAO ; Pengfei CHEN
Journal of Practical Radiology 2019;35(7):1128-1131
Objective Toanalyzetheclinicalefficiencyofendovascularinterventionaltherapyinthetreatmentofsolitarykidney withrenalaneurysm.Methods FromJune2014toDecember2017,7casesofsolitarykidneypatientscombinedwithrenalaneurysm werecollected,including4casesofrenalaneurysmlocatedinthemainrenalartery,1caseinrenalsegmentalarteryand2casesinthe renalparenchyma.4casesofmainrenalarteryaneurysmsweretreatedwithstentimplantation;1caseofrenalsegmentalarteryaneurysm was treatedwithstent-assistedcoilembolization;2casesofrenalparenchymaaneurysm wererespectivelytreatedwithpolyvinylalcohol (PVA)embolizationandPVA withcoilembolization.After1month,3months,6monthsandevery6months,therenaldopplerexamination,blood routine,urineroutine,renalfunctionandotherbiochemicalexaminationswerereviewed,andrenalarterialCTAorrenalangiographywereperformed whennecessary.Results Thesuccessrateofoperationwas100%in7solitarykidneypatientswithrenalaneurysm,andtheaneurysmswere graduallyreducedafteroperationwithoutseriousadversereactionsandcomplications.Norecanalizationorrecurrenceofrenalaneurysmwasfound duringthefollow-up,andtherenalfunctionwasbetterthanbefore.Conclusion Endovascularinterventionaltherapyinthetreatment ofsolitarykidneywithrenalaneurysmisminimallyinvasiveandlessrisky.Anditismoretargetedandflexibleforthetreatmentof solitarykidneywithdifferenttypesofrenalaneurysm.
6.Guiding-acupuncture for dry eye syndrome.
Wenzhang XIE ; Liang ZENG ; Ying TAO ; Yingfan ZHOU ; Ran ZHAO ; Xinyun HUANG ; Wenguang HOU ; Ren ZHANG ; Lei ZONG
Chinese Acupuncture & Moxibustion 2018;38(2):153-158
OBJECTIVETo observe the clinical efficacy differences between different needling methods for dry eye syndrome.
METHODSSixty patients of dry eye syndrome were randomly divided into an observation group and a control group, 30 cases (60 eyes) in each group. Shangjingming (Extra), Xiajingming (Extra), Tongziliao (GB 1), Cuanzhu (BL 2), Fengchi (GB 20), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3) and Taichong (LR 3) were selected in the two groups. The control group was treated with conventional acupuncture, while the observation group was treated with guiding-acupuncture. Electroacupuncture (EA) was used at bilateral Tongziliao (GB1) and Cuanzhu (BL 2), 30 min per treatment. The treatment was given three times per week. Totally 1-month treatment (12 treatments) was given. The eye symptom score, breakup time of tear film (BUT), Schirmer Ⅰ test (SⅠT) and visual analogue scale (VAS) score were compared before and after treatment in the two groups. The clinical efficacy was compared between the two groups.
RESULTSCompared before treatment, the eye symptom score, BUT, SⅠT and VAS score were improved after treatment in the two groups (all<0.001); the improvements of eye symptom score and SⅠT in the observation group were superior to those in the control group (both<0.05). The differences of BUT and VSA score between the two groups were not significant (both>0.05). The total effective rate was 86.7% (52/60) in the observation group, which was superior to 73.3% (44/60) in the control group (<0.05). .
CONCLUSIONThe conventional EA and guiding-acupuncture combined with EA are both effective for dry eye syndrome, and the efficacy of guiding-acupuncture combined with EA is superior to that of conventional EA.
7. Endoscopicretrograde cholangio-pancreatography management of long-term complications after pancreaticoduodenectomy
Wenguang WU ; Wenjie ZHANG ; Jun GU ; Mingning ZHAO ; Hao WENG ; Mingzhe WENG ; Yi ZHANG ; Chunying QU ; Leiming XU ; Yingbin LIU ; Xuefeng WANG
Chinese Journal of Surgery 2018;56(11):833-836
Objective:
To investigate the feasibility and effectiveness of endoscopicretrograde cholangio-pancreatography(ERCP)in the management of long-term complications after pancreaticoduodenectomy.
Methods:
From January 2009 to July 2018, the clinical data of 62 patients with biliary or pancreatic long-term complications after pancreatoduodenectomy were reviewed at Department of General Surgery, and the corresponding ERCP were carried out in the multi-disciplinary cooperation.There were 39 males and 24 females.The age was 56.5 years(aging from 13 to 76 years). The time of treatment was 3 months to 20 years after pancreatoduodenectomy.The long-term biliopancreatic complications after pancreatoduodenectomy included 51 cases of biliary calculi, 42 cases of bilioenteric anastomotic stenosis with proximal bile duct dilatation, and 11 cases of pancreaticointestinal anastomosis stenosis with distal pancreatic duct dilatation.All patients received conventional duodenoscopy or single-balloon enteroscopy assisted ERCP under general anesthesia.
Results:
A total of 95 ERCP were performed in 62 patients, averaging 1.5 times per case.The long-term complications of cholangiopancreatic after pancreatoduodenectomy(ERCP indications) included 56 times of bile duct stones(58.9%), 45 times of bilioenteric anastomatic stricture(47.4%), 11 times of recurrent pancreatitis(11.6%), 6 cases(6.3%) of bilioenteric anastomatic foreign body, 3 times of intrahepatic bile duct stenosis(3.2%). Among the 95 times, 82 times(86.3%) achieved endoscopic endoscopy, 76 times(80.0%) were diagnosed successfully, and 72 times(75.8%) were successfully treated with ERCP.Small intestinal perforation occurred in 1 patient undergoing duodenoscopy, and then healed by surgical repair.
Conclusion
Multi-disciplinary collaboration of ERCP is safe and effective in the treatment of long-term complications after pancreaticoduodenectomy, but the long-term effect still needs further clinical follow-up.
8.LncRNAs expression profile of ankylosing sporidylitis revealed by microarray
Xiaowu ZHONG ; Chengjiao YAO ; Yufeng QING ; Yaxi YAO ; Yonglong HE ; Qibin YANG ; Mingcai ZHAO ; Wenguang XIE ; Jingguo ZHOU
Journal of Chinese Physician 2017;19(2):214-219
Objective To investigate the expression profile variation of long non-coding RNAs (lncRNAs) in ankylosing sporidylitis (AS) and explore the role of lncRNAs in the pathogenesis of AS.Methods The peripheral blood mononuclear cells of AS patients and health controls (HC) were used to detect for differently expressed lncRNAs by microarray.The roles of lncRNAs were predicted with GO and pathway analysis.The results were verified by real time-polymerase chain reaction (PCR).Results A total of 148 lncRNAs and 134 mRNAs were detected,which had more than 2-fold differentially expressed in AS patients.Bioinformatics analysis found that GO term enrichment included protein binding,regulation of transcription,metabolism,signal transduction,et al.and might involve in toll-like receptor pathway,protein kinase,complement pathway,notch signaling pathway and so on.The expressions of three lncRNAs were estimated by real time-PCR which found that consistent with that of microarrays.Among these,D90064 was the most aberrantly expressed lncRNAs.Conclusions Several lncRNAs expression was changed significantly in AS patients in comparison with HC,which implies that those different lncRNAs may have an important role in the development and progression of AS.
9.Endovascular interventional therapy for Cockett syndrome associated with deep vein thrombosis of left lower extremity
Guorui ZHAO ; Jianzhuang REN ; Xuhua DUAN ; Wenguang ZHANG ; Pengfei CHEN ; Tai KANG ; Qinghui ZHANG ; Chaoyang WANG ; Donglin KUANG ; Fangzheng LI ; Xinwei HAN
Journal of Interventional Radiology 2017;26(6):522-526
Objective To evaluate the clinical effect of endovascular interventional therapy in treating Cockett syndrome associated with deep vein thrombosis (DVT) of left lower extremity.Methods The clinical data of a total of 256 patients with Cockett syndrome complicated by DVT of left lower extremity,who were admitted to authors' hospital during the period from January 2011 to January 2015,were retrospectively analyzed.The patients were treated with catheter-directed thrombolysis,balloon dilatation of the occluded or narrowed venous segment,and/or stent implantation.The circumference differences of the affected limbs before and after treatment and the long-term patency rates were compared.Results Of the 256 patients with Cockett syndrome complicated by DVT of left lower extremity,complete dissolution of thrombus was achieved in 232 (90.6%) and partial dissolution of thrombus in 24 (9.4%).The circumference difference of thigh and calf was (7.12±2.15) and (4.57±2.81) cm respectively before and after treatment.Iliac vein reconstruction was carried out in 206 patients,among them simple balloon dilatation was employed in 46 and balloon dilatation together with stent implantation was adopted in 160.The patients were followed up for 9-24 months with a mean of 15 months.In simple balloon dilatation group,3 patients lost touch with the authors during the following-up period,26 patients (60.5%) developed iliac vein occlusion and post-embolization syndrome occurred in 21 patients (48.8%).In balloon dilatation plus stent implantation group,11 patients lost touch with the authors during the following-up period,stenosis or occlusion of the stent was seen in 13 patients (8.7%),post-embolization syndrome was observed in 15 patients (10.1%).The differences in vascular stenosis or occlusion and in the occurrence of post-embolization syndrome between the two groups were statistically significant (P<0.001).Conclusion For the treatment of Cockett syndrome complicated by DVT of left lower extremity,catheter-directed thrombolysis and balloon dilatation combined with stent implantation carry definite clinical curative effect.
10.Diagnosis and differential diagnosis for solitary fibrous tumor in the abdomen and pelvis by CT
Huaping LIU ; Wenzheng LI ; Xiaoping YI ; Yigang PEI ; Hui LIU ; Wei ZHAO ; Wenguang LIU ; Jiale HOU ; Ghimire OBIN
Journal of Central South University(Medical Sciences) 2017;42(4):406-412
Objective:To study the CT features for solitary fibrous tumor (SFT) in the abdomen and pelvis and to improve the diagnostic accuracy.Methods:Fourteen patients with SFT were collected in our hospital from January,2011 to December,2015.Characteristic of images were analyzed and compared for 10 SFT,which located outside the abdominal organs with extragastrointestinal stromal tumors (EGIST),leiomyosarcoma,and schwannoma.Results:Necrosis and cystic formation were frequently present in SFT in the abdomen and pelvis.CE-CT showed serpentine vessels along the periphery,while pattern of enhancement was maplike inhomogeneous progressive.Comparing with the EGIST or schwannoma,the difference of CT value in non-contrast and the arterial phase were statistically significant (P<0.05).The numbers of peritumoral circuity vessel were significantly different between SFT and EGIST (~=18.27,P<0.008) or between SFT and schwannoma (x2=19.25,P<0.008).Comparing with the leiomyosarcoma or schwannoma,SFT located outside the abdominal organs.We found that tumor necrosis rate was significantly different between SFT and leiomyoscarcoma (x2=8.00,P<0.008).Conclusion:SFT in the abdomen and pelvis show certain CT characteristics.The CT value in noncontrast and at the arterial phase,tumor necrosis rate,and serpentine vessels along the periphery were pivotal in differentiating SFT from leiomyosarcoma,EGIST and schwannoma.

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