1.Pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective
Nan DING ; Lixin PAN ; Changlin LIAN ; Zhifeng XU ; Yukai WANG ; Fen ZHANG ; Guanghua ZHAO ; Xiaojue LIANG ; Wenjie LAI ; Weiqi ZENG ; Jingjuan CHEN ; Guohua ZHANG
Chinese Journal of Neuromedicine 2024;23(4):333-339
Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.
2.Effect of radiation therapy and prognostic factors in hepatocellular cancer patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis
Ting YE ; Zhaochong ZENG ; Shisuo DU ; Jing SUN ; Zhifeng WU ; Yixing CHEN ; Ping YANG ; Yong HU ; Qianqian ZHAO ; Jianying ZHANG
Chinese Journal of Radiological Medicine and Protection 2021;41(6):431-435
Objective:To study the effects of radiotherapy and the prognostic factors in hepatocellular cancer (HCC) patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis (LNM).Methods:We retrospectively analyzed 56 HCC patients with cardiophrenic angle or superior diaphragmatic LNM who were treated with or without external beam radiation therapy (EBRT) in Zhongshan Hospital of Fudan University from Jan 2010 to Aug 2020. Patients were divided into two groups according to whether they received radiotherapy, EBRT group and non-EBRT group, and each group had 28 patients. Radiation fields included or excluded primary tumor in EBRT group, and the cardiophrenic angle or superior diaphragmatic LNM did not receive any local treatment in non-EBRT group. The response rate, survival rate, local control rate, prognostic risk factors of the two groups were studied.Results:After EBRT, the partial response rate and complete response rate were 32.1%(9/28) and 32.1%(9/28). The median survival rate of EBRT group was 16.1 months (95% CI 9.00-23.21, RR=3.63) vs. 6.9 months (95% CI 4.63-8.77, RR=1.06) for the non-EBRT group, with statistically significant difference ( χ2=15.53, P<0.05). Cardiophrenic angle or superior diaphragmatic lymph nodes 1-year local control rate for EBRT group and non-EBRT group were 37.0% vs. 10.7%, with statistically significant difference ( χ2=5.28, P<0.05). Since diagnosis of cardiophrenic angle or superior diaphragmatic LNM, 4 patients (14.3%) in the EBRT group vs. 13 patients (46.4%) in the non-EBRT group had higher alpha-fetoprotein (AFP) level after 3 months compared with the AFP before EBRT ( χ2=6.84, P<0.05). Multivariate analysis showed that multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L, no EBRT were poor prognostic factors. Conclusions:EBRT can prolong overall survival and improve the control rate of lymph node of HCC patients with cardiophrenic angle or superior diaphragmatic LNM. Patients with multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L and no EBRT have poor prognosis.
3.Significance of the levels of Twist and Vimentin proteins in oral squamous cell carcinoma
GAO Wenfeng ; WANG Zhiping ; XU Jing ; SONG Zhifeng ; ZENG Shuguang
Journal of Prevention and Treatment for Stomatological Diseases 2018;26(10):639-643
Objective:
To investigate the levels of the Twist and Vimentin proteins in oral squamous cell carcinoma (OSCC) and analyze the clinical significance of Twist and Vimentin.
Methods:
Eighty-five samples of OSCC and fifteen samples of normal oral mucosa were collected. Immunohistochemistry (SP method) was used to detect the expression of proteins, including Twist and vimentin. The relationship among these proteins and clinical pathological parameters was analyzed using SPSS statistical software.
Results :
In the normal group, 13.3% (2/15) of samples were positive for the Twist protein; this value was significantly lower than that in OSCC group (80.0%, 66/85) (χ2=26.98, P < 0.001). The expression of Twist was associated with clinical stage (χ2=5.40, P=0.02) and lymph node metastasis (χ2=8.35, P=0.006), while no correlations were found between the expression of Twist and sex (χ2=0.23, P=0.63), age (χ2= 0.31, P=0.58), location (χ2=1.46, P=0.235) or degree of differentiation (χ2=1.52, P=0.47). Additionally, 6.7% of samples (1/15) were positive for vimentin; this value was significantly lower than that in OSCC group (74.1%, 63/85) (χ2=20.71, P < 0.001). The expression of vimentin was associated with clinical stage (χ2=4.51, P=0.034) and lymph node metastasis (χ2=6.75, P=0.009), while no correlations were found between the expression of vimentin and sex (χ2=0.40, P=0.53), age (χ2=0.17, P=0.68), location (χ2=0.74,P=0.39) or degree of differentiation (χ2=4.58, P=0.10). Spearman correlation analyses showed that Twist protein expression was positively correlated with vimentin (r=0.578, P<0.05).
Conclusion
Our data demonstrate that in OSCC, Twist and vimentin levels were upregulated, and Twist protein expression was positively correlated with vimentin, which indicates that both Twist and vimentin may be involved in the occurrence of OSCC.
4.Clinical effect of self-made Sanjin-Weiwei decoction for patinets with upper urinary tract calculi after extracorporeal shock wave lithotripsy
Dongxiang ZHENG ; Liang ZHONG ; Zhifeng HUANG ; Song WU ; Ye ZENG
International Journal of Traditional Chinese Medicine 2017;39(12):1073-1076
Objective To study the clinical effect of Self-made Sanjin-Weiwei decoction for patinets with upper urinary tract calculi after extracorporeal shock wave lithotripsy (ESWL). Methods A total of 200 patients with upper urinary tract calculi after ESWL in our hospital from January 2015 to Octomber 2016 were enrolled in this study. The subjects were divided into the control group (n=100) and the treatment group (n=100) randomly. The control group were treated with conventional treatment after ESWL, and the treatment group were treated with conventional treatment plus the Self-made Sanjin-Weiwei decoction after ESWL,and the two groups were treated for 45 days. The clinical effects of both groups were compared. The first time average row stone time and renal colic average frequency of both groups after treatment was compared. The stone platoon net rate of both groups after 1 month, 2 months, 3 months were compared. The incidence of adverse reactions, like dry mouth, nausea, painful urination, blood in urine, of both groups during the treatment were compared. Results The total effect rate of the treatment group was 86.0%, significantly higher than 62.0% of the control group(χ 2=14.969,P<0.001).The first time average row stone time(4.18 ± 1.30 d vs.7.52 ± 2.08 d,t=13.617)and renal colic average frequency(0.67 ±0.21 vs.1.55 ±0.87,t=9.833)of the treatment group were significantly lower than the control group (P<0.05). The stone platoon net rate of the treatment group after 1 month (93.0% vs.74.0%,χ 2=13.101),2 months(98.0% vs.82.0%,χ 2=14.222),3 months(100.0% vs.84.0%,χ 2=17.391)were significantly higher than the control group (P<0.05). The incidence of adverse reactions (7.0% vs. 15.0%, χ2=4.735)of the treatment group were significantly lower than the control group(P<0.05).Conclusions The Self-made Sanjin-Weiwei decoction for patinets with upper urinary tract calculi after ESWL has a good effect and low incidence of adverse reactions, can reduce the renal colic and improve the stone platoon net rate.
5.Value of MRI in predicting intradiscal cemment leakage during percutaneous vertebral augmentation
Jinhui CAI ; Qingyu LIU ; Yurong ZENG ; Zhifeng LIU ; Yaoqin RUAN ; Donghua GUO ; Zhen WANG
Chinese Journal of Medical Imaging Technology 2017;33(7):1061-1065
Objective To assess the value of preoperative MRI in predicting the incidence of cement leakage into adjacent discs during percutaneous vertebral augmentation (PVA) for osteoporotic vertebral compression fracture (OVCF).Methods Clinical and radiological characteristics of 127 patients who were treated with PVA for OVCF were analyzed retrospec tively.The following clinical data of these patients were analyzed,including gender,age,location of treated vertebral body and surgical approach.The image features of endplate injury,fracture line extended to the endplate,adjacent intervertebral dick injury and intravertebral cleft were evaluated on the preoperative MRI.The incidence of cement leakage into the adjacent disc were compared for the above factors with statistical methods.Results Totally 127 patients were enrolled in our study,including 179 treated vertebral bodies,358 endplates and 341 adjacent intervertebral discs.The incidence of intradiscal cement leakage was 57.73% (56/97) in endplate injury sign,60.98% (25/41) in fracture line extended to endplate sign,35.91%(51/142) in adjacent discs injury sign and 55.56%(20/36) inintravertebral cleft sign.The differences were statistically significant on preoperative MRI in patients with the above signs compared to those who had not (P<0.05).The incidence of intradiscal cement leakage in percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) were 26.67%(16/60) and 42.86%(51/119),respectively,which was significant different (P=0.035).For bone cement volume ≤ 5 ml vertebral bodies,the incidence of intradiscal cement leakage was 31.19 % (34/109),lower than bone cement volume > 5 ml vertebral bodies (47.14% [33/70],P=0.031).There was no statistically significant association between intradiscal cement leakage and age,gender and location of treated vertebral body (P>0.05).Conclusion Preoperative MRI can predict the leakage of bone cement into adjacent discs effectively during PVA.The PKP and the lower volume of bone cement injection can reduce the risk of intradiscal cement leakage.
6.The characteristics of cardiac systolic and diastolic function changes in human immunodeficiency virus-infected patients
Ling LUO ; Yanling LI ; Ling LI ; Yicong YE ; Zhifeng QIU ; Yang HAN ; Yong ZENG ; Taisheng LI
Chinese Journal of Infectious Diseases 2017;35(6):348-351
Objective To understand the changes of cardiac systolic and diastolic function in human immunodeficiency virus (HIV)-infected patients without evidence of cardiac disease in China.Methods Forty-two HIV-infected patients who were followed up in the Department of Infectious Diseases at Peking Union Medical College Hospital without cardiac involvement were recruited.All the HIV-infected patients had received highly active antiroviral therapy (HAART) for more than 12 months with viral suppression.And 30 age and sex matched healthy subjects without cardiac disease manifestations were enrolled as controls.Every group members underwent transthoracic echocardiography evaluation.The indexes of cardiac systolic and diastolic function between HIV-infected patients and healthy controls were compared.Results Diastolic abnormality occurred in 20 cases in HIV-infected group and 6 cases in control group, with statistically significant difference (χ2=5.79, P=0.007).The E wave deceleration time (EDT) in HIV-infected patients were significantly decreased than healthy controls ([161.87±21.64] ms vs.[190.34±37.22], t=-3.20, P=0.002).There were no significant differences of E/A ratio ([1.16±0.35] vs.[1.19±0.26]), E/Ea ratio ([5.43±1.99] vs.[5.78±0.91]), isovolumic relaxation time (IVRT), ([93.18±20.34] ms vs.[93.57±18.55]ms), Ea ([10.18±2.80] cm/s vs.[11.45±2.75] cm/s) between HIV-infected patients and controls (t=1.13,1.53,0.67 and 0.29, respectively, all P>0.05).Among cardiac systolic function markers, left ventricular ejection fractions in HIV-infected patients and control group were (66.7±6.4)% and (68.7±4.2)%, respectively.And left ventricular shortening rates were (37.08±4.79)% and (38.17±3.96)%, respectively.Both showed no significant difference between the two groups (t=-1.51 and-1.00, respectively, both P>0.05).Conclusions Compared with control group, subclinical cardiac diastolic dysfunction is more frequently observed in HIV-infected patients.However, there are no significant differences of cardiac systolic function markers between HIV-infected patients and controls.
7.Finite element analysis of femoral neck fracture with different fixation ways
Zhifeng XIA ; Ming LIANG ; Yafeng LI ; Guannan ZENG
Chinese Journal of Tissue Engineering Research 2016;20(31):4630-4636
BACKGROUND:Finite element method is widely used in the femoral neck fracture, but the study concerning different fixation methods of femoral neck fracture is not much. OBJECTIVE:To analyze biomechanical properties of different fixation methods for femoral neck fracture using finite element analysis. METHODS:The femur of voluntters was scanned with CT, at thickness 0.6 mm, from the site above the greater trochanter of the femur. Scanning data were saved in .DICOM format. Data of right proximal femur were imported into Mimics software. Osteotomy was performed according to Pauwels I type fracture. Models of two tensile force screws, ful y threaded hol ow screw and proximal femoral locking plate were established. Three-dimensional finite element method was used to analyze stress distribution, stress concentration position, displacement distribution and maximum displacement in different models of femoral neck fracture with different internal fixation methods. RESULTS AND CONCLUSION:(1) The maximum stress value of two lag screws model was biggest. The maximum stress value of ful y threaded hol ow screw model was minimized. The maximum stresses of two lag screws model, ful y threaded hol ow screw model and proximal femoral locking plate model al were concentrated in the fixed end of fractures. (2) The femoral maximum stress of two lag screws model was biggest. The femoral maximum stress value of proximal femoral locking plate model was minimized. The femoral maximum stresses of two lag screws model, ful y threaded hol ow screw model and proximal femoral locking plate model al were concentrated in the medial femoral smal rotor near and medial femoral and fixation contact points. (3) The maximum displacement of two lag screws model was biggest. The maximum displacement of ful y threaded hol ow screw model was minimized. The maximum displacement of two lag screws model, ful y threaded hol ow screw model and proximal femoral locking plate model al was in the femoral head. (4) The maximum displacement value of two lag screws model fixed place was biggest. The maximum displacement value of ful y threaded hol ow screw model fixed place was minimized. The maximum displacement value of two lag screws model was biggest at femoral head. The maximum displacement value of ful y threaded hol ow screw model was minimized at femoral head. (5) Results showed that the treatment effect of ful y threaded hol ow screw on Pauwels I fractures was better than other two fixation methods.
8.Diagnostic value of 64-slice spiral CT on in-stent restenosis after PCI in patients with coronary heart disease
Jia FU ; Zhifeng SHUAI ; Weihua ZENG ; Fan OUYANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2015;24(2):172-174
Objective:To explore the diagnostic value of 64‐slice spiral CT for in‐stent restenosis (ISR) after percuta‐neous coronary intervention (PCI) in patients with coronary heart disease (CHD) .Methods :A total of 120 CHD patients after PCI received 64‐slice spiral CT angiography and routine coronary angiography (CAG ) respectively . Then coronary ISR was assessed .Results:With CAG as the gold standard ,sensitivity ,specificity ,positive predictive value and negative predictive value were 87.5% ,95.3% ,80.0% and 97.3% respectively for 64‐slice spiral CT cor‐onary angiography in diagnosis of ISR .Conclusion :The 64‐slice spiral CT coronary angiography possesses high sensitivity and accuracy diagnosing coronary in‐stent restenosis ,which can be used as one of noninvasive measures for postoperative follow‐up after percutaneous coronary intervention .
9.Effects and mechanisms of periostin overexpression on invasion and migration of the nasopharyngeal carcinoma 6-10B cell line
Huijie WANG ; Jinfeng SHI ; Yuanjie XIE ; Guqing ZENG ; Yalan DU ; Xingqiong HUANG ; Zhifeng LONG ; Jiangdong YU ; Meixiang LI
Acta Anatomica Sinica 2014;(4):500-506
Objective To explore the effects and mechanisms of periostin overexpression on migration and invasion of nasopharyngeal carcinoma ( NPC) cell line.Methods The recombinant plasmids [ pCMV-neo ( +)-periostin ] and control plasmids [pCMV-neo (+)] were transfected into 6-10B cells using lipofectamine 2000TM reagent.The expression of periostin was detected with PCR and Western blotting .Transwell chamber invasion assay was employed to assay the migration and invasion of 6-10B cells before and after transfection .A gelatin zymogram was used to detect the activity of MMP-2 and MMP-9 in cultivated supernatant of 6-10B cells before and after transfection .The expression of integrin-αvβ5 was detected by immunohistochemistry ( IHC) in 6-10Bperiostin cells, 6-10Bvector cells and 6-10B cells as well as normal nasopharyngeal mucosa ( NNM) and NPC and at the same time periostin also was detected by immumohistochemistry in NNM and NPC, and densitometry analysis using image-pro plus 6.0 software, and the correlation between periostin and integrin-αvβ5 on NPC was assayed with statistics .Results Over expression of periostin promoted cell migration and invasion.The expression levels of integrin-αvβ5 in primary NPC and 6-10Bperiostin cells were significantly higher than those in NNM and 6-10Bvector, 6-10B cells.The expression in NPC of integrin-αvβ5 showed positively correlated with the expression of periostin (r=0.682, P<0.01).Conclusion Periostin plays an important role in regulation of cell migration and invasion probably by combining with integrin-αvβ5 to improve the activities of MMPs .
10.Mechanisms of quinolones resistance in Acinetobacter baumannii and homology analysis among the strains
Hui ZENG ; Wanqing ZHOU ; Zhifeng ZHANG
International Journal of Laboratory Medicine 2014;(10):1261-1262,1265
Objective To explore the mechanisms of quinolones resistance in Acinetobacter baumannii and homology analysis a-mong the strains .Methods 25 strains of quinolones-resistant Acinetobacter baumannii isolated clinically were collected .Kirby-Bauer(K-B) detection was utilized to detect the sensitivity of conventional drugs ,and polymerase chain reaction (PCR) was em-ployed to detect quinolone resistance-related genes gyrA and parC which were verified by restriction enzyme digestion and sequen-cing ,repetitive extragenic palindrome(REP)-PCR was adopted to analyze the strain homology .Results Multiple resistances to 12 kinds of antibacterial agents were found among the 25 strains of Acinetobacter baumannii which were sensitive only to minocycline and amikacin ,with sensitive rates were 48 .0% and 32 .0% ,respectively ,and were all sensitive to polymyxin B [minimal inhibitory concentration(MIC)≤2 μg/mL] .gyrA and parC genes were found in the all strain .Mutation TCA→TTA(Ser→Leu) at coden 83 in gyrA gene existed in 25 strains ,mutation TCG→TTG(Ser→Leu) at coden 80 in parC gene existed in 23 strains ,mutation GAA→GGA(Glu→Gly) at coden 84 in parC gene existed in 2 strains .REP-PCR showed that the strains had high degree of homology . Conclusion Quinolone-resistant Acinetobacter baumannii has high degree of homology ,existing gyrA and parC gene mutations .


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