1.in vitro Model for Targeting Tumor Vasculature Using Immunoliposome
Jie MA ; Zhikai HAN ; Liren CAO
Chinese Journal of Cancer Biotherapy 1994;0(01):-
Objective: Based on tumor angiogenesis theory, a target system of tumor endothelial cells was established to investigate the cytotoxicity against tumor vascular endothelium by an drug loaded immunoliposome.Methods: Sterically stabilized liposomes containing doxorubicin were used for conjugation to a monoclonal antibody (MAb) as a drug-vascular targeting device. The MAb M5/114 directly against MHC Ⅱ, which was expressed by vascular endothelial cells was employed. Binding of cholesteryl ether (CHE) labeled anti-MHC Ⅱ immunoliposomes to endothelial cells (SVEC ) in vitro was detected by a binding assay. Cytotoxicity of drug loaded immunoliposome to endothelial cells was determined by MTT assay.Results: At least 3-fold increase in binding for the targeted liposomes was observed. This data suggest highly selective binding of M5/114-immunoliposomes to MHC Ⅱ expressing endothelial cells. Moreover, the cytotoxicity produced by drug loaded M5/114-immunoliposome was greatly enhanced compared with that by non-targeted liposomes. Conclusion: This is the first report using immunoliposome to target endothelial cells. The results demonstrate that immunoliposome directly against tumor vascular endothelial cells might provide a general treatment for solid tumors.
2.Changes of plasma endostatin levels in nude mice bearing human nasopharyngeal carcinoma
Huiling YANG ; Miaorong SHE ; Zhikai MA ; Hui GUO ; Qin ZHENG ; Xiurong SU
Chinese Journal of Pathophysiology 2000;0(10):-
0.05]. At 20, 30 and 40 days concentration of endostatin[(212.80?85.91) ?g/L,(293.63?62.53) ?g/L, (271.57?32.45) ?g/L, respectively] were higher than that of the control group (P
3.An in vitro experimental study on the physical and elution properties of PMMA bone cement loaded with rifampicin, iso-niazid, pyrazinamide and moxifloxacin
Wenxin MA ; Weidong JIN ; Qian WANG ; Zili WANG ; Zhikai LIN ; Min JIANG ; Yuhang SUN ; Guoliang SUN ; Yanni MA ; Jianghua DU
Chinese Journal of Orthopaedics 2016;36(11):735-744
Objective To investigate the feasibility of Antituberculotic?loaded bone cement (ATLBC) prepared by mix?ing the anti?TB drugs Rifampicin (RFP), Isoniazid (INH), Pyrazinamid (PZA), Moxifloxacin (MFX) with Palacos R PMMA bone cement in Total Joint Arthroplasty treatment for Joint Tuberculosis. Methods Forty grams of Palacos R bone cement powder without antibiotics was mixed with 1 or 2 grams of RFP, INH, PZA and MFX respectively. According to ISO 5833:2002 stan?dard, 8 groups of ATLBC standard test specimen were prepared as experiment group and Palacos R PMMA bone cement with?out antibiotics was prepared as control group. Physical properties (such as the average dough time, curing time, maximum tem?perature), mechanical strength (such as the compressive strength, the bending resistance strength, the modulus of elasticity) and the concentrations of eluant drug in different time points of ATLBC were detected. Results In RFP (1 g), RFP (2 g), INH (1 g) and INH (2 g) group, the average dough time and curing time were longer than those in control group, which exceeded the standard scope of ISO, while the average maximum temperature was significantly lower than that in control group. The INH ( 1 g) group and INH (2 g) group hardened after mixing for 14 days. The RFP (1 g) group and RFP (2 g) group hardened after mixing for 30 days. Twenty minutes after mixing and hardening, the compressive strength, bending resistance strength and modulus of elastic?ity were significantly lower than the specified values of ISO standard. The physical properties and mechanical strength in PZA ( 1 g) group, PZA (2 g) group, MFX (1 g) group, MFX (2 g) group and control group were in accordance with the specified values of ISO standard, and they hardened after 20 minutes. In RFP (1 g) group, RFP (2 g) group, INH (1 g) group, INH (2 g) group, PZA (1 g) group, PZA (2 g) group, MFX (1 g) group and MFX (2 g) group, the concentration of eluant could maintain for 3 days, 7 days, 90 days, 90 days, 45 days, 60 days, 60 days and 60 days respectively. Conclusion RFP and INH mixing with Palacos R PMMA bone cement can hinder the aggregation of bone cement so they are unsuitable for preparing ATLBC. PZA and MFX mixing with Palacos R PMMA bone cement do not affect the physical properties of bone cement, with excellent mechanical strength and elu?tion properties. Because the minimal inhibitory concentration of PZA is higher and its antimicrobial activity maintains shorter time, while MFX maintains longer time in antimicrobial activity, it's more suitable for the preparation of ATLBC.
4.Effects of Micrococcus luteus Rpf and Rpf domain protein on growth of Mycobacterium tuberculosis
Ailin FAN ; Wen JIAN ; Shanluan ZHEN ; Changhong SHI ; Yueyun MA ; Maigui YANG ; Yinlan BAI ; Zhikai XU ; Xiaoke HAO
Chinese Journal of Microbiology and Immunology 2009;29(6):503-506
Objective To purify Micrococcus luteus Rpf and Rpf domain fusion protein, and to in-vestigate its effects on growth of Mycobacterium tuberculosis. Methods The recombinant plasmids pPro-EXHT-Rpf and pPro-EXHT-Rpf domain were expressed in E. Coli DHSa and then purified under denaturing condition via Ni-NTA purification system and confirmed by Western blot. The biochemical property of the M. Luteus Rpf and Rpf domain was analyzed by stimulating the resuscitation of M. Tuberculosis H37Ra which were in non-culturable' condition. Results The Rpf and Rpf domain products achieved 95% and 93% pure respectively, and the molecular weight was 30 x 103 and 12 x 103, the yield of purification was about 471 mg/L and 337 mg/L of the culture. The M. Luteus Rpf and Rpf domain from the E. Coli showed activity of stimulating the resuscitation of M. Luteus and M. Tuberculosis H37Ra in non-cuhurable' condition which could be inhibited by monoclonal antibodies of M. Luteus Rpf domain remarkably. Conclusion It was dem-onstrated that the purification of Rpf and Rpf domain have high biological activity for further functional, pharmacological and clinical investigations, and M. Luteus Rpf domain protein is fully active as M. Lateus full-length Rpf.
5.Effect of Inhibiting Upstream Transcription Factor 2 Expression on Proliferation and Apoptosis of Gastric Cancer BGC-823 Cells
Xubin WANG ; Shenshuo GAO ; Zhikai ZHANG ; Yan MA ; Xiaobo GUO
Cancer Research on Prevention and Treatment 2022;49(12):1217-1222
Objective To investigate the effect of upstream transcription factor 2 (USF2) on the proliferation and apoptosis of human gastric cancer BGC-823 cells. Methods Lipofectamine?3000 transfection reagent was used to transfect USF2 siRNA into BGC-823 cells (siRNA-USF2 group). Blank control and negative control (siRNA-NC) groups were also prepared. The mRNA and protein expression levels of USF2 in transfected BGC-823 cells were detected by real-time fluorescence quantitative PCR and Western blot, respectively. The proliferation and clone formation abilities of BGC-823 cells in each group were investigated by CCK-8 and plate cloning assay. The apoptosis of gastric cancer cells was examined by flow cytometry. The expression levels of PCNA and apoptosis-related proteins Bax and Bcl-2 in BGC-823 cells were measured by Western blot. Results Compared with those in the blank control and siRNA-NC groups, the mRNA and protein expression levels of USF2 significantly decreased in the siRNA-USF2 group (
6.The clinical efficacy of pathologic vertebral surgery for thoracic and lumbar tuberculosis
Jiandang SHI ; Yuanyuan LIU ; Qian WANG ; Weidong JIN ; Zili WANG ; Wenxin MA ; Jun CHEN ; Huiqiang DING ; Haoning ZHAO ; Zhikai LIN ; Zhaohui GE ; Jianwei SI ; Guangqi GENG ; Ningkui NIU ; Guoliang SUN ; Zongqiang YANG
Chinese Journal of Orthopaedics 2016;36(11):681-690
Objective To discuss the clinical efficacy of surgical treatment of pathologic vertebral surgery for thoracic and lumbar tuberculosis. Methods All of 322 cases of thoracic and lumbar spinal tuberculosis patients from December 2003 to June 2014 were retrospectively analyzed in our department. All patients were underwent debridement, fusion and nerve decompres?sion surgery. According to different fixed methods, patients were divided into pathologic vertebral surgery group (fixation complet?ed within lesions invaded motion unit) including 91 males and 100 females, with an average age of 41.53 years, and non?pathologic vertebral surgery group (long segments or short segment fixation) including 61 males and 70 females, with an average age of 42.72 years. We observed the tuberculosis cure rate, degrees of deformity, pain and neurological recovery, operative time, blood loss and complications by follow?up. Results The average follow?up time was 75.52 months in pathologic vertebral surgery group and 76.21 months in non?pathologic vertebral surgery group. The total number of pathologic vertebras in pathologic vertebral surgery group and non?pathologic vertebral surgery group were 277 and 218 respectively, and the average was 1.45 and 1.66. The total number of fixed segments was 277 in pathologic vertebral surgery group and 485 in non?pathologic vertebral surgery group, and the average fixed segments was 1.45 and 3.70. The cure rate was 85.86%in pathologic vertebral surgery group and 85.49%in non?pathologic vertebral surgery group at 6 months postoperatively, and 98.95%and 98.47%at the last follow?up time, with no signifi?cant difference between groups. Graft fusion rate was 89.00%in pathologic vertebral surgery group and 89.31%in non?pathologic vertebral surgery group 6 months postoperatively, 98.38%and 98.47%at the last follow?up time, without significant difference. In lumbar spine, the average correction of Cobb's angle was 12.4° in pathologic vertebral surgery group and 13.1° in non?pathologic vertebral surgery group, and the average angle loss was 1.3 and 1.4°, with no significant difference. In thoracolumbar, the average correction of Cobb’s angle was 10.9°in pathologic vertebral surgery group and 11.1°in non?pathologic vertebral surgery group, and the average angle loss was 1.7°and 1.5° respectively, without significant difference. However, in thoracic, the average correction of Cobb's angle was 10.2° in pathologic vertebral surgery group and 12.7° in non?pathologic vertebral surgery group, and the average angle loss was 3.6° and 2.5°respectively, with significant difference. The mean operation time was 210.45 min in pathologic verte?bral surgery group and 210.45 min in non?pathologic vertebral surgery group, with significant difference. The average blood loss was 726.12 ml in pathologic vertebral surgery group and 726.12 ml in non?pathologic vertebral surgery group, with significant dif?ference. The complication rate was 11.51%in pathologic vertebral surgery group and 11.45%in non?pathologic vertebral surgery group, with no significant difference. Conclusion Pathologic vertebral surgery surgery is a safe, effective and feasible method of operation for treatment of thoracic and lumbar tuberculosis, which can effectively preserve adjacent normal vertebral motion unit features. The thoracic surgery was less satisfactory than the lumbar and thoracolumbar surgery.
7.Selection of the distal fusion level in posterior spinal fusion for Scheuermann kyphosis
Yanjie XU ; Zongshan HU ; Hongru MA ; Zhikai QIAN ; Kiram ABDUKAHAR· ; Ziyang TANG ; Chen LING ; Weibiao LI ; Zhen LIU ; Zezhang ZHU ; Yong QIU
Chinese Journal of Orthopaedics 2021;41(13):834-843
Objective:To investigate the clinical outcomes and complication of posterior surgery for Scheuermann kyphosis fusing to different distal fusion levels.Methods:From January 2012 to December 2017, a consecutive cohort of 34 patients who were treated with posterior spinal instrumented correction and satisfied the inclusion criteria were retrospectively reviewed, including 29 males and 5 females, aged 17.1±4.3 years (range, 12-30 years). All of the patients had a minimum follow-up of 2 years. According to the distal fusion level, patients were divided into 2 groups. Group sagittal stable vertebra (SSV) (22 cases) included patients whose lowest instrumented vertebra (LIV) was SSV; Group SSV-1 (12 cases) included patients who had a LIV one level above the SSV. Radiographic parameters including global kyphosis (GK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured in the standing radiographs before and after operation and at the latest follow up. Intraoperative and postoperative complications were recorded. The Scoliosis Research Society-22 questionnaire (SRS-22) were conducted at pre-operation and the final follow up to evaluate the clinical outcomes. The sagittal radiographic parameters and the incidence of distal junctional kyphosis (DJK) were compared between the two groups.Results:There were no significant differences in terms of age, sex, radiographic measurements and scores of SRS-22 between two groups preoperatively ( P>0.05). The correction rates of GK in the SSV group and the SSV-1 group were 42.8%±7.6% and 43.2%±8.4% ( t=0.151, P=0.881) respectively. While the correction rates loss were 1.2%±5.2% and 3.9%±7.2% ( t=0.767, P=0.449) at the latest follow up. No significant difference was observed in terms of other radiographic parameters ( P>0.05). During the postoperative follow up period, 3 patients (16.7%) in SSV group and 2 patients (13.6%) in SSV-1 group developed DJK. The incidence of DJK did not show any significant difference between two groups ( χ2=0.057, P=0.812). At the final follow-up, the function scores of SRS-22 in SSV-1 group (4.1±0.6) was significantly higher than SSV group (3.7±0.5) ( t=2.300, P=0.028) and there was no significant difference in the rest of the domain ( P>0.05). Conclusion:Compared with stopping at SSV, fusion to SSV-1 could achieve comparable curve correction with the preservation of more lumbar motility. Moreover, it would not increase the risk of DJK. As a result, we recommend selecting SSV-1 as the ideal LIV for SK patients.
8.Age- and gender-related sagittal spinal-pelvic alignment in Chinese adult population: a multicenter study with 786 asymptomatic subjects
Zongshan HU ; Hongru MA ; Zhikai QIAN ; Kiram ABDUKAHAR· ; Ziyang TANG ; Weibiao LI ; Zezhang ZHU ; Ziping LIN ; Zhenyao ZHENG ; Yong QIU ; Zhen LIU
Chinese Journal of Orthopaedics 2021;41(13):844-855
Objective:To establish age- and gender-based normative values of sagittal spinal-pelvic alignment in Chinese adult population, and to investigate influence of age, gender and ethnicity on sagittal spinal-pelvic alignment in Chinese normal adults.Methods:A total of 786 asymptomatic Chinese adult volunteers aged between 20 and 89 years were prospectively recruited from different spine centers. The inclusion criteria were: 1) age between 20 to 89 years old; and 2) Oswestry disability index (ODI) scored lower than 20. The exclusion criteria were: 1) previous history of spinal, pelvic or lower limb pathologies that could affect the spine; 2) presence of recent and/or regular back pain; 3) previous surgeries on spine, pelvic and/or lower limb; and 4) pregnancy. Demographic characteristics of these subjects including age, gender, body weight and height were recorded. During the enrollment of volunteers, 16 groups were defined based on the age (20 s, 30 s, 40 s, 50 s, 60 s, 70 s and 80 s) and gender. Whole body biplanar standing EOS X-ray radiographs were acquired to evaluate the sagittal alignment. Spinal-pelvic parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (T 5-T 12, TK), lumbar lordosis (L 1-S 1, LL), lower lumbar lordosis (L 4-S 1, LLL), global tilt (GT), T1 pelvic angle (TPA) and sagittal vertical axis (SVA) were measured. Values of PI-LL and lordosis distribution index (LLL/LL, LDI) were calculated. Radiographic measurements of 100 subjects were randomly selected to determine the intra- and inter-observer reliabilities using inter- and intra-class correlation coefficients (ICC). The spinal-pelvic parameters were compared among volunteers between different age and gender groups. The comparison was also made among various ethnic population. Results:The mean value was 23.7±7.1 kg/m 2 for BMI and 6.9%±2.5% (range, 0-18%) for ODI score. Each sagittal spinal-pelvic parameter was presented with mean value and standard deviationbased on age and gender. The ICCs of radiographic measurements ranged from 0.89 to 0.95, suggesting good to excellent intra- and inter-observer reliabilities. Significant differences were observed between males and females in multiple sagittal parameters (all P values <0.05). Compared to the male subjects, significantly higher values of PI (41.4° for male vs. 45.0° for female, P<0.001), PT (10.7° for male vs. 13.9° for female, P<0.001), PI-LL (-0.5° for male vs. 1.8° for female, P<0.001), and GT (10.9° for male vs. 13.5° for female, P<0.001) were documented in female subjects. Males had significantly higher values of LLL (28.6° for male vs. 26.6° for female, P<0.001) and LDI (0.68 for male vs. 0.63 for female, P<0.001). PI-LL, SVA, GT and TPA increased with aging from Group 40 s to Group 80 s, while LL, LLL and LDI decreased gradually, and TK decreased slowly with aging. Comparison of sagittal spinal-pelvic parameters between different ethnic subjects showed that Chinese adult population presented lower PI, SS, TK and LL as compared with American population; lower PI, SS and LL as compared with Japanese population. But the variation trend with aging tended to be consistent among different ethnic populations. Conclusion:Age- and gender-based normative values of sagittal spinal-pelvic alignment were established in asymptomatic Chinese adult population. Sagittal spinal-pelvic alignment varies with age and gender, and presented different compensation mechanism among different ethnic populations. Therefore, to achieve balanced sagittal alignment, age, gender and ethnicity should be take intoconsideration when planning spine correction surgery.
9.Midterm clinical outcomes of second sacral alar-iliac screw fixation technique utilized in neuromuscular scoliosis with severe pelvic obliquity
Ziyang TANG ; Zongshan HU ; Zezhang ZHU ; Zhikai QIAN ; Kelamu ABUDUHAKAER· ; Hongru MA ; Yong QIU ; Zhen LIU
Chinese Journal of Orthopaedics 2021;41(21):1536-1544
Objective:To evaluate the clinical outcomes and complications of second sacral alar-iliac (S 2AI) technique utilized in adult patients with neuromuscular scoliosis, and to evaluate the impact on patients' quality of life. Methods:All of 11 patients (6 males and 5 females) applying S 2AI technique from January 2014 to December 2016 were retrospectively reviewed. The average age of the patients was 39.6±12.7 years. Among them, 8 cases were poliomyelitis, 2 cases were spinal muscular atrophy and 1 case was muscular dystrophy. All of 11 patients underwent posterior spinal fusion and utilized S 2AI screws for pelvic fixation. All patients were taken anteroposterior and lateral radiographs of the entire spine. Cobb's angle, spinal pelvic obliquity (SPO), regional kyphosis (RK), sagittal vertical axis (SVA) were recorded at pre-operation, post-operation and last follow-up. The Scoliosis Research Society (SRS)-22 questionnaires and Oswestry disability index (ODI) were utilized to evaluate the patient-reported outcomes. All complications were also recorded. Repeated measurement analysis of variance, t-test or non-parametric test was used to analyzed the data, respectively. Results:The average follow-up period was 62.4±10.8 months. The pre-operative Cobb angle was 98.0°±24.0°, and the post-operative Cobb angle was 60.7°±20.8°, of which difference was significant ( Z=3.015, P=0.003). The correction rate of Cobb angles was 57.2%±17.7%. 1-year after operation, the Cobb angle was 62.8°±23.6°, no loss of correction was found ( Z=0.294, P=0.797). And at last follow-up, the Cobb angle was 61.6°±21.7°, the correction maintained well ( Z=0.603, P=0.594). The pre-operative, post-operative, 1-year post-operative and last follow-up spinal pelvic obliquity were 37.0°±11.8°, 21.5°±11.6°, 23.2°±10.1° and 21.1°±8.6°. The significant improvement was obtained ( Z=2.934, P=0.003) and no loss of correction was found ( Z=0.690, P=0.519; Z=0.000, P=1.000). The pre-operative, post-operative, 1-year post-operative and last follow-up regional kyphosis were 46.8°±23.6°, 18.6°±10.6°, 18.9°±11.4° and 19.5°±9.8°. The significant improvement was obtained postoperatively ( Z=4.364, P<0.001) and remained stable at the last follow-up ( Z=0.074, P=0.945; Z=0.271, P=0.838). When compared the pre- and post-operative sagittal vertical axis, no significant difference was detected. In these patients, one patient had rod breakage and underwent revision, one patient suffered deep infection, and recovered by debridement surgery, one patient suffered from severe pain in the lower back and relieved with conservative treatment. Conclusion:The S 2AI technique utilized in patients with neuromuscular scoliosis could obtain satisfying clinical outcomes and provides safe, durable fixation with low rates of complications.
10.Collateral Flow in Magnetic Resonance Angiography:Prognostic Value for Vertebrobasilar Stenosis With Stroke Recurrence
Long YAN ; Ying YU ; Kaijiang KANG ; Zhikai HOU ; Min WAN ; Weilun FU ; Rongrong CUI ; Yongjun WANG ; Zhongrong MIAO ; Xin LOU ; Ning MA
Journal of Clinical Neurology 2022;18(5):507-513
Background:
and Purpose Intracranial vertebrobasilar atherosclerotic stenosis (IVBAS) is a major cause of posterior circulation stroke. Some patients suffer from stroke recurrence despite receiving medical treatment. This study aimed to determine the prognostic value of a new score for the posterior communicating artery and the P1 segment of the posterior cerebral artery (PCoA-P1) for predicting stroke recurrence in IVBAS.
Methods:
We retrospectively enrolled patients with severe IVBAS (70%–99%). According to the number of stroke recurrences, patients were divided into no-recurrence, single-recurrence, and multiple-recurrences groups. We developed a new 5-point grading scale, with the PCoA-P1 score ranging from 0 to 4 based on magnetic resonance angiography, in which primary collaterals were dichotomized into good (2–4 points) and poor (0 or 1 point). Stroke recurrences after the index stroke were recorded. Patients who did not experience stroke recurrence were compared with those who experienced single or multiple stroke recurrences.
Results:
From January 2012 to December 2019, 176 patients were enrolled, of which 116 (65.9%) had no stroke recurrence, 35 (19.9%) had a single stroke recurrence, and 25 (14.2%) had multiple stroke recurrences. Patients with single stroke recurrence (odds ratio [OR]= 4.134, 95% confidence interval [CI]=1.822–9.380, p=0.001) and multiple stroke recurrences (OR=6.894, 95% CI=2.489–19.092, p<0.001) were more likely to have poor primary collaterals than those with no stroke recurrence.
Conclusions
The new PCoA-P1 score appears to provide improve predictions of stroke recurrence in patients with IVBAS.