1.Experimentation of effect of PD-1 inhibitor on myocardial inflammation microenvironment and radiation-induced injury
Kaiyan ZHOU ; Lingfeng LIU ; Li CAO ; Gang WANG ; Chaofen ZHAO ; Huaxiang KUANG ; Yinxiang HU ; Haojia ZHANG ; Shengfa SU ; Bing LU
Chinese Journal of Radiation Oncology 2022;31(1):79-84
Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.
2.The role of miR-21 in Endostar combined with X-ray irradiation of cardiac fibroblasts
Dongdong CAO ; Weiwei OUYANG ; Xing ZHAO ; Shengfa SU ; Jun ZHANG ; Shimei FU ; Zhangxin FENG ; Qingsong LI ; Zhu MA ; Wengang YANG ; Xiaxia CHEN ; Bing LU
Chinese Journal of Radiation Oncology 2022;31(4):370-375
Objective:To investigate the implication of micro RNA-21(miR-21) in Endostar combined with X-ray irradiation of cardiac fibroblasts (CF).Methods:Rat CFs were used in this experiment and been divided into the blank control group, 10 Gy X-ray irradiation group, Endostar group, 10 Gy X-ray+ Endostar group, 10 Gy X-ray+ Endostar+ NC mimic group (negative control 1), 10 Gy X-ray+ Endostar+ miR-21 mimic group, 10 Gy X-ray+ Endostar+ NC inhibitor group (negative control 2) and 10 Gy X-ray+ Endostar+ miR-21 inhibitor group. The proliferation of CF was determined by Methyl thiazolyl tetrazolium (MTT) assay. The expression level of Collagen Ⅰ protein was analyzed by Western blot. The expression levels of Collagen Ⅰ and miR-21 mRNA were assayed by real-time quantitative polymerase chain reaction (q-PCR).Results:In the 10 Gy X-ray+ Endostar+ miR-21 mimic group, the CF proliferation, Collagen Ⅰ and miR-21 mRNA were increased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group, and negative control group 1 (all P<0.05). In the 10 Gy X-ray+ Endostar+ miR-21 inhibitor group, the CF proliferation and expression levels of Collagen Ⅰ mRNA were decreased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group and negative control group 2(all P<0.05). Conclusions:The CF proliferation and Collagen Ⅰ expression are increased when the expression level of miR-21 gene is simulated. When inhibiting the expression of miR-21 gene, the CF proliferation and Collagen Ⅰ expression are reduced.
3.Comparison of techniques between concave distraction or convex resection in the treatment of congenital cervicothoracic scoliosis
Shuo CAO ; Xin CHEN ; Feifei ZHOU ; Yanbin ZHAO ; Yinze DIAO ; Shengfa PAN ; Fengshan ZHANG ; Li ZHANG ; Tian XIA ; Weishi LI ; Yu SUN
Chinese Journal of Orthopaedics 2022;42(7):413-425
Objective:To compare the technique between concave distraction and convex resection in the treatment of congenital cervicothoracic scoliosis and evaluate its curative effect.Methods:Data of congenital cervicothoracic scoliosis patients from January 2010 to January 2020 were collected, among which 5 were males and 3 were females. The patients' age was 12.5±4.5 years old (range 6-20 years old). One case had C 7 wedged vertebra, 4 cases had T 1 hemivertebra and unbalanced vertebra, 2 cases had T 2 hemivertebra and 1 case had fused facet joint and wedged lamina in T 1. All patients had different degrees of vertebra fusion. Convex resection technique (one stage anterior and posterior combined hemivertebrae resection and annular osteotomy) was used to treat 4 cases before 2015; Concave distraction technique (A combination of anterior and posterior release, intervertebral space and facet space distraction, cage placed and fusion) was used to treat 4 cases after 2015 and 2 of them had 2 segments distraction. Perioperative neurological, vascular and wound related complications were recorded. The main parameters were structure Cobb angle, cephalic and caudal compensatory Cobb angle, mandibular incline, neck tilt, shoulder balance and head shift were measured pre-operation, post-operation and at the last follow-up. Results:All patients' surgeries were completed successfully. In convex resection group, the duration of surgery was 201±100 min (range 113-300 min) per vertebra, the estimated blood loss was 294±153 ml (range 100-450 ml) per vertebra, the hospital stay was 14±3 d (range 11-18 d) and follow up time was 51±11 months (range 36-60 months). In concave distraction group, the duration of surgery was 117±14 min (range 101-129 min) per vertebra, the estimated blood loss was 119±36 ml (range 85-167 ml) per vertebra, hospital stay was 17±3 d (range 14-20 d) and follow up time was 28±21 months (range 12-60 months). Convex resection group had longer operation time and more blood loss per vertebra than concave distraction group. In convex resection group, structural Cobb angle was 45.1°±21.0° pre-operation and 22.7°±15.3° post-operation, which was corrected significantly ( Z=6.53, P=0.038). The correction rate was 54.8%±30.9%. Cephalic compensatory Cobb angle was 22.1°±8.2° pre-operation and 8.2°±5.8° post-operation, which was corrected significantly ( F=6.01, P=0.049). The correction rate was 66.8%±15.1%. Mandible incline was 7.8°±3.1° pre-operation and 3.5°±1.5° post-operation, which was corrected significantly ( F=8.02, P=0.018). The correction rate was 51.0%±29.7%. In concave distraction group, structural Cobb angle was 32.2°±27.2° pre-operation and 16.3°±16.7° post-operation, which was corrected significantly ( F=7.43, P=0.024) . The correction rate was 59.0%±24.7%. Caudal compensatory Cobb angle was 18.9°(17.2°, 32.1°) pre-operation and 9.5°±10.3° post-operation, which was corrected significantly ( Z=6.00, P=0.049). The correction rate was 64.0%±24.1%. Clavicle angle was 3.9°±2.3° pre-operation and 0.3°±0.4° post-operation, which was corrected significantly ( F=1.75, P=0.040). The correction rate was 97.0% (48.5%, 99.8%). There was no significant difference in the correction rate of all radiographic parameters between the two groups. At the last follow-up, the patients' appearance of head, neck and shoulder were improved compared with those before surgery. In convex resection group, 2 patients showed nerve root stimulation symptoms postoperatively on convex side. One patient developed C 5 nerve root palsy which weakened deltoid muscle and the other patients presented with reduced triceps muscle strength. In concave distraction group, one patient developed C 5 nerve root palsy on convex side. All these symptoms recovered by conservative treatment 3 months after operation. Conclusion:It is safe and effective to treat congenital cervicothoracic scoliosis with convex resection technique and concave distraction technique. The concave distraction technique has the advantages of more safety, less operating time, less blood loss and easier to perform and has a wider application prospect.
4.The application of distraction on the concave side in the treatment of congenital cervical scoliosis
Shuo CAO ; Yu SUN ; Weishi LI ; Feifei ZHOU ; Yanbin ZHAO ; Shengfa PAN ; Xin CHEN ; Yinze DIAO ; Tian XIA ; Fengshan ZHANG ; Li ZHANG
Chinese Journal of Orthopaedics 2021;41(13):903-910
Objective:To explore the safety, feasibility, and short-term outcome ofdistraction on the concave side in the treatment of patients with congenital cervical scoliosis.Methods:Between August 2015 and December 2019, 11 patients with congenital cervical scoliosis underwent distraction technique on concave side, among which 5 were males and 6 were females. Age was 9.9±3.1 years old (range 6-16 years old). The primary cervical spine deformity was hemi-vertebra with different degrees of vertebra fusion. 7 cases were in C 3, 3 cases were in C 4 and 1 case was in C 5. Anterior-posterior combined approach was used. Firstly, discectomy and soft tissue release on concave side were made through anterior approach, then distraction on concave side and fusion with internal fixation were made through posterior approach and at last fixation and fusion in anterior approach were made. In this study we measured structure Cobb angle, compensatory Cobb angle, mandibular incline, shoulder balance and the angle difference of trapezius muscle preoperation and post operation. Perioperative neurological,vascular and wound related complicationswere recorded. Results:All patients' surgeries were completed successfully. Eight patients received single site distraction and 3 patients received distraction in two sites. The duration of surgery was 466±141 min (range 150-659 min), the estimated blood losswas 387±191 ml (range 100-660 ml) and follow up time was 12.2±9.5 months (range 3-24 months). Structural Cobb angle was 28.9°±13.1° pre-operation and 7.4°(3.0°, 27.7°) post-operation at 3 months, which was corrected significantly ( Z=-2.934, P=0.003). The correction rate was 58.1±26.1% (range 18.8%-97.6%). Structural Cobb angle was 13.2°±12.3°at 1 year post operation and had no significant difference compared with 3 months post operation ( t=1.960, P=0.107). Compensatory Cobb angle was 18.3°±6.1° pre-operation and 9.4°±7.3° post-operation at 3 months, which was corrected significantly ( t= 5.071, P<0.001) and the correction rate was 51.3%±28.3% (range 2.4%-94.7%). Compensatory Cobb angle was 8.9°±7.7° at 1 year follow up and was corrected significantly ( t=5.253, P=0.003) compared to 3 months after surgery and the correction rate was 61.4%±26.9%. Two patients developed C 5 nerve root dysfunction and 1 patient developed numbness on the index and middle fingers after surgery. All of them occurred on the concave side and recovered by conservative treatment. Conclusion:The application of distraction on the concave side in the treatment of congenitalcervical scoliosis is with good feasibility and clinical safety. Short-term follow-up showed excellent resultswith a promising future.
5.Recombinant human endostatin reduces radiation-induced myocardial fibrosis in rats
Huaxiang KUANG ; Shilin XU ; Weiwei OUYANG ; Chaofen ZHAO ; Xiaoyang LI ; Xiaxia CHEN ; Wengang YANG ; Zhu MA ; Bing LU ; Shengfa SU
Chinese Journal of Radiological Medicine and Protection 2020;40(5):343-348
Objective:To assess the effects of recombinant human endostatin (rh-ES) on radiation-induced myocardial fibrosis.Methods:Totally 40 SD rats were randomly divided into 4 groups, including A group as normal control, B group receiving rh-ES with a dosage of 6 mg·kg -1·d -1, in traperitoneal injection, for 14 consecutive days, C group with local heart irradiation delivered to the precordial region of rats in five fractions with a dose of 25 Gy, D group receiving rh-ES as the same as B group and local heart irradiation as C group. At 1 and 3 months after irradiation, five rats were killed under anesthesia. Mason staining was used to observe myocardial injury and fibrosis. Western blotting was used to detect the expression of TGF-β1, CTGF and COL-I in myocardium. Results:Masson staining showed that no obvious myocardial fibrosis was found in group B at 1 month and 3 months after irradiation, while collagen fibers were distributed in myocardium in groups C and D. One month after irradiation, the result of semi-quantitative analysis showed that the CVF in group A was (5.20 ±0.75)%, which was significantly lower than that in group C (10.12 ±2.17)% ( t=4.74、4.93, P<0.01) and the CVF in group D (10.32 ±1.36), and the CVF of group C was similar to that of group D ( P<0.01). Three months after irradiation, CVF in group C (13.17±2.67)% was still higher than that in group A (5.23 ±1.32)% ( t=4.49, P<0.01), but lower than that in group D (16.92 ±3.58)% ( t=3.19, P<0.05). One month after irradiation, the expression of TGF-β1 in group A was 0.441 ±0.063, lower than that in group C (0.817 ±0.079, t=5.81, P<0.01). Three months after irradiation, the expression of TGF-β1 in group A was 0.501 ±0.110, lower than that in group C (0.832 ±0.150, t=4.19, P<0.01), and the expression of TGF-β1 in group D was 1.403 ±0.133, which was significantly higher than that in group C ( t=7.24, P<0.01). Conclusions:Radiation can cause the formation of myocardial fibrosis, and recombinant human endostatin may aggravate the formation of late radiation fibrosis.
6.Consistencyanalysisofpreoperativeultrasoundand MSCTindiagnosing microvascularinvasioninhepatocellularcarcinoma
Lianfeng LIU ; Danke SU ; Junjie LIU ; Hang LI ; Zhanling DING ; Shengfa ZHAO
Journal of Practical Radiology 2019;35(5):752-755,779
Objective Toinvestigatetheconsistencyofultrasoundand MSCTindiagnosing microvascularinvasion (MVI)in hepatocellularcarcinoma,andtocomparethediagnosticefficiencyofbothtwomethods.Methods TheultrasoundandMSCTdataof 82patientswithhepatocellularcarcinomawerecollected.Accordingtothepostoperativepathologicalresults,theconsistencyanddiagnostic efficiencyofultrasoundandMSCTindiagnosingMVIinhepatocellularcarcinomawerecompared.Results Accordingtothepostoperative pathologicalfindingsof82patients,30caseswerepositiveofMVI,while52caseswerenegative.ThepreoperativeMSCTandultrasound examinations had a strong consistency (Cohen’s Kappa=0.829 ,P<0.001 ).The sensitivity ,specificity and accuracy of preoperative ultrasoundinpredictingtheMVIinhepatocellularcarcinomawere76.67% (23/30),67.31% (35/52)and70.73% (58/82),respectively. Thesensitivity,specificityandaccuracyofpreoperativeMSCTinpredictinghepatocellularcarcinomaMVIwere83.33% (25/30),73.08%(38/52)and75.61% (63/82),respectively.Conclusion Preoperativeultrasoundand MSCThavegoodconsistencyandhighdiagnostic efficiencyindiagnosing MVIinhepatocellularcarcinoma.
7.Mid-term clinical outcomes of anterior cervical internal fixation and fusion for Hirayama disease
Xin CHEN ; Shengfa PAN ; Feifei ZHOU ; Yanbin ZHAO ; Yu SUN
Chinese Journal of Orthopaedics 2019;39(8):485-490
Objective To assess the mid-term clinical and radiological outcomes of anterior cervical internal fixation and fusion for the treatment of Hirayama disease and to evaluate the clinical significance and value of this procedure.Methods All of 31 patients underwent anterior cervical internal fixation and fusion were retrospectively analyzed with a minimum of 5 years follow-up in our hospital between May 2008 and May 2011,whose disease progressively deteriorated after six-month's conservative therapy(neck collar)preoperatively.There were 30 males and 1 female with an average age of 19.0±2.7 years which ranged from 16 to 27.The clinical outcomes included forearm and hand muscle atrophy and strength.The radiological outcomes included range of motion(ROM)of the whole cervical spine and unstable segments,as well as venous flow empty phenomena and "snake eyes" sign on MRI in the flexed position.All were recorded at 3 month,1 year,3 year and 5-6 years follow-up time points after surgery.The preoperative and postoperative quantitative variables were analyzed by paired t test,and a P<0.05 was used to indicate statistical significance.Results All the patients showed no further progression of symptoms of muscular weakness or atrophy.At the end of 5-6 years follow-up,24 of the 31 patients(77.4%)showed improved muscle strength and 16 of the 31 patients(51.6%)showed improved atrophy.Thirty-one patients had a forearm muscle strength of 4 to 5 at the last follow-up,with an average of 4.9±0.3,which was superior to preoperative 0 to 5(3.6±1.0);grip strength was 3 to 5 kg,with an average of 3.9±0.7 kg,significanthigher than 1 to 3.8 kg(2.5±0.8 kg)before surgery.Score of muscle strength of the 31 patients at the end of 5-6 years' follow-up was 4.9±0.3(4 to 5),which was significantly higher than preoperative.Postoperative X-rays at the end of 5-6 years' follow-up revealed that all the cases' internal fixation was at the proper position,and no losing or broken of the internal fixation were identified.Dynamic X-rays of cervical spine showed the range of motion(ROM)of the whole cervical spine was significantly decreased after the operation.The ROM of preoperation was 77.8o±12.70 and that of 5—6 years postoperation was 27.90±7.60.The unstable segments of cervical spine became stable postoperatively.The flexible position MRI of cervical spine showed the spinal cord was completely relieved,without new compression.Venous flow empty phenomena disappeared and no "snake eyes" sign was identified.Conclusion Anterior cervical internal fixation and fusion is an effective surgical treatment for Hirayama disease and may provide preferable mid-term clinical and radiological outcomes.This procedure has clinical significance and value in terms of control of the progression and outcome of this disease.
8.Evaluations of hand dysfunction by brief Michigan hand questionnaire in patients with Hirayama disease treated with surgery
Yanbin ZHAO ; Yilong ZHANG ; Yu SUN ; Shaobo WANG ; Li ZHANG ; Fengshan ZHANG ; Shengfa PAN ; Yinze DIAO ; Xin CHEN ; Feifei ZHOU
Chinese Journal of Orthopaedics 2019;39(8):491-495
Objective To investigate the clinical efficacy of anterior cervical surgery by comparative analyzing hand dysfunction using brief Michigan hand questionnaire(Brief MHQ)in Hirayama disease patients.Methods From Aug 2011 to Dec 2016,27 patients of hirayama disease who underwent surgery were enrolled in this study.The study group consisted of 27 men.The mean follow-up period was 41.1 months.The levels of surgery included 18 cases of C4-C7,6 cases of C3-C6,2 cases of C4-C6 and 1 case of C5-T1.Brief MHQ were evaluated for the 27 patients.According to the Wilcoxon analysis,the unchanged domains were analyzed with the multifactor Logistic regression analysis by preoperative duration of symptoms,age of onset,and number of affected extremities.Dynamic flexion-extension lateral X-rays were performed at baseline and at final follow-up.Results No failure of internal fixation was detected on dynamic flexion-extension lateral X-rays.Five domains of preoperative Brief MHQ had lower scores,including Function,Satisfaction,Aesthetics,Activities of daily living,Work domain.With the exception of Aesthetics and Pain domain,all the other four domains showed significant improvement after surgery.The total score was 38.44±5.83 at base-line and 43.19±4.47 at follow-up.The score of Function was 5.19±1.36 at baseline 6.37±1.15 at follow-up;The score of Satisfaction was 5.56±1.22 at baseline 6.60±1.05 at follow-up;The score of Activities of daily living was 6.33±1.84 at baseline 7.60±1.47 at follow-up;The score of Work was 6.85±1.75 at baseline 7.67±1.33 at follow-up.The risk factors of postoperative outcomes reported in the literature included duration of disease at the time of surgery,age of onset,and extremity involvement.According to the Logistic regression,pre-operation duration was the risk factor for Aesthetics domain and the cut-off time was 1.75 years.Conclusion Four domains of Brief MHQ score were improved significantly after anterior surgery for patients with hirayama disease.Brief MHQ was useful to evaluate the hand dysfunction and clinical efficacy in patients with hirayama disease.
9.Clinical values of contrast-enhanced ultrasound in diagnosis and classification of portal vein tumor thrombosis
Hongxue LI ; Junjie LIU ; Shengfa ZHAO ; Xiang LI ; Ting ZHOU ; Yang PENG ; Hang LI
Journal of Jilin University(Medicine Edition) 2016;42(2):380-384
Objective:To explore the clinical application values of contrast-enhanced ultrasound in the diagnosis and classification of portal vein tumor thrombosis (PVTT)by comparing with enhanced CT.Methods:43 patients with PVTT confirmed by clinic and pathology were selected, and the accuracy rates of the diagnosis and clinic classification of contrast-enhanced ultrasound and enhanced CT were compared. Results:The characteristic of PVTT in contrast-enhanced ultrasound was“quick in fast out”;88.4% (38/43)of PVTT were hyper-enhancement in the arterial phase, 81.4% (35/43 ) of PVTT were hypo-enhancement in the vein phase, and all tumor thrombosis showed hypo-enhancement in the delay phase. The diagnostic accuracy rate of contrast-enhanced ultrasound in PVTT was 100%,and the accuracy rate of enhanced CT was 97.7% (42/43).The classification accuracy rate of contrast-enhanced ultrasonic was 95.3% (41/43),and the accuracy rate of enhanced CT was 93.0% (40/43 );there was no statistically significant difference between two methods (P > 0.05 ). Conclusion:Dynamiccontrast-enhanced ultrasonography can display the blood perfusion characteristics of PVTT, and displays the actual infiltrating tumor thrombosis. Ultrasonic imaging and enhanced CT in the qualitative diagnosis of PVTT and clinical classification have a good consistency.Contrast-enhanced ultrasound can be used as an important imaging method to evaluate the PVTT before treatment.
10.The correlation between patient selection and heterotopic ossification after cervical artificial disc replacement
Feifei ZHOU ; Yu SUN ; Yanbin ZHAO ; Fengshan ZHANG ; Shengfa PAN ; Zhongjun LIU
Chinese Journal of Orthopaedics 2015;35(4):362-367
Objective To analysis the correlation between patient selection and heterotopic ossification (HO) after cervical artificial disc replacement.Methods Data of 48 patients with cervical spondylosis (34 cervical spondylotic myelopathy and 14 nerve-root type) who had undergone Bryan cervicadisc replacement from December 2003 to December 2008 were reviewed retrospectively,and all the patients had been followed up for more than 5 years.There were 21 males and 27 females with an average age of 42 years old (range,20-53 years).There were 38 single level replacement (C3-4 3 cases,C4-5 5 cases,C5-6 28 cases,C6-7 2 cases),9 double level replacement (C4-5,C5 6 4 cases;C5-6,C6-7 5 cases) and 1 three level replacement (C3-4,C4 5,C5-6) as a total of 59 surgical segments.The occurrence of HO was defined by McAfee classification on cervical lateral X-ray.Four factors were used in patient selection including gender,range of motion (ROM) of the target level,alignment of the functional spine unit (FSU) of the index level,and the disc height ratio between surgical level and the adjacent levels.The correlation between these four factors and HO was evaluated by logistic regression.The receiver operating characteristic (ROC) curve and area under the ROC curve were used to evaluate the significant result of logistic regression and the optimal diagnostic value.Results 48 patients were all followed up for an average period of 70.3 months (range,60-120 months).The occurrence rate in this study was 33.9% (20/59 segments).Only one factor,the disc height ratio of the target level and its adjacent levels,presented statistical correlation with HO.ROC analysis showed that the area under the ROC curve of disc height ratio was 0.813 and the optimal diagnostic threshold was 0.9.Conclusion The disc height ratio of the target level and adjacent levels was the only patient selective factor correlated with the occurrence of HO.For those with disc height loss exceeding 10% comparing to adjacent levels,it is not indicated for cervical artificial disc replacement with Bryan prosthesis.

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