1.Re-understanding of the mechanism of coagulation disorder in liver cirrhosis
Rongrong SUN ; Na HE ; Fenna ZHANG ; Xinyi ZHANG ; Ziyi WANG ; Hui WANG ; Nana BIAN ; Honglin YAN
Journal of Clinical Hepatology 2024;40(3):616-620
The liver plays an important regulatory role in maintaining the dynamic balance of coagulation and anticoagulation in the body. Such dynamic balance is fragile in patients with liver cirrhosis, and the risk of bleeding can be increased due to reductions in coagulation factors and platelet count and excessive fibrinolysis; meanwhile, thrombus can be formed due to the increases in von Willebrand factor and coagulation factor Ⅷ, the reductions in anticoagulant protein C and anticoagulant protein S, the increase in thrombin-generating potential, and alterations in antifibrinolytic components. This article reviews the mechanisms of coagulation disorder in liver cirrhosis, so as to help clinicians with the prevention and treatment of bleeding or thrombotic disorders in patients with liver cirrhosis.
2.Application of"rotation-correction loop technique"in the retrieval of complex inferior vena cava filters
Jie HU ; Maolin QIAO ; Qinqin TIAN ; Heng WANG ; Sheng YAN ; Wenbo ZHAO ; Yongbin SHI ; Peilu SHI ; Miao XING ; Haifeng LI ; Haijiang JIN ; Ping WANG ; Wenkai CHANG ; Yuwen WANG ; Honglin DONG
Journal of Interventional Radiology 2024;33(3):289-294
Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P<0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)
3.Influence of Guizhi Jia Longgu Mulitang on Expression of IL-10 and TNF-α in Insomnia Rats with Sensory Dysfunction Dominated by Lung
Jinhong WU ; Xingping ZHANG ; Deqi YAN ; Ruining LIANG ; Xu CHEN ; Zhengting LIANG ; Honglin JIA ; Hui WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):20-27
ObjectiveTo investigate the effects of Guizhi Jia Longgu Mulitang on the expression difference of interleukin-10 (IL-10) and tumor necrosis factor -α (TNF-α) in related organs of insomnia rats with sensory dysfunction dominated by lung and study the mechanism of Guizhi Jia Longgu Mulitang in improving insomnia. MethodSD rats were randomly divided into the blank group, model group, western medicine group, and traditional Chinese medicine (TCM) group, with 10 rats in each group. The rats were deprived of sleep by shallow water environment method in a long platform, and the modeling lasted for 42 d. The blank group and model group were given 0.05 mL·kg-1 normal saline by gavage, and the western medicine group and TCM group were given drugs during modeling. To be specific, the western medicine group was given 0.105 mg·kg-1 dexzopiclone tablet by gavage, while the TCM group was given 7 600 mg·kg-1 Guizhi Jia Longgu Mulitang by gavage, both lasting for 28 days. After successful modeling, the Morris water maze experiment was performed on the 42nd day to detect the motion and spatial memory ability of rats. The levels of IL-10 and TNF-α in serum were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression of IL-10 and TNF-α in the lung and brain tissue of rats was detected by Western blot. The levels of IL-10 and TNF-α in the lung and brain tissue of rats were detected by immunohistochemistry. ResultCompared with the blank group, the sleep stages non-rapid eye movement ( NREM ) and rapid eye movement ( REM ) of the model group were significantly shortened (P<0.5, P<0.01), and the wake stage was significantly increased (P<0.01). The total time and distance of platform exploration were significantly increased (P<0.01). In the target quadrant (the third quadrant), the percentage of exploration time and the times of crossing the platform were significantly decreased (P<0.01). ELISA results showed that the serum IL-10 level was significantly decreased (P<0.01), and TNF-α level was significantly increased (P<0.01). The results of Western blot showed that the protein expression of IL-10 in brain and lung tissue of rats was significantly decreased (P<0.01), and the protein expression of TNF-α was significantly increased (P<0.01). The results of immunohistochemistry showed that the expression of IL-10 in the brain and lung tissue of rats was significantly decreased (P<0.01), and that of TNF-α was significantly increased (P<0.01). Compared with the model group, the NREM stage and REM stage of the western medicine group and the TCM group were significantly increased (P<0.5, P<0.01), and the wake stage was shortened (P<0.5). The total time and distance of platform exploration were significantly decreased (P<0.01). In the target quadrant (the third quadrant), the percentage of exploration time and the times of crossing the platform were significantly increased (P<0.05, P<0.01). The serum IL-10 level was significantly increased (P<0.01), and the serum TNF-α level was significantly decreased according to the ELISA results (P<0.01). The results of Western blot showed that the protein expression of IL-10 in brain tissue and lung tissue was significantly increased (P<0.01), and the protein expression of TNF-α was significantly decreased (P<0.01). The results of immunohistochemistry showed that the expression of IL-10 in brain tissue and lung tissue was significantly increased (P<0.05, P<0.01), and the expression of TNF-α was significantly decreased (P<0.05, P<0.01). ConclusionGuizhi Jia Longgu Mulitang can improve the expression of IL-10 and TNF-α in brain and lung tissue of insomnia rats with sensory dysfunction dominated by lung, prolong sleep time, and then improve insomnia. The mechanism may be related to improving the expression level of inflammatory factors.
4.Multi-task learning for automated classification of hypertensive heart disease and hypertrophic cardiomyopathy using native T1 mapping
Honglin ZHU ; Yufan QIAN ; Xiao CHANG ; Yan ZHOU ; Jian MA ; Rong SUN ; Shengdong NIE ; Lianming WU
International Journal of Biomedical Engineering 2024;47(4):342-348
Objective:To automatically classify hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) based on mul-titask learning algorithm using native T1 mapping images.Methods:A total of 203 patients admitted to Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University from January 2017 to December 2021 were enrolled, including 53 patients with HHD, 121 patients with HCM, and 29 patients with normal control (NC). Native T1 mapping images of all enrolled patients were acquired using MRI and processed by a multi-task learning algorithm. The classification performance of each model was validated using ten-fold crossover, confusion matrix, and receiver operator characteristic (ROC) curves. The Resnet 50 model based on the original images was established as a control.Results:The ten-fold crossover validation results showed that the MTL-1 024, MTL-64, and MTL-all models showed better performance in terms of area under the curve (AUC), accuracy, sensitivity, and specificity compared to the Resnet 50 model. In the classification task, the MTL-64 model showed the best performance in terms of AUC (0.942 1), while the MTL-all model reached the highest value in terms of accuracy (0.852 2). In the segmentation task, the MTL-64 model achieved the best results with the Dice coefficient (0.879 7). The confusion matrix plot showed that the MTL model outperforms the Resnet 50 model based on the original image in terms of overall performance. The ROC graphs of all MTL models were significantly higher than the original image input Resnet 50 model.Conclusions:Multi-task learning-based native T1 mapping images are effective for automatic classification of HHD and HCM.
5.Factors influencing the efficacy of neoadjuvant therapy in breast cancer assessed by RCB as well as the prognostic value of RCB in neoadjuvant therapy (with video)
Xianli JU ; Honglin YAN ; Xiaokang KE ; Feng GUAN ; Aoling HUANG ; Jingping YUAN
Chinese Journal of Endocrine Surgery 2023;17(5):518-523
Objective:The residual cancer burden (RCB) evaluation system was used to analyze the influencing factors of the efficacy of neoadjuvant therapy in breast cancer, and to explore the prognostic value of RCB evaluation in neoadjuvant therapy.Methods:Clinicopathologic data and postoperative RCB grading of 364 breast cancer patients who underwent neoadjuvant therapy in Renmin Hospital of Wuhan University from Nov. 2019 to Nov. 2022 were collected. Chi-square test was used to analyze the relationship between RCB grading and clinicopathological parameters, and Spearman’s rank correlation analysis was performed to evaluate the correlation between RCB grading and clinicopathological characteristics. Factors influencing pathologic complete response (pCR) were analyzed by Logistic regression. Kaplan-Meier survival analysis and log-rank test were used to evaluate cumulative survival.Results:Among the 364 patients who underwent neoadjuvant therapy, 129 cases of RCB grade 0 and 235 cases of RCB gradeⅠ-Ⅲ (including 46 cases of RCB gradeⅠ, 109 cases of RCB grade Ⅱ and 80 cases of RCB grade Ⅲ) were obtained after surgery. Histological classification ( χ 2=21.757, P=0.000), estrogen receptor (ER) ( χ 2=52.837, P=0.000), progesterone receptor (PR) ( χ 2=55.658, P=0.000), human epidermal growth factor receptor-2 (HER2) ( χ2=89.040, P=0.000), Ki67 expression ( χ2=12.927, P=0.005), molecular typing ( χ 2=80.793, P=0.000) and preoperative lymph node status ( χ 2=25.764, P=0.000) were all associated with postoperative RCB grading. Further correlation analysis showed that histological grade ( r=-0.229, P=0.000), HER2 expression ( r=-0.465, P=0.000) and Ki67 expression ( r=-0.179, P=0.000) were negatively correlated with RCB grading, while ER ( r=0.352, P=0.000), PR ( r=0.379, P=0.000) and lymph node metastasis ( r=0.214, P=0.000) were positively correlated with RCB grading. Logistic regression analysis showed that high histological grade, negative expression of ER, PR and AR, positive expression of HER2, high proliferation index of Ki67 and no lymph node metastasis were favorable factors for postoperative pCR, and PR, AR and HER2 were independent predictors of postoperative pCR. Kaplan-Meier survival analysis showed significant differences in postoperative cumulative survival among patients with different RCB grades ( P=0.004) . Conclusions:Postoperative RCB grading of breast cancer is closely related to many clinicopathological features before neoadjuvant therapy and survival prognosis. Clinicopathological factors closely related to RCB grading are also important influencing factors affecting the pCR of patients with neoadjuvant therapy. Therefors, RCB grading has a high prognostic value.
6.Preliminary study on the clinical application of four cytokines in serum of autoimmune diseases
Wei LI ; Ziyan WU ; Leili MAO ; Xinyao ZHANG ; Songxin YAN ; Honglin XU ; Futai FENG ; Shulan ZHANG ; Yongzhe LI
Chinese Journal of Laboratory Medicine 2023;46(11):1173-1179
Objectives:the purpose of this study was to systematically evaluate the clinical value of cytokines in autoimmune diseases (AID). It was a kind of complex disease, and its pathogenesis involved cytokines, autoantibodies, immune cells and other immune factors. Especially some AID, such as Adult still′s disease (AOSD) and Takayasu arteritis(TA), had no specific biomarkers at present. This study was a retrospective case-control study.Methods:the data of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) in 834 AID patients from January 2019 to August 2022 were collected, and the serum levels of those cytokines in 30 healthy controls (HC) were detected at the same time. And AOSD, TA, systemic lupus erythematosus (SLE) and Behcet′s syndrome (BS) were divided into active group and inactive group. In addition, we also made a subgroup analysis of two important organs involved in SLE (kidney and nervous system). GraphPad Prism 9 and R 4.2.2 software were used. Nonparametric tests (Kruskal-Wallis H test, Mann-Whitney U test) were used to compare the differences among groups, and Dunn′s method was used to correct the false positive caused by multiple tests. Results:To compare the level of IL-6 in each group, except Behcet syndrome (BS) group and antiphospholipid syndrome (APS) group, the serum IL-6 level of AID group was higher than that of HC group, with antineutrophil cytoplasmic antibodies associated vasculitis(AAV) [3.85(2.00,8.55) pg/ml], idiopathic inflammatory myopathies(IIM) [7.80(2.50,6.50)pg/ml], IgG4-related disease(IgG4RD) [3.65(2.08,12.83) pg/ml], rheumatoid arthritis (RA) [5.50(2.20,16.10) pg/ml], SLE[4.70(2.75,16.55) pg/ml], Sj?gren syndrome(SS) [3.20(2.00,8.90) pg/ml], systemic sclerosis(SSc) [2.70(2.00,8.90) pg/ml], TA[3.40 (2.00,6.50) pg/ml], other AID diseases[4.40(2.00,11.10) pg/ml], especially AOSD [15.20(2.10, 39.20) pg/ml]. After correction, the differences were statistically significant ( P c<0.05). At the same time, the levels of serum TNF-α [7.40(5.60,10.95) pg/ml]and IL-10 [5.00(5.00, 7.58) pg/ml] in AOSD group were significantly higher than those in HC group[7.15(5.93,8.00) pg/ml,5.00(5.00,5.00) pg/ml] after correction ( P c<0.05). At the same time, the levels of serum TNF-α and IL-10 in AOSD group were higher than those in HC group. The serum levels of IL-6 and IL-8 in patients with active AOSD, BS, SLE and TA were significantly higher than those in patients without active disease (all P<0.05). In addition, the level of serum IL-8 in lupus nephritis group was significantly higher than that in non-lupus nephritis group ( P<0.05). At the same time, the serum levels of IL-6, IL-8 and TNF-α in neuropsychiatric lupus erythematosus group were significantly higher than those in non-neuropsychiatric lupus erythematosus group ( P<0.05), but there was no significant difference in IL-10 between neuropsychiatric lupus group and non-neuropsychiatric lupus erythematosus group. Conclusions:there was a close relationship between AID and cytokines. At present, the change of serum IL-6 level was the most classic one in clinical routine.
7.Expression and clinical significance of plasma methylated SEPT 9 gene in patients with primary liver cancer
Na HE ; Gong FENG ; Fenna ZHANG ; Shuai HAO ; Rong LI ; Ziqi ZHAO ; Yawen TIAN ; Honglin YAN
Chinese Journal of Hepatology 2023;31(3):265-270
Objective:To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer.Methods:393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests.Results:367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant ( χ2 = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant ( χ2 = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant ( χ2 = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion:In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.
8.The role of Caspase-1/GSDMD-mediated cell pyroptosis in anti-tumor effect of cisplatin in triple-negative breast cancer
Honglin YAN ; Jingping YUAN ; Juan WU ; Feng GUAN ; Bin LUO ; Xiaoyan WU ; Xiaokang KE ; Xiuxue YUAN
Chinese Journal of Endocrine Surgery 2022;16(2):137-143
Objective:To investigate the role of Caspase-1/gasdermin D (GSDMD) -mediated cell pyroptosis in anti-tumor effect of cisplatin (DDP) in triple-negative breast cancer (TNBC) .Methods:HE staining and immunohistochemical staining were performed to detect the morphological changes and the expression of pyroptosis/apoptosis pathway related proteins in TNBC tissues before and after DDP-based neoadjuvant chemotherapy (NACT) . The TNBC cell line MDA-MB-231 was treated with DDP and the morphological changes were observed. The type of cell death induced by DDP was analyzed by Annexin V-FITC/PI double staining and flow cytometry. Lactate dehydrogenase (LDH) release assay and ELISA were performed to detect the release of LDH and inflammatory factors (IL-18 and IL-1β) in cell culture supernatant after DDP treatment. Western blot (WB) was performed to detect the expression of pyroptosis/apoptosis pathway related proteins in cells after DDP treatment. MDA-MB-231 cells treated with DDP were co-treated with caspase-1 specific inhibitor to inhibit pyroptois or co-treated with caspase-3 specific inhibitor to inhibit apoptosis. The effect of caspase-1 inhibitor or caspase-3 inhibitor on the anti-tumor effect of DDP was detected by MTT assay, clone formation assay, transwell assay and would healing test.Results:Reactive changes in the breast surgical specimen after DDP-based NACT included cell swelling and inflammatory cell aggregation around the tumor bed, which were more similar to pyroptosis. The up-regulation of key molecules of pyroptosis pathway post-NACT was significantly higher than that of key molecules of apoptosis pathway. Further experiments in vitro showed that DDP could induce MDA-MB-231 cells to show pyroptosis-like changes characterized by large bubbles blowing from the cellular membrane. Flow-cytometry analyses showed that the death type of MDA-MB-231 cells caused by DDP was mainly Annexin V +PI + cells (mainly lytic cells, such as pyroptosis) . Additionally, DDP treatment induced significant activation of caspase-1 and GSDMD, increased the release of LDH, IL-18 and IL-1β, however, the activation level of caspase-3, which dominates the apoptosis pathway, was significantly lower than that of caspase-1/GSDMD. Moreover, caspase-1 inhibitors (blocking the classical pyroptosis pathway) had a significantly greater inhibitory effect on the anti-tumor effect of DDP than caspase-3 inhibitors (blocking the apoptosis pathway) . Conclusion:Caspase-1/GSDMD mediated pyroptosis may play a leading role in the anti-tumor effect of DDP in triple-negative breast cancer.
9.Near infrared spectroscopy assessed oxygenated hemoglobin with sleep quality among college students
REN Honglin, BIAN Yueran, ZHANG Yan, QIU Min, XIANG Nian,WU Huifen, XIAO Qiang, LI Xiaonan
Chinese Journal of School Health 2022;43(3):425-428
Objective:
Functional near infrared spectroscopy (fNIRS) was used to assess brain oxygenated hemoglobin (Oxy Hb) activation in college students with different sleep quality under the verbal fluency task (VFT), so as to better provide a theoretical basis for the neural mechanism for sleep quality improvement of college students.
Methods:
A simple random sampling method was used to investigate 96 college students from one university during 2020 and 2021. According to the results of the Pittsburgh Sleep Quality Index(PSQI), participants were divided into 3 groups: good sleep quality group( n =45), moderate group( n =33), and poor group( n =18). The 53 channel near infrared spectroscopy to collect cerebral blood oxygen signals under the VFT task. Association between oxygenated hemoglobin with sleep quality was analyzed.
Results:
About 18.75% of college students reported sleep quality problems, including long sleep latency (0.97±0.97) and poor subjective sleep quality (0.96±0.72). There was a significant negative correlation between PSQI score and average oxygenated hemoglobin (Avg HbO) index of dorsolateral prefrontal lobe ( r =-0.23, P =0.03). The Avg HbO index differed significantly between good and poor sleep quality groups on dorsolateral prefrontal lobe( P =0.05).
Conclusion
This study verified that there is a positive correlation between sleep quality and cognitive ability among college students. The fNIRS technique could accurately collect blood oxygen signals from dorsolateral prefrontal lobe during cognitive tasks, which proves to be an effective tool for identifying sleep quality of college students.
10.Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (version 2022)
Zhengwei XU ; Dingjun HAO ; Liming CHENG ; Baorong HE ; Bohua CHEN ; Chen CHEN ; Fei CHE ; Jian CHEN ; Qixin CHEN ; Liangjie DU ; Shunwu FAN ; Zhong FANG ; Shiqing FENG ; Yanzheng GAO ; Haishan GUAN ; Zhong GUAN ; Hua JIANG ; Weimin JIANG ; Dianming JIANG ; Jun JIANG ; Yue JIANG ; Lijun HE ; Yuan HE ; Bo LI ; Tao LI ; Jianjun LI ; Xigong LI ; Yijian LIANG ; Bin LIN ; Bin LIU ; Bo LIU ; Yong LIU ; Zhibin LIU ; Xuhua LU ; Chao MA ; Lie QIAN ; Renfu QUAN ; Hongxun SANG ; Haibo SHEN ; Jun SHU ; Honghui SUN ; Tiansheng SUN ; Jun TAN ; Mingxing TANG ; Sheng TAO ; Honglin TENG ; Yun TIAN ; Jiwei TIAN ; Qiang WANG ; Xinwei WANG ; Jianhuang WU ; Peigen XIE ; Weihong XU ; Bin YAN ; Yong YANG ; Guoyong YIN ; Xiaobing YU ; Yuhong ZENG ; Guoqing ZHANG ; Xiaobo ZHANG ; Jie ZHAO ; Yue ZHU
Chinese Journal of Trauma 2022;38(11):961-972
Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.


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