Objective To observe the biocompatibility of a biomimetic designing of a multi-grade compositions in repairing articular cartilage and subchondral bone in animal bodies and repair the fullthickness defects in articular cartilage with the compositions and to study the regenerated cartilage histomorphologically. Methods Biocompatibility study: Acute general toxicity test, Haemolysis test, subcutaneous implantation test and chronic toxicity test. Articular cartilage defects repaired experimental study :The models of defects in articular cartilage were made artificially in both condylus lateralis femoris of mature rabbits. Implanted with the biomimetic designing of a multi grade compositions randomly at one side as the experimental group and the other side were untreated as the control group. The rabbits were killed at 4, 6, 8and 12 weeks after operation, respectively, with 6 ones at each time, and the macroscopic, histological, ultrastroctural examinations and semi-quantity cartilage scoring employing Wakitanifa repaired cartilage value system were performed. Results Biocompatibility study: (1) The rabbits' weight in experimental group kept growing .(2) Haemolysis rate of rats to different concentrations of diffusion solution was＜5%.(3) In chronic toxic reaction, rabbits' liver and kidney function was not different compared with the control groups at 12weeks and the index before operation. Articular cartilage defects repaired experimental study: 4-8 weeks after operation, the defects in the experimental group were partly filled with hyaline cartilage. Twelve weeks after operation, the defects in the experimental group were completely filled with mature hyaline cartilage.However, fibrous tissues were seen in the control group all the time. At 4, 6, 8, and 12 weeks postoperatively, the Wakitanifa cartilage scores were (7.60±0.98), (5.69±0.58), (4.46±0.85) and (4.35±0.12), respectively,in the experimental group and (10.25±1.05), (9.04±0.96), (8.96±0.88) and (8.88±0.68), respectively, in the control group. Differences between the control group and the experimental group were significant. Conclu sion The biomimetic designing of a multi-grade compositions has good biocompatibility and may induce cartilage regeneration to repair the full-hickness defects of articular cartilage.

BACKGROUND: Previous studies have confirmed that in the animal models of articular cartilage defects and osteoarthritis, the chondrocytes can overexpress the matrix metal oproteinases. Various abnormal stimuli are likely to break the balance between matrix metal oproteinase and tissue inhibitor of metal oproteinase, thus leading to degeneration of extracel ular matrix of articular cartilage, as wel as the decline and offset of cartilage chondrocytes. OBJECTIVE: To observe the effect of cyclic tensile strain on the expression of matrix metal oproteinases during the repairing process of rabbit articular cartilage defects. METHODS: The animal models of articular cartilage defects were established, and chondrocytes were separated for culture at 10 weeks after operation. The chondrocytes on the non-surgical side were considered as the normal group, and the chondrocytes on the surgical side were randomly divided into high cyclic tensile strain group, low cyclic tensile strains group and control group, and the load amplitude was sin10%. Then 0.1, 1.0 and 0 Hz cyclic tensile strains were loaded respectively. The expressions of matrix metal oproteinases 2, 3, 9 and 13 in each group were detected with reverse transcription-PCR at 24, 48 hours, 1, 2 and 4 weeks after loading cyclic tensile strain. RESULTS AND CONCLUSION: There were significant differences in the expressions of matrix metal oproteinases 2, 3, 9 and 13 at 24 hours after loading cyclic tensile strain between the normal group and the control group (P < 0.05); and there were significant differences in the expressions between the high cyclic tensile strain group and the low cyclic tensile strain group at 1, 2 and 4 weeks after loading cyclic tensile strain (P < 0.05).At the same time, the expressions of matrix metal oproteinases 2, 3, 9 and 13 in the low cyclic tensile strain group were continued to decline, and there were significant differences in the expressions after loading cyclic tensile strain for 24 hours and 4 weeks (P < 0.05). The results indicate that mechanical load can affect the expression of matrix metal oproteinases in the healing process of rabbit articular cartilage defects. In the cel ular and molecular level, the incidence and development of pathological articular cartilage defect and stress should affect each other.

Objective To investigate the biological mechanisms and feasibility of collagen/hydroxyapatite scaffolds for repairing articular cartilage and subchondral bone defects. Methods 45 New Zealand white rabbits were included. Full-thickness articular cartilage defect models were established in experiment and control groups and the biomaterial scaffolds were implanted in the experiment group. The animals were sacrificed in the 4th, 6th and 8th week after the operation respectively. Histological scores were performed by semi-quantity cartilage scoring system and the expressions of matrix metalloproteinases (MMPs)-2, 3, 9 and 13 mRNA in the synovialis were detected with RT-PCR. Results The repaired tissues were totally hyaline cartilages in the experiment group 2 weeks after operation and there were no repaired tissues in the control group. There were significant differences between these 2 groups in Wakitani scores (P<0.01). The activation and expression of MMP-2, 3, 9 decreased in the experiment group (P<0.05), but the activation of MMP-13 sustained and the expression of MMP-13 could be detected during the observed period (P>0.05). Conclusion The new biological scaffold can alleviate the inflammatory and protect the cartilages by inhibiting the expression of MMPS, which promote the reconstruction of articular cartilage in rabbits.

Purpose: Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. Materials and Methods: Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. Results: CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. Conclusion CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

Objective:To compare the efficacy of fusion and non-fusion hybrid operation with Dynesys system with the traditional fusion operation with rigid instrumentation in the patients with multi-segment lumbar degenerative disease.Methods:A total of 30 patients with multi-segment lumbar degenerative disease who were subjected to operation from January 2017 to October 2019 in Shenzhen People's Hospital were included in the study. There were 13 males and 17 females, age: 60.8±13.2 years, range: 25 to 83 years. 28 patients with two segments, 1 with three segments, and 1 with four segments. The patients were divided into two groups, i.e the hybrid operation group (13 cases, 9 males and 4 females, average age: 56.6 years, range: 25 to 83 years) versus the traditional fusion group (17 cases, 4 males and 13 females, average age: 63.9 years, range: 46 to 80 years). The main outcome measures were visual analogue scale (VAS), Oswestry disability index (ODI), range of motion (ROM), adjacent segment degeneration (ASD) and complications.Results:There were no statistically significant differences in operation data, such as operation time, intraoperative blood loss, postoperative drainage volume and length of hospitalization, between the two groups. There were no significant differences for ROM in the surgical segments between the two groups before operation (hybrid group and traditional group were 9.6°±4.9° vs. 8.9°±6.1°, t=0.341, P=0.736, respectively). However, after 12 months follow-up, the ROM disappeared in the traditional group and was partially preserved in the hybrid group, with statistically significant differences (hybrid group and traditional group were 5.4°±2.7° vs. 0°, t=9.104, P=0.001, respectively). There was a statistical difference in intervertebral disc height between the two groups at 12 months post-operation, though no statistical difference was found before operation (8.8±1.9 mm vs. 10.5±1.7 mm, t=2.927, P=0.006). There was no statistically significant difference in the intervertebral disc height of the upper adjacent vertebrae between the two groups before and after operation. There were statistically significant differences in ODI scores before operation (63.4%±11.0% vs. 71.3%±9.2%, t=2.146, P=0.041), and 12 months post-operation (17.2%±2.1% vs. 15.5%±2.3%, t=2.091, P=0.046), while no statistical difference was found in VAS scores. Conclusion:The fusion and non-fusion hybrid operation with Dynesys system has comparable clinical efficacy with the traditional fusion operation with rigid instrumentation in the treatment of multisegment lumbar degenerative disease. Meanwhile, the hybrid surgery can preserve the motion of surgical segments and provide a dynamic stability of the vertebral body. The hybrid surgery can be used as a new surgical method for multi-segment lumbar degenerative disease.

Objective:To investigate the predictive value of heparin binding protein (HBP) for sepsis.Methods:From June 2019 to December 2020, 188 patients admitted to the department of emergency of Hunan Provincial People's Hospital were enrolled. The patients were divided into non-sepsis group (87 patients) and sepsis group (101 patients) according to Sepsis-3 criteria. Gender, age, white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), HBP, sequential organ failure assessment (SOFA) score, quick SOFA (qSOFA) score, modified early warning score (MEWS) and patients' recent medication history were recorded, the differences in the above indicators between the two groups were compared. The risk factors of sepsis were analyzed by Logistic regression. Spearman correlation analysis was used to analyze the correlation between HBP, PCT, CRP and SOFA score to evaluate the predictive value of HBP, PCT and CRP for the severity of septic organ failure. Receiver operating characteristic curve (ROC curve) were drawn to evaluate the diagnostic value of HBP, PCT and CRP for sepsis.Results:Compared with the non-sepsis group, the sepsis group had significantly higher levels of HBP, PCT, CRP, WBC, SOFA score, qSOFA score, and MEWS [HBP (μg/L): 55.46 (24.57, 78.49) vs. 5.90 (5.90, 9.01), PCT (μg/L): 6.83 (1.75, 30.64) vs. 0.23 (0.12, 0.75), CRP (mg/L): 67.35 (26.23, 123.23) vs. 4.45 (2.62, 47.22), WBC (×10 9/L): 11.84 (7.18, 16.06) vs. 6.58 (5.47, 8.99), SOFA score: 6 (4, 8) vs. 0 (0, 0), qSOFA score: 2 (1, 3) vs. 0 (0, 1), MEWS: 4 (3, 6) vs. 1 (0, 2)], the length of hospital stay was significantly prolonged [days: 10 (4, 17) vs. 0 (0, 7)], and the mortality was significantly increased [29.7% (30/101)vs. 4.6% (4/87)], with statistical significance (all P < 0.05). Correlation analysis showed that HBP, PCT and CRP were significantly positively correlated with SOFA score ( r values were 0.60, 0.33, and 0.38, respectively, all P < 0.01), among which HBP had the strongest correlation, CRP was the second, and PCT was the weakest. Logistic regression analysis showed that HBP, PCT and CRP levels were independent risk factors for sepsis [odds ratio ( OR) were 1.015, 1.094, 1.067, 95% confidence intervals (95% CI) were 1.007-1.022, 1.041-1.150, 1.043-1.093, all P < 0.01]. ROC curve analysis showed that HBP, PCT and CRP all had some diagnostic value for sepsis [the area under ROC curve (AUC) were 0.92, 0.87, 0.80, 95% CI were 0.88-0.97, 0.82-0.92, 0.74-0.87, respectively, all P < 0.01]. Among them, the diagnostic efficacy of HBP was higher when the cut-off value was ≥15.11 μg/L, its sensitivity and specificity were 86.14% and 89.66%, respectively, which were higher than the sensitivity (81.19%) and specificity (80.46%) when the PCT cut-off value was≥ 1.17 μg/L. However, CRP had the best sensitivity of 94.06% for the diagnosis of sepsis but lacked of specificity (63.22%). Conclusion:HBP can be used as a biological indicator for predicting sepsis and can assess the severity of organ failure in septic patients.