Potential Use of Extracellular Vesicles in the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a major cause of low back pain, and several studies have evaluated the efficacy of extracellular vesicles (EVs) in the treatment of IVDD. The databases PubMed, Embase, and Cochrane Library were systematically searched from inception to the end of 2022 to identify studies investigating the therapeutic potential of cell-derived EVs for IVDD treatment. The following outcome measures were utilized: magnetic resonance imaging (MRI) Pfirrmann grading system, disc height index (DHI), histological grading, and apoptosis rate. A comprehensive meta-analysis was conducted, including a total of 13 articles comprising 19 studies involving 218 experimental animals. Comparative analysis between normal cell-derived EVs and placebo revealed significant reductions in MRI grade, increased DHI values, decreased nucleus pulposus cell apoptosis rates, and improved tissue grades. These findings collectively demonstrate the effective inhibition of IVDD through the application of EVs derived from cells. In conclusion, this study provides an updated synthesis of evidence supporting the efficacy of EVs as a promising therapeutic approach for IVDD treatment.

Sequencing and bioinformatics analysis of miRNA from rat endplate chondrogenic exosomes.

Exosomes have a key role in various diseases, such as arthritis, heart disease and respiratory disease. Exosomes from various sources have also been indicated to improve intervertebral disc degeneration. However, the role of endplate chondrogenic exosomes in intervertebral disc degeneration has remained largely elusive. The aim of the present study was to compare exosomal microRNA (miRNA) expression patterns in endplate chondrocytes before and after degeneration, and their potential roles in the pathogenesis of intervertebral disc degeneration (IVDD). Endplate chondrocytes were extracted from rats and cultured to obtain pre- and post-degeneration chondrocytes. Exosomes were obtained from the chondrocytes by centrifugation. The two groups of exosomes were subjected to small RNA sequencing, miRNA identification, novel miRNA prediction, quantitative analysis of miRNA expression and differentially expressed (DE) miRNA screening, in addition to miRNA target gene (TG) prediction and TG functional annotation and enrichment analysis. The percentage of miRNAs isolated from the exosomes before and after degeneration was found to differ. A total of 58 DE miRNAs were analyzed, the expression levels of which were significantly different post-degeneration compared with pre-degeneration. Cell experiments were also performed, in which the exosomes were co-cultured with nucleus pulposus (NP) cells. The results indicated that the chondrocyte-derived exosomes were taken up by the NP cells and influenced the expression of aggrecan and collagen 1A and 2A, suggesting that they may inhibit IVDD via their action on NP cells. The specific miRNAs present in exosomes during IVDD may be used to develop new targets for the treatment and diagnosis of this condition. DE exosomal miRNAs derived from endplate cartilage pre- and post-degeneration may be associated with the risk of IVDD and could help to distinguish patients with IVDD. Furthermore, the expression of certain miRNAs may be associated with disease progression, which may contribute to understanding the pathophysiology of IVDD from an epigenetic perspective.

A Comparative Study of Total Knee Arthroplasty and Unicondylar Knee Arthroplasty in the Treatment of Knee Osteoarthritis.

Objective: To compare the clinical efficacy of total knee arthroplasty (TKA) and unicondylar knee arthroplasty (UKA) in the treatment of knee osteoarthritis (KOA). Methods: A retrospective analysis was conducted on 30 patients admitted to the Department of Orthopaedics of Yijishan Hospital from 2020 to 2021. The patients were divided into UKA group (n = 15) and TKA group (control, n = 15). The intraoperative situation and postoperative clinical indicators of patients in the two groups were collected and compared, such as operation time, intraoperative blood loss, length of hospital stay, postoperative complications, and postoperative functional recovery. Postoperative functional recovery was investigated by the visual analogue pain scale (VAS), knee score scale (HSS), and knee range of motion (ROM) scores 5 days after surgery. Results: Perioperative indexes in the UKA group were significantly lower than those in the TKA group, including operation time, intraoperative blood loss, first time going to the ground, and length of hospital stay. VAS, HSS, and ROM scores in the two groups were significantly improved after surgery compared with those before surgery. However, ROM scores in the UKA group were significantly better than in the TKA group. In terms of early postoperative complications, there was one case of venous thrombosis of lower limbs in the UKA group, while in the TKA group there was one case of delayed wound healing due to diabetes, and one case of deep infection. Conclusion: Both UKA and TKA are very successful options for the treatment of KOA, but the use of UKA can promote the recovery of postoperative knee function, reduce postoperative complications, and achieve more satisfactory than expected results.

[A case-control study:the clinical efficacy of total laminectomy with lateral mass screw fixation and single open-door laminoplasty for cervical spinal cord injury without fracture and dislocation].

OBJECTIVE: To compare the clinical effects of total laminectomy with lateral mass screw fixation and single open-door laminoplasty in the treatment of cervical spinal cord injury without fracture and dislocation. METHODS: The clinical data of 75 patients with cervical spinal cord injury without fracture and dislocation treated from December 2014 to April 2020 were retrospectively analyzed, including 65 males and 10 females, aged from 33 to 83 years old with an average of (60.1±11.4) years. According to surgical method, the patients were divided into observation group (36 cases) and control group (39 cases). The observation group was treated with C3-C6 single open-door laminoplasty. In the control group, the C3-C6 whole lamina was opened by "uncovering", and the lateral mass screw was fixed and fused. The general conditions including operation time, intraoperative blood loss, hospital stay and complications such as axial pain, cerebrospinal fluid leakage, postoperative C5 nerve palsy were recorded. Visual analogue scale(VAS), Nurick pain scale, Japanese Orthopaedic Association(JOA) scores and American Spinal Injury Association(AISA) injury scale were used to evaluate the improvement of clinical symptoms and related functional recovery 12 months after operation. RESULTS: There were no statistically significant differences in operation time, intraoperative blood loss and hospital stay between two groups(P>0.05). There were statistically significant differences in JOA, VAS, ASIA and Nurick scores of the all patients between 12 months after surgery and before surgery (P<0.05), and there was no significant difference between groups. There was significant difference in the incidence of C5 nerve root palsy and axial pain between two groups(P<0.05), but there was no significant difference in the complications of cerebrospinal fluid leakage between two groups (P>0.05). CONCLUSION: Total laminectomy with lateral mass screw fixation and single open-door laminoplasty in treating cervical spinal cord injury without fracture and dislocation can obtain satisfactory results in restoring nerve function, alleviating pain and improving daily behavior, but single open-door laminoplasty has the advantages of less trauma and low incidence of complications.

[Value of a new predictive model in evaluating short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure].

OBJECTIVE: To establish a predictive model and investigate its value in evaluating short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). METHODS: Patients with HBV-ACLF admitted to Tianjin Second People's Hospital and Beijing Youan Hospital, Capital Medical University from May 2015 to October 2018 were enrolled. The data of gender, age, laboratory markers at admission, model for end-stage liver disease (MELD) score and clinical complications were collected for analysis. According to the prognosis on 12-week, patients were divided into survival group and death group. Univariate analysis and binary Logistic regression analysis were used to test the risk factors for short-term prognosis of the patients with HBV-ACLF, and a prediction model was established. The accuracy of each index and the established model were verified by the receiver operating characteristic (ROC) curve. RESULTS: A total of 148 patients with HBV-ACLF were enrolled in the study, 91 cases survived while 57 cases died during the 12-week period. The age, total bilirubin (TBIL), neutrophil percentage (NEUT%), hepatitis B surface antigen (HBsAg), MELD score of death group were higher than those of survival group [age (years old): 50.00 (44.50, 55.00) vs. 43.00 (34.00, 53.00), TBIL (µmol/L): 310.30 (240.70, 405.70) vs. 266.40 (184.20, 360.20), NEUT%: (74.52±13.05)% vs. (66.64±12.35)%, lgHBsAg (kU/L): 3.72 (3.29, 3.92) vs. 2.97 (2.49, 3.78), MELD score: 24.27 (19.71, 27.40) vs. 21.88 (18.83, 24.38), all P < 0.05], while albumin (ALB), total cholesterol (CHO), prothrombin activity (PTA) and alpha-fetoprotein (AFP) were lower than those of survival group [ALB (g/L): 29.80 (27.05, 31.05) vs. 30.80 (28.00, 33.90), CHO (mmol/L): 1.98 (1.50, 2.38) vs. 2.49 (2.05, 3.01), PTA: (30.37±7.09)% vs. (32.94±6.03)%, AFP (µg/L): 21.54 (9.28, 51.54) vs. 66.16 (24.50, 152.80), all P < 0.05]. Logistic regression analysis showed that NEUT%, HBsAg and AFP were independent risk factors for short-term prognosis of patients with HBV-ACLF [odds ratio (OR) was 77.843, 1.439, 0.995, respectively, all P < 0.05]. According to the results of regression analysis, the NHA-ACLF model (NEUT%+HBsAg+AFP) was established. The formula was logit (NHA-ACLF) = -5.441+5.688×NEUT%+0.430×lgHBsAg-0.005×AFP. The area under the ROC curve (AUC) of the NHA-ACLF model for pred HBV-ACLF patients was 0.790, which was better than NEUT% (AUC = 0.696), lgHBsAg (AUC = 0.670), AFP (AUC = 0.703) and MELD score (AUC = 0.640). When the cut-off value of NHA-ACLF model score was 0.459, the sensitivity was 73.7%, and the specificity was 79.1%. CONCLUSIONS: NEUT%, HBsAg and AFP are independent predictive indicator for short-term prognosis in patients with HBV-ACLF. Compared with MELD score, the risk assessment model NHA-ACLF has a greater value in predicting the short-term prognosis of patients with HBV-ACLF.

Composition of "gold juice" using an ancient method based on intestinal microecology.

OBJECTIVE: To identify potentially effective bacterial components of gold juice, a traditional Chinese medicine treatment used for fecal microbiota transplantation. METHODS: Fecal samples were collected from five healthy children (two boys and three girls; mean age, 7.52 ± 2.31 years). The children had no history of antibiotic use or intestinal microecological preparation in the preceding 3 months. Fresh fecal samples were collected from children to prepare gold juice in mid-to-late November, in accordance with traditional Chinese medicine methods, then used within 7 days. Finally, 16S rDNA sequence analysis was used to identify potentially effective bacterial components of gold juice. QIIME software was used for comparisons of microbial species among gold juice, diluent, filtrate, and loess samples. RESULTS: Microflora of gold juice exhibited considerable changes following "ancient method" processing. Microbial components significantly differed between gold juice and filtrate samples. The gold juice analyzed in our study consisted of microbes that synthesize carbohydrates and amino acids by degrading substances, whereas the filtrate contained probiotic flora, Bacteroides, and Prevotella 9. CONCLUSIONS: This study of microbial components in gold juice and filtrate provided evidence regarding effective bacterial components in gold juice, which may aid in clinical decisions concerning fecal microbiota transplantation.

[Study on the application value of MELD-Na, CLIF-C OFs, COSSH-ACLFs and NLR scoring systems in patients with hepatitis B virus related acute-on-chronic liver failure].

OBJECTIVE: To verify the accuracy of the model for end-stage liver disease-sodium (MELD-Na), chronic liver failure consortium organ failure score (CLIF-C OFs), Chinese Group on the Study of Severe Hepatitis B-Acute-on-chronic Liver Failure score (COSSH-ACLFs) and neutrophil-to-lymphocyte ratio (NLR) scoring systems in patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) and to explore its value in clinical application. METHODS: The clinical data (gender, age, disease stage) and laboratory indicators [alanine transferase (ALT), glutamate transaminase (AST), total bilirubin (TBil), albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), serum sodium (Na), prothrombin activity (PTA), international standardized ratio (INR), neutrophils count (NEU) and lymphocytes count (LYM)] of 163 patients with HBV-ACLF from July 2010 to July 2018 in Tianjin Second People's Hospital were retrospectively analyzed. After 8 weeks of admission, the patients were divided into death group (90 cases) and survival group (73 cases) according to survival status. The MELD-Na, CLIF-C OFs, COSSH-ACLFs scores and NLR of death group and survival group were compared, and a multivariate Logistic regression analysis was used to analyze the independent risk factors for HBV-ACLF. Propensity score analysis was used to demonstrate the accuracy of the method and receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of the independent risk factors. RESULTS: There were no significant differences in gender, disease stage, ALB, BUN, Cr, Na, NEU on admission between the two groups (all P > 0.05). The age [years old: 43.00 (34.00, 53.00) vs. 50.00 (42.50, 55.00)] and serum levels of ALT [U/L: 252.90 (61.43, 613.33) vs. 359.10 (115.15, 784.70)], AST [U/L: 146.15 (90.88, 449.30) vs. 237.80 (109.00, 635.05)], TBil [µmol/L: 265.10 (183.10, 347.60) vs. 307.50 (229.90, 405.55)] and INR [2.13 (1.91, 2.46) vs. 2.29 (2.02, 2.94)] in survival group were lower than those in death group and the PTA [%: 34.00 (28.00, 38.00) vs. 31.00 (24.00, 36.00)] and LYM [×109/L: 1.37 (0.72, 1.79) vs. 0.85 (0.51, 1.39)] levels were significantly higher than those in death group (both P < 0.05). The MELD-Na [17.99 (16.60, 19.63) vs. 19.16 (17.43, 20.80)], CLIF-C OFs [9.00 (8.00, 9.00) vs. 9.00 (9.00, 10.00)], COSSH-ACLFs [4.87 (4.63, 5.48) vs. 5.47 (5.07, 5.80)] and NLR [2.86 (2.21, 5.19) vs. 4.38 (2.54, 8.46)] were lower in survival group than those of the death group (all P < 0.05). Logistic regression analysis showed that CLIF-C OFs [odds ratio (OR) = 0.532, 95% confidence interval (95%CI) was 0.380-0.744, P < 0.05] and NLR (OR = 0.901, 95%CI was 0.835-0.972, P < 0.05) were the independent risk factors for the prognosis of HBV-ACLF. After propensity score matching, the data of 59 cases in each group were successfully matched, there were no significant differences in age, gender, disease stage, ALT, AST, TBil, ALB, BUN, Cr, Na, PTA, INR and NEU between the two groups (all P > 0.05), and statistically significant difference in the baseline LYM [×109/L: 1.35 (0.74, 1.73) vs. 0.81 (0.51, 1.30)] were found between the survival group and the death group. The CLIF-C OFs, COSSH-ACLFs scores and NLR were lower in survival group compared with those of the death group [CLIF-C OFs: 9.00 (8.00, 9.00) vs. 9.00 (8.00, 10.00), COSSH-ACLFs: 4.99 (4.69, 5.64) vs. 5.34 (5.03, 5.81), NLR: 2.85 (2.21, 5.72) vs. 4.38 (2.47, 10.20), all P < 0.05] and CLIF-C OFs (OR = 0.593, 95%CI was 0.401-0.878, P < 0.05) and NLR (OR = 0.593, 95%CI was 0.401-0.878, P < 0.05) were still as the independent risk factors for the prognosis of HBV-ACLF. The sensitivity of CLIF-C OFs ≥ 9 and NLR ≥ 3.14 to forecast the 8-week clinical outcome of HBV-ACLF patients were 76.7% and 67.1%, the specificity were 48.9% and 56.7%, and AUC were 0.662 and 0.623. CLIF-C OFs was combined with NLR to increase the specificity of forecasting the 8-week clinical outcome of HBV-ACLF patients to 77.8%. CONCLUSIONS: CLIF-C OFs and NLR scores are independent risk factors affecting the clinical outcome of HBV-ACLF, and have better clinical value in predicting the prognosis of HBV-ACLF. Combined application of the two scores will be more beneficial to the prognosis of HBV-ACLF.

A hybrid gene selection method based on gene scoring strategy and improved particle swarm optimization.

BACKGROUND: Gene selection is one of the critical steps in the course of the classification of microarray data. Since particle swarm optimization has no complicated evolutionary operators and fewer parameters need to be adjusted, it has been used increasingly as an effective technique for gene selection. Since particle swarm optimization is apt to converge to local minima which lead to premature convergence, some particle swarm optimization based gene selection methods may select non-optimal genes with high probability. To select predictive genes with low redundancy as well as not filtering out key genes is still a challenge. RESULTS: To obtain predictive genes with lower redundancy as well as overcome the deficiencies of traditional particle swarm optimization based gene selection methods, a hybrid gene selection method based on gene scoring strategy and improved particle swarm optimization is proposed in this paper. To select the genes highly related to out samples' classes, a gene scoring strategy based on randomization and extreme learning machine is proposed to filter much irrelevant genes. With the third-level gene pool established by multiple filter strategy, an improved particle swarm optimization is proposed to perform gene selection. In the improved particle swarm optimization, to decrease the likelihood of the premature of the swarm the Metropolis criterion of simulated annealing algorithm is introduced to update the particles, and the half of the swarm are reinitialized when the swarm is trapped into local minima. CONCLUSIONS: Combining the gene scoring strategy with the improved particle swarm optimization, the new method could select functional gene subsets which are significantly sensitive to the samples' classes. With the few discriminative genes selected by the proposed method, extreme learning machine and support vector machine classifiers achieve much high prediction accuracy on several public microarray data, which in turn verifies the efficiency and effectiveness of the proposed gene selection method.

IOUS and CE-IOUS during hepatic resection for patients with hepatocellular carcinoma in liver cirrhosis1.

PURPOSE: To retrospectively evaluate the role of intraoperative ultrasonography (IOUS) and contrast-enhanced IOUS (CE-IOUS) for the patients with hepatocellular carcinoma (HCC) undergoing hepatic resection (HR). METHODS: Twenty-one consecutive patients who had undergone HR for HCC were included in this study. The patients were subject to preoperative imaging modalities including preoperative ultrasonography (Pre-US) and preoperative contrast-enhanced ultrasonography (Pre-CEUS). All the patients then underwent intraoperative ultrasonography (IOUS) and contrast-enhanced intraoperative ultrasonography (CE-IOUS) during surgery. The visualization of primary HCC and additional lesions of all patients were analyzed. RESULTS: Twenty-one HCCs were detected during Pre-US and the remaining six lesions (28.6%) were detected during IOUS and CE-IOUS. Thus the treatment plan was changed in 28.6% of patients. Twenty-one HCCs (diameter, 0.6-3.0 cm; mean±SD, 1.98±0.85 cm) were measured on Pre-US and remeasured on IOUS (diameter, 0.9-3.3 cm; mean±SD, 2.19±0.84 cm) (p < 0.001). The 6 additional lesions consisted of three moderately differentiated HCCs, one cholangiocarcinoma (ICC), and two high-grade dysplastic nodules (DNs). The mean maximal diameter of the 6 additional lesions was 0.83 cm (range: 0.6-1.1 cm). The malignancy associated features such as capsule interruption, echo heterogeneity, hypo-echoic rim, and a nodule in nodule pattern were more often depicted on IOUS than on Pre-US (all p < 0.01). On CEUS, 19 (90.5%) of 21 HCCs were hyper-enhanced in the arterial phase and washed out from the portal phase to the late phase; the remaining two (9.5%) were hypoenhanced. On CE-IOUS, tumor vasculatures were classified as four patterns: 11 (52.4%) exhibited netlike pattern, 7 (33.3%) annular pattern, 2 (9.5%) mixed pattern, and 1 (4.8%) radial pattern. 3 mHCCs and 2 DNs of six additional nodules had similar greyscale imagining features on IOUS, but they showed different enhancement patterns on CE-IOUS. The ICC showed slightly heterogeneous enhancement during the arterial phase and hypo-enhancement during the portal phase. CONCLUSIONS: IOUS detects more lesions and the treatment plan is changed in 28.6% of patients. HCCs were larger on IOUS than on Pre-US. The typical imaging features of HCCs were better depicted on IOUS in comparison with Pre-US. CE-IOUS can catch the details of microcirculation perfusion of HCCs more sensitively than CEUS. Both IOUS and CE-IOUS were able to provide more decision information during surgery.