Immunogenicity and protective efficacy of Ag85A and truncation of PstS1 fusion protein vaccines against tuberculosis.

Tuberculosis (TB) is an important public health problem, and the One Health approach is essential for controlling zoonotic tuberculosis. Therefore, a rationally designed and more effective TB vaccine is urgently needed. To enhance vaccine efficacy, it is important to design vaccine candidates that stimulate both cellular and humoral immunity against TB. In this study, we fused the secreted protein Ag85A as the T cell antigen with truncated forms of the mycobacterial cell wall protein PstS1 with B cell epitopes to generate vaccine candidates, Ag85A-tnPstS1 (AP1, AP2, and AP3), and tested their immunogenicity and protective efficacy in mice. The three vaccine candidates induced a significant increase in the levels of T cell-related cytokines such as IFN-γ and IL-17, and AP1 and AP2 can induce more balanced Th1/Th2 responses than AP3. Strong humoral immune responses were also observed in which the production of IgG antibodies including its subclasses IgG1, IgG2c, and IgG3 was tremendously stimulated. AP1 and AP2 induced early antibody responses and more IgG3 isotype antibodies than AP3. Importantly, the mice immunised with the subunit vaccine candidates, particularly AP1 and AP2, had lower bacterial burdens than the control mice. Moreover, the serum from immunised mice can enhance phagocytosis and phagosome-lysosome fusion in macrophages, which can help to eradicate intracellular bacteria. These results indicate that the subunit vaccines Ag85A-tnPstS1 can be promising vaccine candidates for tuberculosis prevention.

[Design of combined lower limb elastic compression device and comparative study with elastic bandage].

OBJECTIVE: To compared with the modified Robert Jones bandage of 3M elastic bandage, to evaluate the fitness, convenience, safety and comfort of the modular combination lower limb elastic compression device. METHODS: Forty healthy adult college students, including 28 males and 12 females, aged 16 to 25 (20.3±2.2) years old and weighing 40 to 81 (60.4±20.2) kg, were randomly divided into two groups with 40 samples in each group. According to the body surface parameters of Chinese lower limbs and guided by the concept of modularization, a group of modular combined lower limb elastic compression device was designed. Each module was combined to evaluate the fitness of the modular combined compression device in thelength and circumference of the lower limbs. The left and right lower limbs were randomly paired and divided into groups, with 40 samples in each group. The convenience of the operation time, adjustment times and required time were compared between two groups. The safety of the two groups after 24 hours of application of pressure injury was compared. The subjective pain feeling changes within 24 hours were recorded by visual analogue scale (VAS) to evaluate the comfort. RESULTS: The device was composed of several elastic compression outer lining modules with different length and width of 15 cm, an inner lining module for buffering, positioning and attaching the main body, and an elastic ankle compression module. The length of the elastic compression outer lining module covers the circumference of the human lower limbs. The length of a single outer lining module increased from 15 cm to 80 cm every 5 cm interval, and the length of a single inner lining module increased from 62 cm to 83 cm every 3 cm interval. After the modules were selected and combined, the length and circumference of the lower limbs can reach 100% fitness. The operation time of the first placement(118.23±7.33) s and re operation(60.08±5.88) s of experimental group were significantly shorter than those of control group (164.68±8.93) s and re operation (131.23±7.91) s. The adjustment times (3) and operation time (3.50±0.71) s of experimental group were significantly shorter than those of control group(11)and operation time(139.00±5.66) s (P<0.05), but there was no significant difference between two groups (P>0.05). The VAS score of experimental group was significantly lower than that of control group at each time point (P<0.01). CONCLUSION: The modular combined elastic compression device has good fitness, better placement and flexible adjustment, convenience and safety, and better comfort than modified Robert Jones bandage of 3M elastic bandage.

Down-Regulation of Ribosomal Protein RPS21 Inhibits Invasive Behavior of Osteosarcoma Cells Through the Inactivation of MAPK Pathway.

OBJECTIVE: The goal of our present study was to explore the expression level, biological function, and underlying molecular mechanism of ribosomal protein s21 (RPS21) in human osteosarcoma (OS). METHODS: Firstly, we evaluated the expression of RPS21 in OS tissue samples based on the Gene Expression Omnibus (GEO) datasets and also measured the RPS21 expression of OS cell lines (MG63, and U2OS) by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA interference method was used to reduce the expression of RSP21 in the OS cells. Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, and transwell assays were conducted to measure the proliferation, migration, and invasion of OS cells. The mitogen-activated protein kinase (MAPK) pathway-related proteins levels were examined by Western blot. RESULTS: Our analyses showed that the expression of RPS21 was significantly increased in OS, compared with normal samples. Upregulation of RPS21 was associated with worse outcomes of OS patients. Knockdown of RPS21 suppressed OS cell proliferation, colony-forming ability, migration, and invasion capacities. Moreover, down-regulation of RPS21 inactivated the MAPK signaling pathway. CONCLUSION: RPS21 plays an oncogenic candidate in OS development via regulating the activity of MAPK pathway; therefore, it may serve as a novel therapeutic target for OS treatment.

Effect of Cholecystectomy on the Occurrence of Knee Osteoarthritis.

OBJECTIVE: To evaluate the effect of cholecystectomy on the occurrence of knee osteoarthritis (KOA). METHODS: The present study was a case-control study with a retrospective, cross-sectional, and longitudinal study design. The clinical data for knee osteoarthritis in the Second Hospital of Shanxi Medical University from January 2016 to September 2018 was analyzed. Clinical data, including gender, age, height, weight, smoking, alcohol abuse, prior medical history, and previous surgical history, were recorded. A logistic regression model was used for the univariate and multivariate analysis. RESULTS: A total of 1659 patients with KOA (KOA group) and 1195 limb fracture patients (control group) were included in this study. Among the 1659 patients with KOA, 388 patients were male and 1271 were female, while among the 1195 patients in the control group, 638 patients were male and 557 patients were female. The period between cholecystectomy and knee osteoarthritis onset ranged from 0.5 years to 17 years; the average interval time was 8.73 ± 2.11 years. The age at disease onset was significantly older when compared to the control group, while the body mass index in the KOA group was significantly higher when compared to the control group (P < 0.05). There were 97 patients undergoing cholecystectomy in the KOA group and there were 15 patients undergoing cholecystectomy in the control group. The proportion of cholecystectomy in the two groups was statistically significant. After the univariate analysis, there was a statistically significant difference in distribution between the two groups (P < 0.05). The multivariate logistic regression analysis revealed that there was a significant difference in the distribution of these two groups (P < 0.05), indicating that cholecystectomy is associated with the occurrence of KOA. CONCLUSION: There is a close relationship between cholecystectomy and KOA. However, the specific mechanism remains unknown and should be further researched.

The effectiveness of a self-made modular elastic compression device for patients with a fracture of the tibia and fibula.

BACKGROUND: To evaluate the effectiveness of a self-made modular elastic compression device for patients with a fracture of the tibia and fibula. METHODS: Fifty-nine healthy adult patients with a unilateral fracture of the tibia and fibula were randomly divided into an experimental group and a control group. The experimental group was given the self-made combined elastic compression device for the compression treatment of the affected limbs after the operation. The main endpoints included the convenience, safety, and effectiveness of the self-made modular elastic compression device for patients with a fracture of the tibia and fibula. RESULTS: There were 29 cases in the experimental group and 30 cases in the control group. There were no significant differences between the two groups in the general data: age, gender, fracture site, and cause of injury. The preoperative swelling elimination time was 3.3 ± 1.2 days, and the postoperative swelling elimination time was 3.1 ± 1.4 days in the experimental group; the preoperative swelling elimination time was 6.3 ± 1.2 days, and the postoperative swelling elimination time was 7.3 ± 1.2 days in the control group. The preoperative and postoperative swelling degree in the experimental group was shorter than those in the control group. The difference in the postoperative detumescence time between the experimental group (3.1 ± 1.4 days) and the control group (7.3 ± 1.2 days) was significant, and the total hospital stay was 8.1 ± 1.5 days in the experimental group and 13 ± 2.5 days in the control group with a statistical significance of P < 0.05. The change of discharge hemoglobin volume (11.2 ± 6.5 g/L) of the experimental group was lower than that of the control group (3.5 ± 1.2 days), the total drainage volume was 260 ± 50 ml, and the change of admission and discharge hemoglobin volume was 30.3 ± 10.4 g/L. Specifically, although the difference in the average hospital stay between the two groups was statistically significant, the difference was only 1 day, and the clinical difference was not significant. However, in the change of the cumulative drainage volume and hemoglobin volume, the experimental group that was given compression therapy was significantly lower than the control group with a statistical significance (P < 0.05). The pressure injury (4 cases) in the experimental group was significantly lower than that in the control group (8 cases) (P < 0.05). CONCLUSION: A modular combined elastic compression device in patients with a tibial and fibular fracture can significantly accelerate a patient's rehabilitation, shorten the hospital stay, reduce blood loss, relieve the patient's pain, and relieve the patient's social-economic burden during recovery.

Correlation between an ABO Blood Group and Primary Femoral Head Necrosis: A Case-Control Study.

OBJECTIVE: To investigate the relationship between primary femoral head necrosis (ONFH) and an ABO blood group. METHODS: This study was a retrospective case-control trial. An analysis of the clinical data of an ABO blood group with 516 patients (case group) with ONFH and 489 limb-fracture patients (control group) without previous hip pain was obtained from the Second Hospital of Shanxi Medical University from November 2015 to November 2018. The clinical data included gender, age, height, weight, a history of smoking, alcohol abuse, prior medical history, hormone use, and ABO blood type. A logistic regression model was used for univariate and multivariate analysis. RESULTS: From November 2015 to November 2018, there were 267 males and 249 females in the 516 cases of ONFH in the case group. The control group included 289 males and 200 females. In terms of age, the average age of the case group was significantly lower than that of the control group. In terms of body mass index (BMI), the BMI of the case group was significantly higher than that of the control group (P < 0.05). From the previous medical history of patients in the two groups (coronary heart disease, hypertension, cerebrovascular disease, diabetes, and peripheral vascular disease), there was no significant difference between the two groups from a statistical perspective (P < 0.05). However, according to the risk factors of ONFH (smoking, alcohol abuse, hyperlipidemia, and hormone-use history), there were significant differences between the case group and the control group. There was no statistical difference in the quantitative distribution ratio of the four blood types - A, B, O, and AB - between the case group and the control group. The outcomes of logistic multiple regression analysis presented that there was no significant correlation between the occurrence of ONFH and blood type A, B, AB, and O (P > 0.05). However, there are significant differences in the disease progression between the different blood types. There was a significant difference in the progression of disease between type A and type O. Among them, patients with ONFH and type A blood had the fastest progression with an average of 2.318 years, and the slowest progression was found in type O blood with an average of 5.15 years. CONCLUSIONS: The ABO blood group has no correlation with the occurrence of ONFH, but the ABO blood type is closely related to the disease progression of ONFH.

[Application of passive image-free navigation system for total knee arthroplasty].

Total knee arthroplasty(TKA) has been the final clinical treatment of knee osteoarthritis at the final stage, postoperative limb and prosthesis alignment restoration directly affect clinical effect. In recent years, computer-assisted surgery has been used in TKA and obtained satisfied results. There paper has investigated that the use of computer-assisted systems could improve soft tissue balance after TKA, improve accuracy of installation of prosthesis, recover limb alignment and decrease intro-blood loss, postoperative fat embolism. Although computer-assisted navigation is not mainstream, with the continuous improvement of technology and innovation, the computer-assisted surgery could exert a more important role in TKA, and considerably beneficial effect on improvement of postoperative clinical effects.

Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation.

Chemokine stromal cell-derived factor-1 (SDF-1) is a powerful chemoattractant for the localization of CXCR4-positive bone marrow mesenchymal stem cells (BMSCs) into the bone marrow. We studied the effects of SDF-1 on the cartilage defect repair by recruiting BMSCs and promoting its chondrogenic differentiation in vitro and in vivo. Chemotaxis analysis with Transwell plate showed that SDF-1 could recruit BMSCs through SDF-1/CXCR4 axis. Real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and Western blot results suggested that the levels of type II collagen and GAG were increased after incubating BMSCs with SDF-1 compared with the without SDF-1 group. More positive BrdU-labeled BMSCs were detected at the cartilage defect region in the SDF-1 + poly [lactide-co-glycolide] (PLGA) scaffold group (SP) in which those animals showed a smooth and transparent cartilage tissue with a strong staining of toluidine blue and type II collagen compared with the no-SDF-1 groups. ICRS score suggested that the repair effect in the SDF-1 + PLGA-treated animals was improved compared with PLGA scaffold group alone at 4 and 8 weeks after surgery; the repair effect from the SDF + PLGA-treated animals was significantly improved compared with the PLGA alone at 12 weeks after surgery. Our in vitro and in vivo results indicated the following: (1) SDF-1 could recruit the BMSCs into cartilage defect area. (2) SDF-1 induces BMSCs expressing type II collagen and GAG, which may accelerate the BMSCs transforming into chondrocytes under the cartilage microenvironment in vivo. (3) PLGA scaffold attached with SDF-1 remarkably promoted the cartilage defect repairing. The defected cartilage was filled with transparent cartilage 12 weeks after the surgery, which shared a similar structure with the adjacent normal cartilage. Taken together, this research provides a new strategy for cartilage defect repairing.

Nutrition and degeneration of articular cartilage.

PURPOSE: To determine the importance of synovial fluid (SF) or subchondral bone marrow (BM) as nutrition sources in cartilage degeneration. METHODS: Ninety-five-month-old male rabbits were randomly divided into 5 groups according to sources of nutrition: SFBM-both; BM-only; SF-only; None-SFBM; and Free plug (unrestricted). Nutrition to 4-mm-diameter cylindrical osteochondral plugs created on the trochlea of the distal femurs was obstructed by Polyvinyl Chloride (PVC) cap. Cartilage changes were assessed after 4, 8, and 12 weeks by histology, immunohistochemistry, and real-time PCR. RESULTS: Cartilage in the BM-only group suffered the greatest damage, followed by the None-SFBM and SF-only groups. Apoptosis was increased in the BM-only and None-SFBM groups compared with others. Cartilage was significantly thinner at all time points in the BM-only and None-SFBM groups when compared with SFBM-both and Free plug, whereas in the SF-only group, this difference occurred after 8 weeks. Compared with SFBM-both and Free plug, expression of collagen II and aggrecan mRNAs in all groups was decreased but MMP-3 increased, respectively. CONCLUSION: Our data indicate that SF-derived nutrition is the dominant source of sustenance for adult cartilage structure and function. Cartilage damage is observed when the only nutrition source is the BM.

A randomized multicenter phase II clinical trial of mitoxantrone-loaded nanoparticles in the treatment of 108 patients with unresected hepatocellular carcinoma.

Previous studies have demonstrated that intravenous administration of mitoxantrone-loaded polybutylcyanacrylate nanoparticles (DHAD-PBCA-NPs) could allow increased cytotoxicity in hepatic tumors. Therefore, we evaluated the activity and toxicity of DHAD-PBCA-NPs and DHAD injection in individuals with unresected hepatocellular carcinoma. For the DHAD-PBCA-NPs arm the objective response rate was 10.5%, 61.4% patients had stable disease, and 28.1% patients had progression. For the DHAD injection arm no objective response was found, 45.1% patients had stable disease, and 54.9% patients had progression. There were significant differences in both stable disease and progressive disease between the two groups (P< .05). The median survival periods of the DHAD-PBCA-NPs group and the DHAD injection group were 5.46 months and 3.23 months, respectively. Leukopenia was observed in 47.4% and 74.5% of the DHAD-PBCA-NPs arm and the DHAD injection arm, respectively. Meanwhile, anemia was noted in 65% and 37.3% of the DHAD-PBCA-NPs arm and the DHAD injection arm, respectively. FROM THE CLINICAL EDITOR: Intravenous administration of mitoxantrone-loaded polybutylcyanacrylate nanoparticles (DHAD-PBCA-NPs) allows increased cytotoxicity in hepatic tumors and prolonged the median survival periods to 5.46 months compared to 3.23 months in controls.

[Evaluation of topotecan combined with cisplatin in the treatment of small cell lung cancer].

BACKGROUND: To evaluate the effects and toxicities of topotecan combined with cisplatin in the treatment of small cell lung cancer (SCLC). METHODS: Twenty-six patients with SCLC diagnosed by pathologic or cytologic examination were treated with topotecan 1.25 mg/(m²*d) on days 1-5 and cisplatin 25 mg/(m²*d) on days 1-3. The chemotherapy was repeated every 21 days as a cycle. RESULTS: Out of 26 evaluable patients, 3 achieved complete response and 11 achieved partial response with an overall response rate of 53.8%. The response rates were 75.0% and 35.7% in 12 previously untreated patients and 14 patients with prior chemotherapy, respectively. In addition, one of eight refractory patients and two of five patients with brain metastasis got partial responses. The median survival period was 27 weeks and one-year survival rate was 38.5%. Myelosuppression was the major dose-limiting toxicity. CONCLUSIONS: Topotecan combined with cisplatin is effective for SCLC and it toxicity is tolerable.