Improving outcomes in intracerebral hemorrhage through microglia/macrophage-targeted IL-10 delivery with phosphatidylserine liposomes.

Intracerebral hemorrhage (ICH) remains the most lethal type of stroke, and effective clinical therapies that can speed up hematoma resolution after ICH are still lacking. While the beneficial effects of IL-10 on ICH recovery have been demonstrated, the clinical translation of IL-10 requires effective delivery methods by which sufficient IL-10 can be delivered to ICH-affected regions in the brain. Here we report the use of a phosphatidylserine (PS) liposome (PSL)-based nanoparticle system for microglia/macrophage-targeted delivery of IL-10 in ICH. We first prepared IL-10-conjugated PSL (PSL-IL10) and characterized their immunomodulating effects in vitro. Then we evaluated the therapeutic effects, including hematoma absorption, short-term outcomes, and neuroinflammation, of intranasally administered PSL-IL10 (3 µg IL-10 per mouse, 2 h post-ICH) in a collagenase-induced ICH mouse model. We also isolated microglia/macrophages from the mouse brains with ICH to analyze their morphology, phagocytosis ability, and polarization. Our study reveals that, 1) PSL-IL10 treatment resulted in significantly improved outcomes and accelerated hematoma resolution in the acute phase of ICH; 2) PSL-IL10 inhibited glial activation and down-regulated pro-inflammatory cytokine production; 3) PSL-IL10 induced Iba1+ cells with a stronger phagocytosis ability; 4) PSL-IL10 activated STAT3 and upregulated CD36 expression in microglia/macrophage. These findings collectively show that PSL-IL10 is a promising nanotherapeutic for effectively ameliorating ICH.

High expression of FABP4 in colorectal cancer and its clinical significance.

OBJECTIVES: To investigate the relationship between the fatty acid-binding protein 4 (FABP4) and colorectal cancer (CRC). METHODS: Using an enzyme-linked immunosorbent assay (ELISA), we measured the expression of FABP4 in plasma of 50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls. The content of the visceral fat area (VFA) as seen with abdominal computed tomography (CT) scanning was measured by ImageJ software. The expression levels of FABP4, E-cadherin, and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry. RESULTS: The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group (22.46 vs. 9.82 ng/mL; P<0.05). The concentration of plasma FABP4 was related to the tumor, node, metastatis (TNM) stage and lymph node metastasis and was independent of age, body mass index (BMI), tumor size and location, and the degree of differentiation of CRC. The concentration of plasma FABP4 was positively correlated with high VFA and lipoprotein-a (LPA) (P<0.05); but it was not correlated with total cholesterol (TG), total triglyceride (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), or apolipoprotein AI (Apo-AI). The expression of FABP4 protein in CRC tissues was positively correlated with the degree of CRC differentiation, tumor stage, and lymph node metastasis. The level of FABP4 protein was negatively correlated with E-cadherin protein (r=-0.3292, P=0.0196) and positively correlated with Snail protein (r=0.5856, P<0.0001). CONCLUSIONS: High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients. FABP4 protein was highly expressed in CRC tissues and associated with TNM stage, differentiation, and lymph node metastasis of CRC. The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression, suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition (EMT).

FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport.

BACKGROUND: The prognosis of colon cancer is poor for metastasis, while the mechanism, especially adipocytes related, is not yet clear. The purpose of this study is to determine the effects of fatty acid binding protein 4 (FABP4), a transporter for lipids, on colon cancer progression. METHODS: The distribution of lipids and FABP4 was tested in the colon cancer tissues and adjacent normal tissues, and their relationship was also verified in vitro. Experiments about cellular invasion, migration and proliferation were performed to detect the impacts of FABP4 on the biological behaviors of colon cancer, and the positive results were checked in vivo. Meanwhile, the regulatory role of FABP4 in the energy and lipid metabolism was evaluated by the levels of triglyceride, ATP, LDH, glycerol and NEFA. At last, GO and KEGG analysis based on FABP4 overexpressed cells was performed, and the AKT pathway and epithelial-mesenchymal transition (EMT)-related proteins were determined by Western blot. RESULTS: Higher accumulation of lipids and stronger FABP4 transcription were observed in colon cancer tissues. Having been incubated with adipose tissue extract and overexpressed FABP4, colon cancer cells demonstrated enhanced lipid accumulation. In functional experiments, co-culture with adipose tissue extract significantly enhanced the invasion and migration of colon cancer cells, as well as the energy and lipid metabolism, and all these processes were reversed by FABP4 inhibitor. In addition, the metastasis of FABP4-overexpressed colon cancer cells was also significantly enhanced in vitro and in vivo. In terms of mechanism, the bioinformatics analysis showed that FABP4 was enriched in 11 pathways related to metabolic processes in FABP4 overexpressed cells. Finally, FABP4 overexpression improved EMT progression of colon cancer, as evidenced by the upregulation of Snail, MMP-2 and MMP-9, the downregulation of E-cadherin. The expression of p-Akt was also elevated. CONCLUSION: FABP4 overexpression could increase FAs transport to enhance energy and lipid metabolism, and activate AKT pathway and EMT to promote the migration and invasion of colon cancer cells.

Intraarticular Injection of Allogenic Mesenchymal Stem Cells has a Protective Role for the Osteoarthritis.

BACKGROUND: Researchers initially proposed the substitution of apoptotic chondrocytes in the superficial cartilage by injecting mesenchymal stem cells (MSCs) intraarticularly. This effect was termed as bio-resurfacing. Little evidence supporting the treatment of osteoarthritis (OA) by the delivery of a MSC suspension exists. The aim of this study was to investigate the effects of injecting allogenic MSCs intraarticularly in a rat OA model and to evaluate the influence of immobility on the effects of this treatment. METHODS: We established a rat knee OA model after 4 and 6 weeks and cultured primary bone marrow MSCs. A MSC suspension was injected into the articular space once per week for 3 weeks. A subgroup of knee joints was immobilized for 3 days after each injection, while the remaining joints were nonimmobilized. We used toluidine blue staining, Mankin scores, and TdT-mediated dUTP-biotin nick end labeling staining to evaluate the therapeutic effect of the injections. Comparisons between the therapy side and the control side of the knee joint were made using paired t-test, and comparisons between the immobilized and nonimmobilized subgroups were made using the unpaired t-test. A P value < 0.05 was considered significant. RESULTS: The three investigative approaches revealed less degeneration on the therapy sides of the knee joints than the control sides in both the 4- and 6-week groups (P < 0.05), regardless of immobilization. No significant differences were observed between the immobilized and nonimmobilized subgroups (P > 0.05). CONCLUSIONS: Therapy involving the intraarticular injection of allogenic MSCs promoted cartilage repair in a rat arthritis model, and 3-day immobility after injection had little effect on this therapy.

[Imaging reasons for periprosthetic femoral fractures during the operation of total hip arthroplasty with anatomic prosthesis].

OBJECTIVE: To explore the imaging reasons for periprosthetic femoral fractures during the operation of total hip arthroplasty with anatomic prosthesis. METHODS: The fracture group consisted of 7 cases with periprosthetic femoral fracture (PPFF) and the non-fracture group 21 cases without PPFF during the operation of total hip arthroplasty (THA) among the 144 cases of primary THA with anatomic prosthesis. The preoperative plain films of hip joint were taken to calibrate the Sharp's angle, centre edge (CE) angle, femoral neck shaft angle, femoral anteversion angle of neck, bowing angle of proximal femoral shaft part, width of narrowest part in proximal femoral shaft. For each case, surgical details, age, height and weight were recorded. The results were analyzed with independent sample t test by software SPSS 17.0. RESULTS: No significant difference existed in general situation, Sharp's angle and CE's angle between two groups. And there were significant differences in femoral neck shaft angle (P = 0.040), femoral anteversion angle of neck (P = 0.026), bowing angle of proximal femoral shaft part (P = 0.024), width of narrowest part in proximal femoral shaft (P = 0.021). CONCLUSION: Dysplasia of proximal femur is a major cause of periprosthetic femoral fracture during the operation of total hip arthroplasty with anatomic prosthesis.

Improvement of intertrochanteric bone quality in osteoporotic female rats after injection of polylactic acid-polyglycolic acid copolymer/collagen type I microspheres combined with bone mesenchymal stem cells.

PURPOSE: Osteoporosis mainly involves cancellous bone, and the spine and hip, with their relatively high cancellous bone to cortical bone ratio, are severely affected. Studies of bone mesenchymal stem cells (BMSCs) from osteoporotic patients and animal models have revealed that osteoporosis is often associated with reduction of BMSCs' proliferation and osteogenic differentiation. Our aim was to test whether polylactic acid-polyglycolic acid copolymer(PLGA)/collagen type I(CoI) microspheres combined with BMSCs could be used as injectable scaffolds to improve bone quality in osteoporotic female rats. METHODS: PLGA microspheres were coated with CoI. BMSCs of the third passage and were cultured with PLGA/CoI microspheres for seven days. Forty three-month-old female non-pregnant SD rats were ovariectomized to establish osteoporotic animal models. Three months after being ovariectomized, the osteoporotic rats were randomly divided into five groups: SHAM group, PBS group, cell group, microsphere (MS) group, and cell+MS group. Varying materials were injected into the intertrochanters of each group's rats. Twenty rats were sacrificed at one month and three months post-op, respectively. The femora were harvested in order to measure the intertrochanteric bone mineral density (BMD) with DEXA and trabecular thickness (Tb.Th), percentage of trabecular area (%Tb.Ar), bone volume fraction (BV/TV) and trabecular spacing (Tb.Sp) with Micro CT. One-way ANOVA and Kruskal-Wallis tests were used. RESULTS: BMSCs seeded on PLGA/CoI microspheres had a nice adhesion and proliferation. At one month post-op, the BMD (0.33 ± 0.01 g/cm(2)), Tb.Th (459.65 ± 28.31 µm), %Tb.Ar (9.61 ± 0.29 %) and Tb.Sp (2645.81 ± 94.91 µm) of the cell+ MS group were better than those of the SHAM group and the cell group. At three months post-op, the BMD (0.32 ± 0.01 g/cm(2)), Tb.Th (372.81 ± 38.45 µm), %Tb.Ar (6.65 ± 0.25 %), BV/TV (6.62 ± 0.25 %) and Tb.Sp (1559.03 ± 57.06 µm) of the cell + MS group were also better than those of the SHAM group and the cell group. CONCLUSION: The PLGA/CoI microspheres combined with BMSCs can repair bone defects more quickly. This means that PLGA/CoI microspheres combined with BMSCs can promote trabecular reconstruction and improve bone quality in osteoporotic rats. This scaffold can provide a promising minimally invasive surgical tool for enhancement of bone fracture healing or prevention of fracture occurrence which will in turn minimize complications endemic to patients with osteoporosis.

[The etiologies and prevention of patellar instability after un-resurfaced total knee arthroplasty].

OBJECTIVE: To investigate the etiologies and prevention of patellar instability after total knee arthroplasty (TKA). METHODS: From September 1997 to April 2005, 94 patients (105 knees) underwent TKA without patellar resurfacing. All of them were osteoarthritis. Ten patients (14 knees) were performed with Rotation Knee (RK) prostheses. Forty patients were performed with mobile bearing TACK prostheses, and 44 patients with GEMINI prostheses. Subluxation and tilt of patella were evaluated by X-rays before or after operation. RESULTS: The incidence of patellar instability after operation was 28.6% in patients who had genu valgus deformity, and was 29.5% in whom had patellar instability preoperative. The incidence of patellar instability in RK, TACK, and GEMINI group was 28.6%, 20.9%, and 16.7% respectively after operations. Four patients had obvious femoral or tibial components malrotation. CONCLUSIONS: The etiologies of patellofemoral instability include pre-operative conditions, prosthetic design, and improper positioning of the prosthetic component. So the suitable component design and skillful operative technique will help the surgeon to avoid this complication.

Augmentation of pedicle screw fixation strength using an injectable calcium sulfate cement: an in vivo study.

STUDY DESIGN: An in vivo landrace model of cement augmentation of pedicle screw was established, and axial pull-out tests and histological analysis were performed. OBJECTIVE: To investigate the long-term in vivo biomechanical performance of pedicle screws augmented with calcium sulfate cement. SUMMARY OF BACKGROUND DATA: Little information is available on the long-term biomechanical performance of pedicle screws augmented with calcium sulfate cement in vivo. METHODS: Ten pedicle screws were implanted into the lumbar vertebrae of 15 adult females landraces weighing 105 to 115 kg. The pedicle screws were augmented with Polymethyl methacrylate (PMMA), augmented with the calcium sulfate cement, or not augmented. The landraces were randomized into 3 study periods of day 1, 6 weeks, and 12 weeks. At the end of the assigned study periods, the animals were killed and axial pull-out tests and histological analyses were conducted on the isolated specimen vertebrae. RESULTS: No significant difference was found among the 1-day, 6-week,and 12-week control group (P > 0.18), no significant difference was found among the 1-day, 6-week and 12-week PMMA group (P > 0.59), and no significant difference was found among the 1-day, 6-week and 12-week calcium sulfate group (P > 0.27). The maximum POS of the PMMA groups was significantly greater than that of the calcium sulfate groups (P < 0.002), the maximum POS of the calcium sulfate groups was significantly greater than that of the control groups (P < 0.004). Histologically progressive absorption of the calcium sulfate was evident. The bone walls around the screws in the 12-week calcium sulfate group were statistically significantly thicker than that of the 12-week control group and that of the 12-week PMMA group. CONCLUSION: Results of this study demonstrate that the injectable calcium sulfate cement can significantly improve the immediate POS of pedicle screw fixation, and this effect can be maintained even if the calcium sulfate cement has been absorbed completely, which may result from that the calcium sulfate cement resorption paralleled bone ingrowth.

[Surgical treatment for degenerative lumbar scoliosis associated with spinal stenosis].

OBJECTIVE: To study surgical techniques for degenerative lumbar scoliosis associated with lumbar stenosis and evaluate their clinical significane. METHODS: Thirty-two patients with degenerative lumbar scoliosis associated with spinal stenosis were treated by techniques of posterior lumbar interbody fusion or posterolateral fusion and pedicle screws. There were 18 male and 14 female with 56.8 years old on the average (ranging from 49 to 75 years). There were no evident change of lumberlordosis in 15 cases, and lumber lordosis were obvious loss associated with lumbar subluxation in 17 cases. The correcting, the improvement of back and leg pain, complications and followed-up results were analyzed retrospectively. RESULTS: Thirty-two cases were followed-up for 6 to 39 months (the average time of 13 months). The average correction rate of scoliosis was 58.0% and the rate of pain relief was (80.2 +/- 5.8)%. There were two cases of dura sac laceration, two cases of nerve roots injury and a case of pseudoarthritis. During followed-up, correction rate and height of disc spaces were not lost. Shift of interbody cages were no displaced; all the internal fixation got well fusion and the rate of fusion for the bone graft was 96.9%. CONCLUSION: Posterior pedicle screws combined with interbody fusion or posterolateral fusion is a safe and effective surgical treatment for degenerative lumbar scoliosis associated with lumbar stenosis.

[Change in the joint line after total knee arthroplasty].

OBJECTIVE: To investigate the change in joint line after knee arthroplasty. METHODS: A total of 43 patients had 25 primary cruciate-retaining total knee replacements (Link Gemini MKII) and 25 rotational knee replacements (Link Endo-Model Rotational Knee System) sacrificing collateral ligaments and cruciate ligaments. Lateral radiographs were made both preoperatively and postoperatively. The change in the relative position of the joint line preoperatively and postoperatively was defined as the difference between the perpendicular distance from the weight-bearing surface of the tibial plateau to the tibial tubercle of the natural tibia (JL) and perpendicular distance from the weight-bearing surface of the prosthetic tibial component to the tibial tubercle (JL'). This distance was JL'-JL. The statistical differences between 2 groups were analyzed. RESULTS: The distance of JL'-JL was 2.0 mm (-1.3 - 7.2 mm) in 22 patients with Gemini replacement, whereas the distance was 3.1 mm (-1.5 - 12.3 mm) in the other patients with rotational knee system. The difference was significant. CONCLUSIONS: If the collateral ligaments and cruciate ligaments are removed during the knee replacement operations, the prosthetic joint line is likely to be malpositioned proximally. The fibular styloid and medial or lateral epicondylar reference points can be used to determine proper position of the joint line during operation.

[The manufacture of pelvic mirror physical model using rapid prototyping].

OBJECTIVE: To study the manufacture of pelvic mirror physical model using rapid prototyping and the accuracy of the models. METHODS: The pelvic CT images were acquired by spiral CT thin slice scanning, and the slicing data of pelvis were created from these CT images by computer image-processing. Then the pelvic mirror physical model was manufactured using rapid prototyping. The model of a cadaver pelvis and the pelvic model of an experimental dog were manufactured respectively using the method above, and the accuracy of the models were examined. RESULTS: The model of the cadaver pelvis manufactured with this method was very similar to the cadaver pelvis. So was the pelvic model of the experimental dog. CONCLUSION: The manufacture of pelvic mirror physical model using rapid prototyping was feasible, and the models were quite accurate.