Objective To observe and explore the effects of adipose-derived stem cells (ADSCs)-hyaluronic acid (HA) composite on heal ing of wound combined with radiation injury. Methods The ADSCs were harvested from the fat tissue in groin of 10 inbred Sprague Dawley (SD) rats and were isolated and cultured by enzyme digestion. The ADSCs-HA composite wasprepared with ADSCs (5 × 106 cells/mL) at passage 6 and HA (10 mg/mL). Thirty inbred SD rats, 15 males and 15 females, were randomly divided into groups A (n=10), B (n=10), and C (n=10). A 2 cm × 2 cm full-thickness skin defect was made on the rat back before 20 Gy 60Co radiation exposure. One week after debridement, wounds were treated by petrolatum gauze in group A as the control group, by HA (0.4 mL) and petrolatum gauze in group B, and by ADSCs-HA composite (0.4 mL) and petrolatum gauze in group C. The microvessel density (MVD) and the distribution of CD90 positive cells were observed at 1st, 2nd, 3rd, and 4th weeks. Results The wound heal ing was slower, and wound did not heal at 4th week and still filled with granulation tissue in group A; the wound heal ing of group B was faster than that of group A, and the wound did not heal completely with depression in the center at 4th week; the wound healed completely with epidermil izated surface and no obvious depression at 4th week in group C. The histological observation showed that MVD was significantly higher in group C than in groups A and B at the 1st, 2nd, and 3rd weeks (P lt; 0.05), and in group B than in group A at the 3rd week (P lt; 0.05); MVD was significantly higher in groups B and C than in group A (P lt; 0.05), but no significant difference was found between groups B and C (P gt; 0.05) at 4th week. No CD90 positive cell was found in groups A and B; CD 90 positive cells were observed in group C and gradually decreased with time. Conclusion ADSCs-HA composite can accelerate heal ing of wound combined with radiation injury by promoting and controll ing wound angiogenesis.
Objective To investigate the change of the femoral offset and hip center of rotation (COR) after using Jumbo cups in total hip arthroplasty (THA) revision. Methods The clinical data of 23 patients who underwent THA revision using Jumbo cups between January 2010 and May 2015 were retrospectively analyzed. Morselized bone graft was performed on 8 cases, morselized bone graft combined with structural bone graft on 10 cases. There were 10 males and 13 females, aged 65.4 years on average (range, 51-77 years). The disease duration was 1-24 years (mean, 8.57 years). The reasons for revision included aseptic loosening in 21 cases and periprosthetic infection in 2 cases. The Harris hip score and visual analogue scale (VAS) were 43.04±5.05 and 5.70±0.97 before operation respectively. According to the Paprosky acetabular defect classification, there were 5 cases of type I, 5 cases of type II A, 3 cases of type II B, 6 cases of type II C, and 4 cases of type III A. The X-ray films showed that the femoral offset was (40.65±4.09) mm for normal side and was (44.04±5.08) mm for affected side at preoperation, showing significant difference (t=4.098,P=0.000). Ten patients underwent femoral offset reconstruction (43.48%) but 13 patients did not (56.52%) before operation. The COR was reconstructed in 10 cases (43.48%); COR elevation was observed in 11 cases (47.83%), and COR decline in 2 cases (8.69%) before operation. Results Primary healing of incision was obtained in all patients, with no complication of infection, vascular injury, deep vein thrombosis, dislocation of the joint, or fracture around prosthesis. All the patients were followed up 12-76 months (mean, 22.48 months). The Harris hip score and VAS were 82.09±4.53 and 0.74±0.62 at 1 year after operation respectively, showing significant differences when compared with preoperative scores (t=37.831,P=0.000;t=22.318,P=0.000). The X-ray films showed that the femoral offset was (43.87±3.57) mm for affected side at 1 year after operation, showing no significant difference when compared with preoperative one (t=0.250,P=0.805), but significant difference was found between affected side and normal side (t=5.591,P=0.000). The femoral offset was restored in 16 patients (69.57%) and was not restored in 7 patients (30.43%) after operation. The COR was restored in 15 patients (65.22%) and was not restored in 8 patients (34.78%). Conclusion Using Jumbo cups or combined with morselized or structural bone graft is effective in restoring hip COR and femoral offset at the maximum limit in THA revision, with good short-term outcome and improved stability of acetabular prosthesis.
Objective To construct and verify a genetically engineered mouse model which is similar to clinical sporadic colorectal cancer and simultaneously expresses KrasLSL-G12D/- and Smad4loxp/loxp genes. Methods The Krastm4Tyj/J mouse and Smad4tm2.1Cxd/J mouse were transformed into the genetic background, and the genotypes of the offspring mice were identified by the PCR to obtain the mice expressed simultaneously KrasLSL-G12D/- and Smad4loxp/loxp genes. The LentivirusCre-IRES-Luciferase was injected into the submucosa of the model mice and the tumorigenicity was observed under the IVIS system. The tumor tissues of the model mice were sampled and the HE staining was used to verify the tumorigenicity of the model mice. Results The genetically engineered mouse model which could simultaneously express KrasLSL-G12D/- and Smad4loxp/loxp genes was obtained by the breeding and selection. The mouse intestinal epithelial cell carcinogenesis was successfully induced by the viral vector containing Cre recombinase. Conclusion Mouse model expressed simultaneously KrasLSL-G12D/- and Smad4loxp/loxp genes is capable of sporadic tumorigenicity by Cre recombinase and could simulate pathological process of human sporadic colorectal cancer.
ObjectiveTo summarize the biomarkers related to the efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC).MethodReviewed and summarized the literatures on the basic and clinical application of biomarkers related to programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors and their combination with targeted therapy.ResultsThe combination of immunotherapy and targeted therapy had brought great hope for the treatment of patients with advanced HCC, but there were still some patients who could not benefit from it. Recent studies had shown that expression of PD-L1 in tumor tissue, tumor mutational burden, tumor-infiltrating lymphocytes, peripheral immune cells, circulating tumor DNA, gut microbiome, and so on, could predict the efficacy of immunotherapy or targeted therapy combined with immunotherapy for HCC.ConclusionsThere is no specific biomarker to predict the efficacy of immunotherapy and its combination regimen for HCC. More prospective studies are needed to confirm the predictive value of these biomarkers and to establish a multi-factor predictive model or immune score to screen patients who may benefit, which is of great significance for precise immunotherapy of HCC.
Objective To summarize the important role of tumor associated neutrophils (TANs) in the occurrence, development and prognosis of hepatocellular carcinoma (HCC). Methods The basic and clinical application research literatures on the correlation between TANs and the occurrence, development and prognosis of HCC were reviewed. Results As the most abundant inflammatory cells in human body, neutrophils were also an important part of the immunosuppressive microenvironment of HCC, which was closely related to the occurrence and development, immune escape and drug sensitivity of HCC. In the tumor microenvironment, the interaction between TANs, HCC cells and other components such as neutrophil extracellular traps was regulated by a variety of signal pathways. Some parameters related to neutrophils, such as neutrophils to lymphocytes ratio, had been used as effective biomarkers for predicting the clinical prognosis of HCC patients. Conclusions The exact role of neutrophils in HCC remains to be further studied. With the continuous accumulation of research results on the function of tumor associated immunosuppressive neutrophils and new therapies targeting neutrophils, more patients with HCC will benefit from immunotherapy and personalized targeted therapy.
Objective To investigate the effectiveness of free anterolateral thigh flap (ALTF) with fascia lata in repairing diabetic foot ulcers (DFUs) with bone exposure. Methods Between January 2019 and January 2021, 20 patients with DFUs with bone exposure were admitted. There were 17 males and 3 females with a median age of 57.5 years (range, 48-76 years). There were 10 cases of Wagner grade 3 and 10 cases of grade 4. The DFUs formed 1 to 14 months, with a median time of 3 months. The patients underwent CT angiography, which showed extensive atherosclerosis in both lower limbs; 6 of them were severely narrowed or occluded and underwent percutaneous transluminal angioplasty. The size of wound ranged from 7 cm×6 cm to 27 cm×10 cm after applied first-stage debridement combined with vacuum sealing drainage treatment. In the second-stage, free ALTF with fascia lata was used to repair wounds and partial defects of tendons. The size of flap ranged from 8 cm×5 cm to 28 cm×11 cm. The wound of the donor site was sutured directly. The survival of the flap, the healing time of the wound, and the complications were recorded. The laser speckle blood flow imaging system was used to detect the blood perfusion of the flap and the skin around the flap at 2 weeks and 6 months after operation. The foot function was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) score at 6 months after operation. Results After operation, effusion under the flap happened in 6 cases, which cured after symptomatic treatment. Flaps survived completely in 14 cases. The tissue necrosis at the edges of the flaps occurred in 3 cases and healed after dressing changes. Venous crisis of flaps occurred in 3 cases, of which 1 case was completely necrotic after exploration, and the other 2 cases were partially alive. The wounds of 3 cases were repaired with skin grafts after debridement and dressing. The flap survival rate was 95.0%, and the limb salvage rate was 100%. The wound healing time after flap transplantation was 14-30 days, with an average of 19.1 days. Two patients had recurrence of peripheral skin ulcers of the flaps within 1 month after healing, which healed after conservative dressing changes. Eighteen cases of incisions at donor site healed by first intention, 2 cases had local skin necrosis and healed by debridement and suture. All patients were followed up 6-30 months, with a median time of 11 months. The texture, appearance, and elasticity of the flaps were good. All patients could walk alone without pain. At 6 months after operation, the AOFAS score was 75.9±11.9, which was significantly different from that (44.7±18.4) before operation (t=−7.025, P=0.000). The blood perfusion value increased from (38.1±7.8) PU at 2 weeks to (42.7±10.3) PU, and the difference was significant (t=−4.680, P=0.001). Conclusion Free ALTF with fascia lata has a rich blood supply and a high survival rate. It can be used to repair DFUs with bone exposure. After the free skin flap healed, it can promote revascularization of the affected foot, reduce the probability of ulcer recurrence, and avoid amputation.