Comparison of Locking Plate Alone and Locking Plate Combined with 3D Printed Polymethylmethacrylate Augmentation in Treating Proximal Humerus Fractures in the Elderly.

BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.

Management of segmental defects post open distal femur fracture using a titanium cage combined with the Masquelet technique A single-centre report of 23 cases.

INTRODUCTION: The segmental bone defects post open distal femur fracture presents a reconstructive challenge, which often requires extreme solutions. The present study reviewed a new treatment strategy which used a cylindrical titanium mesh cage as an adjunct to the Masquelet technique. METHODS: We retrospectively reviewed a consecutive series of 23 patients treated for segmental bone defects post open distal femur fracture using a titanium mesh cage combined with the Masquelet technique under a 2-staged protocol in our institution from 2017 to 2021. The study group consisted of 13 men and 10 women with an average age of 44.1 years. The surgical debridement was performed with antibiotic polymethylmethacrylate (PMMA) cement spacer implanted into the bone defect combined with cement-wrapped plate stabilization, or antibiotic beads with vacuum sealing drainage (VSD) to cover the wound. The second stage of the Masquelet technique for bone defect repair began at least 4-6 weeks after the first stage, once all signs of possible infection were eliminated. After the cement spacer was removed, the definitive reconstruction was completed with exchange to a cylindrical titanium mesh cage filled with cancellous autograft within the induced membrane. The bone defect with cage was stabilized with a distal femoral Less Invasive Stabilization System (LISS). The radiological and clinical records of the enrolled patients were retrospectively analyzed. RESULTS: The mean follow-up was 38.6 months. The average number of operations before the second stage was 1.3. The mean interval between the two stages was 12.7 weeks. The average length of the defect measured 8.3 cm (ranging from 6.1 to 12.4 cm). All the defects filled with autograft within the cage achieved bony union, with a mean healing time of 8.4 months. At the latest follow-up, the mean knee extension measured 6.2° (ranging from 0° to 20°), and the mean flexion measured 101.8° (ranging from 60° to 120°). Complications included two instances of superficial stitch abscess, which eventually healed. CONCLUSIONS: The use of a titanium cage implanted into an induced membrane in a 2-staged Masquelet protocol could achieve satisfactory clinical outcomes in cases of segmental defects following open distal femur fractures.

[Regulative effect of active components of Cistanche deserticola on intestinal dysbacteriosis induced by antibiotics in mice].

Objective: To study the effects of Cistanche deserticola and its active components Cistanche deserticola polysaccharide and Echinacoside on intestinal flora of antibiotic-associated diarrhea (AAD) mice. Methods: Forty-eight Balb/c mice were randomly divided into control (Con) group, AAD Group, inulin (Inu) group, Cistanche deserticola (RCR) group, Cistanche deserticola polysaccharide (RCRDT) group and Echinacoside (Ech) group with 8 mice in each group. The diarrhea model of mice was induced by intragastric administration of lincomycin hydrochloride(3 g/kg) for 7 days, and then treated by intragastric administration of INU(5 g/kg), RCR(5 g/kg), RCRDT(200 mg/kg) and ECH (60 mg/kg),0.2 ml once a day for 7 days, Con group and AAD group were given the same volume of normal saline. By observing general signs of mice, colon HE staining, 16S rDNA high-throughput sequencing analysis, the effects of Cistanche deserticola, Cistanche deserticola polysaccharide and Echinacea glycoside on the imbalance of intestinal flora induced by antibiotics in mice were evaluated. Results: Compared with Con group, AAD group mice lost weight, presented obvious diarrhea symptoms, inflammatory changes in colon tissue and decreased intestinal flora diversity (P＜0.05) indicating the success of the model. Compared with AAD group, the weight and diarrhea of INU, RCR, RCRDT and ECH groups were significantly improved, and the colon pathology of ECH group was restored to normal level. Compared with AAD group, RCR group, RCRDT group and ECH group had significantly decreased intestinal Firmicutes, increased Blautia and Lachnoclostridium, and decreased Clostridium_sensu_stricto_1 (P＜0.05) . In ECH group, the abundance and diversity of intestinal microflora were returned to normal level, and the structure of intestinal microflora was well adjusted, the contents of Bacteroides, Flavonifractor, Agathobacter, Lachnoclostridium and Prevotella-9 were increased (P＜0.01). Conclusion: Both Cistanche deserticola and its active components cistanche deserticola polysaccharide and echinacoside can regulate the intestinal flora imbalance caused by antibiotics and improve the symptoms of AAD, especially echinacoside.

Effects of rutin on osteoblast MC3T3-E1 differentiation, ALP activity and Runx2 protein expression.

As a flavonoid, rutin has been found to have a wide range of biological functions, such as resisting inflammation and oxidation, and preventing cerebral hemorrhage and hypertension. It has been found to play an important role in osteoporosis and other orthopedic diseases in recent years. MC3T3-E1 cells were randomly divided into a control group, a rutin-1 group (0.01 mmol/L), a rutin-2 group (0.05 mmol/L) and a rutin-3 group (0.1 mmol/L). Osteogenic differentiation of cells was induced by osteogenic induction fluid. The control group was treated with the maximum dose of drug solvent. 2~3 days later, the solvent was replaced with fresh osteogenic induction fluid containing rutin. After a certain period of routine culture, the cells were collected for subsequent experiments. The expression of Runx2 gene in cells in all groups was detected by Real-time PCR; the expression of Runx2 protein was detected by Western blot and immunocytochemistry; the activity of ALP was detected by reagent kit method; osteogenic differentiation was analyzed by alizarin red staining. The results of Real-time PCR showed that, compared with the control group, the treatment of cells with rutin can significantly increase the expression of Runx2 gene (p<0.05); the higher the concentration, the higher the expression of Runx2 gene, and significant differences were found among groups in which different concentrations were used (p<0.05); the results of Western blot and IHC showed that the expression trend of Runx2 protein in each group was consistent with PCR results. In drug treatment groups, the activity of ALP was significantly higher than that in the control group (p<0.05); there were significant differences among groups in which different concentrations were used (p<0.05). The results of alizarin red staining showed that calcified nodules were formed in all groups and that the area of calcified nodules formed in groups treated with rutin was greater than that in the control group; the greater the concentration, the larger the area. Rutin can promote osteoblastic differentiation; and the greater the concentration, the more effective it is.

Effects of Rapamycin Combined with Cisplatin on Tumor Necrosis Factor TNF-α in MG-63 Cells.

Rapamycin (RAPA) and cisplatin (CDDP) are used as clinical drugs in the treatment of various tumors, but there are few studies on the combination of RAPA and CDDP. Tumor necrosis factor α (TNF-α) plays an important role in tumorigenesis and development. This study is to explore the effects of RAPA combined with CDDP on the expression of TNF-α in osteosarcoma MG-63 cells. MG-63 cells were routinely cultured and divided into a control group, a RAPA group (20 µM), a CDDP group (20 µM), and a RAPA + CDDP group (20 µM + 20 µM). The four groups were treated with drugs for 24 and 48 h, respectively. Real-time polymerase chain reaction (PCR), Western blot (WB), and immunocytochemistry (ICC) were adopted to detect the expression of TNF-α gene and protein. The results of PCR showed that both the separate drug use and drug combination could significantly lower the relative expression quantity of TNF-α gene (*P < 0.5), but the combination was more effective (*P < 0.5); the expression quantity of TNF-α gene in the RAPA + CDDP group at 48 h was much lower than that at 24 h (***P < 0.001). The results of WB showed that both the separate drug use and drug combination could significantly lower the relative expression quantity of TNF-α protein, and the combination was more effective than separate drug use (*P < 0.05) and more effective at 48 h (***P < 0.001); the expression quantity of TNF-α protein in the same group at 48 h was much lower than that at 24 h (*P < 0.05). The results of ICC showed that both the separate drug use and drug combination could significantly lower the relative expression quantity of TNF-α protein, and the combination was more effective than separate drug use (**P < 0.01) and more effective at 48 h (***P < 0.001); the expression quantity of TNF-α protein in the same group at 48 h was much lower than that at 24 h (**P < 0.01). RAPA combined with CDDP can significantly reduce the expression of TNF-α in MG-63 cells, which is time dependent.

In vitro effects of recombinant adenovirus-mediated bone morphogenetic protein 2/vascular endothelial growth factor 165 on osteogenic differentiation of bone marrow mesenchymal stem cells.

Mouse bone marrow mesenchymal stem cells C3H10T1/2 were divided into Ad-BMP2 (bone morphogenetic protein 2) group, Ad-VEGF165 (vascular endothelial growth factor 165) group, Ad-VEGF165 + Ad-BMP2 group, empty adenovirus group and control group. BMP2 and VEGF165 were highly co-expressed in Ad-VEGF165 + Ad-BMP2 group. Ad-BMP2 and Ad-VEGF165 + Ad-BMP2 groups, especially the latter (P < 0.05), had significantly higher expression levels of osteocalcin, osteoprotegerin, and osteopontin mRNA and OPN protein (P < 0.05). Ad-VEGF165 + Ad-BMP2 group had highest alkaline phosphatase (ALP) activity, strongest ALP staining and most calcium salt deposits (P < 0.05). Combining VEGF165 obviously enhanced the inducing effects of BMP2 on osteogenic differentiation capacity of C3H10T1/2 cells.

Inhibition of mitochondrial glutaminase activity reverses acquired erlotinib resistance in non-small cell lung cancer.

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has been approved based on the clinical benefit in non-small cell lung cancer (NSCLC) patients over the past decade. Unfortunately, cancer cells become resistant to this agent via various mechanisms, and this limits the improvement in patient outcomes. Thus, it is urgent to develop novel agents to overcome erlotinib resistance. Here, we propose a novel strategy to overcome acquired erlotinib resistance in NSCLC by inhibiting glutaminase activity. Compound 968, an inhibitor of the glutaminase C (GAC), when combined with erlotinib potently inhibited the cell proliferation of erlotinib-resistant NSCLC cells HCC827ER and NCI-H1975. The combination of compound 968 and erlotinib not only decreased GAC and EGFR protein expression but also inhibited GAC activity in HCC827ER cells. The growth of erlotinib-resistant cells was glutamine-dependent as proved by GAC gene knocked down and rescue experiment. More importantly, compound 968 combined with erlotinib down-regulated the glutamine and glycolysis metabolism in erlotinib-resistant cells. Taken together, our study provides a valuable approach to overcome acquired erlotinib resistance by blocking glutamine metabolism and suggests that combination of EGFR-TKI and GAC inhibitor maybe a potential treatment strategy for acquired erlotinib-resistant NSCLC.

Periosteal osteosarcoma: a review of clinical evidence.

Periosteal osteosarcoma (PO) is a rare primary malignant bone tumor and a variant of osteosarcoma. It is a surface lesion without evidence of medullary involvement. The radiologic appearance of periosteal osteosarcoma is a broad-based surface soft-tissue mass that causes extrinsic erosion of thickened underlying diaphyseal cortex and perpendicular periosteal reaction extending into the soft-tissue component. The tumour presents as non-homogeneous masses of speculated osteoid matrix progressively denser from the periphery to their cortical base. The average age is around 28 and the most common location is the proximal third of the femur; with all the lesions diaphyseal in location. The treatment usually indicated is amputation, but in selected cases, radical segmental resection is appropriate. Long-term disease-free survival is possible after resection of the local recurrence. Limb-salvage therapy seems to offer survival equivalent to amputation, and there does not seem to be a substantial risk of late recurrence, dedifferentiation, or disease progression. The current review also highlights on various rare occurrences of periosteal osteosarcoma including the one of calcaneum, fifth metatarsal, mandible cranium, jaws, clavicle, maxilla, sphenoid bone with extensive periosteal extension, metacarpal in a paediatric age group and bilateral metachronous periosteal osteosarcoma. Recent findings relating to genetic factors governing the pathogenesis of PO is also presented.

Cdc42 induces EGF receptor protein accumulation and promotes EGF receptor nuclear transport and cellular transformation.

Cdc42 is a Ras-related small GTP-binding protein. A previous study has shown that Cdc42 binding to the γ subunit of the coatomer protein complex (γCOP) is essential for Cdc42-regulated cellular transformation, but the molecular mechanism involved is not well understood. Here, we demonstrate that constitutively-active Cdc42 binding to γCOP induced the accumulation of epithelial growth factor receptor (EGFR) in the cells, sustained EGF-stimulated extracellular signal-regulated kinase (ERK), JUN amino-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) signaling and promoted cell division. Moreover, constitutive Cdc42 activity facilitated the nuclear translocation of EGFR, and this indicates a novel mechanism through which Cdc42 might promote cellular transformation.

[Immunological research of rat osteoblast xenotransplantation].

OBJECTIVE: To detect the immunoreaction after osteoblast xenotransplantation and to investigate the possibility of heterogenic osteocyte transplantation and tissue engineered bone reconstruction. METHODS: Rat osteoblasts were isolated by two-part bony digestion/elements in culturing, and incubated in vitro at 37 degrees C, 5% carbon dioxide for 5 days until they multiplied and formed a monolayer on the bottom of dish. Twenty-eight rabbits were divided into 3 groups. Autograft of osteoblasts(group A), xenograft of osteoblasts(group B) and normal saline(group C) were implanted into the rectus abdominus muscle. The immunological and histological observations were performed after 1, 2, 4 and 8 weeks of transplantation. RESULTS: Cultured cells reached confluence within 5 days and was identified as osteoblasts by ALP staining and Bon kossa staining. The result of host versus graft reaction was negative. In group B, specific antibody reaction was detected 2 weeks and 4 weeks after transplantation. Cell mediated cytotoxicity was detected after 2 weeks, reached the peak value 4 weeks later, and then began to decline 8 weeks later. HE staining showed mass inflammatory cells and no ectopic ossification after 8 weeks. CONCLUSION: Heterogenic osteoblast transplantation will lead to an obvious change in host humoral and cellular immunity and lost the ability of bone formation. So, it can not be used for the reliable cell sources for osteocyte transplantation or tissue-engineering bone reconstruction.