Case report of double superior vena cava and double odd vein with hypoplastic left brachiocephalic vein.

Persistent left superior vena cava (PLSVC) is a common venous variation that is usually accompanied by an absence of the left brachiocephalic vein, and displays a higher incidence in patients with congenital heart disease. Here, the case of a 57-year-old male patient who was found to have PLSVC on chest computed tomography (CT) during screening for gastric cancer metastasis at the Affiliated Hospital of Qinghai University, is described. Further coronal CT and three-dimensional reconstruction of the chest revealed the patient's double superior vena cava (DSVC), double odd veins, and left brachiocephalic vein dysplasia. The patient did not have congenital heart disease and the case was associated with dysplasia of the left brachiocephalic vein, indicating an unusual and rare venous abnormality. At the time of writing, the patient was receiving antitumour therapy.

Modular revision strategy with bispherical augments in severe acetabular deficiency reconstruction.

PURPOSE: Reconstruction of severe acetabular deficiency is extremely challenging in total hip arthroplasty (THA) revisions. Novel bispherical augments were designed to fill acetabular bone loss and facilitate restoration of hip center of rotation (HCOR). Current study aims to compare the outcomes of bispherical augments and tantalum augments. METHODS: Between July 2017 and December 2018, bispherical augments (BA group) were implanted in 25 patients (25 hips) and 22 patients (22 hips) underwent porous tantalum augments (TA group) reconstruction in revision THA. Clinical and radiographic results were evaluated for 25 hips in BA group and 20 hips in TA group at the final follow-up. The mean duration of follow-up was 2.9 years (range, 2.2 ~ 3.7) in BA group and 2.9 years (range, 2.3 ~ 3.8) in TA group. RESULTS: Harris hip scores, HCOR, and leg length discrepancy (LLD) correction did not differ between the treatment groups. The bispherical augments were located more closer to the medial-superior part (zone II) of acetabular shell while the majority of tantalum augments were located at the lateral-superior part (zone I) (P = 0.010). More screws were used in the BA group for augment fixation (mean 2.1 vs. 1.3) (P = 0.000). There was no evidence of loosening or migration in all hips. Only one dislocation occurred in BA group and treated with closed reduction, no recurrence of instability up to the final follow-up. CONCLUSION: The clinical and radiological outcomes of bispherical augments were comparable with tantalum augments; this technique was a reliable alternative method in severe acetabular deficiency reconstruction.

Association of LINC00673 rs11655237 polymorphism with pediatric glioma susceptibility in a Chinese population.

BACKGROUND: Previous researches have suggested that LINC00673 rs11655237 C>T polymorphism might be correlated to cancer susceptibility. However, its correlation with pediatric glioma is unknown. Therefore, this study aimed to determine whether LINC00673 rs11655237 C>T polymorphism is correlated with pediatric glioma. METHODS: In total, we included 399 subjects from South China. The Student's t-test was performed to evaluate age differences between glioma cases and controls. Differences in the categorical variables between the two groups were assessed using the χ2 test. A logistic regression was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI). RESULTS: We conducted this case-control study to investigate the association between LINC00673 polymorphism and pediatric glioma susceptibility. Our results revealed that LINC00673 rs11655237 C>T polymorphism was not correlated to pediatric glioma susceptibility in a Chinese population (CC/CT compared with TT: adjusted OR =2.49, 95% CI: 0.87-7.15, P=0.091). Furthermore, a stratified analysis also indicated LINC00673 rs11655237 C>T polymorphism did not increase the risk of glioma in different subgroups. CONCLUSIONS: Our study revealed that LINC00673 rs11655237 C>T polymorphism was not correlated to pediatric glioma susceptibility in a Chinese population. In the future, further exploration of this genetic factor in relation to glioma susceptibility will require a larger sample size to verify the current findings.

The correlation between polymorphisms in the XPC gene and glioma susceptibility in a Chinese pediatric population.

BACKGROUND: A previous study revealed that single nucleotide polymorphisms (SNPs) in coding genes play a key role in tumorigenesis, genetic disorders, and drug resistance. Xeroderma pigmentosum group C (XPC) protein is a key DNA damage recognition factor that is required for maintaining the genomic stability. However, the correlation between XPC polymorphisms and glioma susceptibility is still unclear. Hence, this study aimed to investigate the correlation between XPC polymorphisms and pediatric glioma susceptibility. METHODS: A total of 399 participants (171 glioma patients and 228 controls) were enrolled to evaluate the correlation between XPC polymorphism and pediatric glioma susceptibility. The count data of two groups was analyzed by chi-squared (χ2) test. Moreover, logistic regression was used to assess the strength of XPC polymorphisms associated with glioma susceptibility. RESULTS: We identified that XPC rs1870134 G>C reduced pediatric glioma susceptibility. Compared to participants with rs1870134 GG/GC genotypes, those with rs1870134 CC genotype had a significantly lower risk for glioma [adjusted odds ratio (AOR) =0.10, 95% confidence interval (CI): 0.01 to 0.78, P=0.028]. Patients with 4-5 genotypes have higher risk of glioma than those with 0-3 genotypes (AOR =1.59, 95% CI: 1.04 to 2.43, P=0.031). The stratified analysis showed that the risky effects of rs2228000 CT/TT genotypes and rs2229090 GC/CC genotypes were more predominant among children aged ≥60 months, astrocytic tumors, and clinical stage I. CONCLUSIONS: We found for the first time that XPC polymorphisms had a statistically significant correlation with pediatric glioma susceptibility in a Chinese population. The XPC rs2228000 CT/TT and rs2229090 GC/CC genotypes could both increase the risk of pediatric glioma in subgroups with females, astrocytic tumors, and clinical stage I. The XPC polymorphism has potential to be a useful adjunct method to screen pediatric glioma.

Efficacy and Safety of Apatinib for Elderly Patients with Advanced or Metastatic Gastric Cancer After Failure of at Least First-Line Chemotherapy: A Multi-Center, Single-Arm, Phase II Study.

BACKGROUND: Apatinib improves progression-free survival and overall survival with an acceptable safety profile in Chinese patients with chemotherapy-refractory advanced or metastatic gastric cancer. However, the efficacy and safety of apatinib are unclear for elderly patients. This study was undertaken to prospectively investigate the efficacy and safety of apatinib for elderly patients with unresectable advanced or metastatic gastric cancer, who experienced progression to at least one lines of chemotherapy. METHODS: This open-label, single-arm, phase II study enrolled patients aged ≥60 years with advanced gastric cancer, who experienced progression to one or more lines of chemotherapy at five centers in China. Patients received apatinib in an oral dose of 500mg or 250mg daily according to the research physicians' decision. The primary end point was progression-free survival, and the secondary end points were objective response rate, disease control rate, overall survival, and safety. RESULTS: Forty-eight patients were enrolled between June 2017 and September 2019. The median age was 65.5 years (range 60-80 years). Twenty-seven patients (56.3%) started treatment with an initial dose of 500 mg and 21 patients (43.7%) with 250 mg. The median progression-free survival and overall survival were 3.00 months (95% confidence interval, 2.17-3.84) and 8.10 months (95% confidence interval, 4.35-11.85), respectively. The objective response rate and disease control rate assessed by the investigators were 16.7% and 72.9%, respectively. The common side effects were fatigue (58.3%), hypertension (47.9%), abdominal pain (33.3%), proteinuria (29.2%), leukopenia (22.9%), and neutropenia (20.8%). Hypertension (22.9%) was the major grade 3/4 toxicity. CONCLUSION: These data suggest that apatinib is effective and relatively tolerable for elderly patients with unresectable advanced or metastatic gastric cancer who have received at least first-line chemotherapy.

A Social Media-Promoted Educational Community of Joint Replacement Patients Using the WeChat App: Survey Study.

BACKGROUND: Much effort has been made to optimize the results of total hip arthroplasty and total knee arthroplasty. With the rapid growth of social media use, mobile apps, such as WeChat, have been considered for improving outcomes and patient satisfaction after total hip arthroplasty and total knee arthroplasty. OBJECTIVE: We aimed to evaluate the effectiveness of a WeChat-based community as an intervention for overall patient satisfaction. METHODS: The study was conducted among discharged in-hospital patients who received hip or knee procedures in the First Affiliated Hospital of the University of Science and Technology of China from April 2019 to January 2020. An educational online social community was constructed with the WeChat app. Participants willing to join the community were enrolled in a WeChat group and received 3 months of intervention and follow-up. Those who were not willing to use the account were included in a control group and received routine publicity via telephone, mail, and brochures. The Danish Health and Medicine Authority patient satisfaction questionnaire was used to score perioperative patient education and overall satisfaction. The contents in the group chat were analyzed using natural language processing tools. RESULTS: A total of 3428 patients were enrolled in the study, including 2292 in the WeChat group and 1236 in the control group. Participants in the WeChat group had higher overall satisfaction scores than those in the control group (mean 8.48, SD 1.12 vs mean 6.66, SD 1.80, P<.001). The difference between the two groups was significant for primary surgery based on subgroup stratification. To control confounding factors and explore the effects of WeChat participation as a mediating variable between perioperative patient education and overall satisfaction, hierarchical regression was utilized. An interpatient interaction model was found in the community group chat, and it contributed to overall satisfaction. Patients in the group with more interpatient interactions were more likely to have better overall satisfaction. CONCLUSIONS: The social media-promoted educational community using WeChat was effective among joint replacement patients. Provision of more perioperative education is associated with more active patient participation in the community and therefore more patient satisfaction in terms of the overall joint procedure. Community group chat could facilitate interactions among patients and contribute to overall satisfaction.

A novel redox-responsive ursolic acid polymeric prodrug delivery system for osteosarcoma therapy.

Ursolic acid (UA), found widely in nature, exerts effective anti-tumoral activity against various malignant tumors. However, the low water solubility and poor bioavailability of UA have greatly hindered its translation to the clinic. To overcome these drawbacks, a simple redox-sensitive UA polymeric prodrug was synthesized by conjugating UA to polyethylene glycol using a disulfide bond. This formulation can self-assemble into micelles (U-SS-M) in aqueous solutions to produce small size micelles (∼62.5 nm in diameter) with high drug loading efficiency (∼16.7%) that exhibit pH and reduction dual-sensitivity. The cell and animal studies performed using the osteosarcoma MG-63 cell line and MG-63 cancer xenograft mice as the model systems consistently confirmed that the U-SS-M formulation could significantly prolong the circulation in blood and favor accumulation in tumor tissue. Targeted accumulation allows the U-SS-M to be effectively internalized by cancer cells, where the rapid release of UA is favored by a glutathione-rich and acidic intracellular environment, and ultimately achieves potent antitumor efficacy.

YTHDF1 rs6090311 A>G polymorphism reduces Hepatoblastoma risk: Evidence from a seven-center case-control study.

Various factors modulate the risk of hepatoblastoma. In this study, we aimed to investigate whether single nucleotide polymorphisms (SNPs) in the YTHDF1 gene could predispose to hepatoblastoma. We used TaqMan assay to genotype two YTHDF1 SNPs (rs6011668 C>T and rs6090311 A>G) in a Chinese population composed of 313 subjects with hepatoblastoma and 1446 controls from seven hospitals. We then evaluated the associations of these two SNPs with hepatoblastoma risk using unconditional logistic regression. We found that rs6090311 G allele exhibited a significant association with decreased hepatoblastoma risk [AG vs. AA: adjusted odds ratio (OR)=0.75; 95% confidence interval (CI)=0.58-0.98, P=0.033; AG/GG vs. AA: adjusted OR=0.76, 95% CI=0.59-0.97, P=0.029]. Furthermore, the combined analysis of protective genotypes revealed that subjects carrying two protective genotypes were less likely to have hepatoblastoma than those with 0-1 protective genotypes (adjusted OR=0.75, 95% CI=0.59-0.96, P=0.022). Subjects ≥17 months of age had decreased hepatoblastoma risk, in case that they carried rs6090311 AG/GG (adjusted OR=0.63, 95% CI=0.44-0.91, P=0.012), or two protective genotypes (adjusted OR=0.63, 95% CI=0.44-0.91, P=0.012). False-positive report probability analysis validated the reliability of the significant results. Preliminary functional annotations revealed that rs6090311 G was correlated with decreased expression of its surrounding genes in the expression quantitative trait locus (eQTL) analysis. In conclusion, our results indicate that the rs6090311 A>G in the YTHDF1 gene is related to decreased hepatoblastoma risk.

[Effectiveness of proximal femur reconstruction combined with total hip arthroplasty for Crowe type â £ developmental dysplasia of hip].

OBJECTIVE: To investigate the early effectiveness of proximal femur reconstruction combined with total hip arthroplasty (THA) in the treatment of adult Crowe type Ⅳ developmental dysplasia of the hip (DDH). METHODS: Between May 2015 and March 2018, 29 cases (33 hips) suffering from Crowe type Ⅳ DDH were treated with proximal femur reconstruction combined with THA. Of the 29 cases, there were 6 males (7 hips) and 23 females (26 hips), aged from 24 to 74 years with an average age of 44.9 years. The preoperative Harris hip score was 44.0±12.0. Gait abnormalities were found in all of the 33 hips with positive Trendelenburg sign, and the lower limb discrepancy was (3.8±1.6) cm. Preoperative X-ray films and CT both indicated serious anatomical abnormalities, including complete dislocation of the affected hip with significant move-up of the greater trochanter, abnormal development of the femoral neck, abnormal anterversion angle and neck-shaft angle, dysplasia of proximal femur and dysplasia of medullary cavity. The operation time, intraoperative blood loss, transfusion rate, and complications were recorded. The Gruen and DeLee-Charnley zoning methods were used to evaluate the aseptic loosening of the prosthesis on X-ray films. The Harris score was used to evaluate hip function. The lower limb discrepancy was calculated and compared with the preoperative value. RESULTS: The operation time ranged from 80 to 240 minutes, with an average of 124.8 minutes. The intraoperative blood loss ranged from 165 to 1 300 mL, with an average of 568.4 mL. Seventeen patients (51.5%) received blood transfusion treatment. All the incisions healed by first intention without infection or deep vein thrombosis. All patients were followed up 19-53 months, with an average of 33 months. One patient had posterior hip dislocation because of falling from the bed at 4 weeks after operation, and was treated with manual reduction and fixation with abduction brace for 4 weeks, and no dislocation occurred during next 12-month follow-up. Two patients developed sciatic nerve palsy of the affected limbs after operation and were treated with mecobalamin, and recovered completely at 12 weeks later. Trendelenburg sign was positive in 3 patients and mild claudication occurred in 4 patients after operation. X-ray films showed that all the osteotomy sites healed at 3-6 months after operation, and no wire fracture was observed during the follow-up. The Harris score was 89.8±2.8 and lower limb discrepancy was (0.6±0.4) cm at last follow-up, both improved significantly ( t=-22.917, P=0.000; t=11.958, P=0.000). The prosthesis of femur and acetabulum showed no obvious loosening and displacement, and achieved good bone ingrowth except 2 patients who had local osteolysis in the area of Gruen 1 and 7 around the femoral prosthesis, but no sign of loosening and sinking was observed. CONCLUSION: The treatment of Crowe Ⅳ DDH with proximal femur reconstruction and THA was satisfactory in the early postoperative period. The reconstruction technique of proximal femur can effectively restore the anatomical structure of proximal femur, which is one of the effective methods to deal with the deformity of proximal femur.

Comprehensive Analysis of lncRNA and miRNA Expression Profiles and ceRNA Network Construction in Osteoporosis.

Multiple profiling studies have identified a number of non-coding RNAs associated with the pathogenesis of human diseases. However, the exact regulatory mechanisms and functions of these non-coding RNAs in the development of osteoporosis have not yet been explored. Transcriptome gene expression and miRNA microarray data from peripheral blood monocytes of five high hip bone mineral density (BMD) subjects and five low hip BMD subjects were analyzed. Differentially expressed mRNAs, lncRNAs, and miRNAs were identified and subjected to functional enrichment analysis. Additionally, protein-protein interaction (PPI), lncRNA-mRNA, and mRNA-lncRNA-miRNA competing endogenous RNA (ceRNA) networks were constructed. Differential analysis revealed that 297 mRNAs, 151 lncRNAs, and 38 miRNAs were significantly differentially expressed between peripheral blood monocytes from high and low hip BMD subjects. Key genes including ACLY, HSPA5, and AKT1 were subsequently identified in the PPI network. Additionally, differentially expressed lncRNAs were primarily enriched in the citrate cycle (TCA cycle), biosynthesis of antibiotics, and carbon metabolism pathways. Finally, the mRNA-lncRNA-miRNA network revealed several key ceRNA regulatory relationships among the transcripts and non-coding RNAs. Key mRNAs and non-coding RNAs identified in the networks represent potential biomarkers or targets in the diagnosis and management of osteoporosis. Our findings represent a resource for further functional research on the ceRNA regulation mechanism of non-coding RNA in osteoporosis.

Silencing of RBP­JK promotes the differentiation of bone marrow mesenchymal stem cells into vascular endothelial cells.

Bone marrow mesenchymal stem cells (BM­MSCs) are important for postnatal angiogenesis and are suitable for use in construction of blood vessels by tissue engineering. The present study aimed to investigate the influence of recombination signal binding protein for immunoglobulin kappa J region (RBP­JK) on the differentiation of BM­MSCs into vascular endothelial cells, and to assess the underlying mechanisms. BM­MSCs were isolated and identified by flow cytometry. Lentiviral vectors encoding RBP­JK shRNA (shRBPJK) were constructed to knockdown RBP­JK expression and endothelial differentiation of BM­MSCs was induced. The experimental groups were treated with: empty lentiviral vector (vector group), growth factors (bFGF and VEGF; induced group), shRBPJK (shRBPJK group), and growth factors + shRBPJK (induced + shRBPJK group). The expression of endothelial markers, vascular endothelial growth factor receptor 2 (Flk­1), and von Willebrand factor (vWF) were detected by immunofluorescence. Additionally, in vitro blood vessel formation and phagocytosis were assessed using acetylated LDL, Dil complex and the underlying molecular mechanisms evaluated by western blotting. BM­MSCs were separated and transduced with shRBPJK to reduce RBP­JK expression. Compared with the vector group, the expression of the endothelial cell markers, Flk­1 and vWF, in vitro tubule formation, and phagocytosis ability increased, while the expression levels of p­AKT/AKT and p­NF­κB/NF­κB were significantly decreased (P<0.05) in the induced, shRBPJK, and induced + shRBPJK groups. Compared with the induced group, the expression of Flk­1 and vWF, the number of tubules, and phagocytosis were higher in the induced + shRBPJK group, while the expression levels of p­AKT/AKT and p­NF­κB/NF­κB were lower (P<0.05). Collectively, the present data indicated that silencing of RBP­JK promotes the differentiation of MSCs into vascular endothelial cells, and this process is likely regulated by AKT/NF­κB signaling.

LMO1 Super-Enhancer rs2168101 G>T Polymorphism Reduces Wilms Tumor Risk.

Wilms tumor is one of the most prevalent pediatric malignancies in childhood cancer worldwide. A genome-wide association study recognized that LIM domain only 1 (LMO1) increases the risk of oncogenic potential. An association has been found that LMO1 gene polymorphisms are associated with the susceptibility to Wilms tumor. One hundred forty-five children with Wilms tumor and 531 cancer-free children were included in this hospital-based case-control study. Five potentially functional polymorphisms in the LMO1 gene (rs2168101 G>T, rs1042359 A>G, rs11041838 G>C, rs2071458 C>A and rs3750952 G>C) were genotyped by the TaqMan method. The association between selected polymorphisms and Wilms tumor susceptibility was measured by calculating the odds ratio (OR) and the 95% confidence interval (CI). Only rs2168101 G>T polymorphism was found to have a significant protective effect against Wilms tumor (GT vs. GG: adjusted OR=0.58, 95% CI=0.39-0.88, P=0.010; GT/TT vs. GG: adjusted OR=0.67, 95% CI=0.46-0.97, P=0.034). Moreover, carriers of 3-5 protective genotypes had significantly lower tumor risk than carriers of 0-2 protective genotypes (adjusted OR=0.62, 95% CI=0.42-0.91, P=0.022). The stratified analysis showed that the protective effect of rs2168101 GT/TT was predominant in males, and rs2071458 GT/TT was predominant in females. Regarding the combined risk genotypes, the analysis indicated that the 3-5 protective genotypes collectively decreased Wilms tumor risk in females. These results suggest that LMO1 gene rs2168101 G>T polymorphism may help prevent Wilms tumor, but this conclusion should be verified in other populations and additional studies.

Curcumin suppresses wilms' tumor metastasis by inhibiting RECK methylation.

Wilms' tumor (WT) is the most common kidney tumor of children. The transformation suppressor gene RECK, which codes membrane-anchored glycoprotein, frequently downregulates multiple matrix metalloproteinases in tumors. And curcumin, which is a polyphenlic compound separated from turmeric, has antitumor effects on various cancers. However, the correlation of WT, RECK and curcumin is still unrevealed. In this study, we evaluated that the methylation degree of RECK was much higher in WT than in adjacent non-tumor tissues. And RECK methylation was closely associated with tumor metastasis in WT patients. After curcumin treatment, the level of RECK methylation was decreased significantly. And the expression of MMP2 and MMP9 was reduced consequently. Moreover, the proliferation, invasion and migration ability of WT cells were suppressed after curcumin treatment. Meanwhile, the apoptosis rate of WT cells was increased simultaneously. In nude mice model, curcumin restrained ability of tumorigenicity and promoted apoptosis of WT cells. Together, our results suggest that the RECK methylation can serve as a prognostic biomarker of WT. Moreover, curcumin could inhibit RECK methylation, thereby abates the expression of MMPs, and suppresses the tumor progression and metastasis of WT.

In Vitro and in Vivo Study of 3D-Printed Porous Tantalum Scaffolds for Repairing Bone Defects.

Porous tantalum (Ta) scaffold is a novel implant material widely used in orthopedics including joint surgery, spinal surgery, bone tumor surgery, and trauma surgery. However, porous Ta scaffolds manufactured using the traditional method have many disadvantages. We used selective laser melting (SLM) technology to manufacture porous Ta scaffolds, and the pore size was controlled to 400 µm. The compressive strength and elastic modulus of the porous scaffolds were evaluated in vitro. To evaluate the osteogenesis and osseointegration of Ta scaffolds manufactured by SLM technology, cytocompatibility in vitro and osseointegration ability in vivo were evaluated. This porous Ta scaffold group showed superior cell adhesion and proliferation results of human bone mesenchymal stem cells (hBMSCs) compared with the control porous Ti6Al4V group. Moreover, the alkaline phosphatase (ALP) activity at day 7 and the semiquantitative analysis of Alizarin red staining at day 21 demonstrated that osteogenic differentiation of hBMSCs was enhanced in the Ta group. The porous Ta scaffold was implanted into a cylindrical bone defect with a height and diameter of 1 and 0.5 cm, respectively, in the lateral femoral condyle of New Zealand rabbits. Radiographic analysis showed that the new bone formation in Ta scaffolds was higher than that in Ti6Al4V scaffolds. Histological images indicated that compared with porous Ti6Al4V scaffolds, Ta scaffolds increased bone ingrowth and osseointegration. The porous Ta scaffold manufactured by SLM not only has a regular pore shape and connectivity but also has controllable elastic modulus and compressive strength. Moreover, the osteogenesis and osseointegration results in vitro and in vivo were improved compared with those of the porous Ti6Al4V scaffold manufactured using the same technology. These findings demonstrate that the porous Ta scaffold manufactured by SLM is potentially useful for orthopedic clinical application.

Paclitaxel-betulinic acid hybrid nanosuspensions for enhanced anti-breast cancer activity.

Paclitaxel-betulinic acid hybrid nanosuspensions (PTX-BA-NP) with increased anti-breast cancer activity were developed. The resultant nanosuspensions (NP) had a mean particle size of 282.54 ± 5.4 nm, a polydispersity index of approximately 0.242 ± 0.02, a zeta potential of -19.7 ± 0.19 mV and a redispersibility index of 103.3 ± 0.01%. The cumulative dissolution percentage of PTX coarse powder and PTX-BA-NP dried powder at 60 min were 15.4% and 90.8%, respectively. MCF-7 cell-based testing showed that treatment with PTX-BA-NP led to more PTX-BA-NP accumulation in the cytoplasm of breast cancer cells, less cell cycle arrest in the G2-M phase, more cell cycle arrest in the G0-G1 phase, more apoptosis-induced cell death and stronger inhibition of cell migration than paclitaxel nanosuspensions (PTX-NP). Biodistribution studies showed that tumor accumulation levels at 12 h in the PTX-BA-NP group were approximately 2.67- and 2.33-fold higher than the levels in the Taxol® and PTX-NP groups, respectively. In vivo antitumor efficacy demonstrated that PTX-BA-NP exerted the strongest tumor inhibition among the four groups, with a tumor inhibition rate of 47.79 ± 2.28%, followed by PTX-NP (35.05 ± 5.55%), Taxol® (22.67 ± 6.01%) and betulinic acid nanosuspension (BANP) (14.38 ± 6.02%). These findings indicate that PTX-BA-NP holds great promise for breast cancer therapy.

Dual modulation of bone formation and resorption with zoledronic acid-loaded biodegradable magnesium alloy implants improves osteoporotic fracture healing: An in vitro and in vivo study.

Osteoporotic fracture (OPF) remains a major clinical challenge for skeletal regeneration. Impaired osteogenesis and excessive remodeling result in prolonged and poor quality of fracture healing. To augment bone formation and inhibit excessive resorption simultaneously, we constructed a biodegradable magnesium-based implant integrated with the anti-catabolic drug zoledronic acid (ZA); this implant exhibits controllable, sustained release of magnesium degradation products and ZA in vitro. The extracts greatly stimulate the osteogenic differentiation of rat-bone marrow-derived mesenchymal stem cells (rBMSCs), while osteoclastogenesis is inhibited by ZA. Implantation of intramedullary nails to fix femur fracture in ovariectomy-induced osteoporotic rats for up to 12 weeks demonstrates magnesium implants alone can enhance OPF repair through promoting callus formation compared to conventional stainless steel, while the combinatory treatment with local ZA release from implant coating further increases bone regeneration rate and callus size, remarkably improves bone quality and mechanical strength and suppresses osteoclasts and bone remodeling, due to the synergistic effect of both agents. The slow and uniform degradation of the implant ensures a steady decrease in bending force, which meets clinical requirements. In summary, biodegradable magnesium-based implants can locally co-deliver magnesium degradation products and zoledronic acid in a controlled manner, and can be superior alternatives for the reconstruction of osteoporosis-related fracture. STATEMENT OF SIGNIFICANCE: Management of osteoporotic fracture has posed a major challenge in orthopedics, as the imbalance between diminished osteogenesis and excessive bone remodeling often leads to delayed and compromised fracture repair. Among various efforts expended on augmenting osteoporotic fracture healing, herein we reported a new strategy by engineering and utilizing a biodegradable magnesium-based implant integrated with local drug delivery, specifically, zoledronic acid (ZA)-loaded polylactic acid/brushite bilayer coating on a biodegradable Mg-Nd-Zn-Zr alloy (denoted as Mg/ZA/CaP), aiming to combine the favorable properties of Mg and zoledronic acid for simultaneous modulation of bone formation and bone resorption. In vitro and in vivo studies demonstrated its superior treatment efficacy along with adequate degradation. It stimulated new bone formation while suppressing remodeling, ascribed to the local release of magnesium degradation products and zoledronic acid. To our knowledge, the enhanced fracture repair capability of Mg-based implants was for the first time demonstrated in an osteoporotic fracture animal model. This innovative biodegradable Mg-based orthopedic implant presents great potential as a superior alternative to current internal fixation devices for treating osteoporotic fracture.

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process.

Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague-Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better fracture healing.

Upregulation of Akt signaling enhances femoral fracture healing by accelerating atrophic quadriceps recovery.

Muscle damage and disuse muscular atrophy are detrimental for fracture healing. It has been reported that the Akt signaling pathway plays a role in skeletal muscle hypertrophy and atrophy. The aim of this study was to further investigate whether promoting local muscle function through regulating Akt signaling affects fracture healing. For this purpose, we combined a rat model of short-term atrophy of the quadriceps with a femoral fracture model. In brief, botulinum toxin-A (BTX) were administered locally into the quadriceps one week before femur osteotomy to induce muscle atrophy. For the following weeks after BTX treatment, animals received injection of the Akt activator SC79 (20mg/kg/week) or the Akt inhibitor MK2206 (100mg/kg/week). We found that SC79 significantly accelerated the recovery of quadriceps weight and fiber size after BTX treatment. Moreover, animals that received SC79 injection showed greater bone callus volumes and superior femur mechanical properties. Immunological analysis revealed that the expression levels of the muscle-specific marker myosin heavy chain (MHC) were increased while expression of a negative regulator of muscle mass and function, myostatin, was decreased after SC79 treatment. Furthermore, SC79 increased the mRNA levels of the myogenic regulatory factors MyoD, MRF4 and Myf5 and promoted myotube formation in vitro. Taken together, these findings reveal that SC79 could accelerate the recovery of reversible muscular atrophy induced by BTX and subsequently promote fracture healing through activation of the Akt signaling pathway, which suggests its therapeutic potential in orthopedics.

Transcriptome Profiling Analysis of Wolf Spider Pardosa pseudoannulata (Araneae: Lycosidae) after Cadmium Exposure.

Pardosa pseudoannulata is one of the most common wandering spiders in agricultural fields and a potentially good bioindicator for heavy metal contamination. However, little is known about the mechanisms by which spiders respond to heavy metals at the molecular level. In the present study, high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and to identify differentially expressed genes (DEGs) after cadmium exposure. We obtained 60,489 assembled unigenes, 18,773 of which were annotated in the public databases. A total of 2939 and 2491 DEGs were detected between the libraries of two Cd-treated groups and the control. Functional enrichment analysis revealed that metabolism processes and digestive system function were predominately enriched in response to Cd stress. At the cellular and molecular levels, significantly enriched pathways in lysosomes and phagosomes as well as replication, recombination and repair demonstrated that oxidative damage resulted from Cd exposure. Based on the selected DEGs, certain critical genes involved in defence and detoxification were analysed. These results may elucidate the molecular mechanisms underlying spiders' responses to heavy metal stress.

The Effects of Cadmium Exposure on Fitness-Related Traits and Antioxidant Responses in the Wolf Spider, Pardosa pseudoannulata.

The objective of the present study was to assess the ecotoxicological responses of Pardosa pseudoannulata to a common environmental pollutant, cadmium. Third-instar spiderlings and adult spiders were exposed to sublethal concentrations of CdCl2 solution in their drinking water. The Cd content in P. pseudoannulata adults increased significantly with the number of days of exposure to a 0.2 mM CdCl2 solution, when exposed to 2 mM CdCl2 solution, the Cd content in the spiders increased sharply in the first two (male) or three (female) weeks, and then no significant changes were recorded following with the next three (male) or two (female) weeks exposure. Exposure of spiders to Cd contaminated drinking water resulted in reduced body mass, delayed development, fewer eggs and increased mortality. Significantly higher activities of superoxide dismutase, catalase and glutathione-S-transferase were recorded in the spiders after 7 day exposure to 0.2 mM CdCl2 solution. However, longer-term exposures or increased Cd concentrations did not result in significantly higher antioxidant enzyme activity relative to control treatment.