As the society is aging, the increasing prevalence of osteoporosis has generated huge social and economic impact, while the drug therapy for osteoporosis is limited due to multiple targets involved ...in this disease. Zhuangguguanjie formulation (ZG) is extensively used in the clinical treatment of bone and joint diseases, but the underlying mechanism has not been fully described. This study aimed to examine the therapeutic effect and potential mechanism of ZG on postmenopausal osteoporosis. The ovariectomized (OVX) mice were treated with normal saline or ZG for 4 weeks after ovariectomy following a series of analyses. The bone mass density (BMD) and trabecular parameters were examined by micro-CT. Bone remodeling was evaluated by the bone histomorphometry analysis and ELISA assay of bone turnover biomarkers in serum. The possible drug–disease common targets were analyzed by network pharmacology. To predict the potential biological processes and related pathways, GO/KEGG enrichment analysis was performed. The effects of ZG on the differentiation phenotype of osteoclasts and osteoblasts and the predicted pathway were verified
in vitro
. The results showed that ZG significantly improved the bone mass and micro-trabecular architecture in OVX mice compared with untreated OVX mice. ZG could promote bone formation and inhibit bone resorption to ameliorate ovariectomy-induced osteoporosis as evidenced by increased number of osteoblast (N.Ob/Tb.Pm) and decreased number of osteoclast (N.Oc/Tb.Pm) in treated group compared with untreated OVX mice. After identifying potential drug–disease common targets by network pharmacology, GO enrichment analysis predicted that ZG might affect various biological processes including osteoblastic differentiation and osteoclast differentiation. The KEGG enrichment analysis suggested that PI3K/Akt and mTOR signaling pathways could be the possible pathways. Furthermore, the experiments
in vitro
validated our findings. ZG significantly down-regulated the expression of osteoclast differentiation markers, reduced osteoclastic resorption, and inhibited the phosphorylation of PI3K/Akt, while ZG obviously up-regulated the expression of osteogenic biomarkers, promoted the formation of calcium nodules, and hampered the phosphorylation of 70S6K1/mTOR, which can be reversed by the corresponding pathway activator. Thus, our study suggested that ZG could inhibit the PI3K/Akt signaling pathway to reduce osteoclastic bone resorption as well as hamper the mTORC1/S6K1 signaling pathway to promote osteoblastic bone formation.
We have performed a meta-analysis combining data for more than 11 000 individuals. It provides compelling evidence for a positive association between a functional single-nucleotide polymorphism (SNP) ...in the 5′-UTR of GDF5 (+104T/C; rs143383) and osteoarthritis (OA) in European and Asian populations. This SNP has recently been reported to be associated with OA in Japanese and Han Chinese populations. Attempts to replicate this association in European samples have been inconclusive, as no association was found in the case–control cohorts from the UK, Spain and Greece when studied individually. However, the pooled data of UK and Spain found an association of the T-allele with an odds ratio (OR) of 1.10. Although the European studies had adequate power to replicate the original findings from the Japanese cohort (OR = 1.79), these results suggest that the role of the GDF5 polymorphism may not be as strong in Europeans. To clarify whether the European studies were hampered by insufficient power, we combined new data from the UK and the Netherlands with the three published studies of Europe and Asia. The results provide strong evidence of a positive association of the GDF5 SNP with knee OA for Europeans as well as for Asians. The combined association for both ethnic groups is highly significant for the allele frequency model (P = 0.0004, OR = 1.21) and the dominant model (P < 0.0001, OR = 1.48). These findings represent the first highly significant evidence for a risk factor for the development of OA which affects two highly diverse ethnic groups.
Purpose. The purpose of this retrospective study was to determine the association between preoperative soleal vein (SV) diameter and deep vein thrombosis (DVT) following total joint arthroplasty ...(TJA). Methods. A total of 402 patients were enrolled, with 229 patients undergoing total knee arthroplasty (TKA) and 173 patients undergoing total hip arthroplasty (THA). Ultrasonography was performed 1-3 days preoperatively, on postoperative days 1, 3, and 7, or before discharge and during follow-up. The SV diameter was assessed preoperatively. Univariate analysis and multivariate logistic regression analysis were used to compare parameters between the DVT group and the non-DVT group. Results. 78 patients (19.4%) were found to have DVT during hospitalization and after discharge and 14 patients (3.5%) developed symptomatic DVT. Multiple regression analysis showed that SV diameter, advanced age, and surgery type were independent predictors of postoperative DVT. In the logistic regression analysis for symptomatic DVT, SV diameter was found to be the only predictor. In the receiver operating characteristics (ROC) analysis for the value of SV diameter in diagnosing DVT, the area under curve (AUC) was 0.701 ((95% CI 0.636-0.766), P<0.001) and when the cut-off value of SV diameter was set at 0.57 cm, the sensitivity and specificity of SV diameter were 62.7% and 72.1%, respectively. Conclusions. SV diameter was an independent risk factor for total and symptomatic DVT after TJA. Preoperative ultrasound screening of the SV diameter may be beneficial for the prevention of postoperative DVT.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial.
A total of ...116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively.
None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications.
The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications.
In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Deep vein thrombosis is one of the common complications of orthopedic surgery. Studies indicated that genetic factors played a considerable role in the pathogenesis of deep vein thrombosis. ...Endothelial nitric oxide synthase which encoded by nitric oxide synthase 3 (NOS3), can generate nitric oxide in endothelial cells. As a predominant regulator for vascular homeostasis, nitric oxide might be involved in the pathogenesis of thrombosis. It had been proved that the NOS3 polymorphism (rs1799983) was associated with the development of cardiovascular diseases. Our objective was to evaluate the association between the NOS3 polymorphism (rs1799983) and deep vein thrombosis after orthopedic surgery in Chinese Han population. The polymorphism was genotyped in 224 subjects with deep vein thrombosis after orthopedic surgery and 580 controls. Allele and genotype frequencies were compared between subjects with deep vein thrombosis and control subjects. The allele and genotype frequencies of the NOS3 polymorphism (rs1799983) were significantly different between subjects with deep vein thrombosis and control subjects. There were also significant differences when the subjects were stratified by gender, surgery type and hypertension status. These findings suggested that the NOS3 polymorphism (rs1799983) was associated with susceptibility to the deep vein thrombosis after orthopedic surgery in Chinese Han population, and NOS3 might play a role in the development of deep vein thrombosis after orthopedic surgery.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previous studies have suggested that leptin works as a key regulator in the pathogenesis of osteoarthritis (OA), and genetic factors modulate OA. This study assessed the contribution of leptin gene ...(LEP) polymorphism(s) to knee OA among Han Chinese. Three tag single-nucleotide polymorphisms (SNPs) covering all those LEP SNPs of which the minor allele frequencies were over 10% were selected. Study subjects (697 patients and 699 controls) were divided into four groups (underweight, normal weight, overweight and obese) by body mass index (BMI). Allele and genotype frequencies in the three tag SNPs were significantly different in the normal weight and overweight groups. In the normal weight, overweight and obese groups, BMI (P=4.3 × 10(-5), 0.012 and 0.009, respectively) and gender (P=3.5 × 10(-22), 5.1 × 10(-23) and 2.1 × 10(-8), respectively) were effective factors. Age was an independent effective factor in the overweight group (P=0.009). Haplotypes were associated with OA in the normal weight group (CAT, P=0.015) and the overweight group (AGC, P=0.015). Our results suggest an association between LEP and knee OA in the normal weight and overweight groups among Han Chinese.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The purpose of this study was to analyze femoral shaft sagittal parameters in Chinese osteoarthritis (OA) patients undergoing total knee arthroplasty (TKA) and identify whether the parameters in the ...coronal plane could be predictors of those in the sagittal plane.
Standard long-standing anteroposterior and femoral lateral radiographs of 50 lower limbs in 50 Chinese OA patients were included. Sagittal femoral bowing angle (sFBA), angle between femoral distal anterior cortex axis and sagittal mechanical axis (DACSMA), angle between femoral distal anterior cortex axis and sagittal distal anatomic axis (DACSDAA), and angle between femoral sagittal mechanical axis and sagittal distal anatomic axis (SMADAA) were measured. Then the relationship between femoral shaft parameters in the sagittal and coronal planes were identified, including coronal femoral bowing angle (cFBA), valgus angle, hip-knee-ankle angle (HKA), length of femur (LF), femoral offset, femoral neck stem angle (FNS), and mechanical lateral distal femoral angle (mLDFA). A two-sided Pearson correlation coefficient was obtained to identify the correlations between parameters in the coronal and sagittal planes. P values <0.05 were considered statistically significant.
The mean sFBA was 15.08° ± 3.79°, the mean DACSMA was 1.35° ± 2.70°, the mean DACSDAA was -2.66° ± 2.05°, and the mean SMADAA was 4.01° ± 2.55°. No correlation between parameters in the coronal and sagittal planes was found.
In this study, the discreteness of DACSMA, DACSDAA, and SMADAA in Chinese OA patients is high and this may affect the position of femoral prosthesis after TKA using the conventional intramedullary device. No parameters in the coronal plane are found correlated with those in the sagittal plane.
Researchregistry2337.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Diabetic complications can be ameliorated by inhibiting excessive oxidative stress with antioxidants. To enhance therapeutic intervention, it is crucial to develop intelligent scaffolds for efficient ...delivery of antioxidants to diabetic wounds. This study introduces reversible boronic bonds to create an intelligent antioxidant hydrogel scaffold. This study modifies gelatin methacryloyl (GelMA) with 4‐carboxyphenyboronic acid (CPBA) to synthesize a derivative of GelMA (GelMA‐CPBA), and then photo cross‐links GelMA‐CPBA with (−)‐epigallocatechin‐3‐gallate (EGCG) to form GelMA‐CPBA/EGCG (GMPE) hydrogel. The GMPE hydrogel responds to changes in glucose levels, and more EGCG is released as glucose level increases due to the dissociation of boronic ester bonds. The GMPE hydrogel shows good biocompatibility and biodegradability, and its mechanical property is similar to that of the skin tissue. Both in vitro and in vivo results demonstrate that the GMPE hydrogel scaffolds effectively eliminate reactive oxygen species (ROS), reduce the inflammation, and promote angiogenesis, thereby improve collagen deposition and tissue remodeling during diabetic wound healing. This strategy offers new insight into glucose‐responsive scaffolds, and this responsive antioxidan hydrogel scaffold holds great potential for the treatment of chronic diabetic wounds.
Incorporating glucose‐sensitive and reversible boronic ester bonds enables the hydrogel with a unique glucose‐responsive antioxidant release that helps scavenge excessive reactive oxygen species (ROS). This allows the hydrogel to scavenge excessive ROS and inhibits inflammation, while promoting angiogenesis and collagen deposition. As a result, the GMPE hydrogels are able to accelerate the repair of diabetic wounds.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The naturally tight entanglement of fibers in bacterial cellulose (BC) results in low printability when BC is used as a bioink for printing scaffolds. In this study, neat BC was treated by ...TEMPO-mediated oxidation (TO-BC) and maleic acid (MA-BC) to prepare homogeneous BC dispersions to fabricate scaffolds for bone regeneration. Results showed that the treatments released individual fibrils in the corresponding uniform dispersions without impairing inherent crystalline properties. Compared with TO-BC, MA-BC hybridized with gelatin could endow the gel with improved rheological properties and compression modulus for 3D printing. Both TO-BC and MA-BC dispersions showed good osteoblast viability. However, MA-BC possessed more pronounced ability to express osteogenic marker genes and formation of mineralized nodules in vitro. Compared with TO-BC-based gelatin scaffolds, MA-BC-based gelatin scaffolds showed a better ability to stimulate the regeneration of rat calvaria, demonstrating a higher bone mineral density of newly formed bone and trabecular thickness in vivo.
•TEMPO and MA treatments can liberate individual fibrils in BC dispersion.•MA treated BC endows gelatin with better compression modulus for 3D printing.•MA treated BC shows best performance for bone regeneration in vitro and in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The factors, kinetics, and driving forces on the basic model protein loading into porous Hep/CaCO3 microparticles were well investigated.
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•The adsorption obeyed pseudo second-order ...kinetics and Langmuir adsorption model.•Doping heparin and pH greatly influenced the maximum capacity of lysozyme loading.•Electrostatic interaction mainly contributed to lysozyme adsorption.•Orientation of lysozyme shifted between “side on” and “end on” at different pH.•The bioactivity of released lysozyme retained after release-reloading cycles.
Porous CaCO3 microparticles are considered as one of the most popular and effective carriers for protein loading. Most of current studies have centered on elucidating particle formation and enhancing the protein loading efficiency, very few reports on the kinetics, driving forces and factors on protein loading process. Here, we took lysozyme as the basic model protein to investigate the kinetics, driving forces on protein loading and factors controlling loading efficiency into porous Hep/CaCO3 microparticles by various techniques (protein quantification assay, QCM-D, SEM, BET, Zeta sizer, TGA, CLSM, CD spectrum, bioactive assay). As revealed, the adsorption process obeyed the pseudo second-order kinetics and Langmuir adsorption model. Doping heparin greatly influenced the detailed texture, pore size, surface area, and maximum loading capacity of lysozyme (LCLys,m). The dependence of LCLys,m on pH reflected the electrostatic interaction mainly contributed to lysozyme adsorption, especially below IEP of lysozyme. But the hydrophobic interaction also played the critical role on lysozyme adsorption at pH around IEP of lysozyme. Accompanying with pH change, the lysozyme orientation shifted from “side on” at lower pH to “end on” at pH around IEP. At proper concentration of NaCl (CNaCl), the loaded lysozyme could be released from Hep/CaCO3 microparticles, making them available for lysozyme reloading. Most importantly, such release-reloading cycle didn’t disturb the bioactivity of released lysozyme and following reloading ability. We believe our work will contribute to understand protein adsorption behaviors, improve protein loading efficacy, biomaterials design, tissue engineering and disease treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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