Associations of vitamin D receptor polymorphisms with risk of Alzheimer's disease, Parkinson's disease, and mild cognitive impairment: a systematic review and meta-analysis.

Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by binding to vitamin D receptor (VDR). Associations between VDR gene polymorphism and Alzheimer's disease (AD), Parkinson's disease (PD), and mild cognitive impairment (MCI) risk has been investigated extensively, but the results remain ambiguous. The aim of this study was to comprehensively assess the correlations between four VDR polymorphisms (FokI, BsmI, TaqI, and ApaI) and susceptibility to AD, PD, and MCI. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the relationship of interest. Pooled analyses suggested that the ApaI polymorphism decreased the overall AD risk, and the TaqI increased the overall PD susceptibility. In addition, the BsmI and ApaI polymorphisms were significantly correlated with the overall MCI risk. Stratified analysis by ethnicity further showed that the TaqI and ApaI genotypes reduced the AD predisposition among Caucasians, while the TaqI polymorphism enhanced the PD risk among Asians. Intriguingly, carriers with the BB genotype significantly decreased the MCI risk in Asian descents, and the ApaI variant elevated the predisposition to MCI in Caucasians and Asians. Further studies are need to identify the role of VDR polymorphisms in AD, PD, and MCI susceptibility.

Shunt rate of ductus arteriosus and ductus venosus in middle and late fetuses and their application value in the evaluation of fetal growth restriction.

Objective: To explore the Shunt rate of ductus arteriosus (DA) and ductus venosus (DV) in middle and late fetuses and their application value in the evaluation of fetal growth restriction (FGR). Methods: In this retrospective observational study, we reviewed the clinical data of the patients who admitted to the Second Affiliated Hospital of Wenzhou Medical University from September 10, 2017 to November 27, 2018, and finally included 44 normal women at 28-31 weeks of pregnancy (Normal group) and 15 pregnant women with fetal growth restriction (FGR) within 28-31 weeks of gestation (FGR group). We measured blood flows of the DA (QDA), pulmonary artery (QPA), DV (QDV), and umbilical vein (QUV) and the shunt rates of the DA and DV (QDA/QPA and QDV/QUV, respectively) in all fetuses. We compared the mean variables between groups using the Normal group means as the normal reference values for analysis. Results: DA shunt rate was linearly and positively correlated with gestational age (Y=1.455X+2.787; r=0.767, P<0.01), while the DV shunt rate was linearly and negatively correlated with gestational age (Y=-2.791X+126.885; r=0.761, P<0.01). The DA shunt rates (QDA/QPA) of fetuses in the normal were higher than those in the FGR groups, but the differences between the two groups were not statistically significant (P > 0.05). The DV shunt rates (QDV/QUV) of fetuses in the normal were significantly lower than those in the FGR groups (P < 0.05). The DV shunt rates in the FGR group were significantly higher than those in the normal group with differences being statistically significant at 30-30+6 and 31-31+6 gestational weeks (P < 0.05) The receiver operating characteristic curve (ROC curve) showed that the higher the shunt rate, the worse the birth outcome of a fetus with FGR. Conclusions: The DV shunt rate in middle- and late-stage fetuses can predict the fetal birth outcome, and the higher the shunt ratio, the worse the birth outcome of FGR fetuses.

Histone H3K9 demethylase JMJD2B/KDM4B promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells by regulating H3K9me2 on RUNX2.

Background: A variety of proteins including epigenetic factors are involved in the differentiation of human bone marrow mesenchymal stem cells. These cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice versa) after commitment. Further in-depth study of their epigenetic alterations may make sense. Methods: Chromatin Immunoprecipitation-PCR (ChIP-PCR) was used to detect the methylation enrichment status of H3K9me2 in the Runx2 promoter, alizarin red and alkaline phosphatase (ALP) staining were used to detect osteogenic differentiation and mineralization ability, western blot and quantitative RT-PCR were used to measure the differential expression of osteogenesis-related proteins and genes. Recombinant Lentivirus mediated gain-of-function and loss-of-function study. The scale of epigenetic modification was detected by laser confocal. Results: Our results showed that compared with human bone marrow mesenchymal stem cells (hBMSCs) without osteogenic differentiation treatment, hBMSCs after osteogenic differentiation significantly promoted osteogenic differentiation and mRNA expression such as JMJD2B/KDM4B, osteogenesis-related genes like Runx2 and FAM210A in hBMSCs cells, suggesting that upregulation of JMJD2B/KDM4B is involved in the promoting effect of osteogenesis. After overexpression and silencing expression of JMJD2B, we found a completely opposite and significant difference in mRNA expression of osteogenesis-related genes and staining in hBMSCs. Overexpression of JMJD2B/KDM4B significantly promoted osteogenic differentiation, suggesting that JMJD2B/KDM4B could promote osteogenesis. In addition, ChIP-PCR showed that overexpression of JMJD2B/KDM4B significantly reversed the methylation enrichment status of H3K9me2 in Runx2 promoter. Furthermore, overexpression of JMJD2B/KDM4B significantly reverses the inhibitory effect of BIX01294 on H3K9me2, suggesting that JMJD2B/KDM4B regulates the osteogenic differentiation of hBMSCs by changing the methylation status of H3K9me2 at the Runx2 promoter. Conclusions: Taken together, these results suggest that JMJD2B/ KDM4B may induce the osteogenic differentiation of hBMSCs by regulating the methylation level of H3K9me2 at the Runx2 promoter.

Combination of Fusiform Capsulectomy of the Posterior Capsule and Percutaneous Flexion Tendon Release in the Treatment of Fused Knee with Severe Flexion Contracture During Total Knee Arthroplasty-A Report of Six Cases.

Purpose: This clinical research aims to assess the safety and efficacy of a combination of fusiform capsulectomy of the posterior capsule and percutaneous flexion tendon release in the treatment of a fused knee with severe flexion contracture during total knee arthroplasty (TKA). Methods: A retrospective analysis was performed in three patients (six knees) who had preoperative severe bony fused flexion contracture (>80°) prior to TKA and received a combination of fusiform capsulectomy of posterior capsule and percutaneous flexion tendon release during TKA between January 2016 and December 2019. The range of motion (ROM), knee functional score, postoperative complications, and radiographic results were evaluated. Result: Three patients (six knees) were enrolled in this study. The mean duration of follow-up was 42.83 ± 15.77 months. The postoperative knee ROM was 100.0 (76.0, 102.75) (p < 0.01). The knee society score (KSS) clinical score increased from a preoperative 30.0 (25.0, 36.0) to a postoperative 64.0 (65.0, 78.0) (p < 0.01), and the KSS function score increased from a preoperative 0.0 (0.0, 30.0) to a postoperative 55.0 (40.0, 55.0) (p < 0.01). No implant loosening, infection, neurovascular complications, or revision were recorded in the cohort until the last follow-up. Conclusion: The technique of a combination of fusiform capsulectomy of the posterior capsule and percutaneous flexion tendon release is an effective and safe method during primary TKA for a fused knee with severe flexion contracture.

Correcting severe flexion contracture with fusiform capsulectomy of posterior capsule during total knee arthroplasty.

PURPOSE: This study aimed to evaluate the safety and efficacy of fusiform capsulectomy of posterior capsule in correcting severe flexion contracture during total knee arthroplasty (TKA). METHODS: A retrospective analysis was performed in the patients who had preoperative severe flexion contracture (> 30 degrees) prior to TKA and received fusiform capsulectomy of posterior capsule during TKA between December 2013 and November 2018. Range of motion (ROM), knee functional score, forgotten joint score (FJS), post-operative complications, and radiographic results were collected and evaluated. RESULT: Twenty patients (32 knees) were enrolled in this study. The mean duration of follow-up was 27.19 ± 15.92 months. The flexion contracture improved from pre-operative 37.69 ± 11.79° to post-operative 5.78 ± 4.44° (p < 0.001), and ROM increased from pre-operative 63.50 ± 21.74° to post-operative 97.88 ± 13.20° (p < 0.001). KSS clinical score increased from pre-operative 32.94 ± 11.03 to post-operative 82.34 ± 10.73 (p < 0.001), and KSS function score increased from pre-operative 28.97 ± 18.43 to post-operative 68.75 ± 15.96 (p < 0.001). The post-operative FJS was 76.08 ± 2.14. There was no implant loosening, infection, obvious haematoma formation, resultant instability, neurovascular complications, or revision for any reasons in the cohort until the last follow-up. CONCLUSIONS: The technique of fusiform capsulectomy of posterior capsule to correct the severe flexion contracture during primary TKA is safe and effective and could provide good short-term results.

Lysine-Specific Demethylase 4A Regulates Osteogenic Differentiation via Regulating the Binding Ability of H3K9me3 with the Promoters of Runx2, Osterix and Osteocalcin.

A well-studied subject of epigenetics, the histone methylation located at lysine and arginine is overseen via methyltransferases and demethylases. Lysine-specific demethylase 4A (KDM4A) comprises a lysine demethylase and possesses specificity for H3K9me3 and H3K36me3, which is capable of being used in order to activate histone transcription. Our team examined the expression of KDM4A within Sprague Dawley (SD) rats and further investigated the mechanism via which this phenomena regulates osteogenic variation within the present study. The overexpression of KDM4A facilitated the process of osteoblast differentiation in bone mesenchymal stem cells (BMSC), while the knocking down differentiation via osteoblast was restrained via the suppression of the expression of Runx2, Osterix, alkaline phosphatase (ALP), and osteocalcin (OCN). Knocking down KDM4A lowered levels of the promoter expression of Runx2, osterix, and OCN, and raised levels of H3K27me3 expression. The results demonstrated that KDM4A possesses a crucial role within the differentiation of osteoblasts and furthermore regulates the expression of Runx2, Osterix, and OCN via H3K9me3. The present research may provide new insights into the treatment of bone healing.

[Application of quadriceps snip in complex total knee arthroplasty].

OBJECTIVE: To explore the safety and effectiveness of quadriceps snip in complex total knee arthroplasty (TKA). METHODS: A clinical data of 19 cases (29 knees) with complex TKA assisted with quadriceps snip between January 2016 and May 2017 were retrospectively analyzed. There were 9 males (13 knees) and 10 females (16 knees). The age of patients ranged from 34 to 66 years (mean, 50.2 years). Four patients (8 knees) were ankylosing spondylitis, 5 patients (7 knees) were rheumatoid arthritis, and 10 patients (14 knees) were knee osteoarthritis. The average disease duration was 10.9 years (range, 8-15 years). There were 12 knees of Kellgren-Lawrence grade Ⅲ and 17 knees of Kellgren-Lawrence grade Ⅳ. The range of motion (ROM) of knee was (19.86±7.23)°. The clinical and function scores of knee society score (KSS) were 47.86±11.26 and 15.52±11.21, respectively. Postoperative complications, ROM, KSS scores, extensor lag, and prosthesis loosening were observed to evaluate the effectiveness. RESULTS: All incisions healed by first intention, and no infection or cardiovascular and cerebrovascular accidents occurred. All patients were followed up 25-39 months (mean, 30.3 months). At last follow-up, the ROM of knee was (91.03±7.30) °, the KSS clinical score was 83.62±9.99 and functional score was 66.38±7.89, showing significant differences when compared with preoperative ones ( P<0.05). Postoperative extensor lag (10°, 10°, 15°) occurred in 3 cases. There was no evidence of prosthesis loosening or osteolysis on X-ray films during follow-up. CONCLUSION: The application of quadriceps snip in complex TKA can effectively improve the operative field exposure and reduce incidence of complications such as patella tendon tearing, patella fracture, and quadriceps tendon injury. The surgical technique of Krackow tendon suture can effectively guarantee early rehabilitation without occurrence of other complications.

Efficacy of Xianling Gubao capsule in treating sarco-osteopenia: Protocol for a systematic review and meta-analysis.

BACKGROUND: Sarco-osteopenia (SOP) is a new type of geriatric syndrome, resulting from the combination of sarcopenia (SP) and osteoporosis (OP). Xianling Gubao capsule (XLGBC), made from several traditional Chinese medicine, is reported to have a therapeutic effect on diseases of bones and joints. This protocol will be designed to assess the efficacy of XLGBC in the treatment of SOP. METHODS: Relevant randomized controlled trial literatures evaluating the effect of XLGBC on patients with SOP will be obtained by searching the following 7 electronic databases: Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical and Medical Database (CBM), and Wanfang Database, from inception to March 2019. The primary outcomes will be bone mineral density, skeletal muscle mass index, handgrip strength, and gait speed. Stata V.13.0 software will be used for data synthesis and analysis, sensitivity analysis, subgroup analysis, and risk of bias assessment. Reporting bias will be evaluated utilizing a funnel, with Egger tests assessing funnel plot symmetries. Quality of evidence will be evaluated according to guidance of the Recommendations Assessment, Development, and Evaluation guideline. RESULT: This study will provide a rational synthesis of current evidences for XLGBC on SOP. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of XLGBC on SOP. ETHICS AND DISSEMINATION: This systematic review will be contributed to peer-reviewed publications, aiming to provide evidence about efficacy of XLGBC on SOP. TRIAL REGISTRATION NUMBER: CRD42019128223.

The failure experience of complex total hip arthroplastyin osteopetrosis: case report and literature review.

There is rare literature elaborating the complex total hip arthroplasty (THA) in patients with osteopetrosis who experienced malunion from femoral neck fracture. We have summarized the failure experience of the complex THA in osteopetrosis. Learned from the resurgery in the case reported by this paper, we recommend to highlight the initial stability of the prosthesis and not to overestimate the potency of fracture healing in the complex THA in osteopetrosis.

Saikosaponin a inhibits RANKL-induced osteoclastogenesis by suppressing NF-κB and MAPK pathways.

Inflammatory cytokines play an important role in osteoclastogenesis. Saikosaponin a (SSa) possesses anti-inflammatory activity. However, the role of SSa in osteoporosis is still unclear. Therefore, the objective of this study was to investigate the effects of SSa on receptor activator of the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and signaling pathway by in vitro assay. In mouse bone marrow monocytes (BMMs), SSa suppressed RANKL plus macrophage colony-stimulating factor (M-CSF)-induced osteoclast differentiation in a dose-dependent manner. Moreover, SSa decreased osteoclastogenesis-related marker proteins expression, including NFATc1, c-fos and cathepsin K. At molecular levels, SSa inhibited RANKL-induced IκBα phosphorylation, p65 phosphorylation and NF-κB luciferase activity in RAW264.7 cells. And SSa also suppressed RANKL-induced p-38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these findings suggest that SSa suppresses osteoclastogenesis through inhibiting RANKL-induced p-38, ERK, JNK and NF-κB activation. SSa is a novel agent in the treatment of osteoclast-related diseases, such as osteoporosis.

[EFFECTIVENESS OF UC ULTRA-CONGRUENT ROTATING PLATFORM PROSTHESIS IN TREATMENT OF KNEE OSTEOARTHRITIS].

OBJECTIVE: To explore the effectiveness of UC ultra-congruent rotating platform prosthesis in the treatment of knee osteoarthritis by comparing with fixed-bearing implant. METHODS: The clinical data were retrospectively analyzed, from 98 patients (98 knees) with knee osteoarthritis undergoing primary total knee arthroplasty between January 2011 and December 2012. The UC ultra-congruent rotating platform prosthesis was used in 56 cases (mobile-bearing group) and fixed-bearing implant was used in 42 cases (fixed-bearing group). There was no significant difference in gender, age, side, weight, disease duration, grading of arthritis, the number of varus and valgus malformation, preoperative range of motion of the knee, the Knee Society Score (KSS) score, the visual analogue scale (VAS) score, femorotibial angle, tibial angle, and articular surface angle between 2 groups (P > 0.05). The operation time (including anesthetic time), intraoperative blood loss, hospitalization time, total hospitalization expenses, postoperative range of motion of the knee, the KSS score, and the VAS score were compared. The femorotibial angle, tibial angle, and articular surface angle were measured on the basis of anteroposterior and lateral X-ray films, and prosthesis loosening was observed. RESULTS: There was no significant difference in the operation time, intraoperative blood loss, and hospitalization time between 2 groups (P > 0.05), while the total hospitalization expenses of fixed-bearing group were significantly lower than those of the mobile-bearing group (t = 8.506, P = 0.000). The patients were followed up 16-30 months in the mobile-bearing group, and for 16-38 months in the fixed-bearing group. Postoperative complications occurred in 3 cases (7.14%) of the fixed-bearing group (1 case of fat liquefaction of incision, 1 case of joint stiff, and 1 case of anterior knee pain), and in 3 cases (5.36%) of the mobile-bearing group (1 case of delayed wound healing, and 2 cases of anterior knee pain); there was no significant difference in the complication rate between 2 groups (χ2 = 0.133, P = 0.516). At last follow-up, the KSS score, VAS score, range of motion of the knee, femorotibial angle, tibial angle, and articular surface angle were superior significantly to those before operation in both groups (P < 0.05), but no significant difference was found between 2 groups (P > 0.05). No radiographic signs of radiolucent line, prosthetic dislocation, patellar dislocation, prosthetic loosening, and fracture was found. CONCLUSION: UC ultra-congruent rotating platform prosthesis in the treatment of knee osteoarthritis can effectively improve the knee joint function and relief pain, which has the same short-term effectiveness in fixed bearing implant.