Janus kinase inhibitors and adverse events of acne in dermatologic indications: a systematic review and network meta-analysis.

Background: The occurrence of acne in patients treated with Janus kinase (JAK) inhibitors for skin diseases is a potential issue, which may reduce treatment adherence.Purpose: To systematically analyzes randomized clinical trials (RCTs) of JAK inhibitors in dermatological indications for the risk of acne as an adverse event.Methods: A meta-analysis of odds ratios (ORs) for acne incidence was conducted. Data were quantitatively synthesized using random-effects meta-analysis. Surface under the cumulative ranking curve (SUCRA) values representing the relative ranking probabilities of treatments were obtained. Analyses were performed using R statistical software version 4.4.0.Results: A total of 11,396 patients were included from 24 studies. The incidence of acne for JAK inhibitors was ranked according to the SUCRA as follows: JAK1 inhibitors > TYK2 inhibitors > combined JAK1 and JAK2 inhibitors > combined JAK1 and TYK2 inhibitors > JAK3 + TEC inhibitors > pan-JAK inhibitors. ORs were higher for longer durations of drug use and larger dosages. Subgroup analyses by disease indication revealed increased ORs for psoriasis (5.52 [95% CI, 1.39-21.88]), vitiligo (4.15 [95% CI, 1.27-13.58]), alopecia areata (3.86 [95% CI, 1.58-9.42]), and atopic dermatitis (2.82 [95% CI, 1.75-4.54]). The use of JAK inhibitors in patients with systemic lupus erythematosus (SLE) may not significantly increase the incidence of acne.Conclusions: There are higher rates of acne following treatment with JAK inhibitors for dermatologic indications, particularly with longer durations and larger dosages. Pan-JAK inhibitors exhibit the lowest incidence of acne.

Serum Metabolomic and Lipidomic Profiling Reveals the Signature for Postoperative Obesity among Adult-Onset Craniopharyngioma.

Craniopharyngioma patients often suffer from a diminished quality of life after surgery, which is usually associated with metabolic disorders and hypothalamic obesity. However, the precise etiology of these conditions remains elusive. To identify the metabolic changes after surgery, we conducted a cross-sectional study using metabolomic and lipidomic analysis to profile metabolic alterations in adult-onset craniopharyngioma patients with postoperative obesity. A cohort of 120 craniopharyngioma patients who had undergone surgery were examined. Differential analyses, including clinical characteristics, serum metabolome, and lipidome, were conducted across distinct body mass index (BMI) groups. Our findings indicated no statistically significant differences in age, sex, and fasting blood glucose among postoperative craniopharyngioma patients when stratified by BMI. However, a noteworthy difference was observed in uric acid and blood lipid levels. Further investigation revealed that alterations in metabolites and lipids were evidently correlated with increased BMI, indicating that postoperative obesity of craniopharyngioma patients affected their whole-body metabolism. Additionally, the multi-omics analysis identified specific metabolites and lipids, including uric acid and DG(18:2/20:4), as contributors to the metabolic disorders associated with postoperative obesity of craniopharyngioma patients. This work provides valuable insight into the involvement of metabolites and lipids in metabolic disorders subsequent to craniopharyngioma surgery.

[Research progress on weak state of lateral wall in intertrochanteric fractures].

Objective: To review the research progress of the weak state of the lateral wall in intertrochanteric fracture, in order to provide clinical references. Methods: The relevant research literature on the lateral wall of intertrochanteric fracture at home and abroad in recent years was summarized and analyzed in terms of morphology, fracture line in coronal plane, and bone density. Results: Assessment of weak state of the lateral wall is particularly important in the treatment of intertrochanteric fractures. Lateral wall thickness is the main way to assess the weak state of the lateral wall, but there are still problems. Many scholars at home and abroad have studied various aspects such as width, height, and length of the anterior cortex, but there is a lack of a comprehensive assessment method. Coronal fractures affect lateral wall morphology and are difficult to detect on X-ray films, requiring vigilance on the part of the clinician. Further research is needed to clarify the correlation between bone density and the weak state of the lateral wall. The femur lesser trochanter fractures interacts with the latertal wall, and the lesser trochanter fracture exacerbates the weak state. The soft tissue around the lateral wall also affects the weak state, so attention must be paid to protecting the soft tissues during operation. Conclusion: There are more methods for assessing the weak state of the lateral wall, but none of them has formed a unified standard. Most of the current studies assess the weak state from a single perspective and lack a comprehensive assessment of all aspects affecting the lateral wall. Fewer studies have been conducted to assess the residual lateral wall function after a partial fracture of the lateral wall, and further research is needed.

Enhanced Selectivity in 4-Quinolone Formation: A Dual-Base System for Palladium-Catalyzed Carbonylative Cyclization with Fe(CO)5.

The use of gaseous CO in Pd-catalyzed carbonylative quinolone synthesis presents challenges related to safety and precise pressure control. In response, a streamlined non-gaseous synthesis of 4-quinolone compounds has been developed. This study introduces a tunable CO-releasing system utilizing Fe(CO)5 activated by a dual-base system of piperazine and triethylamine. This alternative liquid CO resource facilitates the palladium-catalyzed carbonylative C-C coupling and subsequent intramolecular cyclization. By tuning the tandem kinetics of carbonylation and cyclization, this non-gaseous method achieves the successful synthesis of 22 distinct 4-quinolones with excellent yields. This is achieved through the three-component condensation of sub-stoichiometric amounts of Fe(CO)5 with 2-iodoaniline and terminal alkynes. Operando mechanistic studies have revealed a novel CO transfer mechanism that facilitates homogeneous carbonylative cyclization, distinguishing this method from traditional techniques. In addition to addressing safety concerns, this approach also provides precise control over selectivity, with significant implications for pharmaceutical research and the efficient synthesis of pharmaceutical and bioactive compounds.

Finite element analysis of the effect of residual lateral wall volume on postoperative stability in intertrochanteric fractures.

BACKGROUND: Lateral wall fractures represent crucial risk factors for postoperative internal fixation failure in intertrochanteric femoral fractures. However, no consensus exists on the type of lateral wall fracture requiring interventional management. This study aimed to investigate the effect of residual lateral wall volume on the postoperative stability of intertrochanteric femur fractures with associated lateral wall fractures, providing valuable reference for the clinical management of the lateral wall. METHODS: Eleven bone defect models of intertrochanteric femur fractures with varying residual lateral wall volumes were constructed using finite element analysis. These models were fixed with proximal femoral nail antirotation (PFNA). Simulations of von Mises stress and displacement distribution of the PFNA and femur during normal walking were conducted. Statistical analysis was performed to assess the correlation between volume and the maximum von Mises stresses and displacements of the PFNA and femur. RESULTS: In all 11 models, the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and femur occurred at the same locations. As residual lateral wall volume increased, the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and maximum femoral displacement gradually decreased. However, the overall trend of the maximum femoral von Mises stress gradually decreased. At 70% retention of the residual lateral wall volume, there was a more pronounced change in the value of the maximum stress change of the helical blade and the intramedullary nail. Statistical analysis, including the Shapiro-Wilk test and Pearson correlation analysis, demonstrated a significant negative correlation between volume and the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and femur. Linear regression analysis further confirmed this significant negative correlation. CONCLUSION: Finite element analysis of the residual lateral wall revealed a significant correlation between volume and the postoperative stability of intertrochanteric femur fractures. A volume of 70% may serve as the threshold for stabilizing the residual lateral wall. Volume emerges as a novel index for evaluating the strength of the residual lateral walls.

Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial.

BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Ciliogenesis requires sphingolipid-dependent membrane and axoneme interaction.

Cilium formation and regeneration requires new protein synthesis, but the underlying cytosolic translational reprogramming remains largely unknown. Using ribosome footprinting, we performed global translatome profiling during cilia regeneration in Chlamydomonas and uncovered that flagellar genes undergo an early transcriptional activation but late translational repression. This pattern guided our identification of sphingolipid metabolism enzymes, including serine palmitoyltransferase (SPT), as essential regulators for ciliogenesis. Cryo-electron tomography showed that ceramide loss abnormally increased the membrane-axoneme distance and generated bulged cilia. We found that ceramides interact with intraflagellar transport (IFT) particle proteins that IFT motors transport along axoneme microtubules (MTs), suggesting that ceramide-IFT particle-IFT motor-MT interactions connect the ciliary membrane with the axoneme to form rod-shaped cilia. SPT-deficient vertebrate cells were defective in ciliogenesis, and SPT mutations from patients with hereditary sensory neuropathy disrupted cilia, which could be restored by sphingolipid supplementation. These results reveal a conserved role of sphingolipid in cilium formation and link compromised sphingolipid production with ciliopathies.

An antagonistic pleiotropic gene regulates the reproduction and longevity tradeoff.

The antagonistic pleiotropy theory of aging proposes that genes enhancing fitness in early life limit the lifespan, but the molecular evidence remains underexplored. By profiling translatome changes in Caenorhabditis elegans during starvation recovery, we find that an open reading frame (ORF) trl-1 "hidden" within an annotated pseudogene significantly translates upon refeeding. trl-1 mutant animals increase brood sizes but shorten the lifespan and specifically impair germline deficiency­induced longevity. The loss of trl-1 abnormally up-regulates the translation of vitellogenin that produces copious yolk to provision eggs, whereas vitellogenin overexpression is known to reduce the lifespan. We show that the TRL-1 protein undergoes liquid­liquid phase separation (LLPS), through which TRL-1 granules recruit vitellogenin messenger RNA and inhibit its translation. These results indicate that trl-1 functions as an antagonistic pleiotropic gene to regulate the reproduction­longevity tradeoff by optimizing nutrient production for the next generation.

Wnt signaling polarizes cortical actin polymerization to increase daughter cell asymmetry.

Asymmetric positioning of the mitotic spindle contributes to the generation of two daughter cells with distinct sizes and fates. Here, we investigated an asymmetric division in the Caenorhabditis elegans Q neuroblast lineage. In this division, beginning with an asymmetrically positioned spindle, the daughter-cell size differences continuously increased during cytokinesis, and the smaller daughter cell in the posterior eventually underwent apoptosis. We found that Arp2/3-dependent F-actin assembled in the anterior but not posterior cortex during division, suggesting that asymmetric expansion forces generated by actin polymerization may enlarge the anterior daughter cell. Consistent with this, inhibition of cortical actin polymerization or artificially equalizing actin assembly led to symmetric cell division. Furthermore, disruption of the Wnt gradient or its downstream components impaired asymmetric cortical actin assembly and caused symmetric division. Our results show that Wnt signaling establishes daughter cell asymmetry by polarizing cortical actin polymerization in a dividing cell.

Icariin inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells via inhibition of reactive oxygen species production by reducing the expression of NOX1 and NOX4.

Icariin (ICA), isolated from Herba Epimedii, is a natural flavonoid glycoside that possesses antioxidant properties and inhibits osteoclastogenesis. However, the mechanism underlying osteoclastogenesis inhibition by ICA remains unclear. Here, we investigated the effects of ICA on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells. ICA inhibited the expression of osteoclastogenesis-related genes in RAW264.7 cells induced by RANKL. ICA could inhibit osteoclastogenesis without inhibiting the viability of RAW264.7 cells. In addition, ICA inhibited reactive oxygen species production in RANKL-induced RAW264.7 cells. ICA reduced the expression of nuclear factor in activated T cells, cytoplasmic 1, and tartrate-resistant acid phosphatase, which are osteoclast-related molecules. Moreover, ICA decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX), specifically NOX1 and NOX4, in RANKL-induced RAW264.7 cells. Our findings suggest that ICA can be used as a potential therapeutic agent for osteolytic diseases such as osteoporosis.

Postoperative bisphosphonate do not significantly alter the fusion rate after lumbar spinal fusion: a meta-analysis.

BACKGROUND: To evaluate the effect of postoperative BP treatment on improving the fusion rate after lumbar spinal fusion surgery by performing a meta-analysis of randomized controlled trials (RCTs) and other comparative cohort studies. METHODS: A comprehensive search of PubMed, EMBASE, the Web of Science, and the Cochrane Central Register of Controlled Trials was performed for RCTs and other comparative cohort studies on the effect of BP treatment on improving the fusion rate after lumbar spinal fusion surgery. The primary outcome measures were the number of patients with bone formation grades A, B, and C at 12 months of follow-up; fusion rates at 12 and 24 months of follow-up; vertebral compression fracture (VCF) at 12 and 24 months of follow-up; pedicle screw loosening at 24 months of follow-up; and cage subsidence, the Oswestry disability index (ODI), and the visual analogue score (VAS) at 12 months of follow-up. The final search was performed in July 2020. RESULTS: Seven studies with 401 patients were included. Compared with the placebo, BP treatment did not significantly alter the number of patients with bone formation grades A, B, and C, or the VAS at the 12-month follow-up or the fusion rates at the 12- and 24-month follow-ups. In addition, compared with the placebo, BPs significantly reduced the risks of VCF at the 12- and 24-month follow-ups, pedicle screw loosening at the 24-month follow-up, and cage subsidence and the ODI at the 12-month follow-up. CONCLUSIONS: Postoperative BPs do not clearly improve bone formation and the fusion rate, but they reduce VCF, cage subsidence, and loosening of pedicle screws after lumbar fusion surgery compared with the control treatment.

LncRNA small nucleolar RNA host gene 8 promotes cell growth and migration of osteosarcoma in vitro and in vivo by functioning as a ceRNA of microRNA-876-5p.

Osteosarcoma (OS) is the most leading primary malignant tumor of the bone in adolescents and young adults worldwide. Increasing data have suggested that long non-coding RNA (lncRNA) small nucleolar RNA host gene 8 (SNHG8) plays a key role in the progression of various types of human malignancy. However, the roles and potential mechanisms of SNHG8 in OS remain unclear. In this study, we found that SNHG8 levels were obviously upregulated in OS tissues and cell lines. High expression of SNHG8 was significantly correlated with increased tumor size and advanced Enneking stage, and predicted a poor prognosis of OS patients. Functional assays revealed that SNHG8 knockdown inhibited OS cell growth and migration in vitro, and restrained tumor growth of OS in nude mice in vivo. Mechanistically, SNHG8 functioned as a competing endogenous RNA (ceRNA) of miR-876-5p in OS cells. Notably, knockdown of miR-876-5p reversed the inhibitory effects of SNHG8 inhibition on OS cell proliferation and migration. In conclusion, our study suggested that SNHG8 stimulates cell growth and migration of OS cells by functioning as a ceRNA of miR-876-5p, indicating SNHG8 may be served as a novel prognostic biomarker and therapeutic target for the treatment of OS.

Simvastatin inhibits the adipogenesis of bone marrow­derived mesenchymal stem cells through the downregulation of chemerin/CMKLR1 signaling.

Simvastatin is effective in the treatment of osteoporosis, partly through the inhibition of the adipogenesis of bone­marrow derived mesenchymal stem cells (BMSCs). The present study focused on the mechanisms responsible for the inhibitory effects of simvastatin on adipogenesis and examined the effects of simvastatin on the expression of peroxisome proliferator­activated receptor γ (PPARγ), chemerin, chemokine­like receptor 1 (CMKLR1), G protein­coupled receptor 1 (GPR1) and the adipocyte marker gene, adiponectin. BMSCs were isolated from 4­week­old female Sprague­Dawley (SD) rats, and adipogenesis was measured by the absorbance values at 490 nm of Oil Red O dye. The expression of each gene was evaluated by western blot analysis or reverse transcription­quantitative PCR (RT­qPCR). The expression of chemerin increased during adipogenesis, while CMKLR1 exhibited a trend towards a decreased expression. On days 7 and 14, the simvastatin­treated cells exhibited a downregulated expression of chemerin, whereas the upregulated expression of its receptor, CMKLR1 was observed. The results also revealed that CMKLR1 is required for adipogenesis and the simvastatin­mediated inhibitory effect on adipogenesis. Simvastatin regulated adipogenesis by negatively modulating chemerin­CMKLR1 signaling. Importantly, simvastatin stimulation inhibited the upregulation of PPARγ and PPARγ­mediated chemerin expression to prevent adipogenesis. Treatment with the PPARγ agonist, rosiglitazone, partially reversed the negative regulatory effects of simvastatin. On the whole, the findings of the present study demonstrate that simvastatin inhibits the adipogenesis of BMSCs through the downregulation of PPARγ and subsequently prevents the PPARγ­mediated induction of chemerin/CMKLR1 signaling.

Comparison between Minimally Invasive Plate Osteosynthesis and Conventional Open Plating for Midshaft Clavicle Fractures: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to compare the functional outcome and complications in midshaft clavicle fractures receiving minimally invasive plate osteosynthesis and conventional open plating. METHODS: Relevant studies were searched in the databases of Medline, EMBASE, Cochrane Library, Ovid, and Web of Science from inception to March 1, 2019. Pooled data were analyzed with Cochrane Collaboration's Review Manager 5.3. RESULTS: A total of 7 studies were included, of which 2 were randomized controlled trials, 3 were retrospective cohort studies, and 2 were prospective cohort studies including 316 patients. No statistical differences in functional outcome (weighted mean difference [WMD] = 0.99, P = 0.12), operation time (WMD = -10.44, P = 0.07) and time to bone union (WMD = -0.23, P = 0.70) were observed between the two groups. However, minimally invasive plate osteosynthesis reduced rates of skin numbness (odds ratio (OR) = 0.25, 95% CI : 0.13 to 0.48; P < 0.0001) and complications (OR = 0.33, 95% CI : 0.16 to 0.71; P = 0.005) compared with conventional open plating. CONCLUSION: This systematic review and meta-analysis found no differences in terms of functional outcomes, operation time, and fracture healing time between minimally invasive plate osteosynthesis and conventional open plating. However, minimally invasive plate osteosynthesis had apparent advantages in rates of skin numbness and complications.

The medial femoral wall can play a more important role in unstable intertrochanteric fractures compared with lateral femoral wall: a biomechanical study.

BACKGROUND: The major objective of the present study is to investigate the differences in the load and strain changes in the intertrochanteric region of human cadaveric femora between the loss of medial or lateral wall and after treatment with proximal femoral nail antirotation (PFNA). METHODS: After measuring the geometry of the proximal femur region and modeling the medial or lateral wall defect femoral models, six pairs of freshly frozen human femora were randomly assigned in the medial or lateral wall group. According to a single-leg stance model, an axial loading was applied, and the strain distribution was measured before and after PFNA implantation. The strains of each specimen were recorded at load levels of 350, 700, and 1800 N and the failure load. Paired t test was performed to assess the differences between two groups. RESULTS: The failure mode of almost all defect model femora was consistent with that of the simulated type of intertrochanteric fractures. After the PFNA implantation, the failure mode of almost all stabilized femora was caused by new lateral wall fractures. The failure load of the lateral wall group for defect model femora was significantly higher than that of the medial wall group (p < 0.001). However, the difference disappeared after the PFNA was implanted (p = 0.990). The axial stiffness in all defect model femora showed the same results (p < 0.001). After the PFNA implantation, the axial stiffness of the lateral wall group remained higher than that of the medial wall group (p = 0.001). However, the axial stiffness of the lateral wall group showed that the femora removed from the lateral wall were higher than the PFNA-stabilized femora (p = 0.020). For the axial strain in the anterior wall after the PFNA implantation, the strain of the lateral wall group was significantly lower than that of the medial group (p = 0.003). Nevertheless, for the axial strain of the posterior wall after the PFNA implantation, the strain of the medial wall group was significantly lower than that of the lateral group (p < 0.001). CONCLUSIONS: In summary, this study demonstrated that PFNA is an effective intramedullary fixation system for treating unstable intertrochanteric fractures. Compared with the lateral wall, the medial femoral wall is a more important part in the intertrochanteric region. We suggest that in treating intertrochanteric femoral fractures with medial wall fractures, the medial wall fragment should be reset and fixed as much as possible.

Comparison of intramedullary fixation and arthroplasty for the treatment of intertrochanteric hip fractures in the elderly: A meta-analysis.

BACKGROUND: More and more studies conduct to compare intramedullary fixation (IMF) with arthroplasty in treating intertrochanteric hip fractures, but it remains controversy. The aim of this meta-analysis was to find out whether IMF or arthroplasty was more appropriate for treating intertrochanteric hip fractures in elderly patients. METHODS: Relevant studies were searched in the electronic databases of PubMed, Embase, and The Cochrane Central Register of Controlled Trials from January 1980 to September 2016 with English language restriction. Surgical information and postoperative outcomes were analyzed using RevMan 5.3 version. RESULTS: A total of 1239 patients from 11 studies which satisfied the eligibility criteria were included. Compared with IMF, the use of arthroplasty reduced implant-related complications (odds ratio [OR]: 2.05, P = .02) and reoperation rate (OR: 7.06, P < .001), and had similar length of hospital stay (weighted mean difference [WMD]: -0.41, P = .63). However, IMF reduced blood loss (WMD: -375.01, P = .001) and transfusion requirement (OR: 0.07, P < .001), shorter operation time (WMD: -18.92, P = .010), higher Harris hip score (WMD: 4.19, P < .001), and lower rate of 1-year mortality (OR: 0.67, P = .02) compared with arthroplasty. CONCLUSION: The main treatment of intertrochanteric hip fractures is internal fixation using IMF. In the absence of concrete evidence, arthroplasty should be undertaken with caution in carefully selected patient and surgeon should be aware of the increased complexity of doing the arthroplasty in these elderly patients. Further high-quality randomized controlled trials (RCTs) are needed to provide robust evidence and evaluate the treatment options.

CED-10-WASP-Arp2/3 signaling axis regulates apoptotic cell corpse engulfment in C. elegans.

Efficient clearance of apoptotic cells is essential for tissue homeostasis in metazoans. Genetic studies in Caenorhabditis elegans have identified signaling cascades that activate CED-10/Rac1 GTPase and promote actin cytoskeletal rearrangement during apoptotic cell engulfment. However, the molecular connection between CED-10 activation and actin reorganization remains elusive. Here, we provide evidence that CED-10 binds to the Arp2/3 nucleation promoting factor WASP; CED-10 recruits WASP and Arp2/3 to apoptotic cell corpses in the phagocytes. The loss of WASP and Arp2/3 impaired cell corpse engulfment. Furthermore, we uncover that a WASP-activating factor SEM-5/GRB2 functions in the phagocytes to promote cell corpse clearance. Together, our results suggest CED-10 reorganizes the actin cytoskeleton by recruiting the WASP-Arp2/3 actin nucleation factors during apoptotic cell engulfment.

Suppression of Evi1 promotes the osteogenic differentiation and inhibits the adipogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro.

Osteoporosis (OP) is considered a complex disease with a strong genetic impact, mainly affecting post-menopausal women and is also a common cause of fracture. Elucidating the molecular mechanisms that regulate the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is crucial to developing treatment strategies to combat OP. In the present study, we found that ectopic viral integration site­1 (Evi1) was highly expressed during the process of adipogenesis of rat BMSCs. Notably, Evi1 levels markedly increased on day 3 of adipogenic differentiation following the addition of adipogenic induction supplements. In addition, we interfered with the expression of the Evi1 gene in the adipogenesis of BMSCs by supplementing adenoviral plasmids and measured the expression levels of bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), peroxisome proliferator­activated receptor γ2 (PPARγ2) and lipoprotein lipase (LPL) by RT-qPCR and western blot analysis. The mRNA and protein levels of osteogenic and adipogenic markers in the BMSCs were up­ and downregulated, respectively following the silencing of siEvi1. Our experimental results substantiate that the suppression of Evi1 in BMSCs by RNA interference inhibits adipogenic differentiation, while it promotes osteogenic differentiation. The results from our study demonstrated that the Evi1 gene may be targeted as a therapeutic strategy for promoting bone formation.

Bone marrow-derived mesenchymal stem cells expressing the Shh transgene promotes functional recovery after spinal cord injury in rats.

Spinal cord injury (SCI) is one of the most disabling diseases. Cell-based gene therapy is becoming a major focus for the treatment of SCI. Bone marrow-derived mesenchymal stem cells (BMSCs) are a promising stem cell type useful for repairing SCI. However, the effects of BMSCs transplants are likely limited because of low transplant survival after SCI. Sonic hedgehog (Shh) is a multifunctional growth factor which can facilitate neuronal and BMSCs survival, promote axonal growth, prevent activation of the astrocyte lineage, and enhance the delivery of neurotrophic factors in BMSCs. However, treatment of SCI with Shh alone also has limited effects on recovery, because the protein is cleared quickly. In this study, we investigated the use of BMSCs overexpressing the Shh transgene (Shh-BMSCs) in the treatment of rats with SCI, which could stably secrete Shh and thereby enhance the effects of BMSCs, in an attempt to combine the advantages of Shh and BMSCs and so to promote functional recovery. After Shh-BMSCs treatment of SCI via the subarachnoid, we detected significantly greater damage recovery compared with that seen in rats treated with phosphate-buffered saline (PBS) and BMSCs. Use of Shh-BMSCs increased the expression and secretion of Shh, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), improved the behavioral function, enhanced the BMSCs survival, promoted the expression level of neurofilament 200 (NF200), and reduced the expression of glial fibrillary acidic protein (GFAP). Thus, our results indicated that Shh-BMSCs enhanced recovery of neurological function after SCI in rats and could be a potential valuable therapeutic intervention for SCI in humans.

[Protective effect of glial cell line-derived neurotrophic factor infused into the tube setted into cavitas subarachnoidealis on spinal front corner motor neurons].

OBJECTIVE: To investigate the effect of exogenous glial cell line-derived neurotrophic factor (GDNF) infused into the cavitas subarachnoidealis on cornu anterius medullae spinalis motor neurons after sciatic nerve axotomy. METHODS: Forty-eight healthy SD rats were divided into 2 groups randomly: GDNF group and NS group. The left sciatic nerve in rats were cut off. And then 0.9% saline (6 microl) and GDNF solution (6 microl) were injected into cavitas subarachnoidealis at L4-L6 in NS group and GDNF group,respectively. The rats were sacrificed on postoperative 1, 2, 4 and 8 weeks respectively. Their specimen of L4-L6 spinal cord were taken at different time and sectioned. The HE staining, Nissl staining and cholinesterase (ChE) staining in motor neurons were used for counting of motor neurons. RESULTS: In GDNF group the number of motor neurons in cornu anterius medullae spinalis and the ChE activity were higher than that of NS group. CONCLUSION: The exogenous GDNF infused into the cavitas subarachnoidealis are supposed to protect the degenerated spinal motor neuron from death after sciatic nerve injury.