Bmi-1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging.

With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi-1 co-localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1-driven Bmi-1 knockout in bone-marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1-driven Bmi-1 overexpression showed a contrasting phenotype to Prx1-driven Bmi-1 knockout in BMSCs. Regarding mechanism, Bmi-1-RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313 bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi-1-EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region -1605 to -1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1-driven Bmi-1 overexpression rescued the SOP induced by Prx1-driven Bmi-1 knockout in BMSCs. Thus, Bmi-1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1-driven Bmi-1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP.

An unusual Ogden type V tibial tubercle avulsion fracture: a case report and literature review.

BACKGROUND: Ogden type V tibial tubercle avulsion fracture is an unusual type of physial injury. Thus, little is known about its mechanism of injury and treatment. The type of osteosynthesis is variable and depends on the experience of the surgeon. We commonly used cancellous screws fixation combined with tension band wiring for displaced fracture of the anterior tibial tuberosity. CASE PRESENTATION: The present manuscript describes a case of a Han nationality 13-year-old boy who presented with severe pain of the left knee, which began after landing following a high jump. He had no significant past medical history apart from a high body mass index of 30.3. Radiographs revealed that he had an unusual Ogden type V tibial tubercle avulsion fracture. He was treated by open reduction and combined fixation with cannulated screws and tension-band wiring. After 3 months, the fracture healed without any complications or knee symptoms with full range of motion. He underwent reoperation for symptomatic hardware, which was removed at 5 months after initial surgery, and returned to his prior level of sporting activity at 1 year follow-up. CONCLUSION: Our case suggests that excellent functional outcome could be achievable by open reduction with the combination of internal fixation and tension-band wiring for Ogden type V tibial tubercle avulsion fracture. This type of osteosynthesis could not only achieve anatomical reduction and stable fixation for such fractures, but also avoid further damage to the proximal tibial epiphysis, which prevents serious complications, such difference in leg length.

Lipopolysaccharide-induced bacterial infection model: microRNA-370-3p participates in the anti-infection response by targeting the macrophage TLR4-NLRP3 caspase-1 cellular pyroptosis pathway.

OBJECTIVE: To explore the effect of miR-370-3p on LPS triggering, in particular its involvement in disease progression by targeting the TLR4-NLRP3-caspase-1 cellular pyroptosis pathway in macrophages. METHODS: Human macrophage RAW264.7 was divided into 6 groups: control, LPS, LPS + inhibitor-NC, LPS + miR-370-3p inhibitor, LPS + mimics-NC and LPS + miR-370-3p mimics. RT-qPCR was used to detect the expression level of miR-370-3p and analyzed comparatively. CCK-8 and flow cytometry assays were used to detect cell viability and apoptosis. ELISA assay was used to detect the levels of IL-1ß and TNF-α in the supernatant of the cells. The WB assay was used to detect TLR4, NLRP3, Caspase-1 and GSDMD levels. RESULTS: After LPS induction, macrophage miR-370-3p levels decreased, cell viability decreased, and apoptosis increased. At the same time, the levels of TLR4, NLRP3, Caspase-1 and GSDMD increased in the cells, and the levels of IL-1ß and TNF-α increased in the cell supernatant. Compared with the LPS group, the significantly higher expression level of miR-370-3p in the cells of the LPS + miR-370-3p mimics group was accompanied by significantly higher cell viability, significantly lower apoptosis rate, significantly lower levels of TLR4, NLRP3, Caspase-1, and GSDMD in the cells, and significantly lower levels of IL-1ß and TNF-α in the cell supernatant. CONCLUSION: MiR-370-3p may be involved in anti-infective immune responses by targeting and inhibiting the macrophage TLR4-NLRP3-caspase-1 cellular pyroptosis pathway.

Tetramethylpyrazine Nitrone (TBN) Reduces Amyloid ß Deposition in Alzheimer's Disease Models by Modulating APP Expression, BACE1 Activity, and Autophagy Pathways.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with age. A wealth of evidence indicates that the amyloid ß (Aß) aggregates result from dyshomeostasis between Aß production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aß reduction represent a promising strategy for AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with potential for the treatment of AD. Previously, we demonstrated that TBN markedly enhanced cognitive functions and decreased the levels of Aß, APP, BACE 1, and hyperphosphorylated tau in 3×Tg-AD mice. However, the mechanism by which TBN inhibits Aß deposition is still unclear. In this study, we employed APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months, and N2a/APP695swe cells treated with TBN (300 µM) to explore the mechanism of TBN in Aß reduction. Our results indicate that TBN significantly alleviated cognitive impairment and reduced Aß deposition in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway, inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, and decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-ß, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aß levels likely by reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery.

BACKGROUND: Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery. METHODS: We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis. RESULTS: The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14-4.57; p = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26-5.02; p = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59-11.82; p = 0.004) were independently associated with stroke recurrence. CONCLUSIONS: The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

An arabinoxylan (AOP70-1) isolated from Alpinia oxyphylla alleviates neuroinflammation and neurotoxicity by TLR4/MyD88/NF-κB pathway.

Alpinia oxyphylla is famous for its neuroprotective and memory-improving effects. A crude polysaccharide AO70 from A. oxyphylla remarkably ameliorated neuroinflammation and cognitive dysfunction in Alzheimer's disease mice. This study aimed to explore the bioactive component of AO70 and its mechanism of action. A homogeneous polysaccharide (AOP70-1) rich in arabinose and xylose was purified from AO70, which was consisted of α-L-Araf-(1→, →5)-α-L-Araf-(1→, ß-D-Xylp-(1→,→2,4)-ß-D-Xylp-(1→, →2,3,4)-ß-D-Xylp-(1→, α-L-Rhap-(1→, α-D-Manp-(1→, →4)-α-D-Glcp-(1→, →4)-α-D-GlcpA-(1→, ß-D-Galp-(1→, →2)-α-D-Galp-(1→, →6)-α-D-Galp-(1 â†’ and →3,6)-α-D-Manp-(1 →. AOP70-1 (2.5, 5, 10 µM) significantly suppressed NO, IL-1ß, and TNF-α production in a concentration-dependent manner and inhibited the migration of BV2 microglia. AOP70-1 inhibited LPS-mediated activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein (MyD88), and nuclear factor kappa B (NF-κB). Moreover, AOP70-1 exerted neuroprotection on SH-SY5Y cells and primary neurons by reducing neuronal apoptosis (72 %, 44 %), alleviating ROS accumulation (63 %, 55 %), and improving mitochondrial membrane potential (63 %, 77 %). Overall, AOP70-1 is one of the major bioactive components in AO70 from A. oxyphylla, which has great potential in the prevention and treatment of neuroinflammation.

Whole-exome sequencing identifies high-confidence genes for tic disorders in a Chinese Han population.

BACKGROUND: Tic disorder (TD) is a polygenic neurodevelopmental disorder with high susceptibility. However, identifying high-confidence risk genes has been challenging due to poor replication across multiple studies. METHODS: Whole-exome sequencing was performed on 390 TD patients and 372 unaffected individuals in a Chinese Han population. Analysis of variance, burden analysis and in silico prediction were used to identify candidate genes for TD. To facilitate data analysis and to focus on high-confidence genes, we defined a panel of 160 genes as known causal or candidate TD genes from previous studies. Gene enrichment and protein-protein interaction analysis were utilized to detect potential novel TD risk genes. RESULTS: Totally, 14 variants across 12 known TD candidate genes were considered potential susceptibility variants. Ten variants across 10 known TD candidate genes were identified as potential disease-causing variants. Burden analysis identified variants of 28 known genes were significantly excess in TD patients. In addition, 354 previously unproven TD genes are over-represented in patients. Genes enriched in the PI3K-Akt signaling, sphingolipid metabolism and serotonergic synaptic pathways, as well as those interacting with FN1, were considered potential new candidate genes for TD. CONCLUSIONS: This is the largest WES study focusing on TD patients in a Chinese Han population. Several variants recurring in our cohort were identified as high-confidence risk loci for TD. Moreover, we provided potential new risk genes that may be prioritized for further investigation.

Meta-analysis of the clinical efficacy and safety of single versus dual plate in the treatment of comminuted distal femur fractures.

Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.

Intramedullary nailing for floating knee injury complicated by pulmonary fat embolism: A case report and literature review.

A 28-year-old man involved in a serious motorcycle accident was admitted to our hospital with comminuted fractures of the ipsilateral femoral shaft and tibial shaft, as well as multiple fractures of the right lower limb, including the proximal fibula, medial malleolus, and the third and fourth distal metatarsals. In addition, the patient suffered a skin contusion and laceration of the right foot. On the first day of admission, this patient suddenly developed tachycardia, pyrexia, and tachypnoea, and was immediately transferred to the ICU for further treatment due to a CT-diagnosed pulmonary fat embolism (FE). As a symptomatic treatment, he received a prophylactic dose of low-molecular-weight heparin for 10 days, after which his condition improved. A Doppler ultrasound of the lower leg and a follow-up chest CT angiography were performed, which excluded any remaining thrombus and verified that the pulmonary FE had improved without deterioration. Closed-reduction and retrograde intramedullary nailing were performed for the femoral shaft fractures, while antegrade intramedullary nailing was performed for the tibial shaft fractures under general anaesthesia. In the three-year follow-up, the patient had recovered with good function of the right limb, without any respiratory discomfort. Both the femoral and tibial shaft fractures finally resolved without any further treatment. Ipsilateral femoral and tibial shaft fractures should undergo surgical stabilisation as early as possible to avoid pulmonary FEs. It is still controversial whether intramedullary nailing is suitable for floating knee injuries complicated by pulmonary FEs. However, if patients with pulmonary FEs require intramedullary nailing, we suggest that surgery should be performed after at least one week of anticoagulant use, when patient vital signs are stable and there is no sign of dyspnoea. In addition, patients should try to avoid reaming during the operation to prevent and decrease "second hit" for the lung.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Effects of different psychosocial interventions on death anxiety in patients: a network meta-analysis of randomized controlled trials.

Objective: This research intended to assess and compare influence of psychosocial interventions in death anxiety in patients, providing evidence-based guidance for both patients and healthcare providers. Design: The present study exclusively gathered randomized controlled trials by comprehensively searching across multiple databases, comprising of PubMed, Embase, Cochrane Library, Web of Science, and Scopus. The methodological quality of the enrolled studies involved in the analysis was assessed using the Cochrane bias risk assessment tool, and data analysis was performed utilizing appropriate software. Results: This research, encompassing 15 randomized controlled trials with a cumulative sample size of 926 patients, spanned from the earliest possible date to December 2023. The findings of network meta-analysis unveiled that the Rational-Emotive Hospice Care Therapy significantly reduced death anxiety among patients (Sequentially Updated Cumulative Ranking Analysis: 100%). Conclusion: The ranking plot of the network suggested that the rational-emotive hospice care therapy exhibited superior efficacy as a psychological treatment for reducing the death anxiety of patients.Systematic review registration: [https://clinicaltrials.gov/], identifier: [CRD42023484767].

Neuroinflammation of Microglial Regulation in Alzheimer's Disease: Therapeutic Approaches.

Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and cognitive function. The pathogenesis of AD is intricate and not yet fully understood. Neuroinflammation, particularly microglial activation-mediated neuroinflammation, is believed to play a crucial role in increasing the risk, triggering the onset, and hastening the progression of AD. Modulating microglial activation and regulating microglial energy metabolic disorder are seen as promising strategies to intervene in AD. The application of anti-inflammatory drugs and the targeting of microglia for the prevention and treatment of AD has emerged as a new area of research interest. This article provides a comprehensive review of the role of neuroinflammation of microglial regulation in the development of AD, exploring the connection between microglial energy metabolic disorder, neuroinflammation, and AD development. Additionally, the advancements in anti-inflammatory and microglia-regulating therapies for AD are discussed.

Orbital Magneto-Nonlinear Anomalous Hall Effect in Kagome Magnet Fe_{3}Sn_{2}.

It has been theoretically predicted that perturbation of the Berry curvature by electromagnetic fields gives rise to intrinsic nonlinear anomalous Hall effects that are independent of scattering. Two types of nonlinear anomalous Hall effects are expected. The electric nonlinear Hall effect has recently begun to receive attention, while very few studies are concerned with the magneto-nonlinear Hall effect. Here, we combine experiment and first-principles calculations to show that the kagome ferromagnet Fe_{3}Sn_{2} displays such a magneto-nonlinear Hall effect. By systematic field angular and temperature-dependent transport measurements, we unambiguously identify a large anomalous Hall current that is linear in both applied in-plane electric and magnetic fields, utilizing a unique in-plane configuration. We clarify its dominant orbital origin and connect it to the magneto-nonlinear Hall effect. The effect is governed by the intrinsic quantum geometric properties of Bloch electrons. Our results demonstrate the significance of the quantum geometry of electron wave functions from the orbital degree of freedom and open up a new direction in Hall transport effects.

Effectively solve the obstacle in the old residential building energy-saving renovation from the perspective of a four-party evolutionary game.

Although the government highly focuses on old residential building energy-saving renovation (ORBESR), many hinders still exist and the efficiency of it is still low. This paper proposes a four-party evolutionary game model to study the impact of relative stakeholders' choices, involving developers, residents, neighborhood councils, and governments. Using this model, this paper studies what influences the conflicts between developers and residents take on the efficiency of ORBESR. In addition, what influence the residents, neighborhood councils, and developers' strategies will take on the ORBESR under the condition of evolutionary stability strategy. This paper finally concludes that governments could propose high penalties first to accelerate the stability of the system, then suitable subsidies to relieve the financial burden and to achieve high efficiency. The governments could provide a suitable plan for residents' investment to promote residents' participation. The neighborhood councils arouse the ways and facilities to help residents understand and participate in the ORBESR and try to solve the conflicts between developers and residents can improve the residents' participation and the developers' willingness to implement the ORBESR.

Relationship between motor dysfunction, the respiratory muscles and pulmonary function in stroke patients with hemiplegia: a retrospective study.

BACKGROUND: The interaction between motor dysfunction and respiratory functions in stroke patients with hemiplegia are not fully understood, particularly with regard to the relationship between changes in trunk control, balance, and daily activities, and changes in respiratory muscle strength and pulmonary volume. Investigating this relationship will facilitate the optimization of stroke rehabilitation strategies. METHODS: Clinical history data were collected from 134 patients to analyze the relationship between motor function scales scores and spirometric data. The data from 60 patients' data were used to evaluate the relationship between motor function scales scores and spirometric data at baseline and after 3-weeks rehabilitation. RESULTS: (1) Patients with lower scores on Trunk impairment Scale (TIS), Berg Balance Scale (BBS) and Barthel Index (BI) had weaker respiratory muscle strength and pulmonary function. (2) Stroke patients' BBS and BI scores showed differences between normal and unnormal maximal inspiratory pressure (MIP), but not in TIS. (3) Improvements in motor function led to promotion of enhanced respiratory function. Patient exhibited less MIP improvement at the severe level of TIS and BBS. CONCLUSIONS: Patients with hemiplegia exhibited diminished respiratory muscle strength and pulmonary function at a more severe motor dysfunction level. Impaired inspiratory muscle strength was associated with reduced balance ability and limitations in activities required for daily living. Enhanced motor function improved respiration and rehabilitation programs should prioritize the activation of diaphragm function to improve overall outcomes.

[Meta-analysis of clinical efficacy of ankle arthrodesis and total ankle arthroplasty in the treatment of end-stage ankle arthritis].

OBJECTIVE: To systematically review the clinical efficacy of total ankle arthroplasty (TAA) and ankle arthrodesis (AA) in the treatment of end-stage ankle arthritis. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched for articles published in the treatment of end-stage ankle arthritis with AA or TAA from the establishment of the database to June 2021. Bias risk tool was used to evaluate the quality of the literature. The American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale(AOFAS), visual analog scale (VAS), ankle osteoarthritis scale(AOS), gait analysis (pace, frequency, stride), range of motion (ROM), satisfaction, complications and reoperation rate were analyzed by meta-analysis between AA and TAA groups by RevMan 5.3 software. RESULTS: A total of 12 articles were included, including 1 050 patients in the AA group and 3 760 patients in the TAA group, totaling 4 810 patients. Meta-analysis showed that the total score of AOFAS[MD=-3.12, 95%CI(-9.02, 2.96), P=0.31], pain score [MD=1.60, 95%CI(-1.35, 4.54), P=0.29], alignmentl score[MD=-0.04, 95%CI(-0.52, 0.44), P=0.88], VAS[MD=0.10, 95%CI(-0.49, 0.68), P=0.74], and AOS total score [MD=-4.01, 95%CI(-8.28, 0.25), P=0.06], the difference was not statistically significant (P>0.05). The score of AOFAS functional in TAA group was significantly higher than that in TAA group[MD=44.22, 95%CI(-8.01, -0.43), P=0.03]. There was no significant difference in gait analysis between the two groups (P>0.05). Postoperative ROM [MD=-4.93, 95%CI(-6.35, -3.52), P<0.000 01] and change in ROM from preoperative to follow-up[MD=-5.74, 95%CI(-8.88, -2.61), P=0.0003] between two groups, the difference was statistically significant. There was no significant difference in satisfaction between the two groups [OR=1.011, 95%CI(0.46, 2.23), P=0.98]. Complications [OR=1.61, 95%CI(1.26, 2.06), P=0.0002] and non-revision reoperation [OR=1.61, 95%CI(1.17, 2.21), P=0.003] were significantly lower in the TAA group than in the AA group. There was no significant difference in the rate of revision and reoperation(P>0.05) between the two groups [OR=1.02, 95%CI(0.37, 2.78), P=0.97]. CONCLUSION: The clinical efficacy of AA is similar to that of TAA, but the non revision reoperation rate and main surgical complications of TAA are significantly reduced. Therefore, further high-quality methodological research and long-term follow-up are needed to confirm this conclusion.

Correction: Study on the controllability of the fabrication of single-crystal silicon nanopores/nanoslits with a fast-stop ionic current-monitored TSWE method.

[This corrects the article DOI: 10.1038/s41378-023-00532-0.].

Curculigo orchioides polysaccharide COP70-1 stimulates osteogenic differentiation of MC3T3-E1 cells by activating the BMP and Wnt signaling pathways.

The crude polysaccharide CO70 isolated from Curculigo orchioides could alleviate ovariectomy-induced osteoporosis in rats. To clarify the bioactive components, a new heteropolysaccharide (COP70-1) was purified from CO70 in this study, which was consisted of ß-D-Manp-(1→, →4)-α-D-Glcp-(1→, →4)-ß-D-Manp-(1→, →3,4)-ß-D-Manp-(1→, →4,6)-ß-D-Manp-(1→, and →4,6)-α-D-Galp-(1→. COP70-1 significantly promoted the osteoblastic differentiation of MC3T3-E1 cells through improving alkaline phosphatase activity, the deposition of calcium as well as up-regulating the expression of osteogenic markers (RUNX2, OSX, BSP, OCN, and OPN). Furthermore, COP70-1 stimulated the expression of critical transcription factors of the BMP and Wnt pathways, including BMP2, p-SMAD1, active-ß-catenin, p-GSK-3ß, and LEF-1. In addition, LDN (BMP pathway inhibitor) and DKK-1 (Wnt pathway inhibitor) suppressed the COP70-1-induced osteogenic differentiation of MC3T3-E1 cells. Therefore, COP70-1 was one of the bioactive constituents of C. orchioides for targeting osteoblasts to treat osteoporosis by triggering BMP/Smad and Wnt/ß-catenin pathways.

The Efficacy and Cognitive Impact of Perampanel Monotherapy in Patients with Self-Limited Epilepsy with Centrotemporal Spikes: A Retrospective Analysis.

Objective: The third generation of antiepileptic medication (ASM) perampanel (PER), is mostly used as an add-on treatment for refractory epilepsy patients, and rarely used as a monotherapy. This study aims to observe the efficacy and assess the cognitive effects of PER monotherapy in patients with self-limited epilepsy with centrotemporal spikes (SeLECTS). Patients and Methods: Through screening, 86 patients who were first diagnosed with SeLECTS and treated with PER monotherapy were included in this study. All patients were followed up at least 12 months, and Evaluated the efficacy and safety of PER by observing the seizures of patients. At the same time, we used the P300 event-related potential (ERP) component and Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) to evaluate the cognitive changes in children before and after treatment with PER. Results: Ten percent of the children experienced adverse effects, such as dizziness, gait instability, and irritability. The drug retention rate at the last follow-up was 98.83%. Further more, the P300 ERP component and WISC-IV tests were performed no significant difference before and 12 months after PER monotherapy in SeLECTS children. Conclusion: The third-generation of ASM PER monotherapy had a clear effect in children with SeLECTS. A small dose of PER can control seizures well and has no obvious effect on cognitive development.