A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY.

Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Ångstrom-scale silver particles (AgÅPs) and determined the anti-tumor efficacy of fructose-coated AgÅPs (F-AgÅPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgÅPs and aimed to assess whether F-AgÅPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgÅPs-induced anti-osteosarcoma effects. Methods: A modified method was developed to prepare smaller F-AgÅPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgÅPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgÅPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays in vitro were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgÅPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgÅPs-induced apoptosis. Results: The newly obtained F-AgÅPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgÅPs were excreted through feces. F-AgÅPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK). Conclusion: Our study suggests the promising prospect of F-AgÅPs as a powerful selective anticancer agent for osteosarcoma therapy.

Improving revascularization is one of the major measures in fracture treatment. Moderate local inflammation triggers angiogenesis, whereas systemic inflammation hampers angiogenesis. Previous studies showed that Akkermansia muciniphila (A. muc), a gut probiotic, ameliorates systemic inflammation by tightening intestinal barrier. In this study, fractured mice intragastrically administrated with A. muc were found to display better fracture healing than mice treated with vehicle. Notably, more preosteclasts positive for platelet-derived growth factor-BB (PDGF-BB) were induced by A. muc at 2 weeks post fracture, coinciding with increased formation of type H vessels, a specific vessel subtype that couples angiogenesis and osteogenesis and can be stimulated by PDGF-BB. Moreover, A. muc treatment significantly reduced gut permeability and inflammation at early stage. Dextran Sulfate Sodium (DSS) was used to disrupt the gut barrier to determine the role of gut barrier in fracture healing and whether A. muc still can stimulate bone fracture healing. As expected, A. muc evidently improved gut barrier, reduced inflammation, and restored the impaired bone healing and angiogenesis in DSS-treated mice. Our results suggest that A. muc reduces intestinal permeability and alleviates inflammation, which probably induces more PDGF-BB positive preosteoclasts and type H vessel formation in callus, thereby promoting fracture healing. This study provides the evidences about the involvement of type H vessels in fracture healing and suggests the potential of A. muc as a promising strategy for bone healing.

Objectives We aimed to investigate whether skeletal‐specific H‐type blood vessels exist in alveolar bone and how they function in alveolar bone remodeling. Materials and Methods H‐type vessels with high expression of CD31 and Endomucin (CD31hiEmcnhi) were immunostained in alveolar bone. Abundance and age‐related changes in CD31hiEmcnhi endothelial cells (H‐ECs) were detected by flow cytometry. Osteoprogenitors association with H‐type vessels and bone mass were detected in tooth extraction model of alveolar bone remodeling by immunohistofluorescence and micro‐CT, respectively. Transcription and expression of H‐EC feature genes during in vitro Notch inhibition were measured by RT‐qPCR and immunocytofluorescence. Results We verified that H‐type vessels existed in alveolar bone, the abundance of which was highest at infancy age, then decreased but maintained a constant level during aging. In tooth extraction model, H‐ECs significantly increased with concomitant perivascular accumulation of Runx2+ osteoprogenitors and gradually augmentation of bone mass. Notch inhibition of in vitro cultured H‐ECs resulted in decreased expression levels of Emcn and hes1, but not Pecam1 or Kdr genes, with decreased expression levels of H‐EC numbers, accordingly. Conclusions The present study suggests that H‐type vessels promote osteogenesis during alveolar bone remodeling. Notch signaling pathway regulates expression of Emcn and possibly determines fate and functions of alveolar H‐ECs.

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IntroductionThis study aimed to assess the prevalence of hypertension and to explore the disparities of its risk factors among urban and rural elderly.MethodData of hypertensive patients were collected from the China Health and Retirement Longitudinal Study (CHARLS) 2015. Stratified sample households were selected from 450 villages or communities of 150 counties from 28 provinces. Multivariable logistic regression was performed to analyze the factors correlated with hypertension.ResultsPrevalence of HBP was 47.6% (95% CI [45.2%–50.1%]) in total and it was close between urban and rural population (48.6% vs 47.2%). Factors associated with HBP were different between urban and rural areas. In urban areas, hypertension was significantly associated with literacy and diabetes in both genders, high BMI level and smoke quitters in males, and physical activity and dyslipidemia in females. In rural areas, hypertension was significantly associated with older age, higher BMI level in both males and females, and dyslipidemia in males.ConclusionsThe prevalence are about the same among urban and rural residents, but their risk factors vary from each other. Disparity in the risk factors between urban and rural population should be taken into consideration for further intervention.

Introduction: Antipsychotic drugs are the main therapy for schizophrenia and have been widely used in mental disorder fields. However, the research on the safety of antipsychotic drugs in the real-world is rare. The purpose of this research is to evaluate the safety of antipsychotic drugs based on real-world data.Methods: ADR reports collected by the Henan Adverse Drug Reaction Monitoring Center from 2016 to 2020 were analyzed. We described the safety of antipsychotic drugs by descriptive analysis and four signal mining methods. Meanwhile, the risk factors for serious adverse reactions of antipsychotics were identified.Results: A total of 3363 ADR reports related to antipsychotics were included. We found that the number of adverse drug reaction reports and the proportion of serious adverse reactions have increased year by year from 2016 to 2020. Most adverse drug reactions occurred within 3 months after taking the medicine. The symptoms caused by typical antipsychotics and atypical antipsychotics were different and dyskinesia was more common in typical antipsychotics. Most patients improved or recovered after treatment or intervention while only one patient had sequelae. Low-level hospitals, psychiatric hospitals, youth, and old age could increase the risk of serious adverse reactions. Four off-label signals were found through signal mining, including amisulpride-pollakiuria, ziprasidone-dyspnoea, quetiapine-urinary incontinence, olanzapine-hepatic function abnormal.Conclusion: We found that most ADRs occurred within 3 months after taking the medicine, so close observation was required for patients during the first 3 months of treatment. The ADRs of antipsychotics involved multiple organ-system damages but were not serious. It might be recommended to take alternative drugs after a serious ADR occurred. The symptoms caused by typical APDs and atypical APDs were different. For patients with typical APDs, dyskinesia was more common and should be given special attention. Statistics showed that low-level hospitals, psychiatric hospitals, youth, and old age were risk factors for serious ADRs. The four off-label signals obtained by signal mining should be paid special attention, including amisulpride-pollakiuria, ziprasidone-dyspnoea, quetiapine-urinary incontinence, and olanzapine-hepatic function abnormal.

Adverse drug reactions (ADRs) may be a serious public health problem and have received widespread attention in recent years. This study has analyzed the factors leading to the occurrence of serious ADRs (SADRs), determined the factors affecting the prognosis of patients with severe adverse reactions at different levels of medical institutions, and finally made corresponding recommendations for the monitoring, prevention, and treatment of SADRs. We used descriptive analysis and chi-square test to analyze the year, age, gender, proportion of SADRs, and the results of the ADRs in the report. Use the logistic regression to analyze the factors affecting the prognosis of SADRs in different levels of medical institutions. A total of 387 642 people’s 394 037 ADRs were collected from the Henan Provincial Adverse Drug Reaction Monitoring Center from 2016 to 2020. Among them 35 742 cases of serious ADRs (9.1%), 96.1% were eventually relieved or cured, but 39 cases of SADRs caused death. The main causes of death included hemorrhages, organ failure, and allergies. Age, number of medication and illnesses, level of medical institution, history of adverse reactions, and type and method of medication were all factors that affected the severity of ADR. The prognosis of SADRs is worse than normal ADRs. The ADRs in autumn and winter and new adverse reactions are unique risk factors found in this study. The elderly and patients with multiple diseases or taking multiple drugs should pay attention to their adverse reactions. They should be closely observed within a week after taking the medicine. The supervision of patients with a history of allergies and new adverse reactions should be strengthened by primary medical institutions, and in nonprimary medical institutions should paid attention with past medical histories, and use imported drugs and biological agents with caution to ensure the safety and health of patients.