Burden evaluation and prediction of osteoarthritis and site-specific osteoarthritis coupled with attributable risk factors in China from 1990 to 2030.

OBJECTIVE: This study aimed to estimate and predict the burden of osteoarthritis (OA) and site-specific OA (hip, knee, hand, and others) from 1990 to 2030 and their attributable risk factors in China. METHOD: Data were obtained from the Global Burden of Diseases 2019. The burden was estimated by analyzing the trends of prevalence, incidence, and disability-adjusted life years (DALY). Population attributable risk (PAR) was calculated to assess the impact of high body mass index (BMI). The prediction from 2020 to 2030 was implemented by Bayesian age-period-cohort analysis. RESULTS: In China, prevalent cases, DALY, and incident cases of OA increased to 132.81 million, 4.72 million, and 10.68 million, respectively. Age-standardized rates (ASRs) of prevalence, DALYs, and incidence increased for OA and site-specific OA, especially for hip OA. Site-specific OA showed different susceptible peaking ages, and the burden for those over 50 years old became serious. Female preference existed in the trends for knee OA but not in those for hip, hand, and other OA. PARs of high BMI continued to increase, impacting knee OA more than hip OA and showing female preference. In the next decade, incident cases for OA and site-specific OA will continue to increase, despite that the ASR of OA incidence will decrease. CONCLUSIONS: OA and site-specific OA remain huge public health challenges in China. The burden of OA and site-specific OA is increasing, especially among people over 50 years old. Health education, exercise, and removing modifiable risk factors contribute to alleviate the growing burden. Key Points • In China, the burden of osteoarthritis and site-specific osteoarthritis (hip, knee, hand, and others) as well as the Risk Factor (high body mass index) increased greatly from 1990 to 2019. • It is estimated that incident cases for OA and site-specific OA will continue to increase, despite that the ASR of OA incidence will decrease.

A parathyroid hormone related supramolecular peptide for multi-functionalized osteoregeneration.

Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering, but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber. Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification. Herein, a multi-functional supramolecular peptide, P1R16, is developed by coupling a bioactive factor, parathyroid hormone related peptide 1 (PTHrP-1), to the basic supramolecular peptide RADA16-Ⅰ via solid-phase synthesis. It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-Ⅰ to form nanofiber hydrogels, thus coupling PTHrP-1 to hydrogel matrix. P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner, and P1R16/RADA16-Ⅰ nanofiber hydrogels promote osteogenesis, angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen (Col) scaffolds. Abundant red blood marrow formation, ideal osteointegration and adapted degradation are observed in the 50% P1R16/Col scaffold group. Therefore, this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.

An urban energy recycling system that recycles the waste heat from industry for deicing on urban road in winter-taking Harbin as an example.

Northern cities in China have frequently suffered from ice and snow disasters. On the other hand, Harbin mainly relies on coal-fired plants for heating during the winter time. However, coal-fired plants produce a significant amount of air pollution through the production of numerous hazardous gases. This thesis proposed an urban energy recycling system that uses waste gas from heating facilities to recycle waste heat and reduce air pollution in northern cities during the winter. This research made a hypothesis that wintertime ice and snow on city streets could be melted by using waste heat of waste gases from heating industries. The methodology of this research can be divided into three parts: Firstly, the principle of the energy recycling system is designed based on investigation. Secondly, a simulation experiment is used to analyze the system's difficulties. According to the experiment, when an icy road is far away from the heating industry, ice melting efficiency is low. Finally, this research proposed a method for system improvement based on the findings of the experiment. The system's environmental and social benefits will likely lead to its future application in northern Chinese cities even if there are many application-related difficulties, such as the high cost of construction.

A Novel PTH-Related Peptide Combined With 3D Printed Macroporous Titanium Alloy Scaffold Enhances Osteoporotic Osseointegration.

Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local sustained release. A novel PTHrP (PTHrP-2) that can be used locally to promote osseointegration of macroporous titanium alloy scaffold (mTAS) and counteract implant slippage in osteoporosis patients is designed. In vitro, PTHrP-2 enhances the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) within the mTAS. Further, it promotes proliferation, migration, angiogenesis-related protein expression, and angiogenesis in human umbilical vein endothelial cells (HUVECs). Compared to PTH(1-34), PTHrP-2 can partially weaken the osteoclast differentiation of RAW 264.7 cells. Even in an oxidative stress microenvironment, PTHrP-2 safeguards the proliferation and migration of BMSCs and HUVECs, reduces reactive oxygen species generation and mitochondrial damage, and partially preserves the angiogenesis of HUVECs. In the Sprague-Dawley (SD) rat osteoporosis model, the therapeutic benefits of PTHrP-2-releasing mTAS (mTASP2 ) and ordinary mTAS implanted for 12 weeks via micro-CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTASP2 exhibits high bone growth rate, without osteophyte formation. Consequently, PTHrP-2 exhibits unique local synthesis properties and holds the potential for assisting the osseointegration of alloy implants in osteoporosis patients.

Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review.

Purpose: Levothyroxine is a common prescribed drug. Many medications and food, however, can interfere with its bioavailability. The aim of this review was to summarize the medications, food and beverages that interact with levothyroxine and to assess their effects, mechanisms and treatments. Methods: A systematic review on interfering substances that interact with levothyroxine was performed. Web of Science, Embase, PubMed, the Cochrane library, grey literature from other sources and the lists of references were searched for human studies comparing the levothyroxine efficacy with and without interfering substances. The patient characteristics, drug classes, effects and mechanism were extracted. The NHLBI study quality assessment tools and the JBI critical appraisal checklist were used to assess the quality of included studies. Results: A total of 107 articles with 128 studies were included. Drugs interactions were revealed in calcium and iron supplements, proton pump inhibitors, bile acid sequestrants, phosphate binders, sex hormones, anticonvulsants and other drugs. Some food and beverage could also induce malabsorption. Proposed mechanisms included direct complexing, alkalization, alteration of serum thyroxine-binding globulin levels and acceleration of levothyroxine catabolism via deiodination. Dose adjustment, administration separation and discontinuation of interfering substances can eliminate the interactions. Liquid solutions and soft-gel capsules could eliminate the malabsorption due to chelation and alkalization. The qualities of most included studies were moderate. Conclusion: Lots of medications and food can impair the bioavailability of levothyroxine. Clinicians, patients and pharmaceutical companies should be aware of the possible interactions. Further well-designed studies are needed to provide more solid evidence on treatment and mechanisms.

Omentin-1 ameliorates experimental inflammatory bowel disease via Nrf2 activation and redox regulation.

AIMS: Omentin-1 production is decreased in patients with IBD. However, the specific role of Omentin-1 in IBD has not been fully elucidated. This study aimed to investigate the expression and role of Omentin-1 in IBD and the potential mechanisms. MAIN METHODS: We collected human serum and colon biopsy samples at the Wuhan Union Hospital. Omentin-1 recombinant protein was injected intraperitoneally in a DSS-induced experimental IBD mouse model. Omentin-1 levels were measured in IBD patients, colitis mice, and LPS-induced HT-29 cells. Omentin-1 and/or a Nrf2 specific inhibitor (ML385) were administered to DSS mice and LPS-induced HT-29 cells. The effects of Omentin-1 on inflammation, intestinal barrier function, Nrf2 pathway, oxidative stress, and NF-κB signaling were detected in vivo and in vitro. KEY FINDINGS: Serum Omentin-1 levels were significantly reduced in UC and CD patients compared with controls (173.7 (IQR, 120.1-221.2) ng/ml, 80.8 (43.8-151.8) ng/ml, and 270.7 (220.7-306.5) ng/ml, respectively). The levels of Omentin-1 were also significantly lower in colitis mice and LPS-induced HT-29 cells. Omentin-1 treatment effectively ameliorated inflammation and impaired intestinal barrier, decreased ROS and MDA levels, and increased GSH and SOD production in the DSS-induced colitis mice and LPS-induced HT-29 cells. Mechanically, Omentin-1 repaired the intestinal barrier by activating Nrf2, then improving oxidative stress and inhibiting NF-κB signaling. Furthermore, the interaction between Omentin-1 and Nrf2 was identified. SIGNIFICANCE: Omentin-1 activates the Nrf2 pathway to regulate redox balance, ultimately protecting intestinal barrier function and reducing intestinal inflammation. In general, Omentin-1 can be used as a promising therapeutic target for IBD.

Zn-Sr-sintered true bone ceramics enhance bone repair and regeneration.

Bone defects are one of the toughest challenges faced by orthopedic surgeons worldwide, especially at critical sizes, which are caused by severe trauma, malignancy, or congenital disease. The ideal bone tissue-engineered scaffold for bone regeneration is the one that has good osteoconductivity, osteoinductivity, pore structure, and antibacterial properties. Metal ions have been recognized in recent years to be essential regulators of bone metabolism, and they are widely used for bone tissue engineering. In particular, zinc ions are of interest because of their ideal biocompatibility, osteogenesis-promoting properties, and antibacterial properties. Moreover, the dual role of strontium (Sr) in promoting osteogenesis and inhibiting osteolysis provides academic support for Zn-Sr co-doped scaffolds. Based on true bone ceramics (TBC), Zn-Sr-sintered scaffolds with good pore structures were prepared using immersion-calcination. The biocompatibility, cell adhesion, osteogenic properties, and antibacterial activity of Zn-Sr-sintered TBC scaffolds in bone marrow mesenchymal stem cells (BMSCs) are superior to those of control TBC scaffolds. The Zn-Sr-sintered TBC scaffold was used to repair rat cranial defects. Its good in vivo repair performance was confirmed by osseointegration and inward bone growth compared with that of the control TBC scaffold. Zn0.25Sr0.20-TBC is an ideal material for bone repair because of its good biocompatibility and favorable in vitro osteogenic properties.

Antimicrobial peptides for bone tissue engineering: Diversity, effects and applications.

Bone tissue engineering has been becoming a promising strategy for surgical bone repair, but the risk of infection during trauma repair remains a problematic health concern worldwide, especially for fracture and infection-caused bone defects. Conventional antibiotics fail to effectively prevent or treat bone infections during bone defect repair because of drug-resistance and recurrence, so novel antibacterial agents with limited resistance are highly needed for bone tissue engineering. Antimicrobial peptides (AMPs) characterized by cationic, hydrophobic and amphipathic properties show great promise to be used as next-generation antibiotics which rarely induce resistance and show potent antibacterial efficacy. In this review, four common structures of AMPs (helix-based, sheet-based, coil-based and composite) and related modifications are presented to identify AMPs and design novel analogs. Then, potential effects of AMPs for bone infection during bone repair are explored, including bactericidal activity, anti-biofilm, immunomodulation and regenerative properties. Moreover, we present distinctive applications of AMPs for topical bone repair, which can be either used by delivery system (surface immobilization, nanoparticles and hydrogels) or used in gene therapy. Finally, future prospects and ongoing challenges are discussed.

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition).

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.

Platelet-Derived TGF (Transforming Growth Factor)-ß1 Enhances the Aerobic Glycolysis of Pulmonary Arterial Smooth Muscle Cells by PKM2 (Pyruvate Kinase Muscle Isoform 2) Upregulation.

BACKGROUND: Metabolic reprogramming is a hallmark of pulmonary arterial hypertension. Platelet activation has been implicated in pulmonary arterial hypertension (PAH), whereas the role of platelet in the pathogenesis of PAH remains unclear. METHODS: First, we explored the platelet function of semaxanib' a inhibitor of VEGF receptor (SU5416)/hypoxia mice and monocrotaline-injected rats PAH model. Then we investigated pulmonary arterial smooth muscle cell aerobic glycolysis after being treated with platelet supernatant. TGF (transforming growth factor)-ßRI, pyruvate kinase muscle 2, and other antagonists were applied to identify the underlying mechanism. In addition, platelet-specific deletion TGF-ß1 mice were exposed to chronic hypoxia and SU5416. Cardiopulmonary hemodynamics, vascular remodeling, and aerobic glycolysis of pulmonary arterial smooth muscle cell were determined. RESULTS: Here, we demonstrate that platelet-released TGF-ß1 enhances the aerobic glycolysis of pulmonary arterial smooth muscle cells after platelet activation via increasing pyruvate kinase muscle 2 expression. Mechanistically, platelet-derived TGF-ß1 regulate spyruvate kinase muscle 2 expression through mTOR (mammalian target of rapamycin)/c-Myc/PTBP-1(polypyrimidine tract binding protein 1)/hnRNPA-1(heterogeneous nuclear ribonucleoprotein A1) pathway. Platelet TGF-ß1 deficiency mice are significantly protected from SU5416 plus chronic hypoxia-induced PAH, including attenuated increases in right ventricular systolic pressure and less pulmonary vascular remodeling. Also, in Pf4cre+ Tgfb1fl/fl mice, pulmonary arterial smooth muscle cells showed lower glycolysis capacity and their pyruvate kinase muscle 2 expression decreased. CONCLUSIONS: Our data demonstrate that TGF-ß1 released by platelet contributes to the pathogenesis of PAH and further highlights the role of platelet in PAH.

Atrial Natriuretic Peptide Attenuates Colitis via Inhibition of the cGAS-STING Pathway in Colonic Epithelial Cells.

Atrial Natriuretic Peptide (ANP) has known anti-inflammatory effects. However, the role of ANP in Ulcerative colitis (UC) remains unclear. This study aimed to explore the expression and function of ANP in UC, and its potential regulatory role in the stimulator of interferon genes (STING) pathway. Human colon biopsy and serum samples were collected between September 2018 and December 2019 at Wuhan Union Hospital. Levels of ANP and its receptors and STING pathway components were detected in people with UC and mice with dextran sulfate sodium (DSS)-induced colitis. These mice and HT-29 cells were treated with ANP and an agonist of the STING pathway. The level of inflammation, STING pathway, gut barrier, and endoplasmic reticulum (ER) stress-induced autophagy were measured. We found that the levels of ANP and its receptor decreased and the STING pathway activated statistically in people with UC and the mouse model of colitis. ANP treatment attenuated DSS-induced colitis and inhibited STING pathway phosphorylation in colonic tissue and epithelial cells. An interaction between cGAS and NPR-A was verified. ANP repaired the gut barrier and inhibited ER stress-induced autophagy via the STING pathway. ANP may thus alter colonic barrier function and regulate ER stress-induced autophagy as a promising therapy for UC.

BAFF Blockade Attenuates DSS-Induced Chronic Colitis via Inhibiting NLRP3 Inflammasome and NF-κB Activation.

Background: BAFF production is increased in IBD patients. However, the specific role of BAFF in IBD is still uncovered. This study aimed to investigate the expression and function of BAFF in experimental colitis and the potential mechanisms. Methods: BAFF levels in the serum and colon tissues were measured by ELISA in DSS-induced colitis mice. Mouse-derived BAFF antibody was administered in DSS mice. The changes of body weight, disease activity index (DAI) scores, colon length, spleen weight, histopathological damage, inflammatory indicators, NF-κB signaling, and NLRP3 inflammasome were assayed in DSS mice and control. LPS-primed RAW264.7 cells and bone marrow derived macrophages (BMDMs) were treated with BAFF blockage and recombinant mouse BAFF. Inflammatory associated cytokines, NLRP3 inflammasomes and NF-κB signaling were detected among groups. Results: BAFF production was elevated systemically and locally in colitis mice. BAFF blockade improved the body weight loss, DAI scores, colon length, spleen weight, and histopathological damage in colitis mice. Immunoflurescence analysis revealed that elevated macrophages in mucosal lamina propria were the primary source of BAFF in the colon. NLRP3 inflammasome and NF-κB signaling pathway activation were dramatically inhibited in DSS mice treated with BAFF blockage. In LPS-primed RAW264.7 cells/BMDMs, BAFF blockade decreased the activation of NLRP3 inflammasome (NLPR3, ASC, cleaved IL-1ß, cleaved caspase 1) via inhibiting NF-κB signaling pathway. Moreover, LPS synergizes with BAFF to promote inflammatory factor secretion and expression of NF-κB signaling pathway in RAW264.7 cells. Conclusions: These results suggested that BAFF blockade protected against colitis partially by relieving inflammation, inhibiting intestinal NLRP3 inflammasome and NF-κB signaling pathway from macrophages. BAFF plays an important role in inflammation regulation in IBD, thus providing a novel idea for further research on colitis and experimental evidences for novel potential therapeutic target in IBD.