OBJECTIVEDiabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODSThis two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N 5 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sexand age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTSOf 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P 5 0.01) and more fatal cases (20.3% vs. 10.5%, P 5 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age ‡70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONSCOVID-19 patients with diabetes had worse outcomes compared with the sex-and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.

The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1β were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1β-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.

A hallmark of aged mesenchymal stem/progenitor cells (MSCs) in bone marrow is the pivot of differentiation potency from osteoblast to adipocyte coupled with a decrease in self-renewal capacity. However, how these cellular events are orchestrated in the aging progress is not fully understood. In this study, we have used molecular and genetic approaches to investigate the role of forkhead box P1 (FOXP1) in transcriptional control of MSC senescence. In bone marrow MSCs, FOXP1 expression levels declined with age in an inverse manner with those of the senescence marker p16INK4A. Conditional depletion of Foxp1 in bone marrow MSCs led to premature aging characteristics, including increased bone marrow adiposity, decreased bone mass, and impaired MSC self-renewal capacity in mice. At the molecular level, FOXP1 regulated cell-fate choice of MSCs through interactions with the CEBPβ/δ complex and recombination signal binding protein for immunoglobulin κ J region (RBPjκ), key modulators of adipogenesis and osteogenesis, respectively. Loss of p16INK4A in Foxp1-deficient MSCs partially rescued the defects in replication capacity and bone mass accrual. Promoter occupancy analyses revealed that FOXP1 directly represses transcription of p16INK4A. These results indicate that FOXP1 attenuates MSC senescence by orchestrating their cell-fate switch while maintaining their replicative capacity in a dose- and age-dependent manner.

Accumulating evidence suggests that activation of proinflammatory M1-type macrophages in the synovium plays a vital role in the progression of osteoarthritis (OA). Redundant nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ) are key factors that drive macrophages to polarize to the M1 type. Herein, modified zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) have been synthesized. By regulating intracellular gases and reprogramming the metabolism phenotype, modified NPs transformed macrophage polarization from proinflammatory M1 to anti-inflammatory M2 phenotype. Specifically, S-methylisothiourea hemisulfate salt was loaded into ZIF-8 NPs to inhibit inducible nitric oxide synthase, hence reducing NO production. Catalase was encapsulated to catalyze the production of oxygen (O 2 ) from H 2 O 2 . Results demonstrated that modified NPs were capable of catalyzing H 2 O 2 to produce O 2 and eliminate NO, hence inhibiting hypoxia-inducible factor 1α, further rescuing mitochondrial function. Moreover, anti-CD16/32 antibody modification could prolong the retention time of NPs in knee joints of OA mice with anterior cruciate ligament transection. More significantly, modified NPs suppressed M1 macrophages and upregulated M2 macrophage infiltration in the synovium, further inhibiting cartilage degeneration. This ZIF-8 NP-based gas regulation and metabolic reprogramming strategy may pave a new avenue for OA treatment.