Abstract Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow–derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell–cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid–binding Ig-like lectin 15 (Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.
Apoptosis, fibrosis and NLRP3 inflammasome activation are involved in the development of diabetic cardiomyopathy (DCM). Human recombinant relaxin-3 (H3 relaxin) is a novel bioactive peptide that inhibits cardiac injury; however, whether H3 relaxin prevents cardiac injury in rats with DCM and the underlying mechanisms are unknown.To investigate the effect of H3 relaxin on DCM, we performed a study using H3 relaxin treatment in male Sprague-Dawley (SD) rats with streptozotocin (STZ)-induced diabetes (DM). We measured apoptosis, fibrosis and NLRP3 inflammasome markers in the rat hearts four and eight weeks after the rats were injected with STZ (65 mg/kg) by western blot analysis. Subsequently, 2 or 6 weeks after the STZ treatment, the rats were treated with H3 relaxin [2 µg/kg/d (A group) or 0.2 µg/kg/d (B group)] for 2 weeks. Cardiac function was evaluated by echocardiography to determine the extent of myocardial injury in the DM rats. The protein levels of apoptosis, fibrosis and NLRP3 inflammasome markers were used to assess myocardial injury. In addition, we determined the plasma levels of IL-1β and IL-18 using a Milliplex MAP Rat Cytokine/Chemokine Magnetic Bead Panel kit.The protein expression of cleaved caspase-8, caspase-9 and caspase-3 as well as fibrosis markers increased at 4 and 8 weeks in the STZ-induced diabetic hearts compared with the levels in the control group. Furthermore, the NLRP3 inflammasome was substantially activated in STZ-induced diabetic hearts, leading to increased IL-1β and IL-18 levels. Compared with the DM group, the A group exhibited substantially better cardiac function. The protein levels of apoptosis markers were attenuated by H3 relaxin, indicating that H3 relaxin inhibited myocardial apoptosis in the hearts of diabetic rats. The protein expression of fibrosis markers was inhibited by H3 relaxin. Additionally, the protein expression and activation of the NLRP3 inflammasome were also effectively attenuated by H3 relaxin.This study is the first to demonstrate that H3 relaxin plays an anti-apoptotic, anti-fibrotic and anti-inflammatory role in DCM.
Intratumoral bacteria might play essential roles in tumorigenesis in different cancer types. However, its features and potential roles in hepatocellular carcinoma (HCC) are largely unknown.
The aim of this study was to assess the benefits of a mobile-enabled app through Lilly Connected Care Program (LCCP) in achieving blood glucose control and adhering to self-monitoring of blood glucose in patients with type 2 diabetes mellitus (T2DM).This retrospective study included T2DM patients who were initiated on insulin therapy (mostly premixed insulin) after failure to respond to oral antidiabetic drugs. Patients were provided with glucometers enabled with synchronous data transmission to healthcare providers and family members. The primary objective was to assess the benefits of LCCP based on changes in fasting blood glucose (FBG) and postprandial glucose (PPG) levels from baseline to 12 weeks. Paired t-test was used to assess the change in blood glucose (BG) from baseline to week 12.In total, 14,085 T2DM patients were recruited. Compared with baseline, significant reductions in FBG and PPG were evident at week 12 (FBG: -0.39 mmol/L; PPG: -0.79 mmol/L; both P < 0.001). Furthermore, at week 12, the proportion of patients attaining a target glucose level of FBG <7.0 mmol/L and PPG <10.0 mmol/L was 25.37% and 59.68%, respectively, with a statistically significant increase compared with that at baseline (6.74% and 45.59%, respectively, both P < 0.001). The frequent monitoring of patients could gain a higher target achievement of FBG (28.1% vs 24.2%) and PPG (64.4% vs 55.1%) than the occasional monitoring patients. Additionally, the incidence of hypoglycemia gradually decreased and was significantly lower than the baseline level.In T2DM patients with poor glycemic control, the application of mobile enabled intervention (LCCP) along with insulin significantly reduced the hypoglycemia while improving glycemic control during period of naïve initiating insulin therapy. Additionally, the high frequency of BG self-monitoring was associated with better glycemic control.
Purpose: To describe the extent of delays in insulin initiation, analyze its impact on glycemic control, and explore factors influencing delayed insulin initiation among Chinese type 2 diabetes mellitus (T2DM) patients. Methods: A real-world, retrospective cohort study with regional electronic health records from Fuzhou, southeast China was conducted among T2DM patients. Adult patients uncontrolled with oral antidiabetic drugs (OADs; HbA 1c ≥ 7%) and initiated on insulin treatment were included. Time to insulin initiation was described. After propensity-score matching, Wilcoxon rank-sum test and chi-square test were used to compare follow-up HbA 1c (first HbA 1c 3 months after insulin initiation) between timely (initiated insulin within 6 months after OAD failure) and delayed (initiated after 6 months) insulin-initiation groups. Sensitivity analysis was also performed by linear and logistic regression. Factors associated with delayed insulin initiation were explored using logistic regression. Results: A total of 940 patients were included, with mean±SD age 66.3± 11.9 years. In sum, 328 had HbA 1c recorded 3 months after insulin initiation. After propensity-score matching (1:1 matching), 184 patients were included for further analysis. Median follow-up HbA 1c was lower in the timely-initiation group than the delayed-initiation group (7.25% vs 8.25%, P =0.009). Patients in the timely initiation group also had higher odds of achieving HbA 1c < 7% (OR=3.15, P =0.001). Results were confirmed by logistic regression. Hypertension, coronary artery disease, baseline HbA 1c , and hospital level at insulin initiation were associated with delays in insulin initiation. Conclusion: Timely insulin initiation after OAD failure is associated with better glycemic control. Keywords: type 2 diabetes mellitus, therapeutic inertia, delayed insulin initiation, glycemic control, HbA 1c
Abstract Purpose Evaluating risk factors of mortality and characters in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination of China. Methods A total of 104 HMs were included with a median follow-up of 45 days. Results The overall mortality rate was 9.6%. In multivariable analyses, 1 or more comorbidities (P = 0.014), lactic dehydrogenase > 300 u/l (P = 0.014), albumin < 35 g/l (P = 0.017) and active malignancy (P = 0.009) were associated with severe and critical COVID-19. Conversely, patients who received 3 vaccinations had a lower possibility of severe infection (P = 0.022). Active malignancy and lactic dehydrogenase > 300 u/l were risk factors associated with higher mortality in multivariable analyses (P = 0.03; P = 0.038, respectively). We also found that the duration of a positive SARS-CoV-2 PCR test and the time to stable pneumonia by chest computed tomography scan in the severe and critical infection subgroups were significantly longer than those in the moderate infection group (P = 0.03 and P = 0.002, respectively). Conclusions These findings may contribute to guiding the management of HMs during the pandemic, and emphasizing the importance of starting treatment of aggressive HMs for earlier remission.
To investigate the prevalence of parasitic infections in market-sold aquatic products in Shanghai Municipality, and to understand the knowledge and practice towards food-borne parasitic diseases among residents, so as to provide insights into the surveillance and control of food-borne parasitic diseases. Freshwater products, seawater products and pickled products were randomly obtained from agricultural trade markets, supermarkets, retail stores and restaurants in Huangpu, Putuo, Minhang and Qingpu districts of Shanghai Municipality from 2020 to 2023. Parasite metacercariae and larvae were detected in these aquatic products using pressing method, digestion method and the dissection method, and the detection of parasitic infection was compared in different types of aquatic products. In addition, the knowledge and practice towards food-borne parasitic diseases were investigated among residents aged 10-80 years old who randomly selected from agricultural trade markets, supermarkets, community streets and other population concentration areas in these four districts by questionnaire in 2023, and the awareness of food-borne parasitic diseases knowledge and percentage of healthy behaviors formation were analyzed. A total of 2 109 aquatic products sampled from Huangpu, Putuo, Minhang and Qingpu districts of Shanghai Municipality from 2020 to 2023 were detected, and there were 317 products detected with parasitic infections, with an overall detection rate of 15.03%. There were 8 products detected with parasitic infections in 1 221 freshwater products, with a detection rate of 0.66%, and Clonorchis sinensis was the predominant parasite, which was detected in Pseudorasbora parva, Rhodeus amarus and Carassius auratus. There were 82 products detected with parasitic infections in 501 seawater products, with a detection rate of 16.37%, and Anisakis was the predominant parasite, which was detected in Trichiurus lepturus, Larimichthys polyactis, Pneumatophorus japonicus, Collchthys lucidus, Mugil cephalus, Larimichthys crocea, Scomberomorus niphonius, Stromateoides argenteus and Cololabis saira. There were 227 products detected with parasitic infections in 387 pickled products, with a detection rate of 58.66%, and the prevalence rates of Echinostoma metacercariae were 76.27% (225/295) in Bullacta exarata and 11.11% (2/18) in crab pastes, respectively (χ2 = 159.511, P < 0.05). No Paragonimus infection was found in freshwater shrimps, crabs and pickled products, and no Diphyllobothrium latum larvae infection was detected in freshwater and seawater fish. Questionnaire surveys showed that the awareness of food-borne parasitic diseases knowledge was 79.00% (222/281), and the percentages of washing hands before and after meals, not drinking filtered water or tap water directly, not eating raw or semi-raw food, being willing to change special dietary preferences or bad living habits for health, and being willing to learn more about food-borne parasitic diseases knowledge were 99.64% (280/281), 72.24% (203/281), 56.23% (158/281), 96.80% (272/281) and 97.51%(274/281) among residents living in Huangpu, Putuo, Minhang and Qingpu districts, respectively. There are food-borne parasite contaminations in market-sold aquatic products in Shanghai Municipality. Although residents are aware of food-borne parasitic diseases knowledge, sustainable surveillance of food-borne parasitic diseases and improved health education are required to minimize the risk of human parasitic infections.
Green tea is one of the most widely consumed beverages in Asia. While a possible protective role of green tea against various chronic diseases has been suggested in experimental studies, evidence from human studies remains controversial.We conducted this study using data from Shanghai Men's Health Study (SMHS) and Shanghai Women's Health Study (SWHS), two population-based prospective cohorts of middle-aged and elderly Chinese adults in urban Shanghai, China. Hazard ratios (HR) and 95% confidence intervals (CI) for risk of all-cause and cause-specific mortality associated with green tea intake were estimated using Cox proportional hazards regression models.During a median follow-up of 8.3 and 14.2 years for men and women, respectively, 6517 (2741 men and 3776 women) deaths were documented. We found that green tea consumption was inversely associated with risk of all-cause mortality (HR 0.95; 95% CI, 0.90-1.01), particularly among never-smokers (HR 0.89; 95% CI, 0.82-0.96). The inverse association with cardiovascular disease (CVD) mortality (HR 0.86; 95% CI, 0.77-0.97) was slightly stronger than that with all-cause mortality. No significant association was observed between green tea intake and cancer mortality (HR 1.01; 95% CI, 0.93-1.10).Green tea consumption may be inversely associated with risk of all-cause and CVD mortality in middle-aged and elderly Chinese adults, especially among never smokers.
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