Ultra rapid lispro improves postprandial glucose control versus lispro in combination with basal insulin: a study based on CGM in type 2 diabetes in China.

Aim: To evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China. Methods: This was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups. Results: A total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303). Conclusion: URLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.

The role of green tea intake in thromboprophylaxis of venous thromboembolism in patients with cancer.

Background: Green tea intake has been reported to improve the clinical outcomes of patients with cardiovascular diseases or cancer. It may have a certain role in the development of venous thromboembolism (VTE) among cancer patients. The current study aimed to address this issue, which has been understudied. Methods: We carried out a retrospective study to explore the role of green tea intake in cancer patients. Patients with and without green tea intake were enrolled in a 1:1 ratio by using propensity scoring matching. The primary and secondary outcomes were VTE development and mortality 1 year after cancer diagnosis, respectively. Results: The cancer patients with green tea intake (n = 425) had less VTE development (10 [2.4%] vs. 23 [5.4%], p = 0.021), VTE-related death (7 [1.6%] vs. 18 [4.2%], p = 0.026), and fatal pulmonary embolism (PE) (3 [0.7%] vs. 12 [2.8%], p = 0.019), compared with those without green tea intake (n = 425). No intake of green tea was correlated with an increase in VTE development (multivariate hazard ratio (HR) 1.758 [1.476-2.040], p < 0.001) and VTE-related mortality (HR 1.618 [1.242-1.994], p = 0.001), compared with green tea intake. Patients with green tea intake less than 525 mL per day had increased VTE development (area under the curve (AUC) 0.888 [0.829-0.947], p < 0.001; HR1.737 [1.286-2.188], p = 0.001) and VTE-related mortality (AUC 0.887 [0.819-0.954], p < 0.001; HR 1.561 [1.232-1.890], p = 0.016) than those with green tea intake more than 525 mL per day. Green tea intake caused a decrease in platelet (p < 0.001) instead of D-dimer (p = 0.297). The all-cause mortality rates were similar between green tea (39 [9.2%]) and non-green tea (48 [11.3%]) intake groups (p = 0.308), whereas the VTE-related mortality rate in the green tea intake group (7 [1.6%]) was lower than that of the non-green tea intake group (18 [4.2%]) (p = 0.026). The incidences of adverse events were similar between the green tea and non-green tea intake groups. Conclusion: In conclusion, the current study suggests that green tea intake reduces VTE development and VTE-related mortality in cancer patients, most likely through antiplatelet mechanisms. Drinking green tea provides the efficacy of thromboprophylaxis for cancer patients.

Design, synthesis, and biological evaluation of novel chrysin derivatives as poly(ADP-ribose) polymerase 1 (PARP1) inhibitors for the treatment of breast cancer.

In this study, we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly (ADP-ribose) polymerase 1 (PARP1). Among these derivatives, compound 5d emerged as the most effective chrysin-based inhibitor of PARP1, with an IC50 value of 108 nmol·L-1. This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage. Furthermore, 5d induced apoptosis and caused an extended G1/S-phase in these cell lines. Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1. In vivo, in a xenograft model, 5d effectively reduced tumor growth by downregulating PARP1 expression. Overall, compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

Effects of the Mesoporous Filler and Oleophilic Property on the Tribological Behavior of Polyetheretherketone Composites.

Porous composites, such as polyimide and polyetheretherketone (PEEK) polymer composites, became more attractive as a result of excellent specific strength, lightweightness, and smart lubrication. However, revealing the influence of a porous filler on the friction behaviors of polymer composites remains a challenge. The current work examines the effects of the pore structure and wettability on the mechanical and tribological performances of polymer composites reinforced with fillers. Three kinds of particles (non-porous, porous, and oleophobic porous) act as fillers within PEEK, respectively. It was identified that adding porous zeolite particles into PEEK slightly decreased the mechanical property. The zeolite particles significantly increased the oil adsorption of the composite, leading to a significant increase in the friction coefficient at 10 wt % content. However, the friction coefficient of the PEEK composite filled with 20 wt % modified zeolite was relatively low as a result of the weak adsorption. The interface analyses indicated that the thickness of the oil film was controlled via porous structures, changing the lubrication regime of the tribopair. The reason is the appropriate adsorption of oil and the release of zeolite from the composites during the friction process. These results can offer technical guidance to control the friction behaviors of composites under oil-lubricating conditions by a porous particle and pore modification.

NtARF11 positively regulates cadmium tolerance in tobacco by inhibiting expression of the nitrate transporter NtNRT1.1.

Heavy metal cadmium (Cd) is widespread in contaminated soil and an important factor limiting plant growth. NO3- (nitrate) affects Cd uptake and thus changes Cd tolerance in plants; however, the underlying molecular regulatory mechanisms have not yet been elucidated. Here, we analyzed a novel gene, NtARF11 (auxin response factor), which regulates Cd tolerance in tobacco via the NO3- uptake pathway, through experiments with NtARF11-knockout and NtARF11-overexpression transgenic tobacco lines. NtARF11 was highly expressed under Cd stress in tobacco plants. Under Cd stress, overexpression of NtARF11 enhanced Cd tolerance in tobacco compared to that in wild-type tobacco, as shown by the low Cd concentration, high chlorophyll concentration, and low accumulation of reactive oxygen species in NtARF11-overexpressing tobacco. Moreover, low NO3- concentrations were observed in NtARF11-overexpressing tobacco plants. Further analyses revealed direct binding of NtARF11 to the promoter of the nitrate transporter NtNRT1.1, thereby negatively regulating its expression in tobacco. Notably, NtNRT1.1 knockout reduced NO3- uptake, which resulted in low Cd concentrations in tobacco. Altogether, these results demonstrate that the NtARF11-NtNRT1.1 module functions as a positive regulator of Cd tolerance by reducing the Cd uptake in tobacco, providing new insights for improving Cd tolerance of plants through genetic engineering.

Anti-coronavirus and anti-pulmonary inflammation effects of iridoids, the common component from Chinese herbal medicines for the treatment of COVID-19.

The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC50 of 14.3 µM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1ß and IL-8 at 10 µM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.

Federated Learning With Only Positive Labels by Exploring Label Correlations.

Federated learning (FL) aims to collaboratively learn a model by using the data from multiple users under privacy constraints. In this article, we study the multilabel classification (MLC) problem under the FL setting, where trivial solution and extremely poor performance may be obtained, especially when only positive data with respect to a single class label is provided for each client. This issue can be addressed by adding a specially designed regularizer on the server side. Although effective sometimes, the label correlations are simply ignored and thus suboptimal performance may be obtained. Besides, it is expensive and unsafe to exchange user's private embeddings between server and clients frequently, especially when training model in the contrastive way. To remedy these drawbacks, we propose a novel and generic method termed federated averaging (FedAvg) by exploring label correlations (FedALCs). Specifically, FedALC estimates the label correlations in the class embedding learning for different label pairs and utilizes it to improve the model training. To further improve the safety and also reduce the communication overhead, we propose a variant to learn fixed class embedding for each client, so that the server and clients only need to exchange class embeddings once. Extensive experiments on multiple popular datasets demonstrate that our FedALC can significantly outperform the existing counterparts.

Gastric emptying in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes and the impact of 4-week insulin pump therapy.

AIM: To evaluate gastric emptying (GE) and the glycaemic response to a 75-g oral glucose load in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12-15 months after insulin pump therapy. MATERIALS AND METHODS: Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75-g glucose drink containing 150 mg 13C-acetate, to determine the gastric half-emptying time, and underwent assessment of plasma glucose and serum insulin, C-peptide and glucagon-like peptide-1 (GLP-1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re-assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12-15 months, GE was re-measured in 14 of the T2D participants. RESULTS: At baseline, participants with T2D exhibited substantially augmented fasting and post-glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP-1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP-1 secretion was attenuated, fasting and post-glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12-15 months of follow-up. CONCLUSIONS: In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short-term insulin pump therapy. The effect on GE is maintained for at least 12 months.

Gastric emptying is slower in women than men with type 2 diabetes and impacts on postprandial glycaemia.

AIM: To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). METHODS: In cohort 1, 70 newly diagnosed, treatment-naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75-g glucose drink containing 150 mg 13C-acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi-solid mashed potato meal, labelled with 100 µl 13C-octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). RESULTS: Gastric emptying was slower in female than male subjects in both cohorts (both p < .01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p < .05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p < .001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p < .05). CONCLUSIONS: Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume-adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D.

Transition role of entangled data in quantum machine learning.

Entanglement serves as the resource to empower quantum computing. Recent progress has highlighted its positive impact on learning quantum dynamics, wherein the integration of entanglement into quantum operations or measurements of quantum machine learning (QML) models leads to substantial reductions in training data size, surpassing a specified prediction error threshold. However, an analytical understanding of how the entanglement degree in data affects model performance remains elusive. In this study, we address this knowledge gap by establishing a quantum no-free-lunch (NFL) theorem for learning quantum dynamics using entangled data. Contrary to previous findings, we prove that the impact of entangled data on prediction error exhibits a dual effect, depending on the number of permitted measurements. With a sufficient number of measurements, increasing the entanglement of training data consistently reduces the prediction error or decreases the required size of the training data to achieve the same prediction error. Conversely, when few measurements are allowed, employing highly entangled data could lead to an increased prediction error. The achieved results provide critical guidance for designing advanced QML protocols, especially for those tailored for execution on early-stage quantum computers with limited access to quantum resources.

Characteristic cembrane-type diterpenoids with nitric oxide inhibitory activity from the gum resin of Boswellia carterii Birdw.

Five new characteristic cembrane-type diterpenoids (olibacartiols A-E, 1-5) were acquired from the gum resin of Boswellia carterii. The structures of these diterpenoids were characterized by detailed spectroscopic analysis, and compounds 1-3 were unambiguously confirmed by single-crystal X-ray diffraction experiments. The anti-inflammatory activities of the isolated compounds were evaluated using LPS-induced BV2 cell model and compounds 2-5 showed moderate NO inhibitory effects with IC50 values of 8.84 ±â€¯1.02, 9.82 ±â€¯1.95, 9.75 ±â€¯2.24, and 7.39 ±â€¯1.24 µM, respectively.

Carsim-based simulation study on the performances of raised speed deceleration facilities under different profiles.

OBJECTIVE: Studying the optimal profile shape and size of deceleration facilities suitable for low-speed environment roads under different speed control intervals. METHODS: Simulation modeling of deceleration facilities with various profile shapes and sizes and for vehicles in different speed intervals was performed using the vehicle dynamics simulation software Carsim. The height jumped by a vehicle's wheels, the vertical force on the wheels, and the vertical acceleration of the vehicle were used as indicators of ride comfort and operational stability for the various deceleration facility profiles. RESULTS: stability and comfort were related to the contour of the deceleration facility. Vertical forces were positively related to vehicle jump height, but the jump heights of vehicles passing through deceleration mounds with different planes at the same speed were not significantly different with increasing height. When the vehicle is traveling slowly, the vertical impact force on the vehicle is not significantly related to the speed loss of the vehicle. CONCLUSIONS: Within the speed range of 20-60 km/h and profile heights of 3-10.5 cm, the effectiveness ratings of circular high width and parabolic were basically at level 2 and level 3, but the circular high width had a more stable jump height and was the best profile form, followed by sinusoidal and parabolic, then isosceles trapezoidal, and lastly conventional speed bumps.

Gastric emptying of a glucose drink is predictive of the glycaemic response to oral glucose and mixed meals, but unrelated to antecedent glycaemic control, in type 2 diabetes.

BACKGROUND: Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. METHODS: Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. RESULTS: Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = -0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = -0.34, P = 0.012) and dinner (r = -0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. CONCLUSIONS: In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.

NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin.

BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

Role of NLRP3 in Parkinson's disease: Specific activation especially in dopaminergic neurons.

Parkinson's disease (PD) is a neurodegenerative disorder with motor symptoms like bradykinesia, tremors, and balance issues. The pathology is recognized by progressively degenerative nigrostriatal dopaminergic neurons (DANs) loss. Its exact pathogenesis is unclear. Numerous studies have shown that nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) contributes to the pathogenesis of PD. Previous studies have demonstrated that the over-activation of NLRP3 inflammasome in microglia indirectly leads to the loss of DANs, which can worsen PD. In recent years, autopsy analyses of PD patients and studies in PD models have revealed upregulation of NLRP3 expression within DANs and demonstrated that activation of NLRP3 inflammasome in neurons is sufficient to drive neuronal loss, whereas microglial activation occurs after neuronal death, and that inhibition of intraneuronal NLRP3 inflammasome prevents degeneration of DANs. In this review, we provide research evidence related to NLRP3 inflammasome in DANs in PD as well as focus on possible mechanisms of NLRP3 inflammasome activation in neurons, aiming to provide a new way of thinking about the pathogenesis and prevention of PD.

Arthroscopic fixation techniques for tibial eminence fractures in pediatric patients: a review.

The introduction of new internal fixation devices and arthroscopic techniques has led to significant changes in the surgical treatment of tibial eminence fractures (TEFs) in children. In recent years, arthroscopic surgery has arisen as the gold standard for the treatment of TEFs. This popularity of arthroscopic techniques has reduced surgical complications and improved patient prognosis. In this paper, we investigate the current situation of the use of arthroscopic fixation techniques for pediatric TEFs. We searched the PubMed database using the terms "arthroscopic treatment and tibial eminence," "arthroscopic treatment and tibial spine," "tibial eminence avulsion", "tibial spine fracture", with no limit on the year of publication. From these articles, we reviewed the use of various arthroscopic TEFs fixation techniques reported in the current literature. Overall, we found that the choice of fixation method seems to have no effect on clinical outcomes or imaging results. However, if an easy, strong fixation that is less prone to epiphyseal damage is desired, as a junior practitioner, the anchor technique should be mastered first, whereas for senior practitioners, a variety of fixation techniques for TEFs should be mastered, including anchors, sutures, and screws, so that personalized fixation can be achieved with the least amount of trauma, operative time, and complications. Higher quality studies are needed in the future to provide Useful evidence to determine the optimal fixation technique in terms of clinical outcomes, function, and complications.

International Normalized Ratio Predicts Recurrence and Bleeding in Patients With Acute Venous Thromboembolism Who Undergo Direct Oral Anticoagulants.

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort (n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)(P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)(P < .001). The cutoff value of INR was 2.1. In the prospective cohort (n = 202), the calibration showed that there were 4 (50%) patients with VTE recurrence, 156 (97.5%) patients with non-recurrence and bleeding (non-R&B), and 20 (58.8%) patients with bleeding in the low (INR < 0.9)(n = 8), intermediate (0.9 ≤ INR ≤ 2.1)(n = 160), and high (INR > 2.1)(n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.

Projection of Mortality Burden Attributable to Nonoptimum Temperature with High Spatial Resolution in China.

The updated climate models provide projections at a fine scale, allowing us to estimate health risks due to future warming after accounting for spatial heterogeneity. Here, we utilized an ensemble of high-resolution (25 km) climate simulations and nationwide mortality data from 306 Chinese cities to estimate death anomalies attributable to future warming. Historical estimation (1986-2014) reveals that about 15.5% [95% empirical confidence interval (eCI):13.1%, 17.6%] of deaths are attributable to nonoptimal temperature, of which heat and cold corresponded to attributable fractions of 4.1% (eCI:2.4%, 5.5%) and 11.4% (eCI:10.7%, 12.1%), respectively. Under three climate scenarios (SSP126, SSP245, and SSP585), the national average temperature was projected to increase by 1.45, 2.57, and 4.98 °C by the 2090s, respectively. The corresponding mortality fractions attributable to heat would be 6.5% (eCI:5.2%, 7.7%), 7.9% (eCI:6.3%, 9.4%), and 11.4% (eCI:9.2%, 13.3%). More than half of the attributable deaths due to future warming would occur in north China and cardiovascular mortality would increase more drastically than respiratory mortality. Our study shows that the increased heat-attributable mortality burden would outweigh the decreased cold-attributable burden even under a moderate climate change scenario across China. The results are helpful for national or local policymakers to better address the challenges of future warming.