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The liver is composed of hepatocytes, cholangiocytes, Kupffer cells, sinusoidal endothelial cells, hepatic stellate cells (HSCs) and dendritic cells; all these functional and interstitial cells contribute to the synthesis and secretion functions of liver tissue. However, various hepatotoxic factors including infection, chemicals, high‐fat diet consumption, surgical procedures and genetic mutations, as well as biliary tract diseases such as sclerosing cholangitis and bile duct ligation, ultimately progress into liver cirrhosis after activation of fibrogenesis. Melatonin (MT), a special hormone isolated from the pineal gland, participates in regulating multiple physiological functions including sleep promotion, circadian rhythms and neuroendocrine processes. Current evidence shows that MT protects against liver injury by inhibiting oxidation, inflammation, HSC proliferation and hepatocyte apoptosis, thereby inhibiting the progression of liver cirrhosis. In this review, we summarize the circadian rhythm of liver cirrhosis and its potential mechanisms as well as the therapeutic effects of MT on liver cirrhosis and earlier‐stage liver diseases including liver steatosis, nonalcoholic fatty liver disease and liver fibrosis. Given that MT is an antioxidative and anti‐inflammatory agent that is effective in eliminating liver injury, it is a potential agent with which to reverse liver cirrhosis in its early stage.

Acquiring road information is important for smart cities and sustainable urban development. In recent years, significant progress has been made in the extraction of urban road information from remote sensing images using deep learning (DL) algorithms. However, due to the complex shape, narrowness, and high span of roads in the images, the results are often unsatisfactory. This article proposes a Seg-Road model to improve road connectivity. The Seg-Road uses a transformer structure to extract the long-range dependency and global contextual information to improve the fragmentation of road segmentation and uses a convolutional neural network (CNN) structure to extract local contextual information to improve the segmentation of road details. Furthermore, a novel pixel connectivity structure (PCS) is proposed to improve the connectivity of road segmentation and the robustness of prediction results. To verify the effectiveness of Seg-Road for road segmentation, the DeepGlobe and Massachusetts datasets were used for training and testing. The experimental results show that Seg-Road achieves state-of-the-art (SOTA) performance, with an intersection over union (IoU) of 67.20%, mean intersection over union (MIoU) of 82.06%, F1 of 91.43%, precision of 90.05%, and recall of 92.85% in the DeepGlobe dataset, and achieves an IoU of 68.38%, MIoU of 83.89%, F1 of 90.01%, precision of 87.34%, and recall of 92.86% in the Massachusetts dataset, which is better than the values for CoANet. Further, it has higher application value for achieving sustainable urban development.

Background Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. Methods A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. Results A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0–2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older ( p = 0.01), with higher rate in current smokers ( p = 0.04), higher rate in hypertensives ( p = 0.05), lower SaO 2 ( p = 0.004), and higher prevalence of secondary bacterial infections during acute phase ( p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01–1.15, p = 0.02). Pulmonary functions of total lung capacity ( p = 0.008) and residual volume ( p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. Conclusion During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.

Synovial hyperplasia, a profound alteration in the structure of synovial tissue, is the basis for cumulative joint destruction in rheumatoid arthritis (RA). It is generally accepted that controlling synovial hyperplasia can delay the progression of RA. As one of the most intensively studied isoforms of acid-sensing ion channels (ASICs), ASIC1a contributes to various physiopathologic conditions, including RA, due to its unique property of being permeable to Ca2+. However, the role and the regulatory mechanisms of ASIC1a in synovial hyperplasia are poorly understood. Here, rats induced with adjuvant arthritis (AA) and human primary synovial fibroblasts were used in vivo and in vitro to investigate the role of ASIC1a in the proliferation of RA synovial fibroblasts (RASFs). The results show that the expression of ASIC1a was significantly increased in synovial tissues and RASFs obtained from patients with RA as well as in the synovium of rats with AA. Moreover, extracellular acidification improved the ability of RASFs colony formation and increased the expression of proliferation cell nuclear antigen (PCNA) and Ki67, which was abrogated by the specific ASIC1a inhibitor psalmotoxin-1 (PcTX-1) or ASIC1a-short hairpin RNA (ASIC1a-shRNA), suggesting that extracellular acidification promotes the proliferation of RASFs by activating ASIC1a. In addition, the activation of c-Raf and extracellular signal-regulated protein kinases (ERKs) signaling was blocked with PcTX-1 or ASIC1a-shRNA and the proliferation of RASFs was further inhibited by the ERK inhibitor (U0126), indicating that ERK/MAPK signaling contributes to the proliferation process of RASFs promoted by the activation of ASIC1a. These findings gave us an insight into the role of ASIC1a in the proliferation of RASFs, which may provide solid foundation for ASIC1a as a potential target in the treatment of RA. As an extracellular proton sensor, ASCIC1a can be activated by acidification to promote the proliferation of synovial fibroblasts in rheumatoid arthritis via ERK/MAPK signaling. This effect is abolished by the specific ASIC1a inhibitor psalmotoxin-1 or ASIC1a-silencing

An increasingly number of low- and middle-income countries have developed and implemented a national policy towards universal coverage of healthcare for their citizens over the past decade. Among them is China which has expanded its population coverage by health insurance from around 29.7% in 2003 to over 90% at the end of 2010. While both central and local governments in China have significantly increased financial inputs into the two newly established health insurance schemes: new cooperative medical scheme (NCMS) for the rural population, and urban resident basic health insurance (URBMI), the cost of healthcare in China has also been rising rapidly at the annual rate of 17.0%% over the period of the past two decades years. The total health expenditure increased from 74.7 billion Chinese yuan in 1990 to 1998 billion Chinese yuan in 2010, while average health expenditure per capital reached the level of 1490.1 Chinese yuan per person in 2010, rising from 65.4 Chinese yuan per person in 1990. The repaid increased population coverage by government supported health insurance schemes has stimulated a rising use of healthcare, and thus given rise to more pressure on cost control in China. There are many effective measures of supply-side and demand-side cost control in healthcare available. Over the past three decades China had introduced many measures to control demand for health care, via a series of co-payment mechanisms. The paper introduces and discusses new initiatives and measures employed to control cost escalation of healthcare in China, including alternative provider payment methods, reforming drug procurement systems, and strengthening the application of standard clinical paths in treating patients at hospitals, and analyses the impacts of these initiatives and measures. The paper finally proposes ways forward to make universal health coverage in China more sustainable.

Background Interest in local food has been growing, driven by increased attention from consumers, supporting policies, and interest in offering supply by local producers. Nonetheless, a definition of “local food” remains elusive, varying with purposes, geographies, and perceptions. This study quantifies online media mentioning local food in 2018–2021 using online and social media listening and analytics. In addition, a sub-search devoted to local food security and access was conducted due to a high proportion of mentions devoted to food security in the initial search. Variations in mentions and net sentiment quantified for individual US states are also presented. Results The local food pantry sub-search arose after finding a large share of the general local food media was referencing local food access rather than production or other topics. The interest in local food access was more apparent during crises periods, such as the COVID-19 pandemic, during which even a larger portion of mentions are devoted to the local food pantry sub-search topic. Mentions quantified from the sub-search are mostly expressing concerns about worsened food insecurity during the pandemic and encouraging others to do things like donate food to local pantries. Conclusions Online and social media can play an important role towards active communication in local communities on topics, such as food availability and access. In addition, online media can facilitate more efficient emergency management.

Acid-sensitive ion channel 1a (ASIC1a) is a member of the extracellular H+ activated cation channel family. Studies have shown that tissue acidification contributes to the formation of microvessels in rheumatoid arthritis (RA) synovial tissue, but its underlying mechanisms remain unclear. The purpose of this study was to investigate the role of tissue acidification in microvascular formation of arthritic synovial tissue and the effect of ASIC1a on vascular endothelial growth factor (VEGF) release from arthritic synovial tissue. Our results indicate that ASIC1a expression, VEGF expression, and microvessel density (MVD) are elevated in RA synovial tissue and adjuvant arthritis (AA) rat synovial tissue. When AA rats were treated with ASIC1a-specific blocker psalmotoxin-1 (PcTx-1), the expression of ASIC1a, VEGF expression, and MVD were all reduced. Acidification of RA synovial fibroblasts (RASF) can promote the release of VEGF. PcTx-1 and ASIC1a-short hairpin RNA can inhibit acid-induced release of VEGF. In addition, the ASIC1a overexpression vector can promote acid-induced VEGF release. This indicates that extracellular acidification induces the release of VEGF by RASF via ASIC1a. These findings suggest that blocking ASIC1a mediates the release of VEGF from synoviocytes may provide a potential therapeutic strategy for RA therapy. Both ASIC1a and VEGF are highly expressed in rheumatoid arthritis synovial tissue and are associated with vascular disease. Interfering with ASIC1a in vitro using silencing, blocking, and overexpression interferes with the release of VEGF under acid stimulation. Blocking ASIC1a in the articular cavity of rats with adjuvant arthritis not only reduces the expression of VEGF in the synovium, but also reduces the proliferation and lesions of blood vessels and interferes with the development of the disease.

Background Coronary artery disease (CHD) is one of the major public health problems worldwide. International guidelines recommend ongoing management of metabolic abnormalities and improved prognosis through combined aerobic and resistance exercise (CE), and the aim of this study was to investigate the effects of CE and exercise dose on cardiorespiratory fitness, as measured by maximum oxygen uptake (VO2max), in patients with CHD. Methods We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science, with the search limited to the date of the inception of the database to January 2025 to identify randomized controlled trials (RCTs). Pairwise and regression meta-analyses of these results were conducted using Bayesian stratified models based on random effects. Results The 12 RCTs included a total of 697 patients. The results show that CE significantly increased the VO 2 max of coronary heart disease patients compared with the control group that did not exercise (MD = 3.1 ml/kg/min; 95%CrI: 2.57, 3.64; GRADE: Low). In addition, there is a nonlinear positive correlation between the weekly CE dose and the level of improvement in VO 2 max, with a minimum dose of 310 METs-min/week. The magnitude of VO 2 max improvement is more pronounced in patients with lower baseline cardiorespiratory fitness and gradually decreases with age. Conclusion CE showed significant benefit in improving cardiorespiratory function in patients with CHD. In addition, even lower doses of CE (≥ 310 MET-min/week) improved cardiorespiratory fitness, and the gain was progressively apparent before reaching a critical threshold. The findings suggest that clinical practice should tailor exercise regimens to patient age and baseline VO 2 max.

The use of tissue adhesive patches provides a promising therapeutic approach for sutureless repair of soft tissue injuries. However, existing tissue adhesive patches are confronted with serious challenges for clinical applications in the soft tissue environments with biological fluids and dynamic movements. Either their mechanical toughness does not match that of soft tissues, or they fail to establish effective interfacial bonding with tissues in wet conditions. The imbalance between the mechanical cohesion and interfacial adhesion of existing tissue adhesive patches severely restricts their conformal integration with wet surfaces of soft tissues in dynamic biological environments, leading to adhesion failure in clinical applications. Here, this study reports the design, fabrication, and preclinical therapeutic performance of a dual-layer silk-based adhesive patch (named SF patch) that quickly and conformally adheres to various soft tissues regardless of surrounding biological environments. The intimate microscopic structural connection between the highly tough hydrogel matrix layer and thin bioadhesive layer contributes to high mechanical cohesion and robust interfacial adhesion properties of the SF patch, thereby enabling sufficient integration with wet surfaces of soft tissues to withstand the interference of dynamic tissue movements. Ex vivo porcine and in vivo rat models validate its therapeutic efficacy for sutureless sealing and repair of gastrointestinal defects and peripheral nerve injuries. This SF patch is potentially valuable for clinical applications towards internal soft-tissue repair and functional reconstruction. Robust mechanical toughness and tight conformal integration with soft tissues are important for clinical applications of adhesive patches. The silk-based adhesive patch achieves a great balance of high mechanical cohesion and strong adhesion properties regardless of surrounding biological environments. Rat gastric perforation and sciatic nerve transection models validate its therapeutic efficacy for sutureless repair of soft tissue injuries. [Display omitted] •Highly tough and conformal dual-layer silk fibroin-based adhesive patch is proposed.•The patch achieves a balance between mechanical cohesion and interfacial adhesion.•The patch conformally adheres to various soft tissues in wet biological environments.•The patch provides effective sutureless sealing and repair of soft tissue injuries.

Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), = 0.009; OR 0.461, 95% CI (0.241-0.883), = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.