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ObjectiveTo construct an evaluation index system for the development level of county-level chronic disease management centers, providing a basis for evaluating and comparing the construction of these centers. MethodsFocusing on the key points of county-level chronic disease management center construction and combining relevant literature, a candidate index database was constructed. Twenty-nine experts in the field of chronic disease management were selected to conduct two rounds of Delphi consultation to determine the evaluation index system for the development level of county-level chronic disease management centers, and the analytic hierarchy process was used to determine the index weights. ResultsThe active participation rates of experts in the two rounds of Delphi consultation were 90.91% and 96.67%, respectively, with expert authority coefficients of 0.85 and 0.84, and Kendall′s W of 0.15 and 0.20 (both P < 0.001). After two rounds of consultation, a final evaluation index system for the development level of county-level chronic disease management centers was constructed, consisting of 5 dimensions and 45 indicators: organizational management and basic conditions, chronic disease management informatization, county-township collaborative management of chronic diseases, capacity building and quality control of chronic disease management, and quality and effectiveness of chronic disease management. The weights of the 5 dimensions were 0.212 2, 0.180 1, 0.219 4, 0.179 4, and 0.208 9, respectively. ConclusionThe evaluation index system for the development level of county-level chronic disease management centers constructed in this study is reasonable, practical, representative, and instructive, providing a reference basis for evaluating the development level of these centers and key directions for subsequent construction.

Abstract. Background:. Studies that comprehensively address the characteristics of centenarian deaths are rare. The present study aimed to depict the characteristics of centenarian deaths in China and their changing trends. Methods:. Data on centenarian deaths between 2013 and 2020 were obtained from the national mortality surveillance system of China, including date, place of death (PoD), and underlying cause of death (CoD). Descriptive analyses were performed to understand the epidemiological characteristics, and a joinpoint regression model was adopted to examine the changing trends in the proportions of different PoDs, CoDs among centenarians, and centenarian deaths accounting for all deaths and deaths among people aged 65 years and older. Results:. There were 46,938 registered centenarian deaths between 2013 and 2020 that included 34,311 females (73.10%) and 12,627 males (26.90%). January (12.05%), February (9.99%), and December (9.74%) were the top three months with the highest number of deaths. The proportions of deaths that occurred in homes, hospitals, and nursing homes were 81.71%, 13.63%, and 2.68%, respectively. The proportion of deaths in nursing homes increased by 9.60% (95% confidence intervals [CIs], 6.4–12.9%) from 2014 to 2020. Heart disease (35.72%) was the leading cause of death, followed by respiratory diseases (17.63%), cerebrovascular disease (15.60%), and old age (11.22%). The proportion of respiratory diseases decreased by 4.8% (95% CI, –8.8 to –0.7%), and the proportion of deaths from old age decreased by 2.3% (95% CI, –4.4 to –0.1%) per year. Shanghai had the highest proportions of deaths in hospitals (39.38%) and nursing homes (14.68%). Sichuan had the highest proportion of deaths attributed to respiratory diseases (32.30%), while Jiangsu (26.58%) and Zhejiang (23.61%) had the highest proportions of deaths from old age. Conclusion:. Unlike other countries, centenarian deaths in China are characterized by a higher proportion of home and heart disease deaths, and this death pattern differs across provinces.

ObjectiveTo explore the relationship between the deep medullary vein (DMV) score and atrophy in patients with cerebral small vessel disease (CSVD).MethodsImaging and clinical data from 125 patients with CSVD from January to December 2022 were reviewed. Normalized gray matter volume (GM_N) was calculated by dividing the gray matter volume by the whole brain volume. DMV scoring is conducted using susceptibility-weighted magnetic resonance imaging, wherein the DMV area is partitioned into six distinct regions: bilateral frontal, parietal, and occipital regions. Each region undergoes assessment based on the clarity and consistency of DMV visibility. Subsequently, the scores from these six regions are summed, resulting in a score ranging from 0 to 18 points.ResultsDMV score was associated with GM_N (r = −0.376, p

BackgroundThis systematic review and meta-analysis aim to evaluate the effects of cognitively engaging Physical Activity (PA) interventions on Executive Function (EF) in children and adolescents. It examines how different intervention modalities, durations, frequencies, and session lengths influence these effects.MethodsWe followed the PRISMA guidelines and searched PubMed, SPORTDiscus, Embase, and Web of Science for relevant studies. Studies were included if they were Randomized Controlled Trials (RCTs) focusing on PA with cognitive elements targeting EF in healthy children and adolescents. Data were extracted and effect sizes computed using Standardized Mean Differences (SMDs).ResultsFrom an initial 1,635 articles, 23 studies with 2,857 participants were included. The overall effect of cognitively engaging PA on EF was significant (SMD = 0.32, 95% CI 0.14–0.51), with notable improvements in inhibitory control (SMD = 0.35) and working memory (SMD = 0.34). High heterogeneity was observed (I2 = 91.1%). Moderator analyses revealed that interventions lasting more than 6 weeks, with sessions over 20 min and conducted more than twice a week, were particularly effective.ConclusionCognitively engaging PA interventions positively impact EF in children and adolescents, particularly in inhibitory control. Effective interventions are characterized by longer duration, higher frequency, and extended session lengths. These findings underscore the importance of integrating cognitive challenges within PA programs to enhance EF, warranting future research and practical applications in educational and developmental settings.

During minimal invasive surgery (MIS), the laparoscope only provides a single viewpoint to the surgeon, leaving a lack of 3D perception. Many works have been proposed to obtain depth and 3D reconstruction by designing a new optical structure or by depending on the camera pose and image sequences. Most of these works modify the structure of the conventional laparoscopes and cannot provide 3D reconstruction of different magnification views. In this study, we propose a laparoscopic system based on double liquid lenses, which provide doctors with variable magnification rates, near observation, and real-time monocular 3D reconstruction. Our system composes of an optical structure that can obtain auto magnification change and autofocus without any physically moving element, and a deep learning network based on the Depth from Defocus (DFD) method, trained to suit inconsistent camera intrinsic situations and estimate depth from images of different focal lengths. The optical structure is portable and can be mounted on conventional laparoscopes. The depth estimation network estimates depth in real-time from monocular images of different focal lengths and magnification rates. Experiments show that our system provides a 0.68-1.44x zoom rate and can estimate depth from different magnification rates at 6fps. Monocular 3D reconstruction reaches at least 6mm accuracy. The system also provides a clear view even under 1mm close working distance. Ex-vivo experiments and implementation on clinical images prove that our system provides doctors with a magnified clear view of the lesion, as well as quick monocular depth perception during laparoscopy, which help surgeons get better detection and size diagnosis of the abdomen during laparoscope surgeries.

Marine antimicrobial peptides (AMPs) represent a promising source for combating infections, especially against antibiotic-resistant pathogens and traditionally challenging infections. However, traditional drug discovery methods face challenges such as time-consuming processes and high costs. Therefore, leveraging machine learning techniques to expedite the discovery of marine AMPs holds significant promise. Our study applies machine learning to develop marine AMPs, focusing on Crassostrea gigas mucus rich in antimicrobial components. We conducted proteome sequencing of C. gigas mucous proteins, used the iAMPCN model for peptide activity prediction, and evaluated the antimicrobial, hemolytic, and cytotoxic capabilities of six peptides. Proteomic analysis identified 4490 proteins, yielding about 43,000 peptides (8–50 amino acids). Peptide ranking based on length, hydrophobicity, and charge assessed antimicrobial potential, predicting 23 biological activities. Six peptides, distinguished by their high relative scores and promising biological activities, were chosen for bactericidal assay. Peptides P1 to P4 showed antimicrobial activity against E. coli, with P2 and P4 being particularly effective. All peptides inhibited S. aureus growth. P2 and P4 also exhibited significant anti-V. parahaemolyticus effects, while P1 and P3 were non-cytotoxic to HEK293T cells at detectable concentrations. Minimal hemolytic activity was observed for all peptides even at high concentrations. This study highlights the potent antimicrobial properties of naturally occurring oyster mucus peptides, emphasizing their low cytotoxicity and lack of hemolytic effects. Machine learning accurately predicted biological activity, showcasing its potential in peptide drug discovery.

ObjectiveTo examine the prevalence and influencing factors of multimorbidity among community diabetic patients in six provincial-level administrative divisions (PLADs) of China for providing evidence to disease management and multimorbidity prevention in the patients. MethodsUsing stratified multistage random sampling, we selected 6 713 adult patients ( ≥ 18 years) with type 2 diabetics registered in local basic public health service systems in urban communities and rural villages in Tianjin and Chongqing municipality and Guangdong, Hubei, Heilongjiang, Gansu province. Relevant information of the participants were collected via face-to-face surveys with a self-designed questionnaire from December 2021 to March 2022 and analyzed using descriptive statistics and logistic regression. ResultsMultimorbidity was reported by 3235 (51.93%) of the 6230 patients with eligible responses. The top three most reported multimorbidities were hypertension (reported by 44.77% of the patients), coronary heart disease (12.34%) and stroke (4.65%) and the number (proportion) of the patients with one, two, and three or more multimorbidities were 2190 (35.15%), 754 (12.10%), and 291 (4.67%), respectively, with the most prevalent multimorbidity of diabetes and hyperten-sion reported by 29.15% of the patients. Multivariate unconditional logistic regression analysis indicated that aged 45 years and older, living in northern regions, having alcohol consumption and a diabetes duration of 10 years and more were significant risk factors for multimorbidity; whereas, being married was a significant protective factor. ConclusionThe prevalence of chronic disease comorbidity is relatively high and mainly influenced by age, marital status, living region, alcohol consumption and diabetes duration among community diabetic patients in urban and rural areas of six PLADs in China.

The present study aimed to determine the capsular serotype distribution and antimicrobial drug resistance patterns of Haemophilus influenzae from children in the Kunming region of China. This information could guide policymakers in clinical treatment. In the present study, H. influenzae isolates were tested for their serotypes, antimicrobial susceptibility pattern, and presence of β-lactamases. One-hundred forty-eight H. influenzae strains isolated from children 0–2 years old were investigated for capsular types by glass slide agglutination and molecular methods, and biotyped by the biochemical reactions. The drug resistance-encoding genes TEM-1, ROB-1, and the ftsI gene mutations PBP3-3, and PBP3-BLN were detected with real-time quantitative polymerase chain reaction (qPCR). The prevalence of β-lactamase-producing strains (60.3%) was significantly higher (p < 0.05) than non-enzyme-producing strains. β-Lactamase-producing strains were multidrug resistant to various antibiotics such as ampicillin, tetracycline, sulfamethoxazole/trimethoprim, chloramphenicol, cefuroxime, and cefaclor. Among β-lactamase-producing strains, the detection rates of the TEM-1, PBP3-BLN, PBP3-s, and ROB-1 were 54.1%, 18.9%, 11.8%, and 6.9%, respectively. The biotyping results show that most H. influenzae strains were of type II and III. Non-typeable H. influenzae (NTHi) accounted for 89.3% of the strains. NTHi strains were the most prevalent in this region; most belonged to biological types II and III. β-Lactamase-positive ampi-cillin-resistant (BLPAR) strains were prevalent among H. influenzae isolates in this region.

Real-time monitoring of physiological indicators inside the body is pivotal for contemporary diagnostics and treatments. Implantable electrodes can not only track specific biomarkers but also facilitate therapeutic interventions. By modifying biometric components, implantable electrodes enable in situ metabolite detection in living tissues, notably beneficial in invasive glucose monitoring, which effectively alleviates the self-blood-glucose-managing burden for patients. However, the development of implantable electrochemical electrodes, especially multi-channel sensing devices, still faces challenges: (1) The complexity of direct preparation hinders functionalized or multi-parameter sensing on a small scale. (2) The fine structure of individual electrodes results in low spatial resolution for sensor functionalization. (3) There is limited conductivity due to simple device structures and weakly conductive electrode materials (such as silicon or polymers). To address these challenges, we developed multiple-channel electrochemical microneedle electrode arrays (MCEMEAs) via a separated functionalization and assembly process. Two-dimensional microneedle (2dMN)-based and one-dimensional microneedle (1dMN)-based electrodes were prepared by laser patterning, which were then modified as sensing electrodes by electrochemical deposition and glucose oxidase decoration to achieve separated functionalization and reduce mutual interference. The electrodes were then assembled into 2dMN- and 1dMN-based multi-channel electrochemical arrays (MCEAs), respectively, to avoid damaging functionalized coatings. In vitro and in vivo results demonstrated that the as-prepared MCEAs exhibit excellent transdermal capability, detection sensitivity, selectivity, and reproducibility, which was capable of real-time, in situ glucose concentration monitoring.

Two acid thickeners, ADMC and ADOM, were prepared by aqueous solution polymerization using acrylamide (AM) and methacryloyloxyethyl trimethyl ammonium chloride (DMC) as raw materials, with or without the introduction of octadecyl polyoxyethylene ether methacrylate (OEMA). It was characterized by FTIR, 1H NMR, and the fluorescence spectra of pyrene. The double-layer thickening mechanism of ADOM was proved by comparing the thickening and rheological properties of ADMC and ADOM tested by a six-speed rotary viscometer and a HAKKE MARSIV rheometer during the acidification process. The results showed that the synthetic product was the target product; the first stage of the self-thickening ADOM fresh acid solution during high-temperature acidification was mainly affected by Ca2+ concentration, and the second stage of self-thickening was mainly affected by temperature. The residual viscosity of the 0.8 wt% ADOM residual acid solution was 250, 201.5, and 61.3 mPa·s, respectively, after shearing at 90, 120, and 150 °C for 60 min at a shear rate of 170 s−1. The thickening acid ADOM with a hydrophobic association structure has good temperature resistance and shear resistance, which can be used for high-temperature deep-well acid fracturing. In addition, no metal crosslinking agent was introduced in the system to avoid damage to its formation, and ADOM exhibited good resistance to Ca2+, which could provide ideas for the reinjection of the acidizing flowback fluid. It also has certain advantages for environmental protection.

Summary: Background: The disease burden of gastrointestinal disease (GD) in China is high, with significant variation across provinces. A comprehensive agreed set of indicators could guide rational resource allocation to support better GD outcomes. Methods: This study collected data from multiple sources, including national surveillance, surveys, registration systems, and scientific research. Literature reviews and Delphi methods were used to obtain monitoring indicators; the analytic hierarchy process was used to determine indicator weights. Findings: The China Gastrointestinal Health Index (GHI) system consisted of four dimensions and 46 indicators. The weight of the four dimensions from high to low included the prevalence of gastrointestinal non-neoplastic diseases and gastrointestinal neoplasms (GN) (0.3246), clinical treatment of GD (0.2884), prevention and control of risk factors (0.2606), and exposure to risk factors (0.1264). The highest indicator weight of GHI rank was the successful smoking cessation rate (0.1253), followed by the 5-year survival rate of GN (0.0905), and the examination rate of diagnostic oesophagogastroduodenoscopy (0.0661). The overall GHI for China in 2019 was 49.89, varying from 39.19 to 76.13 across all sub-regions. The top five sub-regions in the total GHI score were in the eastern region. Interpretation: GHI is the first system designed to monitor gastrointestinal health systematically. In the future, data from sub-regions of China should be used to test and improve the GHI system for its impact. Funding: This research was supported by the National Health Commission of China, the First Affiliated Hospital of Naval Medical University (2019YXK006), and the Science and Technology Commission of Shanghai Municipality (21Y31900100).

Bivalves are species-rich mollusks with prominent protective roles in coastal ecosystems. Across these ancient lineages, colony-founding larvae anchor themselves either by byssus production or by cemented attachment. The latter mode of sessile life is strongly molded by left-right shell asymmetry during larval development of Ostreoida oysters such as Crassostrea hongkongensis. Here, we sequenced the genome of C. hongkongensis in high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry. Importantly, loss of the homeobox gene Antennapedia (Antp) and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves. Comparative transcriptomic analysis shows a conspicuous divergence between left-right asymmetrical C. hongkongensis and symmetrical Pinctada fucata in their expression profiles. Especially, a couple of orthologous transcription factor genes and lineage-specific shell-related gene families including that encoding tyrosinases are elevated, and may cooperatively govern asymmetrical shell formation in Ostreoida oysters.

Abstract Background Chronic pain is a common disease; about 20% of people worldwide suffer from it. While compared with the research on the prevalence and management of chronic pain in developed countries, there is a relative lack of research in this field in China. This research aims to construct the China Pain Health Index (CPHI) to evaluate the current status of the prevalence and management of chronic pain in the Chinese population. Methods The dimensions and indicators of CPHI were determined through literature review, Delphi method, and analytical hierarchy process model, and the original values ​​of relevant indicators were obtained by collecting multi-source data. National and sub-provincial scores of CPHI (2020) were calculated by co-directional transformation, standardization, percentage transformation of the aggregate, and weighted summation. Results The highest CPHI score in 2020 is Beijing, and the lowest is Tibet. The top five provinces are Beijing (67.64 points), Shanghai (67.04 points), Zhejiang (65.74 points), Shandong (61.16 points), and Tianjin (59.99 points). The last five provinces are Tibet (33.10 points), Ningxia (37.24 points), Guizhou (39.85 points), Xinjiang (39.92 points), and Hainan (40.38 points). The prevalence of chronic pain is severe in Heilongjiang, Chongqing, Guizhou, Sichuan, and Fujian. Guizhou, Hainan, Xinjiang, Beijing, and Guangdong display a high burden of chronic pain. The five provinces of Guangdong, Shanghai, Beijing, Jiangsu, and Zhejiang have better treatment for chronic pain, while Tibet, Qinghai, Jilin, Ningxia, and Xinjiang have a lower quality of treatment. Beijing, Shanghai, Qinghai, Guangxi, and Hunan have relatively good development of chronic pain disciplines, while Tibet, Sichuan, Inner Mongolia, Hebei, and Guizhou are relatively poor. Conclusion The economically developed provinces in China have higher CPHI scores, while economically underdeveloped areas have lower scores. The current pain diagnosis and treatment situation in economically developed regions is relatively good, while that in financially underdeveloped areas is rather poor. According to the variations in the prevalence and management of chronic pain among populations in different provinces in China, it is necessary to implement chronic pain intervention measures adapted to local conditions.

Objective(s): This study aimed to investigate the potential effects of wasp venom (WV) from Vespa magnifica on antithrombosis in rats with inferior vena cava (IVC) thrombosis.Materials and Methods: The thrombosis rat model was established by improving the IVC stenosis, in which rats were subjected to IVC ligation for 75 min. Rats were administered argatroban (IP) or WV (s.c.) for 4 hr after IVC thrombosis. The weight, inhibition rate, and pathological morphology of the thrombosis induced by IVC ligation and the variation in four coagulation parameters, coagulation factors, and CD61+CD62P+ were simultaneously determined in IVC rats.Results: The thrombus formed as a result of IVC ligation was stable. Compared with the control group, the weight of the thrombus was significantly reduced in the argatroban group. Thrombus weight was reduced by treatment with 0.6, 0.2, and 0.05 mg/kg WV, with inhibition rates of 52.19%, 35.32%, and 28.98%, respectively. Inflammatory cells adhered to and infiltrated the vessel wall in the IVC group more than in the sham group. However, the pathological morphology and CD61+CD62P+ of the WV treatment groups tended to be normal. Conclusion: We improved the model of IVC thrombosis to be suitable for evaluation of antithrombotic drugs. Our findings demonstrated that WV could inhibit IVC thrombosis associated with reducing coagulation factors V and CD61+CD62p expression in rats.

IntroductionThe Hippo signaling pathway is an evolutionarily conserved signaling cascade that plays a crucial role in regulating cell proliferation, differentiation, and apoptosis. It has been shown to be a key regulator of cell fate and cellular homeostasis in various immune processes. Despite its well-established functions in vertebrate immunity, its roles in marine invertebrate immunity remain poorly understood. Therefore, our present work provides fresh mechanistic insights into how the Hippo pathway orchestrates hemocytic functions in Crassostrea hongkongensis, with implications for studies on its major forms and modifications in animal evolution.MethodThe complete set of Hippo pathway genes, including SAV1, MOB1, LATS, YAP/TAZ, TEAD, and MST, were identified from the C. hongkongensis genome. Quantitative PCR assays were conducted to examine the mRNA expression levels of these genes in different tissues and the levels of these genes in hemocytes before and after bacterial challenges. The study also examined the crosstalk between the Hippo pathway and other immune pathways, such as the AP-1 and p53-dependent p21 signaling cascades. RNA interference was used to knock down MST and TEAD, and MST is a core orchestrator of non-canonical Hippo signaling, to investigate its impact on phagocytosis and bacterial clearance in hemocytes.ResultThe results demonstrated that members of the Hippo pathway were highly expressed in hemocytes, with their expression levels significantly increasing following bacterial challenges. Crosstalk between the Hippo pathway and other immune pathways triggered hemocytic apoptosis, which functioned similarly to the canonical Mst-Lats-Yap signaling pathway in Drosophila and mammals. Knocking down MST resulted in increased phagocytosis and boosted the efficiency of bacterial clearance in hemocytes, presumably due to mobilized antioxidant transcription by Nrf for maintaining immune homeostasis.DiscussionThis study provides novel insights into the regulatory mechanisms underlying the Hippo pathway in immune responses of C. hongkongensis hemocytes. The study highlights the importance of the Hippo pathway in maintaining immune homeostasis and orchestrating hemocytic functions in oysters. Moreover, this study demonstrates the divergence of the Hippo pathway's roles in marine invertebrate immunity from mammalian observations, indicating the need for further comparative studies across species. These findings have significant implications for future research aimed at elucidating the evolutionary trajectory and functional diversity of the Hippo signaling pathway in animal evolution.

ObjectiveTo analyze the quality of life (QoL) and its influencing factors among diabetes mellitus patients two years after undergoing a community-based diabetes self-management and to provide references for improving medical service to diabetes. MethodsFrom August to October of 2013, 1 653 diabetic patients were recruited in 84 communities in three cities (Beijing, Shanghai and Chongqing) and three provinces (Jiangsu, Guangdong and Zhejiang) to carry out a 2-month diabetes self-management group intervention. A follow-up survey was conducted during September – December 2015 to analyze changes in QoL and its influencing factors before and after the self-management intervention. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used in QoL evaluation. ResultsAmong the 1 653 diabetic patients recruited in 2013, 1 603 (96.98%) completed a baseline survey, of which, 1 299 patients were followed up and 304 (18.96%) were lost to follow-up in 2015. Compared to those before the intervention, the patients′ median (quartile range, QR) of SF-36 physical health score increased significantly two years after the self-management intervention (76.50 [23.75] vs. 75.00 [25.00], Z = – 2.53; P = 0.011), but the patients′ median (QR) of SF-36 mental health score was not significantly different (78.44 [25.03] vs. 78.44 [23.31], P > 0.05). The results of unconditional multivariate logistic regression analysis demonstrated that two years after receiving the diabetes self-management intervention, the patients suffering from diabetes 5 years or more and smoking were less likely to have an increased physical health score, while those with an improved self-efficacy were more likely to have an increased physical health score; the patients with following characteristics were less likely to have an increased mental health score: female, with medication reimbursement by medical insurance for urban workers, having complication of other chronic disease, smoking, and being capable of self-injection of insulin or not needing insulin injection. ConclusionThe quality of life was improved to a certain extent among a group of community diabetic patients in China two years after a self-management intervention and the improvement was influenced by the patients′ gender, major payer of the medication cost, disease course, comorbidity of other chronic diseases, self-efficacy, smoking, and self-injection of insulin.

It is estimated that 89% of mortalities could be attributed to chronic and non-communicable diseases (NCDs) currently in China and NCDs are the most serious diseases which cause the disease burden in Chinese population. Since 1980s, World Health Organization has been advocating the application of health promotion strategies to improve population health. Recapitulating the evolution of health promotion policies, we can find that comprehensive actions (such as developing healthy public policy, creating supportive environments for health, strengthening community action, building up personal skills, and reorienting health services) can effectively reduce the burden caused by NCDs. The implementation framework of health in all policies is in favor of the government commitments on maintaining population health, by which it can lead to a path for multi-sectoral cooperation to solve complex social determinants that affect health.

Leaf springs, as vital suspension components in trucks, endure various forces such as torsion, compression, tension and impact, rendering them highly susceptible to fatigue and fracture risks, thereby posing a significant threat to vehicle safety. During the production process of leaf springs, surface decarburisation can easily occur, leading to the formation of numerous surface rolling defects. These defects exert varying influences on the initiation of fatigue crack. This study investigates the influence of various forms of rolling defects caused by decarburisation on fatigue crack initiation in 50CrMnMoNbAT leaf spring through experimental and numerical analysis of fatigue fracture behaviour. The results indicate that fracture locations in the leaf springs are predominantly concentrated approximately 297 mm and 698 mm from the ends. Furthermore, the occurrence of surface decarburisation during the rolling process engenders a significant number of surface rolling defects. Surface defects in leaf springs can be categorised into three forms: Parallel defect, Parcel defect and Occlusal defect. In terms of defect propagation rate, rolling defects on the concave surface are most prone to initiate fatigue cracks, with Occlusal defects exhibiting the highest likelihood of developing internal cracks and the fastest crack propagation rate. [ABSTRACT FROM AUTHOR]

The Apextrin C-terminal (ApeC) domain is a new protein domain largely specific to aquatic invertebrates. In amphioxus, a short-form ApeC-containing protein (ACP) family is capable of binding peptidoglycan (PGN) and agglutinating bacteria via its ApeC domain. However, the functions of ApeC in other phyla remain unknown. Here we examined 130 ACPs from gastropods and bivalves, the first and second biggest mollusk classes. They were classified into nine groups based on their phylogenetics and architectures, including three groups of short-form ACPs, one group of apextrins and two groups of ACPs of complex architectures. No groups have orthologs in other phyla and only four groups have members in both gastropods and bivalves, suggesting that mollusk ACPs are highly diversified. We selected one bivalve ACP (CgACP1; from the oyster Crossostrea gigas) and one gastropod ACP (BgACP1; from the snail Biomphalaria glabrata) for functional experiments. Both are highly-expressed, secreted short-form ACPs and hence comparable to the amphioxus ACPs previously reported. We found that recombinant CgACP1 and BgACP1 bound with yeasts and several bacteria with different affinities. They also agglutinated these microbes, but showed no inhibiting or killing effects. Further analyses show that both ACPs had high affinities to the Lys-type PGN from S. aureus but weak or no affinities to the DAP-type PGN from Bacillus subtilis. Both recombinant ACPs displayed weak or no affinities to other microbial cell wall components, including lipopolysaccharide (LPS), lipoteichoic acid (LTA), zymosan A, chitin, chitosan and cellulose, as well as to several PGN moieties, including muramyl dipeptide (MDP), N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc). Besides, CgACP1 had the highest expression in the gill and could be greatly up-regulated quickly after bacterial challenge. This is reminiscent of the amphioxus ACP1/2 which serve as essential mucus lectins in the gill. Taken together, the current findings from mollusk and amphioxus ACPs suggest several basic common traits for the ApeC domains, including the high affinity to Lys-type PGN, the bacterial binding and agglutinating capacity, and the role as mucus proteins to protect the mucosal surface.

Abstract Background The aim of the present study was to explore the brain active characteristics of patients with irritable bowel syndrome with diarrhea (IBS-D) using resting-state functional magnetic resonance imaging technology. Methods Thirteen IBS-D patients and fourteen healthy controls (HC) were enrolled. All subjects underwent head MRI examination during resting state. A voxel-based analysis of fractional amplitude of low frequency fluctuation (fALFF) maps between IBS-D and HC was performed using a two-sample t-test. The relationship between the fALFF values in abnormal brain regions and the scores of Symptom Severity Scale (IBS-SSS) were analyzed using Pearson correlation analysis. Results Compared with HC, IBS-D patients had lower fALFF values in the left medial superior frontal gyrus and higher fALFF values in the left hippocampus and right precuneus. There was a positive correlation between the duration scores of IBS-SSS and fALFF values in the right precuneus. Conclusion The altered fALFF values in the medial superior frontal gyri, left hippocampus and right precuneus revealed changes of intrinsic neuronal activity, further revealing the abnormality of gut-brain axis of IBS-D.

Abstract Background To establish and validate a radiomics-based model for predicting liver cirrhosis in patients with hepatitis B virus (HBV) by using non-contrast computed tomography (CT). Methods This retrospective study developed a radiomics-based model in a training cohort of 144 HBV-infected patients. Radiomic features were extracted from abdominal non-contrast CT scans. Features selection was performed with the least absolute shrinkage and operator (LASSO) method based on highly reproducible features. Support vector machine (SVM) was adopted to build a radiomics signature. Multivariate logistic regression analysis was used to establish a radiomics-based nomogram that integrated radiomics signature and other independent clinical predictors. Performance of models was evaluated through discrimination ability, calibration and clinical benefits. An internal validation was conducted in 150 consecutive patients. Results The radiomics signature comprised 25 cirrhosis-related features and showed significant differences between cirrhosis and non-cirrhosis cohorts (P

In order to study the thermal response of carbon fiber epoxy resin composites in fire, considering the pyrolysis process in fire, the nonlinear thermal response equations were established, and a finite difference method was used to calculate and analyse the material's internal time-dependent temperature progressions and carbonization subjected to one-sided heat flux. The theoretical results from the established thermal response equations were validated against experimental data and a good agreement was observed.As the heating time increases, the carbonized layer range gradually expands, the temperature changes tend to be stable, and the distribution of material temperature with depth position is changed from nonlinear to linear. With the increment of the depth, temperature rise rate is decreased, the time of carbon fiber epoxy resin composites reaching the pyrolysis temperature is increased, the carbonization process is slowed down, and the peak change of density with temperature moves toward the low temperature with the increased depth. The residual mass fraction of materials at different depth in the pyrolysis reaction zone is slightly different at the same temperature, the residual mass fraction is decreased and the degree of carbonization is increased as the depth increases.

Vibrio species are ubiquitously distributed in marine environments, with important implications for emerging infectious diseases. However, relatively little is known about defensive strategies deployed by hosts against Vibrio pathogens of distinct virulence traits. Being an ecologically relevant host, the oyster Crassostrea hongkongensis can serve as an excellent model for elucidating mechanisms underlying host-Vibrio interactions. We generated a Vibrio alginolyticus mutant strain (V. alginolyticus△vscC) with attenuated virulence by knocking out the vscC encoding gene, a core component of type III secretion system (T3SS), which led to starkly reduced apoptotic rates in hemocyte hosts compared to the V. alginolyticusWT control. In comparative proteomics, it was revealed that distinct immune responses arose upon encounter with V. alginolyticus strains of different virulence. Quite strikingly, the peroxisomal and apoptotic pathways are activated by V. alginolyticusWT infection, whereas phagocytosis and cell adhesion were enhanced in V. alginolyticus△vscC infection. Results for functional studies further show that V. alginolyticusWT strain stimulated respiratory bursts to produce excess superoxide (O2•−) and hydrogen peroxide (H2O2) in oysters, which induced apoptosis regulated by p53 target protein (p53tp). Simultaneously, a drop in sGC content balanced off cGMP accumulation in hemocytes and repressed the occurrence of apoptosis to a certain extent during V. alginolyticus△vscC infection. We have thus provided the first direct evidence for a mechanistic link between virulence of Vibrio spp. and its immunomodulation effects on apoptosis in the oyster. Collectively, we conclude that adaptive responses in host defenses are partially determined by pathogen virulence, in order to safeguard efficiency and timeliness in bacterial clearance.

Introduction The rapid rise in the prevalence of diabetes has a negative impact on patients’ quality of life. Diabetes self-management group education is cost-effective and efficient for patients to control blood glucose. However, there are no consistent standards for self-management group education, and its long-term effects (≥12 months) are unclear. Although a few systematic reviews evaluated the long-term effects, they did not make clear provisions on the content of self-management, and the number and sample size of included studies were small, which may lead to misclassification bias and reporting bias. Therefore, we plan to conduct this systematic review to evaluate the long-term effects of self-management group education and determine the effects of different self-management characteristics on glycosylated haemoglobin (HbA1c).Methods and analysis We will retrieve Chinese databases (Wanfang, Chinese Hospital Knowledge Warehouse) and English databases (PubMed, ScienceDirect, EMBASE, Web of Science, Bailian Platform, Cochrane Central Register of Controlled Trials, Google Scholar) for randomly controlled trials and cluster randomly controlled trials of which participants are adults with type 2 diabetes mellitus. We will manually search citation lists and trial registries, and consult authors to obtain relevant articles. The retrieval time range will be from the establishment of the database to July 2020 to avoid omitting relevant studies. The primary outcome will be HbA1c. The secondary outcomes will be fasting plasma glucose, postprandial blood glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, body mass index, waist circumference and death event. Two reviewers will independently conduct article screening and assessment of risk of bias, with a third reviewer arbitrating if necessary. We will give priority to the use of meta-analysis to evaluate the pooled effects of all outcomes. For the outcomes of unrecognised sources of heterogeneity, missing data and less than three related studies, narrative synthesis approach will be used.Ethics and dissemination Ethical approval is not required for this systematic review. We plan to present the findings in a peer-reviewed scientific journal, relevant and responsible organisations, and training meetings.PROSPERO registration number CRD42020209011.

Objective To observe the effect of zoledronic acid on the reduction of acute bone loss and fracture rate in elderly postoperative patients with intertrochanteric fracture. Methods From August 2012 to January 2015, a total of 482 patients with senile osteoporotic femoral intertrochanteric fracture, who accepted proximal femoral intramedullary fixation under anesthesia were analysed. The patients were divided into two groups. Treatment group (353 cases) were treated with 100 mL/5 mg of zoledronic acid injection in 1 week after operation, as well as orally taken 600 mg/d of calcium carbonate and active vitamin D3 400 IU/d. Control group (129 cases) were given the same dose of calcium carbonate and active vitamin D3 orally. Efficacy evaluation were conducted during different periods of medication Results Compared with pre‐medication, indexes of bone metabolism (TARP‐5b, CTX) in the treatment group were brought down, especially significantly statistically different after 12 months of medication. The treatment group performed superior to control group in alleviating the pain of back and posture changing (P

Background/Objective: This study is a case–control study to explore risk and protective factors, including clinical data and bone mineral density (BMD), affecting vertebral body fragility fracture in elderly men and postmenopausal women. In addition, we investigate the effectiveness of lumbar spine BMD by quantitative computed tomography (QCT) in discriminating vertebral fragility fracture. Methods: In this case–control study, 52 males and 198 females with vertebral fragility fracture were compared with sex- and age-matched healthy controls to analyse the risk factors that may affect vertebral fragility fracture. The L1–L3 vertebral BMDs were measured by QCT. The difference in risk factors between fracture cases and controls were analysed using student t test and Mann–Whitney U test. The correlation between BMD, age, height and weight were analysed using univariate analysis. Multiple logistic regression analysis was used to study statistically significant indexes. The receiver operating characteristic curve was used to calculate the cut-off values for positive and negative predictive values of BMD for vertebral fracture discrimination. Results: In males, body weight and BMD were significantly different between the fracture group and the control group, whereas BMD was only weakly correlated with age (r = −0.234). In females, only BMD was significantly different between the fracture and control groups. BMD was weakly correlated with height (r = 0.133) and weight (r = 0.120) and was moderately correlated with age (r = −0.387). There was no correlation between BMD and the remaining variables in this study. In both men and women, the BMD (p = 0.000) was the independent protective factor against vertebral fracture. The cut-off values of vertebral BMD for fractures were 64.16 mg/cm3 for males and 55.58 mg/cm3 for females. QCT-measured BMD has a high positive predictive value and negative predictive value for discriminating vertebral fragility fracture across a range of BMD values. Conclusion: This study suggests that BMD is closely related to vertebral fragility fracture and that QCT is an effective technique to accurately discriminate vertebral fragility fracture. The translational potential of this article: The spine BMD measured by QCT is closely related to fracture, which may allow clinicians to more accurately discriminate which individuals are likely to experience vertebral fragility fracture. Keywords: Bone mineral density, Quantitative computed tomography, Vertebral fragility fracture

Hemocyanins present in the hemolymph of invertebrates are multifunctional proteins that are responsible for oxygen transport and play crucial roles in the immune system. They have also been identified as a source of antimicrobial peptides during infection in mollusks. Hemocyanin has also been identified in the cephalopod ancestor Nautilus, but antimicrobial peptides derived from the hemocyanin of Nautilus pompilius have not been reported. Here, the bactericidal activity of six predicted peptides from N. pompilius hemocyanin and seven mutant peptides was analyzed. Among those peptides, a mutant peptide with 15 amino acids (1RVFAGFLRHGIKRSR15), NpHM4, showed relatively high antibacterial activity. NpHM4 was determined to have typical antimicrobial peptide characteristics, including a positive charge (+5.25) and a high hydrophobic residue ratio (40%), and it was predicted to form an alpha-helical structure. In addition, NpHM4 exhibited significant antibacterial activity against Gram-negative bacteria (MBC = 30 μM for Vibrio alginolyticus), with no cytotoxicity to mammalian cells even at a high concentration of 180 µM. Upon contact with V. alginolyticus cells, we confirmed that the bactericidal activity of NpHM4 was coupled with membrane permeabilization, which was further confirmed via ultrastructural images using a scanning electron microscope. Therefore, our study provides a rationalization for the development and optimization of antimicrobial peptide from the cephalopod ancestor Nautilus, paving the way for future novel AMP development with broad applications.

Summary: Chloride ion plays critical roles in modulating immunological interactions. Herein, we demonstrated that the anion channel CLIC2α mediates Cl− flux to regulate hemocytes functions in the Pacific oyster (Crassostrea gigas). Specifically, during infection by Vibrio parahemolyticus, chloride influx was activated following onset of phagocytosis. Phosphorylation of Akt was stimulated by Cl− ions entering host cells, further contributing to signal transduction regulating internalization of bacteria through the PI3K/Akt signaling pathway. Concomitantly, Cl− entered phagosomes, promoted the acidification and maturation of phagosomes, and contributed to production of HOCl to eradicate engulfed bacteria. Finally, genomic screening reveals CLIC2α as a major Cl− channel gene responsible for regulating Cl− influx in oysters. Knockdown of CLIC2α predictably impeded phagosome acidification and restricted bacterial killing in oysters. In conclusion, our work has established CLIC2α as a prominent regulator of Cl− influx and thus Cl− function in C. gigas in bacterial infection contexts.

Crassostrea hongkongensis (Hong Kong oyster) is an ecologically and economically valuable shellfish endemic to South/Southeast Asia. Due to ocean acidification and warming waters, they have become increasingly vulnerable to invading microbes including Vibrio parahaemolyticus, a significant foodborne human pathogen. In recent years, outbreaks of V. parahaemolyticus have emerged as a perennial phenomenon in parts of the world, necessitating to better understand the biology of host-pathogen interactions in this under-examined marine invertebrate. Although an immunologically relevant autophagy apparatus has been identified in Crassostrea gigas, an evolutionarily close mollusk cousin, the precise mechanistic details of C. hongkongensis autophagy during V. parahaemolyticus infection are still wanting. Here, we compellingly demonstrated that in vivo V. parahaemolyticus challenge robustly triggered autophagic signaling in C. hongkongensis hemocytes peaking at 6 h post-infection, which subsequently promoted bacterial clearance and dampened premature apoptosis. Simultaneously, a large surplus of adenosine monophosphate (AMP) and elevations in reactive oxygen species (ROS, specifically mitochondrial O2– and cellular H2O2) formation were observed post-infection. Extrinsically applied AMP and ROS could synergistically induce AMP-activated protein kinase (AMPK) phosphorylation to stimulate downstream autophagic events. V. parahaemolyticus infection-induced autophagy was pharmacologically shown to be AMPK-dependent in vivo. Overall, our results establish autophagy as a crucial arm of host defense against Vibrio infections in mollusks, and provide new insights into the underappreciated roles of ROS and AMP as co-regulators of autophagy.

Hemocytes play unequivocally central roles in host immune defense of bivalve mollusks, though the exact mechanisms underlying their functional differentiation are only partially understood. To this end, granulocytes and hyalinocytes were sorted via flow cytometry from hemocytes of the Pacific oyster Crassostrea gigas, and consequently quantitative transcriptomic analysis revealed a striking array of differentially expressed genes (DEGs), which were globally upregulated in granulocytes, dedicating to functional differentiation among oyster hemocytes. Our network of DEGs illustrated actively engaged signaling pathways, with Cdc42/Cdc42l being a core regulator of pathway network, which was validated by a dramatically reduced capacity for hemocyte phagocytosis in the presence of Cdc42 inhibitors. Additionally, a number of transcription factors were identified among DEGs, including ELK, HELT, and Fos, which were predominantly expressed in granulocytes. The AP-1 transcription factor Fos was confirmed to facilitate functional differentiation of hemocytes in an assay on binding to target genes by the AP-1 binding site, consistent with downstream phagocytosis and ROS production. Importantly, Cdc42/Cdc42l were also regulated by the expression of Fos, providing a possible regulatory mechanism-guided hemocyte functional differentiation. Findings in this study have bridged a knowledge gap on the mechanistic underpinnings of functional differentiation of hemocytes in a marine invertebrate C. gigas, which promise to facilitate research on the evolution of immune defense and functional differentiation of phagocyte in higher-order and more recent phyla.