Search

Abstract Background Currently, no normal ultrasound data of the fetuses during the 20–40 gestation have been obtained for references of fetal growth and development. If such ultrasound data existed for prenatal diagnosis of possible diseases and abnormalities, neonates would be able to get timely treatment immediately after birth. This study was thus performed to obtain ultrasound parameters of normal fetuses during the 20–40 week gestation and the distribution of ultrasound parameters with the gestational age for references of detecting potential fetal diseases and abnormalities. Methods Normal fetuses without any abnormalities were enrolled, and the ultrasound parameters of the general biology, arteries, and aorta were measured and analyzed. Results 417 normal fetuses were enrolled. A significant (P

Abstract Background The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population. Methods Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods. Results The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p

Abstract Background Severe trauma accounts for a main factor inducing mortality for individuals aged

Background ICU patients have a high incidence of VTE. The American College of Chest Physicians antithrombotic practice guidelines recommend assessing the risk of VTE in all ICU patients. Although several VTE risk assessment tools exist to evaluate the risk factors among hospitalized patients, there is no validated tool specifically for assessing the risk of VTE in ICU patients. Methods A retrospective corhort study was conducted between June 2018 and October 2022. We obtained data from the electronic medical records of patients with a variety of diagnoses admitted to a mixed ICU. Multivariable logistic regression analysis was used to evaluate the independent risk factors of VTE. Receiver operating characteristic (ROC) curves were used to analyse the predictive accuracy of different tools. Results A total of 566 patients were included, and VTE occurred in 89 patients (15.7%), 62.9% was asymptomatic VTE. A prediction model (the ICU-VTE prediction model) was derived from the independent risk factors identified using multivariate analysis. The ICU-VTE prediction model included eight independent risk factors: history of VTE (3 points), immobilization ≥4 days (3 points), multiple trauma (3 points), age ≥70 years (2 points), platelet count >250 × 10 3 /μL (2 points), central venous catheterization (1 point), invasive mechanical ventilation (1 point), and respiratory failure or heart failure (1 point). Patients with a score of 0–4 points had a low (1.81%) risk of VTE. Patients were at intermediate risk, scoring 5–6 points, and the overall incidence of VTE in the intermediate-risk category was 17.1% (odds ratio [OR], 11.1; 95% confidence interval [CI], 4.2-29.4). Those with a score ≥7 points had a high (44.1%) risk of VTE (OR, 42.6; 95% CI, 16.4-110.3). The area under the curve (AUC) of the ICU-VTE prediction model was 0.838, and the differences in the AUCs were statistically significant between the ICU-VTE prediction model and the other three tools (ICU-VTE score, Z = 3.723, P

Abstract To investigate the instent restenosis rate of sirolimus-coated stents in percutaneous coronary intervention (PCI) and risk factors for in-stent restenosis, patients with unstable angina (UA) caused by coronary artery stenosis were enrolled, and all clinical and imaging data were analyzed. Among 143 enrolled patients with UA aged 35–83 (mean 60.9 ± 10.0) years enrolled, there were 114 (79.7%) male and 29 (20.3%) female patients. Arterial stenosis was present in one coronary artery in 6 (4.2%) patients, in two coronary arteries in 20 (14.0%) patients, in three arteries in 116 (81.1%), and in four coronary arteries in 1 (0.7%) patient. Stenting was successfully performed in all (100%) patients, and 181 stents were deployed. The quantitative flow ratio (QFR) was 0.92 ± 0.03 (range 0.84–0.96) immediately after stenting, and the TIMI was grade 3 in all patients. The diameter of the stents deployed ranged 2.25–4 mm (mean 3.04 ± 0.44) with a length ranging 10 mm to 104 mm (mean 32.73 ± 15.5). Follow-up angiography was performed in all patients with a duration of 1–92 (mean 15.0 ± 18.8) months. Instent restenosis ≥ 50% occurred in 25 (17.5%) patients. In univariate logistic regression analysis, significant (P

After reconstructing the anterior cruciate ligament (ACL), unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing stage. With good biological features and high formability, Magnesium-Zinc-Gadolinium (ZG21) wires are developed to bunch the tendon graft for matching the bone tunnel during transplantation. Microstructure, tensile strength, degradation, and cytotoxicity of ZG21 wire are evaluated. The rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT, histology, and mechanical test. The SEM/EDS, immunochemistry, and in vitro assessments are performed to investigate the underlying mechanism. Material tests demonstrate the high formability of ZG21 wire as surgical suture. Micro-CT shows ZG21 wire degradation accelerates tunnel bone formation, and histologically with earlier and more fibrocartilage regeneration at the healing interface. The mechanical test shows higher ultimate load in the ZG21 group. The SEM/EDS presents ZG21 wire degradation triggered calcium phosphate (Ca-P) deposition. IHC results demonstrate upregulation of Wnt3a, BMP2, and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of healing. In vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a, β catenin, ocn and opn to stimulate osteogenesis. Ex vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon tissue. In conclusion, the ZG21 wire is feasible for tendon graft bunching. Its degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction.

Abstract We employ an evolutionary game model to investigate the interaction between firms’ engagement in corporate social irresponsibility (CSI) behaviors (without violating laws) and consumers’ perception of corporate social responsibility (CSR) within a consumer market. The core paradox revolves around the trade-off between firms benefiting from pursuing economic performance without adhering to social responsibility and the maximization of social welfare achieved when firms are socially responsible, and consumers possess strong CSR perception. Through an asymmetric two-population evolutionary game model, we identify two distinct scenarios of evolutionary stable strategies based on different industrial environments. Additionally, the evolution of a healthy market is contingent upon an increase in consumers’ bargaining power, although it is also influenced by the initial states of the two-group system, resulting in path dependence as a significant feature of the system’s evolutionary equilibrium. Furthermore, we observe that the added willingness to pay for CSR, while not impacting the evolutionary outcomes, could increase the likelihood of a healthy market when consumers’ bargaining power is high. These findings underscore the diverse dynamics of firms’ CSI behaviors, which depend on transaction costs, industrial structure, and consumers’ willingness to pay, offering valuable insights from a micro perspective.

Tuberculosis (TB) is a chronic bacterial disease, as well as a complex immune disease. The occurrence, development, and prognosis of TB are not only related to the pathogenicity of Mycobacterium tuberculosis (Mtb), but also related to the patient’s own immune state. The research and development of immunotherapy drugs can effectively regulate the body’s anti-TB immune responses, inhibit or eliminate Mtb, alleviate pathological damage, and facilitate rehabilitation. This paper reviews the research progress of immunotherapeutic compounds for TB, including immunoregulatory compounds and repurposing drugs, and points out the existing problems and future research directions, which lays the foundation for studying new agents for host-directed therapies of TB.

Abstract Background The vein of Marshall (VOM) ethanol infusion is increasingly performed in combination with catheter ablation in atrial fibrillation (AF). The cannulation of the VOM can sometimes be challenging. This study aimed to evaluate the double-wire technique in cases of difficult cannulation of the VOM. Case presentation Patients with AF scheduled for combined catheter ablation and VOM ethanol infusion were consecutively enrolled. The procedure was performed via the femoral vein. If the regular cannulation technique with one angioplasty wire failed or took more than 20 min, the double-wire technique using a stabilizing wire and a cannulation wire was performed. The unique technique was used mainly in two scenarios, when the Eustachian ridge was too prominent as a barrier for catheter manipulation or when the VOM ostium was close to the coronary sinus ostium. Of 162 patients scheduled for VOM ethanol infusion, the double-wire technique was applied in 6 (3.7%) patients and led to a 100% successful cannulation rate of the VOM. Of the six patients, two had a prominent Eustachian ridge, and four had a VOM ostium close to the coronary sinus ostium. The mean cannulation time was 33.3 ± 7.3 min. The ethanol infusion was successfully performed in 5 patients. One patient had a collateral circulation in the distal VOM, and ethanol infusion was not performed. Conclusions The double-wire technique can facilitate VOM cannulation and ethanol infusion in challenging cases. Word count : 231.

ABSTRACTEngineering microbial hosts to synthesize pyruvate derivatives depends on blocking pyruvate oxidation, thereby causing severe growth defects in aerobic glucose-based bioprocesses. To decouple pyruvate metabolism from cell growth to improve pyruvate availability, a genome-scale metabolic model combined with constraint-based flux balance analysis, geometric flux balance analysis, and flux variable analysis was used to identify genetic targets for strain design. Using translation elements from a ~3,000 cistronic library to modulate fxpK expression in a bicistronic cassette, a bifido shunt pathway was introduced to generate three molecules of non-pyruvate-derived acetyl-CoA from one molecule of glucose, bypassing pyruvate oxidation and carbon dioxide generation. The dynamic control of flux distribution by T7 RNAP-mediated synthetic small RNA decoupled pyruvate catabolism from cell growth. Adaptive laboratory evolution and multi-omics analysis revealed that a mutated isocitrate dehydrogenase functioned as a metabolic switch to activate the glyoxylate shunt as the only C4 anaplerotic pathway to generate malate from two molecules of acetyl-CoA input and bypass two decarboxylation reactions in the tricarboxylic acid cycle. A chassis strain for pyruvate derivative synthesis was constructed to reduce carbon loss by using the glyoxylate shunt as the only C4 anaplerotic pathway and the bifido shunt as a non-pyruvate-derived acetyl-CoA synthetic pathway and produced 22.46, 27.62, and 6.28 g/L of l-leucine, l-alanine, and l-valine by a controlled small RNA switch, respectively. Our study establishes a novel metabolic pattern of glucose-grown bacteria to minimize carbon loss under aerobic conditions and provides valuable insights into cell design for manufacturing pyruvate-derived products.IMPORTANCEBio-manufacturing from biomass-derived carbon sources using microbes as a cell factory provides an eco-friendly alternative to petrochemical-based processes. Pyruvate serves as a crucial building block for the biosynthesis of industrial chemicals; however, it is different to improve pyruvate availability in vivo due to the coupling of pyruvate-derived acetyl-CoA with microbial growth and energy metabolism via the oxidative tricarboxylic acid cycle. A genome-scale metabolic model combined with three algorithm analyses was used for strain design. Carbon metabolism was reprogrammed using two genetic control tools to fine-tune gene expression. Adaptive laboratory evolution and multi-omics analysis screened the growth-related regulatory targets beyond rational design. A novel metabolic pattern of glucose-grown bacteria is established to maintain growth fitness and minimize carbon loss under aerobic conditions for the synthesis of pyruvate-derived products. This study provides valuable insights into the design of a microbial cell factory for synthetic biology to produce industrial bio-products of interest.

Alzheimer’s disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD.

ObjectiveTuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). The purpose of this study was to explore the relationship between the number of natural killer (NK) cells and adaptive immune status, and disease severity in TBM patients.MethodsWe conducted a retrospective study on 244 TB patients and 146 healthy control subjects in the 8th Medical Center of the PLA General Hospital from March 2018 and August 2023.ResultsThe absolute count of NK cells in the peripheral blood of TBM patients was significantly lower than that in normal controls (NC), latent tuberculosis infection (LTBI), and non-severe TB (NSTB) patients (p 0.05). The absolute counts of lymphocyte subsets in TBM combined with other active TB group, etiology (+) group, IGRA (−) group, and antibody (+) group were lower than that in simple TBM group, etiology (−) group, IGRA (+) group, and antibody (−) group, respectively. The CD3+ T, NK, and B cells in BMRC-stage III TBM patients were significantly lower than those in stage I and stage II patients (p

Background and objective: Hemorheology and blood glucose are commonly used to estimate the risks of thrombosis and stress hyperglycemia after anaesthesia. The sequence of acupoint stimulation might influence the therapeutic effects of acupuncture. In the current study, we aimed at investigating the effect of different acupuncture sequences of “Huiyangjiuzhen” acupoints on the blood glucose and hemorheology in anesthetized rabbits. Methods: Twenty-five rabbits were randomly divided into five groups, including the control group (CG), the positive-sequence group (PSG), the reverse-sequence group (RSG), the disorder-sequence group (DSG), and the random group (RG). Except for the CG and RG, the rabbits in other groups were acupunctured with different sequences of “Huiyangjiuzhen''acupoints when the rabbits were anesthetized. The acupoints in rabbits of the RG were chosen randomly. The levels of blood glucose and hemorheology indexes before and after anaesthesia was detected. Results: In the PSG, Hηb 200/s, Mηb 30/s, Hηr 200/s, ERI, hematocrit and plasma viscosity levels were decreased, and the blood glucose level was not changed. In the DSG, the levels of Mηb 30/s and hematocrit were decreased, and the blood glucose was increased. In the CG, RSG and RG, no hemorheology indexes were changed and the blood glucose was increased. Conclusion: “Huiyangjiuzhen” acupuncture could decrease the risks of post-operative thrombosis and stress hyperglycemia in anesthetized rabbits. This effectiveness depends on both acupuncture and acupuncture sequence at the “Huiyangjiuzhen” acupoints.

Objective. Intensive care unit (ICU)-acquired weakness often occurs in patients with invasive mechanical ventilation (IMV). Early active mobility may reduce ICU-acquired weakness, improve functional status, and reduce disability. The aim of this study was to investigate whether high-intensity early mobility improves post-ICU discharge functional status of IMV patients. Methods. 132 adult patients in the ICU who were undergoing IMV were randomly assigned into two groups with a ratio of 1 : 1, with one group received high-intensity early mobility (intervention group, IG), while the other group received conventional treatment (control group, CG). The functional status (Barthel Index (BI)), capacity of mobility (Perme score and ICU Mobility Scale (IMS)), muscle strength (Medical Research Council sum scores (MRC-SS)), mortality, complication, length of ICU stay, and duration of IMV were evaluated at ICU discharge or after 3-month of ICU discharge. Results. The patient’s functional status was improved (BI scores 90.6 ± 18.0 in IG vs. 77.7 ± 27.9 in CG; p=0.005), and capacity of mobility was increased (Perme score 17.6 ± 7.1 in IG vs. 12.2 ± 8.5 in CG, p

Abstract Background Myopia and obesity in children and adolescents have become serious public health problems that endanger public health, especially in China. Unhealthy lifestyle behaviors are environmental drivers of both myopia and obesity. This protocol describes a study to evaluate the effectiveness of “22510SS”, that is 2 h of daytime outdoor activities (‘2’); Limit screen time to no more than 2 h per day (‘2’); Consume at least 5 servings of fruits and vegetables daily (‘5’); Attain 1 h of physical activity daily (‘1’); Consume 0 sugar-sweetened beverages (‘0’); Reasonable sleep duration (‘S’); Regular supervision (‘S’). A school-based, multifaceted intervention strategy for myopia and obesity prevention, and to assess and explore the implementation of “22510SS” with regards to acceptability, feasibility, adoption, usage and maintenance. Methods and analysis This study aims to develop a comprehensive intervention strategy "22510SS" based on the socio-ecological model, and A two-arm cluster randomized trial with a parallel-group of a 1:1 allocation ratio in 36 primary and secondary schools to test its evidence-based intervention programs on the effects and implementation of myopia and obesity epidemics in children and adolescents in grades 4 and 7. The primary outcomes will include differences in visual acuity, body mass index, outdoor activity indicators, screen time, fruit and vegetable intake, high-quality protein intake, sugar-sweetened beverage intake, sleep duration, and level of monitoring among children and adolescents. Secondary outcomes will assess the acceptability, feasibility, uptake, use, and maintenance of the intervention. Effects on the primary and secondary outcomes will be analyzed using linear and logistic regression analyses, as well as difference-in-difference analysis, taking into account cluster effects and possible confounding factors. Process assessments will also be conducted through quantitative and qualitative analyses, including acceptability, feasibility, gender, adoption, implementation, and sustainability. Discussion This study will evaluate the effectiveness of “22510SS” and examine its implementation in the school-based network nesting family and clinic. Following this intervention study, the integrated intervention program focused on myopia and obesity among children and adolescents have great potential to be implemented in China to promote and support healthy lifestyle behavior change and reduce the risk of myopia and obesity in children and adolescents. Trial registration NCT05275959. Registered 23 Mach 2022.

Background: The vein of Marshall (VOM) ethanol infusion improves rhythm control in atrial fibrillation (AF). The identification and cannulation of the VOM can be technically challenging. This study aimed to assess the angiographic morphology of the VOM and investigate its value in the VOM ethanol infusion. Methods: Patients with AF (n = 162) scheduled for combined catheter ablation and VOM ethanol infusion were enrolled. The VOM morphologic features in the right anterior oblique (RAO), the left anterior oblique (LAO), and the LAO cranial views were analyzed. The impact of morphology on the identification and cannulation of the VOM was investigated. Results: The VOM was identified in 159 (98.1 %) and cannulated in 150 (92.6 %) patients. The VOM identification rate in the RAO and LAO/LAO cranial view was 97.3 % and 89.3 %, respectively. Of 134 patients with VOM identification in the LAO/LAO cranial view, 104 (77.6 %) had a VOM ostium clock location (VOMoClock) of ≤3 and 3–4 o'clock. The VOM cannulation success rate in the ≤3, 3–4, 4–5, and 5–6 o'clock groups was 100 %, 92.6 %, 88.5 %, and 77.8 %, respectively (p = 0.032). The median (interquartile range) cannulation time in the four groups was 10.5 (6.3), 12.0 (9.0), 13.0 (23.0), and 34.0 (30.0) minutes, respectively (p

Photoacoustic (PA) theranostics is a new emerging field that uniquely combines diagnosis and treatment in one modality. However, its current status is compromised by the indispensable dependence on nonreversible phase-change nanoprobes that provides one-time-only action. Here, we demonstrate a picosecond-laser-pumped ultrafast PA cavitation technique for highly efficient shockwave theranostics, guaranteeing sustained PA cavitation by using non-phase-change nanoprobes. Theoretical simulations validate that, when compressing the excitation laser pulse width to hundred-picosecond, the thermal confinement effects of a conventional nanoprobe will induce transient heating of the extremely thin surrounding liquid layer of the nanoprobes beyond its cavitation point in a localized area at nanoscale, resulting in intense cavitation and PA shockwaves by the environment rather than the nanoprobes. Both cellular and mouse model experiments have demonstrated the highly effective anti-tumor effects. This method provides a sustainable, reproducible, and highly effective strategy for PA theranostics, prefiguring great potential for the clinical applications.

Abstract Aim To investigate the ability of critical care nurses to identify pressure injury and incontinence‐associated dermatitis and analyse the possible influencing factors. Design Cross‐sectional survey. Methods This study was conducted at 24 hospitals across 12 provinces in China. A self‐made electronic questionnaire was used. Nurses identified and judged injuries according to the information provided. Results The average identification score for pressure injury and incontinence‐associated dermatitis was 9.00 ± 3.51 points, and only 2.16% of nurses scored ≥16 points. The average correct identification rate for pressure injury and incontinence‐associated dermatitis was 45%. The correct identification rate for stage 1 pressure injury was the highest, while those for stage 3, stage 4, deep tissue pressure injury and unstageable pressure injury were all lower than 50%; incontinence‐associated dermatitis was also easily misjudged. Nurses' educational backgrounds, professional titles, job positions, hospital levels and learning frequency were the factors that affected their ability to identify pressure injury and incontinence‐associated dermatitis.

The microstructure and texture evolutions of the Mg–2Zn–0.5Mn–0.2Ca–0.3Nd–0.7La alloy were investigated by hot compression tests, which carried out in the temperatures range of 250–400 °C and strain rates range of 0.001–1 s−1. The thermal deformation behavior of the alloy was reflected by the hyperbolic sine function relationship, which was applicable to all stresses conditions due to the calculated value of α∗σp was 1.0. The thermal processing map based upon the dynamic material model was built. In addition, the suitable and unsuitable hot working regions were analyzed combined with microstructures. The results show that the dynamic recrystallization (DRX) mechanism of the hot compression deformation microstructure of the alloy was discontinuous dynamic recrystallization (DDRX). There were plenty of extension twins in some coarse deformed grains and these twins form a new //TD texture, which led to the weakening the //CD texture.

This study uses biform game models to examine firms’ patent deployment strategies that involve a choice between appropriating a patented technology to gain a unique competitive advantage or licensing the technology to a competitor in the product market. It addresses the question of under what circumstances firms use a patent appropriation strategy over a licensing strategy, or vice versa. By incorporating competitive and cooperative settings, this study develops theory and propositions to illustrate the mechanisms by which patent deployment strategies are chosen by an innovator or follower in a product market as a function of the characteristics of innovation, transaction costs, bargaining power, strategic interactions, and other market conditions. This study contributes to the literature by distinguishing between patent appropriability and value appropriation in a transactional network under rivalry. The model and its extensions provide new insights into appropriation strategies for patent portfolios, which are important intellectual assets in a knowledge-based economy.

Background and aims Hyperuricaemia can lead to gout and is associated with an increased risk of cardiometabolic disease. We aimed to investigate the prevalence of hyperuricaemia and its related factors in Chinese children and adolescents.Methods We pooled data from 11 population-based studies comprising 54,580 participants aged 3–19 years. The sex- and age-standardized prevalence of hyperuricaemia was estimated overall and by sex, age, weight status, geographic region and survey year.Results Serum uric acid (SUA) increased gradually from 3 to 11 years with no significant sex difference, and then increased dramatically during 11–15 years. The estimated overall prevalence of hyperuricaemia was 23.3% (26.6% in boys and 19.8% in girls, p 50,000 children and adolescents aged 3–19 years, we found that the prevalence of hyperuricaemia was high in overall population and subgroups of sex, age, obesity, region and survey year.Meaning: Our findings indicate that hyperuricaemia is an important health problem in Chinese children and adolescents, and effective intervention strategies are needed to reduce its burden.

Summary: Background: Arterial stiffening is central to the vascular ageing process and a powerful predictor and cause of diverse vascular pathologies and mortality. We investigated age and sex trajectories, regional differences, and global reference values of arterial stiffness as assessed by pulse wave velocity (PWV). Methods: Measurements of brachial-ankle or carotid-femoral PWV (baPWV or cfPWV) in generally healthy participants published in three electronic databases between database inception and August 24th, 2020 were included, either as individual participant-level or summary data received from collaborators (n = 248,196) or by extraction from published reports (n = 274,629). Quality was appraised using the Joanna Briggs Instrument. Variation in PWV was estimated using mixed-effects meta-regression and Generalized Additive Models for Location, Scale, and Shape. Findings: The search yielded 8920 studies, and 167 studies with 509,743 participants from 34 countries were included. PWV depended on age, sex, and country. Global age-standardised means were 12.5 m/s (95% confidence interval: 12.1–12.8 m/s) for baPWV and 7.45 m/s (95% CI: 7.11–7.79 m/s) for cfPWV. Males had higher global levels than females of 0.77 m/s for baPWV (95% CI: 0.75–0.78 m/s) and 0.35 m/s for cfPWV (95% CI: 0.33–0.37 m/s), but sex differences in baPWV diminished with advancing age. Compared to Europe, baPWV was substantially higher in the Asian region (+1.83 m/s, P = 0.0014), whereas cfPWV was higher in the African region (+0.41 m/s, P

Abstract Our previous research developed a novel tuberculosis (TB) DNA vaccine ag85a/b that showed a significant therapeutic effect on the mouse tuberculosis model by intramuscular injection (IM) and electroporation (EP). However, the action mechanisms between these two vaccine immunization methods remain unclear. In a previous study, 96 Mycobacterium tuberculosis (MTB) H37Rv‐infected BALB/c mice were treated with phosphate‐buffered saline, 10, 50, 100, and 200 μg ag85a/b DNA vaccine delivered by IM and EP three times at 2‐week intervals, respectively. In this study, peripheral blood mononuclear cells (PBMCs) from three mice in each group were isolated to extract total RNA. The gene expression profiles were analyzed using gene microarray technology to obtain differentially expressed (DE) genes. Finally, DE genes were validated by real‐time reverse transcription‐quantitive polymerase chain reaction and the GEO database. After MTB infection, most of the upregulated DE genes were related to the digestion and absorption of nutrients or neuroendocrine (such as Iapp, Scg2, Chga, Amy2a5), and most of the downregulated DE genes were related to cellular structural and functional proteins, especially the structure and function proteins of the alveolar epithelial cell (such as Sftpc, Sftpd, Pdpn). Most of the abnormally upregulated or downregulated DE genes in the TB model group were recovered in the 100 and 200 μg ag85a/b DNA IM groups and four DNA EP groups. The pancreatic secretion pathway downregulated and the Rap1 signal pathway upregulated had particularly significant changes during the immunotherapy of the ag85a/b DNA vaccine on the mouse TB model. The action targets and mechanisms of IM and EP are highly consistent. Tuberculosis infection causes rapid catabolism and slow anabolism in mice. For the first time, we found that the effective dose of the ag85a/b DNA vaccine immunized whether by IM or EP could significantly up‐regulate immune‐related pathways and recover the metabolic disorder and the injury caused by MTB.

Cirsium japonicum var. maackii (CJ), a perennial herb from the Compositae family, is a traditional antihypertensive, uretic antihepatitis, and antihemorrhagic medicine in Korea. However, CJ reported has minimal immune-enhancing effects. We investigated whether fermentation with Pediococcus pentosaceus (P. p) increases the immune efficacy of CJ through in vitro, ex vivo and in vivo. Results showed that CJ and P. p fermentation (PCJ) produced nitric oxide, induced immune-related cytokine secretion, and up-regulated the MAPK and NF-κB signaling pathways in RAW 264.7 cells. Furthermore, PCJ markedly stimulated proliferation and Th1 and Th2 response by inducing the production of cytokines in splenocytes. Oral administration of PCJ significantly alleviated cyclophosphamide (CTX)-induced immunosuppression in mice, as evidenced by increased immune-related cytokine production and improved gut microbiota. These results suggest that PCJ could have a positive impact on the development of functional food with the ability on immunomodulation and intestinal microenvironment improvement.

BackgroundAbout a quarter of the world’s population with latent tuberculosis infection (LTBI) are the main source of active tuberculosis. Bacillus Calmette Guerin (BCG) cannot effectively control LTBI individuals from developing diseases. Latency-related antigens can induce T lymphocytes of LTBI individuals to produce higher IFN-γ levels than tuberculosis patients and normal subjects. Herein, we firstly compared the effects of M. tuberculosis (MTB) ag85ab and 7 latent DNA vaccines on clearing latent MTB and preventing its activation in the mouse LTBI model.MethodsA mouse LTBI model was established, and then immunized respectively with PBS, pVAX1 vector, Vaccae vaccine, ag85ab DNA and 7 kinds of latent DNAs (including rv1733c, rv2660c, rv1813c, rv2029c, rv2628, rv2659c and rv3407) for three times. The mice with LTBI were injected with hydroprednisone to activate the latent MTB. Then, the mice were sacrificed for the bacterial count, histopathological examination, and immunological evaluation.ResultsUsing chemotherapy made the MTB latent in the infected mice, and then using hormone treatment reactivated the latent MTB, indicating that the mouse LTBI model was successfully established. After the mouse LTBI model was immunized with the vaccines, the lung colony-forming units (CFUs) and lesion degree of mice in all vaccines group were significantly decreased than those in the PBS group and vector group (P

ObjectiveTo investigate how serum 25-hydroxyvitamin D (25[OH]D) affects height growth velocity and the risk of low bone mineral density (BMD) in children.DesignA population-based prospective cohort study.Patients and methodsA total of 10 450 participants with complete follow-up records from a cohort were included in the current study. Serum 25(OH)D concentrations were measured at baseline and 2-year follow-up, and the average of 2-time measurements was used for analysis. Low BMD was defined as calcaneus speed of sound Z-score ≤ −1. The associations of vitamin D with height growth velocity and the risks of incident low BMD were evaluated using adjusted β and risk ratio (RR).ResultsAfter multivariable adjustment, an inverse L-shaped association between serum 25(OH)D concentrations and height growth velocity was observed, leveling off up to 40–60 nmol/L. Overall, each 10 nmol/L higher serum 25(OH)D concentration was associated with a 0.15 cm/year higher height growth velocity (P < 0.001) and a 7% decreased risk of low BMD [RR (95%CI): 0.93 (0.87~0.98)]. Compared to those with vitamin D deficiency, participants who had sufficient vitamin D had a 22% lower risk for low BMD [RR(95%CI): 0.78 (0.62~0.98)]. However, no significant associations between vitamin D and the risk of low BMD were found in overweight and obese children.ConclusionThese findings highlight the importance of maintenance of sufficient 25(OH)D concentrations and healthy body weight during childhood in height growth and bone health promotion.

Visceral adipose tissue secretes cytokines to regulate the homeostasis of organs. Here, the authors show that epididymal white adipose tissue-secreted osteopontin induces lipophagocytic mobilization of macrophages and promotes bone matrix degradation via activating osteoclasts.

Abstract There is no consistent conclusion on which adiposity measure is best to predict cardiovascular risk factors in youth. The present study aims to assess the performance of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in predicting abnormal left ventricular structure in Chinese hypertensive youth. A total of 1180 youth aged 6–17 years with hypertension from the China Child and Adolescent Cardiovascular Health Study were included in this study. Logistic regression model, receiver operator characteristic (ROC) curve analysis and net reclassification improvement (NRI) method were used to assess performance of BMI, WC, and WHtR in predicting left ventricular hypertrophy (LVH) and left ventricular geometry (LVG). A 1-standard deviation increment in any of three indexes in predicting LVH and LVG were similar, e.g., with the odds ratios and 95% confidence intervals of 1.34 (1.16–1.55), 1.25 (1.08–1.45) and 1.40 (1.20–1.62), respectively. In addition, ROC analysis and NRI method confirmed the similar performance of three adiposity indexes in predicting LVH and LVG. In conclusion, BMI, WC and WHtR had similar performance in predicting abnormal left ventricular structure in Chinese hypertensive youth, but all three indexes had limited value in prediction. WHtR is a simple and convenient adiposity index for screening youth at high risk of target organ damage.

ObjectiveLittle is known about pre-pandemic cardiovascular health (CVH) status and its temporal variation in Chinese children. Thus, we aimed to evaluate the secular trends and associated factors of CVH in Chinese urban children from 2004 to 2019.MethodsWe identified 32,586 individuals in Beijing, aged 6 to 18 years, from three independent cross-sectional studies conducted in 2004, 2014, and 2019, respectively. CVH was assessed by 7 metrics according to modified American Heart Association criteria, including smoking, physical activity, diet, body mass index, total cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression was used to assess the associations between sociodemographic characteristics and the ideal CVH status.ResultsThe proportion of ideal CVH decreased from 27.7% (boys 26.6%, girls 28.9%) in 2004 to 4.2% (boys 3.8%, girls 4.8%) in 2014, and then increased to 16.2% (boys 13.5%, girls 18.9%) in 2019. Overall, ideal smoking was the most prevalent CVH component during 2004–2019 (2004, 97.5%; 2014, 92.9%; 2019, 98.0%), while ideal physical activity (2004, 27.6%; 2014, 14.4%; 2019, 28.0%) and dietary intake (2004, 26.0%; 2014, 10.7%; 2019, 23.5%) were the least prevalent components. Notably, the proportion of ideal body mass index (2004, 77.5%; 2019, 59.7%) and blood pressure (2004, 73.6%; 2019, 67.3%) continuously decreased from 2004 to 2019. Girls, parental normal weight status, free of family CVD history, and lower levels in fat mass were associated with higher odds of ideal CVH.ConclusionThe cardiovascular health in Chinese urban children deteriorated during 2004–2019. Distinct strategies are required to mitigate socioeconomic inequity in the intervention of CVH promotion.

ObjectiveTo evaluate the prevalence of hyperglycemia and dyslipidemia among different body composition and investigate the associations of body composition indicators, especially the muscle mass, with glucose and lipids metabolism in children and adolescents.MethodsThis nationwide cross-sectional study included 8,905 children and adolescents aged 6 to 18 years. All participants underwent dual-energy x-ray absorptiometry and their blood-concentrated glucose and lipids (including TC, TG, LDL-C and HDL-c) were measured. Mixed model, hierarchical analysis, and piecewise regression were used to study the effect of body composition indicators, especially the muscle mass, on glucose and lipids metabolism.ResultsThe greatest prevalence of high total cholesterol (TC, 6.9% and 6.9%) and high triglyceride (22.3% and 6.6%) was found in both boys and girls with high muscle mass and high fat mass, and girls with high muscle mass and high fat mass also had the highest prevalence of hyperglycemia (7.1%). After fat stratification, higher muscle mass was associated with lower odds of hyperglycemia (OR = 0.62; 95%CI: 0.46,0.84; P = 0.002) and muscle mass was inversely associated with TC (β = −0.07; 95%CI: -0.12,-0.03; P < 0.001) in boys with normal fat mass, but high muscle mass was not significantly associated with hyperglycemia and TC in high-fat-mass group (P = 0.368 and 0.372).ConclusionsThe body composition phenotype of high muscle and high fat mass have the highest prevalence of dysglycemia and dyslipidemia. Higher muscle mass was associated with a lower risk of hyperglycemia and TC levels in individuals only with normal fat mass.

ABSTRACT Latent tuberculosis infection (LTBI) is the primary source of tuberculosis (TB) but there is no suitable detection method to distinguish LTBI from active tuberculosis (ATB). In this study, five antigens of Mycobacterium tuberculosis belonging to LTBI and regions of difference (RDs) were selected to predict Th1 and cytotoxic T lymphocyte (CTL) epitopes. The immunodominant Th1 and CTL peptides were identified in mouse models, and their performance in distinguishing LTBI from ATB was determined in mice and humans. Ten Th1 and ten CTL immunodominant peptides were predicted and synthesized in vitro. The enzyme-linked immunosorbent spot assay results showed that the combination of five Th1 peptides (area under the curve [AUC] = 1, P

Abstract Peripheral nerve injury is a challenging orthopedic condition that can be treated by autograft transplantation, a gold standard treatment in the current clinical setting. Nevertheless, limited availability of autografts and potential morbidities in donors hampers its widespread application. Bioactive scaffold‐based tissue engineering is a promising strategy to promote nerve regeneration. Additionally, magnesium (Mg) ions enhance nerve regeneration; however, an effectively controlled delivery vehicle is necessary to optimize their in vivo therapeutic effects. Herein, a bisphosphonate‐based injectable hydrogel exhibiting sustained Mg2+ delivery for peripheral nerve regeneration is developed. It is observed that Mg2+ promoted neurite outgrowth in a concentration‐dependent manner by activating the PI3K/Akt signaling pathway and Sema5b. Moreover, implantation of polycaprolactone (PCL) conduits filled with Mg2+‐releasing hydrogel in 10 mm nerve defects in rats significantly enhanced axon regeneration and remyelination at 12 weeks post‐operation compared to the controls (blank conduits or conduits filled with Mg2+‐absent hydrogel). Functional recovery analysis reveals enhanced reinnervation in the animals treated with the Mg2+‐releasing hydrogel compared to that in the control groups. In summary, the Mg2+‐releasing hydrogel combined with the 3D‐engineered PCL conduit promotes peripheral nerve regeneration and functional recovery. Thus, a new strategy to facilitate the repair of challenging peripheral nerve injuries is proposed.

Abstract Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P

Introduction: We previously demonstrated that magnesium ions (Mg2+) was a novel therapeutic alternative for osteoarthritis (OA) through promoting the hypoxia inducible factor-1α (HIF-1α)-mediated cartilage matrix synthesis. However, oxidative stress can inhibit the expression of HIF-1α, amplify the inflammation that potentially impairs the therapeutic efficacy of Mg2+ in OA. Vitamin (VC), a potent antioxidant, may enhance the efficacy of Mg2+ in OA treatment. This study aims to investigate the efficacy of combination of Mg2+ and VC on alleviating joint destruction and pain in OA. Material and methods: Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline, MgCl2 (0.5 mol/L), VC (3 mg/ml) or MgCl2 (0.5 mol/L) plus VC (3 mg/ml) at week 2 post-operation, twice weekly, for 2 weeks. Joint pain and pathological changes were assessed by gait analysis, histology, western blotting and micro-CT. Results: Mg2+ and VC showed additive effects to significantly alleviate the joint destruction and pain. The efficacy of this combined therapy could sustain for 3 months after the last injection. We demonstrated that VC enhanced the promotive effect of Mg2+ on HIF-1α expression in cartilage. Additionally, combination of Mg2+ and VC markedly promoted the M2 polarization of macrophages in synovium. Furthermore, combination of Mg2+ and VC inhibited osteophyte formation and expressions of pain-related neuropeptides. Conclusions: Intra-articular administration of Mg2+ and VC additively alleviates joint destruction and pain in OA. Our current formulation may be a cost-effective alternative treatment for OA.

In this study, the effects of Curtobacterium proimmune K3 lysates, isolated from Panax ginseng beverages, on splenocytes and cyclophosphamide (CTX)-induced immunosuppressed mice were investigated. Treatment with C. proimmune K3 lysates stimulated splenocyte proliferation and increased cytokine secretion in vitro and splenocytes ex vivo. Treatment with C. proimmune K3 lysates alleviated CTX-induced immunosuppression by modulating innate immunity in vivo, by recovering immune organ index and natural killer cell cytotoxicity, as well as by stimulating the adaptive immune system, via restoration of splenic lymphocyte proliferation, delayed-type hypersensitivity response, and IgG and IgA content. Moreover, C. proimmune K3 lysates treatment remarkably enhanced cytokine production in the spleen and thymus, compared with CTX-immunosuppressed mice. Our results suggest C. proimmune K3 lysates hold potential as a novel immunomodulatory agent for use in therapeutic purposes or as an ingredient in functional foods.

ABSTRACT Importance Extensive population‐based studies have explored the prevalence of primary hypertension (HTN) in children and adolescents. However, there is little published data on the characteristics of different types of pediatric HTN and the causes of secondary HTN. Objective To investigate the characteristics of different types of pediatric HTN and the causes of secondary HTN in a hospital setting. Methods The study cohort comprised pediatric inpatients (

ABSTRACT Importance Several methods have been established in recent decades that allow use of spot urine to estimate dietary sodium intake. However, their accuracies have been controversial in children. Objective To validate the performance of three commonly used methods—the Kawasaki, Tanaka, and International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) methods. Additionally, this study explored the accuracies of the Tanaka and INTERSALT methods by using spot urine samples taken at four separate times. Method Forty‐one adolescents aged 14 to 16 years completed two non‐consecutive 24‐hour urine collections and their mean values were used as reference data. The second‐morning urine was used for assessment with the Kawasaki method; a casual spot urine and spot urine samples taken at four separate times (morning, afternoon, evening, and overnight) were used for assessment with the Tanaka and INTERSALT methods. Results The mean differences were 1801 mg, 542 mg, 47 mg, and −31 mg for the Kawasaki, Tanaka, INTERSALT1 (with potassium), and INTERSALT2 (without potassium) methods with their required spot urine, respectively. The proportions of relative difference levels within ± 10% were 4.9% for the Kawasaki method, 19.5% for the Tanaka method, 36.6% for the INTERSALT1 method, and 36.6% for the INTERSALT2 method. Interpretation The INTERSALT method seemed to provide minimally biased estimations of mean population sodium intake with casual spot urine. However, there is a need to be cautious regarding inconsistencies in estimation among different levels of sodium intake. The methods assessed in this study were unable to accurately estimate sodium intake at the individual level.

ABSTRACT Importance Childhood and adolescence are critical periods for lifelong bone mineral accrual, but few studies have determined the impact of childhood adiposity on adult bone density. Objective To determine the long‐term impact of childhood adiposity on adult areal bone mineral density (aBMD) and the effect of adult adiposity on this relationship. Methods We conducted a longitudinal study of 1156 adults (56.3% men), for whom skinfold thickness (SFT) had been measured during childhood (6–18 years) and fat mass percentage (FMP) and aBMD were measured during adulthood (29–43 years). Adult aBMD in the lumbar spine (LS), femoral neck (FN), arms, and legs was measured using dual‐energy X‐ray absorptiometry. The direct effect of childhood SFT and its indirect effect through adult FMP on adult aBMD were estimated using general linear regression and a causal steps approach. Results Significant positive associations between childhood SFT and adult aBMD were found in the LS in men (β = 0.089, P = 0.044) and in all the skeletal sites in women. With respect to the adult fat–bone relationship, high adult FMP was associated with low aBMD in most of the sites in men, but with high FN aBMD in women (β = 0.144, P = 0.002). Moreover, suppressive effects of adult FMP on the associations between childhood SFT and adult aBMD in the LS (−34.8%) and legs (−67.1%) of men, and a positive effect on the FN aBMD in women (17.0%) were identified. Interpretation Childhood adiposity appears to have a positive long‐term effect on adult aBMD, which may be reduced by adiposity in adult men but reinforced by adiposity in adult women.

ABSTRACT Importance The impact of long‐term burden of excessive body weight, beginning in childhood, on inflammatory status in adulthood has been poorly described. Objective To characterize the longitudinal body mass index (BMI) trajectory from childhood and examine its relationship with inflammatory status in adulthood. Methods We included 1285 adults who had 4–15 repeat measurements of BMI from childhood to adulthood. The area under the curve (AUC) of growth curves was calculated to characterize long‐term burden (total AUC) and trends (incremental AUC) of BMI. Results After adjusting for covariates, higher values of BMI in terms of childhood and adulthood, as well as total and incremental AUC, were strongly associated with elevated levels of adult C‐reactive protein (CRP) in the four race‐sex groups. There were significant differences in linear and nonlinear curve parameters between the normal and high CRP groups for all race‐sex groups (P < 0.01). Compared with participants who had consistently low BMI in both childhood and adulthood, participants with high BMI in adulthood had higher CRP levels (P < 0.001), irrespective of their childhood BMI status; participants with high BMI in childhood but low BMI in adulthood had similar adult CRP levels. Interpretation The impact of excessive body weight on inflammation is cumulative and exacerbated over time. The influence of childhood overweight/obesity on inflammatory status in adulthood can be alleviated by reducing adiposity in adulthood.

This study was aimed at screening differentially expressed genes (DEGs) and exploring the potential immune mechanism induced by the Bacillus Calmette-Guerin (BCG) vaccine in a humanized mouse model. Candidate DEGs between mice vaccinated with BCG or injected with PBS were identified through transcriptomics, and their biological functions, signaling pathways, and protein interaction networks were analyzed through bioinformatics. A total of 1035 DEGs were identified by transcriptomics: 398 up-regulated and 637 down-regulated. GO analysis indicated that these DEGs were significantly enriched in cell adhesion, oxygen transport, receptor complex, carbohydrate binding, serine-type endopeptidase activity, and peroxidase activity terms. KEGG analysis indicated that these DEGs were involved in the Rap1 signaling pathway, axon guidance, PI3K-Akt signaling pathway, natural killer cell mediated cytotoxicity, and cytokine-cytokine receptor interaction. Protein interaction network analysis demonstrated that the Myc, Vegfa, and Itgb3 proteins had the highest aggregation degree, aggregation coefficient, and connectivity. The BCG vaccine induced 1035 DEGs in humanized mice. Among them, the differentially expressed down-regulated genes myc and itgb3 involved in the PI3K-Akt signaling pathway may play essential roles in the immune mechanism of the BCG vaccine.

Abstract Objective Neuroblastoma (NBL) is an extra‐cranial solid tumor in children. This study was attempted to investigate the regulatory mechanism of long noncoding RNA LINC01410 (LINC01410) on NBL. Methods The expression of LINC01410, miR‐506‐3p, and WEE1 in NBL was evaluated by quantitative real time polymerase chain reaction. The proliferation and colony formation ability of NBL cells were analyzed by MTT and colony formation assay. Flow cytometry assay was executed to measure the apoptosis and cell cycle. Dual‐luciferase reporter assay was used to detect the targeted relationships among LINC01410, miR‐506‐3p, and WEE1. Additionally, the role of LINC01410 on NBL in vivo was evaluated according to a tumor xenograft model. Results The expression of LINC01410 and WEE1 was enhanced and miR‐506‐3p was inhibited in NBL. LINC01410 knockdown attenuated the cell proliferation, colony formation ability, and inhibited tumor growth. Moreover, LINC01410 silencing facilitated the apoptosis and arrested the cell cycle. LINC01410 interacted with miR‐506‐3p to elevate the WEE1 expression in NBL. Additionally, miR‐506‐3p inhibition or WEE1 overexpression weakened the reduction effects of sh‐LINC01410 on cell proliferation, colony formation ability, apoptosis, and cell cycle. Conclusions Knockdown of LINC01410 inhibited the development of NBL by miR‐506‐3p/WEE1 axis in vitro, which could serve as a potential therapeutic target for NBL therapy.

Background and ObjectivesVitamin D has been indicated to play an important role in the optimal function of the cardiovascular system. However, with limited evidence, it remains unclear whether vitamin D status transition during childhood would affect cardiometabolic risk factors. Thus, we aimed to identify the associations of the longitudinal trajectory of vitamin D status with cardiometabolic risk factors in children.MethodsA total of 10,482 participants with complete follow-up records from a large population-based prospective cohort study were included in this analysis. The 25-hydroxyvitamin D [25(OH)D] concentrations, blood pressure, blood lipids, and fasting blood glucose were determined. Vitamin D deficiency was defined as serum 25(OH)D concentrations below 30 nmol/L according to the Institute of Medicine recommendations. Based on the vitamin D status at baseline and follow-up, we identified four possible trajectories: (1) persistent non-deficiency (reference); (2) baseline non-deficiency to follow-up deficiency; (3) baseline deficiency to follow-up non-deficiency; (4) persistent deficiency. The relationships between cardiometabolic risk factors and vitamin D trajectories were evaluated using adjusted risk ratios (RRs).ResultsOverall, 35.1 and 24.2% of participants had vitamin D deficiency at the baseline and follow-up, respectively, and 15.1% were under the condition of persistent vitamin D deficiency. Compared to children with persistent non-deficiency, those who shifted from non-deficiency at baseline to deficiency at follow-up had a 2.09-fold (95% CI: 1.36, 3.23) increased risk of high triglyceride (TG). Besides, children with altered vitamin D status from deficiency to non-deficiency during follow-up were still at a significantly higher risk of high total cholesterol (TC) than the reference group [RR (95% CI): 1.39 (1.04, 1.86)]. Finally, children with persistent vitamin D deficiency were at the highest risks of high TC [RR (95% CI): 1.61 (1.18, 2.19), Ptrend < 0.001], high low-density lipoprotein cholesterol (LDL-C) [RR (95% CI): 1.53 (1.04, 2.27), Ptrend = 0.046], and high TG [RR (95% CI): 1.96 (1.34, 2.87), Ptrend = 0.003].ConclusionOur results suggest that persistent vitamin D deficiency might increase the risk of dyslipidemia in children, and vitamin D deficiency could have has short- and long-term effects on TG and TC, respectively.

Abstract The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene‐related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type‐H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES‐enhanced osteoporotic fracture healing. This proof‐of‐concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.

Tuberculosis (TB) is a serious public health problem worldwide. The combination of various anti-TB drugs is mainly used to treat TB in clinical practice. Despite the availability of effective antibiotics, effective treatment regimens still require long-term use of multiple drugs, leading to toxicity, low patient compliance, and the development of drug resistance. It has been confirmed that immune recognition, immune response, and immune regulation of Mycobacterium tuberculosis (Mtb) determine the occurrence, development, and outcome of diseases after Mtb infection. The research and development of TB-specific immunotherapy agents can effectively regulate the anti-TB immune response and provide a new approach toward the combined treatment of TB, thereby preventing and intervening in populations at high risk of TB infection. These immunotherapy agents will promote satisfactory progress in anti-TB treatment, achieving the goal of “ultra-short course chemotherapy.” This review highlights the research progress in immunotherapy of TB, including immunoreactive substances, tuberculosis therapeutic vaccines, chemical agents, and cellular therapy.

BackgroundTuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines.MethodsIn this study, eleven candidate proteins of Mycobacterium tuberculosis were selected to predict peptides with high-affinity binding capacity for the HLA-DRB1*01:01 molecule. The immunodominant peptides were identified with the enzyme-linked immunospot assay (ELISPOT) and linked in silico to result in a novel polypeptide vaccine in Escherichia coli cells. The vaccine’s protective efficacy was evaluated in humanized and wild-type C57BL/6 mice. The potential immune protective mechanisms were explored with Enzyme-linked Immunosorbent Assay (ELISA), flow cytometry, and ELISPOT.ResultsSix immunodominant peptides screened from 50 predicted peptides were used to construct a new polypeptide vaccine named MP3RT. After challenge with M. tuberculosis, the colony-forming units (CFUs), lung lesion area, and the number of inflammatory cells in humanized mice rather than wild-type mice vaccinated with MP3RT were significantly lower than these in mice immunized with PBS. The humanized mice vaccinated with MP3RT revealed significant increases in IFN-γ cytokine production, IFN-γ+ T lymphocytes, CD3+IFN-γ+ T lymphocytes, and the MP3RT-specific IgG antibody.ConclusionsTaken together, MP3RT is a promising peptides-based TB vaccine characterized by inducing high levels of IFN-γ and CD3+IFN-γ+ T lymphocytes in humanized mice. These new findings will lay a foundation for the development of peptides-based vaccines against TB.