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Background With accumulating evidence suggesting that CVD has its origins in childhood obesity. The purpose of this study was to determine the effect of a real-world school-based high-intensity interval training intervention on body composition, cardiorespiratory fitness and cardiometabolic markers in obese boys aged 10 to 13 years. Methods Forty-five adolescent boys with obesity (age = 11.2 ± 0.7 years, BMI = 24.2 ± 1.0 kg/m 2 ), were randomized to high-intensity interval training group (HIIT, n  = 15), moderate-intensity continuous training group (MICT, n  = 15), or a control group (CON, n  = 15). The intervention groups performed three weekly exercise sessions over 12 weeks. HIIT group performed two sets of eight bouts of 15 s run at high-intensity [90 ~ 100% maximal aerobic speed (MAS)] separated by eight bouts of 15 s recovery run at low-intensity (50% MAS), MICT group performed 30 min run at moderate intensity (60 ~ 70% MAS) and CON group were instructed to continue their normal behaviors. All participants had indices of body composition, cardiorespiratory fitness (CRF) and cardiometabolic markers measured at baseline and post-intervention. Statistical differences between and within groups were determined by use of two-way analysis of variance (ANOVA) with repeated measures. Results Following the school-based training program, BMI and body fat mass decreased (BMI: − 1.8 kg/m 2 vs. – 1.2 kg/m 2 , P  < 0.01; FM: − 1.6 kg, P  < 0.05 vs. -3.7 kg, P  < 0.01) in HIIT and MICT group, but there was no significant difference between the two interventions; V ˙ O 2 peak both increased significantly in two intervention groups, and the increment of HIIT group was significantly greater than that of MICT (6.1 mL/kg/min vs. 3.8 mL/kg/min, P  < 0.01), Visceral adipose tissue was significant decrease in HIIT group (− 53 g vs. -17 g, P  < 0.01) whilst the MICT group experienced a significant decrease in body fat percentage (− 3.1 ± 1.0 kg, P  < 0.01), but there were no significant difference between the two interventions. Low-density lipoprotein cholesterol decreased only in HIIT group (− 17.2%, P  < 0.05). Significant decrease in the usual index of insulin resistance (HOMA-IR) occurred in HIIT and MICT groups (− 27.3 and − 28.6%, respectively; P  < 0.05). Conclusions Our results demonstrated that high-intensity interval training based on running can be used to improve the physical health of obese adolescents in school. Further investigations involving a larger cohort of participants, taken from different schools, is recommended. Trial registration title Effect of High Intensity Interval Training on Obese Children and Adolescents, time 16/12/2017, ID ChiCTR-IOR-17013992 , website http://www.chictr.org.cn

Virtual reality (VR) technology has shown significant potential in improving the social skills of children and adolescents with autism spectrum disorder (ASD). This study aimed to systematically review the evidence supporting the effectiveness of VR technology in improving the social skills of children and adolescents with ASD. The search for eligible studies encompassed 4 databases: PubMed, Web of Science, IEEE, and Scopus. Two (XY and JW) researchers independently assessed the extracted studies according to predefined criteria for inclusion and exclusion. These researchers also independently extracted information regarding gathered data on the sources, samples, measurement methods, primary results, and data related to the main results of the studies that met the inclusion criteria. The quality of the studies was further evaluated using the Physiotherapy Evidence Database scale. This review analyzed 14 studies on using VR technology interventions to improve social skills in children and adolescents with ASD. Our findings indicate that VR interventions have a positive effect on improving social skills in children and adolescents with ASD. Compared with individuals with low-functioning autism (LFA), those with high-functioning autism (HFA) benefited more from the intervention. The duration and frequency of the intervention may also influence its effectiveness. In addition, immersive VR is more suitable for training complex skills in individuals with HFA. At the same time, nonimmersive VR stands out in terms of lower cost and flexibility, making it more appropriate for basic skill interventions for people with LFA. Finally, while VR technology positively enhances social skills, some studies have reported potential adverse side effects. According to the quality assessment using the Physiotherapy Evidence Database scale, of the 14 studies, 6 (43%) were classified as high quality, 4 (29%) as moderate quality, and 4 (29%) as low quality. This systematic review found that VR technology interventions positively impact social skills in children and adolescents with ASD, with particularly significant effects on the enhancement of complex social skills in individuals with HFA. For children and adolescents with LFA, progress was mainly observed in basic skills. Immersive VR interventions are more suitable for the development of complex skills. At the same time, nonimmersive VR, due to its lower cost and greater flexibility, also holds potential for application in specific contexts. However, the use of VR technology may lead to side effects such as dizziness, eye fatigue, and sensory overload, particularly in immersive settings. These potential issues should be carefully addressed in intervention designs to ensure user comfort and safety. Future research should focus on optimizing individualized interventions and further exploring the long-term effects of VR interventions. International Platform of Registered Systematic Review and Meta-analysis Protocols INPLASY202420079U1; https://inplasy.com/inplasy-2024-2-0079/.

Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response via various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation.

Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation. For the effective delivery of CDDP, the CDDP-polyphenol nanocomplexes were prepared, and catalase and copper ions were incorporated to fortify structural integrity, enhance glutathione (GSH) responsiveness, and ameliorate tumor hypoxia. Additionally, BV2 microglial cells were engineered to overexpress programmed death-1 (PD-1), and the membrane is employed for nanocomplex coating, effectively blocking the CDDP-induced upregulation of programmed death ligand 1 (PD-L1). Furthermore, the angiopep-2 peptide was modified to efficiently cross the blood brain barrier and specifically target GBM cells. In vitro analyses confirmed potent cytotoxicity and characteristic induction of pyroptosis. In vivo assays corroborated the enhancement of tumor targeting, culminating in an obvious suppression of tumor proliferation. A notable activation of immune cells was observed within tumors and lymph nodes, indicative of a synergistic effect of chemotherapy and immunotherapy, underscoring its potential as a safe and efficacious therapeutic strategy against GBM.

Photodynamic therapy (PDT) is a promising strategy with significant clinical application potential for tumor treatment. However, the tumor hypoxia and limited efficacy against tumor metastasis present significant limitations in the clinical application of PDT. To alleviate tumor hypoxia for PDT against tumor growth and metastasis, we developed a self-oxygenated immunoliposome by encapsulating the catalase (CAT) within the liposome cavity and loading the photosensitizer chlorin e6 (Ce6) and immunoadjuvant MPLA in the lipid bilayer of the immunoliposome (CAT@LP-Ce6-A). Subsequently, we fused it with the cancer cell membrane (CCM) to create the hybrid immunoliposome (CAT@LP-CCM-Ce6-A). The in vitro and in vivo anti-cancer efficacy of CAT@LP-CCM-Ce6-A-based photodynamic immunotherapy (PDIT) was evaluated. CAT@LP-CCM-Ce6-A were characterized by size, zeta potential, transmission electron microscopy (TEM), Coomassie bright blue staining, UV spectrophotometer, and standard Goth's method. Cellular uptake, cell viability, reactive oxygen species ( O ) generation, calreticulin exposure, and ability to promote BMDCs maturation of CAT@LP-CCM-Ce6-A were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy, and in vivo safety of CAT@LP-CCM-Ce6-A were investigated in orthotopic triple-negative breast cancer (TNBC) lung metastasis mouse models. CAT@LP-CCM-Ce6-A was successfully developed via the thin film hydration and co-extrusion method. The loading capacity of Ce6 and CAT was 4.7 ± 0.9% and 8.5 ± 0.9% respectively. CAT@LP-CCM-Ce6-A exhibited improved cellular uptake efficiency and cytotoxicity under laser irradiation against TNBC. Furthermore, CAT@LP-CCM-Ce6-A possessed enhanced anti-enzymatic degradation ability and promotion of DC maturation. In TNBC-bearing mice, CAT@LP-CCM-Ce6-A-based PDIT demonstrated remarkable therapeutic effect and antitumor immunity while maintaining minimal systemic toxicity. CAT@LP-CCM-Ce6-A could be employed as an innovative approach for self-oxygenated photodynamic immunotherapy against cancer.

Chemotherapy is still one of the major approaches in triple-negative breast cancer (TNBC) treatment. The development of new formulations for classic chemotherapeutic drugs remains interests in studies. Camptothecin (CPT) is powerful antitumor agents in TNBC treatment though its clinic applications are limited by its low water solubility and systemic toxicity. To prepare a spatiotemporal controllable CPT nano-formulation, we construct a ROS-responsive self-assembly nanoparticle by combining hydrophobic CPT and hydrophilic 5-floxuridine (FUDR). A ROS-sensitive thioketal (TK) linker is used to prepare CPT-TK-FUDR (CTF). Next, we introduced IR780-based phototherapy to elicit massive ROS regeneration due to the endogenous ROS is not sufficient. IR780 is modified with hyaluronic acid (HA) to prepare HA-modified IR780 (HAIR) for its biocompatibility and tumor targeting ability improvement. CTF and HAIR self-assemble to form an attractive nano-bomb (HAIR/CTF NPs). HA accurately guides the NPs to tumor sites via HA-receptor recognition on tumor cells. After internalization, overexpressed intracellular HAase in tumor cells disassembles the NPs to free the contents. Due to the presence of IR780 molecules, the scheduled irradiation of 808 nm laser induces massive reactive oxygen species (ROS) generation, which further result in the cleavage of TK linker for free drugs release. Additionally, ROS-mediated photodynamic therapy (PDT) and near-infrared laser-mediated photothermal therapy (PTT) synergistically worked to eradicate tumor cells. Then immunogenic cell death (ICD) was evoked by CPT and phototherapy to amplify antitumor immunity, thereby achieving primary and abscopal tumor inhibition. In conclusion, the HAIR/CTF nano-bomb realized spatiotemporal controllable drug release, exciting tumor eradication and attractive anti-metastasis efficacy via combination chemo/photo/immunotherapy, offering a valuable reference for the re-development of classic drug in future clinical practice. Graphical Abstract

The most effective patient support interventions in low- and middle-income countries remain a research gap in World Health Organization consolidated guidelines on tuberculosis. We explored the impact of a partial drug cost-exemption policy (including cycloserine, moxifloxacin, linezolid, and clofazimine) implemented in Guangxi Zhuang Autonomous Region, China, on treatment outcomes among local multidrug-resistant tuberculosis (MDR-TB) patients. This case-control study enrolled 424 MDR-TB patients receiving anti-TB treatment between 2020 and 2022 in Guangxi Zhuang Autonomous Region. Data on demographics, treatment regimen, drug cost-exemption status, and adverse reactions were extracted from electronic medical records. Multivariable logistic regression analysis was used to identify factors associated with successful treatment outcomes. Among the 424 enrolled MDR-TB patients, 212 (50.0%) had successful treatment outcomes, including 79 cured (18.6%) and 133 treatment completed (31.4%). Unfavorable outcomes were observed in 212 patients (50.0%), comprising 190 lost to follow-up (44.8%), 19 deaths (4.5%), and 3 treatment failures (0.7%). Multivariable analysis revealed that female sex (aOR = 2.99, 95% CI: 1.55-5.78), absence of adverse drug reactions (aOR = 11.58, 95% CI: 3.81-35.18), and receiving drug cost-exemption (aOR = 37.47, 95% CI: 10.97-127.96) were associated with favorable treatment outcomes. Furthermore, receiving an increasing number of exempted drugs was progressively associated with higher treatment success. Compared to one drug exemption, the aOR for successful outcomes was 3.24 (95% CI: 2.16-4.87) for two-drug cost-exemption and 5.13 (95% CI: 2.73-9.65) for three-drug cost-exemption. This nested case-control study demonstrates that implementing drug cost-exemption support policy is associated with significantly improved MDR-TB treatment success rates in resource-limited, high-burden settings in China.

Background Clinical evidence of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced non‐small cell lung cancer (NSCLC) was limited. Recombinant human endostatin (rh‐endostatin), an antiangiogenic drug, and camrelizumab, an anti‐PD‐1 antibody, have been approved for the treatment of advanced NSCLC in China. This study aimed to investigate the efficacy and safety of rh‐endostatin plus camrelizumab and chemotherapy in the treatment of advanced NSCLC. Methods Eligible patients were enrolled and received camrelizumab (200 mg, day 1) every 3 weeks and continuous intravenous infusion of rh‐endostatin (70 mg/day, days 1–3) and cisplatin combined with pemetrexed (for adenocarcinoma) or paclitaxel (for NSCLC other than adenocarcinoma) every 3 weeks. Primary endpoint was progression‐free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. Results Overall, 27 patients were included, and 25 patients were eligible for efficacy evaluation. For these 25 patients, ORR was 48.15% (13/27) and DCR was 85.19% (23/27). With a median follow‐up of 10.37 months, the median PFS was 8.9 (95% CI: 4.23–13.57) months. Median OS was not reached. Overall, 96.3% of patients experienced at least one treatment‐related adverse event, and grade 3 TRAEs occurred in 9 (33.3%) patients. No unexpected AEs were observed. Conclusion Rh‐endostatin plus camrelizumab and chemotherapy showed favorable efficacy and safety profile in patients with advanced NSCLC, representing a promising treatment regimen for these patients. Rh‐endostatin combined with camrelizumab plus chemotherapy treating advanced NSCLC showed ORR of 48.15% and DCR of 85.19%, with a median PFS of 8.9 months. The safety profile was comparable with former studies, representing Rh‐endostatin combined with camrelizumab and chemotherapy as a promising treatment regimen in advanced‐stage NSCLC patients.

This study aims to compare the differences in medical insurance reimbursement for TB treatment in Guangxi and to analyze the effects of such variations, thereby contributing to the enhancement of TB care and control. A survey was conducted across 49 randomly selected TB-designated hospitals in Guangxi using structured questionnaires and patient records. Missing data were addressed via median imputation. Non-parametric test was used to analyse and compare the differences in treatment outcomes among hospitals of different levels and types, with a value less than 0.05 as the test criterion. Logistic regression analysis was performed to evaluate the independent effects of medical insurance reimbursement, hospital level, hospital type and service ability on TB treatment outcomes. The Urban Employee Basic Medical Insurance provided significantly higher reimbursement floors, ceilings, and rates compared to the Urban Resident Basic Medical Insurance (URBMI). Tertiary hospitals offered higher reimbursement floors for inpatient care but lower reimbursement rates compared to secondary hospitals. Despite policy reimbursement rates for TB treatment consistently exceeding 60%, the actual reimbursement rates often fell short of these benchmarks, especially in specialist hospitals and secondary care facilities. URBMI reimbursement ceiling for pulmonary TB of inpatients was positively associated with treatment success. Additionally, a lower URBMI reimbursement floor for pulmonary TB of inpatients was linked to higher disease mortality rates. Areas exhibited lower treatment success rates and higher case fatality rates shared common socioeconomic characteristics, including smaller populations, lower per capita output values, depressed production values, and lower disposable incomes among the rural population. This study underscores the importance of equitable medical insurance reimbursement policies, and targeted reforms, such as raising URBMI reimbursement ceilings and enforcing real-time monitoring of actual reimbursements, are critical to mitigate disparities in TB care.

The entrance and exit area of parking facilities has the characteristics of high concentration of urban traffic and prominent traffic intertwining phenomenon, which easily induces rapid congestion of mixed heterogeneous traffic at specific times and local locations and quickly spreads to the entire road section or even a larger area. In order to better understand the congestion distribution characteristics and propagation effects of access section of the parking entrance and exit from the mid and microperspective, a 5 m ∗ lane width pixel grid is used to divide the frontage road research. It also proposes a spatially robust autoregressive model and complex network tools suitable for analysis of local traffic flow to analyze it. The results show that as spatial scale increases, the congestion propagation decreases sharply and spatial adjacency within the fourth order can account for more than 90% of the propagation; the frontage road to the entrance and exit is the place where the congestion first happens, and the congestion gradually attenuates as it propagates to the inner lane and the upstream of the road segments; the lateral congestion propagation attenuates faster, so the area affected by congestion is mainly distributed in the outermost lane. This paper can provide theoretical guidance for alleviating traffic congestion in the entrance and exit areas of parking facilities and has theoretical and empirical significance.