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The diagnosis and treatment of non-small cell lung cancer in clinical settings face serious challenges, particularly due to the lack of integration between the two processes, which limit real-time adjustments in treatment plans based on the patient’s condition and drive-up treatment costs. Here, we present a multifunctional pH-sensitive core-shell nanoparticle containing quercetin (QCT), termed AHA@MnP/QCT NPs, designed for the simultaneous diagnosis and treatment of non-small cell lung cancer. Mechanistic studies indicated that QCT and Mn 2+ exhibited excellent peroxidase-like (POD-like) activity, catalysing the conversion of endogenous hydrogen peroxide into highly toxic hydroxyl radicals through a Fenton-like reaction, depleting glutathione (GSH), promoting reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum, and inducing ferroptosis. Additionally, Mn 2+ could activate the cGAS-STING signalling pathway and promote the maturation of dendritic cells and infiltration of activated T cells, thus inducing tumor immunogenic cell death (ICD). Furthermore, it exhibited effective T2-weighted MRI enhancement for tumor imaging, making them valuable for clinical diagnosis. In vitro and in vivo experiments demonstrated that AHA@MnP/QCT NPs enabled non-invasive imaging and tumor treatment, which presented a one-stone-for-two-birds strategy for combining tumor diagnosis and treatment, with broad potential for clinical application in non-small cell lung cancer therapy. Graphical Abstract

The insufficient infiltration and functional inhibition of CD8+ T cells due to tumor microenvironment (TME) are considered enormous obstacles to anti‐tumor immunotherapy. Herein, a pH‐responsive core‐shell manganese phosphate nanomodulator co‐loading siPD‐L1 and Mn2+ into nanoparticles coated with hyaluronic acid was prepared, which was aimed at the bidirectional reprogramming the tumor microenvironment: (1) “Brakes off,” restoring CD8+ T cells function by siPD‐L1 knockdowning PD‐L1 expression of tumor cells; (2) “Step on the accelerator,” promoting CD8+ T cells infiltration in tumors tissue based on the multidimensional immune effects of Mn2+ (immunogenic cell death induced the enhancing cGAS‐STING pathway, the proliferation and maturation of relative immune cells). Additionally, this strategy could induce macrophage polarization and inhibit the regulatory T cells in tumor site. This work provided a manganese phosphate nanomodulator to reprogram the immune TME for an enhanced comprehensive anti‐tumor effect of triple negative breast cancer, which offers a robust method for tumor immunotherapy in future clinical applications. To enhance the comprehensive treatment effect of triple‐negative breast cancer, a pH‐responsive core‐shell manganese phosphate nano‐regulator was prepared to reprogram the tumor microenvironment bi‐directionally. (1) “Brakes off”: Using siPD‐L1 to inhibit PD‐L1 expression to restore CD8+ T cell function. 2) “Step on the accelerator”: Based on Mn2+’s effect, promoting CD8+ T cell infiltration and maturation.

Joint dislocations significantly impact public health. However, a comprehensive study on the incidence, distribution, and risk factors for joint dislocations in China is lacking. We conducted the China National Joint Dislocation Study, which is a part of the China National Fracture Study conducted to obtain the national incidence and risk factors for traumatic fractures, and to investigate the incidence and risk factors for joint dislocations. For this national retrospective epidemiological study, 512,187 participants were recruited using stratified random sampling and probability-proportional-to-size method from January 19 to May 16, 2015. Participants who sustained joint dislocations of the trunk, arms, or legs (skull, sternum, and ribs being excluded) in 2014 were personally interviewed to obtain data on age, educational background, ethnic origin, occupation, geographic region, and urbanization degree. The joint-dislocation incidence was calculated based on age, sex, body site, and demographic factors. The risk factors for different groups were examined using multiple logistic regression. One hundred and nineteen participants sustained 121 joint dislocations in 2014. The population-weighted incidence rate of joint dislocations of the trunk, arms, or legs was 0.22 (95% confidence interval [CI]: 0.16, 0.27) per 1000 population in 2014 (men, 0.27 [0.20, 0.34]; women, 0.16 [0.10, 0.23]). For all ages, previous dislocation history (male: OR 42.33, 95% confidence interval [CI]: 12.03-148.90; female: OR 54.43, 95% CI: 17.37-170.50) and alcohol consumption (male: OR 3.50, 95% CI: 1.49-8.22; female: OR 2.65, 95% CI: 1.08-6.50) were risk factors for joint dislocation. Sleeping less than 7 h/day was a risk factor for men. Compared with children, women aged ≥15 years (female 15-64 years: OR 0.16, 95% CI: 0.04-0.61; female ≥65 years: OR 0.06, 95% CI: 0.01-0.41) were less likely to sustain joint dislocations. Women with more than three children were at higher dislocation risk than women without children (OR 6.92, 95% CI: 1.18-40.78). The up-to-date data on joint dislocation incidence, distribution, and risk factors can be used as a reference for national healthcare, prevention, and management in China. Specific strategies for decreasing alcohol consumption and encouraging adequate sleeping hours should be developed to prevent or reduce dislocation incidents. Chinese Clinical Trial Registry, ChiCTR-EPR-15005878.

This paper explores the operation mechanism of the superjunction structure in RC-IGBTs based on carrier distribution and analyzes the advantages and challenges associated with its application in RC-IGBTs for the first time. A Partial Schottky Collector Superjunction Reverse Conduction IGBT (PSC-SJ-RC-IGBT) is proposed to address these issues. The new structure eliminates the snapback phenomenon. Furthermore, by leveraging the unipolar conduction of the Schottky diode and its fast turn-off characteristics, the proposed device significantly reduces the turn-off power consumption and reverse recovery charge. With medium pillar doping concentration, the turn-off loss of the PSC-SJ-RC-IGBT decreases by 54.1% compared to conventional superjunction RC-IGBT, while the reverse recovery charge is reduced by 52.6%.

AbstractBackground:Joint dislocations significantly impact public health. However, a comprehensive study on the incidence, distribution, and risk factors for joint dislocations in China is lacking. We conducted the China National Joint Dislocation Study, which is a part of the China National Fracture Study conducted to obtain the national incidence and risk factors for traumatic fractures, and to investigate the incidence and risk factors for joint dislocations.Methods:For this national retrospective epidemiological study, 512,187 participants were recruited using stratified random sampling and probability-proportional-to-size method from January 19 to May 16, 2015. Participants who sustained joint dislocations of the trunk, arms, or legs (skull, sternum, and ribs being excluded) in 2014 were personally interviewed to obtain data on age, educational background, ethnic origin, occupation, geographic region, and urbanization degree. The joint-dislocation incidence was calculated based on age, sex, body site, and demographic factors. The risk factors for different groups were examined using multiple logistic regression.Results:One hundred and nineteen participants sustained 121 joint dislocations in 2014. The population-weighted incidence rate of joint dislocations of the trunk, arms, or legs was 0.22 (95% confidence interval [CI]: 0.16, 0.27) per 1000 population in 2014 (men, 0.27 [0.20, 0.34]; women, 0.16 [0.10, 0.23]). For all ages, previous dislocation history (male: OR 42.33, 95% confidence interval [CI]: 12.03-148.90; female: OR 54.43, 95% CI: 17.37-170.50) and alcohol consumption (male: OR 3.50, 95% CI: 1.49-8.22; female: OR 2.65, 95% CI: 1.08-6.50) were risk factors for joint dislocation. Sleeping less than 7 h/day was a risk factor for men. Compared with children, women aged ≥15 years (female 15-64 years: OR 0.16, 95% CI: 0.04-0.61; female ≥65 years: OR 0.06, 95% CI: 0.01-0.41) were less likely to sustain joint dislocations. Women with more than three children were at higher dislocation risk than women without children (OR 6.92, 95% CI: 1.18-40.78).Conclusions:The up-to-date data on joint dislocation incidence, distribution, and risk factors can be used as a reference for national healthcare, prevention, and management in China. Specific strategies for decreasing alcohol consumption and encouraging adequate sleeping hours should be developed to prevent or reduce dislocation incidents.Trial Registration:Chinese Clinical Trial Registry, ChiCTR-EPR-15005878.

To assess the economic impact of maternal death on rural Chinese households during the year after maternal death. A prospective cohort study matched 183 households who had suffered a maternal death to 346 households that experienced childbirth without maternal death in rural areas of three provinces in China. Surveys were conducted at baseline (1-3 months after maternal death or childbirth) and one year after baseline using the quantitative questionnaire. We investigated household income, expenditure, accumulated debts, and self-reported household economic status. Difference-in-Difference (DID), linear regression, and logistic regression analyses were used to compare the economic status between households with and without maternal death. The households with maternal death had a higher risk of self-reported \"household economy became worse\" during the follow-up period (adjusted OR = 6.04, p<0.001). During the follow-up period, at the household level, DID estimator of income and expenditure showed that households with maternal death had a significant relative reduction of US$ 869 and US$ 650, compared to those households that experienced childbirth with no adverse event (p<0.001). Converted to proportions of change, an average of 32.0% reduction of annual income and 24.9% reduction of annual expenditure were observed in households with a maternal death. The mean increase of accumulated debts in households with a maternal death was 3.2 times as high as that in households without maternal death (p = 0.024). Expenditure pattern of households with maternal death changed, with lower consumption on food (p = 0.037), clothes and commodity (p = 0.003), traffic and communication (p = 0.022) and higher consumption on cigarette or alcohol (p = 0.014). Compared with childbirth, maternal death had adverse impact on household economy, including higher risk of self-reported \"household economy became worse\", decreased income and expenditure, increased debts and changed expenditure pattern.

Background Despite the positive outcomes of the use of noninvasive positive pressure ventilation (NPPV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), NPPV fails in approximately 15% of patients with AECOPD, possibly because the inspiratory pressure delivered by conventional low-intensity NPPV is insufficient to improve ventilatory status for these patients. High-intensity NPPV, a novel form that delivers high inspiratory pressure, is believed to more efficiently augment alveolar ventilation than low-intensity NPPV, and it has been shown to improve ventilatory status more than low-intensity NPPV in stable AECOPD patients. Whether the application of high-intensity NPPV has therapeutic advantages over low-intensity NPPV in patients with AECOPD remains to be determined. The high-intensity versus low-intensity NPPV in patients with AECOPD (HAPPEN) study will examine whether high-intensity NPPV is more effective for correcting hypercapnia than low-intensity NPPV, hence reducing the need for intubation and improving survival. Methods/design The HAPPEN study is a multicenter, two-arm, single-blind, prospective, randomized controlled trial. In total, 600 AECOPD patients with low to moderate hypercapnic respiratory failure will be included and randomized to receive high-intensity or low-intensity NPPV, with randomization stratified by study center. The primary endpoint is NPPV failure rate, defined as the need for endotracheal intubation and invasive ventilation. Secondary endpoints include the decrement of arterial carbon dioxide tension from baseline to 2 h after randomization, in-hospital and 28-day mortality, and 90-day survival. Patients will be followed up for 90 days after randomization. Discussion The HAPPEN study will be the first randomized controlled study to investigate whether high-intensity NPPV better corrects hypercapnia and reduces the need for intubation and mortality in AECOPD patients than low-intensity NPPV. The results will help critical care physicians decide the intensity of NPPV delivery to patients with AECOPD. Trial registration ClinicalTrials.gov, NCT02985918 . Registered on 7 December 2016.

To identify the immediate economic impact of maternal death on rural Chinese households. Results are reported from a study that matched 195 households who had suffered a maternal death to 384 households that experienced a childbirth without maternal death in rural areas of three provinces in China, using quantitative questionnaire to compare differences of direct and indirect costs between two groups. The direct costs of a maternal death were significantly higher than the costs of a childbirth without a maternal death (US$4,119 vs. $370, p<0.001). More than 40% of the direct costs were attributed to funeral expenses. Hospitalization and emergency care expenses were the largest proportion of non-funeral direct costs and were higher in households with maternal death than the comparison group (US$2,248 vs. $305, p<0.001). To cover most of the high direct costs, 44.1% of affected households utilized compensation from hospitals, and the rest affected households (55.9%) utilized borrowing money or taking loans as major source of money to offset direct costs. The median economic burden of the direct (and non-reimbursed) costs of a maternal death was quite high--37.0% of the household's annual income, which was approximately 4 times as high as the threshold for an expense being considered catastrophic. The immediate direct costs of maternal deaths are extremely catastrophic for the rural Chinese households in three provinces studied.