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The novel concept of subjective cognitive decline (SCD) in Parkinson's disease (PD) refers to subjective cognitive impairment without concurrent objective cognitive deficits. This study aimed to determine the prevalence and affective correlates of SCD in de novo PD patients.A total of 139 de novo PD patients underwent comprehensive neuropsychological evaluation. PD patients with SCD (PD-SCD) did not meet the diagnostic criteria for mild cognitive impairment in PD (PD-MCI) based on the Movement Disorder Society Level II Criteria and were defined by a Domain-5 Score ≥1 on the Non-Motor Symptoms Questionnaire. Affective symptoms were measured using the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA).In de novo PD cohort, the prevalence of SCD was 28.1%. PD-SCD patients performed significantly better than PD-MCI patients on tests of five cognitive domains. The more commonly affected domains in PD-SCD patients were memory (28.2%) and attention/working memory (25.6%). Multivariable linear regression analysis revealed that PD-SCD was significantly associated with both HAMD (β = 4.518, 95% CI = 0.754-8.281, p = .019) and HAMA scores (β = 4.259, 95% CI = 1.054-7.464, p = .010). Furthermore, binary logistic regression analysis revealed that higher HAMD (OR = 1.128, 95% CI = 1.019-1.249, p = .020) and HAMA scores (OR = 1.176, 95% CI = 1.030-1.343, p = .017) increased the risk of PD-SCD.Our findings suggest that SCD is highly prevalent in de novo PD patients. The presence of PD-SCD is suggestive of an underlying affective disorder.

Long noncoding RNAs (lncRNAs) have been reported as critical modulators in many diseases including preeclampsia. Since the association between lncRNA BNIP3P1 and its cognate gene BNIP3 in preeclampsia has been revealed previously, this study aimed to further explore the function and mechanism of BNIP3P1 in preeclampsia. EdU and TUNEL assays revealed that BNIP3P1 or BNIP3 overexpression inhibited trophoblast cell proliferation and enhanced cell apoptosis in preeclampsia. As suggested by western blot analysis, the protein levels of apoptotic markers in the cells were affected by BNIP3P1 or BNIP3 overexpression. The binding between miR-128-3p and BNIP3P1 (or BNIP3) was explored by luciferase reporter assays. Mechanistically, BNIP3P1 bound to miR-128-3p to upregulate BNIP3 expression by acting as a competing endogenous RNA (ceRNA). Importantly, BNIP3P1 was found to inactivate the mTOR signaling pathway. In conclusion, BNIP3P1 inhibited trophoblast cell proliferation and enhanced cell apoptosis in preeclampsia by targeting the miR-128-3p/BNIP3/mTOR signaling pathway.

We sought to provide clinical evidence of the potential influence of ovariectomy (OVX) on intervertebral disk degeneration.We retrospectively reviewed patients with a history of OVX who visited our hospital for lower back pain. In addition, 60 age-matched patients without OVX were randomly selected as control subjects. Next, the following demographic data were recorded and compared among groups: age, body mass index, duration of OVX, history of smoking, alcohol use, hypertension, diabetes, cardiocerebrovascular disease, hyperlipemia, osteoporosis, and degenerative spondylolisthesis. Next, the severity of lumbar disk degeneration, evaluated by the modified Pfirrmann grading system, was compared between groups. Data analyses were performed with SPSS 20.0. software.A total of 15 OVX (unilateral, n = 10; bilateral, n = 5) patients were included with a mean age of 62.40 ± 10.64. The average durations of OVX were 21.33 ± 9.24 years. There existed no remarkable intergroup differences in the demographic data (P0.05). Overall, the average Pfirrmann grading scores from L1/2 to L5/S1 presented as L1/2L2/3L3/4 ≤ L5/S1 ≤ L4/5, with no marked differences between groups (P0.05). Nevertheless, OVX groups displayed a relatively higher score at each level than non-OVX group. Moreover, the scores from L3/4 to L5/S1 were higher in the bilateral OVX group relative to the unilateral OVX group while they were equal at L1/2 and L2/3.Our findings demonstrated that OVX contributed to the progression of lumbar disk degeneration to some extent, but it appeared to be a long-term event.

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When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby promoting muscle growth and remodeling and repair of trauma. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. Therefore, we hypothesized that, when muscles are injured, myoblast-derived exosomes may regulate muscle repair and regeneration. Here, we investigated the underlying mechanism by applying C2C12-derived exosomes to injured mouse skeletal muscles. The expression levels of skeletal muscle regeneration factors paired box 7 and lipid-promoting factor peroxisome proliferator-activated receptor γ were upregulated, whereas the expression levels of fibrosis factors collagen-1 and α-smooth muscle actin decreased. The expression of proliferating cell nuclear antigen was elevated after applying C2C12-derived exosomes to SCs. Application of C2C12-derived exosomes to fibro-adipogenic progenitors resulted in an increase in peroxisome proliferator-activated receptor γ expression and adipogenesis capacity, whereas α-smooth muscle actin expression and fibrosis capacity decreased. Analysis of the transcriptome and proteome of SCs after treatment with exosomes showed the involvement of multiple biological processes, including proliferation and differentiation of SCs, muscle regeneration, skeletal muscle atrophy, and the inflammatory response after muscle injury. Hence, our data suggest that C2C12-derived exosomes can promote the regeneration of skeletal muscle fibers, accelerate the production of fat from damaged muscles, inhibit the fibrosis of damaged muscles, and accelerate injury repair, which is related to exosome-mediated regulation of the proliferation of SCs, differentiation of fibro-adipogenic progenitors, and modulation of SC mRNA expression and protein formation and decomposition.

To study the alterations of sleep quality and circadian rhythm genes expressions upon elderly thyroid nodule patients, the risk factors associated with thyroid malignancies, and the potential relationship involved. The elderly people enrolled in our study were divided into three groups according to the thyroid histopathology: malignant nodule group, benign nodule group, and normal group, and the clinical data and sleep quality were collected. Among the patients of surgery, 56 fresh thyroid tissues were collected for real-time PCR, immunohistochemistry and western blotting analysis of CLOCK, BMAL1, CRYs and PERs. Poor sleep quality, sleep latency and daytime dysfunction were the independent risk factors of malignant nodule after adjusted by other impacts. The expression levels of CLOCK, BMAL1 and PER2 in thyroid malignant group were significantly higher than benign and normal groups, while CRY2 was decreased, p

HIV incidence in sub-Saharan Africa declined substantially between 2000 and 2015. In this analysis, we consider the relative associations of nine structural and individual determinants with this decline. A linear mixed effects model of logged HIV incidence rates versus determinants was used. The data were from mathematical modelling as part of the 2019 Global Burden of Disease Study in 43 sub-Saharan African countries. We used forwards selection to determine a single final model of HIV incidence rate. The association of economic variables and HIV knowledge with incidence was found to be driven by education, while ART coverage had the largest impact on other determinants’ coefficients. In the final model, education years per capita contributed the most to explaining variation in HIV incidence rates; a 1-year increase in mean education years was associated with a 0.39 (− 0.56; − 0.2, t = − 4.48 p

Background and objective Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson’s disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). Methods A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. Results After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (− 1.43 scores [− 2.50, − 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (− 3.56 scores [− 5.77, − 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. Conclusion ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432

Summary Background Vision loss is an important public health issue in China, but a detailed understanding of national and regional trends in its prevalence and causes, which could inform health policy, has not been available. This study aimed to assess the prevalence, causes, and regional distribution of vision impairment and blindness in China in 1990 and 2019. Methods Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used to estimate the prevalence of moderate and severe vision impairment and blindness in China and compare with other Group of 20 (G20) countries. We used GBD methodology to systematically analyse all available demographic and epidemiological data at the provincial level in China. We compared the age-standardised prevalences across provinces, and the changes in proportion of vision loss attributable to various eye diseases in 1990 and 2019. We used two different counterfactual scenarios with respect to population structure and age-specific prevalence to assess the contribution of population growth and ageing to trends in vision loss. Findings In 2019, the age-standardised prevalence was 2·57% (uncertainty interval [UI] 2·28–2·86) for moderate vision impairment, 0·25% (0·22–0·29) for severe vision impairment, and 0·48% (0·43–0·54) for blindness in China, which were all below the global average, but the prevalence of moderate and severe vision impairment had increased more rapidly than in other G20 countries from 1990 to 2019. The prevalence of vision loss increased with age, and the main causes of vision loss varied across age groups. The leading causes of vision impairment in China were uncorrected refractive error, cataract, and macular degeneration in both 1990 and 2019 in the overall population. From 1990 to 2019, the number of people with moderate vision impairment increased by 133·67% (from 19·65 to 45·92 million), those with severe vision impairment increased by 147·14% (from 1·89 to 4·67 million), and those with blindness increased by 64·35% (from 5·29 to 8·69 million); in each case, 20·16% of the increase could be explained by population growth. The contributions to these changes by population ageing were 87·22% for moderate vision impairment, 116·06% for severe vision impairment, and 99·22% for blindness, and the contributions by age-specific prevalence were 26·29% for moderate vision impairment, 10·91% for severe vision impairment, and −55·04% for blindness. The prevalence and specific causes of vision loss differed across provinces. Interpretation Although a comprehensive national policy to prevent blindness is in place, public awareness of visual health needs improving, and reducing the prevalence of moderate and severe vision impairment should be prioritised in future work. Funding China National Key Research and Development Programme and Beijing Municipal Special Funds for Medical Research on Public Welfare Development and Reform.

This study was aimed to explore magnetic resonance imaging (MRI) based on deep learning belief network model in evaluating serum bile acid profile and adverse perinatal outcomes of intrahepatic cholestasis of pregnancy (ICP) patients. Fifty ICP pregnant women diagnosed in hospital were selected as the experimental group, 50 healthy pregnant women as the blank group, and 50 patients with cholelithiasis as the gallstone group. Deep learning belief network (DLBN) was built by stacking multiple restricted Boltzmann machines, which was compared with the recognition rate of convolutional neural network (CNN) and support vector machine (SVM), to determine the error rate of different recognition methods on the test set. It was found that the error rate of deep learning belief network (7.68%) was substantially lower than that of CNN (21.34%) and SVM (22.41%) ( P < 0.05 ). The levels of glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) in the experimental group were dramatically superior to those in the blank group ( P < 0.05 ). Both the experimental group and the blank group had notable clustering of serum bile acid profile, and the experimental group and the gallstone group could be better distinguished. In addition, the incidence of amniotic fluid contamination, asphyxia, and premature perinatal infants in the experimental group was dramatically superior to that in the blank group ( P < 0.05 ). The deep learning confidence model had a low error rate, which can effectively extract the features of liver MRI images. In summary, the serum characteristic bile acid profiles of ICP were glycoursodeoxycholic acid, glycochenodeoxycholic acid, and glycocholic acid, which had a positive effect on clinical diagnosis. The toxic effects of high concentrations of serum bile acids were the main cause of adverse perinatal outcomes and sudden death.

Injury-induced fibroblast-to-myofibroblast differentiation is a key event of renal fibrosis. Yes-associated protein (YAP), a transcriptional coactivator, plays an important role in fibroblast activation and Smad transcriptional activity to promote transforming growth factor-β (TGF-β)-induced differentiation from fibroblasts to myofibrolasts. Macrophage stimulating 1/2 (MST1/2), a negative regulator of YAP, also increases in fibroblasts by TGF-β stimulation. Here, we examined whether MST1/2, as a negative regulator, attenuated YAP and TGF-β/Smad signaling in fibroblasts to reduce fibrosis. MST1/2 and YAP expression levels increased in platelet-derived growth factor receptor-α (PDGFRα)

Although statins are the cornerstone of lipid management, hardly any of the existing studies on statin treatment of dyslipidemia in nephrotic syndrome (NS) addressed patient-centered outcomes of cardiovascular events.To evaluate whether statin treatment impacts the outcomes of cardiovascular events in patients with NS.A single-center, retrospective, nested case-control study analyzed data from the First Affiliated Hospital of Army Medical University.Patients diagnosed with NS from January 1, 1999, to November 30, 2014, were selected and followed up for 5 years.A total of 2706 patients with NS were enrolled in this study cohort. Among these, 115 patients diagnosed with cardiovascular disease (CVD) at the end of the observational period and 235 CVD-free controls enrolled by 1:2 matching with gender, age, and index time were included in the study. Propensity score matching was used to match (1:1) the baseline characteristics of the cases and controls. The chi-square test was performed based on whether the patient used a statin as an exposure factor, and binary logistic regression analysis of the association between cardiovascular events and statin therapy duration was conducted. Subgroup analyses for relevant variables were also performed. The chi-square test showed that statin therapy was significantly associated with a reduction in CVD risk in patients with NS (p = 0.002). Furthermore, the risk of cardiovascular events in patients with NS decreased as the length of statin treatment increased (OR = 0.82 [95% CI 0.73-0.89], p 0.001).For NS patients with dyslipidemia, statin therapy may be used to decrease CVD risk, and extended treatment was associated with more significant risk reduction.

Mortality statistics are fundamental to public health decision making. Mortality varies by time and location, and its measurement is affected by well known biases that have been exacerbated during the COVID-19 pandemic. This paper aims to estimate excess mortality from the COVID-19 pandemic in 191 countries and territories, and 252 subnational units for selected countries, from Jan 1, 2020, to Dec 31, 2021.All-cause mortality reports were collected for 74 countries and territories and 266 subnational locations (including 31 locations in low-income and middle-income countries) that had reported either weekly or monthly deaths from all causes during the pandemic in 2020 and 2021, and for up to 11 year previously. In addition, we obtained excess mortality data for 12 states in India. Excess mortality over time was calculated as observed mortality, after excluding data from periods affected by late registration and anomalies such as heat waves, minus expected mortality. Six models were used to estimate expected mortality; final estimates of expected mortality were based on an ensemble of these models. Ensemble weights were based on root mean squared errors derived from an out-of-sample predictive validity test. As mortality records are incomplete worldwide, we built a statistical model that predicted the excess mortality rate for locations and periods where all-cause mortality data were not available. We used least absolute shrinkage and selection operator (LASSO) regression as a variable selection mechanism and selected 15 covariates, including both covariates pertaining to the COVID-19 pandemic, such as seroprevalence, and to background population health metrics, such as the Healthcare Access and Quality Index, with direction of effects on excess mortality concordant with a meta-analysis by the US Centers for Disease Control and Prevention. With the selected best model, we ran a prediction process using 100 draws for each covariate and 100 draws of estimated coefficients and residuals, estimated from the regressions run at the draw level using draw-level input data on both excess mortality and covariates. Mean values and 95% uncertainty intervals were then generated at national, regional, and global levels. Out-of-sample predictive validity testing was done on the basis of our final model specification.Although reported COVID-19 deaths between Jan 1, 2020, and Dec 31, 2021, totalled 5·94 million worldwide, we estimate that 18·2 million (95% uncertainty interval 17·1-19·6) people died worldwide because of the COVID-19 pandemic (as measured by excess mortality) over that period. The global all-age rate of excess mortality due to the COVID-19 pandemic was 120·3 deaths (113·1-129·3) per 100 000 of the population, and excess mortality rate exceeded 300 deaths per 100 000 of the population in 21 countries. The number of excess deaths due to COVID-19 was largest in the regions of south Asia, north Africa and the Middle East, and eastern Europe. At the country level, the highest numbers of cumulative excess deaths due to COVID-19 were estimated in India (4·07 million [3·71-4·36]), the USA (1·13 million [1·08-1·18]), Russia (1·07 million [1·06-1·08]), Mexico (798 000 [741 000-867 000]), Brazil (792 000 [730 000-847 000]), Indonesia (736 000 [594 000-955 000]), and Pakistan (664 000 [498 000-847 000]). Among these countries, the excess mortality rate was highest in Russia (374·6 deaths [369·7-378·4] per 100 000) and Mexico (325·1 [301·6-353·3] per 100 000), and was similar in Brazil (186·9 [172·2-199·8] per 100 000) and the USA (179·3 [170·7-187·5] per 100 000).The full impact of the pandemic has been much greater than what is indicated by reported deaths due to COVID-19 alone. Strengthening death registration systems around the world, long understood to be crucial to global public health strategy, is necessary for improved monitoring of this pandemic and future pandemics. In addition, further research is warranted to help distinguish the proportion of excess mortality that was directly caused by SARS-CoV-2 infection and the changes in causes of death as an indirect consequence of the pandemic.BillMelinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

Summary Background Air pollution is an important public health concern in China, with high levels of exposure to both ambient and household air pollution. To inform action at provincial levels in China, we estimated the exposure to air pollution and its effect on deaths, disease burden, and loss of life expectancy across all provinces in China from 1990 to 2017. Methods In all 33 provinces, autonomous regions, municipalities, and special administrative regions in China, we estimated exposure to air pollution, including ambient particulate matter pollution (defined as the annual gridded concentration of PM2·5), household air pollution (defined as the percentage of households using solid cooking fuels and the corresponding exposure to PM2·5), and ozone pollution (defined as average gridded ozone concentrations). We used the methods of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 to estimate deaths and disability-adjusted life-years (DALYs) attributable to air pollution, and what the life expectancy would have been if air pollution levels had been less than the minimum level causing health loss. Findings The average annual population-weighted PM2·5 exposure in China was 52·7 μg/m3 (95% uncertainty interval [UI] 41·0–62·8) in 2017, which is 9% lower than in 1990 (57·8 μg/m3, 45·0–67·0). We estimated that 1·24 million (95% UI 1·08–1·40) deaths in China were attributable to air pollution in 2017, including 851 660 (712 002–990 271) from ambient PM2·5 pollution, 271 089 (209 882–346 561) from household air pollution from solid fuels, and 178 187 (67 650–286 229) from ambient ozone pollution. The age-standardised DALY rate attributable to air pollution was 1513·1 per 100 000 in China in 2017, and was higher in males (1839·8 per 100 000) than in females (1198·3 per 100 000). The age-standardised death rate attributable to air pollution decreased by 60·6% (55·7–63·7) for China overall between 1990 and 2017, driven by an 85·4% (83·2–87·3) decline in household air pollution and a 12·0% (1·4–22·1) decline in ambient PM2·5 pollution. 40·0% of DALYs for COPD were attributable to air pollution, as were 35·6% of DALYs for lower respiratory infections, 26·1% for diabetes, 25·8% for lung cancer, 19·5% for ischaemic heart disease, and 12·8% for stroke. We estimated that if the air pollution level in China was below the minimum causing health loss, the average life expectancy would have been 1·25 years greater. The DALY rate per 100 000 attributable to air pollution varied across provinces, ranging from 482·3 (371·1–604·1) in Hong Kong to 1725·6 (720·4–2653·1) in Xinjiang for ambient pollution, and from 18·7 (9·1–34·0) in Shanghai to 1804·5 (1339·5–2270·1) in Tibet for household pollution. Although the overall mortality attributable to air pollution decreased in China between 1990 and 2017, 12 provinces showed an increasing trend during the past 27 years. Interpretation Pollution from ambient PM2·5 and household burning of solid fuels decreased markedly in recent years in China, after extensive efforts to control emissions. However, PM2·5 concentrations still exceed the WHO Air Quality Guideline for the entire population of China, with 81% living in regions exceeding the WHO Interim Target 1, and air pollution remains an important risk factor. Sustainable development policies should be implemented and enforced to reduce the impact of air pollution on long-term economic development and population health. Funding Bill & Melinda Gates Foundation; and China National Key Research and Development Program.

Renal fibrosis leads to end-stage renal disease, but antifibrotic drugs are difficult to develop. Chronic kidney disease often results in muscle wasting, and thereby increases morbidity and mortality. In this work, adeno-associated virus (AAV)-mediated overexpressing miR-29a was hypothesized to counteract renal fibrosis and muscle wasting through muscle–kidney crosstalk in unilateral ureteral obstruction (UUO) mice. miR-29a level was downregulated in the kidney and skeletal muscle of UUO mice. The secretion of exosome-encapsulated miR-29a increased in cultured skeletal muscle satellite cells and HEK293 renal cells after stimulation with serum from UUO mice. This result was confirmed by qPCR and microRNA deep sequencing in the serum exosomes of mice with obstructed ureters. A recombinant AAV-miR-29a was generated to overexpress miR-29a and injected into the tibialis anterior muscle of the mice 2 weeks before UUO surgery. AAV-miR-29a abrogated the UUO-induced upregulation of YY1 and myostatin in skeletal muscles. Renal fibrosis was also partially improved in the UUO mice with intramuscular AAV-miR-29a transduction. AAV-miR-29a overexpression reversed the increase in transforming growth factor β, fibronectin, alpha-smooth muscle actin, and collagen 1A1 and 4A1 levels in the kidney of UUO mice. AAV-green fluorescent protein was applied to trace the AAV route in vivo, and fluorescence was significantly visible in the injected/uninjected muscles and in the kidneys. In conclusion, intramuscular AAV-miR-29a injection attenuates muscle wasting and ameliorates renal fibrosis by downregulating several fibrotic-related proteins in UUO mice.

Patients with degenerative lumbar spondylolisthesis (DLS) often suffer from years of low back pain (LBP) due to instability of the lumbar spine and the reduction of disc height. Since January 2016, we have performed oblique lateral interbody fusion (OLIF) on 154 patients. Among these, 56 patients who suffered from DLS underwent OLIF with stand-alone cages. Forty-two patients with a follow-up time that exceeded 1-year were enrolled for this study. The forty-two patients were followed up for at least one year. Operation segments ranged from L3-4 to L4-5. All the patients were with 1-level fusion. The mean postoperative ventral-disc height and dorsal-disc height increased significantly compared with preoperative (P<0.05). A significant postoperative increase was also observed in the mean operative segmental lordotic angle and the whole lumbar lordotic angle (P<0.05). Compared with preoperative, the postoperative VAS significantly decreased with no significant increase in the VAS in the last follow-up. The LBP was significantly relieved. The mean postoperative VAS of LBP decreased significantly compared with the preoperative ((1.6 ± 0.8) vs. (7.8 ± 0.8)). Postoperative complications included psoas major abscess and intervertebral space infection (1/56). Except for one patient whose cage subsided during the last follow-up, the other patients had good cage position. The one whose cage collapsed complained no symptoms including LBP. OLIF with stand-alone cages should be considered as a safe and effective option which can effectively alleviate LBP for the treatment of DLS.

As an indispensable component of store-operated CaInflammatory and matched normal intestinal tissues were collected from IBD patients to investigate the expression of STIM1. Intestinal epithelium-specific STIM1 conditional knockout mice (STIM1STIM1 could regulate intestinal epithelial homeostasis. STIM1 was augmented in the inflammatory intestinal tissues of IBD patients. In dextran sodium sulfate-induced colitis, STIM1 deficiency in intestinal epithelium reduced the loss of goblet cells through alleviating endoplasmic reticulum stress induced by disturbed CaOur results establish STIM1 as a crucial regulator for the maintenance of the intestinal barrier during colitis and provide a potential target for IBD treatment.

The expression of microRNA‑383 (miR‑383) is downregulated in a variety of tumor tissues, and it exhibits antiproliferative activity in non‑small cell lung cancer cells. In the present study, an association between the downregulation of miR‑383 expression and the deletion of chr8p22 in patients with lung adenocarcinoma was identified. The promoting effect of miR‑383 on cisplatin sensitivity was verified both in vivo and in vitro. Additionally, it was revealed that the expression of RNA binding motif protein 24 (RBM24) protein was regulated by and negatively correlated with miR‑383 expression. Ectopic expression of RBM24 or inhibition of miR‑383 decreased the chemosensitivity of parental A549 cells, whereas knockdown of RBM24 in cisplatin‑resistant A549 cells increased chemosensitivity. Mechanistically, miR‑383 interfered with the activation of nuclear factor κB (NF‑κB) signaling through repression of RBM24‑mediated phosphorylation of Rel‑like domain‑containing protein A and inhibitor α of NF‑κB. Taken together, the downregulation of miR‑383 induced RBM24 expression, which was mediated through the activation of NF‑κB signaling, to contribute to chemotherapy resistance in lung adenocarcinoma cells. The results of the present study highlight potential therapeutic targets for the clinical reversal of the chemotherapy resistance in lung adenocarcinoma.

Background Pneumoconiosis refers to a class of serious diseases threatening the health of workers exposed to coal or silicosis dust. However, the burden of pneumoconiosis is unavailable in China. Methods Incident cases, deaths, and disability-adjusted life years (DALYs) from pneumoconiosis and its subtypes in China were estimated from the Global Burden of Disease Study 2019 using a Bayesian meta-regression method. The trend of the burden from pneumoconiosis was analyzed using percentage change and annualized rate of change (ARC) during the period 1990–2019. The relationship between subnational socio-demographic index (SDI) and the ARC of age-standardised death rate was measured using Spearman’s Rank-Order Correlation. Results In 2019, there were 136.8 (95% uncertainty interval [UI] 113.7–162.5) thousand new cases, 10.2 (8.1–13.6) thousand deaths, and 608.7 (473.6–779.4) thousand DALYs from pneumoconiosis in China. Of the global burdens from pneumoconiosis, more than 60% were in China. Both the total number of new cases and DALYs from pneumoconiosis was keeping increasing from 1990 to 2019. In contrast, the age-standardised incidence, death, and DALY rates from pneumoconiosis and its subtypes, except for the age-standardised incidence rate of silicosis, and age-standardised death rate of asbestosis, experienced a significant decline during the same period. The subnational age-standardised death rates were higher in western China than in eastern China. Meanwhile, the subnational ARC of age-standardised death rates due to pneumoconiosis and its subtypes were significantly negatively correlated with SDI in 2019. Conclusion China suffers the largest health loss from pneumoconiosis in the world. Reducing the burden of pneumoconiosis is still an urgent task in China.

Background Cold-inducible RNA binding protein (CIRP) is a newly discovered proto-oncogene. In this study, we investigated the role of CIRP in the progression of non-small cell lung cancer (NSCLC) using patient tissue samples, cultured cell lines and animal lung cancer models. Methods Tissue arrays, IHC and HE staining, immunoblotting, and qRT-PCR were used to detect the indicated gene expression; plasmid and siRNA transfections as well as viral infection were used to manipulate gene expression; cell proliferation assay, cell cycle analysis, cell migration and invasion analysis, soft agar colony formation assay, tail intravenous injection and subcutaneous inoculation of animal models were performed to study the role of CIRP in NSCLC cells; Gene expression microarray was used to select the underlying pathways; and RNA immunoprecipitation assay, biotin pull-down assay, immunopurification assay, mRNA decay analyses and luciferase reporter assay were performed to elucidate the mechanisms. The log-rank (Mantel-Cox) test, independent sample T-test, nonparametric Mann-Whitney test, Spearman rank test and two-tailed independent sample T-test were used accordingly in our study. Results Our data showed that CIRP was highly expressed in NSCLC tissue, and its level was negatively correlated with the prognosis of NSCLC patients. By manipulating CIRP expression in A549, H460, H1299, and H1650 cell lines, we demonstrated that CIRP overexpression promoted the transition of G1/G0 phase to S phase and the formation of an enhanced malignant phenotype of NSCLC, reflected by increased proliferation, enhanced invasion/metastasis and greater tumorigenic capabilities both in vitro and in vivo. Transcriptome sequencing further demonstrated that CIRP acted on the cell cycle, DNA replication and Wnt signaling pathway to exert its pro-oncogenic action. Mechanistically, CIRP directly bound to the 3′- and 5′-UTRs of CTNNB1 mRNA, leading to enhanced stability and translation of CTNNB1 mRNA and promoting IRES-mediated protein synthesis, respectively. Eventually, the increased CTNNB1 protein levels mediated excessive activation of the Wnt/β-catenin signaling pathway and its downstream targets C-myc, COX-2, CCND1, MMP7, VEGFA and CD44. Conclusion Our results support CIRP as a candidate oncogene in NSCLC and a potential target for NSCLC therapy.

Summary Objective We examined whether auricular acupressure (AA) at four specifically preselected AA points can alleviate knee pain and decrease non-steroidal anti-inflammatory drugs (NSAIDs) consumption and its adverse effects for osteoarthritis patients. Methods Sixty-two patients (more than 40 years) with knee osteoarthritis of Kellgren–Lawrence grades of I or II upon radiographic classification were enrolled in this randomized, sham-controlled prospective study, and divided into two groups (AA group and control group). The AA group received true AA by embedding vaccaria seeds at four specific AA points (knee joint, shenmen, subcortex and sympathesis) ipsilateral to the knee osteoarthritis site, while the control group received four nonacupuncture points on the auricular helix. Visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, the number of patients who needed celecoxib pills and adverse effects were recorded. Results VAS and WOMAC scores in the AA group were significantly lower than that in the control group (P Conclusion Auricular acupressure plays a role in analgesic effect and can effectively decrease NSAIDs requirements without causing adverse events for the treatment of human knee osteoarthritis.

BACKGROUND Trigger finger is a very common disorder that occurs in both adults and children. Trigger finger presents mainly as pain and limited movement of the affected digit. This report describes a modified percutaneous needle release and an evaluation of its clinical efficacy to treat trigger thumb. MATERIAL AND METHODS Trigger thumb of 11 patients was released percutaneously using a specially designed needle (0.8×100 mm) with a planus tip. Complete release was ensured when no more grating sound was heard and the needle moved freely at the tip. Pain-related functional score was evaluated preoperatively and at 3 months postoperatively. Resolution of Notta's node, triggered or locked, Quinnell's criteria, and patient satisfaction were also assessed at 3 months after the operation. RESULTS After the percutaneous trigger thumb release, the overall visual analog scale (VAS) and pain-related functional scores declined significantly (P

Aims. Coronary artery disease (CAD) represents the leading cause of death worldwide. Accumulating evidence also suggests that sirtuins (SIRTS) have been associated with CAD. The present study was aimed at investigating the association between 12 gene polymorphisms for SIRTs and the development of CAD in a Chinese population. Materials and Methods. 12 SNPs (rs12778366 ( T > C ), rs3758391 ( T > C ), rs3740051 ( A > G ), rs4746720 ( C > T ), rs7895833 ( G > A ), rs932658 ( A > C ) for SIRT1, rs2015 ( G > T ) for SIRT2, rs28365927 ( G > A ), rs11246020 ( C > T ) for SIRT3, rs350844 ( G > A ), rs350846 ( G > C ), and rs107251 ( C > T ) for SIRT6) were selected and assessed in a cohort of 509 CAD patients and 552 matched healthy controls for this study. Genomic DNA from whole blood was extracted, and the SNPs were assessed using MassARRAY method. Results. TT genotype for rs3758391 and GG genotype for rs7895833 of SIRT1 were at higher risk of CAD, whereas the CC genotype for rs4746720 of SIRT1 was associated with a significantly decreased risk of CAD. The A allele of the rs28365927 of SIRT3 showed a significant decreased risk association with CAD patient group ( P = 0.014 ). Significant difference in genotypes rs350844 ( G > A ) ( P = 0.004 ), rs350846 ( G > C ) ( P = 0.002 ), and rs107251 ( C > T ) ( P ≤ 0.01 ) for SIRT6 was also found between the CAD patients and the healthy controls. Haplotype CTA significantly increased the risk of CAD ( P = 0.000118 , OR = 1.497 , 95 % CI = 1.218 – 1.840 ), while haplotype GCG significantly decreases the risk of CAD ( P = 0.000414 , OR = 1.131 , 95 % CI = 0.791 – 1.619 ). Conclusions. The SNP rs28365927 in the SIRT3 gene and SNP rs350844, rs350846, and rs107251 in the SIRT6 gene present significant associations with CAD in a north Chinese population. Haplotype CTA and GCG generated by rs350846/rs107251/rs350844 in the SIRT6 might also increase and decrease the risk of CAD, respectively.

Small GTPases are signaling molecules in regulating key cellular processes (e.g., cell differentiation, proliferation, and motility) as well as subcellular events (e.g., vesicle trafficking), making them key participants, especially in a great array of coronavirus infection processes. In this review, we discuss the role of small GTPases in the coronavirus life cycle, especially pre-entry, endocytosis, intracellular traffic, replication, and egress from the host cell. Furthermore, we also suggest the molecules that have potent adjuvant activity by targeting small GTPases. These studies provide deep insights and references to understand the pathogenesis of coronavirus as well as to propose the potential of small GTPases as targets for adjuvant development.

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease, and the dysregulated circular RNAs (circRNAs) play key roles in AAA progression. Circ_0092291 was downregulated in AAA patients, but its function in AAA remains unclear. This research was performed for the functional analysis of circ_0092291 and its mechanism exploration with mircoRNA-626 (miR-626) and collagen type IV alpha1 chain (COL4A1) in AAA. Human aortic vascular smooth muscle cells (T/G HA-VSMC) were treated with angiotensin II (Ang II). Levels of circ_0092291, miR-626, and COL4A1 were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Inflammatory cytokines were examined by enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was measured using caspase3 activity assay and flow cytometry. Angiopoiesis was assessed via tube formation assay. The protein analysis was conducted by western blot. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull-down assays were used to validate the molecular binding. Circ_0092291 downregulation was found in AAA samples and Ang II-treated cells. Inflammatory response and cell apoptosis were reduced while angiopoiesis and ECM level were facilitated after overexpression of circ_0092291 in Ang II-treated T/G HA-VSMC cells. MiR-626 was a miRNA target for circ_0092291, and miR-626 inhibition protected T/G HA-VSMC from Ang II-induced cell injury. Moreover, the regulation of circ_0092291 was achieved by serving as a miR-626 sponge in Ang II-treated cells. COL4A1 was affirmed as a target for miR-626 and circ_0092291 resulted in the level change of COL4A1 by sponging miR-626. Additionally, miR-626 downregulation inhibited the cell damages caused by Ang II through increasing the level of COL4A1 and the function of circ_0092291 was attributed to the upregulation of COL4A1. The evidence indicated that circ_0092291 could suppress the Ang II-induced cell dysfunction by targeting the miR-626/COL4A1 signaling axis. Circ_0092291 might improve the diagnosis and treatment of AAA.Key Points.Biological mechanism, Apoptosis, Molecular target.

Connected consciousness refers to the state when external stimuli can enter into the stream of our consciousness experience. Emerging evidence suggests that although patients may not respond behaviorally to external stimuli during anesthesia, they may be aware of their surroundings. In this work, we investigated whether EEG based brain decoding could be used for detecting connected consciousness in the absence of behavioral responses during propofol infusion. A total of 14 subjects participated in our experiment. Subjects were asked to discriminate two types of auditory stimuli with a finger press during an ultraslow propofol infusion. We trained an EEG based brain decoding model using data collected in the awakened state using the same auditory stimuli and tested the model on data collected during the propofol infusion. The model provided a correct classification rate (CCR) of [Formula: see text]% when subjects were able to respond to the stimuli during the propofol infusion. The CCR dropped to [Formula: see text]% when subjects ceased responding and further decreased to [Formula: see text]% when we increased the propofol concentration by another 0.2 [Formula: see text]g/ml. After terminating the propofol infusion, we observed that the CCR rebounded to [Formula: see text]% before the subjects regained consciousness. With the classification results, we provided evidence that loss of consciousness is a gradual process and may progress from full consciousness to connected consciousness and then to disconnected consciousness.

Background Infectious blood meal experiments have been frequently performed with different virus-vector combinations to assess the transmission potential of arthropod-borne (arbo)viruses. A wide variety of host blood sources have been used to deliver arboviruses to their arthropod vectors in laboratory studies. The type of blood used during vector competence experiments does not always reflect the blood from the viremic vertebrate hosts in the field, but little is known about the effect of blood source on the experimental outcome of vector competence studies. Here we investigated the effect of avian versus human blood on the infection and transmission rates of the zoonotic Usutu virus (USUV) in its primary mosquito vector Culex pipiens. Methods Cx. pipiens biotypes (pipiens and molestus) were orally infected with USUV through infectious blood meals containing either chicken or human whole blood. The USUV infection and transmission rates were determined by checking mosquito bodies and saliva for USUV presence after 14 days of incubation at 28 °C. In addition, viral titers were determined for USUV-positive mosquito bodies and saliva. Results Human and chicken blood lead to similar USUV transmission rates for Cx. pipiens biotype pipiens (18% and 15%, respectively), while human blood moderately but not significantly increased the transmission rate (30%) compared to chicken blood (17%) for biotype molestus. USUV infection rates with human blood were consistently higher in both Cx. pipiens biotypes compared to chicken blood. In virus-positive mosquitoes, USUV body and saliva titers did not differ between mosquitoes taking either human or chicken blood. Importantly, biotype molestus had much lower USUV saliva titers compared to biotype pipiens, regardless of which blood was offered. Conclusions Infection of mosquitoes with human blood led to higher USUV infection rates as compared to chicken blood. However, the blood source had no effect on the vector competence for USUV. Interestingly, biotype molestus is less likely to transmit USUV compared to biotype pipiens due to very low virus titers in the saliva. Graphical Abstract

Background How to maximally improve the drainage of intracranial and upper body venous and to reduce neurological complications during thoracic tumor‐causedsuperior vena cava replacement are still clinical problems to be solved. Methods We have innovatively used the bilateral jugular vein‐left femoral vein ECMO shunting to perform mediastinal tumor resection and superior vena cava replacement in a 50‐year‐old woman. Results During the operation, this technique maintained the patient's hemodynamic stability, improved the cerebral oxygen saturation and reduced the cerebral ischemia, hypoxia as well as the neurological complications. Conclusion It is indicated for patients with superior vena cava replacement who are unable to perform venous bypass (such as innominate vein to right atrial bypass) or venous shunting (such as differential pressure drainage from internal jugular vein to femoral vein).

Summary Background Plasmodium vivax exacts a significant toll on health worldwide, yet few efforts to date have quantified the extent and temporal trends of its global distribution. Given the challenges associated with the proper diagnosis and treatment of P vivax , national malaria programmes—particularly those pursuing malaria elimination strategies—require up to date assessments of P vivax endemicity and disease impact. This study presents the first global maps of P vivax clinical burden from 2000 to 2017. Methods In this spatial and temporal modelling study, we adjusted routine malariometric surveillance data for known biases and used socioeconomic indicators to generate time series of the clinical burden of P vivax . These data informed Bayesian geospatial models, which produced fine-scale predictions of P vivax clinical incidence and infection prevalence over time. Within sub-Saharan Africa, where routine surveillance for P vivax is not standard practice, we combined predicted surfaces of Plasmodium falciparum with country-specific ratios of P vivax to P falciparum . These results were combined with surveillance-based outputs outside of Africa to generate global maps. Findings We present the first high-resolution maps of P vivax burden. These results are combined with those for P falciparum (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The burden of P vivax malaria decreased by 41·6%, from 24·5 million cases (95% uncertainty interval 22·5–27·0) in 2000 to 14·3 million cases (13·7–15·0) in 2017. The Americas had a reduction of 56·8% (47·6–67·0) in total cases since 2000, while South-East Asia recorded declines of 50·5% (50·3–50·6) and the Western Pacific regions recorded declines of 51·3% (48·0–55·4). Europe achieved zero P vivax cases during the study period. Nonetheless, rates of decline have stalled in the past five years for many countries, with particular increases noted in regions affected by political and economic instability. Interpretation Our study highlights important spatial and temporal patterns in the clinical burden and prevalence of P vivax . Amid substantial progress worldwide, plateauing gains and areas of increased burden signal the potential for challenges that are greater than expected on the road to malaria elimination. These results support global monitoring systems and can inform the optimisation of diagnosis and treatment where P vivax has most impact. Funding Bill & Melinda Gates Foundation and the Wellcome Trust.

A number of studies have implicated that microRNAs (miRNAs) play a critical role in the development of gestational diabetes mellitus (GDM). However, the role of miR-657 in GDM remains vague up to date. We aim to investigate the modifying effect of miR-657 on GDM, which will provide new insight into the pathogenesis of GDM and may help to identify new diagnostic or therapeutic targets for GDM. Increased expression of miR-657 but decreased expression of interleukin-37 (IL-37) was observed in patients with GDM. Besides, negative association between miR-657 and IL-37 was demonstrated in this study. miR-657 could targetedly regulate IL-37 and enhance the proliferation of mononuclear macrophages. Moreover, miR-657 promoted the generation of inflammatory cytokines (IL-6 and tumor necrosis factor-α [TNF-α]) and activation of nuclear factor κB (NF-κB) in lipopolysaccharide-induced mononuclear macrophages, while its effect was significantly inhibited when exogenous recombinant IL-37 was administrated into cells. Accordingly, dysregulation of miR-657 contributes to the pathogenesis of GDM via IL-37/NF-κB signaling axis.

Background There is a lack of national report of the labour neuraxial analgesia (NA) rates in China in recent years, especially after the national promotion policy. The adverse maternal and perinatal outcomes associated with NA in China are also unknown. The aim of this study is to estimate the trends of NA rates from 2012 to 2019, to evaluate the effect of national policy on promoting NA and to identify the association between NA and adverse outcomes in China. Methods We used the individual data from China’s National Maternal Near Miss Surveillance System (NMNMSS) between 2012 and 2019, covering 438 hospitals from 326 urban districts or rural counties in 30 provinces across China. The analysis was restricted to singleton pregnant women who underwent vaginal delivery at or after 28 completed weeks of gestation. We estimate the trends of NA rates between 2012 and 2019, both at the national and provincial levels using Bayesian multilevel model. We also estimated the effect of the national pilot policy launched in 2018 using interrupted time-series analysis and identified the association between NA and adverse outcomes using modified Poisson regression combined with propensity score analysis. Results Over the study period, 620,851 of 6,023,046 women underwent vaginal delivery with NA. The estimated national NA rates increased from 8.4% in 2012 to 16.7% in 2019. Most provinces experienced the same rapid rise during this period. The national pilot policy accelerated the rise of the rates. No differences were observed between women with NA and without any analgesia in the incidence of uterine atony, placental retention, intrapartum stillbirths and 1- and 5-min Apgar scores lower than 7. However, women with NA had higher incidences of genital tract trauma (adjusted relative risk (aRR) 1.53, 95% confidence interval (CI) 1.04–2.26) and maternal near miss (aRR 1.35, 95% CI 1.08–1.69), only in hospitals which were not covered by the national pilot policy and usually lack of sufficient equipment and personnel. Conclusions The national policy can effectively increase the NA rate. However, as genital tract trauma and maternal near miss may increase in low-resource hospitals, but not in high-resource hospitals, further study is required to identify the reasons.

Aim To investigate the effect of 17β-Estradiol (E2) on intervertebral disc degeneration (IVDD) and the related mechanism. Materials and methods Immunohistochemistry was used to detect the expression of estrogen receptor β (ERβ) within intervertebral discs of humans and rats. After that, rat IVDD model was established by needle puncture and bilateral ovariectomy. Then, the serum E2 level was detected by enzyme linked immunosorbent assay, and the degree of IVDD was evaluated by X-ray, magnetic resonance imaging, hematoxylin and eosin staining, and Safranin O-Fast Green staining. Finally, we used immunohistochemistry and immunofluorescence staining to determine the effect of E2 on nuclear factor kappa-B (NF-κB) signal pathway both in vivo and in vitro. Key findings We identified that IVDD was associated with lower levels of ERβ and ERβ levels were inversely correlated with IVDD. The histological staining and radiological results showed that E2 supplement could alleviate IVDD progression. Additionally, immunohistochemistry staining demonstrated that E2 could inhibit nucleus pulposus cell (NPC) apoptosis, matrix metalloproteinases (MMPs) synthesis, and degradation of extracellular matrix (ECM) by inhibiting the activation of NF-κB signal pathway. Furthermore, immunofluorescence staining showed that the above effects of E2 on the NF-κB signal pathway could be blocked by the estrogen receptor antagonist ICI182780 in vitro. Finally, inhibition of NF-κB signal pathway by BAY11-7082 could reduce MMPs synthesis and ECM degradation of NPCs. Significance Collectively, these findings indicated that E2 could effectively ameliorate IVDD by inhibiting NPC apoptosis via inhibition of NF-κB signal pathway.

Altered placental development and function lead to placental diseases such as preeclampsia (PE) which is mainly characterized by insufficient trophoblast invasion and abnormally invasive placenta disorders. Long noncoding RNAs (lncRNAs) are widely reported to function as crucial players in the pathogenesis of PE. The present investigation clarified the role of lncRNA small nucleolar RNA host gene 16 (SNHG16) in PE. RT-qPCR was used to measure gene expression. The proliferation of trophoblast cells was examined using CCK-8 and EdU assays. Trophoblast migration and invasion were assessed using wound healing and transwell assays. The apoptosis was estimated by flow cytometry. Luciferase reporter and RNA pull-down assays were performed to explore the molecular mechanisms in trophoblast cells. We found that SNHG16 was downregulated in placenta from patients with PE. Moreover, SNHG16 depletion significantly inhibited trophoblast cell proliferation, migration, and invasion and stimulated apoptosis, while SNHG16 overexpression exerted an opposite effect. Subsequently, we confirmed that SNHG16 acted as a competing RNA (ceRNA) of miR-218-5p that was verified to directly target LASP1. Both miR-218-5p depletion and LASP1 upregulation antagonized the effect of SNHG16 knockdown on HTR-8/SVneo cell functions. In conclusion, SNHG16 facilitates trophoblast cell migration and invasion by the miR-218-5p/LASP1 axis.

This research was to explore the adoption value of computed tomography (CT) images based on adaptive statistical iterative reconstruction (ASIR) algorithm in the evaluation of probiotics combined with ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy (ICP). A total of 82 patients with ICP were selected as the research subjects and they were randomly rolled into experimental group (380 mg probiotics enteric-soluble capsule twice a day, combined with 90 mg ursodeoxycholic acid soft capsule three times a day) and control group (90 mg ursodeoxycholic acid soft capsule three times a day), with 41 cases in each. The treatment course was four months. The ASIR algorithm was constructed and applied to the CT image analysis and diagnosis of ICP patients. The effects of filtering back projection (FBP) reconstruction and ASIR algorithm on CT image quality, denoising degree, and artifacts of ICP patients were compared. Moreover, blood indicator levels of ICP patients before and after treatment were assessed. The results showed that the SD values of liver and gallbladder (20.77 Hu and 27.58 Hu) in the reconstructed image of the ASIR algorithm were significantly lower than those of the FBP algorithm (40.58 Hu and 45.63 Hu) ( P < 0.05 ). The SNR values of the liver and gallbladder (3.68 and 2.05) of the reconstructed image were significantly higher than those of the FBP algorithm (1.91 and 1.19) ( P < 0.05 ). The overall image quality after ASIR reconstruction (3.92 points) was significantly better than that of the FBP algorithm (2.36 points), and the image noise score (3.21 points) reconstructed by the FBP algorithm was higher than that by the ASIR algorithm (1.83 points). The artifact score of FBP reconstructed image (4.47 points) was greatly higher than that of ASIR algorithm (2.26 points) ( P < 0.05 ). Before treatment, there was no remarkable difference in the indexes between the two groups of patients ( P > 0.05 ). After treatment, the γ-glutamyltransferase (γ-GT) and alkaline phosphatase (ALP) levels (327.55 U/L and 778.15 μmol/L) of the experimental group of ICP patients were higher than those of the control group (248.63 U/L and 668.43 μmol/L), with substantial difference between the two groups ( P < 0.05 ). The blood ammonia (BA) level (151.09 μmol/L) of the experimental group was lower than that of the control group (178.46 μmol/L), and the difference between the two groups was remarkable ( P < 0.05 ). To sum up, the CT image denoising degree based on ASIR algorithm was high, with few artifacts and good overall quality. Probiotics combined with ursodeoxycholic acid in the treatment of ICP can effectively improve the liver function and intestinal flora of patients, which was of great significance in the clinical diagnosis and treatment of the disease.

Background The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs P = 0.022). Conclusions CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.

Background Restenosis is a serious problem in patients who have undergone percutaneous transluminal angioplasty. Endothelial injury resulting from surgery can lead to endothelial dysfunction and neointimal formation by inducing aberrant proliferation and migration of vascular smooth muscle cells. Exosomes secreted by mesenchymal stem cells have been a hot topic in cardioprotective research. However, to date, exosomes derived from mesenchymal stem cells (MSC-Exo) have rarely been reported in association with restenosis after artery injury. The aim of this study was to investigate whether MSC-Exo inhibit neointimal hyperplasia in a rat model of carotid artery balloon-induced injury and, if so, to explore the underlying mechanisms. Methods Characterization of MSC-Exo immunophenotypes was performed by electron microscopy, nanoparticle tracking analysis and western blot assays. To investigate whether MSC-Exo inhibited neointimal hyperplasia, rats were intravenously injected with normal saline or MSC-Exo after carotid artery balloon-induced injury. Haematoxylin-eosin staining was performed to examine the intimal and media areas. Evans blue dye staining was performed to examine re-endothelialization. Moreover, immunohistochemistry and immunofluorescence were performed to examine the expression of CD31, vWF and α-SMA. To further investigate the involvement of MSC-Exo-induced re-endothelialization, the underlying mechanisms were studied by cell counting kit-8, cell scratch, immunofluorescence and western blot assays. Results Our data showed that MSC-Exo were ingested by endothelial cells and that systemic injection of MSC-Exo suppressed neointimal hyperplasia after artery injury. The Evans blue staining results showed that MSC-Exo could accelerate re-endothelialization compared to the saline group. The immunofluorescence and immunohistochemistry results showed that MSC-Exo upregulated the expression of CD31 and vWF but downregulated the expression of α-SMA. Furthermore, MSC-Exo mechanistically facilitated proliferation and migration by activating the Erk1/2 signalling pathway. The western blot results showed that MSC-Exo upregulated the expression of PCNA, Cyclin D1, Vimentin, MMP2 and MMP9 compared to that in the control group. Interestingly, an Erk1/2 inhibitor reversed the expression of the above proteins. Conclusion Our data suggest that MSC-Exo can inhibit neointimal hyperplasia after carotid artery injury by accelerating re-endothelialization, which is accompanied by activation of the Erk1/2 signalling pathway. Importantly, our study provides a novel cell-free approach for the treatment of restenosis diseases after intervention.

RATIONALE Compared with traditional labelling reagents used in proteomics, maleic anhydride is milder and can be easily removed under certain conditions, thus simplifying chemical derivatization. METHODS The proposed strategy combined a site-specific chemical labelling reaction with mass spectrometry. Site-selective, reversible N-terminal maleylation was controlled by pH. RESULTS Selective maleyl N-terminal labelling was achieved with high efficiency under the optimized reaction conditions. The demaleylation conditions were also optimized. The sequence coverage of histone H4 increased from 77% to 95% after the maleyl labels were removed, and the number of maleylated peptides was five times that of the unlabelled peptides. We further verified the reversible and selective N-terminal labelling properties of maleic anhydride through propionylation labelling at the peptide/protein level. CONCLUSIONS A new method for site-selective maleylation of the N-terminal amino groups of a peptide was explored. Through the optimization experiment, good efficiency was achieved for this labelling reaction. The reversibility of maleylation labelling was also explored and applied for the identification of post-translational modifications of histones. Thus, site-selective, reversible, pH-induced N-terminal labelling using maleic anhydride has greater potential for application in proteomics than any other labelling methods.

INTRODUCTION: Leptin (LEP) is a peptide hormone that acts via leptin receptor (LEPR) binding. Genetic evidence from different human populations has implicated LEP/LEPR in the pathogenesis of coronary artery disease (CAD), and suggests that certain LEP/LEPR gene polymorphisms may increase the risk of CAD. The aim of this study was to assess two single nucleotide polymorphisms (SNPs) in LEP genes (rs2167270 and rs7799039) and two in LEPR genes (rs6588147, rs1137100) for association with CAD. METHODS: We enrolled 271 North Chinese Han CAD patients, and 113 healthy age- and sex-matched controls. Genomic DNA was extracted from whole blood, and the four SNPs were assessed using a MassArray system. RESULTS: The G allele frequency at rs2167270 was significantly higher among CAD cases than among controls. The AG genotype at rs7799039 was associated with a significantly decreased risk of CAD unlike the AA genotype used as the reference. The A allele was significantly associated with the CAD patient group. Interestingly, statistically significant differences in genotype and allele frequency at LEP rs2167270 and rs7799039 existed among females but not among males. CONCLUSIONS: The current study detected a significant association between genetic variations at LEP rs7799039 and rs2167270 and the risk of CAD in a north Chinese population, and revealed that LEP rs2167270 and rs7799039 gene polymorphisms might act as predisposing factors for CAD.

Objective We investigated whether pre-anesthesia dynamic frontal-parietal functional connectivity was correlated with the observed interindividual differences in propofol susceptibility. Methods Three resting-state EEG datasets were used in the study (N = 29, N = 21 and N = 20). We estimated the pre-anesthesia strength and fluctuations of frontal-parietal functional connectivity by using sliding-window analysis. Propofol served as the sole anesthetic drug, and it was administered by using a target-controlled infusion system. Individual susceptibility to propofol was assessed by the induction time, from infusion onset until a bispectral index value of 60 was reached, for subjects in dataset-1 and dataset-2, and susceptibility was assessed by behavioral data for subjects in the external dataset. Results We observed in the three datasets that subjects with high susceptibility to propofol had lower pre-anesthesia strength and lower fluctuation of frontal-parietal functional connectivity than the low-susceptibility group at alpha band. Moreover, the induction time was significantly correlated with the estimated pre-anesthesia frontal-parietal functional connectivity measures. We also validated the robustness of these findings by using different window lengths in sliding-window analysis. Conclusions Subjects with weaker pre-anesthesia dynamic frontal-parietal communication are more likely to be anesthetized. Significance These observations suggest that the titration procedure for propofol should consider the pre-anesthesia brain functional state.

Publisher's version (útgefin grein), Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (>= 65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0-100 based on the 2.5th and 97.5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target-1 billion more people benefiting from UHC by 2023-we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45.8 (95% uncertainty interval 44.2-47.5) in 1990 to 60.3 (58.7-61.9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2.6% [1.9-3.3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010-2019 relative to 1990-2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0.79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388.9 million (358.6-421.3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3.1 billion (3.0-3.2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968.1 million [903.5-1040.3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people-the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close-or how far-all populations are in benefiting from UHC., Lucas Guimaraes Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (Capes) -Finance Code 001, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG). Olatunji O Adetokunboh acknowledges South African Department of Science & Innovation, and National Research Foundation. Anurag Agrawal acknowledges support from the Wellcome Trust DBT India Alliance Senior Fellowship IA/CPHS/14/1/501489. Rufus Olusola Akinyemi acknowledges Grant U01HG010273 from the National Institutes of Health (NIH) as part of the H3Africa Consortium. Rufus Olusola Akinyemi is further supported by the FLAIR fellowship funded by the UK Royal Society and the African Academy of Sciences. Syed Mohamed Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. Marcel Ausloos, Claudiu Herteliu, and Adrian Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDSUEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Till Winfried Barnighausen acknowledges support from the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. Juan J Carrero was supported by the Swedish Research Council (2019-01059). Felix Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. Vera Marisa Costa acknowledges support from grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundacao para a Ciencia e a Tecnologia (FCT), IP, under the Norma TransitA3ria DL57/2016/CP1334/CT0006. Jan-Walter De Neve acknowledges support from the Alexander von Humboldt Foundation. Kebede Deribe acknowledges support by Wellcome Trust grant number 201900/Z/16/Z as part of his International Intermediate Fellowship. Claudiu Herteliu acknowledges partial support by a grant co-funded by European Fund for Regional Development through Operational Program for Competitiveness, Project ID P_40_382. Praveen Hoogar acknowledges the Centre for Bio Cultural Studies (CBiCS), Manipal Academy of Higher Education(MAHE), Manipal and Centre for Holistic Development and Research (CHDR), Kalghatgi. Bing-Fang Hwang acknowledges support from China Medical University (CMU108-MF-95), Taichung, Taiwan. Mihajlo Jakovljevic acknowledges the Serbian part of this GBD contribution was co-funded through the Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. Aruna M Kamath acknowledges funding from the National Institutes of Health T32 grant (T32GM086270). Srinivasa Vittal Katikireddi acknowledges funding from the Medical Research Council (MC_UU_12017/13 & MC_UU_12017/15), Scottish Government Chief Scientist Office (SPHSU13 & SPHSU15) and an NRS Senior Clinical Fellowship (SCAF/15/02). Yun Jin Kim acknowledges support from the Research Management Centre, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/0001). Kewal Krishan acknowledges support from the DST PURSE grant and UGC Center of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India. Manasi Kumar acknowledges support from K43 TW010716 Fogarty International Center/NIMH. Ben Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. Ivan Landires is a member of the Sistema Nacional de InvestigaciA3n (SNI), which is supported by the Secretaria Nacional de Ciencia Tecnologia e Innovacion (SENACYT), Panama. Jeffrey V Lazarus acknowledges support by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III/ESF, European Union [CP18/00074]). Peter T N Memiah acknowledges CODESRIA; HISTP. Subas Neupane acknowledges partial support from the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital. Shuhei Nomura acknowledges support from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). Alberto Ortiz acknowledges support by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. George C Patton acknowledges support from a National Health & Medical Research Council Fellowship. Marina Pinheiro acknowledges support from FCT for funding through program DL 57/2016 -Norma transitA3ria. Alberto Raggi, David Sattin, and Silvia Schiavolin acknowledge support by a grant from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4 -Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). Daniel Cury Ribeiro acknowledges support from the Sir Charles Hercus Health Research Fellowship -Health Research Council of New Zealand (18/111). Perminder S Sachdev acknowledges funding from the NHMRC Australia. Abdallah M Samy acknowledges support from a fellowship from the Egyptian Fulbright Mission Program. Milena M Santric-Milicevic acknowledges support from the Ministry of Education, Science and Technological Development of the Republic of Serbia (Contract No. 175087). Rodrigo Sarmiento-Suarez acknowledges institutional support from University of Applied and Environmental Sciences in Bogota, Colombia, and Carlos III Institute of Health in Madrid, Spain. Maria Ines Schmidt acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. Sheikh Mohammed Shariful Islam acknowledges a fellowship from the National Heart Foundation of Australia and Deakin University. Aziz Sheikh acknowledges support from Health Data Research UK. Kenji Shibuya acknowledges Japan Ministry of Education, Culture, Sports, Science and Technology. Joan B Soriano acknowledges support by Centro de Investigacion en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Rafael Tabares-Seisdedos acknowledges partial support from grant PI17/00719 from ISCIII-FEDER. Santosh Kumar Tadakamadla acknowledges support from the National Health and Medical Research Council Early Career Fellowship, Australia. Marcello Tonelli acknowledges the David Freeze Chair in Health Services Research at the University of Calgary, AB, Canada., "Peer Reviewed"

Background The Asian bush mosquito Aedes japonicus is invading Europe and was first discovered in Lelystad, the Netherlands in 2013, where it has established a permanent population. In this study, we investigated the vector competence of Ae. japonicus from the Netherlands for the emerging Zika virus (ZIKV) and zoonotic Usutu virus (USUV). ZIKV causes severe congenital microcephaly and Guillain-Barré syndrome in humans. USUV is closely related to West Nile virus, has recently spread throughout Europe and is causing mass mortality of birds. USUV infection in humans can result in clinical manifestations ranging from mild disease to severe neurological impairments. Methodology/Principal findings In our study, field-collected Ae. japonicus females received an infectious blood meal with ZIKV or USUV by droplet feeding. After 14 days at 28°C, 3% of the ZIKV-blood fed mosquitoes and 13% of the USUV-blood fed mosquitoes showed virus-positive saliva, indicating that Ae. japonicus can transmit both viruses. To investigate the effect of the mosquito midgut barrier on virus transmission, female mosquitoes were intrathoracically injected with ZIKV or USUV. Of the injected mosquitoes, 96% (ZIKV) and 88% (USUV) showed virus-positive saliva after 14 days at 28°C. This indicates that ZIKV and USUV can efficiently replicate in Ae. japonicus but that a strong midgut barrier is normally restricting virus dissemination. Small RNA deep sequencing of orally infected mosquitoes confirmed active replication of ZIKV and USUV, as demonstrated by potent small interfering RNA responses against both viruses. Additionally, de novo small RNA assembly revealed the presence of a novel narnavirus in Ae. japonicus. Conclusions/Significance Given that Ae. japonicus can experimentally transmit arthropod-borne viruses (arboviruses) like ZIKV and USUV and is currently expanding its territories, we should consider this mosquito as a potential vector for arboviral diseases in Europe., Author summary Arthropod-borne viruses (arboviruses) cause a high disease burden in humans and animals. Zika virus (ZIKV) causes microcephaly and Guillain-Barré syndrome in humans, whereas Usutu virus (USUV) induces high mortality in birds and neurological disease in humans. The spread of arboviruses such as ZIKV and USUV is determined by the presence of mosquitoes that can transmit these viruses from one vertebrate host to the next. Here, we investigate the risk of transmission of ZIKV and USUV by the Asian bush mosquito Aedes japonicus. This mosquito is invading Europe and is currently present in the Netherlands. We found that field-collected Ae. japonicus mosquitoes can experimentally transmit ZIKV and USUV. Of the orally infected mosquitoes, 3% (ZIKV) and 13% (USUV) showed virus-positive saliva after 14 days at 28°C. We also found that ZIKV and USUV activated the antiviral RNA interference immune response of Ae. japonicus. Moreover, a strong barrier in the mosquito midgut restricted virus dissemination, since 96% (ZIKV) and 88% (USUV) of the mosquitoes injected with ZIKV or USUV showed virus-positive saliva. Additionally, we discovered a narnavirus in Ae. japonicus. Given that Ae. japonicus can transmit ZIKV and USUV, we should consider this mosquito as a potential vector for arboviral diseases in Europe.

Accumulating studies suggest the potential association between epilepsy and vitamin D (VD) in recent years. Vitamin D binding protein (VDBP) is the main VD carrier and can affect the availability of VD and its metabolites. Thus, this study aimed to investigate the association between VDBP polymorphisms and VD level on epilepsy. A total of 220 epilepsy patients and 210 health controls were enrolled and polymorphisms of VDBP (rs4588, rs7041, rs2298849, and rs2282679) genotype were detected using the PCR–ligase detection reaction method. The circulating status of VD metabolites, 25(OH)D and 24,25(OH)2D, was detected by a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and the VD metabolite ratio (VMR), 24,25(OH)2D:25(OH)D, was then calculated. The frequency of rs4588(C>A) and rs2282679(A>C) genotype with AC was significantly lower among the patients relative to the controls [odds ratio, OR = 0.597, 95% confidence interval, CI = 0.401–0.890, p = 0.011 for rs4588(...

The underlying molecular mechanism of lung cancer drug resistance is poorly understood. The mediator of endoplasmic reticulum stress CHOP (DNA damage inducible transcript 3) promotes stress-induced apoptosis and appears to function as a transcription factor in multiple diseases. However, its potential contributions to multidrug resistance in solid tumors is unknown. Here, we investigated CHOP expression in tumor tissues form 69 lung cancer patients, finding that deficient CHOP expression is associated with poor prognosis. Cisplatin-resistant lung cancer cells exhibited lower expression of CHOP compared to that in sensitive lung cancer cells, and silencing or augmenting CHOP expression enhanced or impaired cisplatin resistance, respectively. Mechanistic investigations revealed that CHOP is directly associated with the regulation of autophagy or apoptosis-regulatory genes including LC3-II, death receptor 5 (DR5), and telomere repeat-binding factor 3. Notably, CHOP was identified as a target of miR-146a, and increased miR-146a expression in lung cancer cells was suggested to be responsible for CHOP mRNA down-regulation. Further, animal models confirmed that abnormally expressed miR-146a in lung cancer cells does not affect growth, but rather alters chemotherapy sensitivity. Together, CHOP is a useful prognostic marker and miR-146a is a potential therapeutic target for multidrug-resistant lung cancer.

Background The Sustainable Development Goals (SDGs), adopted by all United Nations (UN) member states in 2015, established a set of bold and ambitious health-related targets to achieve by 2030. Understanding China’s progress toward these targets is critical to improving population health for its 1.4 billion people. Methods and findings We used estimates from the Global Burden of Disease (GBD) Study 2016, national surveys and surveillance data from China, and qualitative data. Twenty-eight of the 37 indicators included in the GBD Study 2016 were analyzed. We developed an attainment index of health-related SDGs, a scale of 0–100 based on the values of indicators. The projection model is adjusted based on the one developed by the GBD Study 2016 SDG collaborators. We found that China has achieved several health-related SDG targets, including decreasing neonatal and under-5 mortality rates and the maternal mortality ratios and reducing wasting and stunting for children. However, China may only achieve 12 out of the 28 health-related SDG targets by 2030. The number of target indicators achieved varies among provinces and municipalities. In 2016, among the seven measured health domains, China performed best in child nutrition and maternal and child health and reproductive health, with the attainment index scores of 93.0 and 91.8, respectively, followed by noncommunicable diseases (NCDs) (69.4), road injuries (63.6), infectious diseases (63.0), environmental health (62.9), and universal health coverage (UHC) (54.4). There are daunting challenges to achieve the targets for child overweight, infectious diseases, NCD risk factors, and environmental exposure factors. China will also have a formidable challenge in achieving UHC, particularly in ensuring access to essential healthcare for all and providing adequate financial protection. The attainment index of child nutrition is projected to drop to 80.5 by 2025 because of worsening child overweight. The index of NCD risk factors is projected to drop to 38.8 by 2025. Regional disparities are substantial, with eastern provinces generally performing better than central and western provinces. Sex disparities are clear, with men at higher risk of excess mortality than women. The primary limitations of this study are the limited data availability and quality for several indicators and the adoption of "business-as-usual" projection methods. Conclusion The study found that China has made good progress in improving population health, but challenges lie ahead. China has substantially improved the health of children and women and will continue to make good progress, although geographic disparities remain a great challenge. Meanwhile, China faced challenges in NCDs, mental health, and some infectious diseases. Poor control of health risk factors and worsening environmental threats have posed difficulties in further health improvement. Meanwhile, an inefficient health system is a barrier to tackling these challenges among such a rapidly aging population. The eastern provinces are predicted to perform better than the central and western provinces, and women are predicted to be more likely than men to achieve these targets by 2030. In order to make good progress, China must take a series of concerted actions, including more investments in public goods and services for health and redressing the intracountry inequities., Shenglan Tang and colleagues report China's current situation and projected achievement of the health related sustainable development goals by 2030., Author summary Why was the study done? China has made impressive progress in the Millennium Development Goals (MDGs) era, which ended in 2015. Despite China’s success in achieving the MDGs, it faces formidable challenges in achieving many targets in the health-related Sustainable Development Goals (SDGs), which have a 2030 target date. Understanding China’s current situation and progress toward achieving these goals is critical to the development of practical solutions for improving population health for its 1.4 billion people in the SDG era. What did the researchers do and find? We conducted an analysis of progress toward the health-related SDGs using data from the Global Burden of Disease (GBD) Study 2016, national surveys, surveillance data from China, and qualitative study results. We developed an index of the attainment of the health-related SDGs, using a scale of 0–100 based on the absolute values of indicators. We adjusted the projection model developed by the GBD 2016 SDG collaborators to produce sex-specific estimates, stratified by province, and explore sex and regional disparities. Around 120 key informants were purposively approached for thematic interviews. This research found that China has achieved several health-related SDG targets, especially on child nutrition and maternal and child health and reproductive health. Nevertheless, China may only achieve 12 out of the 28 selected health-related SDG targets by 2030. There are daunting challenges ahead for China in achieving the targets for child overweight, infectious diseases, noncommunicable disease risk factors, environmental exposure factors, and universal health coverage. Regional disparities were substantial, with eastern coastal provinces generally performing better than central and western provinces in most of the indicators. Sex disparities were clear, with men at higher risk of excess mortality than women. What do these findings mean? To achieve the targets of the health-related SDGs, China must take a series of concerted actions, including increased investment in public goods and services for health, addressing the regional inequities, and tackling the emerging new health challenges to ensure that no one is left behind. In those areas where China has already achieved the SDG targets, the government should synthesize the experiences and good practices that can be applied to the regions/provinces that need to catch up to the level of health development witnessed in developed regions/provinces. The Chinese government needs to examine the root causes of the challenges in achieving the health-related SDGs and develop an action plan to address these causes. The plan should prioritize key policy interventions for target populations and mobilize adequate resources to tackle these health challenges. It is important to address common problems by tackling cross-cutting issues in advancing the health-related SDGs, such as strengthening the enforcement of laws and regulations, establishing effective organizational structures, and human resources development.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations., A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Purpose: Mild cognitive impairment (MCI) is considered to be the clinical transition stage between patients with cognitively intact geriatrics and Alzheimer’s disease (AD). When observed longitudinally, however, a certain proportion of patients with MCI are expected to revert to a cognitively intact state (MCI_R) while others either remain in the MCI state (MCI_S) or deteriorate into AD (MCI_P). It is worthwhile to investigate the divergence in the brain activities of these MCI groups with different post hoc labels. Methods: In this study, we employed the regional homogeneity (ReHo) measure to explore the characteristics of local brain activity in these MCI groups. Results: Compared to age-matched normal controls, our results exhibited that (1) in MCI_R group, ReHo index showed an increase in the left insula and a decrease in the left superior temporal gyrus; (2) in MCI_S group, ReHo index increased in the left orbital part of the inferior frontal gyrus (IFG_orb) and decreased in the left inferior parietal lobe; and (3) in MCI_P group, ReHo index elevated in the left IFG_orb and decreased in the left putamen. Conclusions: The distinct ReHo changes in the individual MCI groups indicated a potential evidence for differentially active interventions for a specific patient with MCI.

Multidrug resistance (MDR) often leads to chemotherapy failure of lung cancer and has been linking to the cellular expression of several DNA transcription‐ and repair‐related genes such as Trps1 and MGMT. However, their roles in the formation of MDR are largely unknown. In this study, overexpression/knockdown, luciferase assay and ChIP assay were performed to study the relationship between Trps1 and MGMT, as well as their roles in MDR formation. Our results demonstrated that Trps1 and MGMT expression both increased in drug‐resistant lung cancer cell line (H446/CDDP). Silencing of Trps1 resulted in downregulation of MGMT expression and decrease in the multidrug sensitivity of H446/CDDP cells, while Trps1 overexpression exhibited the opposite effects in H446 cells. Ectopic expression of MGMT had no effect on Trps1 expression, but enhanced the IC50 values of H446 cells or rescued the IC50 values of Trps1‐silenced H446/CDDP cells in treatment of multidrug. Our data further showed that, mechanistically, Trps1 acted as a transcription activator that directly induced MGMT transcription by binding to the MGMT promoter. Taken together, we consider that upregulation of Trps1 induces MGMT transcription contributing to the formation of MDR in lung cancer cells. Our findings proved potential targets for reversing MDR in clinical chemotherapy of lung cancer.

In this meta-analysis, we evaluated the usefulness of serum thymidine kinase 1 concentration (STK1c) for monitoring the outcome of extensive open surgery in patients with lung cancer. We also compared STK1c between a healthy population and patients with benign and malignant lung tumors to assess its potential value for early detection of lung cancer and for distinguishing between benign lung disease and malignant cancer.Related studies were retrieved from publications in PubMed, Cochrane, China National Knowledge Infrastructure, Wanfang databases, and Internet searches. Correlation was evaluated using weighted mean difference. Fixed or random effect models were selected for data analyses based on heterogeneity tested with the chi-square test. Publication bias was assessed using a funnel plot and Egger's test.Twenty studies were selected for analysis, which showed that STK1c was significantly (p 0.00001) reduced by 41.7% 1 month after extensive open surgery, approximately corresponding to an STK1c half-life of 1 month. STK1c levels were significantly higher in lung cancer patients than in healthy persons (p 0.00001) or in patients with benign lung disease (p 0.00001). There was also a significant difference in STK1c between patients with benign and malignant lung disease (p 0.0001).The half-life of STK1c may be an important tool in the clinical evaluation of surgical response in patients with lung cancer. STK1c may also be beneficial in the early detection of lung cancer.