Burden of drug use disorders in the United States from 1990 to 2021 and its projection until 2035: results from the GBD study.

BACKGROUND: Drug use disorders (DUDs) have emerged as one of the most significant public health crises, exerting a substantial influence on both community health and socio-economic progress. The United States (US) also suffers a heavy burden, it is necessary to figure out the situation from multiple perspectives and take effective measures to deal with it. Therefore, using the data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2021, we evaluated this topic. METHODS: Annual data on DUDs-related burden were collected from the GBD study 2021. We calculated the indicator of estimated annual percentage change (EAPC) to evaluate the changing trend of burden. The Bayesian model for age-period-cohort was introduced to forecast the burden. RESULTS: In 2021, the number and age-standardized rate of prevalence were particularly prominent, with 12,146.95 thousand and 3821.43 per 100,000, respectively. Higher burden was also observed in males, 15-45 years old populations, and opioid use disorders subtype. From 1990 to 2021, the DUDs-related burden increased in the US and all states, especially in West Virginia; and the national death-related burden with the highest increase (EAPC = 7.96). Other significant inverse associations were seen between EAPC, age-standardized rates, and socio-demographic index (SDI). Moreover, in the next 14 years, the projected DUDs burden remains exigent. CONCLUSIONS: The burden of DUDs in the US is heavy and has been enlarging. This study proposes that greater attention should be paid to the strategies in males, the younger population, opioid use disorders, and low-SDI states implemented by decision-makers to achieve goals such as reducing burden.

RNA binding protein Lin28B promotes chronic myeloid leukemia blast crisis by transcriptionally upregulating miR-181d.

The blast crisis (BC) of chronic myeloid leukemia (CML) has poor efficacy against existing treatments and extremely short survival. However, the molecular mechanism of CML-chronic phase (CP) transformation to CML-BC is not yet fully understood. Here, we show that Lin28B, a RNA binding protein, acted as an activator enhancing the transformation to CML-BC by mediating excessive cell proliferation. The level of Lin28B expression was apparently elevated in CML-BC patients compared with newly diagnosed CML-CP patients. The overexpression of Lin28B promoted the proliferation of leukemia cells. Mechanistically, we identified Lin28B as a DNA binding protein by binding to the promoter region of miR-181d and upregulating its expression, which inhibited the expression of Programmed cell death 4 (PDCD4) by binding to the PDCD4 3'UTR region, thereby enhancing the proliferation of CML cells. Overall, the "Lin28B-miR-181d-PDCD4" regulatory axis promoted CML blast crisis. Implications: Our findings highlight the oncogenic role of Lin28B in CML blast crisis, acting as a DNA binding protein which transcriptionally upregulates miR-181d expression.

Impact of Cardiovascular and Cerebrovascular Diseases Mortality on Life Expectancy in Tianjin, 2004 and 2020.

This study aimed to analyze the impact of cardiovascular and cerebrovascular diseases (CCVDs) mortality on Tianjin's life expectancy (LE) in 2004 compared with 2020 using Arriaga's decomposition method. The LE increment for Tianjin residents due to the decrease in CCVDs mortality was 1.54 years (38.7%). Males, females, urban residents, and rural residents contributed 1.29 years (36.83%), 1.76 years (40.25%), 2.11 years (44.41%), and 0.71 years (25.06%), respectively. A total of 38.2% of the LE increment was attributed to deaths from CCVDs in people aged ≥65 years. Cerebral infarction, intracerebral hemorrhage, acute myocardial infarction, and other heart diseases contributed positively to the increase in LE (24.8%, 22.68%, 16.66%, and 11.3%). Sequelae of cerebrovascular disease and other coronary heart diseases contributed negatively to the increase in LE (-25.2% and -17.92%). Therefore, we need to control the risk factors of the elderly, males, rural residents, sequelae of cerebrovascular disease, and other coronary heart diseases.

Jacalin-related lectin 45 (OsJRL45) isolated from 'sea rice 86' enhances rice salt tolerance at the seedling and reproductive stages.

BACKGROUND: Rice (Oryza sativa L.) is one of the most widely cultivated grain crops in the world that meets the caloric needs of more than half the world's population. Salt stress seriously affects rice production and threatens food security. Therefore, mining salt tolerance genes in salt-tolerant germplasm and elucidating their molecular mechanisms in rice are necessary for the breeding of salt tolerant cultivars. RESULTS: In this study, a salt stress-responsive jacalin-related lectin (JRL) family gene, OsJRL45, was identified in the salt-tolerant rice variety 'sea rice 86' (SR86). OsJRL45 showed high expression level in leaves, and the corresponding protein mainly localized to the endoplasmic reticulum. The knockout mutant and overexpression lines of OsJRL45 revealed that OsJRL45 positively regulates the salt tolerance of rice plants at all growth stages. Compared with the wild type (WT), the OsJRL45 overexpression lines showed greater salt tolerance at the reproductive stage, and significantly higher seed setting rate and 1,000-grain weight. Moreover, OsJRL45 expression significantly improved the salt-resistant ability and yield of a salt-sensitive indica cultivar, L6-23. Furthermore, OsJRL45 enhanced the antioxidant capacity of rice plants and facilitated the maintenance of Na+-K+ homeostasis under salt stress conditions. Five proteins associated with OsJRL45 were screened by transcriptome and interaction network analysis, of which one, the transmembrane transporter Os10g0210500 affects the salt tolerance of rice by regulating ion transport-, salt stress-, and hormone-responsive proteins. CONCLUSIONS: The OsJRL45 gene isolated from SR86 positively regulated the salt tolerance of rice plants at all growth stages, and significantly increased the yield of salt-sensitive rice cultivar under NaCl treatment. OsJRL45 increased the activity of antioxidant enzyme of rice and regulated Na+/K+ dynamic equilibrium under salinity conditions. Our data suggest that OsJRL45 may improve the salt tolerance of rice by mediating the expression of ion transport-, salt stress response-, and hormone response-related genes.

Human neural stem cells repress glioma cell progression in a paracrine manner by downregulating the Wnt/ß-catenin signalling pathway.

Neural stem cells (NSCs) play crucial roles in neurological disorders and tissue injury repair through exerting paracrine effects. However, the effects of NSC-derived factors on glioma progression remain unclear. This study aimed to evaluate the effects of human NSC-conditioned medium (NSC-CM) on the behaviour of glioma cells using an in vitro co-culture system. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays revealed that NSC-CM inhibited glioma cell proliferation and growth in a fetal bovine serum (FBS)-independent manner. In addition, our wound-healing assay demonstrated that NSC-CM repressed glioma cell migration, while results from transwell and 3D spheroid invasion assays indicated that NSC-CM also reduced the invasion capacity of glioma cells. Flow cytometry showed that NSC-CM prevented cell cycle progression from the G1 to S phase and promoted apoptosis. Western blotting was used to show that the expression of Wnt/ß-catenin pathway-related proteins, including ß-catenin, c-Myc, cyclin D1, CD44 and Met, was remarkably decreased in NSC-CM-treated glioma cells. Furthermore, the addition of a Wnt/ß-catenin pathway activator, CHIR99021, significantly induced the expression of ß-catenin and Met and increased the proliferative and invasive capabilities of control medium-treated glioma cells but not those of NSC-CM-treated glioma cells. The use of enzyme-linked immunosorbent assays (ELISA) revealed the secretion of some antitumour factors in human and rat NSCs, including interferon-α and dickkopf-1. Our data suggest that NSC-CM partially inhibits glioma cell progression by downregulating Wnt/ß-catenin signalling. This study may serve as a basis for developing future antiglioma therapies based on NSC derivatives.

Dose-response association of polycyclic aromatic hydrocarbon with self-reported trouble sleeping in adults: evidence from the National Health and Nutrition Examination Survey.

Previous epidemiological evidence from large population-based studies on the association between polycyclic aromatic hydrocarbons (PAH) exposure and the risk of sleep disorders is inadequate. To comprehensively examine the relationship between independent and combined PAHs and trouble sleeping, we analyzed data from 8194 participants from the National Health and Nutrition Survey (NHANES) cycles. Multivariate adjusted logistic regression and restricted cubic spline models were applied to assess the relationship between PAH exposure and the risk of trouble sleeping. Bayesian kernel machine regression and weighted quantile sum regression models were used to estimate the combined association of urinary PAHs with trouble sleeping. In the single-exposure analyses, compared with the lowest level, the respective adjusted odds ratios (ORs) for trouble sleeping among subjects from the highest quartile were 1.34 (95% CI, 1.15, 1.56), 1.23 (95% CI, 1.05, 1.44), 1.31 (95% CI, 1.11, 1.54), 1.35 (95% CI, 1.15, 1.58), and 1.29 (95% CI, 1.08, 1.53) for 1-hydroxynaphthalene (1-NAP), 2-hydroxynaphthalene (2-NAP), 3-hydroxyfluorene (3-FLU), 2-hydroxyfluorene(2-FLU), and 1-hydroxypyrene(1-PYR). An overall positive correlation between the PAH mixture and trouble sleeping was observed when the mixture was at the 50th percentile or higher. The current study reveals that PAH metabolites (1-NAP, 2-NAP, 3-FLU, 2-FLU, and 1-PYR) may be detrimental to trouble sleeping. PAH mixture exposure was positively associated with trouble sleeping. The results suggested the potential impacts of PAHs and expressed concerns regarding the potential impact of PAHs on health. More intensive research and monitoring of environmental pollutants in the future will contribute to preventing environmental hazards.

Effects of air pollution control policies on intracerebral hemorrhage mortality among residents in Tianjin, China.

BACKGROUND: Exposure to air pollution is an important risk factor for intracerebral hemorrhage (ICH), which is a major cause of death worldwide. However, the relationship between ICH mortality and air quality improvement has been poorly studied. This study aims to evaluate the impact of the air pollution control policies in the Beijing-Tianjin-Hebei region on ICH mortality among Tianjin residents. METHODS: This study used an interrupted time series analysis. We fitted autoregressive integrated moving average (ARIMA) models to assess the changes in ICH deaths before and after the interventions of air pollution control policies based on the data of ICH deaths in Tianjin collected by the Tianjin Center for Disease Control and Prevention. RESULTS: Between 2009 and 2020, there were 63,944 ICH deaths in Tianjin, and there was an overall decreasing trend in ICH mortality. The intervention conducted in June 2014 resulted in a statistically significant (p = 0.03) long-term trend change, reducing the number of deaths from ICH by 0.69 (95% confidence interval [CI]: -1.30 to -0.07) per month. The intervention in October 2017 resulted in a statistically significant (p = 0.04) immediate decrease of 25.74 (95% CI: -50.62 to -0.85) deaths from ICH in that month. The intervention in December 2017 caused a statistically significant (p = 0.04) immediate reduction of 26.58 (95% CI: -52.02 to -1.14) deaths from ICH in that month. The intervention in March 2018 resulted in a statistically significant (p = 0.02) immediate decrease of 30.40 (95% CI: -56.41 to -4.40) deaths from ICH in that month. No significant differences were observed in the changes of male ICH mortality after any of the four interventions. However, female ICH deaths showed statistically significant long-term trend change after the intervention in June 2014 and immediate changes after the interventions in December 2017 and March 2018. Overall, the interventions prevented an estimated 5984.76 deaths due to ICH. CONCLUSION: During the study period, some interventions of air pollution control policies were significantly associated with the reductions in the number of deaths from ICH among residents in Tianjin. ICH survivors and females were more sensitive to the protective effects of the interventions. Interventions for air pollution control can achieve public health gains in cities with high levels of air pollution.

Efficacy and toxicity of CLAG combined with pegylated liposomal doxorubicin in the treatment of refractory or relapsed acute myeloid leukemia.

BACKGROUND: Refractory and relapsed acute myeloid leukemia (r/rAML) is associated with a difficult prognosis; clinical trials are typically suggested despite lack of a recognized standard of care. Combinatorial chemotherapy regimens utilized for r/rAML salvage play a crucial role in battling this invasive phase. Although it is characterized by a low response rate, CLAG is a traditional regimen used in r/rAML. We aimed to compare the efficacy and toxicity of CLAG+PLD to explore whether there was any improvement with the addition of pegylated liposomal doxorubicin (PLD) to CLAG METHODS: A total of 110 r/rAML patients were retrospectively analyzed from February 2017 to June 2020 at the Medical Center of Hematology, XinQiao Hospital, the 303rd Hospital of the Chinese People's Liberation Army, and Central Hospital of Chang Sha, Hunan Province. The response, overall survival (OS), disease-free survival (DFS), and side effects in 110 r/rAML patients were evaluated retrospectively. Of these, 55 patients were administered CLAG+PLD, while 55 patients received CLAG alone as salvage therapy. RESULTS: In the CLAG+PLD group, there were 27 (49.1%) cases of complete response (CR) with no measurable residual disease (MRD-), 12 (21.8%) cases of CR with positive MRD (MRD+), 5 (9.1%) cases of partial response (PR), 11 (20%) cases of no response (NR), and no cases of death during the cycles. The response rates in the CLAG group were lower: CR was reached in 24 (46.6%) patients with MRD-, 6 (10.9%) patients with MRD+, 10 (18.2%) patients with PR, 13 (23.6%) patients with NR, and 2 (3.6%) patients who passed away, one from infection and the other from cerebral hemorrhage. The median OS and DFS were not attained in the CLAG+PLD group during the 2-year OS and DFS follow-up, while both values were 10 months in the CLAG group (p = 0.023 and p = 0.045, respectively). The results of the Cox regression analysis for the CLAG+PLD group were strongly illustrative of the importance of hematopoietic stem cell transplantation (HSCT) following salvage therapy. No increased toxicity was observed in the CLAG+PLD group. CONCLUSION: CLAG+PLD is a potential salvage regimen for r/r AML that has a similar toxicity profile to CLAG and that improves response rates, 2-year OS, and DFS relative to CLAG.

OsJRL40, a Jacalin-Related Lectin Gene, Promotes Salt Stress Tolerance in Rice.

High salinity is a major stress factor affecting the quality and productivity of rice (Oryza sativa L.). Although numerous salt tolerance-related genes have been identified in rice, their molecular mechanisms remain unknown. Here, we report that OsJRL40, a jacalin-related lectin gene, confers remarkable salt tolerance in rice. The loss of function of OsJRL40 increased sensitivity to salt stress in rice, whereas its overexpression enhanced salt tolerance at the seedling stage and during reproductive growth. ß-glucuronidase (GUS) reporter assays indicated that OsJRL40 is expressed to higher levels in roots and internodes than in other tissues, and subcellular localization analysis revealed that the OsJRL40 protein localizes to the cytoplasm. Further molecular analyses showed that OsJRL40 enhances antioxidant enzyme activities and regulates Na+-K+ homeostasis under salt stress. RNA-seq analysis revealed that OsJRL40 regulates salt tolerance in rice by controlling the expression of genes encoding Na+/K+ transporters, salt-responsive transcription factors, and other salt response-related proteins. Overall, this study provides a scientific basis for an in-depth investigation of the salt tolerance mechanism in rice and could guide the breeding of salt-tolerant rice cultivars.

Association of educational attainment with esophageal cancer, Barrett's esophagus, and gastroesophageal reflux disease, and the mediating role of modifiable risk factors: A Mendelian randomization study.

Background: Observational studies have reported that educational attainment has been related to the risk of esophageal cancer (EC) and its precancerous lesions. However, the causal relationship remains controversial. We aimed to apply the Mendelian randomization (MR) design to determine the causal associations between genetically predicted educational attainment and EC, Barrett's esophagus (BE), and gastroesophageal reflux disease (GERD), and to explore whether modifiable risk factors play a mediating role. Methods: Using summary statistics from genome-wide association studies (GWASs) based on European ancestry individuals of several years in education (EduYears, primary analysis, n = 293,723), college completion (College, secondary analysis, n = 95,427), EC (n = 420,531), BE (n = 361,194), and GERD (n = 420,531), genetic associations between two education phenotypes and EC, BE, and GERD were tested by two-sample MR analyses. Then, two-step MR mediation analyses were used to assess the proportion of the aforementioned association that might be mediated by body mass index (BMI), major depressive disorder (MDD), smoking, drinking, carbohydrates, fat, and protein intake. Results: Genetically predicted EduYears was negatively associated with the risk of EC, BE, and GERD {odds ratio (OR), 0.64 [95% confidence interval (CI) 0.44-0.94], 0.86 (95% CI, 0.75-0.99), and 0.62 (95%CI, 0.58-0.67)}. EduYears was negatively associated with BMI, MDD, and smoking (range of OR: 0.76-0.84). There were positive associations between BMI, smoking with EC, BE, and GERD, as well as between MDD with GERD (range of OR: 1.08-1.50). For individual mediating effect, BMI and smoking mediated 15.75 and 14.15% of the EduYears-EC association and 15.46 and 16.85% of the EduYears-BE association. BMI, MDD, and smoking mediated 5.23, 4.98, and 4.49% of the EduYears-GERD association. For combined mediation, the aforementioned mediators explained 26.62, 28.38, and 11.48% of the effect of EduYears on EC, BE, and GERD. The mediating effects of drinking and dietary composition were not significant in the effect of education on EC, BE, and GERD. Conclusion: Our study supports that genetically predicted higher educational attainment has a protective effect on EC, BE, and GERD, and is partly mediated by reducing adiposity, smoking, and depression.

Identification of Salt Tolerance Related Candidate Genes in 'Sea Rice 86' at the Seedling and Reproductive Stages Using QTL-Seq and BSA-Seq.

Salt stress seriously affects plant growth and development and reduces the yield of rice. Therefore, the development of salt-tolerant high-yielding rice cultivars through quantitative trait locus (QTL) identification and bulked segregant analysis (BSA) is the main focus of molecular breeding projects. In this study, sea rice (SR86) showed greater salt tolerance than conventional rice. Under salt stress, the cell membrane and chlorophyll were more stable and the antioxidant enzyme activity was higher in SR86 than in conventional rice. Thirty extremely salt-tolerant plants and thirty extremely salt-sensitive plants were selected from the F2 progenies of SR86 × Nipponbare (Nip) and SR86 × 9311 crosses during the whole vegetative and reproductive growth period and mixed bulks were generated. Eleven salt tolerance related candidate genes were located using QTL-seq together with BSA. Real time quantitative PCR (RT-qPCR) analysis showed that LOC_Os04g03320.1 and BGIOSGA019540 were expressed at higher levels in the SR86 plants than in Nip and 9311 plants, suggesting that these genes are critical for the salt tolerance of SR86. The QTLs identified using this method could be effectively utilized in future salt tolerance breeding programs, providing important theoretical significance and application value for rice salt tolerance breeding.

Trace elements in hair or fingernail and gastroesophageal cancers: results from a population-based case-control study.

BACKGROUND: Growing evidence suggests that environmental factors probably play important roles in the development of gastroesophageal cancers (GOC), however, the effects of trace elements on GOC remain unclear. OBJECTIVE: To assess the effect of trace elements on GOC and the effect modification by other factors. METHODS: Hair and fingernail samples were collected from GOC cases and controls in a population-based case-control study in Taixing, China, and were used to detect the concentrations of 12 trace elements using inductively coupled plasma mass spectrometry. Unconditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for concentrations of 12 trace elements in association with GOC after adjusting the other factors. RESULTS: A total of 830 hair samples (581 controls and 249 cases) and 895 fingernail samples (559 controls and 336 cases) were included. Compared to the lowest-tertile concentration, the higher tertiles of Ca, Zn, Fe, Al, Cr, Pb, Se, and V were positively associated with GOC, while the higher tertiles of Mg, Mn, Sr, and As were inversely associated with GOC. Significant interactions between the hair level of Cr and two other risk factors, including smoking (P for interaction = 0.044) and alcohol drinking (P for interaction = 0.028), were observed in association with GOC. SIGNIFICANCE: The current study reveals that these 12 trace elements in hair and fingernails are associated with GOC to varying degrees. Further studies and animal experiments are needed to clarify the associations and explore potential mechanisms. IMPACT STATEMENT: The role of trace elements in the development or inhibition of gastroesophageal cancers (GOC) remains unclear. In this study, we further explored the associations between 12 trace elements and GOC based on a population-based case-control study conducted in Taixing, China. Higher levels of Ca, Zn, Fe, Al, Cr, Pb, Se, and V were positively associated with increased GOC, while inverse associations between higher levels of Mg, Mn, Sr, As, and GOC were observed. Observed associations were consistent in hair and fingernail samples. Moreover, interaction effects between hair level of Cr and smoking or alcohol drinking were identified.

Burden of lung cancer along with attributable risk factors in China from 1990 to 2019, and projections until 2030.

OBJECTIVE: This study aimed to identify and project the epidemiological trends and the burden of lung cancer in China. METHODS: We extracted incidence, mortality, disability-adjusted life-years (DALYs) and age-standardized rates of lung cancer in China, between 1990 and 2019, from the Global Burden of Disease Study (2019). The estimated annual percentage change (EAPC) was applied to quantify the trends of lung cancer burden. Furthermore, we used the Bayesian age-period-cohort model to project the incidence and mortality in the next decade. RESULTS: From 1990 to 2019, the estimated national number of lung cancer incident cases increased by 224.0% to 832,920, deaths increased by 195.4% to 757,170 and DALYs increased by 146.1% to 17,128,580, respectively. Meanwhile, the ASIR, ASMR and ASDR showed an upward trend (EAPC of 1.33, 0.94 and 0.42, respectively). The ASIR and ASMR among males were about 2 times more than females, but the increase in ASIR in females (EAPC = 2.24) was more obvious than those in males (EAPC = 0.10) from 2020 to 2030. In China, smoking remained responsible for the highest burden of lung cancer, but the contribution of ambient particulate matter pollution to DALYs increased from 10.6% in 1990 to 22.5% in 2019 in total population. Moreover, we predicted that the number of deaths from lung cancer will increase by 42.7% in China by 2030. CONCLUSION: In China, the burden of lung cancer has been increasing over the past three decades, which highlights more targeted intervention measures are needed to reduce the burden of lung cancer.

Associations between traditional Chinese medicine body constitution and obesity risk among US adults.

Background: Traditional Chinese medicine (TCM) body constitution (BC), primarily determined by physiological and clinical characteristics, is an important process for clinical diagnosis and treatment and play a critical role in precision medicine in TCM. The purpose of the study was to explore whether the distributions of BC types differed by obesity status. Methods: We conducted a study to evaluate BC type in US population during 2012-2016. A total of 191 White participants from Personalized Prevention of Colorectal Cancer Trial (PPCCT) completed a self-administered Traditional Chinese Medicine Questionnaire (TCMQ, English version). In this study, we further compared the distribution of major types of TCM BC in the PPCCT to those Chinese populations stratified by obesity status. Results: We found the Blood-stasis frequency was higher in US White adults, 22.6% for individuals with BMI <30 and 11.2% for obese individuals, compared to 1.4% and 1.8%, respectively, in Chinese populations. We also found the percentages Inherited-special and Qi-stagnation were higher in US White adults than those in Chinese populations regardless of obesity status. However, the proportions of Yang-deficiency were higher in Chinese populations than those in our study conducted in US White adults regardless of obesity status. Conclusions: These new findings indicate the difference in distribution of BC types we observed between US and Chinese populations cannot be explained by the differences in prevalence of obesity. Further studies are needed to confirm our findings and understand the potential mechanism including genetic background and/or environmental factors.