Ferroptosis-associated lncRNA prognostic signature predicts prognosis and immune response in laryngeal squamous carcinoma.

In order to construct a prognostic model of ferroptosis-related lncRNA associated with laryngeal carcinoma and to investigate its prognostic value, RNA sequencing, genomic mutation, and clinical data of laryngeal squamous carcinoma patients were collected from the TCGA database. Patients were randomly divided into train and test groups. Cox regression analysis and lasso regression analysis were performed on the data of patients in the training group, and their independent prognostic effect was validated in the test group and the whole cohort. Data from 123 laryngeal squamous carcinoma patients in the TCGA database were collected. According to previous literature, 484 ferroptosis-related genes were collected, and 912 ferroptosis-related lncRNAs were obtained by co-expression. Cox models suggested six lncRNAs involved in ferroptosis (AC083862.2, CYTOR, AC114296.1, LINC02768, GATA2-AS1, CTB-178M22.2). Patients were divided into high-risk and low-risk groups based on median risk scores. Kapkan-Meier survival curve results showed a statistical difference in survival between the high- and low-risk groups. Receiver operating characteristic curves and principal component analysis demonstrated the high accuracy of the model. Univariate and multifactorial Cox regression analyses and column plots demonstrated risk scores as independent prognostic factors. The distribution of prognostic marker risk scores was correlated with clinical staging. Immune infiltration studies suggested the model was associated with immune checkpoints and multiple immune functions. GATA2-AS1 was able to promote cell proliferation, cell migration, and cell invasion. This study identified six lncRNAs associated with ferroptosis in laryngeal squamous carcinoma as prognostic predictors, which may be promising biomarkers involved in the treatment of laryngeal squamous carcinoma.

Association Between Urinary Stress Incontinence and Levator Avulsion Detected by 3D Transperineal Ultrasound.

PURPOSE: To determine the association between levator avulsion and urinary stress incontinence (USI) by 3/4D transperineal ultrasound. MATERIALS AND METHODS: 842 patients who were admitted to our hospital from 2016 to 2019 were recruited for our study. 3D/4D transperineal ultrasound was performed. After standard interview and clinical evaluation, general conditions and levator hiatus data were collected and measured to compare with each group. The odds ratio (OR) of USI symptoms or ultrasound features with levator avulsion were calculated. RESULTS: A total of 593 women were studied: 204 suffered from levator avulsion (96 cases of left-side avulsion, 80 cases of right-side avulsion and 28 cases of bilateral avulsion) and 389 women had no avulsion. The gravidity and episiotomy conditions of the avulsion groups were significantly different from the no-avulsion group. Significant differences were found in the transverse diameters and anteroposterior diameters between the levator avulsion group and the no-avulsion group, but there was no difference among the avulsion groups, regardless of whether the patient was at rest or performing the Valsalva maneuver. Interestingly, a significant difference was found in the presence of USI symptoms between the uni-avulsion group and the no-avulsion group. The odds ratio (OR) of USI symptoms in the uni-avulsion group is 2.786 (95 %CI, 1.663-4.669), but 0.939 (95 %CI, 0.276-3.199) for the bilateral avulsion and no-avulsion groups. CONCLUSION: Unilateral levator avulsion may be a risk factor for urinary stress incontinence.

A new treatment of an intravesical eroded mesh after TVM: 3 mm trocar-assisted cystoscopic approach.

INTRODUCTION AND HYPOTHESIS: To present a novel technique to remove intravesical eroded mesh through a 3-mm trocar-assisted cystoscopy. METHODS: First, a 3-mm trocar was inserted into the bladder under ultrasound guidance after the bladder had been infused with 600 ml normal saline. Second, we inserted the forceps through the trocar into the bladder and pulled the mesh through the 3-mm trocar. Last, cystoscopic scissors were used to remove the eroded mesh completely. RESULTS: The patient was managed adequately in the inpatient department. The urethral catheter was left in situ for 3 days, and the patient was discharged within 5 days. CONCLUSION: Surgery under 3-mm trocar-assisted cystoscopy offers the advantage of lower risk of morbidity and complications compared to other surgical techniques. It is an effective and feasible procedure for treatment of synthetic mesh erosion into the bladder after TVM surgery.

Incidence and prognosis of thyroid cancer in children: based on the SEER database.

OBJECTIVE: To update the recognition of the trends in the incidence of childhood thyroid cancer (TC) and its prognosis. METHODS: A large-scale sample based on long time-line public database was recruited. Join-point regression model was used to analyze the incidence trend of childhood TC. Univariable and multivariable Cox regression model analyses were applied to explore the survival situation and prognostic factors. RESULTS: The incidence rate of childhood TC increased between 1975 and 2016 from 3.8/million (95% CI 2.6-5.5) to 11.5/million (95% CI 9.2-14.1), AAPC = 2.38% (95% CI 1.98-9.65) and could be divided into two stages of increasing trends. The incidence rate of Trend1 (1975-2005) increased slowly (APC = 1.08%, 95% CI 0.38-1.82) while Trend2 (2005-2016) increased dramatically (APC = 6.77%, 95% CI 4.30-9.28). Annual incidence rate of small size tumor (< 4 cm) and local stage childhood TC increased significantly. The overall cumulative survival rate for childhood TC was high up to 97-99%. Males, black race, MTC type, distant metastasis, tumor size ≥ 4 cm, non-primary cancer were the independent risk factors of childhood TC prognosis. CONCLUSION: A contribution of overdetection to rising pediatric TC rates might not be able to rule out. For clinical implications, screening TC in children with potential specific risk factors is feasible. Over-treatment to small size and local stage TC in children should be avoided.

H19/miR-107/HMGB1 axis sensitizes laryngeal squamous cell carcinoma to cisplatin by suppressing autophagy in vitro and in vivo.

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor, which occurs in the head and neck. Current treatments for LSCC are all largely weakened by increasing drug resistance. Our study aimed to investigate the effects of long noncoding RNA (lncRNA) H19 on drug resistance in LSCC. In our study, we found that the level of H19 was sharply upregulated in LSCC tissues and drug-resistant cells compared with the control. Besides, the expression of high-mobility group B1 (HMGB1) was elevated, and microRNA107 (miR-107) was suppressed in drug-resistant cells compared with the control. Further study revealed that the interference of H19 by short hairpin RNA (shRNA) effectively suppressed high autophagy level and obvious drug resistance in drug-resistant cells. Besides that, miR-107 was predicted as a target of H19 and inhibiting effects of H19 shRNA on autophagy and drug resistance were both reversed by miR-107 inhibitor. Moreover, HMGB1 was predicted as a target of miR-107 in LSCC cells and knockdown of HMGB1 was able to suppress autophagy and drug resistance in LSCC cells. In addition, our investigation demonstrated that H19 shRNA exerted an inhibiting effect on autophagy and drug resistance by downregulating HMGB1 by targeting miR-107. Finally, the in vivo experiment revealed that LV-H19 shRNA strongly suppressed drug resistance compared with the usage of cisplatin individually. Taken together, our research indicated an H19-miR-107-HMGB1 axis in regulating the autophagy-induced drug resistance in LSCC in vitro and in vivo, providing novel targets for molecular-targeted therapy and broadening the research for LSCC.

The impact of the COVID-19 pandemic on the mental health of young people: A comparison between China and the United Kingdom.

PURPOSE: As COVID-19 spreads globally and affects people's health, there are concerns that the pandemic and control policies may have psychological effects on young people (age from 17 to 35 years). This psychological impact might vary in different countries, and thus we compared the prevalence of self-reported psychological distress, loneliness and posttraumatic stress symptoms (PTSS) among young people in the United Kingdom (UK) and China at the beginning of the COVID-19 pandemic. METHODS: Data of this study came from two sources. One source was the first wave of COVID-19 study in Understanding Society, a special wave of the UK household longitudinal study, which provided the high-quality, national-wide representative panel data. The sample comprised 1054 young people. The other source was an online survey on the mental health of 1003 young people from Shanghai, a highly developed area in China. The questionnaire included questions on the prevalence of common mental disorders (cut-off score ≥ 4), loneliness and potential PTSS (cut-off ≥ 33). Univariable analyses were conducted to test the differences in the self-reported prevalence of psychological distress and loneliness between the two groups. Multivariable logistic regression analyses were run to explore the predictors of psychological distress and loneliness among all the young people from England and Shanghai. RESULTS: Among the samples with self-reported psychological distress, the UK sample accounted for 34.4% (n=1054) and the Chinese sample accounted for 14.1% (n=1003). The difference between the two groups was statistically significant (p < 0.001). Additionally, 57.1% of people in the UK and 46.7% in China reported that they sometimes or often felt lonely, of which the difference is statistically significant (p < 0.001). Regression analysis of the entire samples showed that nationality, gender, psychotherapy and loneliness were significant predictors of 12-item General Health Questionnaire scores, while the variables of age and living alone were not. Significant predictors of self-reported loneliness were the nationality, gender, age, living alone and psychotherapy. In China, 123 (12.3%) young people, 49 men (11.3%) and 74 women (13.0%), met the criteria of PTSS symptoms (cut-off scores ≥ 33). These scores were only collected in China. CONCLUSION: This evidence suggests that mental health and loneliness reported by young people were lower in China than that in the UK during the studied period. More research is needed to understand these differences. If the differential negative psychological impacts are confirmed, country-specific measures of prevention and intervention should be adopted to improve the mental health of young people under the ongoing impact of the pandemic.

Forefoot Replantation in a 3-Year-Old Boy: Case Report.

Few reports about successful forefoot replantation in children have been published. In this article, we present a case of a 3-year-old boy with severe complete amputation of the left forefoot from a crushed and degloved injury in a motorcycle accident. The replantation was successfully performed, even though total ischemia time lasted 8 hours, of which 4 hours was cold ischemia time. The child was able to walk without significant difficulties from 4 months postoperatively and led a normal life in school at 2 years of follow-up. In this case, we present the replantation of a high-velocity traumatic partial foot amputation in a child with excellent function and cosmetic outcome.

Comprehensive analysis of differentially expressed profiles of lncRNAs, mRNAs, and miRNAs in laryngeal squamous cell carcinoma in order to construct a ceRNA network and identify potential biomarkers.

OBJECTIVE: This study aimed to uncover a regulatory network comprised of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in laryngeal squamous cell carcinoma (LSCC), to explore its underlying mechanisms and development, and to identify key genetic biomarkers for the prognosis of LSCC. METHODS: Here, we compared mRNA, lncRNA, and miRNA expression profiles between 111 LSCC and 12 adjacent normal tissues using RNA sequencing (RNA-Seq) data from the Cancer Genome Atlas (TCGA) database. Based on the interaction information obtained from miRcode, TargetScan, miRTarBase, and miRDB, a lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed using differentially expressed lncRNAs (DElncRNA), miRNAs (DEmiRNA), and mRNAs (DEmRNA). By assessing the functional enrichment of DEmRNAs in this network, the potential underlying mechanisms were explored. In addition, Kaplan-Meier survival analysis was used to assess genetic biomarkers related to the prognosis of LSCC patients. RESULTS: Upon comparing LSCC and control tissues, 1640 DElncRNAs, 75 DEmiRNAs, and 3217 DEmRNAs were identified. Based on the prediction between lncRNA-miRNA and miRNA-mRNA relationships, we constructed a ceRNA network comprised of 93 lncRNAs, nine miRNAs, and nine mRNAs. This network predicted that two lncRNAs (AC016773.1 and C00299), two mRNAs (DIO1 and STC2), and two miRNAs (hsa-mir-137 and hsa-mir-210) were significant biomarkers of LSCC prognosis according to thorough topological and survival analyses (P < .05). CONCLUSION: Through a ceRNA network analysis, our study identifies new lncRNAs, miRNAs, and mRNAs, which can be used as potential biomarkers of LSCC and as therapeutic targets for treating LSCC, thus laying a foundation for future clinical studies.

Radiomics Analysis of Multiparametric MRI Evaluates the Pathological Features of Cervical Squamous Cell Carcinoma.

BACKGROUND: Robust parameters to evaluate pathological aggressiveness are needed to provide individualized therapy for cervical cancer patients. PURPOSE: To investigate the radiomics analysis of multiparametric MRI to evaluate tumor grade, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis of cervical squamous cell carcinoma (CSCC). STUDY TYPE: Retrospective. SUBJECTS: Fifty-six patients with histopathologically confirmed CSCC. FIELD STRENGTH/SEQUENCE: 3T, axial T2 and T2 with fat suppression (FS), diffusion-weighted imaging (DWI) (multi-b values), axial dynamic contrast enhanced (DCE) MRI (8 sec temporal resolution). ASSESSMENT: Regions of interest were drawn around the tumor on each axial slice and fused to generate the whole tumor volume. Sixty-six radiomics features were derived from each image sequence, including axial T2 and T2 FS, ADC maps, and Ktrans , Ve , and Vp maps from DCE MRI. STATISTICAL TESTS: A univariate analysis was performed to assess each parameter's association with tumor grade and the presence of lymphovascular space invasion (LVSI) and lymph node (LN) metastasis. A principal component analysis was employed for dimension reduction and to generate new discriminative valuables. Using logistic regression, a discriminative model of each parameter was built and a receiver operating characteristic curve (ROC) was generated. RESULTS: The area under the ROC curve (AUC) of anatomical, diffusion, and permeability parameters in discriminating the presence of LVSI ranged from 0.659 to 0.814, with Ve showing the best discriminative value. The AUC in discriminating the presence of LN metastasis and distinguishing tumor grade ranged from 0.747 to 0.850, 0.668 to 0.757, with ADC and Ve showing the best discriminative value, respectively. DATA CONCLUSION: Functional maps exhibit better discriminative values than anatomical images for discriminating the pathological features of CSCC, with ADC maps showing the best discrimination performance for LN metastasis and Ve maps showing the best discriminative value for LVSI and tumor grade. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1141-1148.

Differentiating metastatic from nonmetastatic lymph nodes in cervical cancer patients using monoexponential, biexponential, and stretched exponential diffusion-weighted MR imaging.

OBJECTIVES: To determine the diagnostic value of monoexponential, biexponential and stretched exponential models for identifying lymph nodes (LNs) in patients with cervical cancer. MATERIALS AND METHODS: Fifty female patients with cervical cancer underwent preoperative magnetic resonance imaging. The diffusion parameters of the LNs were calculated by fitting the values to monoexponential, biexponential and stretched exponential models and were compared between the metastatic and non-metastatic LN groups. RESULTS: A total of 157 LNs with high signal intensity on multi-b-value DWI were detected, 41 of which were pathologically shown to be metastatic. Metastatic LNs presented with higher pure water diffusion (D) values, lower perfusion fraction (f) values, higher diffusion heterogeneity (α) values, higher short diameter (Size-S), long diameter (Size-L) and short long diameter ratio (S/L Ratio) than non-metastatic LNs (P<0.05). The Size-S of LNs exhibited the highest diagnostic value, with an area under the curve of 0.844. CONCLUSIONS: Compared with the size parameters, the diffusion parameters derived from multi-b-value diffusion-weighted imaging cannot reliably discriminate metastatic from non-metastatic LNs in daily clinical routine due to limited sensitivity and specificity. KEY POINTS: • Biexponential and stretched exponential diffusion models can help to characterise LN status. • Metastatic LNs present with higher D and α values, lower f values. • Diffusion parameters were less reliable in discriminating LNs than size parameters.

Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging of Cervical Cancer With Different b-Values.

OBJECTIVE: The aims of this study were to evaluate the dependence of diffusion parameters on the b values adopted for intravoxel incoherent motion diffusion-weighted magnetic resonance imaging and to investigate the application value of multiple diffusion parameters obtained from monoexponential and biexponential models in subjects with a normal cervix and in cervical cancer patients. METHODS: A total of 120 female patients with cervical cancer and 21 female control subjects with a normal cervix underwent diffusion-weighted magnetic resonance imaging with 13 b values (0-2000 s/mm) at 3 T. The standard apparent diffusion coefficient (Dst), diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were calculated by fitting with monoexponential and biexponential models at 2 different ranges of b values: 0 to 1000 and 0 to 2000 s/mm. A univariate analysis was performed to identify factors that could distinguish cervical carcinoma from normal cervical tissue. Parameters that correlated with the pathological grade and stage of cervical cancer were also evaluated. Receiver operating characteristic curves were used to evaluate the diagnostic efficiency of every parameter. RESULTS: All the tested parameters, except the D* of the 2 different ranges of b value groups, significantly differed between the patients with cervical carcinoma and control subjects (P < 0.01). D2000, Dst2000, and D1000 showed comparable diagnostic value, with an area under the curve of 0.923, 0.909, and 0.907, respectively. Dst2000, D2000, Dst1000, and D1000 differed significantly among the 3 degrees of cervical stromal infiltration depth (P < 0.05). CONCLUSIONS: D2000 and Dst2000 tended to outperform D1000 in terms of diagnostic efficiency, but there was no significant difference in their ability to differentiate cervical carcinoma from normal cervix. Cervical cancers with lower Dst and D values tended to have greater infiltration depth.

Hypoxia-Responsive Mir-301a and Mir-301b Promote Radioresistance of Prostate Cancer Cells via Downregulating NDRG2.

BACKGROUND MiR-301a and miR-301b are 2 oncomiRs involved in multiple types of cancer. In this study, we explored the expression change of miR-301a and miR-301b in prostate cancer cells in hypoxia and studied their regulation of autophagy and radiosensitivity of prostate cancer cells. MATERIAL AND METHODS QRT-PCR was performed to quantify the expression change of miR-301a and miR-301b in hypoxia. Their effects on autophagy were measured by Western blot analysis, and their effects on radiosensitivity were measured by clonogenic assay and flow cytometry. In addition, the regulation of miR-301a and miR-301b on NDRG2, a tumor-suppressor gene in prostate cancer, was also studied. The effect of miR-301a/b-NDRG2 axis on autophagy and radiosensitivity of prostate cancer cells was further investigated. RESULTS MiR-301a and miR-301b are 2 hypoxia responsive miRNAs that are significantly upregulated in hypoxia in prostate cancer cells. Higher level of miR-301a and miR-301b expression results in elevated autophagy and increased radioresistance in LNCaP cells. MiR-301a and miR-301b simultaneously target NDRG2 and decrease its expression. Knockdown of NDRG2 leads to increased autophagy and radioresistance. CONCLUSIONS MiR-301a and miR-301b are 2 hypoxia-responsive miRNAs that decrease autophagy of prostate cancer cells in hypoxia by targeting NDRG2. Through downregulating NDRG2, miR-301a and miR-301b can promote radioresistance of prostate cancer cells.

[Change on burden of diseases from hypercholesterolemia among the Chinese population from 1990 to 2010].

OBJECTIVE: To quantify the change on burden of disease from hypercholesterolemia in China from 1990 to 2010. METHODS: Related data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010). Population attributable risk was adopted to estimate the burden of disease from hypercholesterolemia. RESULTS: The death and burden of disease from hypercholesterolemia for Chinese residents increased from 98 000 and 2.237 million disability-adjusted of life years (DALY) in 1990 to 281 000 and 5.912 million DALY respectively. In 2010, 251 000 ischemic heart disease and 30 000 ischemic stroke deaths were caused by hypercholesterolemia, accounted for 3.4% (28.1/830.2) of the total deaths. In 2010, the DALY of ischemic heart disease and ischemic stroke attributed to hypercholesterolemia was 5.169 million and 0.743 million respectively. DALY was 3.356 million in male and 2.555 million in female. Years of life lost due to premature mortality (YLL) was 5.268 million, and years lived with disability (YLD) was 0.644 million. CONCLUSION: Hypercholesterolemia is a major risk factor for deaths and life loss in 2010, and the burden of disease and death from hypercholesterolemia increased obviously from 1990 to 2010 in China.

[Analysis of trends and characteristics of mortality of ischemic heart disease over the age of 35 years old in China, 2004-2011].

OBJECTIVE: To analyze the features of distribution and variation trends of mortality of ischemic heart disease over the age of 35 years old in China, 2004-2011. METHODS: A total of 493 274 cases were recruited in the study, the mortality data of the ischemic heart diseases were collected from the national disease surveillance point (DSP) system between 2004 and 2011. The change of ischemic heart disease standardized mortality was described, and the annual change percentage of age group mortality and standardized mortality were analyzed using log linear regression method. RESULTS: In 2004-2011, the standardized mortality of ischemic heart disease over the age of 35 showed an upward trend in each regions of China.In 2004, the ischemic heart disease standardized mortality over the age of 35 was 176.2/100 000 among males and 131.7/100 000 among females in urban areas, and the figures increased to 204.6/100 000 and 147.9/100 000 respectively in 2011.In 2004, the ischemic heart disease standardized mortality over the age of 35 was 164.4/100 000 among males and 122.2/100 000 among females in rural areas, and the figures increased to 236.8/100 000 and 151.5/100 000 respectively in 2011. The ischemic heart disease standardized mortality was lower in rural regions than in urban regions in 2004, but it changed to be higher in rural regions than in urban regions in 2011 both in males and female. The annual growth rate of ischemic heart disease mortality over the age of 35 was separately 5.00% in male and 3.65% in female. The annual growth rate was highest among males in rural areas (7.09%), followed by females in rural areas (5.06%). The growth rate was lowest among females in urban areas (1.69%).It was found that the increasing trends of ischemic heart disease mortality of males both in urban and rural areas, and females in rural areas was statistically significant (P < 0.05). CONCLUSION: The mortality of ischemic heart disease has still been showing an uprising trend, especially in the rural areas.

m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways.

As the second most prevalent malignant tumor of head and neck, laryngeal squamous cell carcinoma (LSCC) imposes a substantial health burden on patients worldwide. Within recent years, resistance to oxidative stress and N6-methyladenosine (m6A) of RNA have been proved to be significantly involved in tumorigenesis. In current study, we investigated the oncogenic role of m6A modified long non coding RNAs (lncRNAs), specifically HOXA10-AS, and its downstream signaling pathway in the regulation of oxidative resistance in LSCC. Bioinformatics analysis revealed that heightened expression of HOXA10-AS was associated with the poor prognosis in LSCC patients, and N (6)-Methyladenosine (m6A) methyltransferase-like 3 (METTL3) was identified as a factor in promoting m6A modification of HOXA10-AS and further intensify its RNA stability. Mechanistically, HOXA10-AS was found to play as a competitive endogenous RNA (ceRNA) by sequestering miR-29 b-3p and preventing its downregulation of Integrin subunit alpha 6 (ITGA6), ultimately enhancing the oxidative resistance of tumor cells and promoting the malignant progression of LSCC. Furthermore, our research elucidated the mechanism by which ITGA6 accelerates Keap1 proteasomal degradation via enhancing TRIM25 expression, leading to increased Nrf2 stability and exacerbating its aberrant activation. Additionally, we demonstrated that ITGA6 enhances γ-secretase-mediated Notch signaling activation, ultimately promoting RBPJ-induced TRIM25 transcription. The current study provides the evidence supporting the effect of m6A modified HOXA10-AS and its downstream miR-29 b-3p/ITGA6 axis on regulating oxidative resistance and malignant progression in LSCC through the Notch and Keap1/Nrf2 pathways, and proposed that targeting this axis holds promise as a potential therapeutic approach for treating LSCC.

Summary of the 2022 Report on Cardiovascular Health and Diseases in China.

ABSTRACT: Recent decades have seen the remarkable development of China in medical accessibility and quality index, and the application of a number of new advanced cardiovascular technologies benefits more patients. However, according to the Annual Report on Cardiovascular Health and Diseases in China published in this article, which was organized and summarized by National Center for Cardiovascular Diseases, there is still a huge population living with risk factors of cardiovascular diseases (CVD), and the morbidity and mortality of CVD are increasing. It is estimated that there are around 330 million patients suffering from CVD currently, including 245 million of hypertension, 13 million of stroke, 45.3 million of peripheral artery disease, 11.39 million of coronary heart disease (CHD), 8.9 million of heart failure, 5 million of pulmonary heart disease, 4.87 million of atrial fibrillation, 2.5 million of rheumatic heart disease, and 2 million of congenital heart disease. Tobacco use, diet and nutrition factors, physical activity, overweight and obesity, and psychological factors are what affect cardiovascular health, while hypertension, dyslipidemia, diabetes, chronic kidney disease, metabolic syndrome, and air pollution are the risk factors for CVD. In this article, in addition to risk factors for CVD, we also report the epidemiological trends of CVD, including CHD, cerebrovascular disease, arrhythmias, valvular heart disease, congenital heart disease, cardiomyopathy, heart failure, pulmonary vascular disease and venous thromboembolism, and aortic and peripheral artery diseases, as well as the basic research and medical device development in CVD. In a word, China has entered a new stage of transforming from high-speed development focusing on scale growth to high-quality development emphasizing on strategic and key technological development to curb the trend of increasing incidence and mortality of CVD.

Quantitative Characterization of Elemental Segregation in Inconel 718 Superalloy by Micro-Beam X-ray Fluorescence Spectroscopy and Its Correlation Study.

Inconel 718 (IN718) nickel-based superalloy is widely used in aerospace and nuclear applications owing to its excellent comprehensive mechanical properties, oxidation resistance, and hot corrosion resistance. However, the elemental segregation caused by heterogeneous solidification during casting has great influence on the mechanical properties. Therefore, accurately characterizing the segregation behavior is necessary. Traditional quantitative characterization of elemental segregation uses various sampling methods, in which only macroscopic segregation results are obtained. In this study, micro-beam X-ray fluorescence (µ-XRF) is used for the quantitative characterization of element micro-segregation in IN718 superalloy. The concentration distributions of Cr, Fe, Mo, Nb, and Ti in IN718 alloy are determined with optimized testing parameters, and the degree of elemental segregation in different regions of the analytical area is calculated. It is found that the segregation degree of Nb and Ti in the testing area is larger than other alloying elements. The correlation between the microstructure distribution and the segregation degree of Nb and Ti has been studied using scanning electron microscopy (SEM) combined with energy-dispersive spectrometry (EDS). There is severe segregation of Nb and Ti in areas where Nb-containing precipitates are accumulated. The distribution of abnormal signals of Nb with a high fluorescence intensity has a close relationship with the area of precipitates-enriched Nb.

Rapid increasing burden of diabetes and cardiovascular disease caused by high body mass index in 1.25 million Chinese adults, 2005-2018.

BACKGROUND: Temporal trends and geographical variations in disease burden for diabetes mellitus (DM) and cardiovascular disease (CVD) attributable to high body mass index (BMI) in China have not been fully elucidated. METHODS: We estimated deaths and years of life lost (YLLs) for DM and CVD attributable to high BMI by age, sex, year, and region from 2005 to 2018 based on pooled data of 1.25 million adults. FINDINGS: Approximately 497,430 (95% uncertainty interval [UI], 470,520-525,720) deaths for DM and CVD were attributable to high BMI in China in 2018, with 453,750 deaths from CVD and 43,700 deaths from DM. Between 2005 and 2018, there was a 17.35% increase in age-standardized mortality rate for DM and CVD attributable to high BMI. The high BMI-related DM and CVD YLL rates increased from 127.46 (95% UI 108.70-148.62) per 100,000 people aged 20-24 years to 5,735.54 (95% UI 4,844.16-6,713.53) per 100,000 people aged ≥80 years, respectively. The highest age-standardized mortality rate for high BMI-related DM and CVD in northeast, northwest, and circum-Bohai Sea regions of China. CONCLUSION: The disease burden for DM and CVD attributable to high BMI increased substantially between 2005 and 2018. Urgent measures are required at both national and regional levels for resource mobilization to slow the growing burden. FUNDING: The work was supported by the National Key Research and Development Program of China, China National Science & Technology Pillar Program, and National Health Commission of the People's Republic of China.

GLTP Is a Potential Prognostic Biomarker and Correlates with Immunotherapy Efficacy in Cervical Cancer.

Cervical cancer (CC) is the fourth most commonly diagnosed cancer in women worldwide. The prognosis of CC patients remains poor. The objective of our study was to explore the potential of glycolipid transfer protein (GLTP) in predicting the prognosis of CC and patients' response to immunotherapy. The expression of GLTP was determined using TCGA and GEO datasets. The prognostic value of GLTP in CC patients was analyzed using Kaplan-Meier analysis and multivariate analysis. The relationships between BTBD10 and immunological checkpoints, immune checkpoint genes, and ferroptosis-related genes were analyzed to explore the impact of GLTP on CC immunotherapy. According to the dysregulated expressions of BTBD10, the IC50 distribution of various targeted medicines was studied. In this study, we found that GLTP expression was distinctly upregulated in CC specimens. However, Kaplan-Meier assays showed that CC patients with low GLTP expressions tended to exhibit a shorter overall survival. Importantly, multivariate assays revealed that GLTP expression was an independent prognostic factor for CC patients. Moreover, we observed that GLTP expression was related to CD4+ T cells, macrophages, and dendritic cells (DCs). Meanwhile, GLTP expressions were associated with those of immune checkpoints, ferroptosis-related genes, and m6A-related genes. The IC50 of Cisplatin, Docetaxel, and Paclitaxel was lower in the high-GLTP-expressing group. Taken together, GLTP was expected to be a prognostic and immunotherapeutic marker for CC.

Engineering CRISPR immune systems conferring GLRaV-3 resistance in grapevine.

Grapevine leafroll-associated virus 3 (GLRaV-3) is one of the causal agents of grapevine leafroll disease (GLD), which severely impacts grapevine production in most viticultural regions of the world. The development of virus-resistant plants is a desirable strategy for the efficient control of viral diseases. However, natural resistant resources have not been reported in the genus Vitis, and anti-GLRaV-3 research has been quite limited in grapevine. In this study, by expressing FnCas9 and LshCas13a, we established a highly effective transgenic construct screening system via an optimized Agrobacterium-mediated transient delivery system in grapevine plantlets. Our study indicated that CRISPR/FnCas9 and LshCas13a caused GLRaV-3 inhibition. Moreover, three vectors-pCR01-CP, pCR11-Hsp70h and pCR11-CP-exhibited the most robust inhibition efficiency compared to those targeting other sites and could be further engineered to generate GLRaV-3-resistant grapevine. In addition, the viral interference efficiency of FnCas9 was dependent on its RNA binding activity. The efficiency of virus inhibition was positively correlated with the level of Cas gene expression. Importantly, we demonstrated that LshCas13a had better interference efficiency against viruses than FnCas9. In summary, this study confirmed that these two RNA-targeting CRISPR mechanisms can confer immunity against viruses in grapevine, providing new avenues to control GLRaV-3 or other RNA viruses in fruit crops.