Age-related wall shear stress changes assessed by vascular vector flow mapping in the carotid arteries of healthy adults: a cross-sectional study.

Background: Wall shear stress (WSS) is related to the pathogenesis of atherosclerosis. WSS is affected by a variety of hemodynamic factors, and there is still a lack of accurate and objective methods for measuring it. This study sought to evaluate hemodynamic changes in WSSmaximum (max), WSSmean, WSSminimum (min) in the common carotid artery of healthy adults of different ages using vascular vector flow mapping (VFM). Methods: A retrospective analysis was conducted on 70 healthy volunteers aged 20-89 years who were recruited from our Ultrasound Department between February 2021 and June 2021. An ultrasound system with a 3-15 MHz probe was used to determine regions of interest (ROIs) of the common carotid artery. VFM-based WSS measurements were obtained by selecting ROIs with optimal image quality from three full cardiac cycles. The participants were divided into the following seven age groups: the 20s group, the 30s group, the 40s group, the 50s group, the 60s group, the 70s group, and the 80s group. The WSS parameters were compared among the age groups. An analysis of variance or a Kruskal-Wallis test was used to evaluate the difference among the groups, and a Pearson analysis and linear regression were used for the correlation and trend analysis. Results: The WSS parameters were quantified using vascular VFM software. The WSSmax, WSSmean, WSSmin differed among the age groups and gradually decreased with age, the elderly were significantly lower than the young. The Pearson correlation coefficient of the WSSmax and age was -0.556 (P<0.001), that of the WSSmean and age was -0.461 (P<0.001), and that of the WSSmin and age was -0.308 (P<0.001). The WSS parameters with age are negatively correlated the carotid intima-media thickness differed between the groups. Conclusions: The carotid WSSmax, WSSmean, WSSmin can be quantitatively and visually analyzed using the vascular VFM technique. In healthy adults of different ages, the carotid WSSmax, WSSmean, WSSmin decreased with age. Our findings about the normal values of carotid WSS maybe have clinical reference value for future studies.

Prediction models of intravenous glucocorticoids therapy response in thyroid eye disease.

Background: Thyroid eye disease (TED) is an autoimmune orbital disease, with intravenous glucocorticoid (IVGC) therapy as the first-line treatment. Due to uncertain response rates and possible side effects, various prediction models have been developed to predict IVGC therapy outcomes. Methods: A thorough search was conducted in PubMed, Embase, and Web of Science databases. Data extraction included publication details, prediction model content, and performance. Statistical analysis was performed using R software, including heterogeneity evaluation, publication bias, subgroup analysis, and sensitivity analysis. Forest plots were utilized for result visualization. Results: Of the 12 eligible studies, 47 prediction models were extracted. All included studies exhibited a low-to-moderate risk of bias. The pooled area under the receiver operating characteristic curve (AUC) and the combined sensitivity and specificity for the models were 0.81, 0.75, and 0.79, respectively. In view of heterogeneity, multiple meta-regression and subgroup analysis were conducted, which showed that marker and modeling types may be the possible causes of heterogeneity (P < 0.001). Notably, imaging metrics alone (AUC = 0.81) or clinical characteristics combined with other markers (AUC = 0.87), incorporating with multivariate regression (AUC = 0.84) or radiomics analysis (AUC = 0.91), yielded robust and reliable prediction outcomes. Conclusion: This meta-analysis comprehensively reviews the predictive models for IVGC therapy response in TED. It underscores that integrating clinical characteristics with laboratory or imaging indicators and employing advanced techniques like multivariate regression or radiomics analysis significantly enhance the efficacy of prediction. Our research findings offer valuable insights that can guide future studies on prediction models for IVGC therapy in TED.

Risk predictive model for the development of hepatocellular carcinoma before initiating long-term antiviral therapy in patients with chronic hepatitis B virus infection.

It is generally acknowledged that antiviral therapy can reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), there remains a subset of patients with chronic HBV infection who develop HCC despite receiving antiviral treatment. This study aimed to develop a model capable of predicting the long-term occurrence of HCC in patients with chronic HBV infection before initiating antiviral therapy. A total of 1450 patients with chronic HBV infection, who received initial antiviral therapy between April 2006 and March 2023 and completed long-term follow-ups, were nonselectively enrolled in this study. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis was used to construct the model. The results were validated in an external cohort (n = 210) and compared with existing models. The median follow-up time for all patients was 60 months, with a maximum follow-up time of 144 months, during which, 32 cases of HCC occurred. The nomogram model for predicting HCC based on GGT, AFP, cirrhosis, gender, age, and hepatitis B e antibody (TARGET-HCC) was constructed, demonstrating a good predictive performance. In the derivation cohort, the C-index was 0.906 (95% CI = 0.869-0.944), and in the validation cohort, it was 0.780 (95% CI = 0.673-0.886). Compared with existing models, TARGET-HCC showed promising predictive performance. Additionally, the time-dependent feature importance curve indicated that gender consistently remained the most stable predictor for HCC throughout the initial decade of antiviral therapy. This simple predictive model based on noninvasive clinical features can assist clinicians in identifying high-risk patients with chronic HBV infection for HCC before the initiation of antiviral therapy.

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study.

RESEARCH QUESTION: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring? DESIGN: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors. RESULTS: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544). CONCLUSION: This study suggests that children born through FET have increased risk of developing food allergy in early childhood.

Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL), a heterogeneous hematological malignancy, is caused by the developmental arrest of normal T-cell progenitors. The development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this disease. In this study, we performed multi-omics integration analysis, which included mRNA expression, chromatin accessibility, and gene-dependency database analyses, to identify potential stage-specific druggable targets and repositioned drugs for this disease. This multi-omics integration helped identify 29 potential pathological genes for T-ALL. These genes exhibited tissue-specific expression profiles and were enriched in the cell cycle, hematopoietic stem cell differentiation, and the AMPK signaling pathway. Of these, four known druggable targets (CDK6, TUBA1A, TUBB, and TYMS) showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in T-ALL. The TUBA1A expression level was higher in the early T cell precursor (ETP)-ALL cells, while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive stage. CDK6 exhibited a U-shaped expression pattern in malignant T cells along the naïve to maturation stages. Furthermore, mebendazole and gemcitabine, which target TUBA1A and TYMS, respectively, exerted stage-specific inhibitory effects on T-ALL cell lines, indicating their potential stage-specific antileukemic role in T-ALL. Collectively, our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

Evidence of microbiota-host dysbiosis between periodontitis and cerebral small vessel disease.

OBJECTIVES: To investigate the correlation between periodontitis and cerebral small vessel disease (CSVD) from the clinical and microbiological aspects. SUBJECTS AND METHODS: Periodontitis patients (CP group, n = 31) and CSVD patients (CSVD group, n = 30) were examined for neurological and periodontal condition. Subgingival plaque was collected and performed using 16S rRNA sequencing. Logistic regression and LASSO regression were used to analyze the periodontal parameters and subgingival microbiota related to CSVD, respectively. Inflammatory factors in gingival crevicular fluid (GCF) were also detected and compared between the two groups. RESULTS: Clinical attachment level (CAL), teeth number and plaque index demonstrated a significant difference between CP and CSVD group, meanwhile, CAL was independently associated with CSVD. Besides, the microbial richness and composition were distinct between two groups. Five genera related to periodontal pathogens (Treponema, Prevotella, Streptococcus, Fusobacterium, Porphyromonas) were screened out by LASSO regression, suggesting a potential association with CSVD. Finally, the levels of inflammatory factors in GCF were statistically higher in CSVD group than those in CP group. CONCLUSIONS: Cerebral small vessel disease patients demonstrated worse periodontal condition, meanwhile the interaction between microbiota dysbiosis and host factors (inflammation) leading to a better understanding of the association between periodontitis and CSVD.

Physical activity changes and related factors in chronic heart failure patients during the postdischarge transition period: a longitudinal study.

BACKGROUND: Physical activity (PA) is essential and effective for chronic heart failure (CHF) patients. A greater understanding of the longitudinal change in PA and its influencing factors during the postdischarge transition period may help create interventions for improving PA. The aims of this study were (1) to compare the change in PA, (2) to examine the influencing factors of PA change, and (3) to verify the mediating pathways between influencing factors and PA during the postdischarge transition period in CHF patients. METHODS: A total of 209 CHF patients were recruited using a longitudinal study design. The Chinese version of the International Physical Activity Questionnaire (IPAQ), Patient-reported Outcome Measure for CHF (CHF-PRO), and the Chinese version of the Tampa Scale for Kinesiophobia Heart (TSK-Heart) were used to assess PA, CHF-related symptoms, and kinesiophobia. The IPAQ score was calculated (1) at admission, (2) two weeks after discharge, (3) two months after discharge, and (4) three months after discharge. Two additional questionnaires were collected during admission. Generalized estimating equation (GEE) models were fitted to identify variables associated with PA over time. We followed the STROBE checklist for reporting the study. RESULTS: The PA scores at the four follow-up visits were 1039.50 (346.50-1953.00) (baseline/T1), 630.00 (1.00-1260.00) (T2), 693.00 (1-1323.00) (T3) and 693.00 (160.88-1386.00) (T4). The PA of CHF patients decreased unevenly, with the lowest level occurring two weeks after discharge, and gradually improving at two and three months after discharge. CHF-related symptoms and kinesiophobia were significantly associated with changes in PA over time. Compared with before hospitalization, an increase in CHF-related symptoms at two weeks and two months after discharge was significantly associated with decreased PA. According to our path analysis, CHF-related symptoms were positively and directly associated with kinesiophobia, and kinesiophobia was negatively and directly related to PA. Moreover, CHF-related symptoms are indirectly related to PA through kinesiophobia. CONCLUSION: PA changed during the postdischarge transition period and was associated with CHF-related symptoms and kinesiophobia in CHF patients. Reducing CHF-related symptoms helps improve kinesiophobia in CHF patients. In addition, the reduction in CHF-related symptoms led to an increase in PA through the improvement of kinesiophobia. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (11/10/2022 ChiCTR2200064561 retrospectively registered).

Optimizing Deep Brain Stimulation in Essential Tremor: A Randomized Controlled Trial for Target Consideration.

BACKGROUND AND OBJECTIVES: The thalamic ventral intermediate nucleus (VIM) is a well-established target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). Increasing data indicate that the posterior subthalamic area (PSA) may be superior, but high-level evidence is limited. We aimed at further comparing the intraindividual efficacy and side effect profile of PSA vs VIM DBS in ET. METHODS: In this randomized, double-blind, crossover trial, 4-contact DBS leads were bilaterally implanted with single-trajectory covering the VIM and PSA. Patients were randomized postsurgery to 2 groups, receiving VIM stimulation (4-7 months) and then PSA stimulation (8-11 months) or vice versa. The primary end point was the difference in improvement from baseline to the end of the VIM vs PSA DBS period in the total score of the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). RESULTS: Ten patients with medically refractory ET were enrolled, and 9 completed the study. The difference between reduction of FTM-TRS total score in the PSA vs VIM DBS period was -7.4 (95% CI: -28.5 to 13.7, P = .328). Clinical benefit was achieved at significantly lower stimulation intensity under PSA DBS. Furthermore, PSA DBS provided greater improvement in head tremor subscore of FTM-TRS (PSA vs VIM: -2.2, P = .020) and disease-specific quality of life (PSA vs VIM: -13.8, P = .046) and induced fewer speech (Dysphonia Severity Index score: P = .043; diadochokinetic rate: P = .007; VDI score: P = .005) and gait disturbances compared with VIM DBS. Seven patients remained with PSA DBS after the crossover phase. CONCLUSION: Our study confirms that PSA-DBS is comparable with VIM-DBS in suppressing tremors, superior in improving disease-specific quality of life, and possibly more effective in reducing head tremor.

Feasibility and safety of computed tomography-guided intrapulmonary injection of indocyanine green for localization of peripheral pulmonary ground-glass nodules.

Background: The early surgical intervention for pulmonary ground-glass nodules (GGNs) has become increasingly important, but accurate identification of these nodules during thoracoscopic surgery poses challenges due to the need for sublobar resections and reliance on visual and tactile perception alone. The prognosis of the procedure is closely tied to the use of precise positioning technology. Thus, it is crucial to develop an accurate positioning technology that can improve patient prognosis. Methods: Clinical data from the cardiothoracic department of a tertiary hospital in Shanghai were collected and analyzed between January 2020 and December 2021. The patients were categorized into 2 groups: an indocyanine green (ICG) group and a hook-wire group. Outcome measures including success rate, complications, procedure time, localization-related pain, and interval time were assessed. Adverse events and reactions were reported and compared between the 2 groups. Results: A total of 62 patients (17 males and 45 females, aged 50.5±13.2 years) were in the ICG group, while 66 patients (23 males and 43 females, aged 48.4±12.9 years) were localized in the hook-wire group. The success rate was comparable between the 2 groups. However, the ICG group showed significant advantages over the hook-wire group in terms of procedure time (22.6±4.4 vs. 24.1±4.9 min; P=0.012), localization-related pain (P<0.001), and interval time [median and interquartile range (IQR): 3 (0.7, 104.9) vs. 1.2 (0.5, 3.3) h; P<0.001]. In the ICG group, there were 11 cases of pneumothorax, 4 cases of hemothorax, and 2 cases of ICG diffusion. In the hook-wire group, there were 24 cases of pneumothorax, 25 cases of hemothorax, and 2 cases of dislodgement. The ICG group had fewer complications, including pneumothorax (P=0.018) and hemothorax (P=0.007), compared to the hook-wire group. Conclusions: Computed tomography (CT)-guided intrapulmonary injection of ICG for preoperative localization of peripheral pulmonary GGNs is a practical and safe technique. It offers advantages in terms of reduced procedure time, localization-related pain, and interval time compared to the hook-wire method. Moreover, the ICG technique results in fewer complications, making it a valuable preoperative localization technique worthy of popularization.

Value of the HFA-PEFF diagnostic algorithms for heart failure with preserved ejection fraction to the inflammatory myopathy population.

OBJECTIVES: The HFA-PEFF score has been validated to hold great diagnostic and prognostic utility for heart failure with preserved ejection fraction (HFpEF). Idiopathic inflammatory myopathy (IIM) is recognized as one of the potential etiologies underlying HFpEF. Here, we intended to investigate the real prevalence of HFpEF in IIM via the HFA-PEFF score and explore the prognostic value of this score. METHODS: Two hundred twenty IIM patients were enrolled for assessment. The cohort was divided into low, intermediate and high tertiles of the HFA-PEFF score. Spearman's correlation analysis was used to explore the association between the score and disease activity. Chi-square test was applied to investigate the distribution discrepancy of HFA-PEFF tertiles among patients with different myositis-specific antibodies (MSAs) or myositis-associated antibodies (MAAs). Univariate and multivariate ordinal regression analyses were performed to screen risk factors for high HFA-PEFF scores. Survival curves were obtained using the Kaplan-Meier method and log-rank tests. RESULTS: In total, 79 (35.9%), 107 (48.6%) and 34 (15.5%) patients were rated low, intermediate and high probability of HFpEF, respectively. The HFA-PEFF score correlated well with disease activity. Patients with positive AMA-M2 scored higher in the HFA-PEFF score (p = 0.011). During follow-up, patients with positive AMA-M2 or anti-SRP antibody developed an inclination towards concentric hypertrophy on echocardiography. Additionally, palpitation symptom, AMA-M2 positivity and elevated serum levels of LDH, cTnI were independent risk factors for high HFA-PEFF scores. Finally, a high-tertile HFA-PEFF score was related to lower overall survival rate (p < 0.001). Patients with positive AMA-M2 had poorer outcomes (p = 0.002). CONCLUSION: HFpEF was prevailing in IIM patients according to the HFA-PEFF score. The HFA-PEFF score correlated well with disease activity and held significant prognostic value. Patients with AMA-M2 antibody were prone to have poor outcomes.

Association of statin use and increase in lipoprotein(a): a real-world database research.

BACKGROUND: There is an increased concern that statins may have an unintended effect of elevated lipoprotein(a) [Lp(a)]. We conducted a large sample real-world study to test the association. METHODS: This retrospective cohort study was conducted using data from an integrated SuValue database, which includes 221 hospitals across China covering more than 200,000 of population with longitudinal follow-up to 10 years. Propensity score matching was applied to identify two comparable cohorts with statin users and non-statin users. Detailed follow-up information such as Lp(a) levels were extracted. The hazard ratio was calculated on Lp(a) changes based on the statin usage cohorts. Detailed subgroup and different characteristic cohorts' analyses were also conducted. RESULTS: After baseline propensity score matching, a total of 42,166 patients were included in a 1:1 matched ratio between statin users and non-statin users. In the case of no difference in low density lipoprotein (LDL-C), Lp(a) was increased significantly with the use of statins (adjusted HR 1.47; 95% confidence interval [CI] 1.43-1.50). Lp(a) increase was observed in various subgroup analyses and different cohorts. The dose intensity of statin was positively associated with the evaluated Lp(a) level. CONCLUSION: The use of statins was associated with an increased risk of Lp(a) elevation compared with non-statin use counterparts. The clinical relevance of these increases needs to be addressed in surrogate marker trials and/or large, cardiovascular outcomes trials.

Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. METHODS: We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. RESULTS: In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. CONCLUSIONS: Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.

D-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro.

BACKGROUND: PM2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM2.5 exposure, and aimed to find a potential intervention for people living in PM2.5 polluted regions. METHODS: Electron microscopy and oil-red staining were conducted to examine the lipid droplet accumulation. Masson's trichrome staining, colony forming, scratch assay and transwell experiment were conducted to evaluate the effect of PM2.5 exposure and D-limonene intervention on the occurrence and progression of LUAD. Potential intervention targets were found by RNA-Seq and verified by luciferase reporter assay. MiR-195 KO mice constructed with CRISPR/Cas9 technology were used to investigate the pivotal role of D-limonene-miR-195-SREBP1/FASN axis. Cohort analysis of lung cancer patients, human LUAD tissues staining and human intervention trial were also conducted to validate the results of cell and animal experiments. RESULTS: Our results showed that PM2.5 exposure induced accumulation of lipid droplets in LUAD cells which accompanied by increased malignant cellular behaviors. PM2.5 exposure led to cleaved N-SREBP1 translocation into nucleus, which activated the de novo lipogenesis pathway. Same changes were also observed in normal lung epithelial cells and normal lung tissue, and mice developed pulmonary fibrosis after long-term exposure to PM2.5. Furthermore, in a cohort of 11,712 lung cancer patients, significant lipid metabolism disorders were observed in higher PM2.5 polluted areas. In view of that, D-limonene was found to inhibit the changes in lipid metabolism through upregulating the expression of miR-195, which inhibited the expression of lipogenic genes (SREBF1/FASN/ACACA) specifically. And a small human intervention trial showed that serum miR-195 was upregulated after oral intake of D-limonene. CONCLUSION: Our findings reveal a new mechanism of pulmonary fibrosis and LUAD that is related to PM2.5 exposure-induced lipid droplet accumulation. We also demonstrate that D-limonene-miR-195-SREBP1/FASN axis is a potential preventive intervention for mediating the progression and development of LUAD induced by PM2.5 exposure. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030200. Registered 25 February 2020, http://www.chictr.org.cn/showproj.aspx?proj=48013.

Utility of vector flow mapping technology in quantitative assessment of carotid wall shear stress in hypertensive patients: A preliminary study.

Background: Blood flowing in the arterial lumen acts on the surface of the vessel wall to form wall shear stress (WSS). To date, there has been limited research on the utility of non-invasive technology in the accurate quantification of carotid WSS in patients with hypertension (HP). Objective: The present study aimed to explore the usage of vascular vector flow mapping (VFM) in the quantitative assessment of carotid WSS in hypertensive patients at an early stage and to validate its clinical utility. Methods: A total of 50 individuals confirmed without carotid plaques were grouped into a HP group (n = 25) and a control (CON) group (n = 25) according to blood pressure. An ALOKA LISENDO 880 Color Doppler Ultrasound with a L441 3-15 MHZ probe was used to obtain a longitudinal section scan to determine the regions of interests (ROIs) of the common carotid artery. VFM-based WSS measurements were obtained by selecting the ROI with optimal image quality from three full cardiac cycles. WSS-derived measurements, including WSSmax, WSSmin, and WSSmean, were analyzed and compared between the HP and CON groups. In addition, the correlations between WSS-derived measurements and the carotid artery intima-media thickness (IMT) were also analyzed. Results: There were significant statistical differences in WSSmax and WSSmean between patients in the HP and CON groups. Specifically, the HP group had significantly decreased WSSmax and WSSmean compared to the CON group (WSSmax: 1.781 ± 0.305 Pa vs. 2.286 ± 0.257 Pa; WSSmean: 1.276 ± 0.333 Pa vs. 1.599 ± 0.293 Pa, both p < 0.001). However, there was no statistical difference in WSSmin between the groups (0.79 ± 0.36 vs. 0.99 ± 0.42, p = 0.080). Additionally, Spearman's correlation analysis indicated that the WSS-derived parameters were negatively correlated with the IMT (p < 0.001). Conclusion: Vascular VFM technology shows promising results in the quantitative assessment of difference in hemodynamics of the vascular flow field between patients with HP and normal controls. Difference in WSS may serve as a potential predictor for the development of arteriosclerosis risks.

Super enhancers: Pathogenic roles and potential therapeutic targets for acute myeloid leukemia (AML).

Acute myeloid leukemia (AML) is a malignant hematological tumor with disordered oncogenes/tumor suppressor genes and limited treatments. The potent anti-cancer effects of bromodomain and extra-terminal domain (BET) inhibitors, targeting the key component of super enhancers, in early clinical trials on AML patients, implies the critical role of super enhancers in AML. Here, we review the concept and characteristic of super enhancer, and then summarize the current researches about super enhancers in AML pathogenesis, diagnosis and classification, followed by illustrate the potential super enhancer-related targets and drugs, and propose the future directions of super enhancers in AML. This information provides integrated insight into the roles of super enhancers in this disease.

Simplified regimen for the management of hypertension with telemedicine and blood pressure self-monitoring (SIMPLE): study protocol for a randomised controlled trial.

INTRODUCTION: Telemedicine and blood pressure (BP) self-monitoring conduces to management of hypertension. Recent hypertension guidelines highly recommended single pill combination (SPC) for the initial treatment of essential hypertension. Based on this fact, an SPC-based telemedicine titration regimen with BP self-monitoring could be a better way in managing hypertension. This trial aims to elucidate whether telemedicine combined with BP self-monitoring is superior to self-monitoring alone during hypertension management. METHODS AND ANALYSIS: This study will be a multicentred, open-labelled, randomised controlled trial. A minimum sample of 358 hypertensive patients with uncontrolled BP from four centres will be included. The intervention group will include BP self-monitoring and tele-monitoring plus a free SPC-based telemedicine titration therapy for 6 months, they will be recommended to take BP measurements at least once every 7 days, in the meantime, researchers will call to give a consultation on lifestyle or titration advice once a fortnight. The control group will be required to self-monitor BP at the same time interval as intervention group, without any therapy change. Primary outcome of the trial will be the difference in systolic blood pressure at 6-month follow-up between intervention and control group, adjusted for baseline variables. Secondary outcomes such as BP control rate, major adverse cardiovascular events, medication adherence, quality of life will be investigated. ETHICS AND DISSEMINATION: Ethics approval was granted by Ethical Committee of Shanghai Tenth People's Hospital (SHSY-IEC-4.1/20-194/01). The results will be disseminated in peer-reviewed literature, and to policy-makers and healthcare partners. TRIAL REGISTRATION NUMBER: ChiCTR2000037217.

Adjuvant Chemotherapy in pT2N0M0 Gastric Cancer: Findings From a Retrospective Study.

Background: There is no global consensus on adjuvant chemotherapy (ACT) for pT2N0M0 gastric cancer. We conducted a retrospective study to reveal the role of ACT in such patients. Methods: Patients with pT2N0M0 gastric cancer who underwent radical resection with D2 lymphadenectomy for primary gastric cancer between January 2012 and May 2016 were included. Kaplan-Meier and Cox regression were used to evaluate overall survival (OS), disease-specific survival (DSS) and predictors of prognosis. Stratified analysis based on high-risk factors was conducted. Results: Of enrolled 307 patients, 111 patients underwent surgery alone and 196 patients received ACT. Surgery alone (HR = 2.913, 95% CI: 1.494-5.682, p = 0.002) and total gastrectomy (HR = 2.445, 95% CI: 1.279-4.675, p = 0.007) were independently associated with decreased OS. With the median follow-up of 73.1 months, the 5-year OS rate was 87.9% and 5-year DSS rate was 91.8%. Patients receiving ACT showed a better 5-year OS rate (92.9 vs. 79.3%, p < 0.001) and DSS rate (96.8 vs. 83.0%, p < 0.001) than patients underwent surgery alone. Patients receiving monotherapy (n = 130) had a relatively poor prognosis compared to patients receiving dual-drug (n = 66) without a significant difference (92.3 vs. 93.9%, p = 0.637). In patients without high-risk factors based on the Chinese Society of Clinical Oncology (CSCO) Guidelines, ACT also provided survival benefit (96.0 vs 82.9%, p = 0.038). Conclusions: ACT was accompanied with higher 5-year OS and DSS rates of patients with pT2N0M0 gastric cancer. Patients with pT2N0M0 gastric cancer, regardless of high-risk factors based on the CSCO guidelines, might be considered candidates for ACT. In regard to the therapy regimen, monotherapy might be the optimal choice, considering the adverse events.

Addition of sintilimab to nanoparticle albumin-bound paclitaxel and S-1 as adjuvant therapy in stage IIIC gastric cancer.

The prognosis of stage III gastric cancer (GC) is not satisfying and the specific chemotherapy regimens for GC of stage IIIC based on the 8th edition of the UICC/AJCC TNM staging system are still inconclusive. Peritoneal recurrence is the common and severe relapse pattern. Nanoparticle albumin-bound paclitaxel (Nab-PTX) is safer and more effective than PTX in the peritoneal metastasis. Clinical trial has demonstrated the safety and efficacy of sintilimab in GC. A combination of Nab-PTX, S-1 and sintilimab could be a promising triplet regimen as adjuvant therapy for GC. The aim of this article is to describe the design of this prospective Dragon-VII trial, conducted to evaluate the safety and efficacy of the combination of Nab-PTX, S-1 and sintilimab. Clinical trial registration: NCT04781413.

Lay abstract The prognosis of stage IIIC gastric cancer is poor and the treatment for it is not satisfying. This is a clinical trial that aims to explore a more effective therapy in gastric cancer patients of stage IIIC. Patients with stage IIIC gastric cancer must meet all of the inclusion criteria and none of the exclusion criteria to be eligible for this trial. The eligible patients will be given eight cycles of combinatory therapy of albumin-bound paclitaxel, a chemotherapy (day 1 and day 8), and S-1, another chemotherapy (days 1 to 14), plus sintilimab, a type of immunotherapy called an immune checkpoint inhibitor (day 1) every 3 weeks and then sintilimab maintenance for up to 12 months.

Short-Term Association of Air Pollutant Levels and Hospital Admissions for Stroke and Effect Modification by Apparent Temperature: Evidence From Shanghai, China.

The epidemiological evidence on relationships between air pollution, temperature, and stroke remains inconclusive. Limited evidence is available for the effect modification by apparent temperature, an indicator reflecting reactions to the thermal environment, on short-term associations between air pollution and hospital admissions for stroke. We used a generalized additive model with Poisson regression to estimate the relative risk (RR) of stroke admissions in Shanghai, China, between 2014 and 2016 associated with air pollutants, with subgroup analyses by age, sex, apparent temperature, and season. During the study period, changes in the daily number of stroke admissions per 10 µg/m3 increase in nitrogen dioxide (at lags 0, 1, 0-1, and 0-2) ranged from 1.05 (95% CI: 0.82%, 2.88%) to 2.24% (95% CI: 0.84%, 3.65%). For each 10 µg/m3 increase in sulfur dioxide concentrations at lags 1, 2, 0-1, and 0-2, the RR of daily stroke admissions increased by 3.34 (95% CI: 0.955%, 5.79%), 0.32 (95% CI: -1.97%, 2.67%), 3.33 (95% CI: 0.38%, 6.37%), and 2.86% (95% CI: -0.45%, 6.28%), respectively. The associations of same-day exposure to nitrogen dioxide with stroke admissions remained significant after adjustment for ozone levels. These associations were not modified by sex, age, apparent temperature, or season. More research is warranted to determine whether apparent temperature modifies the associations between air pollution and stroke admissions.

Analysis of risk factor for pediatric intensive care unit delirium in children: a case-control study.

OBJECTIVE: This study aimed to survey the prevalence of delirium in the pediatric intensive care unit (PICU) and explore the associated risk factors. DESIGN: A retrospective case-control study. SETTING: Two PICUs within a tertiary-A general hospital. PATIENTS: Patients aged from 1 month to 7 years who stayed in either PICU for at least 1 day were included. METHODS: A total of 639 patients admitted to PICU of a tertiary-A general hospital from December 2018 to August 2019 were enrolled. Demographic, clinical, laboratory data and length of stay in the PICU were collected. The patients were screened twice a day with the Chinese version of Cornell Assessment of Pediatric Delirium (CAPD), and were divided into the delirium group and the non-delirium group. A risk factor analysis was conducted, with ICU pediatric delirium as primary outcome, by performing a multivariable logistic regression analysis. RESULTS: Of the 639 patients, the prevalence of ICU pediatric delirium was 31.30%. Of the 200 children with delirium across 3703 study days, 36% children were hyperactive, 41% were hypoactive, and 23% displayed the mixed type of delirium. Univariate analysis and multivariate logistic regression analysis showed that age, PRISM IV score (OR, 2.20; 95% CI, 1.42-3.41), hypoxia (OR, 2.69; 95% CI, 1.53-4.71), metabolic dis-function (OR, 3.73; 95% CI, 2.08-6.71), duration of infection (OR, 1.22; 95% CI, 1.10-1.36), and mechanical ventilation (OR, 3.78; 95% CI, 2.25-6.35) were statistically correlated with ICU pediatric delirium. The ROC curve analysis shows the combination CRP with duration of infection has good predictive performance. CONCLUSIONS: Age, PRISM IV score, ICU retention time, metabolic dis-function, duration of infection, hypoxia, CRP and mechanical ventilation were the independent risk factors for ICU pediatric delirium. We suggest that active preventive measures should be taken to reduce the occurrence of ICU pediatric delirium.