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Objective To analyze and construct systolic blood pressure (SBP) fluctuation trajectory in a community population with hypertension and to analyze the factors influencing different trajectories. Methods This is a community-based retrospective cohort study. A latent class trajectory model was used to identify and construct longitudinal trajectories of blood pressure change. Multinomial logistic regression analysis was performed to identify the associated factors of blood pressure trajectories by adjusting for different confounders. Potential confounding factors were identified using a directed acyclic graph based on a priori knowledge. Results A total of 793 patients with hypertension were enrolled in the analysis. They were divided into 3 groups by LCTM-fitted systolic blood pressure trajectories, namely stable low-level group (n=561, 70.74%), declining group (n=170, 21.44%) and rising group (n=62, 7.82%). Significant differences were observed among the 3 trajectories groups in terms of age, frequency of exercise, ways of follow-up, salt intake, compliance behavior, and referral (P

Heated tobacco products (HTPs) are a recent category of tobacco products, with their relative safety compared to cigarette smoking and potential to help smokers to quit being two reasons why regulators may consider their market approval. Designed to heat tobacco rather than to burn in order to produce aerosol, different heating techniques are applied to commercial HTPs, which may result in differing aerosol formation. Therefore, each product requires separate assessment. This work focuses on a closed-end HTP (coded as HTP-A), which is electrically heated and designed to allow puffing air flow to bypass its tobacco section, resulting in reduced oxygen concentration within the tobacco section during heating and aerosol forming. To provide a preliminary aerosol chemistry and in vitro toxicological screening, this study assessed HTP-A against a commercial electrically heated HTP (IQOSTM, coded as HTP-B) and a 3R4F reference cigarette. Under Health Canada Intense (HCI) smoking regime, the levels of 9 regulatory priority toxicants in the aerosol of HTP-A were either reduced or comparable to those in HTP-B on a per-stick basis. Additionally, both HTPs showed significant reduction (greater than 90%) in comparison to those measured in mainstream smoke of 3R4F cigarette for these toxicants. Using a set of standard in vitro toxicological assays (Ames, Micronucleus and Neutral Red Uptake), the two HTPs showed no observable responses while significant toxicity responses were recorded for 3R4F’s total particulate matter. Based on these preliminary results, the novel closed-end HTP-A design may provide similar toxicological profiles to the comparator HTP-B. Further toxicological and clinical assessments are warranted to evaluate HTP-A’s potential for exposure or disease risk reduction. [Contrib. Tob. Nicotine Res. 32 (2023) 146–156]

BackgroundSevere traumatic brain injuries (TBIs) are an important health issue worldwide, which are associated with harmful side effects. This meta-analysis investigates the cognitive and functional outcomes in severe brain trauma cases. It assesses the impact on memory, verbal and visual abilities, attention, learning, and the presence of depression. The study provides a comprehensive overview of the consequences of severe brain trauma injury on cognitive and functional domains.ObjectiveThe main objective of the current comprehensive meta-analysis study is to assess and analyze the impact of severe TBI on functional and cognitive outcomes, including verbal, visual, attention, learning, memory, and emotional stability.MethodsWe collected data from three online databases, including PubMed, Cochrane Library, and Embase. Case–control trials related to severe TBI association with cognitive and functional outcomes were included. Verbal strength, visual functions, learning abilities, attention, memory, and depression were considered primary outcomes.ResultsWe have included 13 case–control studies with 1,442 subjects in this meta-analysis, which provide adequate data to determine the pooled effect size for targeted outcomes. The effect of severe TBI on the inducement of depression and impairment of memory, verbal, visual, attention, and learning abilities compared to the control group showed statistically significant outcomes (p

Freeze casting is an attractive method for designing lamellar ceramic-aluminum composites with a unique combination of strength and toughness. However, there are few studies on the detailed mechanical properties, especially wear resistance, of lamellar Ti(C,N)/Al–Cu composites. Herein, nacre-inspired Ti(C,N)/Al–Cu composites are fabricated via freeze and squeeze casting, and their mechanical and frictional wear properties are investigated. The results show that compressive strength, bending strength, crack-initiation toughness (KIC), and crack-growth toughness (KJC) of composites are 769.2–996.8 MPa, 547.8 MPa, 13.9 MPa m1/2, and 31.1 MPa m1/2, respectively. The achieved strength and toughness are higher than those of most nacre-inspired ceramic/Al composites. The high damage tolerance is affected by interface binding strength between Ti(C,N) and Al, as well as multiple mechanisms. Moreover, friction and wear properties of composites exhibit obvious anisotropy and the transverse section, i.e., perpendicular to freeze direction, exhibits the best wear resistance with a wear rate of only 0.98 × 10−4 mm3/Nm. This anisotropy can be attributed to the different arrangements of ceramic layers on the different sections, which affects their bearing capacity.

Objective To construct trajectory models of fasting blood glucose fluctuations in type 2 diabetes mellitus (T2DM) patients in community, and analyze the influencing factors of the trajectory of glucose fluctuation in different categories. Methods A retrospective cohort study was carried out on 769 T2DM patients who had health records and been involved in the diabetic management in Shuangbei Community Health Service Center of Shapingba District, Chongqing from 2012 to 2019. Group-based trajectory modelling (GBTM) was employed to identify and construct the fluctuation trajectory of fasting blood glucose in the patients. BIC, AvePP and other evaluation indicators were used to select the optimum subgroup number model. Then the differences in demographic characteristics, health status, medical history, lifestyle, medication compliance, etc were compared among different categories. Multinomial logistic regression model was constructed to explore the influencing factors of different fluctuation trajectories. Results The 769 T2DM subjects were divided into 3 groups of different fluctuation trajectories by GBTM, that is, low-level steady, high-level falling, and medium-level rising groups. Multinomial logistic regression analysis indicated that the patients with a history of hypertension and not taking medication were less likely to be assigned into the high-level falling group than into the low-level steady group, indicating that their high glucose level was not predisposed to a progressive decline (OR=0.50, 95%CI: 0.28~0.90, P=0.021; OR=0.13, 95%CI: 0.03~0.56, P=0.006). However, the subjects who occasionally or not exercised, consumed alcohol or abstained from alcohol were more likely to be assigned into the high-level falling group (OR=2.02, 95%CI: 1.15~3.55, P=0.014; OR=2.32, 95%CI: 1.16~4.63, P=0.017). When compared with the patients with regular medication, those with intermittent medication were more likely to be assigned into the medium-level rising group (OR=6.02, 95%CI: 2.86~12.66, P < 0.001). Conclusion There are different trajectories of dynamic changes in fasting glucose for T2DM patients. History of hypertension, medication adherence, frequency of exercise, and alcohol consumption may be associated with different trajectories of blood glucose fluctuations.

Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam‐like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of L‐oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods: The study adopts a multicenter, randomized, double‐blind, parallel‐group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: L‐oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow‐up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion: There is no robust evidence to suggest that L‐oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565. [ABSTRACT FROM AUTHOR]

Although first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is effective for treating EGFR-mutant non-small cell lung cancer (NSCLC), it is now understood that drug-tolerant persister (DTP) cells escaping from initial treatment eventually drives drug resistance. Here, through integration of metabolomics and transcriptomics, we found that the neurotransmitter acetylcholine (ACh) was specifically accumulated in DTP cells, and demonstrated that treatment with EGFR-TKI heightened the expression of the rate-limiting enzyme choline acetyltransferase (ChAT) in ACh biosynthesis via YAP mediation. Genetic and pharmacological manipulation of ACh biosynthesis or ACh signaling could predictably regulate the extent of DTP formation in vitro and in vivo. Strikingly, pharmacologically targeting ACh/M3R signaling with an FDA-approved drug, darifenacin, retarded tumor relapse in vivo. Mechanistically, upregulated ACh metabolism mediated drug tolerance in part through activating WNT signaling via ACh muscarinic receptor 3 (M3R). Importantly, we showed that aberrant ACh metabolism in patients with NSCLC played a potential role in predicting EGFR-TKI response rate and progression-free survival. Our study therefore defines a therapeutic strategy--targeting the ACh/M3R/WNT axis--for manipulating EGFR TKI drug tolerance in the treatment of NSCLC., Introduction Patients with non-small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) clearly benefit from EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy (1). However, like other [...]

Aim: We aim to identify the specific CD4+ T‐cell subtype influenced by brain‐to‐CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). Method: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T‐cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time‐of‐flight analysis (CyTOF) or fluorescence‐activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) staining. Results: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b‐positive CD4+ T cells, within the affected region. The population of CD4+CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine‐1‐phosphate receptor‐1 (S1PR1) on these cells. Administration of CD4+CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. Conclusion: The infiltration of CD4+CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain‐to‐CLN signaling. [ABSTRACT FROM AUTHOR]