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In addition to considering the main effects, understanding gene‐environment (G × E) interactions is imperative for determining the etiology of diseases and the factors that affect their prognosis. In the existing statistical framework for censored survival outcomes, there are several challenges in detecting G × E interactions, such as handling high‐dimensional omics data, diverse environmental factors, and algorithmic complications in survival analysis. The effect heredity principle has widely been used in studies involving interaction identification because it incorporates the dependence of the main and interaction effects. However, Bayesian survival models that incorporate the assumption of this principle have not been developed. Therefore, we propose Bayesian heredity‐constrained accelerated failure time (BHAFT) models for identifying main and interaction (M‐I) effects with novel spike‐and‐slab or regularized horseshoe priors to incorporate the assumption of effect heredity principle. The R package rstan was used to fit the proposed models. Extensive simulations demonstrated that BHAFT models had outperformed other existing models in terms of signal identification, coefficient estimation, and prognosis prediction. Biologically plausible G × E interactions associated with the prognosis of lung adenocarcinoma were identified using our proposed model. Notably, BHAFT models incorporating the effect heredity principle could identify both main and interaction effects, which are highly useful in exploring G × E interactions in high‐dimensional survival analysis. The code and data used in our paper are available at https://github.com/SunNa‐bayesian/BHAFT. [ABSTRACT FROM AUTHOR]

Background Although studies have demonstrated associations between sleep quality (SQ) and grip strength (GS) in older adults, the direction and underlying mechanisms of this relationship are yet to be better delineated. We aimed to longitudinally investigate the bidirectional association between SQ and GS and the mediating role of depression in this association. Methods Based on 2 nationally representative samples with people aged ≥50 years from the China Health and Retirement Longitudinal Study (CHARLS; 4 200 participants) and English Longitudinal Study of Ageing (ELSA; 5 922 participants), cross-lagged panel models were employed to examine the potential bidirectional relationships between objectively measured GS and self-reported SQ. Results We observed a GS–SQ bidirectional association dominated by GS. After adjusting for potential confounders, a higher GS at T1 predicted better SQ at T2 (ELSA: β = 0.075; CHARLS: β = 0.104, p <.001) and vice versa (ELSA: β = 0.034; CHARLS: β = 0.030, p <.01). Moreover, depression partially mediated the impact of GS on subsequent SQ (ELSA, indirect effect: 0.0057, 95% confidence interval [CI]: 0.0035–0.0084; CHARLS, indirect effect: 0.0086, 95% CI: 0.0051, 0.0131), but not vice versa. Conclusions The results regarding data from both cohorts consistently supported a bidirectional association between GS and SQ and the mediating role of depression in the dominant pathway of this bidirectional relationship. Older adults with a low GS should be made aware of a potentially vicious cycle related to depression that can affect their sleep. Regular screening for depression may help to break this cycle. [ABSTRACT FROM AUTHOR]

Purpose: Ketoprofen (KETO) is a traditional non-steroidal anti-inflammatory drug (NSAIDs) with good analgesic and antipyretic effects. However, as NASIDs, the toxicity of KETO towards gastrointestinal (GI) system might limit its clinical use. S-propargyl-cysteine (SPRC) is an excellent endogenous H2S donor showed wide application in the field of anti-inflammation, anti-oxidative stress, or even the protection of cardiovascular system through the elevation of endogenous H2S concentration. As recently studies reported, co-administration of H2S donor might potentially mitigate the GI toxicity and relevant side effects induced by series of NSAIDs. Methods: In this study, we established a SPRC and KETO co-encapsulated poly (lactic-co-glycolic acid) microsphere ([email protected]), and its particle size, morphology, storage stability and in vitro release profile were firstly investigated. The elevation of endogenous H2S level of [email protected] was then calculated, and the pharmacodynamic study (anti-inflammation and analgesic effects) of [email protected] , SPRC, and KETO towards adjuvant induced arthritis (AIA) in rats were also studied. Finally, to test the potential side effect, the heart, liver, spleen, lung, kidney, stomach, small intestine, and large intestine were resected from rats and examined by H&E staining. Results: A monodispersed [email protected] could be observed under the SEM, and particle size was calculated around 25.12 μm. The loading efficiency (LE) for SPRC and KETO were 6.67% and 2.64%, respectively, while the encapsulation efficiency (EE) for SPRC and KETO were 37.20% and 68.28%, respectively. [email protected] showed a sustained release of SPRC and KETO in vitro, which was up-to 15 days. [email protected] could achieve a long-term elevation of the H2S concentration in vivo, while SPRC showed an instant H2S elevation and metabolize within 6 h. Interestingly, the KETO did not show any influence on the H2S concentration in vivo. After establishment of AIA model, neither SPRC nor KETO showed scarcely anti-inflammation and anti-nociception effect, while conversely, [email protected] showed an obvious mitigation towards paw edema and pain in AIA rats, which indicated an improved anti-inflammation and anti-nociception effect when co-delivery of SRC and KETO. Besides, low stimulation towards major organs in rats observed in any experimental group. Conclusion: A monodispersed was successfully prepared in this study, and [email protected] showed a sustained SPRC and KETO release in vitro and H2S release in vivo. In the pharmacodynamics study, [email protected] not only exhibited an excellent anti-inflammation and analgesic effects in AIA rats but also showed low stimulation towards rats. [ABSTRACT FROM AUTHOR]

Background: Although inflammation has been linked to nonalcoholic fatty liver disease (NAFLD), most studies have focused only on a single indicator, leading to inconsistent results. Therefore, a large prospective study that includes a variety of well-documented single and composite indicators of inflammation is needed. This study aimed to thoroughly investigate the potential associations between different systemic inflammatory indicators and NAFLD in the UK Biobank cohort., Methods: After excluding ineligible participants, 378,139 individuals were included in the study. Associations between systemic inflammatory indicators and hepatic steatosis were assessed using multivariate logistic regression. The relationships between systemic inflammatory indicators and nonalcoholic fatty liver disease were analysed using Cox proportional hazards models, and nonlinear associations were investigated using restricted cubic splines., Results: According to the cross-sectional analysis, systemic inflammatory indicators significantly correlated with hepatic steatosis. Over a median follow-up of 13.9 years, 4,145 individuals developed NAFLD. After sufficient adjustment for confounding factors, CRP levels were found to be nonlinearly positively associated with NAFLD risk ( P <0.001), representing the strongest correlation among the tested relationships; lymphocyte count and the LMR showed an L-shaped correlation; monocyte count and neutrophil count showed a linear positive correlation (all P < 0.001); and the NLR, PLR, and SII showed a U-shaped correlation (all P <0.001)., Conclusions: Multiple systemic inflammatory indicators are strongly associated with the development of NAFLD, and aggressive systemic inflammation management may have a favourable impact on reducing the burden of NAFLD; further randomized controlled studies are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gong, He, Zhu, Feng, Sun, Jiang, Yuan, Shen and Di.)

Purpose: Ketoprofen (KETO) is a traditional non-steroidal anti-inflammatory drug (NSAIDs) with good analgesic and antipyretic effects. However, as NASIDs, the toxicity of KETO towards gastrointestinal (GI) system might limit its clinical use. S-propargyl-cysteine (SPRC) is an excellent endogenous H 2 S donor showed wide application in the field of anti-inflammation, anti-oxidative stress, or even the protection of cardiovascular system through the elevation of endogenous H 2 S concentration. As recently studies reported, co-administration of H 2 S donor might potentially mitigate the GI toxicity and relevant side effects induced by series of NSAIDs., Methods: In this study, we established a SPRC and KETO co-encapsulated poly (lactic-co-glycolic acid) microsphere (SK@MS), and its particle size, morphology, storage stability and in vitro release profile were firstly investigated. The elevation of endogenous H 2 S level of SK@MS was then calculated, and the pharmacodynamic study (anti-inflammation and analgesic effects) of SK@MS, SPRC, and KETO towards adjuvant induced arthritis (AIA) in rats were also studied. Finally, to test the potential side effect, the heart, liver, spleen, lung, kidney, stomach, small intestine, and large intestine were resected from rats and examined by H&E staining., Results: A monodispersed SK@MS could be observed under the SEM, and particle size was calculated around 25.12 μm. The loading efficiency (LE) for SPRC and KETO were 6.67% and 2.64%, respectively, while the encapsulation efficiency (EE) for SPRC and KETO were 37.20% and 68.28%, respectively. SK@MS showed a sustained release of SPRC and KETO in vitro, which was up-to 15 days. SK@MS could achieve a long-term elevation of the H 2 S concentration in vivo, while SPRC showed an instant H 2 S elevation and metabolize within 6 h. Interestingly, the KETO did not show any influence on the H 2 S concentration in vivo. After establishment of AIA model, neither SPRC nor KETO showed scarcely anti-inflammation and anti-nociception effect, while conversely, SK@MS showed an obvious mitigation towards paw edema and pain in AIA rats, which indicated an improved anti-inflammation and anti-nociception effect when co-delivery of SRC and KETO. Besides, low stimulation towards major organs in rats observed in any experimental group., Conclusion: A monodispersed was successfully prepared in this study, and SK@MS showed a sustained SPRC and KETO release in vitro and H 2 S release in vivo. In the pharmacodynamics study, SK@MS not only exhibited an excellent anti-inflammation and analgesic effects in AIA rats but also showed low stimulation towards rats., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Yu et al.)

Objective: To dynamically observe the effects of electroacupuncture (EA) on repair of gastric mucosal lesion in rats with gastric ulcer, and to explore the time-effect relationship and molecular mechanism of EA for gastric ulcer., Methods: A total of 72 SD rats were randomly assigned to a normal group, a model group, a acupoint group and a sham acupoint group, and each group were further divided into a 1-day subgroup, a 4-day subgroup and a 7-day subgroup, 6 rats in each subgroup. The rat model of gastric ulcer was established by using intragastric administration of ethyl alcohol. The rats in the acupoint group were treated with EA at"Zusanli"(ST 36) and"Liangmen"(ST 21); the rats in the sham acupoint group were treated with EA at points 5 mm next to"Zusanli"(ST 36) and"Liangmen"(ST 21); the EA was given 30 min per treatment, once a day. The rats in the normal group and model group were treated with immobilization for 30 min per day, and no EA was given. PR-PCR method was applied to test the expression of proliferating cell nuclear antigen (PCNA) and substance P (SP); Western blot method was applied to test the expression of neurotensin (NT)., Results: After 1-day treatment, the ulcer index in the model group was higher than that in the normal group ( P <0.01), and the expression of PCNA, SP and NT was decreased ( P <0.01, P <0.05); compared with the model group and sham acupoint group, the ulcer index was decreased in the acupoint group (both P <0.05), and the expression of PCNA and SP was up-regulated (all P <0.05) while that of NT was up-regulated (both P <0.01). After 4-day treatment, the ulcer index in the model group was reduced but still higher than that in the normal group ( P <0.05), and the expression of PCNA, SP and NT was up-regulated and higher than that in the normal group (all P <0.01); the ulcer index in the acupoint group was similar to that in the normal group ( P >0.05), and the expression of PCNA and SP was lower than that in the model group ( P <0.01, P <0.05), and the expression of NT was not significantly different from that in the model group ( P >0.05). After 7-day treatment, the differences of indexes above were not significant among the four groups (all P >0.05)., Conclusion: EA at acupoints of stomach meridian has two-way regulation on PCNA and SP and improve the expression of NT in different pathological state of gastric ulcer, which could further improve the repair of gastric ulcer.