Pharmacological evaluation of new generation OXIZID synthetic cannabinoid receptor agonists.

Synthetic cannabinoid receptor agonists (SCRAs) remain one the largest classes of new psychoactive substances, and are increasingly associated with severe adverse effects and death compared to the phytocannabinoid Δ9-tetrahydrocannabinol (THC). In the attempt to circumvent the rapid emergence of novel SCRAs, several nations have implemented 'generic' legislations, or 'class-wide' bans based on common structural scaffolds. However, this has only encouraged the incorporation of new chemical entities, including distinct core and linker structures, for which there is a dearth of pharmacological data. The current study evaluated five emergent OXIZID SCRAs for affinity and functional activity at the cannabinoid CB1 receptor (CB1) in HEK 293 cells, as well as pharmacological equivalence with THC in drug discrimination in mice. All OXIZID compounds behaved as agonists in Gαi protein activation and ß-arrestin 2 translocation assays, possessing low micromolar affinity at CB1. All ligands also substituted for THC in drug discrimination, where potencies broadly correlated with in vitro activity, with the methylcyclohexane analogue BZO-CHMOXIZID being the most potent. Notably, MDA-19 (BZO-HEXOXIZID) exhibited partial efficacy in vitro, generating an activity profile most similar to that of THC, and partial substitution in vivo. Overall, the examined OXIZIDs were comparatively less potent and efficacious than previous generations of SCRAs. Further toxicological data will elucidate whether the moderate cannabimimetic activity for this series of SCRAs will translate to severe adverse health effects as seen with previous generations of SCRAs.

Improvement of astrocytic gap junction involves the anti-depressive effect of celecoxib through inhibition of NF-κB.

CONTEXT: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been shown to exhibit anti-depressive effects in clinical trials. However, the direct mechanism underlying its effect on neuroinflammation remains unclear. Neuroinflammatory reaction from astrocytes leads to depression, and our previous study found that gap junction disorder between astrocytes aggravated neuroinflammatory reaction in depressed mice. OBJECTIVE: To investigate the potential mechanism of celecoxib's effects on astrocytic gap junctions during the central nervous inflammation-induced depression. MATERIALS & METHODS: Stereotaxic injection of lipopolysaccharide (LPS) into the prefrontal cortex (PFC) to establish a model of major depressive disorder (MDD). Celecoxib was administrated into PFC 15 min after LPS injection. The depressive performance was tested by tail suspension test and forced swimming test, and the levels of proinflammation cytokines were determined at mRNA and protein levels. Resting-state functional connection (rsFC) was employed to assess changes in the default mode network (DMN). Additionally, astrocytic gap junctions were also determined by lucifer yellow (LY) diffusion and transmission electron microscope (TEM), and the expression of connexin 43 (Cx43) was measured by western blotting, quantitative polymerase chain reaction, and immunofluorescence. RESULTS: LPS injection induced significant depressive performance, which was ameliorated by celecoxib treatment. Celecoxib also improved rsFC in the DMN. Furthermore, celecoxib improved astrocytic gap junctions as evidenced by increased LY diffusion, shortened gap junction width, and normalized levels of phosphorylated Cx43. Celecoxib also blocked the phosphorylation of p65, and inhibition of p65 abolished the improvement of Cx43. DISCUSSION & CONCLUSION: Anti-depressive effects of celecoxib are mediated, at least in part, by the inhibition of nuclear factor- kappa B (NF-κB) and the subsequent improvement of astrocytic gap junction function.

Organ meat consumption and risk of non-alcoholic fatty liver disease: the Tianjin Chronic Low-grade Systemic Inflammation and Health cohort study.

Prospective cohort studies linking organ meat consumption and non-alcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between organ meat consumption and risk of NAFLD in a general Chinese adult population. This prospective cohort study included a total of 15 568 adults who were free of liver disease, CVD and cancer at baseline. Dietary information was collected at baseline using a validated FFQ. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between organ meat consumption and risk of NAFLD. During a median of 4·2 years of follow-up, we identified 3604 incident NAFLD cases. After adjusting for demographic characteristics, lifestyle factors, vegetable, fruit, soft drink, seafood and red meat consumption, the multivariable hazard ratios (95 % CI) for incident NAFLD across consumption of organ meat were 1·00 (reference) for almost never, 1·04 (0·94, 1·15) for tertile 1, 1·08 (0·99, 1·19) for tertile 2 and 1·11 (1·01, 1·22) for tertile 3, respectively (Pfor trend < 0·05). Such association did not differ substantially in the sensitivity analysis. Our study indicates that organ meat consumption was related to a modestly higher risk of NAFLD among Chinese adults. Further investigations are needed to confirm this finding.

Association Between Handgrip Strength and Type 2 Diabetes: A Prospective Cohort Study and Systematic Review With Meta-analysis.

BACKGROUND: Both absolute (kg) and relative (kg per kg of body weight) handgrip strength (HGS) have been used as indicators of HGS. Multiple studies have explored HGS associations with type 2 diabetes (T2DM); however, prognostic values were inconsistent. We aimed to examine the associations between both absolute and relative HGS and incident T2DM. METHODS: A total of 12,957 participants aged 40 years and older (mean age 51.0 years, 58.4% men) were followed and enrolled in the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) Cohort Study. Cox proportional hazards regression models were used to examine the association of HGS with incident T2DM. Other prospective studies on HGS and risk of T2DM were identified by searching several electronic databases up to November 31, 2021. Meta-analysis was performed by combining the results from the TCLSIH study and previous prospective cohort studies. RESULTS: From the TCLSIH Cohort study, after adjustment, relative HGS was inversely associated with T2DM (hazard ratio per 0.1 higher relative HGS 0.667, 95% confidence interval [CI] 0.616, 0.722). However, no significant association between absolute HGS and incident T2DM was found. The meta-analyses showed that per 5 kg higher HGS was associated with a 5% (95% CI 2%, 8%) lower risk of T2DM and each 0.1 higher relative HGS was associated with a 22% (95% CI 14%, 29%) lower risk of T2DM. CONCLUSION: The results from our cohort study and meta-analysis suggest that relative HGS was better than absolute HGS in predicting incident T2DM. Adiposity was an important factor that mediates the association between HGS and T2DM.

Added sugar intake and its forms and sources in relation to risk of non-alcoholic fatty liver disease: results from the Tianjin Chronic Low-grade Systemic Inflammation and Health cohort study.

It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid v. solid) and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15 538 participants, free of NAFLD, other liver diseases, CVD, cancer or diabetes at baseline (2013-2018 years). Added sugar intake was estimated from a validated 100-item FFQ. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazard ratios (HR) and corresponding 95 % CI for NAFLD risk with added sugar intake. During a median follow-up of 4·2 years, 3476 incident NAFLD cases were documented. After adjusting for age, sex, BMI and its change from baseline to follow-up, lifestyle factors, personal and family medical history and overall diet quality, the multivariable HR of NAFLD risk were 1·18 (95 % CI 1·06, 1·32) for total added sugars, 1·20 (95 % CI 1·08, 1·33) for liquid added sugars and 0·96 (95 % CI 0·86, 1·07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.

Relationship between the consumption of wholegrain and nonalcoholic fatty liver disease: The TCLSIH cohort study.

BACKGROUND & AIMS: Wholegrain contributes a range of beneficial nutrients and is considered to play a role in the prevention of chronic diseases, but evidence of their influence on nonalcoholic fatty liver disease (NAFLD) is limited. We conducted this study to investigate the prospective association between daily wholegrain consumption and NAFLD in the general population. METHODS: This prospective cohort study included a total of 14,968 (42.2% men) inhabitants living in Tianjin, China. Participants without a history of CVD, cancer, alcoholic fatty liver disease, other liver diseases, or NAFLD were followed up for 1-6 years with a median follow-up duration of 4.2 years. Wholegrain consumption was assessed using a validated self-administered food frequency questionnaire. NAFLD was diagnosed with the results of liver ultrasonography without significant alcohol consumption and other causes of liver disease. Cox proportional hazards regression models were used to estimate the association between wholegrain consumption and NAFLD. RESULTS: A total of 3505 (2171 men) first incident cases of NAFLD occurred during 53,303 person-years of follow-up (median follow-up of 4.2 years). After adjusting for several potential confounders and setting "almost never" as the control group, the multivariable hazard ratios (95% confidence intervals) of the NAFLD were 0.82 (0.73, 0.92) when they consuming ≤1 time/week, 0.78 (0.69, 0.88) when they consuming 2-6 time/week and 0.77 (0.66, 0.90) when they consuming ≥1 time/day (p for trend <0.001). CONCLUSION: The results from our prospective study demonstrated that the higher consumption of wholegrain is associated with a decreased risk of NAFLD in Chinese adults.

Green tea consumption and risk of depressive symptoms: Results from the TCLSIH Cohort Study.

BACKGROUND: The prospective studies on the effect of particular type of tea consumption, especially green tea, on depressive symptoms are limited. OBJECTIVE: The aim of this study is to investigate the prospective association between green tea consumption and depressive symptoms in a large general adult population. METHODS: This prospective cohort study investigated 7524 participants aged 25 to 90 years from May 2013 to December 2018 and they were free of cardiovascular disease, cancer, and depressive symptoms at baseline. Green tea consumption was obtained through a validated food frequency questionnaire. Depressive symptoms were assessed by using the Self-Rating Depressive Scale (SDS). The association between green tea consumption and depressive symptoms was analyzed by Cox proportional hazards regression models. RESULTS: A total of 1064 first incident cases of depressive symptoms (SDS ≥45) occurred during 14,661 person-years of follow-up (median follow-up of 2.0 years). In the crude model, the hazard ratios (95% confidence intervals) were 1.00 (reference), 0.95 (0.81, 1.12), 0.97 (0.83, 1.14) and 0.95 (0.79, 1.14), respectively. After adjusting for demographic characteristics, lifestyle factors, and dietary intake, the multivariable adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.88 (0.74, 1.05), 0.84 (0.69, 1.02) and 0.78 (0.63, 0.97), respectively. CONCLUSIONS: The prospective study suggests that frequent green tea consumption is associated with a decreased risk of depressive symptoms in the general Chinese population.

The longitudinal associations between sweet potato intake and the risk of non-alcoholic fatty liver disease: the TCLSIH cohort study.

This study aimed to evaluate the longitudinal association between sweet potato intake and risk of NAFLD in the general adult population. In total, the number of 15,787 participants (males, 42.4%) was included in this prospective cohort study. Sweet potato intake was assessed by using a validated food frequency questionnaire. NAFLD was diagnosed by transabdominal sonography during an annual health examination. Cox proportional hazards regression models were fitted to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) across categories of energy-adjusted sweet potato intake. Compared to participants with the lowest tertile of sweet potato intake, the finally adjusted HRs (95% CIs) of incident NAFLD for those with the highest tertile were 0.87 (0.78, 0.97) in males (p for trend = 0.009); and 1.05 (0.92, 1.21) in females (p for trend = 0.52). Our study revealed that sweet potato intake was inversely associated with the risk of NAFLD in males.

Ultra-processed food consumption and the risk of subclinical thyroid dysfunction: a prospective cohort study.

Background: prospective cohort studies linking ultra-processed foods (UPF) and subclinical thyroid dysfunction (SCTD) are limited, especially in Chinese adults. Objective: we designed a large-scale cohort study to examine whether UPF consumption is a risk factor for SCTD in adults. Methods: this prospective cohort study investigated 8732 participants (mean age: 44.7 ± 10.7 years; 53.3% men). UPF consumption was measured at the baseline using a validated food frequency questionnaire and classified according to the NOVA classification system. SCTD was characterized by abnormal serum thyroid-stimulating hormone levels and normal free thyroxine. Cox proportional hazards regression models were used to examine the association of UPF consumption with the risk of various types of SCTD. Results: during the follow-up period, the incidence rate of subclinical hypothyroidism was 8.3/1000 person-years and that of subclinical hyperthyroidism was 7.0/1000 person-years. After adjusting the potential confounding factors, the multivariable hazard ratios (HRs) (95% confidence intervals) across increasing tertiles of energy-adjusted UPF consumption for subclinical hypothyroidism were 1.00 (reference), 0.82 (0.57, 1.18) and 0.87 (0.60, 1.27) (P for trend = 0.47) and for subclinical hyperthyroidism were 1.00 (reference), 1.09 (0.71, 1.68) and 1.69 (1.12, 2.56) (P for trend = 0.01). Per one standard deviation (58.0 g per 1000 kcal per day) increase in ultra-processed food consumption a 14% increase in risk of subclinical hyperthyroidism was observed (HR = 1.14; 95% CI: 1.00, 1.30; P = 0.04). Further sensitivity analysis showed that the fully adjusted HRs (95% CIs) of subclinical hyperthyroidism across tertiles of the proportion of UPF in weight for subclinical hyperthyroidism were 1.00 (reference), 1.06 (0.69, 1.63) and 1.63 (1.09, 2.46) (P for trend = 0.01). Conclusions: this population-based prospective cohort study has firstly demonstrated that higher UPF consumption was associated with higher risk of subclinical hyperthyroidism in adults. The UMIN clinical trial registry number is UMIN000027174 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031137).

Ultra-processed food intake is associated with grip strength decline in middle-aged and older adults: a prospective analysis of the TCLSIH study.

PURPOSE: Ultra-processed foods make up more than 50% of daily energy consumed in Western countries and are rapidly increasing in China. However, little is known about the association between ultra-processed food intake and muscle strength, a predictor for physical disability in senior years. We aimed to investigate the association of ultra-processed food intake with longitudinal changes in grip strength among middle-aged and older Chinese adults. METHODS: This prospective cohort study included a total of 5409 adults aged 40 years and over (61.3% men). Ultra-processed food intake was obtained by means of a validated food frequency questionnaire and classified according to the NOVA classification system. Grip strength was measured annually using a handheld digital dynamometer. Multivariable linear regression models were used to examine the association between ultra-processed food intake and annualized change in grip strength and weight-adjusted grip strength. RESULTS: In the fully adjusted models, annualized changes in grip strength and weight-adjusted grip strength per 10% increment in the proportion of ultra-processed foods in the diet were - 0.3708 kg (95% confidence interval - 0.5687, - 0.1730; P < 0.001) and - 0.0057 kg/kg (95% confidence interval - 0.0086, - 0.0029; P < 0.0001), respectively. In analyses stratified by age, sex, body mass index, physical activity, hypertension, hyperlipidemia, diabetes, and healthy diet score, such associations were largely consistent in most subgroups (all P for interaction > 0.05). CONCLUSIONS: Our data indicate that higher ultra-processed food intake was associated with faster grip strength decline in middle-aged and older Chinese adults.

[Enlightenment on Medical Equipment Application Quality Management of "Top 10 Health Technology Hazards" in Recent Five Years].

The article briefly introduced the basic situation of "top 10 health technology hazards", which issued by ECRI of United States. We comprehensively analyzes the main contents and characteristics of "top 10 health technology hazards", when issued from 2013 to 2017. Discussing the influence factors of medical devices application quality, which "top 10 health technology hazards" focus on, from human factors, risk of medical devices, information technology and other auxiliary measures. Then we introduced relevant practical measures, and discussed related enlightenment and thinking that combined with working practice.

[New Problems and Improvement Ideas of Medical Equipment Quality Control].

OBJECTIVES: To seek the ways of how to optimize medical equipment quality control, and improve the implementation effect of quality control for improving the quality of the medical equipment and clinical diagnosis and treatment. METHODS: Analysis the new problems of quality control, combined with quality control testing data, adverse events of medical equipments, and practical work of clinical diagnosis and treatment. RESULTS: Medical equipment quality control need to solve specific problems pertinently, and optimize from implementation of comprehensive quality control management system, establish standardized evaluation system and carry out research on new technologies of quality control, and so on. CONCLUSIONS: To solve the new problems promptly and to optimize related work can effectively improve the effect of quality control.

[Practices and Discusses on Medical Equipment Information Management of Military Hospital].

This paper briefly expounds the present situation of medical equipment information management in military hospitals. From basic structure and main function of the software systems, it gives a detailed introduction of the probes and researches on medical equipment information management in recent years. It analyzes the existing problems and shortcomings, combined with the previous achievements and effects, and then it introduces the ideas and goals of the new medical equipment management information system, which now being developed. Then it discusses the key problems of the new system which need to be solved.

Magnetic nanoparticle supported polyoxometalates (POMs) via non-covalent interaction: reusable acid catalysts and catalyst supports for chiral amines.

Magnetic polyoxometalates (POMs) are obtained by a simple sonication between functionalized magnetic nanoparticles and polyoxometalates. This material can be used not only as a highly active acid catalyst, but also as a catalyst support for chiral amines.

Asymmetric bifunctional primary aminocatalysis on magnetic nanoparticles.

MNP-supported chiral primary amine catalysts were developed and evaluated as asymmetric bifunctional enamine catalysts in direct aldol reaction, showing essentially unchanged activity and stereoselectivity after 11 recycles.

Evolution of pyrrolidine-type asymmetric organocatalysts by "click" chemistry.

Click chemistry has been employed to construct a library of the pyrrolidine-type asymmetric organocatalysts. The clicked organocatalysts were evaluated in asymmetric Michael addition of ketones to nitroolefins, showing good catalytic activity and stereoselectivity (up to 100% yield, syn:anti = 99:1, 96% ee).