Abstract
Background
Diabetes increases the risk of hypertension morbidity, but whether this association is varied with glycemic control remains unknown. We aimed to examine the association of ...glycemic control with hypertension among individuals with diabetes.
Methods
Data was from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Participants were categorized as having adequate glycemic control (HbA1c < 7%) and inadequate glycemic uncontrol (HbA1c ≥ 7%) by combining blood glucose tests and physician’s diagnoses in 2011. Incident hypertension was ascertained through self-reported physician diagnoses from 2011 to 2018. Cox proportional hazards regression models were used to examine the effect of glycemic control on hypertension.
Results
Among 436 participants with diabetes in this study, 102 met the glycemic control standard, and 334 were insufficient glycemic control. During 7 years of follow-up, 141 individuals developed hypertension. Compared with adequate glycemic control, the hazard ratio of inadequate glycemic control on hypertension was 1.54 (95% CI, 1.07–2.21) in the multivariate model. Additionally, the influence of glycemic control on hypertension varied based on educational attainment and the presence of depressive symptoms (P for interaction < 0.05).
Conclusions
Insufficient glycemic control was associated with a higher risk of hypertension among individuals with diabetes. Notably, the effect of glycemic control on hypertension was more pronounced among those with lower educational attainment and those exhibiting depressive symptoms. These findings underscore the significance of vigilant glycemic monitoring, educational background considerations, and mental health assessments in managing diabetic individuals.
Interleukin-35 (IL-35) is a novel anti-inflammatory cytokine of IL12 cytokine family, however, the role of IL-35 in patients with AIH and its effect on myeloid-derived suppressor cells (MDSCs) has ...not yet been analyzed. The expression of IL-35 subunits (p35 and EBI3) in liver tissues was quantified by immunochemistry and its correlation with clinical parameters was explored in patients with AIH. The expression of MDSCs and IL-35 receptor (gp130 and IL-12Rβ2) were analyzed using flow cytometry and confocal staining. Besides, we utilized
culture to explore the role of IL-35 on MDSCs expansion and activation. We found that the elevated expression of both IL-35 subunits (EBI3 and p35) in liver tissue was positively associated with degrees of hepatic inflammatory and fibrosis in patients with AIH. Furthermore, the expression of EBI3 in liver was positively correlated with patient age, serum IgG levels and serum AST, and was negatively correlated with hemoglobin and albumin. Moreover, our results showed that ratio of MDSC in peripheral blood increased significantly in AIH patients as compared with healthy controls. Further study showed that CD33, a representative marker of MDSCs, co-localized well with gp130 and IL12Rβ2, suggesting MDSCs as target cell for IL-35. Consistently, MDSCs from AIH displayed a substantial higher abundance of gp130 and IL12Rβ2 and were expanded by IL-35
. IL-35-induced MDSCs showed a significant increase in Nitric oxide (NO) production but not reactive oxygen species (ROS).
IL-35 might play an important role in AIH by regulating MDSCs and it could provide new insights into the therapy of AIH.
Introduction
To promote patients’ referral across healthcare institutions and integrated care delivery, we identified predictors of physicians’ behaviour and intention to refer patients in a county ...medical consortium in China on the basis of the theory of planned behaviour (TPB).
Methods
This census-based cross-sectional study was conducted in Yangxi Hospital Group (YHG). All physicians in county hospitals and township health centres were invited to participate. Structural equation modelling was employed to analyse the relationships between referral intention and behaviour and other TPB variables in the group of whole participants and in sub-groups.
Results
In total, 330 physicians participated in this study. One-third of participants were general practitioners, and half of them were from county hospitals. Referral behaviour of females (
χ
2
= 20.372,
p
< 0.001), who had lower education levels (
χ
2
= 17.859,
p
= 0.001), lower professional title (
χ
2
= 14.963,
p
= 0.005), and lower monthly salary (
χ
2
= 33.753,
p
< 0.001) were less frequent than the others. Among them, 116 (35.2%), 108 (32.7%), and 106 (32.1%) respondents reported that they had never referred patients, had referred patients 1–9 times, and had referred patients over 10 times during the past 3 months, respectively. The mean score of referral intention was 4.23/5 (SD = 0.71). In the model with all participants, a stronger referral intention (
β
= 0.218, 95% CI = 0.080–0.356) was associated with more frequent referral behaviour. The subjective norm (
β
= 0.703, 95% CI = 0.590–0.817) was the strongest predictor of physicians’ referral intention, followed by perceived behavioural control (
β
= 0.234, 95% CI = 0.090–0.378). Mediated by referral intention, subjective norms (
β
= 0.153,
p
< 0.01) and perceived behavioural control (
β
= 0.190,
p
< 0.01) had significant indirect effects on physicians’ referral behaviour. The model with participants in county hospitals showed similar results to the model with all participants. Meanwhile, in the model with participants in township health centres, there were no significant associations between referral behaviour and other TPB constructs.
Conclusion
Physicians’ referral behaviour was influenced by intention, subjective norms, and perceived behavioural control in Chinese county hospitals.
Background/Aims
Abdominal pain can be evoked or exacerbated after gastrointestinal cold stimulation in some patients with diarrhea-predominant irritable bowel syndrome (IBS-D), indicating a low ...temperature-induced sensitization of visceral perception. We investigated the role of vagal transient receptor potential ankyrin 1 (TRPA1, a cold-sensing ion channel) in cold-aggravated visceral mechanonociception in a stress-induced IBS animal model.
Methods
TRPA1 expression was examined in antral biopsies of healthy controls and IBS-D patients. Abdominal symptoms were assessed before and after warm or cold water intake. The visceromotor response (VMR) to colorectal distention (CRD) following intra-antral infusion of cold saline was measured in animals undergoing sham or chronic water avoidance stress. TRPA1 expression, extracellular signalregulated protein kinase 1/2 (ERK1/2) phosphorylation, and neuronal calcium influx in vagal afferents were assessed.
Results
Compared to healthy controls, IBS-D patients displayed elevated antral TRPA1 expression, which was associated with symptom scores after cold (4°C) water intake. Intra-antral infusion of cold saline increased VMR to CRD in naive rats, an effect dependent on vagal afferents. In stressed rats, this effect was greatly enhanced. Functional blockade and gene deletion of TRPA1 abolished the cold effect on visceral nociception. TRPA1 expression in vagal (but not spinal) afferents increased after stress. Moreover, the cold-induced, TRPA1- dependent ERK1/2 activation and calcium influx in nodose neurons were more robust in stressed rats.
Conclusions
Stress-exaggerated visceral mechanonociception after antral cold exposure may involve up-regulation of TRPA1 expression and function on vagal afferents. Our findings reveal a novel mechanism for abnormal gastrointestinal cold sensing in IBS.
(J Neurogastroenterol Motil 2019;25:442-460)
Background & Aims: We have identified that the anterior cingulate cortex (ACC) neurons are responsive to colorectal distention (CRD) and shown that sensitization of ACC neurons occurs in viscerally ...hypersensitive rats. However, the role of the ACC in pain response has not been clearly defined. We aimed to determine if ACC neuron activation enhances visceral pain in viscerally hypersensitive rats and to identify the receptor involved in facilitation of visceral pain. Methods: The nociceptive response (visceromotor response VMR) to CRD was recorded in normal and viscerally hypersensitive rats induced by colonic anaphylaxis. The ACC was stimulated electrically, and ACC lesions were generated with ibotenic acid. l -glutamate, α-amino-3-hydroxy-5-methyl-isoxozole propionic acid receptor antagonist cyanonitroquinoxaline dione, and N -methyl- d -aspartate receptor antagonist aminophosphonopentanoic acid were microinjected into the rostral ACC. Results: Electrical stimulation of the rostral ACC enhanced the VMR to CRD in normal rats. ACC lesions caused a decrease in the VMR in viscerally hypersensitive rats but had no effect in normal rats. ACC microinjection of 2 mmol/L glutamate increased the VMR to CRD (10 mm Hg) in viscerally hypersensitive rats, and 20 mmol/L glutamate induced a more potent VMR in viscerally hypersensitive than in normal rats. Cyanonitroquinoxaline dione did not affect the VMR in either group. Aminophosphonopentanoic acid significantly suppressed the VMR in viscerally hypersensitive rats but not in normal rats. Conclusions: The ACC plays a critical role in the modulation of visceral pain responses in viscerally hypersensitive rats. This process appears to be mediated by enhanced activities of glutamate N -methyl- d -aspartate receptors.
J. Neurochem. (2012) 121, 662–671.
The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up‐regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It ...plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of calcium/calmodulin‐dependent protein kinase II (CaMKII) in synaptic plasticity and behavior learning and memory, we hypothesize that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH states. We performed in vivo electroporation of CaMKII siRNA produced inhibition of colorectal distension‐induced visceromotor response in the VH rats. The NR2B, CaMKII and P‐CaMKII‐Thr286 protein levels were increased in 180%, 220% and 304% fold in the post‐synaptic density (PSD) fraction in VH rats separately. Western blotting following co‐immunoprecipitation showed that P‐CaMKII‐Thr286 bound to NR2B in the PSD, which was increased to 267% of control in VH rats. Administration of CaMKII antagonist Antennapedia‐CaMKIINtide suppressed visceromotor response in VH rats in parallel with decrease of NR2B levels and reduction of the NR2B‐P‐CaMKII‐Thr286 protein complex in PSD. In conclusion, CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit at post‐synaptic site, modulates visceral pain in viscerally hypersensitive state.
We have shown previously, that NR2B receptors in the ACC play a key role for modulating visceral pain, NR2B‐binding targets activate CaMKII to signaling networks in the post‐synaptic density; however, the interaction between these two molecules has not been characterized in visceral hypersensitive state. Phosphorylation of CaMKII at Thr286, which binds to NR2B subunit, is required for NR2B stabilization at post‐synaptic site, and modulates visceral pain in viscerally hypersensitive state. Understanding the molecular mechanism, especially the interaction and post‐synaptic translocation of these two important molecules (CaMKII and NR2B) would provide vital cues for future drug design and clinic therapy for visceral pain in patients such as irritable bowel syndrome (IBS).
Background and Aim: Methyl or 1, N6‐ethenoadenine base lesions are frequent and highly‐mutagenic or ‐carcinogenic events in mammalian DNA. Human AlkB homologue‐2 (hABH2), a homologue of the ...Escherichia coli AlkB protein, has been found to be the principal dioxygenase for the repair of these lesions. Mounting evidence indicates that impaired DNA repair contributes to gastric cancer induction and progression. Whether hABH2 is involved in this malignancy is unknown. The present study was aimed to investigate the expression profile of hABH2 in gastric cancer and the effect of hABH2 on cancer cell growth.
Methods: The expression of hABH2 in 35 pair‐matched gastric neoplastic and adjacent non‐neoplastic tissues, and in five gastric cancer cell lines, was examined by real‐time polymerase chain reaction (PCR), immunohistochemistry, or Western blot. The cell growth was determined using cell‐counting kit‐8 assay. The apoptosis or cell‐cycle analysis was determined using flow cytometry.
Results: The hABH2 expression was downregulated in 68% (24/35) of primary gastric cancers, as determined by real‐time PCR; the hABH2 expression was also substantially decreased in gastric cancer cell lines. Immunohistochemical or Western blot analysis further confirmed the downregulation of hABH2 expression in gastric cancers. The overexpression of hABH2 significantly inhibited the proliferation of gastric cancer cells, and induced G1 arrest of the cell cycle, while hABH2 knockdown promoted cell growth and cell‐cycle progression of gastric cancer cells.
Conclusions: These results suggest that hABH2 is downregulated in a subset of gastric cancers, and might be involved in the molecular mechanism of gastric cancer through inhibiting the proliferation of gastric cancer cells.
Ghrelin receptors are present in the central nervous system. We hypothesized that ghrelin released from the stomach acts as an endocrine substance and stimulates brain stem vagovagal circuitry to ...evoke pancreatic secretion. In an in vivo anesthetized rat model, an intravenous infusion of ghrelin at doses of 5, 10, and 25 nmol increased pancreatic protein secretion from a basal level of 125 +/- 6 to 186 +/- 8, 295 +/- 12, and 356 +/- 11 mg/h, respectively. Pretreatment with atropine or hexamethonium or an acute vagotomy, but not a perivagal application of capsaicin, completely abolished pancreatic protein secretion responses to ghrelin. In conscious rats, an intravenous infusion of ghrelin at a dose of 10 nmol resulted in a 2.2-fold increase in pancreatic protein secretion over basal volume. Selective ablation of the area postrema abolished pancreatic protein secretion stimulated by intravenous infusion of ghrelin but did not alter the increase in pancreatic protein secretion evoked by diversion of bile-pancreatic juice. Immunohistochemical staining showed a marked increase in the number of c-Fos-expressing neurons in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus after an intravenous infusion of ghrelin in sham-lesioned rats; selective ablation of the area postrema eliminated this increase. In conclusion, ghrelin stimulates pancreatic secretion via a vagal cholinergic efferent pathway. Circulating ghrelin gains access to the brain stem vagovagal circuitry via the area postrema, which represents the primary target on which peripheral ghrelin may act as an endocrine substance to stimulate pancreatic secretion.
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