The Influencing Factors of Frailty and Quality of Life in Elderly Patients After Spinal Surgery.

Background: To study the related factors of frailty and quality of life in elderly patients after spinal surgery. Methods: The anxiety, depression, frailty, and quality of life of all patients were assessed by the Anxiety screening scale (GAD-7), Depression screening scale (PHQ-9), Frailty screening scale (FRAIL), and European five-dimensional health scale (EQ-5D-5L) 1 day before surgery (DAY-0). A numeric rating scale (NRS) was used to evaluate patients' pain during activities on the 1st day (POD-1), 3rd day (POD-3), and 30th day (POD-30) after operation. FRAIL scale and EQ-5D-5L were used to evaluate patients' frailty and quality of life on POD-30 and 90th day (POD-90) after the operation. Results: There were significant differences in age, body mass index (BMI), preoperative serum albumin level (ALB), and NRS score on POD-1 between the two groups (P<0.05). Age and PHQ-9 score were positively correlated with EQ-5D-5L score (P<0.05, r Age=0.245, rPHQ-9=0.217), and preoperative ALB level was negatively correlated with EQ-5D-5L score (P<0.05, r ALB=-0.274). Conclusion: The older the age, the larger the BMI and the higher the NRS score on the first day after surgery, the more prone to frailty in elderly patients after spinal surgery; The older age and the lower the preoperative ALB level, the worse the quality of life in elderly patients after spinal surgery.

Investigating alcohol consumption in China via wastewater-based epidemiology.

Alcohol abuse and addiction is a public health issue of global concern. Wastewater-based epidemiology (WBE) is a forceful and effective complementary tool for investigating chemical consumption. This study examined alcohol consumption in major cities of China via WBE and compared WBE estimates with other data sources. A simple and valid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of two alcohol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS) in wastewater. The optimized method was applied to 62 sewage samples collected from wastewater treatment plants (WWTPs) in 31 provincial capital cities across China in the fourth quarter of 2020. The methodology established in this study was validated with the lower limit of quantification (LLOQ) up to 0.1 µg/L, good linearity in the range of 0.1-50 µg/L, intra-day and inter-day precision less than 5.58% and 5.55%, respectively, and the recoveries of the extracts were higher than 97.14%. The consumption range of alcohol estimated via WBE was 6.09 ± 4.56 ethanol/person/day (EPD) in the capital cities of China. Alcohol consumption varies significantly between cities in China, with WBE estimating lower alcohol consumption than WHO and lower than foreign countries. Investing in alcohol consumption based on WBE has great potential to accurately and efficiently estimate alcohol consumption.

The miR-214-5p/Lactoferrin/miR-224-5p/ADAM17 Axis Is Involved in Goat Mammary Epithelial Cells' Immune Regulation.

Lactoferrin (LF) is believed to be an important active protein in goat milk, which plays an anti-inflammatory role. Although LF has been reported to be associated with body health, its exact underlying mechanism remains unclear. Here, we aimed to elucidate the mechanism of this anti-inflammatory effect of LF in vitro. We first identified that miR-214-5p inhibited the expression of LF mRNA and protein in cells through the 3'UTR of LF mRNA. We next identified the alterations in miRNA following LF overexpression in goat mammary epithelial cells (GEMCs). Overexpression of LF significantly increased (p < 0.05) miR-224-5p expression. We further revealed that transcriptional activation of ADAM17, TNF-α, IL-1ß, and IL-6 was efficiently decreased (p < 0.05) in GMECs treated by miR-224-5p mimic. Conversely, knockdown of miR-224-5p increased (p < 0.05) ADAM17, TNF-α, IL-1ß, and IL-6 expression. Additionally, TNF-α, IL-1ß, and IL-6 expression levels were dramatically decreased in GMECs after administration of siADAM17. Herein, we indicate that the miR-214-5p/LF/miR-224-5p/ADAM17 axis is involved in the immune regulation of GEMCs.

Application of wastewater-based epidemiology to estimate the usage of beta-agonists in 31 cities in China.

The illegal use of beta-agonists could cause severe problems to human health. In this study, the usage of beta-agonists in 31 cities across China was estimated using wastewater-based epidemiology (WBE). The proposed method is based on solid-phase extraction (SPE) and LC-MS/MS and was developed and validated to determine the concentration of seven beta-agonists in wastewater. A population model based on cotinine (COT), NH4-N and the flow volume was constructed to estimate the population equivalents for different wastewater treatment plants (WWTPs). Clenbuterol and ractopamine are banned in China for both animal husbandry and medical use, but were nevertheless detected in some wastewater samples at rates of 6.2 % and 4.7 %, respectively (n = 339). The WBE-based consumption of clenbuterol and ractopamine were compared with the acceptable daily intake (ADI) and the health risks were assessed by their hazard quotients (0.26-6.62 for clenbuterol and 9.27 × 10-4-0.05 for ractopamine). Salbutamol, clorprenaline and terbutaline were observed in practically all wastewater samples at concentrations of up to several ng/L, whereas the formoterol and bambuterol concentrations were below the detection limit in all samples. Salbutamol consumption (7.35 ± 4.14 mg/1000 inh/day) was highest among the examined beta-agonists and varied regionally. Beta-agonist consumption based on WBE was higher in some cities than that based on medical survey data, indicating potential illegal use. These results show that WBE can be a straightforward and supplementary method for monitoring beta-agonist usage at the population level and spatially.

Spinal MCP-1 Contributes to Central Post-stroke Pain by Inducing Central Sensitization in Rats.

Central post-stroke pain (CPSP) is a highly refractory form of central neuropathic pain that has been poorly studied mechanistically. Recent observations have emphasized the critical role of the spinal dorsal horn in CPSP. However, the underlying mechanisms remain unclear. In this study, rats were subjected to thalamic hemorrhage to investigate the role of spinal monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine receptor 2 (CCR2) in the development of CPSP. Immunohistochemical staining and ELISA were used to assess the expression changes of c-Fos, Iba-1, GFAP, MCP-1, and CCR2 in the dorsal horn of the lumbar spinal cord following thalamic hemorrhage, and the involvement of spinal MCP-1 in CPSP was examined by performing intrathecal anti-MCP-1 mAb injection to neutralize the spinal extracellular MCP-1. We demonstrated that intra-thalamic collagenase microinjection induced persistent bilateral mechanical pain hypersensitivity and facilitated the spontaneous pain behaviors evoked by intraplantar bee venom injection. Accompanying CPSP, the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn was significantly increased up to 28 days post-intra-thalamic collagenase microinjection. Intrathecal injection of minocycline and fluorocitrate dramatically reverses the bilateral mechanical pain hypersensitivity. Moreover, intra-thalamic collagenase microinjection dramatically induced the up-regulation of MCP-1 but had no effect on the expression of CCR2 in the bilateral lumbar spinal dorsal horn, and MCP-1 was primarily localized in the neuron. Intrathecal injection of anti-MCP-1 mAb was also able to reverse CPSP and reduce the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn. These findings indicated that spinal MCP-1 contributes to CPSP by mediating the activation of spinal neurons and glial cells following thalamic hemorrhage stroke, which may provide insights into pharmacologic treatment for CPSP.

Estimating the prevalence of hypertension in 164 cities in China by wastewater-based epidemiology.

Hypertension is the most common chronic non-infectious disease and a severe problem for public health in China. There were 244.5 million people aged over 18 years in China who had hypertension in 2015, and hypertension-related death accounted for more than 25 % of all causes of death in China every year. To monitor the hypertension prevalence in near real-time, a wastewater-based epidemiology (WBE) approach by using metoprolol acid as a biomarker was conducted in 164 cities in China. LC-MS/MS was utilized to quantify metoprolol acid in sewage, and satisfactory method validation results were achieved. The average concentration of metoprolol acid in sewage was 943.1 ± 671.1 ng/L, and the back-calculated consumption of metoprolol based on metoprolol acid was 932.0 ± 390.5 mg/day/1000inh on average, ranging from 76.7 to 3275.7 mg/day/1000inh. The prevalence of metoprolol was estimated to be 0.83 % ± 0.35 %, and the estimated hypertension prevalence in the population aged over 15 years was ultimately assessed to be 28.56 % ± 10.44 % ranging from 14.28 % to 44.28 % and was consistent with the China Hypertension Survey result of 27.9 %. This research demonstrated that estimating hypertension prevalence by WBE with metoprolol acid as a biomarker is feasible in Chinese cities.

Physiological and pathological roles of Hic­5 in several organs (Review).

Integrins allow cells to adhere to the extracellular matrix and promote the recruitment of other integrins, resulting in the formation of focal adhesion sites at the binding sites. Focal adhesion sites play essential roles in the assembly of the cytoskeleton and are vital in shaping the structure of cells. They also play other regulatory roles by influencing numerous biological functions, such as cell proliferation and apoptosis. Hydrogen peroxide­inducible clone 5 (Hic­5) is a member of the Paxillin family of proteins and is an adhesive plaque scaffolding protein. Its expression can be detected in both vascular and smooth muscle cells. Thus, it plays an essential role in vascular remodeling, as well as in fibrotic diseases. Hic­5 functions as a coactivator of steroid receptors, thus playing a role in steroid hormone­dependent diseases. It also plays a vital role in the invasive metastasis of various types of cancer. Moreover, several studies have demonstrated that Hic­5 plays a critical role in transcriptional regulation, as well as in numerous signaling pathways. Therefore, the inhibition of the functions of Hic­5 may prevent the development or halt the progression of several diseases. Its use as a therapeutic target in future investigations may thus aid in the treatment of several diseases, including various types of cancer. The present review article focused on the expression and functions of Hic­5 in different organs, with the aim of highlighting novel possibilities for future research.

Ropivacaine-induced seizures evoked pain sensitization in rats: Participation of 5-HT/5-HT3R.

Due to the increasing use of local anesthetic techniques in various healthcare settings, local anesthetic toxicity still occurs. Seizures are the most common symptom of local anesthetic toxicity. The relationship between local anesthetic-induced seizures and the sensation of pain has not been established till now. Here, we assessed the development of pain hypersensitivity after ropivacaine-induced seizures (RIS) and the influence of RIS on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. In addition, the involvement of spinal 5-HT/5-HT3R in RIS-induced pain sensitization was investigated. According to a sequential exploratory experimental strategy, we first calculated the 50% seizure dosage of ropivacaine to be 42.66 mg/kg (95% confidence interval: 40.19-45.28 mg/kg). We showed that RIS induced significant bilateral mechanical pain hypersensitivity that lasted around 5 days, accompanied by an increase in spinal 5-HT. Moreover, RIS considerably protracted postsurgical pain and enhanced formalin-induced spontaneous flinching in the second phase. Depletion of spinal 5-HT with intrathecal injection of 5,7-dihydroxytryptamine (5,7-DHT) reduced RIS-induced pain hypersensitivity and prevented the prolonging of postsurgical pain following RIS. Likewise, blocking spinal 5-HT3R by intrathecal administration of ondansetron reversed RIS-induced pain hypersensitivity and attenuated the pronociception of RIS in the formalin test. Our findings revealed that acute RIS led to pain hypersensitivity and had pronociceptive effects on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. Moreover, our data implied that RIS-induced pain sensitization depends on spinal 5-HT/5-HT3R signaling. Thus, targeting the descending serotonergic facilitation system should be an important element of the precise treatment for local anesthetic toxicity.

RMTF-Net: Residual Mix Transformer Fusion Net for 2D Brain Tumor Segmentation.

Due to the complexity of medical imaging techniques and the high heterogeneity of glioma surfaces, image segmentation of human gliomas is one of the most challenging tasks in medical image analysis. Current methods based on convolutional neural networks concentrate on feature extraction while ignoring the correlation between local and global. In this paper, we propose a residual mix transformer fusion net, namely RMTF-Net, for brain tumor segmentation. In the feature encoder, a residual mix transformer encoder including a mix transformer and a residual convolutional neural network (RCNN) is proposed. The mix transformer gives an overlapping patch embedding mechanism to cope with the loss of patch boundary information. Moreover, a parallel fusion strategy based on RCNN is utilized to obtain local-global balanced information. In the feature decoder, a global feature integration (GFI) module is applied, which can enrich the context with the global attention feature. Extensive experiments on brain tumor segmentation from LGG, BraTS2019 and BraTS2020 demonstrated that our proposed RMTF-Net is superior to existing state-of-art methods in subjective visual performance and objective evaluation.

Targeting long noncoding RNA-AQP4-AS1 for the treatment of retinal neurovascular dysfunction in diabetes mellitus.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness in the working-age population, which is characterized by retinal neurodegeneration and vascular dysfunction. Long non-coding RNAs (LncRNAs) have emerged as critical regulators in several biological processes and disease progression. Here we investigated the role of lncRNA AQP4-AS1 in retinal neurovascular dysfunction induced by diabetes. METHODS: Quantitative RT-PCR was used to detect the AQP4-AS1 expression pattern upon diabetes mellitus-related stresses. Visual electrophysiology examination, TUNEL staining, Evans blue staining, retinal trypsin digestion and immunofluorescent staining were conducted to detect the role of AQP4-AS1 in retinal neurovascular dysfunction in vivo. MTT assays, TUNEL staining, PI/Calcein-AM staining, EdU incorporation assay transwell assay and tube formation were conducted to detect the role of AQP4-AS1 in retinal cells function in vitro. qRT-PCR, western blot and in vivo studies were conducted to reveal the mechanism of AQP4-AS1-mediated retinal neurovascular dysfunction. FINDINGS: AQP4-AS1 was significantly increased in the clinical samples of diabetic retinopathy patients, high glucose-treated Müller cells, and diabetic retinas of a murine model. AQP4-AS1 silencing in vivo alleviated retinal neurodegeneration and vascular dysfunction as shown by improved retinal capillary degeneration, decreased reactive gliosis, and reduced RGC loss. AQP4-AS1 directly regulated Müller cell function and indirectly affected endothelial cell and RGC function in vitro. Mechanistically, AQP4-AS1 regulated retinal neurovascular dysfunction through affecting AQP4 levels. INTERPRETATION: This study reveals AQP4-AS1 is involved in retinal neurovascular dysfunction and expected to become a promising target for the treatment of neurovascular dysfunction in DR. FUNDING: This work was generously supported by the grants from the National Natural Science Foundation of China (Grant No. 81800858, 82070983, 81870679 and 81970823), grants from the Medical Science and Technology Development Project Fund of Nanjing (Grant No ZKX17053 and YKK19158), grants from Innovation Team Project Fund of Jiangsu Province (No. CXTDB2017010), and the Science and Technology Development Plan Project Fund of Nanjing (Grant No 201716007, 201805007 and 201803058).

UPLC-MS/MS method for the simultaneous quantification of caffeine and illicit psychoactive drugs in hair using a single-step high-speed grinding extraction - Insights into a cut-off value for caffeine abuse.

Caffeine is a commonly consumed psychoactive substance whose addictive potential has long been reported. Excessive caffeine intake may lead to severe health damage or drug addiction problems; however, studies on the surveillance of caffeine abuse by the Chinese population are lacking. This study aimed to propose a concentration value for caffeine based on hair analysis to distinguish excessive intake from normal consumption, and provide an analytical tool for forensic toxicology investigations of caffeine and other frequently abused drugs. A sensitive and accurate ultra-high performance liquid chromatography-tandem mass spectrometry method was developed to detect caffeine and 13 illicit drugs and their metabolites in hair. Thereafter, this method was employed to test 479 real samples. Briefly, the hair samples were washed with water and acetone, and subsequently extracted by one-step high-speed grinding with acetonitrile-buffer solution. The lower limit of quantifications of 0.05 ng/mg for caffeine and THC, and 0.005 ng/mg for others, were achieved for all substances. The results revealed a mean caffeine concentration of 0.78 (range 0.008-3.5 ng/mg) based on 24 healthy volunteers, 55.0 (range 3.07-292.2 ng/mg) based on 52 self-reported caffeine abuse participants, and 5.78 (range 0-140.34 ng/mg) based on 403 drug addicts. The mean caffeine concentration in hair from self-reported caffeine abusers was 70-fold higher than that in hair from healthy volunteers. A tentative cut-off level of 5.5 ng/mg as an indicator of excessive caffeine consumption was developed based on receiver operating characteristic analysis. Additionally, the assessment of 403 hair samples from drug addicts indicated that illicit drug abusers had potential for caffeine abuse, especially polydrug users. This hair analysis method serves as a useful tool for the large-scale surveillance of caffeine and illicit drug abuse.

Outcomes of present-on-admission pressure injuries at discharge and potential prognostic factors: A historical cohort study in China.

BACKGROUND: The prevalence of present-on-admission pressure injuries (POA-PIs) is much higher than hospital-acquired pressure injuries (HAPIs). But scant attention has been paid to POA-PIs, especially the healing rate and potential prognostic factors. OBJECTIVE: To describe the characteristics of POA-PIs at admission and the outcomes of POA-PIs at discharge, and to explore potential prognostic factors of POA-PIs wound healing. METHODS: This study analyzed electronic health records (EHRs) for 838 POA-PIs among 586 patients from a Chinese tertiary hospital in 2018. The outcomes of POA-PIs were identified into four categories by comparing POA-PIs' wound area and exudation amount scores at admission and discharge: deteriorating, stable, improving, and healed. The generalized estimating equation (GEE) was carried out to screen the prognostic factors of POA-PIs wound healing. RESULTS: Among this population, 66.38% of the patients were male, 44.03% patients had a Braden Score less than 12 and the median of the Charlson comorbidity index was 5. The most common location of POA-PI wounds was the sacrum and the most common stage of them was Stage II. Nearly half of wounds (45.78%) were larger than 15 cm2, 26.61% were deeper than 0.5 cm, and 61.81% of the wounds were painful. When the patients were discharged, 29.71% wounds were healed, 36.16% were in improving status, 25.78% kept stable, and 8.35% wounds were in deteriorating status. Wound depth was the only independent prognostic factor for POA-PIs wound healing. CONCLUSIONS: The healing rate of POA-PIs is quite low, and the only independent prognostic factor of POA-PIs was wound depth.

A 10-Year Prevalence Survey and Clinical Features Analysis of Pressure Injury in a Tertiary Hospital in China, 2009-2018.

OBJECTIVE: To describe the 10-year prevalence of pressure injury (PI) in a tertiary hospital in China and determine the clinical characteristics of inpatients with PI. METHODS: The authors performed a retrospective analysis of PI cases extracted from the electronic health record of a tertiary hospital. The trend of PI prevalence over 10 years was described by estimating the average percent change (EAPC). Comorbidities were described with the Charlson Comorbidity Index (CCI). The clinical characteristics of PI were described using the number of cases and composition ratio. RESULTS: The overall prevalence of PI was 0.59% (5,838/986,404). From 2009 to 2018, the rate increased from 0.19% to 1.00% (EAPC = 22.46%). When stage I PIs were excluded, the prevalence of PI ranged from 0.15% to 0.79% (EAPC = 21.90%). The prevalence of hospital-acquired PI was 0.13%. Prevalence increased with age (Ptrend < .001) and was significantly higher in men than women (P < .001). Patients with PI were more widely distributed in the ICU (20.58%), vasculocardiology department (11.73%), gastroenterology department (10.18%), and OR (8.29%). Of patients with PI, 71.3% had a CCI score 4 or higher. CONCLUSIONS: The PI prevalence in the study facility increased rapidly over the study period. Pressure injuries among patients in the gastroenterology department and in the community deserve more attention. The CCI may be a good indicator for PI risk assessment.

Identification of aberrantly expressed circular RNAs in hyperlipidemia-induced retinal vascular dysfunction in mice.

Hyperlipidemia-induced retinal vascular dysfunction is a complex pathological process. circRNAs are important regulators of biological processes and disease progression. However, the expression pattern of circRNAs in hyperlipidemia-induced retinal vascular dysfunction remains unclear. Herein, we used a murine model of hyperlipidemia and identified 317 differentially expressed circRNAs between hyperlipidemic retinas and normolipidemic retinas by circRNA microarrays. GO analysis indicated that the host genes of dysregulated circRNAs were targeted to cell differentiation (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis revealed that circRNAs-mediated network was mostly enriched in focal adhesion signaling. Notably, circLDB1 was significantly up-regulated in the serum of coronary artery disease patients and aqueous humor of age-related macular degeneration patients. circLDB1 regulated endothelial cell viability, proliferation, and apoptosis in vitro. Thus, circRNAs are the promising targets for the prediction and diagnosis of hyperlipidemia-induced vascular diseases.

Hemoglobin glycation index in relationship to the risk of cardiovascular complication in patients with type 2 diabetes: A systematic review and meta-analysis.

AIM: To estimate the association of hemoglobin glycation index (HGI) level with total mortality and cardiovascular complication risk among patients with T2DM. METHODS: Literatures evaluating the associations of HGI with the risk of cardiovascular outcomes and total mortality in patients with T2DM were systematically searched by using the PubMed and Embase databases from January 2002 to April 2019. Fixed-effects model and random-effects model meta-analyses were used to calculate pooled adjusted hazard ratios (HRs). RESULTS: Six prospective cohort studies and one nest case-control study (comprising n = 37,280) were included in this systematic review. T2DM patients with high HGI level had significant high HRs (95% confidence interval, 95% CI) for cardiovascular complication [1.25 (1.16, 1.36)] and total mortality [1.26 (1.14, 1.39)] compared to intermediate HGI level. For every 1-unit increment in HGI, the average HR (95% CI) were 1.20 (1.00, 1.41) for cardiovascular complication and 1.13 (1.06, 1.19) for total mortality. CONCLUSIONS: The findings suggested that a rising HGI level was associated with the increased risk for cardiovascular complication and total mortality among patients with T2DM.

Epidermal Growth Factor Stimulates Fatty Acid Synthesis Mainly via PLC-γ1/Akt Signaling Pathway in Dairy Goat Mammary Epithelial Cells.

EGF acts as a ligand of the EGF receptor (EGFR) to activate the EGFR-mediated signaling pathways and is involved in the regulation of cell physiology. However, the roles of EGFR mediated signaling pathways in the regulation of lipid metabolism in goat mammary epithelial cells (GMECs) are poorly understood. To evaluate the impact of EGF on GMECs, the triglyceride (TG) content and lipid droplet were detected, using TG assay and immunofluorescence. Further, expression of lipogenic genes, the protein kinase B (Akt), phospholipase C-γ1 (PLC-γ1) and extracellular signal-regulated kinases (ERK)1/2 signaling pathways were measured by real-time polymerase chain reaction and Western blot, respectively. The results showed that the mRNA expression of EGFR gene was significantly upregulated in lactating goat mammary gland tissues compared to non-lactation period (p < 0.05). TG contents in EGF-treated GMECs were significantly increased (p < 0.05), and an increase of lipid droplets was also detected. In vitro studies demonstrated that the mRNA levels of lipogenesis-related FASN, ACC, SCD1, LXRa, LXRb and SP1 genes were positively correlated to the mRNA level of EGFR gene shown by gene overexpression and silencing (p < 0.05). The phosphorylations of Akt, ERK1/2 and PLC-γ1 in GMECs were greatly upregulated in the presence of EGF, and specific inhibitors were capable of blocking the phosphorylation of Akt, ERK1/2 and PLC-γ1. Compared with EGF-treated GMECs, the mRNA levels of FASN, ACC and SCD1 were significantly decreased in GMECs co-treated with PLC-γ1 and Akt inhibitor and EGF (p < 0.05), and TG content was also dropped significantly. These observations implied that EGFR plays an important role in regulating de novo fatty acid synthesis in GMECs, mainly mediated by Akt and PLC-γ1 signaling pathways.

CYP24A1 genetic variants in the vitamin D metabolic pathway are involved in the outcomes of hepatitis C virus infection among high-risk Chinese population.

BACKGROUND AND AIMS: It has been demonstrated that 1,25-hydroxyvitamin-D3-24-hydroxylase, encoded by CYP24A1 gene, is a key enzyme that neutralizes the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in response to hepatitis C virus (HCV) infection. This study aimed to investigate whether CYP24A1 genetic variation is associated with HCV infection outcomes. METHODS: 848 HCV chronically infected subjects, 507 natural clearance subjects, and 1017 uninfected controls were enrolled. Nine single nucleotide polymorphisms (SNPs) in theCYP24A1 gene were genotyped using the Sequenom MassARRAY platform. RESULTS: After adjusting for age, gender, and routes of infection, logistic regression analyses showed that rs6013897-A was associated with an elevated risk of HCV infection (P<0.05). In addition, this study has also demonstrated that rs6068816-T significantly reduced the risk of chronic HCV infection, while rs3787557-C, rs6022999-G, and rs2248359-T significantly increased the risk of chronic HCV infection (all P<0.05). Haplotype analysis suggested that, compared to the most frequent Trs6068816Trs3787557Ars6022999Crs2248359 haplotype, the CTGT haplotype (adjusted OR=1.376, 95% CI=1.092-1.735, P=0.007) and CCAC haplotype (adjusted OR=1.483, 95% CI=1.139-1.929, P=0.003) were associated with an increased risk of chronic HCV infection. CONCLUSION: These findings indicate that SNPs in CYP24A1 gene may contribute to the risk of HCV infection and chronic HCV infection among a high-risk Chinese population.

Effects of dexmedetomidine on postoperative cognitive function in patients undergoing coronary artery bypass grafting.

Effects of dexmedetomidine on postoperative cognitive function in patients undergoing coronary artery bypass grafting were investigated. Eighty patients undergoing systemic anesthesia with extracorporeal coronary artery bypass grafting in The People's Hospital of Guangxi Zhuang Autonomous Region from January 2015 to August 2017 were selected and randomly divided into the observation group (n=40) and control group (n=40). The two groups were treated with dexmedetomidine and equal volume of normal saline, respectively. Moreover, safety indexes including EEG bispectral index (BIS) at 30 min before induction of anesthesia (T0), immediately after intubation (T1), when incision was made (T2), when chest was closed (T3), when operation was completed (T4) and at 6 h after operation (T5), intraoperative circulatory system-related complications, cortisol, epinephrine and norepinephrine levels at the end of surgery as well as anesthesia recovery time and postoperative mechanical ventilation time were recorded and compared. All the patients were followed up for 1 week. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were administered at 1, 3 and 7 days after operation, and the incidence of intraoperative awareness and postoperative cognitive dysfunction was recorded. BIS value in the observation group was lower than that in the control group (P<0.05) at T1-T4 time points, and the BIS value in the observation group was higher than that in the control group (P<0.05) at T5. Incidence rates of intraoperative arrhythmia, hypertension and hypotension in the observation group was significantly lower than those in the control group (P<0.05). At the end of operation, levels of cortisol, epinephrine and norepinephrine in the observation group were significantly lower than those in the control group (P<0.05). Anesthesia recovery time and postoperative mechanical ventilation time in the observation group was significantly shorter than the time in the control group (P<0.05). MMSE and MoCA scores of the observation group were better than those of the control group (P<0.05). The incidence of cognitive impairment and postoperative cognitive impairment in the observation group was significantly lower than those in the control group (P<0.05). Therefore, it is concluded that dexmedetomidine can effectively reduce the incidence of postoperative cognitive impairment in patients undergoing coronary artery bypass grafting, and it is of high safety for circulatory function.

Dexmedetomidine pretreatment attenuates propofol­induced neurotoxicity in neuronal cultures from the rat hippocampus.

Propofol is widely used for the induction and maintenance of pediatric anesthesia. Previous studies have indicated that propofol can induce apoptosis, and damage cognitive and memory functions. Dexmedetomidine is a potent α­2 adrenoceptor agonist with high selectivity. Previous observations have shown that dexmedetomidine exhibits anti­apoptotic qualities. The present study evaluated the neuroprotective effects of dexmedetomidine pretreatment against propofol­induced neurotoxicity in immature hippocampal neurons. The viability and apoptotic rate of the neurons were detected using a Cell Counting Kit­8 assay and flow cytometry. The mRNA and protein expression levels of brain­derived neurotrophic factor (BDNF), B­cell lymphoma­2 (Bcl­2) and phosphorylated­cyclic­AMP response element binding protein (p­CREB) were detected using semiquantitative reverse transcription­polymerase chain reaction and western blot analyses, respectively. These results showed that propofol exposure (100 µM; 3 h) reduced neuronal viability, induced cell apoptosis and decreased the expression levels of BDNF, Bcl­2 and p­CREB. Dexmedetomidine treatment (0.001­100 µM) of the neurons prior to propofol exposure attenuated the propofol­induced neuronal apoptosis and increased expression levels of BDNF, Bcl­2 and p­CREB compared with the propofol only group. In addition, dexmedetomidine at the highest concentration provided superior neuroprotection of neurons. These in vitro data indicated that dexmedetomidine exerted direct neuroprotective effects to prevent cultured hippocampal neuronal injury caused by propofol, accompanied by an increase in the levels of p­CREB, Bcl­2 and BDNF.

Propofol inhibits proliferation and induces neuroapoptosis of hippocampal neurons in vitro via downregulation of NF-κB p65 and Bcl-2 and upregulation of caspase-3.

Propofol is widely used in paediatric anaesthesia and intensive care unit because of its essentially short-acting anaesthetic effect. Recent data have shown that propofol induced neurotoxicity in developing brain. However, the mechanisms are not extremely clear. To gain a better insight into the toxic effects of propofol on hippocampal neurons, we treated cells at the days in vitro 7 (DIV 7), which were prepared from Sprague-Dawley embryos at the 18th day of gestation, with propofol (0.1-1000 µM) for 3 h. A significant decrease in neuronal proliferation and a remarkable increase in neuroapoptosis were observed in DIV 7 hippocampal neurons as measured by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay respectively. Moreover, propofol treatment decreased the nuclear factor kappaB (NF-κB) p65 expression, which was accompanied by a reduction in B-cell lymphoma 2 (Bcl-2) mRNA and protein levels, increased caspase-3 mRNA and activation of caspase-3 protein. These results indicated that downregulation of NF-κB p65 and Bcl-2 were involved in the potential mechanisms of propofol-induced neurotoxicity. This likely led to the caspase-3 activation, triggered apoptosis and inhibited the neuronal growth and proliferation that we have observed in our in vitro systems.