Associations between meteorological variation and rupture of intracranial aneurysm in Fujian, China: A 5-year multicenter study.

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.

Influence of miR-520e-mediated MAPK signalling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2.

We determined the role of miR-520e in the replication of hepatitis B virus (HBV) and the growth of hepatocellular carcinoma (HCC) cells. MiR-520e and EPH receptor A2 (EphA2) in HBV-positive HCC tissues and cells were detected, and we studied the impact of miR-520e and the EphA2 receptor in cellular and murine HBV replication models. We find that MiR-520e was upregulated and EphA2 was downregulated in HBV-positive HCC tissues and cells. MiR-520e was decreased in Huh7-X and HepG2-X cells in which HBx was stably expressed, but was dose-dependently elevated after interfering with HBx. Additionally, miR-520e mimic and si-EphA2 groups were reduced in association with increases in HBV DNA content, HBsAg and HBeAg levels, cell proliferation and were enhanced in the expressions of EphA2, p-p38MAPK/p38MAPK, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2)/ERK1/2 and cell apoptosis. Furthermore, si-EphA2 reversed the promotion effect of miR-520e inhibitor on HBV replication and tumour cell growth. Upregulating miR-520e in rAAV8-1.3HBV-infected mouse resulted in reduced EphA2 in liver tissues and HBV DNA content in serum. We find that MiR-520e was decreased in HBV-positive HCC, while overexpression of miR-520e blocked p38MAPK and ERK1/2 signalling pathways by an inhibitory effect on EphA2 and ultimately reduced HBV replication and inhibited tumour cell growth. These data indicate a role for miR-520e in the regulation of HBV replication.

Prognostic factors affecting the ruptured intracranial aneurysms: A 9-year multicenter study in Fujian, China.

BACKGROUND: A multicenter retrospective study was conducted to explore the factors affecting short-term prognosis and long-term outcomes of intracranial aneurysms (IA) rupture. Further, the prognosis prediction model was constructed based on survival analysis, contributing to the development of prevention strategies for aneurysmal subarachnoid hemorrhage. METHODS: Data of 1280 patients with IA rupture were gathered between 2014 and 2022 in Fujian, China. Logistic regression was implemented to study the short-term prognostic factors of IA rupture. Survival analysis of 911 patients among them was performed to explore the long-term outcome status by Cox risk assessment. Nomogram prognosis models were constructed using R software. RESULTS: The findings displayed that blood type O (OR = 1.79; P = 0.019), high systolic pressure (OR = 1.01; P < 0.001), Glasgow Coma score (GCS) 9-12 (OR = 2.73; P = 0.022), GCS < 9 (OR = 3.222; P = 0.006), diabetes (OR = 2.044; P = 0.040), and high white blood cell count (OR = 1.059, P = 0.040) were core influencing factors for poor short-term prognosis. Survival analysis revealed that age > 60 years (HR = 2.87; P = 0.001), hypertension (HR = 1.95; P = 0.001), conservative (HR = 6.89; P < 0.001) and endovascular treatment (HR = 2.20; P = 0.001), multiple ruptured IAs (HR = 2.37; P = 0.01), Fisher 3 (HR = 1.68; P = 0.09), Fisher 4 (HR = 2.75; P = 0.001), and Hunt-Hess 3 (HR = 0.55; P = 0.05) were the major risk factors for terrible long-term outcomes. CONCLUSIONS: People over 60 years with characteristics of type O blood, high systolic pressure, diabetes, high white blood cell count, and onset GCS < 12 will have more complications and a worse short-term prognosis. Those aged > 60 years with hypertension, conservative and endovascular treatment, multiple ruptured IAs, Fisher ≥ 3 and Hunt-Hess 3 have a greater risk of poor long-term prognosis.

Blood-nerve barrier disruption and coagulation system activation induced by mechanical compression injury participate in the peripheral sensitization of trigeminal neuralgia.

Introduction: The aim of this study was to investigate the effect and possible mechanisms of the blood-nerve barrier (BNB) and the coagulation-anticoagulation system in modulating the mechanical allodynia in a trigeminal neuralgia (TN) rat model induced by chronic compression of the trigeminal root entry zone (TREZ). Methods: Von Frey filaments were applied to determine the orofacial mechanical allodynia threshold. The BNB permeability was evaluated by Evans blue extravasation test. Immunohistochemical staining and laser confocal microscopy were used to measure the length of the depletion zones of the nodes of Ranvier in the TREZ, the diameter of nerve fibers and the length of the nodal gap. The transcriptional levels of prothrombin and endogenous thrombin inhibitor protease nexin-1 (PN-1) in the TREZ of TN rats were assessed by RT-qPCR. A Western blotting assay was performed to detect the expression of paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) in the TREZ. The spatiotemporal expression pattern of thrombin activated receptor (i.e. protease activated receptor 1, PAR1) in TREZ were defined by immunostaining and immunoblotting assays. PAR1 receptor inhibitors SCH79797 were administrated to TN rats to analyze the effect of thrombin-PAR1 on orofacial hyperalgesia. Results: A compression injury of a rat's TREZ successfully induced TN-like behavior and was accompanied by the destruction of the permeability of the BNB and the promotion of prothrombin and thrombin inhibitor protease nexin-1 (PN-1) expression. The expression of the paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) was increased, while the nodal gap length of the nodes of Ranvier was widened and the length of node-depleted zones was shortened. Moreover, the expression of PAR1 within the TREZ was upregulated at an early stage of TN, and administration of the PAR1 antagonist SCH79797 effectively ameliorated orofacial mechanical allodynia. Conclusion: A compression injury of the TREZ increased the permeability of the BNB and induced disturbances in the local coagulation-anticoagulation system, concomitant with the structural changes in the nodes of Ranvier, thrombin-PAR1 may play a critical role in modulating orofacial mechanical hyperalgesia in a TN rat model.

[Effects of the workplace violence on the sub-health status of nurses].

OBJECTIVE: To explore the effects of workplace violence on sub-health status of nurses and to provide the theoretical basis for preventing the workplace violence in the hospitals and improving the health status of nurses. METHODS: A total of 679 nurses were selected by using stratified cluster sampling method. The Chinese version of workplace violence scale (WVS) and sub-health scale were used to measure workplace violence and sub-health status, respectively. RESULTS: The subjects with middle age (30-45 years) were found to have the highest incidence of physical assault (24.5%) and emotional assault (52.2%) as compared with other subjects (P<0.05). The prevalence (23.6%) of emotional assault of subjects with lowest education levels was significantly lower than that of others (P<0.05). The nurses with work shift were more vulnerable to emotional assault (45.1%) than those without work shift (36.8%)(P<0.05). The prevalence of the workplace violence of nurses in the psychiatric department and emergency department was significantly higher than that of nurses in other departments (P<0.05). The results of multivariate analysis showed that workplace violence was an important risk factor for sub-health status of nurses when other potential confounding factors were taken into account. CONCLUSION: The results of present study showed that workplace violence plays an important role in sub-health status of nurses after adjusting other potential confounding factors. It is important to develop the prevention strategies for reducing the incidence of workplace violence and improving the sub-health status of nurses.

Using RNA-Seq to Explore the Hub Genes in the Trigeminal Root Entry Zone of Rats by Compression Injury.

BACKGROUND: Mechanical compression on the trigeminal root entry zone (TREZ) by microvascular is the main etiology of primary trigeminal neuralgia (TN). OBJECTIVES: To study the pathogenesis of TN, hub genes screening in the TREZ of TN in an animal model was performed. STUDY DESIGN: A double blind, randomized study was designed in a controlled animal trial. SETTING: The research took place in the Laboratory of Clinical Applied Anatomy at the School of Basic Medical Science of Fujian Medical University. METHODS: Twelve male rats were randomly divided into a sham operation group and a TN animal model group. TN animal model was induced by chronic compression of trigeminal nerve root (CCT) operation. Gene expression in the TREZ were analyzed by RNA sequencing (RNA-Seq) technique. KEGG analysis, GO analysis, and PPI analysis were performed in the DEGs. Key signaling pathways analyzing by GSEA and the hub genes in the DEGs were also studied. Reverse transcription real-time polymerase chain reaction (RT-qPCR) was used to verify the RNA-Seq results. RESULTS: Transcriptome data showed that 352 genes up-regulated and 59 genes down-regulated in DEGs on post-operation day 21, after CCT operation in the TN group. KEGG analysis revealed that, "neuroactive ligand receptor interaction" and "cytokine cytokine receptor interaction" may be related to the pathogenesis of TN. GO analysis showed "regulation of signing receptor activity", "chemokine activity", and "carbohydrate binging" may be related to TN. The RT-qPCR results were consistent with the test results, indicating that the transcriptome sequencing results were reliable. LIMITATIONS: Although the incidence of TN in female rats was higher than in male rats, we only used male SD rats to establish the TN animal model, to avoid the effect of estrogen on experimental results. This study only presents some respects of RNA-Seq technique and, therefore, did not identify the DEGs at the protein level. The relationship between the DEGs at different levels shoud be done in the future. CONCLUSIONS: Based on the results of RNA-seq, this study discovered 6 hub genes in the TREZ that are closely related to the TN animal model, which provide a potential breakthrough point to explore the pathogenesis of TN.

Enhanced luminescence intensity of near-infrared-sensitized upconversion nanoparticles via Ca2+ doping for a nitric oxide release platform.

Light-induced NO release based on exogenous NO donors has attracted substantial attention in clinical applications; the induction light source usually converts near-infrared light to blue or ultraviolet light. However, the low efficiency of near-infrared light-assisted chemical light energy conversion remains a challenge, especially for NaYF4:Yb3+/Tm3+ photoconverting near-infrared light to ultraviolet (UV) and blue light. In this paper, a luminescence-enhanced strategy is reported by doping Ca2+ into NaYF4:Yb3+/Tm3+ and coating it with NaGdF4 through a two-step solvothermal method. Then, UCNPs modified with methyl-ß-cyclodextrin (M-ß-CD) are loaded on a ruthenium nitrosyl complex [(3)Ru(NO)(Cl)] as nitric oxide release-molecules (NORMs). X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDS) data demonstrated that Ca2+ was successfully doped into NaYF4:Yb3+/Tm3+ nanoparticles as the core, and a pure hexagonal phase, NaYF4, was obtained from the doping of Ca2+. TEM revealed that the crystallinity was significantly improved after Ca2+ doping, and the core-shell structure was successfully synthesized, with NaGdF4 directionally grown on the NaYF4:Ca/Yb/Tm core. Fluorescence tests showed that, especially in the ultraviolet and blue light excitation wavelength regions, the UC emission intensity of the Ca-doped NaYF4:Yb3+/Tm3+@NaGdF4 core-shell UCNPs increased by 302.95 times vs. NaYF4:Yb3+/Tm3+ UCNPs. Finally, the release of NO was tested by the Griess method. Under 980 nm irradiation, the cell viability distinctly decreased with increasing UCNPs@M-ß-CD-NORMs concentration. This study shows that NORM release of NO is triggered by enhanced up-converted UV and blue light, which can be used for the development of UV photo-sensitive drugs.

Ventral tegmental area GABAergic neurons induce anxiety-like behaviors and promote palatable food intake.

The obesity epidemic is a global problem and a great challenge for public health. Overconsumption of food, especially palatable food, is the leading cause of obesity. The precise neural circuits underlying food overconsumption remain unclear and require further characterization. In the present study, we showed that Ca2+ signals of GABAergic neurons within the ventral tegmental area (VTA) increased after the onset of food intake, especially high-fat or high-sugar chow. Optogenetic activation of VTA GABAergic neurons evoked immediate eating of palatable food and significantly increased palatable food intake in satiated mice. Photoinhibition of VTA GABAergic neurons suppressed palatable food intake. Surprisingly, photoactivation of VTA GABAergic neurons suppressed the intake of standard chow in fasted mice, but did not reduce the duration of eating of standard chow. Moreover, we found that photoactivation of these neurons drove a series of anxiety-like behaviors in the open field, elevated plus maze, and marble-burying test. Additionally, we found that VTA GABAergic neurons sent abundant projections to the lateral hypothalamus and photoactivation of GABAergic VTA terminals in the lateral hypothalamus induced overconsumption of palatable food, but not anxiety-like behaviors. Taken together, our results illustrate that GABAergic VTA neurons are a key node in the neural circuitry underlying anxiety-like behavior and over-feeding of palatable food, and that over-excitation of GABAergic VTA neurons may underlie clinical diseases related to anxiety and obesity.

Exploration of high-risk factors for pulmonary embolism in patients undergoing postoperative anti-thrombotic therapy among gynecologic oncology surgery: a retrospective study.

BACKGROUND: The aim of this study was to find the high-risk factors of patients undergoing postoperative anti-thrombotic therapy that had a pulmonary embolism (PE). METHODS: In this retrospective analysis, a total of 35 patients with gynecologic oncological surgery were included from April 3, 2013, to January 12, 2018. Variable characteristic selection (Boruta's method), binary logistic regression (Fifth's method), and elastic network analysis were used to establish models and screen the high-risk factors. The decision curve analysis (DCA) was used to discriminate differences on these models as well. RESULTS: Three models were established, and the clinical efficiency of these three models was similar. Within the risk range of 0.1-0.3, the elastic network model was shown to have a good net benefit rate. The preoperative cholesterol levels were selected in all three models. The high-risk factors that were selected in both models were operative time, preoperative fibrinogen level, crystal rehydration on the day of surgery in the ward, a preoperative low-density lipoprotein (LDL) level, deep venous catheters, and presence of colloids. Other factors included crystal fluid intake during surgery, age, and chemotherapy before surgery. CONCLUSIONS: Positive anti-thrombotic therapy may be required among the patients with increased risk and further research might be needed to verify high-risk factors.

Meteorological Variation Is a Predisposing Factor for Aneurismal Subarachnoid Hemorrhage: A 5-Year Multicenter Study in Fuzhou, China.

OBJECTIVE: The climatic characteristics of aneurysmal subarachnoid hemorrhage (aSAH) have been reported, but consensus has not yet been reached. It is of great significance to elucidate the relationships between meteorological variation and aSAH in regions with specific climate patterns. We analyzed the occurrence of aSAH in the capital city of Fujian Province, China, through a multicenter, 5-year study, and aimed to reveal the meteorological influences on aSAH in the coastal city of eastern Fujian under the subtropical marine monsoon condition. METHODS: A total of 2555 consecutive patients with aSAH in Fuzhou were collected using specialized stroke admission database from January 2013 to December 2017. Meteorological parameters including temperature, atmospheric pressure, and humidity were obtained from China Surface Meteorological Station during the same period. Poisson regression was used to explore the association between meteorological parameters and aSAH to calculate the incidence rate ratios (IRRs) with corresponding 95% confidence intervals (CIs). Generalized additive model analysis further revealed the nonlinear relationships between weather and aSAH. RESULTS: Daily minimum temperature (IRR 0.976, 95% CI 0.958-0.996) and maximum pressure (IRR 1.022, 95% CI 1.001-1.042) were independently correlated with the onset of aSAH. Low temperature (below 16°C) and excessive atmospheric pressure (above 1008 hPa) increased the risk of aSAH. In addition, March in spring and December in winter were the 2 ictus peaks in Fuzhou throughout the year. CONCLUSIONS: Cold and excessive atmospheric pressure are triggers for the occurrence of aSAH; March in spring and December in winter are the predominant onset periods in Fuzhou.

Juniperonic Acid Incorporation into the Phospholipids of Murine Macrophage Cells Modulates Pro-Inflammatory Mediator Production.

Juniperonic acid (JPA; Δ5,11,14,17-20:4), originally identified in certain gymnosperm seeds, is a rare n-3 polyunsaturated fatty acid (PUFA) with lipid-modulating effects on rats and anti-proliferative effects on fibroblast cell proliferation. However, little is known how JPA exerted its immunosuppressive effect. The objective of this study was to investigate whether JPA inhibited the production of inflammatory mediators through the modulation of cellular phospholipid fatty acid compositions. Using standard lipid chemistry techniques in conjunction with argentated column chromatography, high-purity JPA (> 98%) was extracted, isolated, and purified from Biota kernels. When murine RAW264.7 macrophages were incubated with increasing concentrations of JPA, amounts of cellular phospholipid total PUFA, JPA, and Δ7-docosatetraenoic acid (Δ7-DTA; elongation product of JPA) increased in a dose-dependent manner; however, the proportions of total monounsaturated fatty acid (MUFA) and arachidonic acid (AA) decreased. JPA suppressed the production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and the expression of inducible nitric oxide synthase (iNOS) up to 21, 75, 30, and 44%, respectively. The induction of cyclooxygenase-2 (COX-2) over-expression by JPA could account for the doubling of the PGE2 level. Furthermore, JPA suppressed the expression of phosphorylated mitogen-activated protein kinases (MAPK). In a separate study using the mouse ear edema model, we demonstrated that JPA also significantly suppressed inflammation, as measured by ear thickness and biopsy weight. The anti-inflammatory properties of JPA could be due, in part, to the incorporation of JPA into cellular phospholipids with subsequent modulation of membrane-mediated MAPK signaling.

The Influence of Tablet Formulation, Drug Concentration, and pH Modification on the Stability of Extemporaneously Compounded Levothyroxine Suspensions.

Three brands of levothyroxine tablets are currently available in New Zealand (Eltroxin, Mercury Pharma, Synthroid) for extemporaneous compounding into suspensions. This study aims to determine whether tablet brand (i.e., formulation), concentration, storage conditions, as well as pH, impact the stability of compounded levothyroxine suspensions. Using the three available brands of levothyroxine tablets, suspensions were compounded at concentrations of 15 µg/mL and 25 µg/mL and stored at 4°C and 22°C. Samples were withdrawn weekly for 4 weeks, and chemical stability was evaluated using high-performance liquid chromatographic analysis. Physical appearance, ease of resuspension, and pH were also monitored weekly. To evaluate the effect on drug stability, pH modifiers were added to a suspension. As demonstrated by high-performance liquid chromatographic analysis, the suspensions compounded from the Eltroxin and Mercury Pharma tablets were more stable (>90% remaining after 4 weeks) than Synthroid across both storage conditions and concentrations. The drug was more stable at the higher concentration of 25 µg/mL than at 15 µg/mL. Levothyroxine was stable when pH was increased to pH 8 through the addition of sodium citrate; stability was reduced at a lower pH. Storage temperature did not affect the stability of the suspensions during the 4-week study. This is the first study demonstrating the impact of tablet brand, with different excipients, and drug concentrations on stability, and thus the beyond-use date of the compounded levothyroxine liquid formulations. The pH control achieved by sodium citrate, either as an excipient in tablets or an additive during compounding, improved drug stability.

Independent and combined effects of environmental factors and miR-126, miR-143, and miR-145 on the risk of coronary heart disease.

OBJECTIVE: To evaluate the effects of environmental factors and microRNAs (miRNAs) (miR-126, miR-143, and miR-145) on the risk of coronary heart disease (CHD). METHODS: A frequency-matched case-control study (450 patients, 450 controls) was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, miR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction (PCR) in peripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation. RESULTS: Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD. CONCLUSIONS: Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.

Genetic variants in PNPLA3 and risk of non-alcoholic fatty liver disease in a Han Chinese population.

We investigated the possible association between genetic variants in the Patatin like phospholipase-3 (PNPLA3) gene and nonalcoholic fatty liver disease (NAFLD) in a Han Chinese population. We evaluated twelve tagging single-nucleotide polymorphisms (tSNPs) of the PNPLA3 gene in a frequency matched case-control study from Fuzhou city of China (553 cases, 553 controls). In the multivariate logistic regression analysis, the rs738409 GG or GC, and rs139051 TT genotypes were found to be associated with increased risk of NAFLD, and a significant trend of increased risk with increasing numbers of risk genotype was observed in the cumulative effect analysis of these single nucleotide polymorphisms. Furthermore, haplotype association analysis showed that, compared with the most common haplotype, the CAAGAATGCGTG and CGAAGGTGTCCG haplotypes conferred a statistically significant increased risk for NAFLD, while the CGGGAACCCGCG haplotype decreased the risk of NAFLD. Moreover, rs738409 C>G appeared to have a multiplicative joint effect with tea drinking (P<0.005) and an additive joint effect with obesity (Interaction contrast ratio (ICR) = 2.31, 95% CI: 0.7-8.86), hypertriglyceridemia (ICR = 3.07, 95% CI: 0.98-5.09) or hypertension (ICR = 1.74, 95% CI: 0.52-3.12). Our data suggests that PNPLA3 genetic polymorphisms might influence the susceptibility to NAFLD development independently or jointly in Han Chinese.