Chinese hospital staff in anxiety and depression: Not only comfort patients but also should be comforted - A nationwide cross-sectional study.

BACKGROUND: Healthcare professionals are in short supply worldwide, especially in China, which can result in increased stress in the work environment and allostatic load for Chinese hospital staff. This study aimed to investigate the prevalence of anxiety and depressive symptoms and their relationship with total stress, allostatic overload, sleep quality, and episodic memory among Chinese hospital staff. METHOD: In this cross-sectional study, self-assessments including Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire-9 (PHQ-9), PsychoSocial Index (PSI), Pittsburgh Sleeping Quality Index (PSQI), and MemTrax test were used to evaluate participants' anxiety symptoms, depressive symptoms, total stress, allostatic load/overload, sleep quality, and episodic memory. RESULTS: A total of 9433 hospital staff from 304 cities participated. Anxiety prevalence was 21.0 % (95 % confidential interval (CI) 20.2 %, 21.8 %), while the prevalence of depressive symptoms was at 21.4 % (95 % CI 20.5 %, 22.2 %). 79.8 % (95 % CI 79.0 %, 80.6 %) of the hospital staff had allostatic overload. Poor sleep quality affected 50.4 % of participants, and 32.1 % experienced poor episodic memory. LIMITATIONS: This study utilized a convenience sampling approach, relying on an online survey as its data collection method. CONCLUSIONS: Hospital staff in China are facing a stressful environment with a high prevalence of anxiety and depressive symptoms, significant allostatic overload, poor sleep quality, and compromised episodic memory. It is imperative that local management and community structures enhance their support and care for these essential workers, enabling them to manage and withstand the stresses of their professional roles effectively.

Autoimmune encephalitis with posterior reversible encephalopathy syndrome: A case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a neuroimaging-based syndrome and is associated with multifocal vasogenic cerebral edema. Patients with PRES frequently demonstrate headache, seizure, encephalopathy, altered mental function, visual loss and so on. We here report a patient who showed persistent neurologic deficits after PRES and was ultimately diagnosed with autoimmune encephalitis (AE). CASE SUMMARY: This case exhibits a rare imaging manifestation of anti-casper 2 encephalitis which was initially well-matched with PRES and associated vasogenic edema. CONCLUSION: AE should be further considered when the etiology, clinical manifestations, and course of PRES are atypical.

Gastrodin Attenuates Lipopolysaccharide-Induced Inflammatory Response and Migration via the Notch-1 Signaling Pathway in Activated Microglia.

Microglia-mediated neuroinflammation is known to play a pivotal role in the pathogenesis of different neurological diseases. Gastrodin, a phenolic glucoside, has been reported to exert anti-inflammatory effects in activated microglia challenged with lipopolysaccharide (LPS); however, the underlying mechanism has remained obscure. The present study aimed to ascertain if Gastrodin would regulate the Notch signaling pathway involved in microglia activation. We show here that LPS increased the expression of various members of the Notch-1 pathway, including intracellular Notch receptor domain (NICD), recombining binding protein suppressor of hairless (RBP-Jκ) and transcription factor hairy and enhancer of split-1 (Hes-1) in microglia in postnatal rat brain and in BV-2 microglia. Remarkably, Gastrodin was found to markedly attenuate the expression of the above various biomarkers both in vivo and in vitro. Moreover, increased phosphorylation level of ERK, JNK and P38 induced by LPS was attenuated with pretreatment of Notch-1 signaling inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alany1-Sphenyglycinet-butylester (DAPT) as well as Gastrodin. Gastrodin mimicked the effects of DAPT by inhibiting the LPS-induced expression of IL-1ß, IL-6, IL-23, TNF-α and NO. Moreover, lentivirus transfection mediated NICD overexpression inhibited the anti-inflammatory effects of Gastrodin. Furthermore, the activation of Notch-1 signaling promoted microglia migration and Gastrodin could inhibit the migration of activated BV-2 microglia by regulating the Notch-1 signaling pathway. In light of the above, our results indicate that Notch-1 signaling pathway is involved in the anti-inflammatory effects of Gastrodin against LPS-induced microglia activation. These findings provide a new biological target of Gastrodin for the treatment of neuroinflammatory disorders.

Ginsenoside Rg1 Inhibits Microglia Pyroptosis Induced by Lipopolysaccharide Through Regulating STAT3 Signaling.

PURPOSE: Neuroinflammation runs through the whole process of nervous system diseases and brain injury. Inflammasomes are thought to be especially relevant to immune homeostasis, and their dysregulation contributes to pyroptosis. The natural compound Ginsenoside Rg1 has been shown to possess anti-inflammatory effects; however, its underlying mechanisms are not entirely clear. Therefore, this study was undertaken to investigate the role and mechanisms of Rg1 in regulating the production of inflammasomes and pyroptosis of microglia in vivo and in vitro. METHODS: BV-2 microglial cells were pretreated with Rg1, stattic and interleukin-6 (IL-6), and then stimulated with lipopolysaccharide (LPS) (2µg/mL). Hoechst staining and Annexin V-FITC/PI assay were then carried out. The expression levels of cleaved-caspase-1, pro-caspase-1, interleukin-1ß (IL-1ß), mature-IL-1ß, gasdermin D (GSDMD), activated NH(2)-terminal fragment of GSDMD (GSDMD-N), NOD-, LRR- and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), absent in melanoma 2 (AIM2), signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 in BV-2 were detected by Western blotting. Additionally, immunofluorescence staining was used to determine the expression of NLRP3 and p-STAT3 in postnatal rat brain and BV-2 microglia subjected to LPS stimulation and Rg1 pretreatment. The targets of transcription factor STAT3 were predicted by hTFtarget and chromatin immunoprecipitation (ChIP) was used to confirm the interaction between STAT3 and AIM2. RESULTS: We showed here that Rg1 effectively inhibited the expression of inflammasomes and microglia pyroptosis induced by LPS. The targets predicted data of Rg1 from Swiss target prediction database showed STAT3 had the highest thresholds of probability score. Rg1 can regulate the phosphorylation of STAT3, which binds to the promoter region of inflammasome AIM2. CONCLUSION: It is suggested that STAT3 signaling can initiate the transcription activity of AIM2. Rg1 regulates microglia pyroptosis in neuroinflammation induced by LPS through targeting STAT3 signaling.

Gastrodin Inhibits Inflammasome Through the STAT3 Signal Pathways in TNA2 Astrocytes and Reactive Astrocytes in Experimentally Induced Cerebral Ischemia in Rats.

This study was aimed to determine Gastrodin (GAS) and its underlying signaling pathway involved in suppression of inflammasome specifically in reactive astrocytes that are featured prominently in different neurological conditions or diseases including cerebral ischemia. For this purpose, TNA2 astrocytes in cultures were exposed to oxygen-glucose-deprivation (OGD) mimicking hypoxic cerebral ischemia. Separately, TNA2 cells were pretreated with GAS prior to OGD exposure. Additionally, Stattic, an inhibitor of STAT3 signaling pathway, was used to ascertain its involvement in regulating inflammasome in astrocytes exposed to OGD. In parallel to the above, adult rats subjected to middle cerebral artery occlusion (MCAO) with or without GAS pretreatment were sacrificed at different time points to determine the effects of GAS on astrocyte inflammasome. TNA2 astrocytes in different treatments as well as reactive astrocytes in MCAO were processed for immunofluorescence labeling and Western blot analysis for various protein markers. In the latter, protein expression levels of p-STAT3, NLRP3, and NLRC4 were markedly increased in TNA2 astrocytes exposed to OGD. Remarkably, the expression levels of these biomarkers were significantly suppressed by GAS. Of note, GAS especially at dose 20 µM inhibited NLRP3 and NLRC4 expression levels most substantially. Moreover, GAS inhibited the downstream proteins caspase-1 and IL-18. Concomitantly, GAS significantly suppressed the expression of STAT3 and NF-κB signaling pathway. It is noteworthy that Stattic at dose 100 µM inhibited STAT3 pathway and NF-κB activation in TNA2 astrocytes, an effect that was shared by GAS. In MCAO, GAS was found to effectively attenuate p-STAT3 immunofluorescence intensity in reactive astrocytes. Arising from the above, it is concluded that GAS is anti-inflammatory as it effectively suppresses inflammasome in OGD-stimulated astrocytes as well as in reactive astrocytes in MCAO via STAT3 and NF-κB signaling expression coupled with decreased expression of caspase-1 and IL-18.

Gastrodin pretreatment alleviates rat brain injury caused by cerebral ischemic-reperfusion.

Brain damage, including blood-brain barrier (BBB) dysfunction, neurological behavior deficit, cerebral infarction and inflammation, is commonly caused by ischemic-reperfusion (I/R) injury. Prevention of the above biological process defects is considered beneficial for patient recovery after I/R injury. This study was aimed to assess the neuroprotective effect of Gastrodin (GAS), an herbal agent, in experimentally induced cerebral ischemia. Sprague-Dawley adult rats were randomly divided into six groups: Sham-operated control group (Sham), middle cerebral artery occlusion (MCAO) group, GAS (50, 100, and 200 mg/kg) pretreatment + MCAO groups (GAS) and Nimodipine (NIM) + MCAO, namely, the NIM group. Additionally, an OGD/R model using BV-2 microglia was established in vitro to simulate I/R injury. We showed here that the neurological scores of rats in the GAS groups were significantly improved compared with the MCAO group. Moreover, the area of cerebral infarction in the GAS pretreatment groups and the NIM group was significantly reduced. Furthermore, Evans blue leakage volume was significantly reduced with GAS pretreatment notably at dose 100 mg/kg. Expression of matrix metalloproteinase 2 (MMP2) and MMP9 in GAS groups was markedly decreased when compared with MCAO group. In BV-2 microglia exposed to OGD/R given GAS pretreatment, MMP2 and MMP9 positive cells were reduced in numbers. The present results have shown that GAS pretreatment significantly compensated for neurological behavior defects in rats with I/R-induced injury, reduced brain infarction size, reversed BBB impairment, and attenuated inflammation. It is suggested that pretreatment with GAS before surgery is beneficial during recovery from I/R injury.

Gastrodin attenuates proliferation and inflammatory responses in activated microglia through Wnt/ß-catenin signaling pathway.

Microglia contribute to the regulation of neuroinflammation and play an important role in the pathogenesis of brain disorders. Thus, regulation of neuroinflammation triggered by activation of microglia has become a promising therapeutic strategy. Here, we investigated the beneficial effects of Gastrodin in activated microglia and analyzed the underlying molecular mechanisms. Microglia activation was regulated by Gastrodin not only in terms of microglia population size but also production of inflammatory mediators. Gastrodin inhibited the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclin-D1 and Ki67 in lipopolysaccharide (LPS)-stimulated BV-2 or primary microglia. Gastrodin also suppressed the expression of iNOS and Ki67 in activated microglia in three-day-old LPS-injected postnatal rats. In addition, the present results have shown that Gastrodin inhibited LPS-induced phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) at Ser 9 and ß-catenin activity. We further extended our investigation to determine whether Wnt/ß-catenin signaling pathway was involved in the anti-inflammatory and anti-proliferation function of Gastrodin. ß-Catenin antagonist (XAV939) was used to block LPS-mediated upregulation of iNOS, TNF-α, cyclin-D1, nitric oxide (NO) and the number of cells in the G2/M+S phase of cell cycle. Moreover, treatment with LiCl, a special Wnt/ß-catenin pathway agonist significantly blocked Gastrodin-mediated down-regulation of iNOS, TNF-α, cyclin-D1, NO and the number of cells in the G2/M+S phase of cell cycle in LPS-stimulated BV-2 microglia. Taken together, the present results suggested that Gastrodin mediated anti-inflammatory and anti-proliferation effects in activated microglia by modulating the Wnt/ß-catenin signaling pathway.

Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease.

The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case-control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel-Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR=1.212 for T allele, 95% CI=1.097-1.340, p-value=0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR=1.187 for T allele, 95% CI=1.058-1.332, p-value=0.004) and Asian samples (allelic model, pooled OR=1.293 for T allele, 95% CI=1.058-1.580, p-value=0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value=0.0149) and CHB (Chinese, p-value=0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD.

Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways.

BACKGROUND: Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS). METHODOLOGY/PRINCIPAL FINDINGS: BV-2 cells were pretreated with gastrodin (30, 40, and 60 µM) for 1 h and then stimulated with LPS (1 µg/ml) for another 4 h. The effects on proinflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and proinflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), are analysed by double-immunofluorescence labeling and RT-PCR assay. To reveal the mechanisms of action of gastrodin we investigated the involvement of mitogen-activated protein kinases (MAPKs) cascades and their downstream transcription factors, nuclear factor-κB (NF-κB) and cyclic AMP-responsive element (CRE)-binding protein (CREB). Gastrodin significantly reduced the LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1ß and NF-κB. LPS (1 µg/ml, 30 min)-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) and this was inhibited by pretreatment of BV-2 cells with different concentrations of gastrodin (30, 40, and 60 µM). In addition, gastrodin blocked LPS-induced phosphorylation of inhibitor κB-α (IκB-α) (and hence the activation of NF-κB) and of CREB, respectively. CONCLUSION AND IMPLICATIONS: This study indicates that gastrodin significantly attenuate levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibition of the NF-κB signaling pathway and phosphorylation of MAPKs in LPS-stimulated microglial cells. Arising from the above, we suggest that gastrodin has a potential as an anti-inflammatory drug candidate in neurodegenerative diseases.