Dehydration in cerebral venous sinus thrombosis.

AIMS: This study aimed to unravel the dehydration status of patients with cerebral venous sinus thrombosis (CVST) to facilitate the understanding of dehydration in CVST. METHODS: This was a multicenter retrospective study and three populations were recruited, namely, patients with CVST, CVST mimics, and healthy subjects. Blood samples were obtained 1-2 days after admission to assess dehydration status. Stata 15.1 was performed for statistical analysis. RESULTS: A total of 208 patients were diagnosed with CVST, 237 with CVST mimics, and 200 healthy individuals were enrolled. The urine specific gravity (USG, 1.020 [1.014, 1.029] vs. 1.017 [1.011, 1.021]) was higher in patients with CVST than in those with mimics (all p < 0.001). The percentage of USG >1.03 was also higher in CVST (22.6%) than in its mimics (6.3%, p < 0.001). With the development of CVST, USG (acute vs. sub-acute vs. chronic, 1.022 [1.015, 1.033] vs. 1.021 [1.015, 1.031] vs. 1.019 [1.014, 1.025]) decreased. All dehydration-related markers could not differentiate CVST from its mimics and healthy populations, and they were not associated with CVST severity and prognosis (p > 0.05). CONCLUSION: High levels of USG, especially USG >1.013, were more common in patients with CVST. Dehydration-related indices could not characterize CVST and were not associated with CVST severity and prognosis.

Assessing cognitive impairment in home-dwelling Chinese elders aged 80+: a detailed survey of 13,000 participants focusing on demographic factors, social engagement, and disease prevalence.

Introduction: Cognitive Impairment (CI) in the elderly, encompassing conditions ranging from Mild Cognitive Impairment (MCI) to dementia, represents a growing public health concern globally. This study aims to investigate the prevalence and correlates of CI among individuals aged 80 and above. Methods: The study conducts 13,027 elderly individual's door-to-door surveys, followed by the cross-tabulation of analysis data, logistic regression analysis, and health condition assessments to examine various determinants of CI. Results: The current study's key findings demonstrate sub-statical correlations between CI and various factors, including educational attainment, marital status, and gender. Pronounced differences are evident between urban and rural demographics. Furthermore, aspects of social engagement, notably communication proficiency and sensory capabilities, exhibit a strong association with CI. Logistic regression analysis highlights that residing in rural areas (Odds Ratio [OR] = 0.637) and being female (OR = 0.71) are linked to a decreased risk of CI. In contrast, behavioral and health-related variables present a complex picture. Specifically, aggressive behavior (Adjusted OR = 1.881) and symptoms of depression (Adjusted OR = 0.549) contrast with conditions such as asthma (OR= 2.857) and cerebral infarction (OR=1.348), which elevate the risk of CI. Intriguingly, hyperlipidemia (OR= 0.671) appears to confer a protective effect against CI. Conclusion: The study highlights the complexity of factors affecting CI in the elderly, advocating for a comprehensive approach to understanding and managing cognitive health.

Dataset on the effects of psychological care on depression and suicide ideation in underrepresented children.

Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and "left-behind" and "single-parenting" children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

Association between social support and the severity of positive symptoms in rural community-dwelling patients with schizophrenia during the COVID-19 pandemic.

BACKGROUND: This study examined the association between social support and the severity of positive symptoms in rural community-dwelling schizophrenia patients during the COVID-19 pandemic. METHOD: The cross-sectional study included 665 rural community-dwelling schizophrenia patients investigated during the COVID-19 pandemic. Social support was measured using the Social Support Rating Scale, and positive symptoms were assessed using the Positive Scale extracted from the Positive and Negative Syndrome Scale. Multiple linear regression was adopted to examine the association of social support with positive symptoms. RESULT: The scores for total social support, subjective support, objective support and the use of social support were 28.3 ± 5.9, 16.4 ± 5.2, 6.5 ± 1.4 and 5.4 ± 2.8, respectively. Total social support (ß = -0.08, 95%CI: -0.13 to -0.02, P < 0.01) and subjective social support (ß = -0.10, 95%CI: -0.16 to -0.04, P < 0.01) were significantly and negatively associated with the Positive Scale score after adjustment for confounders. Objective social support (ß = 0.11, 95%CI: -0.10 to 0.32, P = 0.31) and the use of social support (ß = -0.03, 95%CI: -0.14 to 0.07, P = 0.53) were not significantly associated with the Positive Scale score. CONCLUSION: The study confirmed the importance of social support, especially subjective support, provided to rural community-dwelling schizophrenia patients during the COVID-19 pandemic. This support should be addressed and strengthened for such patients in emergent events.

Men who have sex with men were more depressed than their counterparts because of lower social support and higher loneliness: A comparative survey among Chinese university students.

BACKGROUND: Poor mental health is prevalent among men who have sex with men (MSM), including MSM university students (MSMUS), causing a significant burden on their health and society. The study aimed to compare the difference in levels of depressive symptoms between Chinese MSMUS and non-MSMUS and test the mediating roles of social support and loneliness in the relationship between MSM status and depressive symptoms among male university students. METHODS: From June to October 2018, a total of 305 MSMUS and 2447 non-MSMUS from two cities in Sichuan province (China) were investigated using questionnaires. RESULTS: The proportion of depression in the MSMUS and non-MSMUS groups was 54.1 % and 36.4 %, respectively. MSM status, social support, and loneliness were all significantly associated with depressive symptoms among Chinese university students. Structural equation modelling showed that the association between MSM status and depressive symptoms was partially mediated by three indirect paths, including 1) via social support (mediated proportion = 19.4 %), 2) via loneliness (mediated proportion = 19.3 %), and 3) via social support and then loneliness (mediated proportion = 16.1 %). CONCLUSIONS: Depression was prevalent among university students in China, especially MSMUS. The findings increased our understanding of the mediating roles of social support and loneliness in the link between MSM status and depressive symptoms among Chinese male university students, which have great implications for designing interventions to improve their mental health. LIMITATION: The cross-sectional study design limited causal inferences.

The role of p53 in anti-tumor immunity and response to immunotherapy.

p53 is a transcription factor that regulates the expression of genes involved in tumor suppression. p53 mutations mediate tumorigenesis and occur in approximately 50% of human cancers. p53 regulates hundreds of target genes that induce various cell fates including apoptosis, cell cycle arrest, and DNA damage repair. p53 also plays an important role in anti-tumor immunity by regulating TRAIL, DR5, TLRs, Fas, PKR, ULBP1/2, and CCL2; T-cell inhibitory ligand PD-L1; pro-inflammatory cytokines; immune cell activation state; and antigen presentation. Genetic alteration of p53 can contribute to immune evasion by influencing immune cell recruitment to the tumor, cytokine secretion in the TME, and inflammatory signaling pathways. In some contexts, p53 mutations increase neoantigen load which improves response to immune checkpoint inhibition. Therapeutic restoration of mutated p53 can restore anti-cancer immune cell infiltration and ameliorate pro-tumor signaling to induce tumor regression. Indeed, there is clinical evidence to suggest that restoring p53 can induce an anti-cancer immune response in immunologically cold tumors. Clinical trials investigating the combination of p53-restoring compounds or p53-based vaccines with immunotherapy have demonstrated anti-tumor immune activation and tumor regression with heterogeneity across cancer type. In this Review, we discuss the impact of wild-type and mutant p53 on the anti-tumor immune response, outline clinical progress as far as activating p53 to induce an immune response across a variety of cancer types, and highlight open questions limiting effective clinical translation.

Association between inflammatory biomarkers and venous thromboembolism: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a common thrombotic vascular disease that has a significant impact on people's well-being and quality of life. A plethora of clinical studies explore the relationship between inflammatory biomarkers and VTE but yield conflicting results. This article proposed to pool these studies to draw a more convincing conclusion. METHODS: We searched several databases for studies before April 2023. Available data was processed using Stata software (version 15.0 SE) and R (version 4.1.2). This meta-analysis has been registered in PROSPERO (CRD42022321815). The VTE in this review encompassed pulmonary embolism, deep vein thrombosis, and cerebral venous thrombosis. RESULTS: A total of 25 articles were finally involved in this study. Our results revealed that higher levels of high-sensitivity C-reactive protein (hs-CRP, MD, 0.63, 95%CI, 0.21-1.05) and C-reactive protein (CRP)> 3ug/ml (OR, 1.52, 95%CI, 1.18-1.96) might be regarded as risk factors for future VTE occurrence. The elevated levels of monocyte (MD, 0.03, 95%CI, 0.00-0.05), hs-CRP (0.85, 0.61-1.08), CRP (0.66, 0.20-1.13) and IL-6 (0.47, 0.25-0.70) might represent the previous VTE; a series of markers such as white blood cell (1.43, 0.88-1.98), neutrophil (1.79, 1.02-2.56), monocyte (0.17, 0.14-0.21), hs-CRP (3.72, 1.45-5.99), IL-6 (5.99, 4.52-7.46), platelet-lymphocyte ratio (33.1, 24.45-41.78) and neutrophil-lymphocyte ratio (1.34, 0.95-1.73) increased during the acute phase of VTE. CONCLUSIONS: In general, activated inflammatory biomarkers might not only be correlated with an increased risk of VTE, but may also give a hint of the occurrence of VTE in clinical settings.

The Associations Between Loneliness, Hopelessness, and Self-control and Internet Gaming Disorder Among University Students Who Were Men Who Have Sex With Men: Cross-sectional Mediation Study.

BACKGROUND: The minority stress model postulates that men who have sex with men (MSM) often encounter multiple stressors because of their sexual minority status, which may lead to psychological problems and maladaptive coping such as addictive behaviors (eg, internet gaming disorder [IGD]). It was hypothesized that hopelessness and loneliness would be associated with IGD via self-control among MSM. OBJECTIVE: This study investigated the prevalence of IGD and its associations with variables related to minority stress (loneliness and hopelessness) among MSM who were university students. Mediation involving such associations via self-control was also explored. METHODS: With informed consent, 305 MSM attending universities in Sichuan, China participated in the study. The validated Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) checklist was used to assess IGD. Multivariable logistic regression adjusted for background factors and structural equation modeling were conducted. RESULTS: The prevalence of IGD was 12.8% (n=39). Logistic regression found that IGD was positively associated with hopelessness and loneliness, and negatively associated with self-control. The structural equation modeling identified three significant paths between hopelessness/loneliness and IGD: (1) hopelessness → lower self-control → higher IGD (full mediation), (2) loneliness → lower self-control → higher IGD (partial mediation: effect size of 28%), and (3) a direct effect from loneliness to IGD. CONCLUSIONS: IGD was prevalent among young MSM and warrants interventions that may try to reduce the level of psychosocial problems such as loneliness and hopelessness and improve self-control. According to the socioecological model, the promotion of social acceptance and reduction in stigma toward MSM are important in reducing loneliness and hopefulness among MSM. Self-control links up the relationships between psychosocial problems and IGD and should be given special attention. Longitudinal studies are warranted to confirm the findings and test new mediations between loneliness/hopelessness and MSM with IGD.

Medication adherence among community-dwelling schizophrenia patients during the COVID-19 pandemic: A cross-sectional study.

OBJECTIVES: This study aims to investigate medication adherence during the COVID-19 pandemic among community-dwelling schizophrenia patients, and to explore the role of social support in improving medication adherence in a rural community sample in China. METHODS: A cross-sectional sample of 800 patients was recruited using a cluster random sampling method in Yingshan County, Sichuan Province. Information on participant demographic characteristics, social support and medication adherence was collected through face-to-face interviews. The data analysis was performed using SAS9.4. Two binary logistic regression models were employed to identify the association between regular medication use and social support. RESULTS: The rate of regular medication adherence among community-dwelling patients with schizophrenia was 41.5%,which was lower than that indicated by recent research(Li et al., 2020) before COVID-19 in western rural China. The mean scores and standard deviation of the patient's objective support, subjective support, and support utilization were 4.94 ± 1.57, 17.03 ± 5.24, and 5.25 ± 2.75, respectively. The social support standard deviation was 27.22 ± 6.32. The crude odds ratio of objective support, subjective support, and support utilization were 0.790 (95%CI:0.713-0.876), 0.999 (95%CI:0.971-1.027), and 1.049 (95%CI:0.995-1.105) respectively. After adjusting for potential factors, the adjusted odds ratio of objective support, subjective support, and support utilization were 0.758 (95%CI:0.673-0.853), 1.030 (95%CI:0.994-1.068), and 1.043 (95%CI:0.985-1.105), respectively. CONCLUSIONS: During the COVID-19 pandemic, community-dwelling schizophrenia patients had a low rate of regular medication adherence. This was particularly true of those who were older adults, less educated and living in rural areas. The results of this study suggest that strengthening social support may effectively improve medication adherence for those patients.

Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer.

TP53 is a tumor suppressor gene that encodes a sequence-specific DNA-binding transcription factor activated by stressful stimuli; it upregulates target genes involved in growth suppression, cell death, DNA repair, metabolism, among others. TP53 is the most frequently mutated gene in tumors, with mutations not only leading to loss-of-function (LOF), but also gain-of-function (GOF) that promotes tumor progression, and metastasis. The tumor-specific status of mutant p53 protein has suggested it is a promising target for cancer therapy. We summarize the current progress of targeting wild-type and mutant p53 for cancer therapy through biotherapeutic and biopharmaceutical methods for (1) boosting p53 activity in cancer, (2) p53-dependent and p53-independent strategies for targeting p53 pathway functional restoration in p53-mutated cancer, (3) targeting p53 in immunotherapy, and (4) combination therapies targeting p53, p53 checkpoints, or mutant p53 for cancer therapy.

Cancer-related fatigue in hospitalised patients treated for lymphoma and its burden on family caregivers.

OBJECTIVE: To investigate the prevalence of cancer-related fatigue (CRF) in patients with lymphoma and to explore the burden of CRF on the family caregivers (FCs). METHODS: A cross-sectional study was conducted in a university-affiliated tertiary care hospital in China. Patients with lymphoma who received treatment in the in-patient ward of the Haematology Department were consecutively recruited. Face-to-face interviews were conducted to gather information related to the patients' sociodemographic characteristics and perceived CRF and its burden on the FCs. Cochran-Armitage trend analysis and Multivariable logistic regression analyses were employed to determine the association between CRF and the FCs' burden. RESULTS: Of the 116 cancer patient-FC dyads, about 70% of patients experienced some level of fatigue, while 51% of unpaid family members suffered some degree of depression. The Cochran-Armitage trend analysis showed that the FCs' burden significantly increased with the severity of CRF. Logistic regression indicated that the FCs of the patients reporting fatigue experienced a higher burden in both the unadjusted and adjusted models. CONCLUSION: The prevalence of CRF appeared to be high among patients with lymphoma. It might be important to design innovative health-promoting practices for ameliorating or preventing the impact of fatigue.

Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by early metastasis, late detection, and poor prognosis. Progress towards effective therapy has been slow despite significant efforts. Novel treatment approaches are desperately needed and autophagy, an evolutionary conserved process through which proteins and organelles are recycled for use as alternative energy sources, may represent one such target. Although incompletely understood, there is growing evidence suggesting that autophagy may play a role in PDAC carcinogenesis, metastasis, and survival. Early clinical trials involving autophagy inhibiting agents, either alone or in combination with chemotherapy, have been disappointing. Recently, evidence has demonstrated synergy between the MAPK pathway and autophagy inhibitors in PDAC, suggesting a promising therapeutic intervention. In addition, novel agents, such as ONC212, have preclinical activity in pancreatic cancer, in part through autophagy inhibition. We discuss autophagy in PDAC tumorigenesis, metabolism, modulation of the immune response, and preclinical and clinical data with selected autophagy modulators as therapeutics.

Cerebral Hemodynamics and Carotid Atherosclerosis in Patients With Subcortical Ischemic Vascular Dementia.

A growing body of evidence indicates that atherosclerosis is correlated with cerebral small vessel disease and contributes to cognitive decline. This study aimed to explore the characteristics and contributions of intracranial hemodynamics and carotid atherosclerosis to cognitive dysfunction in subjects with subcortical ischemic vascular dementia (SIVD). Notably, 44 patients with SIVD, 30 patients with Alzheimer's disease (AD), and 30 healthy controls (HCs) were recruited from our longitudinal MRI study for AD and SIVD (ChiCTR1900027943). The cerebral mean flow velocity (MFV) and pulsatility index (PI) of both anterior and posterior circulations, artery plaque, and lumen diameter in carotid arteries were investigated using transcranial Doppler and carotid ultrasound, respectively. Their correlations with cognitive function were analyzed in patients with dementia. Decreased MFV and increased PI were found in patients with SIVD and AD. Patients with SIVD showed lower MFV and higher PI in the bilateral posterior cerebral arteries compared to patients with AD. Increases in lumen diameter, number of arteries with plaque, and total carotid plaque score were found in patients with SIVD. The Mini-Mental State Examination score was positively correlated with the MFV and negatively correlated with the PI of most major cerebral arteries, while it was negatively correlated with the lumen diameter of the common carotid artery, number of arteries with plaque, and total carotid plaque score in patients with dementia. There were also correlations between these parameters of some arteries and memory and executive function. Our results provide additional evidence suggesting that the pathological changes in macrovascular structure and function are correlated with cognitive impairment in dementia patients with SIVD and to a lesser extent AD.

Long-Term Trends in Stroke Management and Burden Among Low-Income Women in a Rural Area From China (1992-2019): A Prospective Population-Based Study.

Although an increasing number of studies are considering sex-related differences in stroke burden, the trends in stroke burden and management among women in China, especially among low-income women, remain unclear. This study evaluated the long-term trends in stroke management and burden among low-income Chinese women during the period between 1992 and 2019. Stroke burden was assessed using the age-adjusted incidence of first-ever stroke, whereas stroke management was assessed using the rates of neuroimaging diagnoses, hospitalizations, case fatalities, and stroke recurrence. Stroke burden and management were analyzed during four study periods: 1992-1998, 1999-2004, 2005-2012, and 2013-2019. During the 193,385 person-years of surveillance in this study, 597 female stroke patients were identified. The stroke incidences per 100,000 person-years were 88.1 cases during 1992-1998, 145.4 cases during 1999-2004, 264.3 cases during 2005-2012, and 309.8 cases during 2013-2019 (P < 0.001). Between 1992 and 2019, the incidence of stroke significantly increased (6.4% annually) as did the incidence of ischemic stroke (7.8% annually; both, P < 0.001). The rates of neuroimaging diagnoses and hospitalizations significantly increased during the four periods, while the case fatality rates and 1-year recurrence rates decreased significantly for both overall strokes and ischemic strokes, especially among patients ≥45 years old (all, P < 0.001). Among low-income women in China, stroke management is gradually improving, despite the increasing stroke burden. Thus, improved healthcare coverage is needed to further reduce the stroke burden among low-income Chinese women.

Targeting the Integrated Stress Response in Cancer Therapy.

The integrated stress response (ISR) is an evolutionarily conserved intra-cellular signaling network which is activated in response to intrinsic and extrinsic stresses. Various stresses are sensed by four specialized kinases, PKR-like ER kinase (PERK), general control non-derepressible 2 (GCN2), double-stranded RNA-dependent protein kinase (PKR) and heme-regulated eIF2α kinase (HRI) that converge on phosphorylation of serine 51 of eIF2α. eIF2α phosphorylation causes a global reduction of protein synthesis and triggers the translation of specific mRNAs, including activating transcription factor 4 (ATF4). Although the ISR promotes cell survival and homeostasis, when stress is severe or prolonged the ISR signaling will shift to regulate cellular apoptosis. We review the ISR signaling pathway, regulation and importance in cancer therapy.

Epidemiology of Isolated Impaired Glucose Tolerance Among Adults Aged Above 50 Years in Rural China.

INTRODUCTION: Isolated impaired glucose tolerance (i-IGT) is a subtype of prediabetes in which an individual demonstrates elevated 2-h post-glucose load glucose levels but normal fasting plasma glucose levels. However, few studies have explored the prevalence and risk factors of i-IGT among adults in rural China. Thus, we aimed to explore the prevalence and risk factors of i-IGT among adults ≥50 years old in a low-income, rural population in China. MATERIALS AND METHODS: Individuals aged ≥50 years with normal fasting plasma glucose levels were included in the final analysis. Fasting and 2-h venous blood samples were collected to assess the selected parameter measurements. RESULTS: A total of 2175 individuals were included in this study. The i-IGT prevalence was 22.9% and significantly higher among females than among males (P<0.05). Older age [odds ratio (OR), 1.606; 95% confidence interval (CI), 1.101-2.342; P=0.014), hypertension (OR, 1.554; 95% CI, 1.152-2.019; P=0.004), and central obesity (OR, 1.395; 95% CI, 1.099-1.771; P=0.006) were associated with i-IGT. Moreover, white blood cell (OR, 1.089; 95% CI, 1.009-1.175; P=0.029), high-sensitivity C-reactive protein (OR, 1.049; 95% CI, 1.020-1.078; P=0.001), serum uric acid (OR, 1.0003; 95% CI, 1.001-1.004; P=0.001), triglyceride (OR, 1.540; 95% CI, 1.105-2.147; P=0.011), and alanine aminotransferase (OR, 1.012; 95% CI, 1.004-1.021; P=0.004) levels were also linked to i-IGT in the analyzed population. CONCLUSION: Health promotion education and a standardized approach to managing body weight, BP, and lipid and uric acid levels would benefit this low-income population in rural China for reducing the risk of cardiovascular disease.

A subset of CB002 xanthine analogs bypass p53-signaling to restore a p53 transcriptome and target an S-phase cell cycle checkpoint in tumors with mutated-p53.

Mutations in TP53 occur commonly in the majority of human tumors and confer aggressive tumor phenotypes, including metastasis and therapy resistance. CB002 and structural-analogs restore p53 signaling in tumors with mutant-p53 but we find that unlike other xanthines such as caffeine, pentoxifylline, and theophylline, they do not deregulate the G2 checkpoint. Novel CB002-analogs induce pro-apoptotic Noxa protein in an ATF3/4-dependent manner, whereas caffeine, pentoxifylline, and theophylline do not. By contrast to caffeine, CB002-analogs target an S-phase checkpoint associated with increased p-RPA/RPA2, p-ATR, decreased Cyclin A, p-histone H3 expression, and downregulation of essential proteins in DNA-synthesis and DNA-repair. CB002-analog #4 enhances cell death, and decreases Ki-67 in patient-derived tumor-organoids without toxicity to normal human cells. Preliminary in vivo studies demonstrate anti-tumor efficacy in mice. Thus, a novel class of anti-cancer drugs shows the activation of p53 pathway signaling in tumors with mutated p53, and targets an S-phase checkpoint.

P53-independent partial restoration of the p53 pathway in tumors with mutated p53 through ATF4 transcriptional modulation by ERK1/2 and CDK9.

A long-term goal in the cancer-field has been to develop strategies for treating p53-mutated tumors. A novel small-molecule, PG3-Oc, restores p53 pathway-signaling in tumor cells with mutant-p53, independently of p53/p73. PG3-Oc partially upregulates the p53-transcriptome (13.7% of public p53 target-gene dataset; 15.2% of in-house dataset) and p53-proteome (18%, HT29; 16%, HCT116-p53-/-). Bioinformatic analysis indicates critical p53-effectors of growth-arrest (p21), apoptosis (PUMA, DR5, Noxa), autophagy (DRAM1), and metastasis-suppression (NDRG1) are induced by PG3-Oc. ERK1/2- and CDK9-kinases are required to upregulate ATF4 by PG3-Oc which restores p53 transcriptomic-targets in cells without functional-p53. PG3-Oc represses MYC (ATF4-independent), and upregulates PUMA (ATF4-dependent) in mediating cell death. With largely nonoverlapping transcriptomes, induced-ATF4 restores p53 transcriptomic targets in drug-treated cells including functionally important mediators such as PUMA and DR5. Our results demonstrate novel p53-independent drug-induced molecular reprogramming involving ERK1/2, CDK9, and ATF4 to restore upregulation of p53 effector genes required for cell death and tumor suppression.

Increased Cerebrospinal Fluid Uric Acid Levels in Guillain-Barré Syndrome.

Uric acid (UA) is a natural scavenger for peroxynitrite and can reflect antioxidant activity and oxidative stress in several neurological disorders. Changes in serum and cerebrospinal fluid (CSF) levels of UA have been reported in patients with multiple sclerosis and neuromyelitis optica spectrum disorders. The levels of UA in CSF are relatively poorly understood in patients with Guillain-Barré syndrome (GBS). It remains unclear whether UA can play an antioxidant role and reflect oxidative stress in GBS. The purpose of this study is to investigate CSF and serum UA levels in patients with GBS and their relationship with clinical characteristics. The CSF and serum UA levels were detected in 43 patients with GBS, including 14 acute inflammatory demyelinating polyneuropathy (AIDP), 6 acute motor axonal neuropathy (AMAN), 13 with acute motor and sensory axonal neuropathy (AMSAN), 7 Miller Fisher syndrome (MFS), and 3 unclassified, and 25 patients with non-inflammatory neurological disorders (NIND) as controls. Moreover, serum UA levels were also detected in 30 healthy controls. The levels of UA were measured using uricase-based methods with an automatic biochemical analyzer. CSF UA levels were significantly increased in patients with GBS (p = 0.011), particularly in patients with AIDP (p = 0.004) when compared with NIND. Among patients with GBS, CSF UA levels were higher in those with demyelination (p = 0.022), although the difference was not significant after multiple testing correction. CSF UA levels in GBS were positively correlated with serum UA levels (r = 0.455, p = 0.022) and CSF lactate (r = 0.499, p = 0.011). However, no significant correlations were found between CSF UA levels and GBS disability scores. There were no significant differences in serum UA levels among GBS, NIND, and healthy controls. These results suggest that CSF UA may be related to the pathogenesis of demyelination in patients with GBS and may be partially determined by serum UA and the impaired blood-nerve barrier.

Comparisons Between Infectious and Autoimmune Encephalitis: Clinical Signs, Biochemistry, Blood Counts, and Imaging Findings.

OBJECTIVE: Infectious encephalitis (IE) and autoimmune encephalitis (AE) are symptomatically similar in clinic, however essentially different in pathogenesis. Therefore, the objective of this study was to identify specific features to distinguish the two types of encephalitis for early effective diagnosis and treatments through a comparative analysis. METHODS: Fifty-nine IE patients and 36 AE patients were enrolled. The patients with IE were divided into viral encephalitis (VE) and bacterial encephalitis (BE) according to the pathogens in cerebrospinal fluid (CSF). Patients with AE were categorized by with or without neural autoantibodies (NAAb). We further divided patients with NAAb into those with neural cell-surface antibodies (NSAbs) or intracellular antibodies (Abs). Clinical features, laboratory data, and imaging findings were compared between AE, IE, and subgroups. RESULTS: Memory deficits, involuntary movement, and seizures were relatively more commonly presenting symptoms in AE patients (p < 0.05). The positive rate of Pandy test was higher in IE patients (p = 0.007). Decreased leukocyte, erythrocyte, and platelet counts in blood were found in IE patients (p < 0.05). Lower serum calcium level was found in VE compared to BE (p = 0.027). Meanwhile, higher serum calcium level was found in patients with NSAbs compared with intracellular Abs (p = 0.034). However, higher levels of LDH in CSF were found in patients with intracellular Abs (p = 0.009). In magnetic resonance imaging, hippocampus lesions were more commonly present in patients with AE (p = 0.042). Compared with AE patients, more IE patients displayed the background electroencephalogram rhythm of slow-frequency delta (p = 0.013). CONCLUSION: Involuntary movement and memory deficits were more specifically present in AE patients. CSF Pandy, blood routine test and hippocampus lesions detections were potential markers for distinguishing AE and IE. Further, CSF LDH, and serum calcium levels were potentially useful to distinguish subgroups of encephalitis.