Mechanistic Study of Glycyrrhizic Acid Improving Alcoholic Fatty Liver Disease by Modulating the SHP1/SYK Signaling Pathway in Macrophages.

Objective: To investigate glycyrrhizin's effects and molecular mechanisms on the progression of alcoholic fatty liver. Methods: An alcoholic fatty liver model was established, followed by the administration of glycyrrhizin ammonium (20 mg/kg). Liver tissue pathological changes were observed using oil red O staining, and pyroptotic bodies were observed using transmission electron microscopy. Western blot was used to detect the expression of related proteins. To establish a model of alcoholic fatty liver cells to explore the molecular mechanism of glycolic acid in this disease. Results: Glycyrrhizin ammonium reduced the area of oil red staining in liver tissue and the number of pyroptotic bodies decreased the relative protein expression of NOX2, NOX3, p-SYK, STING, p-PDE4B, NLRP3, IL-1ß, GSDMD, Caspase-1, and Caspase-4, and increased the relative protein expression of p-SHP1 and Nrf2. Conclusion: Glycyrrhizin ameliorates the progression of alcoholic fatty liver by modulating the SHP1/SYK signaling pathway in macrophages, thereby inhibiting hepatic lipid peroxidation and pyroptosis.

Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

Regulation of programmed death ligand 1 (PD-L1) expression by TNF-related apoptosis-inducing ligand (TRAIL) in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks targeted therapies. Previous studies have shown that TNBC cells are highly sensitive to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), making it a promising agent for treating TNBC. However, the development of TRAIL resistance limits its further clinical development, and the underlying mechanisms are not fully understood. In this study, we report the role of PD-L1 in TRAIL resistance. Specifically, we found that TRAIL treatment increases PD-L1 expression in TRAIL-sensitive cells and that basal PD-L1 expression is increased in acquired TRAIL-resistant cells. Mechanistically, we found that increased PD-L1 expression was accompanied by increased extracellular signal-regulated kinase (ERK) activation. Using both genetic and pharmacological approaches, we showed that knockdown of ERK by siRNA or inhibition of ERK activation by the mitogen-activated protein kinase kinase inhibitor U0126 decreased PD-L1 expression and increased TRAIL-induced cell death. Furthermore, we found that knockout or knockdown of PD-L1 enhances TRAIL-induced apoptosis, suggesting that PD-L1-mediated TRAIL resistance is independent of its ability to evade immune suppression. Therefore, this study identifies a noncanonical mechanism by which PD-L1 promotes TRAIL resistance, which can be potentially exploited for immune checkpoint therapy.

Early- and late-onset narcolepsy: possibly two distinct clinical phenotypes.

PURPOSE: To investigate the clinical characteristics and the risk factors associated with excessive daytime sleepiness (EDS) in patients with early- and late-onset narcolepsy. METHODS: Patients with narcolepsy were consecutively recruited. All patients were separated into early- and late-onset groups according to the onset age of disease ≤ 15 and > 15 years, respectively. Demographic, clinical, and sleep parameters were compared between the two groups. Linear regressions were performed to examine the risk factors of subjective and objective EDS in patients with early- and late-onset narcolepsy. RESULTS: A total of 101 patients with narcolepsy (median age at recruitment = 18.0 years) were classified into an early-onset group (67 patients with median age at onset = 12.0 years) and a late-onset group (34 patients with median age at onset = 28.5 years). Compared with early-onset group, late-onset group scored significantly higher on Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), sleep paralysis, rapid eye movement (REM) sleep behavior disorder (RBD) questionnaire-Hong Kong (all P < 0.050). UNS-cataplexy and sleep paralysis had significantly positive associations with subjective EDS, and N1%, arousal index, and periodic limb movements index were positively associated with objective EDS in the early-onset group (all P < 0.050). However, these associations were not observed in late-onset narcolepsy. CONCLUSION: Late onset narcolepsy had more severe self-reported narcolepsy symptoms. REM sleep related symptoms and disrupted nighttime sleep were associated with EDS in early-onset narcolepsy. These findings suggest that early- and late-onset narcolepsy may represent two distinct phenotypes.

Biofilm formation, antimicrobial assay, and toxin-genotypes of Clostridium perfringens type C isolates cultured from a neonatal Yangtze finless porpoise.

This is a culture-dependent study with the objective of pure culturing and characterizing pathogenic bacteria from the blowhole, lung, stomach and fecal samples of a neonatal crucially endangered Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) that died 27 days after birth. Bacteria were inoculated using a swab onto blood and MacConkey agar plates and representative isolates were identified through 16S rRNA gene sequence analysis. A total of three Clostridium perfringens type C strains from the fecal samples were isolated. Toxin genes, including cpa, cpb and cpb2, were detected by PCR amplification, whereas the etx, iap and cpe genes were not detected. Biofilm formation of the three strains was then examined. Only one strain was capable of biofilm formation. In addition, isolates showed strong resistance against the antibiotics amikacin (3/3), erythromycin (1/3), gentamicin (3/3), streptomycin (3/3), and trimethoprim (3/3), while sensitivity to ampicillin (3/3), bacitracin (3/3), erythromycin (2/3), penicillin G (3/3), and tetracycline (3/3). The results suggested C. perfringens type C could have contributed to the death of this neonatal porpoise.

Densely granulated adenoma pattern is associated with an increased risk of obstructive sleep apnea in patients with acromegaly.

OBJECTIVES: To explore the prevalence of obstructive sleep apnea (OSA) and the association between the adenoma granulation patterns and OSA in patients with acromegaly. METHODS: An overnight polysomnography (PSG) assessment was carried out on participants with acromegaly. Results classified participants into a non-OSA group, mild to moderate OSA group, and severe OSA group. Morphological and biochemical analyses were performed. Demographic, clinical, biochemical, and polysomnographic data were compared among the three groups. Using logistic regression models, the risk of OSA in acromegalic subjects was estimated. RESULTS: OSA was reported in 36 of 49 patients (74%) with acromegaly. Contrasted with the non-OSA group, OSA patients had a larger proportion of the densely granulated (DG) pattern. The OSA groups with DG acromegaly had a smaller maximum tumor diameter and Vol/2 than those with the sparsely granulated (SG) pattern. Furthermore, a higher growth hormone (GH) level (45.0 ± 36.9 vs 18.6 ± 15.8, P = 0.047) and GH index (28.4 ± 13.8 vs 6.6 ± 8.2, P = 0.003) were found in DG acromegaly patients with severe OSA. Additionally, there was a trend toward higher standardized insulin-like growth factor 1 (IGF-1) in patients with DG acromegaly than in those with SG acromegaly in the severe OSA group. After adjusting for potential confounding variables, the DG pattern was correlated with the risk of OSA (OR = 14.84, 95%CI 1.36-162.20, P = 0.027) in patients with acromegaly. CONCLUSIONS: The findings indicate that a high prevalence of OSA exists in patients with acromegaly, and the DG pattern may be a risk factor for OSA in acromegaly.

[Characteristics of Sleep Electroencephalographic Power in Chronic Insomnia Patients].

OBJECTIVE: To study the sleep electroencephalogram (EEG) power features of patients with chronic insomnia. METHODS: Retrospective analysis was performed with patients who met the ICD-10 diagnostic criteria for chronic insomnia, using polysomnography (PSG) to examine the overnight sleep EEG. The sleep architectures and relative EEG power across five frequency bands during overnight sleep were compared to study the differences between the insomnia and control groups. Furthermore, the correlation between EEG power and various PSG measures was also analyzed. RESULTS: Forty-five subjects were enrolled in the study, including 25 chronic insomniacs (18 females, aged [36.2±10.7] years) and 20 controls (18 females, aged [36.1±7.6] years). Compared to those of the control group, insomnia patients had significantly lower value of delta power ([38.0±6.1] vs. [43.2±5.8], P<0.05) in the NREM1 stage, and increased value of beta power during total NREM, NREM1 and NREM2 (NREM sleep [5.4±2.3] vs. [3.8±1.4], NREM1 [11.3±3.5] vs. [8.7±2.8], and NREM2 [5.7±2.3] vs. [4.4±1.4], all P<0.05). For correlation analyses, in the insomnia group, a significantly positive correlation was found between the delta value during NREM sleep and the duration of NREM3 sleep ( r=0.527). The beta value during NREM sleep was found to be negatively correlated to the duration of NREM3 sleep ( r=－0.767). A positive correlation was found between the beta value during NREM sleep and the duration of NREM1 and NREM2 sleep ( r=0.486 and 0.589, respectively). CONCLUSION: The results suggest that patients with chronic insomnia have decreased low-frequency EEG power, but increased high-frequency EEG power during NREM sleep. The findings indicate that cortex arousal level is elevated in chronic insomniacs during NREM sleep.

Prevalence of Depression or Depressive Symptoms in Patients with Narcolepsy: a Systematic Review and Meta-Analysis.

A meta-analysis was conducted to review the prevalence and associated moderators of depression or depressive symptoms in patients with narcolepsy. An extensive search of the literature yielded 1104 articles and abstracts, of which 31 studies were included in the meta-analysis. Meta-analysis revealed that the overall pooled prevalence of depression or depressive symptoms in patients with narcolepsy was 32% (95% Confidence Interval, 28-36%) with high between-study heterogeneity (Q = 249.77, df = 30, p < 0.001, τ2 = 0.0087, I2 = 88%). An analysis of 13 studies with healthy control groups indicated that narcolepsy was associated with a significantly increased risk of depression or depressive symptoms (Odds Ratio 3.48, 95% Confidence Interval 2.73-4.45; Q = 41.23, df = 12, p < 0.001, τ2 = 0.0087, I2 = 70.9%). The prevalence of depression or depressive symptoms in patients with narcolepsy was significantly affected by study design (Q = 5.05, p = 0.02) and recruitment setting (Q = 5.98, p = 0.01), and was marginally affected by age group (Q = 3.44, p = 0.06). The results indicate that narcolepsy patients should be closely monitored for depression and depressive symptoms and that early screening should be considered. However, these conclusions should be tempered because of high variability between studies. The estimates across studies are very inconsistent, indicating the need for larger, multicenter studies, with stringent case definitions.

Non-motor symptoms are associated with REM sleep behavior disorder in Parkinson's disease: a systematic review and meta-analysis.

OBJECTIVE: Parkinson's disease (PD) is usually accompanied by rapid eye movement sleep behavior disorder (RBD). A systematic review has concluded that motor manifestations are associated with RBD in PD patients, but whether the same is true of non-motor symptoms is unclear. METHODS: A systematic review and meta-analysis was conducted by searching studies related to PD and RBD in PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled where appropriate and used to calculate odds ratios (ORs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic. RESULTS: PD patients with RBD were more likely to be male (OR 1.26, 95% CI 1.14-1.40) and older (MD 1.70 years, 95% CI 1.24-2.16) than those of patients without RBD. Patients with RBD were at a higher risk of non-motor symptoms such as constipation (OR 1.94, 95% CI 1.57-2.38), hallucination (OR 2.62, 95% CI 2.01-3.41), depression (SMD 0.39, 95% CI 0.25-0.53), and cognitive impairment (SMD - 0.29, 95% CI - 0.42 to - 0.17) based on standardized questionnaire scores. Similarly, PD patients with RBD suffered more severe motor symptoms and required higher doses of levodopa therapy. CONCLUSIONS: The available evidence suggests that PD patients with RBD suffer severer non-motor and motor symptoms than those without RBD. A potential explanation is that PD patients with RBD present more diffuse neurodegeneration.

Para-aortic and Right Obturator Lymphadenectomy for Surgical Staging of Advanced Cervical Cancer through the TU-LESS Extraperitoneal Approach.

OBJECTIVE: To present an innovative transumbilical laparoendoscopic single-site (TU-LESS) extraperitoneal approach for lymphadenectomy in a patient with advanced cervical carcinoma. DESIGN: Demonstration of the novel technique through video. SETTING: In advanced cervical cancer, determining the status of the para-aortic lymph nodes is essential because extended-field radiologic therapy is recommended for a patient with positive para-aortic lymph nodes [1]. Nonetheless, the sensitivity and specificity of currently available imaging workup for positive lymph nodes are limited. Surgical staging enables precise evaluation. However, laparotomy has potential wound complications and leads to treatment delay. Multiport laparoscopic transperitoneal and extraperitoneal approaches limit surgeons' ability to reach the para-aortic area or obturator fossa in the same operation [2]. Thus, we take full use of these approaches' advantages and avoid their disadvantages to design a promising minimally invasive surgery approach [3]. INTERVENTIONS: Para-aortic and obturator lymphadenectomy through the TU-LESS extraperitoneal approach was successfully performed without complications. The patient recovered quickly and received subsequent concurrent chemoradiation on schedule. CONCLUSION: TU-LESS extraperitoneal para-aortic lymphadenectomy provides satisfactory exposure and easy access to both the para-aortic area and obturator fossa. In addition, the bowels are uplifted by an extraperitoneal air cushion to achieve excellent exposure and reduce the risk of bowel injury. With quick recovery, the patient could start accurate radiation treatment promptly.

Spinal subdural hematoma and subdural anesthesia following combined spinal-epidural anesthesia: a case report.

BACKGROUND: Subdural anesthesia and spinal subdural hematoma are rare complications of combined spinal-epidural anesthesia. We present a patient who developed both after multiple attempts to achieve combined spinal-epidural anesthesia. CASE PRESENTATION: A 21-year-old parturient, gravida 1, para 1, with twin pregnancy at gestational age 34+ 5 weeks underwent cesarean delivery. Routine combined spinal-epidural anesthesia was planned; however, no cerebrospinal fluid outflow was achieved after several attempts. Bupivacaine (2.5 mL) administered via a spinal needle only achieved asymmetric blockade of the lower extremities, reaching T12. Then, epidural administration of low-dose 2-chlorprocaine caused unexpected blockade above T2 as well as tinnitus, dyspnea, and inability to speak. The patient was intubated, and the twins were delivered. Ten minutes after the operation, the patient was awake with normal tidal volume. The endotracheal tube was removed, and she was transferred to the intensive care unit for further observation. Postoperative magnetic resonance imaging suggested a spinal subdural hematoma extending from T12 to the cauda equina. Sensory and motor function completely recovered 5 h after surgery. She denied headache, low back pain, or other neurologic deficit. The patient was discharged 6 days after surgery. One month later, repeat MRI was normal. CONCLUSIONS: All anesthesiologists should be aware of the possibility of SSDH and subdural block when performing neuraxial anesthesia, especially in patients in whom puncture is difficult. Less traumatic methods of achieving anesthesia, such as epidural anesthesia, single-shot spinal anesthesia, or general anesthesia should be considered in these patients. Furthermore, vital signs and neurologic function should be closely monitored during and after surgery.

A case-control-family study of idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVE: To determine the familial aggregation of idiopathic rapid eye movement sleep behavior disorder (iRBD), neurodegenerative diseases, and related biomarkers. METHODS: A total of 404 and 387 first-degree relatives of 102 patients with iRBD and of 89 controls were recruited, respectively. Among them, 204 and 208 relatives of patients and controls underwent face-to-face clinical assessment, whereas 97 and 75 relatives underwent further video-polysomnographic assessment, respectively. RESULTS: Compared with relatives of controls, relatives of patients demonstrated higher levels of RBD features, including chin tonic electromyography activity (mean = 1.5 ± 7.5 vs 0.3 ± 1.0, p = 0.04) and behavioral events (n [weighted %] = 12 [11.3] vs 2 [1.9], adjusted hazard ratio [aHR] = 7.69, 95% confidence interval [CI] = 1.54-33.33, p = 0.009) during rapid eye movement sleep, probable diagnosis (n [%] = 57 [14.9] vs 20 [4.9], aHR = 3.45, 95% CI = 1.96-6.25, p < 0.001), and definite diagnosis (n [weighted %] = 10 [8.4] vs 2 [1.4], aHR = 5.56, 95% CI = 1.16-25.00, p = 0.03). They also had higher risks of Parkinson disease (3.1% vs 0.5%, aHR = 5.88, 95% CI = 1.37-25.00, p = 0.02), dementia (6.9% vs 2.6%, aHR = 2.44, 95% CI = 1.15-5.26, p = 0.02), constipation (8.3% vs 2.4%, adjusted odds ratio = 4.21, 95% CI = 1.34-13.17, p = 0.01), and motor dysfunction (Movement Disorders Society Unified Parkinson's Disease Rating Scale part III motor score, mean = 1.9 ± 3.2 vs 0.9 ± 2.3, p = 0.002). The unaffected relatives of patients demonstrated a higher likelihood ratio of prodromal Parkinson disease (median [interquartile range] = 0.27 [1.19] vs 0.22 [0.51], p = 0.03). INTERPRETATION: iRBD is familially aggregated from isolated features to full-blown sleep disorder. Relatives of patients carry a higher risk of alpha-synucleinopathy in terms of neurodegenerative diseases and prodromal markers, suggesting a familial aggregation and staging pathology of alpha-synucleinopathy. Ann Neurol 2019;85:582-592.

Longer apnea duration at low altitude in Tibetan and Han highlanders compared with Han lowlanders: A retrospective study.

Prolonged duration of obstructive apnea (OA) has been observed in highlanders after descending to low altitude. It is proposed that due to adaptation to a hypoxic high-altitude environment, Tibetan highlanders (TH) and Han highlanders (HH) would manifest different OA durations at low altitude as compared to Han lowlanders (HL). Data collection on consecutive obstructive sleep apnea patients (167 TH, 210 HH and 233 HL) was performed over a period of 8 years in Chengdu (altitude 500 m). The analyses were performed with non-matched groups and with body mass index and apnea-hypopnea index-matched groups. Significance rankings for mean duration of OA (s) in non-matched groups and matched groups were TH (27.7; 28.6) = HH (25.7; 26.0) > HL (21.7; 21.3), respectively. For the longest OA duration, the significance rankings across three groups with regard to the percentage of patients having a duration longer than 2 min (%) and mean values (s) were TH (26.9; 82) > HH (10.0; 67) > HL (1.3; 50). In terms of nadir and mean oxygen saturation, significant differences were found between TH and HH or HL. In addition, longest and mean OA duration were positively correlated with blood pressure and heart rate, whereas nadir and mean oxygen saturation were negatively correlated with these measures in both non-matched and matched groups, and the correlation was more robust in TH. These findings raise important clinical questions regarding whether such significant prolongation of OA duration and a more severe hypoxic burden among highlanders, especially in TH, may lead to adverse clinical consequences when at low altitude.

Clinical features of multiple system atrophy with or without rapid eye movement behavior disorder: a cross-sectional study in southwest China.

OBJECTIVE: The aim of this study was to investigate the prevalence of rapid eye movement behavior disorder (RBD) in Chinese patients with multiple system atrophy (MSA) and to compare motor and non-motor symptoms and sleep disturbance of MSA patients with and without RBD. METHODS: A total of 55 patients who were consecutively admitted to West China Hospital of Sichuan University from 2016 to 2019 and subsequently diagnosed with probable MSA were enrolled in this cross-sectional study. The diagnosis of RBD was based on the results of video polysomnography (PSG) and a history of abnormal sleep-related behaviors. The patients were divided into two groups: those with RBD and those without. These two groups were then compared in terms of severity of motor symptoms (Unified Multiple System Arophy Rating Scale) and non-motor symptoms (Non-Motor Symptoms Scale, Mini-Mental State Examination score, Epworth Sleepiness Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale) and sleep parameters as recorded on PSG. RESULTS: Of the 55 patients (35 males), 18 (33%, 13 males) were diagnosed with RBD. Patients with or without RBD did not differ in demographic characteristics, clinical features, or sleep parameters based on PSG. CONCLUSION: There was no difference in motor and non-motor symptoms between MSA patients with or without RBD, indicating that the presence of RBD may not be significantly associated with the severity of motor or non-motor dysfunction in MSA.

Sleep disturbance is associated with an increased risk of menstrual problems in female Chinese university students.

PURPOSE: We aimed to investigate the association between sleep disturbance and menstrual problems in female Chinese university students. METHODS: A convenience sample of 1006 female university students participated in this study. Sleep duration, sleep quality, and insomnia symptoms were assessed by the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. A structured questionnaire was used to assess participants' demographics and menstrual characteristics. RESULTS: The prevalence rates of irregular menstrual cycle, heavy menstrual bleeding, menstrual flow length ≥ 7 days, period pain, and premenstrual syndrome were significantly higher in participants with sleep disturbance than those without sleep disturbance (all p < 0.05). After adjusting for potential confounding variables, poor sleep quality and insomnia symptoms were significantly associated with menstrual flow length ≥ 7 days (OR = 1.81, 95% CI = 1.23-2.68, OR = 1.67, 95% CI = 1.13-2.45), period pain (OR = 1.55, 95% CI = 1.02-2.35, OR = 1.56, 95% CI = 1.02-2.37), and premenstrual syndrome (OR = 1.71, 95% CI = 1.30-2.24, OR = 1.93, 95% CI = 1.46-2.56). In addition, poor sleep quality was significantly associated with heavy menstrual bleeding (OR = 1.75, 95% CI = 1.12-2.72), and insomnia symptoms were significantly associated with irregular menstrual cycle (OR = 1.36, 95% CI = 1.02-1.80). However, short sleep duration (≤ 6 h) was only associated with premenstrual syndrome. CONCLUSION: Our results suggested that sleep disturbance is associated with menstrual problems among female university students. More attention should be paid to improving the sleep quality and insomnia symptoms in individuals with menstrual problems.

Hepatitis B virus-regulated growth of liver cancer cells occurs through the microRNA-340-5p-activating transcription factor 7-heat shock protein A member 1B axis.

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Hepatitis B virus (HBV) is one of the leading causes of HCC, but the precise mechanisms by which this infection promotes cancer development are not fully understood. Recently, miR-340-5p, a microRNA (miRNA) that has been identified as a cancer suppressor gene, was found to inhibit the migration and invasion of liver cancer cells. However, the effect of miR-340-5p on cell proliferation and apoptosis in HBV-associated HCC remains unknown. In our study, we show that miR-340-5p plays an important role during HBV infection and hepatocellular carcinoma development. Specifically, this miRNA directly binds to the mRNA encoding activating transcription factor 7 (ATF7), a protein that both promotes cell proliferation and suppresses apoptosis through its interaction with heat shock protein A member 1B (HSPA1B). We further found that miR-340-5p is downregulated by HBV, which enhances ATF7 expression, leading to enhanced cell proliferation and inhibition of apoptosis. Notably, ATF7 is upregulated in HCC tissue, suggesting that HBV may target miR-340-5p in vivo to promote ATF7/HSPA1B-mediated proliferation and apoptosis and regulate liver cancer progression. This work helps to elucidate the complex interactions between HBV and host miRNAs and further suggests that miR-340-5p may represent a promising candidate for the development of improved therapeutic strategies for HCC.

Interaction effect of obstructive sleep apnea and periodic limb movements during sleep on heart rate variability.

We aimed at assessing cardiac autonomic function by heart rate variability during sleep in patients with obstructive sleep apnea and periodic limb movements during sleep, and to compare it with that of patients with obstructive sleep apnea only, periodic limb movements during sleep only, and controls. We also aimed at investigating the interaction effect between apnea-hypopnea index and periodic limb movement index on heart rate variability. Four groups of patients (n = 42 each, total = 168) were identified based on the presence/absence of obstructive sleep apnea and periodic limb movements during sleep: + obstructive sleep apnea/- periodic limb movements during sleep (5 ≤ apnea-hypopnea index < 30 events per hr), - obstructive sleep apnea/+ periodic limb movements during sleep (periodic limb movement index > 15 events per hr), + obstructive sleep apnea/+ periodic limb movements during sleep, - obstructive sleep apnea/- periodic limb movements during sleep (controls). All groups were matched for age, sex and body mass index. Time- and frequency-domain heart rate variability measures were calculated over 5-min periods of stable stage 2 non-rapid eye movement sleep. In patients with both obstructive sleep apnea and periodic limb movements during sleep, LFnu and LF/HF ratio were higher than in those with obstructive sleep apnea only, periodic limb movements during sleep only, and controls, while HFnu was the lowest among the four groups. LFnu, HFnu and LF/HF ratio were significantly and independently associated with minimal oxygen saturation in the + obstructive sleep apnea/+ periodic limb movements during sleep group. There was a significant interaction effect between apnea-hypopnea index and periodic limb movement index on LF/HF ratio (p = 0.038) in patients with obstructive sleep apnea. Patients with elevated apnea-hypopnea index and elevated periodic limb movement index exhibited higher sympathovagal balance compared with those with high apnea-hypopnea index and low periodic limb movement index, and compared with those with low apnea-hypopnea index (regardless of periodic limb movement index). Increased sympathetic activation and decreased parasympathetic control appear to be related to the severity of oxygen desaturation. Apnea-hypopnea index and periodic limb movement index had interactive effects on increased sympathovagal balance in patients with obstructive sleep apnea.

Duloxetine-induced rapid eye movement sleep behavior disorder: a case report.

BACKGROUND: Tricyclic antidepressants and selective serotonin reuptake inhibitors have been reported to induce the symptoms of rapid eye movement (REM) sleep behavior disorder (RBD) or to exacerbate REM sleep without atonia. With this case report, we found an association between typical RBD and duloxetine, a serotonin-noradrenaline reuptake inhibitor. CASE PRESENTATION: We present a case of a 62-year-old woman who experienced enactment behaviors with violent dreams that were associated with increased tonic or phasic chin electromyography activity during REM sleep after treated with duloxetine. RBD symptoms were gradually reduced and completely ceased after discontinuation of duloxetine for 37 days. CONCLUSION: The current case appears to be the first observation of duloxetine-induced RBD. We describe features of RBD induced by duloxetine that are similar and different from that induced by tricyclic antidepressants and selective serotonin reuptake inhibitors.

The role of DCs in the immunopathogenesis of chronic HBV infection and the methods of inducing DCs maturation.

Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Dendritic cells (DCs), as the most efficient professional antigen-presenting cells (APCs), possess the strongest antigen presenting the effect in the body and can stimulate the initial T cell activation and proliferation. DCs of patients with chronic HBV infection are impaired, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. Recently, numerous methods have been developed to induce DCs maturation. To date, recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) combined with interleukin-4 (rhIL-4) has been a classic culture combination to DCs. The recently classified type III interferon group interferon-λ (IFN-λ) displays antiviral, antitumor, and immunoregulatory activity. In our laboratory, we demonstrate that IFN-λ1 combined with rhGM-CSF and rhIL-4 can significantly increase the expression of DC surface molecules and the secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ) in patients with chronic hepatitis B infection. In this review, we emphasize on the role of DCs in the immunopathogenesis of chronic HBV infection. Importantly, we systematic review that the latest update in the current status of knowledge on the methods of inducing DCs maturation in anti-HBV immunity. What's more, we conclude that IFN-λ1 combined with GM-CSF and IL-4 can induce DCs maturation, which could become a possibility to be applied to the autologus dendritic cell vaccine to treat chronic hepatitis B.

Isolation of culturable aerobic bacteria and evidence of Kerstersia gyiorum from the blowhole of captive Yangtze finless porpoises.

Bacterial respiratory illnesses are problematic in aquatic mammals such as the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis; YFP), which is now at a critically endangered status. Yet little is known about the bacteria inhabiting the respiratory tract of YFPs. In this study, we preliminarily characterized the culturable aerobic bacteria from blow samples of captive YFPs. The bacterial diversity was assessed through cultivation by direct exhalation onto Columbia blood agar plates and identification of representative isolates through 16S rRNA gene sequence analysis. In total, eleven bacterial species belonging to four phyla Proteobacteria (71 %), Firmicutes (25 %), Bacteroidetes (3 %) and Actinobacteria (1 %) were identified. Most of these isolates were opportunistic pathogens found in respiratory illnesses in humans and animals. We also reported the first case of Kerstersia gyiorum isolated from an animal. This work provides a preliminary assessment of the bacteria present in the respiratory tract of captive YFPs, which will be an important first step in elucidating the roles of normal microbiota in maintaining respiratory health of YFPs. This study also points out the necessity of future long-term monitoring of blowhole microorganisms in the YFPs and making emergency preparedness plans for respiratory tract infections. These measures can aid in assessing the pathogenic risk of the critically endangered YFP populations.