Frontoparietal paired associative stimulation versus single-site stimulation for generalized anxiety disorder: a pilot rTMS study.

BACKGROUND: At present, the use of repetitive transcranial magnetic stimulation (rTMS) for generalized anxiety disorder (GAD) is limited to single-site interventions. We investigated whether dual-site frontoparietal stimulation delivered using cortical-cortical paired associative stimulation (ccPAS) had stronger clinical efficacy than single-site stimulation in patients with GAD. METHODS: We randomized 50 patients with GAD to 1 Hz rTMS (10 sessions) using 1 of the following protocols: single-site stimulation over the right dorsolateral prefrontal cortex (dlPFC; 1500 pulses per session); single-site stimulation over the right posterior parietal cortex (PPC; 1500 pulses per session); repetitive dual-site ccPAS (rds-ccPAS) over the right dlPFC and right PPC with 1500 pulses per session (rd-ccPAS-1500); or rds-ccPAS over the right dlPFC and right PPC with 750 pulses per session (rd-ccPAS-750). Both rds-ccPAS treatments used a between-site interval of 100 ms. RESULTS: Clinical scores for anxiety, depression and insomnia were reduced in all 4 groups after treatment. We found greater improvements in anxiety symptoms in the rds-ccPAS-1500 group compared to the rds-ccPAS-750 and single-site groups. We found greater improvements in depression symptoms and insomnia in the rds-PAS-1500 group compared to the single-site groups. The rds-ccPAS-1500 group also showed significant or trend-level improvements in anxiety symptoms and insomnia at 10-day and 1-month followup. More patients responded to treatment with rds-ccPAS-1500 than with single-site stimulation. The between-group differences in response rates persisted to the 3-month follow-up. Treatment using rds-ccPAS with a between-site interval of 100 ms induced a more significant improvement than the between-site interval of 50 ms we evaluated in a previous study. LIMITATIONS: These results need to be replicated in a larger sample using sham control and equal-pulse single-site stimulation. CONCLUSION: Frontoparietal rds-ccPAS may be a better treatment option for GAD.

Cryptococcosis in patients with liver cirrhosis: Death risk factors and predictive value of prognostic models.

BACKGROUND: Liver cirrhosis is associated with immune deficiency, which causes these patients to be susceptible to various infections, including cryptococcus infection. Mortality in cirrhotic patients with cryptococcosis has increased. The present study was to explore the risk factors of mortality and the predictive ability of different prognostic models. METHODS: Forty-seven cirrhotic patients with cryptococcosis at a tertiary care hospital were included in this retrospective study. Data on demographics, clinical parameters, laboratory exams, diagnostic methods, medication during hospitalization, severity scores and prognosis were collected and analyzed. Student's t test and Mann-Whitney test were used to compare characteristics of survivors and non-survivors at a 90-day follow-up and cerebrospinal fluid (CSF) manifestations of cryptococcal meningitis. Multivariate Cox regression analysis was used to identify the independent risk factors for mortality. Kaplan-Meier curves were used to analyze patient survival. Receiver operating characteristic (ROC) curves were used to evaluate the different prognostic factors. RESULTS: The 30- and 90-day survival rates were 93.6% and 80.9%, respectively, in cirrhotic patients with cryptococcosis. Cryptogenic liver diseases [hazard ratio (HR) = 7.567, 95% confidence interval (CI): 1.616-35.428, P = 0.010], activated partial thromboplastin time (APTT) (HR = 1.117, 95% CI: 1.016-1.229, P = 0.022) and Child-Pugh score (HR = 2.146, 95% CI: 1.314-3.504, P = 0.002) were risk factors for 90-day mortality in cirrhotic patients with cryptococcosis. Platelet count (HR = 0.965, 95% CI: 0.940-0.991, P = 0.008) was a protective factor. APTT (HR = 1.120, 95% CI: 1.044-1.202, P = 0.002) and Child-Pugh score (HR = 1.637, 95% CI: 1.086-2.469, P = 0.019) were risk factors for 90-day mortality in cirrhotic patients with cryptococcal meningitis. There was significant difference in the percentage of lymphocytes in CSF between survivors and non-survivors [60.0 (35.0-75.0) vs. 95.0 (83.8-97.2), P < 0.001]. The model of end-stage liver disease-sodium (MELD-Na) score was more accurate for predicting 30-day mortality both in patients with cryptococcosis [area under curve (AUC): 0.826, 95% CI: 0.618-1.000] and those with cryptococcal meningitis (AUC: 0.742, 95% CI: 0.560-0.924); Child-Pugh score was more useful for predicting 90-day mortality in patients with cryptococcosis (AUC: 0.823, 95% CI: 0.646-1.000) and those with cryptococcal meningitis (AUC: 0.815, 95% CI: 0.670-0.960). CONCLUSIONS: These results showed that cryptogenic liver diseases, APTT and Child-Pugh score were associated with mortality in cirrhotic patients with cryptococcosis and cryptococcal meningitis. MELD-Na score was important for predicting 30-day mortality, and Child-Pugh score was critical for predicting 90-day mortality.

Role of γδT cells in liver diseases and its relationship with intestinal microbiota.

γδT cells are unconventional T lymphocytes that bridge innate and adaptive immunity. Based on the composition of T cell receptor and the cytokines produced, γδT cells can be divided into diverse subsets that may be present at different locations, including the liver, epithelial layer of the gut, the dermis and so on. Many of these cells perform specific functions in liver diseases, such as viral hepatitis, autoimmune liver diseases, non-alcoholic fatty liver disease, liver cirrhosis and liver cancers. In this review, we discuss the distribution, subsets, functions of γδT cells and the relationship between the microbiota and γδT cells in common hepatic diseases. As γδT cells have been used to cure hematological and solid tumors, we are interested in γδT cell-based immunotherapies to treat liver diseases.

Differential Regional Brain Spontaneous Activity in Subgroups of Mild Cognitive Impairment.

Background: Amnestic mild cognitive impairment (aMCI) has a high conversion risk to Alzheimer's disease (AD). The aMCI patients may have only a memory deficit (single-domain-aMCI, sd-aMCI) or deficits in multiple cognitive domains (multiple-domain-aMCI, md-aMCI). However, differences in intrinsic brain activity between these two sub-types remain unclear. Method: Neuropsychological and resting-state functional magnetic resonance imaging (fMRI) data were acquired from 24 patients with sd-aMCI, 23 patients with md-aMCI, and 32 healthy controls (HCs). We used the fractional amplitude of low-frequency fluctuation (fALFF) to characterize the intensity of spontaneous brain activity. The analysis of covariance (ANCOVA) and post hoc tests was performed to determine the between-group differences in fALFF. Results: We found higher fALFF in left-sided superior-to-middle frontal gyri and middle-to-inferior temporal gyri in sd-aMCI compared to both the md-aMCI and HCs. Conversely, a lower fALFF was found in the left inferior parietal lobe in both the md-aMCI and sd-aMCI patients. The fALFF values in the left middle and inferior temporal gyri were correlated with cognitive performances. Conclusion: The gradual reduction in the left inferior parietal lobe from single to multiple domain aMCI suggest a functional inefficiency underlying cognitive impairment, while increased activity in the frontal and temporal gyri in sd-aMCI rather than md-aMCI might indicate functional compensation. This study indicates differential functional profiles in the sd-aMCI and md-aMCI, which may be helpful for the prediction of the future conversion of aMCI to AD.

Kaposi's sarcoma manifested as lower gastrointestinal bleeding in a HIV/HBV-co-infected liver cirrhosis patient: A case report.

BACKGROUND: Kaposi's sarcoma (KS) is one of the most common cancers in human immunodeficiency virus (HIV)-positive patients and leads to a high prevalence of morbidity and mortality. It usually appears as cutaneous or mucous lesions. Patients with visceral KS are asymptomatic and clinically silent. As the disease advances, patients may progress from a normal condition to exhibiting severe symptoms. CASE SUMMARY: A 27-year-old man presented with a 2-mo history of fever, bearing-down pain, and rectal bleeding. His hepatitis B virus DNA level was 2.7 ×107 IU/mL. Abdominal computed tomography (CT) indicated liver cirrhosis. Before he was admitted to our hospital, he was diagnosed with HIV infection. His CD4 count was 24 cells/µL. Pelvic cavity CT suggested a thickened rectum wall accompanied by multiple enlarged lymph nodes. The patient was initially treated as having haemorrhoidal varices with bleeding, telbivudine for anti-hepatitis B virus treatment, and antibiotics for anti-infection. After half a month of treatment, the patient felt that his lower lumbus ache and bearing-down pain had not improved, and a colonoscopy was conducted. The result revealed a rectal mass that was histologically confirmed as KS with rectal spindle cells that were positive for cluster of differentiation 117 (CD117), CD34, human herpes virus 8, and CD31. He was administered systemic chemotherapy with 36 mg/d liposomal doxorubicin six times. The patient experienced no sign of lower gastrointestinal bleeding again. CONCLUSION: This case highlights the diagnosis of primary KS with lower gastrointestinal bleeding in HIV-positive patients, which means visceral KS could not be excluded. The gold standard relies on colonoscopy and biopsy findings.

Suanzaoren Formulae for Insomnia: Updated Clinical Evidence and Possible Mechanisms.

Insomnia disorder is a widespread and refractory disease. Semen Ziziphi Spinosae, Suanzaoren, a well-known Chinese herbal medicine, has been used for treating insomnia for thousands of years. Here, we aimed to assess the available evidence of Chinese herbal formulae that contains Suanzaoren (FSZR) for insomnia according to high-quality randomized controlled trials (RCTs) and reviewed their possible mechanisms based on animal-based studies. Electronic searches were performed in eight databases from inception to November 2016. The primary outcome measures were polysomnography index and Pittsburgh sleep quality index. The secondary outcome measures were clinical effective rate and adverse events. The methodological quality of RCTs was assessed by Cochrane's collaboration tool, and only RCTs with positive for 4 out of 7 for the Cochrane risk of bias domains were included in analyses. Thirteen eligible studies with 1,454 patients were identified. Meta-analysis of high-quality RCTs showed that FSZR monotherapy was superior to placebo (P < 0.01); FSZR plus Diazepam was superior to Diazepam alone (P < 0.05); there were mixed results comparing FSZR with Diazepam (P > 0.05 or P < 0.05). Furthermore, FSZR caused fewer side effects than that of Diazepam. Suanzaoren contains complex mixtures of phytochemicals including sanjoinine A, Jujuboside A, spinosin and other flavonoids, which has sedative and hypnotic functions primarily mediated by the GABAergic and serotonergic system. In conclusion, the findings of present study supported that FSZR could be an alternative treatment for insomnia in clinic. FSZR exerted sedative and hypnotic actions mainly through the GABAergic and serotonergic system.

Perimesencephalic nonaneurysmal subarachnoid hemorrhage caused by transverse sinus thrombosis: A case report and review of literature.

RATIONALE: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH) is characterized by a pattern of extravasated blood restricted to the perimesencephalic cisterns, normal angiographic findings, and an excellent prognosis with an uneventful course and low risks of complication. The precise etiology of bleeding in patients with PNSAH has not yet been established. The most common hypothesis is that PNSAH is venous in origin. Intracranial venous hypertension has been considered as the pivotal factor in the pathogenesis of PNSAH. The underlying venous pathology such as straight sinus stenosis, jugular vein occlusion may contribute to PNSAH. We describe a patient in whom transverse sinus thrombosis preceded intracranial venous hypertension and PNSAH. These findings supported that the source of the subarachnoid hemorrhage is venous in origin. PATIENT CONCERNS AND DIAGNOSES: A 45-year-old right-handed man was admitted to the hospital with a sudden onset of severe headache associated with nausea, vomiting, and mild photophobia for 6 hours. The patient was fully conscious and totally alert. An emergency brain computed tomography (CT) revealed an acute subarachnoid hemorrhage restricted to the perimesencephalic cisterns. CT angiography revealed no evidence of an intracranial aneurysm or underlying vascular malformation. Digital subtraction angiography of arterial and capillary phases confirmed the CT angiographic findings. Assessment of the venous phase demonstrated right transverse sinus thrombosis. Magnetic resonance imaging confirmed the diagnosis of cerebral venous sinus thrombosis (CVST). Lumbar puncture revealed an opening pressure of 360 mmH2O, suggestive of intracranial venous hypertension. Grave disease was diagnosed by endocrinological investigation. INTERVENTIONS: Low-molecular-weight heparin, followed by oral warfarin, was initiated immediately as the treatment for cerebral venous sinus thrombosis and PNSAH. OUTCOMES: The patient discharged without any neurologic defect after 3 weeks of hospital stay. MR venography revealed recanalization of right transverse sinus at the 6-month follow-up. No clinical or neuroimaging evidence of relapse was detected at 12 months follow-up. LESSONS: Hyperthyroidism may contribute to the development of CVST. The presence of acute transverse sinus thrombosis, as a cause of PNSAH, provides further support for the hypothesis that the source of PNSAH is venous in origin and intracranial venous hypertension plays a critical role in the pathogenesis of PNSAH.

Chinese herbal medicine adjunct therapy in patients with acute relapse of multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Many patients with multiple sclerosis (MS) resort to complementary and alternative medicine, which is used in 33%-80% of MS patients in the developed country. The purpose of this study is to assess the efficacy and safety of Chinese herbal medicine (CHM) as an adjunct therapy of patients with acute relapse of MS. METHODS: Six databases were searched for randomized-controlled trial of CHM for acute relapse of MS. The risk of bias was assessed by using the twelve criteria recommended by the Cochrane Back Review Group. The primary outcome measures of interest are the Expanded Disability Status Score, annual relapse frequency, annual relapse rate, and annual relapse interval. The secondary outcome measures are the clinical efficacy rate and adverse events. The selection criteria of high-frequency herbs for MS are those with cumulative frequency over 50%. We analyzed the data using Review Manager (version 5.3). RESULTS: A total of 1100 participants were included in the 20 studies from 2004 to 2015. The number of risk of bias which met the criteria varied from 5/12 to 7/12. The top 5 most frequently used herbs are ordinally Radix Angelicae Sinensis, Radix Glycyrrhizae, Radix Paeoniae Rubra, Radix Rehmanniae Preparata, and Bombyx Batryticatus. The meta-analysis showed a significant effect of CHM for improving Expanded Disability Status Score (P<0.01), annual relapse frequency (P<0.01) and the total clinical efficacy rate (P<0.01) compared with western conventional treatment. In analysis of annual relapse rate and annual relapse interval, there was a significant difference between CHMs and western conventional treatment (P<0.01). Adverse effects were monitored in 6 studies, and were well tolerated in all MS patients. CONCLUSIONS: The available evidence from present study supported but limited to recommend the routine use of CHM adjuvant therapy for MS because of the poor methodological quality and clinical heterogeneity. However, we identified an area that is worthy of further study. Furthermore, we selected high frequent use of CHMs as a promising candidate for further clinical application and MS trials. Further rigorous randomized-controlled trials are needed.

Efficacy and safety of suanzaoren decoction for chronic insomnia disorder in adults: study protocol for randomised, double-blind, double-dummy, placebo-controlled trial.

BACKGROUND: Insomnia disorder is defined as a combination of dissatisfaction with sleep quantity or quality and a significant negative impact on daytime functioning. Chronic insomnia disorder refers to clinical symptoms of persistent insomnia at least three nights a week for at least 3 months. Prevalence estimates of insomnia disorder range from 12% to 20% in the adult population, with approximately 50% having a chronic course. The potential side effects of hypnotic medications hinder their clinical application. Thus, traditional Chinese medicine is considered as an alternative option for treating insomnia. OBJECTIVE: To evaluate the efficacy and safety of suanzaoren decoction (SZRD), a classic Chinese herbal prescription, for adult chronic insomnia disorder. METHODS/ANALYSIS: This is a randomised, double-blind, double-dummy, placebo-controlled clinical trial. A total of 150 patients with chronic insomnia disorder are randomised, allocated in a ratio of 1:1:1 to three groups: intervention group, control group and placebo group. The intervention group receives SZRD granule plus zolpidem tartrate (ZT) placebo; the control group receives ZT tablet plus SZRD granule placebo; and the placebo group receives ZT placebo and SZRD granule placebo. The patients receive medicine or placebo for 5 weeks and are followed up at 20 weeks. The primary outcome measures are polysomnography and Pittsburgh Sleep Quality Index. Secondary outcome measures are the Insomnia Severity Index, sleep diary and safety assessment. Outcomes will be assessed at baseline and after treatment. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16009198. pre-results.

Astragaloside IV for Experimental Focal Cerebral Ischemia: Preclinical Evidence and Possible Mechanisms.

Astragaloside IV (AST-IV) is a principal component of Radix Astragali seu Hedysari (Huangqi) and exerts potential neuroprotection in experimental ischemic stroke. Here, we systematically assessed the effectiveness and possible mechanisms of AST-IV for experimental acute ischemic stroke. An electronic search in eight databases was conducted from inception to March 2016. The study quality score was evaluated using the CAMARADES. Rev Man 5.0 software was used for data analyses. Thirteen studies with 244 animals were identified. The study quality score of included studies ranged from 3/10 to 8/10. Eleven studies showed significant effects of AST-IV for ameliorating the neurological function score (P < 0.05); seven studies for reducing the infarct volume (P < 0.05); and three or two studies for reducing the brain water content and Evans blue leakage (P < 0.05), respectively, compared with the control. The mechanisms of AST-IV for ischemic stroke are multiple such as antioxidative/nitration stress reaction, anti-inflammatory, and antiapoptosis. In conclusion, the findings of present study indicated that AST-IV could improve neurological deficits and infarct volume and reduce the blood-brain barrier permeability in experimental cerebral ischemia despite some methodological flaws. Thus, AST-IV exerted a possible neuroprotective effect during the cerebral ischemia/reperfusion injury largely through its antioxidant, anti-inflammatory, and antiapoptosis properties.

An Overview of Systematic Reviews of Ginkgo biloba Extracts for Mild Cognitive Impairment and Dementia.

Ginkgo biloba extracts (GBEs) have been recommended to improve cognitive function and to prevent cognitive decline, but earlier evidence was inconclusive. Here, we evaluated all systematic reviews of GBEs for prevention of cognitive decline, and intervention of mild cognitive impairment (MCI) and dementia. Six databases from their inception to September 2015 were searched. Ten systematic reviews were identified, including reviews about Alzheimer's disease (n = 3), about vascular dementia (n = 1), about both Alzheimer's disease and vascular dementia (n = 2), about Alzheimer's disease, vascular dementia and mixed dementia (n = 3), and a review about MCI (n = 1). Based on the overview quality assessment questionnaire, eight studies were scored with at least 5 points, while the other two scored 4 points and 3 points, respectively. Medication with GBEs showed improvement in cognition, neuropsychiatric symptoms, and daily activities, and the effect was dose-dependent. Efficacy was convincingly demonstrated only when high daily dose (240 mg) was applied. Compared with placebo, overall adverse events and serious adverse events were at the same level as placebo, with less adverse events in favor of GBE in the subgroup of Alzheimer's disease patients, and fewer incidences in vertigo, tinnitus, angina pectoris, and headache. In conclusion, there is clear evidence to support the efficacy of GBEs for MCI and dementia, whereas the question on efficacy to prevent cognitive decline is still open. In addition, GBEs seem to be generally safe.