To the Editor: Alterations of circadian rhythms seem to be the casual contribution to sleep disturbances, depression, and other non-motor symptoms in Parkinson's disease (PD).[1,2] By restoring the circadian rhythm, bright light therapy (BLT) might be a potentially new treatment option for PD. However, no studies have conclusively demonstrated the effects of BLT on the non-motor symptoms in PD. Twenty-seven PD patients signed written informed consent and were included in this study. All the patients received 1 h of BLT (10,000 lux) daily within a time frame of 09:00 AM and 11:00 AM for 7 consecutive days. Participants were evaluated for motor and non-motor symptoms before and after the treatment, followed by the assessment of non-motor symptoms on day 28. Finally, 23 PD patients completed the study [Figure 1]. Compared with the baseline, BLT significantly improved daytime sleepiness as assessed by Epworth Sleepiness Scale (ESS, 8.91 ± 5.43 vs. 8.26 ± 4.51, P = 0.032), sleep quality as assessed by Pittsburgh Sleep Quality Index (PSQI, 9.22 ± 4.74 vs. 7.65 ± 3.79, P = 0.042), and Parkinson's Disease Sleep Scale-2 (PDSS-2, 33.65 ± 13.78 vs. 35.96 ± 11.93, P = 0.043). In addition, there were significant differences in Montreal Cognitive Assessment (MoCA) scores (22.17 ± 4.44 vs. 22.91 ± 3.84, P = 0.002) and delayed recall section (1.74 ± 1.91 vs. 2.48 ± 1.75, P = 0.000) between pre- and post-light exposure. There was no significant change in motor symptoms and other non-motor symptoms like depression, anxiety, and autonomic functions. At follow-up, most rating scales that reflected improvement after light exposure were not statistically significant from baseline, except Hamilton Depression Rating Scale (HAMD, 7.96 ± 4.25 vs. 8.52 ± 4.03, P = 0.006). PD patients were divided into PD with EDS and PD without EDS based on ESS scores. Further analysis demonstrated significant improvement in daytime sleepiness in PD with the EDS group after light exposure.Figure 1: The flowchart of study design and patient enrolment. BLT: Bright light therapy; ESS: Epworth Sleepiness Scale; HAMD: Hamilton Depression Rating Scale; MoCA: Montreal Cognitive Assessment; PD: Parkinson's disease; PDSS-2: Parkinson's Disease Sleep Scale-2; PSQI: Pittsburgh Sleep Quality Index. UPDRS: Unified Parkinson's Disease Rating Scale; H&Y: Hoehn & Yahr staging; MMSE: Mini Mental State Examination; HAMA: Hamilton Anxiety Rating Scale; PDQ-39: Parkinson's Disease Questionnaire-39; SCOPA-AUT: Scales for Outcomes in Parkinson's disease- Autonomic; NMSQ: Non-Motor Symptom Questionnaire; FSS: Fatigue Severity Scale; ESS: Epworth Sleepiness Scale; RBDSQ: Rem sleep Behavior Disorder Screening Questionnaire; RBD-HK: Rem sleep Behavior Disorder questionnaire - Hong Kong; MEQ-SA: Morningness - Eveningness questionnaire Self-Assessment version.The strengths of this study lie in the comprehensive assessments of the efficacy of BLT on the non-motor symptoms in PD patients. Besides, scores for each subscale were analyzed for spotting minor improvement of BLT. Finally, to the best of our knowledge, this is a rare report in China yet. There are several limitations to this study. First, the sample size is relatively small and selection bias should be considered. Second, the control group is not included in this study; thus, the possibility of placebo effects could not be excluded. Besides, the place where patients received BLT is not a closed space; therefore, the external light environment changing with seasons could interfere with our experiment. Finally, our study lacks more objective data for clinical assessment, such as data from polysomnography, actigraphy, or data on dynamic changes of cortisol and melatonin. To conclude, BLT for the PD population is still in its infancy. BLT might be a feasible treatment for ameliorating the sleep and cognitive functions in PD patients. Due to the relatively short intervention time and small sample size, the effects of BLT seemed to be mild and temporal. Further randomized controlled trials with larger samples are warranted to clarify the optimal parameters of photobiomodulation and objectively evaluate its effects in the PD population. Funding This work was supported by grants from the Jiangsu Provincial Key R&D Program (No. BE2018658), the Jiangsu Provincial Medical Key Discipline Project (No. ZDXKB2016022), Discipline Construction Program of the Second Affiliated Hospital Soochow University(No. XKTJ-XK202001), the National Natural Science Foundation of China (No. 81801253) and the Natural Science Foundation of Jiangsu Province (BK 20180214). Conflicts of interest None.
To evaluate the efficacy and safety of Xinfeng capsule in patients suffering rheumatoid arthritis (RA). A multi-center parallel-group designed, double-blind, randomized, controlled trial was conducted. Totally 304 RA patients were assigned to two groups: one group was administered Xinfeng capsule (XFC) plus the placebo of leflunomide and the other given leflunomide (LEF) plus the placebo of XFC for twelve weeks. The clinical and laboratory parameters were compared at baseline and fourth, eighth, and twelfth weeks. After twelve-week treatment, patients in two groups all showed some trend of effectiveness when compared in terms of American Rheumatism Association (ACR) recommended 20%, 50%, 70% improvement criteria, but it was insignificant. The validity in ameliorate modified disease activity score (DAS28) and laboratory indexes as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) were also found no difference. The score of health assessment questionnaire (HAQ), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and quality of life questionnaire with rheumatoid arthritis (RAQOL) both lower than the first week and the changes showed no difference. However, the score of SDS dropped more in XFC group than in the other. A total of 147 adverse reaction cases were reported, which shows no difference between the two groups. The most common adverse reactions were hepatic impairment, anemia, leukocytopenia, epigastric discomfort and phalacrosis. XFC demonstrated better improvement in the scores of SDS and compared with those of LEF group.
Previous studies have shown that genetic variants in HLA-DP genes affect disease progression in hepatitis B virus (HBV) infection.We aimed to evaluate possible association between HLA-DPB1 rs9277534 polymorphism and different clinical complications of hepatitis B virus (HBV) infection.Snapshot assay was used to investigate the association of rs9277534 polymorphism in 342 patients with persistent HBV infection and 342 age and gender-matched HBV spontaneous clearance controls. Patients were categorized into asymptomatic HBV carriers (AsC, n = 104), chronic hepatitis B (CHB, n = 116), and liver cirrhosis (LC, n = 122) subgroups.There was a significantly higher proportion of the rs9277534 minor allele A in HBV spontaneous clearance control than that in HBV persistent infection group (OR = 0.58, 95%CI = 0.46-0.73, P < 0.0001). Genotypic analysis showed that GA and AA genotypes were associated with HBV spontaneous clearance (GA: OR = 0.56, 95%CI = 0.40-0.79, P = 0.019; AA: OR = 0.24, 95%CI = 0.14-0.44, P < 0.0001). A significant difference was found between AsC and LC groups in the distribution of AA genotype (OR = 9.32, 95%CI = 1.293-67.14, P = 0.027).Variant at rs9277534 could affect both the spontaneous clearance of HBV infection and progression from asymptomatic HBV carriers to HBV-related liver cirrhosis in Southwest Han Chinese population.
Patients with Alzheimer's disease (AD) commonly show anxiety behaviors, but the molecular mechanisms are not clear and no efficient intervention exists. Here, we found that overexpression of human wild-type, full-length tau (termed htau) in hippocampus significantly decreased the extracellular γ-aminobutyric acid (GABA) level with inhibition of γ oscillation and the evoked inhibitory postsynaptic potential (eIPSP). With tau accumulation, the mice show age-dependent anxiety behaviors. Among the factors responsible for GABA synthesis, release, uptake, and transport, we found that accumulation of htau selectively suppressed expression of the intracellular vesicular GABA transporter (vGAT). Tau accumulation increased miR92a, which targeted vGAT mRNA 3' UTR and inhibited vGAT translation. Importantly, we found that upregulating GABA tones by intraperitoneal injection of midazolam (a GABA agonist), ChR2-mediated photostimulating and overexpressing vGAT, or blocking miR92a by using specific antagomir or inhibitor efficiently rescued the htau-induced GABAergic dysfunctions with attenuation of anxiety. Finally, we also demonstrated that vGAT level decreased while the miR92a increased in the AD brains. These findings demonstrate that the AD-like tau accumulation induces anxiety through disrupting miR92a-vGAT-GABA signaling, which reveals molecular mechanisms underlying the anxiety behavior in AD patients and potentially leads to the development of new therapeutics for tauopathies.
Glucagon-like peptide-1 (GLP-1) promotes insulin secretion, inhibits glucagon secretion, and repairs pancreatic islet cell function to enhance islet cell proliferation and regeneration. Furthermore, it includes a mechanism for weight loss and angiocarpy protection. This study covers the comparison of GLP-1 agonists with DPP-4 inhibitors and GLT-2 inhibitors, the mechanism of GLP-1 agonists, and its research possibilities based on a summary of current clinical tests of GLP-1 receptor agonists.
Abstract Chronic cerebral hypoperfusion (CCH) is identified as a critical risk factor of dementia in patients with cerebrovascular disease. Xiaoshuan enteric-coated capsule (XSECC) is a compound Chinese medicine approved by Chinese State Food and Drug Administration for promoting brain remodeling and plasticity after stroke. The present study aimed to explore the potential of XSECC to improve cognitive function after CCH and further investigate the underlying mechanisms. CCH was induced by bilateral common carotid artery occlusion (BCCAO) in rats. XSECC (420 or 140 mg/kg) treatment remarkably reversed BCCAO-induced cognitive deficits. Notably, after XSECC treatment, magnetic resonance angiography combined with arterial spin labeling noninvasively demonstrated significantly improved hippocampal hemodynamics, and 18 F-FDG PET/CT showed enhanced hippocampal glucose metabolism. In addition, XSECC treatment markedly alleviated neuropathologies and improved neuroplasticity in the hippocampus. More importantly, XSECC treatment facilitated axonal remodeling by regulating the phosphorylation of axonal growth related proteins including protein kinase B (AKT), glycogen synthase kinase-3β (GSK-3β) and collapsin response mediator protein-2 (CRMP2) in the hippocampus. Taken together, the present study demonstrated the beneficial role of XSECC in alleviating BCCAO-induced cognitive deficits by enhancing hippocampal glucose metabolism, hemodynamics and neuroplasticity, suggesting that XSECC could be a useful strategy in cerebral hypoperfusion state and dementia.
Anxiety disorders, prevalent mental health conditions, receive significant attention globally due to their intricate etiology and the suboptimal effectiveness of existing therapies. Research is increasingly recognizing that the genesis of anxiety involves not only neurochemical brain alterations but also changes in gut microbiota. The microbiota-gut-brain axis (MGBA), serving as a bidirectional communication pathway between the gut microbiota and the central nervous system (CNS), is at the forefront of novel approaches to deciphering the complex pathophysiology of anxiety disorders. This review scrutinizes the role and recent advancements in the MGBA concerning anxiety disorders through a review of the literature, emphasizing mechanisms via neural signals, endocrine pathways, and immune responses. The evidence robustly supports the critical influence of MGBA in both the development and progression of these disorders. Furthermore, this discussion explores potential therapeutic avenues stemming from these insights, alongside the challenges and issues present in this realm. Collectively, our findings aim to enhance understanding of the pathological mechanisms and foster improved preventative and therapeutic strategies for anxiety disorders.
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