Abstract Background The red blood cell distribution width‐to‐albumin ratio (RAR) is a novel composite biomarker of inflammation and nutritional status, yet its association with insomnia and underlying mechanisms remain poorly understood. Objective To investigate the association between the RAR and insomnia in two independent cohorts, comprising a nationally representative U.S. population and a Chinese clinical population, and to explore the mediating roles of adiposity and metabolic indicators. Methods We analyzed 20,571 adults from National Health and Nutrition Examination Survey (NHANES) 2005–2014 and 270 participants from the Hangzhou Hospital of Traditional Chinese Medicine (HZ‐TCM) cohort in China. Insomnia was defined using validated questionnaires or clinical diagnoses. Logistic regression, restricted cubic spline analyses, two‐piecewise threshold analyses, and mediation analyses were performed. Results Threshold analysis identified RAR inflection points of 3.52 (NHANES) and 3.44 (HZ‐TCM). Below these thresholds, each unit increase in RAR was associated with a 2.86‐fold increase in insomnia odds in NHANES (OR = 2.86, 95% CI: 2.23–3.68) and a 27.74‐fold increase in the HZ‐TCM cohort (OR = 27.74, 95% CI: 9.11–84.45) (both p < 0.001), whereas no significant association was observed above the thresholds. Conclusions RAR is an independent and robust biomarker for insomnia risk, demonstrating a consistent nonlinear threshold association across both population‐based and clinical cohorts. Central obesity and insulin resistance appear to be important mediating pathways. As an easily accessible composite indicator, RAR holds potential clinical utility for insomnia risk assessment.

Ethnopharmacological relevance: Traditional Chinese medicine has historically used Zhichi Suanzaoren Decoction (ZSD) to alleviate perimenopausal insomnia (PMI). ZSD has demonstrated clinical efficacy in treating PMIrelated symptoms; however, its active constituents and mechanisms of action remain unclear. Aim of the study: The aim of this study was to explore the bioactive components of ZSD using UPLC-Q-TOF/MS, evaluate its efficacy in vivo experiments, and elucidate its potential mechanisms of action-particularly the role of primary hippocampal astrocyte cilia in PMI. Materials and methods: The main components of ZSD were analyzed by UPLC-Q-TOF/MS. A PMI model was established using bilateral ovariectomy, followed by ZSD treatment. Behavioral tests and pentobarbital sodium-induced sleep synergy experiments were used to assess anti-insomnia and anxiolytic effects. Mechanistic studies included ELISA, Nissl staining, immunohistochemistry, transcriptome sequencing, immunofluorescence staining, qRT-PCR, Western blotting, and adeno-associated virus (AAV)-mediated Foxj1 knockdown. Results: A total of 97 chemical components in the aqueous extract of ZSD were identified using UPLC-Q-TOF/MS in positive-and negative-ion modes. ZSD significantly improved sleep and reduced anxiety in PMI mice; increased hippocampal GABA levels; and reduced serum ACTH, CORT, IL-6, TNF-alpha, and IL-1(3 levels. ZSD exerts a protective effect on hippocampal neurons and reduces neuroinflammation. Transcriptomic and protein-level analyses demonstrated that ZSD inhibited Wnt signaling by promoting Foxj1 expression and restoring primary cilia in astrocytes. This led to dual effects: (1) activation of the GSK-3(3/GR signaling pathway, restoring HPA axis function and reversing glucocorticoid resistance; and (2) suppression of (3-catenin nuclear translocation and astrocyte-driven neuroinflammation. Conclusions: ZSD can alleviate insomnia, anxiety, and neuroinflammation in a PMI model. The therapeutic effects are mediated through the restoration of primary astrocyte cilia via Foxj1 upregulation. These findings highlight a previously unrecognized role of primary cilia in the pathogenesis of PMI and provide a scientific rationale for the clinical application of ZSD and traditional Chinese medicine in mood-related disorders.

Given the robust correlation between MAFLD and OSA, FSI may act as a potential indicator for OSA risk. Nevertheless, the correlation between FSI and OSA, along with the potential mediating mechanisms, remains unclear. Our study examined 46,028 NHANES participants from 2005 to 2008 and 2015 to 2020. FSI-OSA correlation was assessed using weighted multivariate logistic regression models, restricted cubic spline curve analysis, threshold effects analysis, and subgroup analysis. We also conducted mediation studies to determine if waist-to-height ratio (WHtR) mediates the FSI-OSA relationship. Each unit increase in the FSI was associated with a 36

ETHNOPHARMACOLOGICAL RELEVANCE:Traditional Chinese medicine has historically used Zhichi Suanzaoren Decoction (ZSD) to alleviate perimenopausal insomnia (PMI). ZSD has demonstrated clinical efficacy in treating PMI-related symptoms; however, its active constituents and mechanisms of action remain unclear. AIM OF THE STUDY:The aim of this study was to explore the bioactive components of ZSD using UPLC-Q-TOF/MS, evaluate its efficacy in vivo experiments, and elucidate its potential mechanisms of action-particularly the role of primary hippocampal astrocyte cilia in PMI. MATERIALS AND METHODS:The main components of ZSD were analyzed by UPLC-Q-TOF/MS. A PMI model was established using bilateral ovariectomy, followed by ZSD treatment. Behavioral tests and pentobarbital sodium-induced sleep synergy experiments were used to assess anti-insomnia and anxiolytic effects. Mechanistic studies included ELISA, Nissl staining, immunohistochemistry, transcriptome sequencing, immunofluorescence staining, qRT-PCR, Western blotting, and adeno-associated virus (AAV)-mediated Foxj1 knockdown. RESULTS:A total of 97 chemical components in the aqueous extract of ZSD were identified using UPLC-Q-TOF/MS in positive- and negative-ion modes. ZSD significantly improved sleep and reduced anxiety in PMI mice; increased hippocampal GABA levels; and reduced serum ACTH, CORT, IL-6, TNF-α, and IL-1β levels. ZSD exerts a protective effect on hippocampal neurons and reduces neuroinflammation. Transcriptomic and protein-level analyses demonstrated that ZSD inhibited Wnt signaling by promoting Foxj1 expression and restoring primary cilia in astrocytes. This led to dual effects: (1) activation of the GSK-3β/GR signaling pathway, restoring HPA axis function and reversing glucocorticoid resistance; and (2) suppression of β-catenin nuclear translocation and astrocyte-driven neuroinflammation. CONCLUSIONS:ZSD can alleviate insomnia, anxiety, and neuroinflammation in a PMI model. The therapeutic effects are mediated through the restoration of primary astrocyte cilia via Foxj1 upregulation. These findings highlight a previously unrecognized role of primary cilia in the pathogenesis of PMI and provide a scientific rationale for the clinical application of ZSD and traditional Chinese medicine in mood-related disorders.

To observe the effectiveness of sleep health management system in improving sleep of people with insomnia problems. A total of 120 college students who had insomnia problems in four universities of Zhejiang Province were randomly divided into sleep management group and blank control group. The sleep management group was given sleep hygiene education and managed sleep health through sleep health management application program, while the blank control group was given sleep hygiene education alone. The improvement of sleep, mood, cognition of sleep and clinical efficacy were compared between the two groups. The scores of Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Dysfunctional Beliefs and Attitudes about Sleep Scale-16 (DBAS-16) and the polysomnography data were used to evaluate efficacy. After the treatment, the score of sleep management group decreased more than that of blank control group, and the polysomnography data showed that the improvement of sleep quality in sleep management group was better than that in blank control group. The above results suggest that the application of sleep health management system can effectively improve the sleep of people with insomnia problems, adjust the sleep structure, regulate emotions and improve the poor cognition of sleep.

Background The incidence and prevalence of Parkinson's disease (PD) are rapidly increasing, leading to significant disease and economic burden. Identifying causal relationships, exposures, risk factors, and molecular processes associated with the occurrence and progression of PD is crucial for the development of prevention and treatment strategies. Methods In this systematic review, we examined evidence regarding causal associations between potential risk factors and PD derived from Mendelian randomization (MR) studies, adhering to PRISMA guidelines. Methodological quality was evaluated based on critical components of MR methodology, including comprehensive instrumental variable analysis and validation of the three key MR assumptions. Results We included methodological details and findings from 41 articles. MR studies provided evidence for causal relationships between BMI, lifestyle, lipid levels, AD, stroke, anxiety, depression, inflammatory bowel disease, rheumatoid arthritis, and PD, although results varied substantially across each category. Conclusions Although this review demonstrates how MR can offer valuable insights into exploring potential therapeutic targets and enhancing our understanding of the pathophysiology of PD, certain methodological limitations in the existing literature hinder the reliability of results and likely contribute to their heterogeneity. We emphasize the importance of future MR studies focusing on lifestyle factors, gut microbiota, and epigenetics.

Background: Cognitive impairment and insomnia are common complications for stroke patients, and often coexist without effective therapy. Modified Suanzaoren decoction (M-SZRD), derived from a famous classic prescription, has been used as an alternative treatment for these patients. The objective of this study is to investigate the effectiveness of M-SZRD in treating post-stroke cognitive impairment with comorbid insomnia symptoms. Methods: A total of 80 participants were randomly assigned into 2 groups to 40 cases in the treatment group (treated with modified Suanzaoren decoction) and 40 cases in the control group (treated with zolpidem). The intervention period was 4 weeks. Cognitive function, sleep quality, depression, and anxiety disorders were evaluated in both groups before and after treatment. Clinical assessment of patients with stroke included National Institutes of Health Stroke Scale and Barthel Index evaluations. Hormone levels of the hypothalamic-pituitary-adrenal and hypothalamus-pituitary-thyroid axis were also measured. Results: Out of the total 80 participants, 5 withdrew during the experiment and did not complete the study, leaving 75 patients for analysis to 38 in the treatment group and 37 in the control group. The findings showed that M-SZRD was more effective than the control group in improving cognitive function (P = .006). However, both groups were found to have a similar effect in improving insomnia (P = .323). There was no significant difference between the 2 groups in terms of activities of daily living and National Institutes of Health Stroke Scale improvement. M-SZRD was superior to the control group in improving depression state (P = .034), but when including dropouts in the intention-to-treat analysis, the difference was not statistically significant (P = .150). Furthermore, the M-SZRD group was better than the control group in reducing cortisol levels (P = .036), and the improvement in serum-free triiodothyronine (FT3) levels was also more significant in the M-SZRD group than in the control group (P = .0007). Conclusion: M-SZRD is a more effective treatment for improving cognitive function in patients with post-stroke cognitive impairment and comorbid insomnia symptoms, possibly by regulating the cortisol levels of the hypothalamic-pituitary-adrenal axis and FT3 levels of the hypothalamus-pituitary-thyroid axis.

Background: Factors affecting subjective perception of sleep are unclear but clinically important. We investigated the dif-ferences in subjective sleep perception of patients with obstructive sleep apnea (OSA) and insomnia disorder (ID). Material/Methods: From our Sleep Medicine Center database, 33 patients with OSA and 69 with ID were selected and assessed with the Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder screen, Patient Health Questionnaire-9, Epworth Sleepiness Scale, Pre-sleep Arousal Scale (PSAS), and polysomnography. Results: In subjective sleep tests, PSQI total score, sleep quality, sleep onset latency (SOL), total sleep time, and sleep efficiency (SE) were higher in patients with ID. In objective sleep tests, patients with OSA had longer total sleep time, shorter SOL, lower percentage of stage N3, less SE, higher percentage of stage N1, more arousals, and higher arousal index. Hyperarousal state evaluation showed cognitive hyperarousal significantly higher with ID. Subjective sleep perception with OSA correlated positively with PSAS total score, cognitive hyperarousal, and percentage of stage N2 and negatively with percentage of REM, apnea-hypopnea index, and desaturation index. Subjective sleep perception of patients with ID correlated positively with PSAS total score, cognitive hy-perarousal, SOL, N3 sleep latency, and REM sleep latency and negatively with SE. Conclusions: Subjective sleep perception of OSA patients was mainly related to sleep structure and respiratory events, and that of ID patients, to sleep latency. Individual cognitive hyperarousal levels may be involved in negative sub-jective sleep perception. Clinicians should be aware that OSA patients may not actually experience adequate sleep.

背景 认知障碍和失眠障碍均是卒中后常见的并发症,两者常以共病形式出现且相互影响,进而影响卒中患者功能康复,延长住院时间.卒中发生后,患者的激素水平及脑血流会发生改变,这可能与卒中并发症存在相关性.目的 分析卒中后认知障碍(PSCI)伴失眠患者的临床资料,并分析其相关因素.方法 选取2018年8月—2020年2月在浙江省立同德医院就诊的门诊及住院卒中患者55例,将PSCI伴失眠患者作为观察组(n=40),卒中后不伴有认知障碍和睡眠障碍者作为对照组(n=15).记录两组一般资料,相关临床量表评分,血清下丘脑-垂体-肾上腺(HPA)轴激素〔促肾上腺激素(ACTH)、皮质醇(CORT)〕、下丘脑-垂体-甲状腺(HPT)轴激素〔促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)〕、同型半胱氨酸(Hcy)和神经特异性烯醇化酶(NSE)水平.采用磁共振动脉自旋标记序列(ASL)测定患者脑血流量(CBF),对两组感兴趣区(ROI)进行比较分析.结果 两组文化程度比较,差异有统计学意义(P<0.05).观察组蒙特利尔认知评估量表(MoCA)评分、Barthel指数低于对照组,美国国立卫生研究院卒中量表(NIHSS)、匹兹堡睡眠质量指数(PSQI)、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评分均高于对照组(P<0.05).两组血清TSH、FT3、FT4水平比较,差异无统计学意义(P>0.05);观察组患者ACTH、CORT水平高于对照组(P<0.05).两组血清Hcy水平比较,差异无统计学意义(P>0.05);观察组血清NSE水平高于对照组(P<0.05).观察组左侧额叶CBF值低于对照组(P<0.05).Spearman秩相关分析结果显示,观察组患者MoCA评分与年龄、NIHSS评分、血清NSE水平呈负相关(rs=-0.321,P=0.043;rs=-0.478,P=0.002;rs=-0.433,P=0.005),与Barthel指数、右顶叶、左顶叶、右侧额叶、左侧额叶、右侧颞叶、右侧枕叶、左侧枕叶、右侧丘脑CBF值呈正相关(rs=0.486,P=0.001;rs=0.639,P=0.003;rs=0.285,P=0.003;rs=0.723,P<0.001;rs=0.530,P=0.020;rs=688,P=0.001;rs=0.705,P=0.009;rs=0.582,P=0.009;rs=0.576,P=0.010);观察组患者PSQI评分与HAMD评分、HAMA评分、血清CORT水平、右侧枕叶CBF值呈正相关(rs=0.603,P<0.001;rs=0.591,P<0.001;rs=0.635,P<0.001;rs=0.593,P=0.007).结论 PSCI伴失眠患者的抑郁、焦虑程度较高,HPA轴相对亢进,血清NSE水平偏高,相关性分析提示PSCI伴失眠患者的睡眠障碍程度与血清CORT水平、HAMD及HAMA评分、右侧枕叶CBF值呈正相关;认知功能与年龄、NIHSS评分、血清NSE水平呈负相关,与Barthel指数和大部分脑区CBF值呈正相关.

Background . Chronic insomnia is a major public health problem, but there are limited effective therapies. Jiawei Suanzaoren Decoction (JW-SZRD) has been used as an alternative option for treating insomnia. This study aimed to investigate the long-term efficacy and safety of JW-SZRD in combination with lorazepam for chronic insomnia. Methods . A total of 207 participants were analyzed in this study. The treatment group (TG) received JW-SZRD and lorazepam orally, and the control group (CG) received lorazepam alone. The Insomnia Severity Index (ISI), the Self-Rating Depression Scale (SDS), the Self-Rating Anxiety Scale (SAS), and the Somatic Self-rating Scale (SSS) were evaluated at baseline, weeks 4, 8, and 12. The MOS 36-item Short Form Health Survey (SF-36) was assessed at baseline and week 12. Adverse effects (AEs) were evaluated by the Treatment Emergent Symptom Scale (TESS). Results . Both TG and CG showed obvious improvements in the sleep onset latency (SOL) (P=0.001 and 0.005) and total sleep time (TST) (P=0.0001 and 0.001). However, TG was more effective than CG at weeks 8 (P=0.02 for SOL, P=0.008 for TST) and 12 (P=0.03 for SOL, P=0.04 for TST), especially in shortening SOL (Cohen’s d = 1.28). The ISI reduction rate in TG was higher than that in CG at weeks 4, 8, and 12 (P=0.008, 0.001 and 0.001). After treatment, TG had lower SAS scores (P=0.0001, 0.007), less somatic symptoms (P<0.05 or 0.01), higher SF-36 scores (P<0.05 or 0.01), better compliance (P=0.0001), and less adverse effects (P<0.05 or 0.01) than those in CG. Conclusion . The combination of JW-SZRD with lorazepam can significantly improve sleep quality with fewer AEs. It is an effective treatment and superior to lorazepam alone for chronic insomnia.

Background: Depression is a common mental disorder with unknown mechanism. Emerging evidence shows that miRNAs play a critical role in the process of depression. Here we reported the cerebrospinal fluid (CSF) miR-16 expression and its association with miR-16 and serotonin transporter (SERT) in the raphe of a rat model of depression. Methods: 20 rats were randomized to the control or CUMS (chronic unpredictable mild stress) group. The rats in the CUMS group underwent CUMS for 21 days, while those in the control group received no treatment. After anesthetization, CSF was collected for the measurement of miR-16. Then raphes from all rats were separated for determination of miR-16 and SERT protein. Results: The expression levels of miR-16 in CSF and raphe of the CUMS group were significantly lower than those of the control group (P=0.007 and 0.031). However, SERT protein in raphe of the CUMS group was obviously increased as compared that of the control group (P=0.005). There was a positive correlation between CSF miR-16 and raphe miR-16 (r=0.95, P=0.000). Meanwhile, negative correlations between miR-16 and SERT protein in raphe (r=-0.70 P=0.02), between CSF miR-16 and raphe SERT protein (r=-0.86, P=0.002) were observed in the CUMS group. Limitations: We have not explored the reason why CSF miR-16 was decreased in the rat model of depression and only tested the association of miR-16 between CSF and raphe. Conclusions: CSF miR-16 was involved in the pathogenesis of depression via reflecting raphe miR-16 level, and thus affecting raphe SERT expression.

Background. Paroxetine does not show satisfactory therapeutic effect for generalized anxiety disorder (GAD) patients for the first 2-4 weeks of medication. Diazepam is always concurrently used although it has some shortcomings such as physical dependence and withdrawal reactions. In this study, we aimed to identify whether modified Suanzaorentang (MSZRT), a combined Chinese formula including Suanzaorentang (SZRT) and Zhizichitang (ZZCT), could control the anxiety of GAD for the first 4 weeks of paroxetine medication. Methods. 156 GAD patients were randomized to the treatment of paroxetine, paroxetine-diazepam, or paroxetine-MSZRT for 4 weeks. Hamilton Anxiety Scale (HAMA) Test and Self-Rating Anxiety Scale (SAS) Test were determined each week as the evaluation of clinical efficacy. Adverse events (AEs) were also closely observed by performing the Treatment Emergent Symptom Scale (TESS) Test. Results. Both paroxetine-MSZRT and paroxetine-diazepam decreased more HAMA and SAS total scores than paroxetine from weeks 1 to 3. Paroxetine-MSZRT as well as paroxetine-diazepam had an obviously higher onset rate than paroxetine in each week. After 4 weeks' treatment, the overall effectiveness rate in the paroxetine-MSZRT group (90.00%) was obviously higher than those of the paroxetine group (74.42%) but did not significantly differ from the paroxetine-diazepam group (93.88%). Conclusion. MSZRT had the treatment effect for GAD when paroxetine was used for the first 4 weeks.

Background The exact cerebral structural and functional mechanisms under the auditory verbal hallucinations (AVHs) in schizophrenia are still unclear. The Deutsch “high-low” word illusion might trigger attentional responses mimicking those under AVHs. Methods We therefore have invited 16 patients with first-episode, paranoid schizophrenia, and 16 age- and gender-matched healthy volunteers to undergo the “oddball” event-related potentials elicited by the illusion. The clinical characteristics of patients were measured with the positive and negative symptom scale. Results Besides the longer reaction time to the illusion, the standard P2 latency was shortened, the N2 latency was prolonged, and both N1 and P3 amplitudes were reduced in patients. The P3 source analyses showed the activated bilateral temporal lobes, parietal lobe and cingulate cortex in both groups, left inferior temporal gyrus in controls, and left postcentral gyrus in schizophrenia. Moreover, the N1 amplitude was positively correlated with the paranoid score in patients. Conclusions Our results were in line with previous neurophysiological and neuroimaging reports of hallucination or auditory processing in schizophrenia, and illustrated a whole process of cerebral information processing from N1 to P3, indicating this illusion had triggered a dynamic cerebral response similar to that of the AVHs had engaged.

Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

Background: Animal and cell line studies demonstrated that miR-16 may be associated with major depressive disorder (MDD) via regulation of the expression of serotonin transporter (SERT) gene. However, human studies about miR-16 of patients with MDD are still lacking. The aim of this study was to investigate the possible involvement of miR-16 in the mechanism of MDD in humans.Methods: Thirty-six drug-free patients with MDD and 30 healthy controls aged between 18 and 45 years old were recruited. 24-item Hamilton depression scale test was performed for each subject. MiR-16 in cerebrospinal fluid (CSF) and blood, as well as serotonin in CSF were assayed by the qRT-PCR or ELBA method. To confirm the role of CSF miR-16 in MDD, animal study about intracerebroventricular injection of anti-miR-16 was also performed. Depression-like behaviors, CSF miR-16 and serotonin, blood miR-16, and raphe SERT protein of rats were also tested.Results: CSF miR-16 in MDD patients was significantly lower than that in controls. It was negatively correlated with Hamilton scores and positively associated with CSF serotonin. However, blood miR-16 was not significantly different between two groups and it was not statistically correlated with CSF miR-16. In animal study, anti-miR-16-treated rats were evaluated to exhibit depression-like behaviors, extremely lower CSF miR-16, significantly higher CSF serotonin, and obviously higher raphe SERT protein than control rats.Limitation: We did not detect SERT protein in human brain due to the impossibility of sample collection.Conclusion: Our study suggested that CSF miR-16 participated in the physiopathology of MDD via the modulation of serotonin transmitter system in brain. (C) 2015 Elsevier B.V. All rights reserved.

BACKGROUND & AIMS:Selective serotonin reuptake inhibitors (SSRIs) are used to treat various psychiatric disorders. However, there are concerns that SSRIs increase the risk for upper gastrointestinal bleeding (UGIB). METHODS:We performed a systematic review and meta-analysis of controlled observational studies to determine whether SSRI use affects the risk for UGIB. Our analysis included all observational studies that compared UGIB development among patients receiving SSRIs vs no treatment. We calculated pooled odds ratios using random- and fixed-effects models. RESULTS:A total of 22 studies (6 cohort and 16 case-control studies) involving more than 1,073,000 individuals were included in our meta-analysis. In comparing SSRI users with patients who had not taken SSRIs, the odds for developing UGIB were 1.55-fold higher (odds ratio, 1.55; 95% confidence interval, 1.35-1.78). In subgroup analyses, the association was greatest for patients who received concurrent therapy with nonsteroidal anti-inflammatory or antiplatelet drugs; we found no significant increase in the risk of developing UGIB among patients receiving concurrent acid-suppressing drugs. CONCLUSIONS:SSRI use was associated with an almost 2-fold increase in the risk of developing UGIB, especially among patients at high risk for GI bleeding (concurrent use of nonsteroidal anti-inflammatory or antiplatelet drugs). This risk might be reduced significantly by concomitant use of acid-suppressing drugs.

BACKGROUND & AIMS:Interferon-α (IFN-α)-induced depression is a major complication to treatment of chronic hepatitis C virus (HCV) infection. Specific serotonin reuptake inhibitors (SSRIs) can be used to treat depression, but it is not clear whether they can prevent depression in patients receiving IFN therapy for chronic HCV infection. METHODS:We performed a meta-analysis by searching the Cochrane Library, PubMed, and EMBASE databases through 2013 for published results from randomized, placebo-controlled trials evaluating the utility of SSRIs in preventing IFN-induced depression in HCV patients. We analyzed data from 7 studies with a total of 662 patients. The incidence of IFN-induced major depression and depression severity were defined as primary outcomes. Sustained virologic response, completion of antiviral therapy, and tolerability were considered secondary outcomes. RESULTS:A meta-analysis of IFN-induced major depression revealed that prophylactic SSRIs reduced the risk of depression, compared with placebo (relative risk [RR], 0.56; 95% confidence interval [CI], 0.37-0.84; P = .005). Proportions of patients achieving a sustained virologic response (RR, 1.02; 95% CI, 0.79-1.32; P = .87) and completing antiviral therapy (RR, 0.98; 95% CI, 0.66-1.44; P = .91) were similar between patients given SSRIs and controls. Prophylactic SSRIs were tolerated in patients with HCV during treatment. CONCLUSIONS:On the basis of a meta-analysis of 7 randomized controlled trials, prophylactic administration of SSRIs to patients with HCV significantly lowered the incidence of IFN-induced major depression, compared with placebo, and the SSRIs were well tolerated.

OBJECTIVE:To analyze the relationship of anxiety state with CD4(+) level and CD4(+)/CD8(+) ratio and to observe the effect of Chinese medicine (CM) treatment on anxiety in chronic hepatitis B (CHB) patients.METHODS:The anxiety state of 120 CHB patients was evaluated based on Hamilton Anxiety Scale (HAMA) scoring. According to the scores, 63 patients with scores ≥14 were classified to anxiety and 57 patients with scores <14 to non-anxiety. The differences in CD4(+) cells and CD4(+)/CD8(+) ratio between patients with anxiety and non-anxiety were analyzed. Moreover, 63 patients with anxiety were randomized into two groups: 31 in the control group were treated with lamivudine (100 mg per day) alone and 32 in the observation group were given equal dosage lamivudine combined with CM treatment depending on syndrome differentiation, all for 12 weeks. The effects of treatment on anxiety state and T-lymphocyte subsets as well as its impact on some CHB-related indices were observed and compared.RESULTS:The anxiety state of CHB patients was negatively correlated with CD4(+) and CD4(+)/CD8(+); the level of CD4(+) in patients with anxiety was significantly lower than that in non-anxiety patients (P<0.01 or P<0.05). After treatment, anxiety state in the observation group was significantly improved, with their HAMA scores significantly lowered (P<0.01), and the levels of CD4(+) and CD4(+)/CD8(+) were significantly higher than those in the control group (P<0.05 or P<0.01). Moreover, the alanine transaminase recovery rate and the HBV-DNA-negative conversion rate in the observation group were significantly higher than those in the control group, respectively (P<0.05).CONCLUSIONS:The anxiety state of CHB patients was related to CD4(+) and CD4(+)/CD8(+) levels. CM treatment could improve the anxiety state and showed certain regulatory effect on the patients' immune system.

Objective: To observe the effect of Chinese medicine therapy for strengthening-Pi ((sic)) and nourishing-Shen ((sic), SPNS) in preventing lamivudine induced YMDD mutation and its immunological mechanism. Methods: One hundred and sixty chronic hepatitis B (CHB) patients with positive HBeAg were equally assigned to two groups at random: the observation group and the control group. Patients in the observation group were treated with lamivudine combined with SPNS, and those in the control group were treated with lamivudine only, with the treatment lasting for 52 weeks in total. Changes in indexes, including liver function, HbeAg, HBV-DNA, YMDD variation, CD4, CD4/CD8 ratio, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), blood routine, renal function, as well as any adverse reactions that occurred in patients, were observed at different time points. Results: The ALT, AST recovery rate and HBV-DNA negatively inversing rate at the 24th week, the 36th week and the 52nd week were all higher (P<0.05); meanwhile, the YMDD mutation rate at the 36th week and the 52nd week was lower (P<0.05) in the observation group than in the control group. The post-treatment levels of CD4, CD4/CD8 ratio, IFN-gamma, and IL-4 as well as the pre-post treatment difference of these indexes in the observation group were significantly different from those in the control group (P<0.05). Conclusion: Chinese medicine SPNS therapy can significantly reduce the YMDD variation of HBV, and the mechanism may be related to its regulation of the CD4 level, CD4/CD8 ratio and Th1/Th2 balance.

Objective: To study the clinical effect of Tongxie Yaofang ((sic),TXYF) Granule in treating diarrhea-predominate irritable bowel syndrome (D-IBS) and its possible mechanism. Methods: A total of 120 patients were assigned to two groups using stratified block randomization, 80 in the intervention group and 40 in the control group. To the intervention group the TXYF granule was given at one package each time, twice a day; the control group was treated with Miyarisan three times a day, two tablets each time. The course of treatment was 4 weeks for both groups. The total efficacy in them was compared, and data of scoring on stool (Bristol method), abdominal pain, abdominal distension, and mental condition were collected before treatment and 2 and 4 weeks after treatment. The activation of mast cells (MCs) of six patients chosen from each group was detected as well before and after treatment. Results: No significant difference between the two groups in terms of the total efficacy or the scores of symptoms before and after treatment was found (P>0.05). The number of activated MCs was decreased in the intervention group after treatment, showing significant difference as compared with that before treatment as well as with that in the control group after treatment (P<0.01). Conclusions: TXYF is an effective preparation for the treatment of D-IBS. It can quickly lessen abdominal pain and distention, improve the property of stool, and improve mental tension and depression in patients. Its mechanism of action might be through the adjustment of MCs activation to decrease visceral hypersensitivity.