Breast cancer is a leading malignancy and a significant cause of mortality in women. The coexistence of depression has been associated with a more aggressive breast cancer progression. Si–Ni–San (SNS), a Traditional Chinese medicine (TCM) formula, has been traditionally used for the treatment of depression. This clinical trial aimed to evaluate the effectiveness and safety of SNS in relieving depression in breast cancer patients, and explore its molecular mechanism. A randomized, double-blind, placebo-controlled crossover trial was conducted in breast cancer patients with mild to moderate depression (MMD). Patients were asked to participate over a four-week SNS treatment and a four-week placebo intervention in randomized order, with a two-week washout period. The primary endpoint was the change of Hamilton Depression Scale-24 (HAMD-24) score. Secondary endpoints were the changes of Functional Assessment of Cancer Therapy—Breast (FACT-B) and syndrome score of Traditional Chinese medicine (TCMSS). Liver function test (LFT) and mental status examination (MSE) were conducted to ensure the safety. Gut microbiota, serum metabolomics, cytokine profiling and T lymphocyte subsets were tested to explore the molecular mechanisms. A total of 53 patients completed the trial. Compared to placebo intervention, SNS treatment significantly reduced HAMD-24 score (4.46 ± 4.403 (95
BackgroundTraditional Chinese medicine (TCM) comprising herbal formulas has been used for millennia to treat various diseases, such as insomnia, based on distinct syndrome types. Although TCM has been proposed to be effective in insomnia through gut microbiota modulation in animal models, human studies remain limited. Therefore, this study employs machine learning and integrative network techniques to elucidate the role of the gut microbiome in the efficacies of two TCM formulas — center-supplementing and qi-boosting decoction (CSQBD) and spleen-tonifying and yin heat-clearing decoction (STYHCD) — in treating insomnia patients diagnosed with spleen qi deficiency and spleen qi deficiency with stomach heat.MethodsSixty-three insomnia patients with these two specific TCM syndromes were enrolled and treated with CSQBD or STYHCD for 4 weeks. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) every 2 weeks. In addition, variations in gut microbiota were evaluated through 16S rRNA gene sequencing. Stress and inflammatory markers were measured pre- and post-treatment.ResultsAt baseline, patients exhibiting only spleen qi deficiency showed slightly lesser severe insomnia, lower IFN-α levels, and higher cortisol levels than those with spleen qi deficiency with stomach heat. Both TCM syndromes displayed distinct gut microbiome profiles despite baseline adjustment of PSQI, ISI, and IFN-α scores. The nested stratified 10-fold cross-validated random forest classifier showed that patients with spleen qi deficiency had a higher abundance of Bifidobacterium longum than those with spleen qi deficiency with stomach heat, negatively associated with plasma IFN-α concentration. Both CSQBD and STYHCD treatments significantly improved sleep quality within 2 weeks, which lasted throughout the study. Moreover, the gut microbiome and inflammatory markers were significantly altered post-treatment. The longitudinal integrative network analysis revealed interconnections between sleep quality, gut microbes, such as Phascolarctobacterium and Ruminococcaceae, and inflammatory markers.ConclusionThis study reveals distinct microbiome profiles associated with different TCM syndrome types and underscores the link between the gut microbiome and efficacies of Chinese herbal formulas in improving insomnia. These findings deepen our understanding of the gut-brain axis in relation to insomnia and pave the way for precision treatment approaches leveraging TCM herbal remedies.
Background Major depressive disorder (MDD) is a life-threatening, debilitating mental health condition. An important factor in the development of depression is endoplasmic reticulum stress (ERS). However, their roles in MDD have not yet been established. The goal of this study was to examine ERS and its underlying molecular mechanisms in MDD. Methods We used data from two microarray datasets (GSE98793 and GSE39653) and the GeneCards database to examine the reticulum stress-related differentially expressed genes (ERSR-DEGs) associated with MDD. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were used to further investigate the function and mechanism of ERS in MDD. Moreover, we constructed protein-protein interaction (PPI) networks to identify hub genes as well as the regulatory network of microRNAs (miRNAs), transcription factors (TFs), and potential drugs related to ERSR-DEGs. CIBERSORT was then used to evaluate the immune activity of MDD samples and conduct a correlation analysis between the hub genes and immune cells. Results In total, 37 ERSR-DEGs and five hub genes were identified (NCF1, MAPK14, CASP1, CYBA, and TNF). Functional enrichment analysis revealed that ERSR-DEGs were predominantly enriched in inflammation-and immunity-related pathways, such as tumor necrosis factor signaling, NF-κB signaling, and Toll-like receptor signaling pathways. Additionally, 179 miRNAs, 25 TFs, and 15 potential drugs were tested for their interactions with the ERSR-DEGs. CIBERSORT found high proportions of Tregs, monocytes, and macrophages M0 in the MDD samples. Among these, hub genes showed a significant correlation with immune cell infiltration in patients with MDD. Conclusions NCF1, MAPK14, CASP1, CYBA, and TNF are potential ERS-related biomarkers for the diagnosis of MDD. Our research has revealed a significant correlation between immune cells and ERS-related genes with MDD. Not only did our study contribute to a better understanding of the regulatory mechanisms of ERS in underlying MDD pathology, but it also established a paradigm for future studies on ERS.
目的 比较分析中医与西医治疗抑郁症随机对照试验(Randomized Controlled Trial,RCT)的结局指标及测量工具使用现状,为今后研究开展提供参考.方法 检索6个临床研究注册平台,获取中医和西医治疗成人抑郁症RCT的注册信息;检索9个中英文数据库,补充中医治疗抑郁症的RCT文献;提取并分析其报告的结局指标及测量工具.结果 共获注册的西医RCT 1033项,中医RCT 195项(注册29项、发表166项).西医RCT使用的结局指标共581个,评价内容全面涵盖心理功能和躯体功能、日常活动能力、环境反应以及生存质量等结局指标域,涉及406个量表.11%研究关注了安全性结局.中医RCT使用的结局指标共118个,评价内容仅涵盖心理功能和躯体功能、药物不良反应和中医证候等结局指标域,涉及14个量表;极少文献使用了中医疗效评价指标;安全性结局报告率为47%;86.7%研究使用汉密尔顿抑郁量表作为测量工具.结论 西医研究使用的结局指标及测量工具涵盖范围广且研究间差异较大,而中医研究使用的结局指标及测量工具范围小且集中.今后开展的抑郁症临床研究在结合研究目的的基础上,可参考国际抑郁症核心指标集,结合中医药潜在作用点来选择结局指标及适合的测量工具以评价中医药疗效和安全性.
Effects of two different models for transport properties, including the approximate model and the collision integral model, on hypersonic flow simulations of Mars entry vehicles are numerically investigated. A least square fitting is firstly performed using the best-available data of collision integrals for Martian atmosphere species within the temperature range of 300–20,000 K. Then, the performance of these two transport properties models are compared for an equilibrium Martian atmosphere gas mixture at 10 kPa and temperatures ranging from 1000 to 10,000 K. Finally, four flight conditions chosen from the trajectory of the Mars Pathfinder entry vehicle are numerically simulated. It is indicated that the approximate model is capable of accurately providing the distributions of species mass fractions and temperatures in the flowfield. Both models give similar translational-rotational and vibrational heat fluxes. However, the chemical diffusion heat fluxes predicted by the approximate model are significantly larger than the results computed by the collision integral model, particularly in the vicinity of the forebody stagnation point, whose maximum relative error of 15% for the super-catalytic case. The diffusion model employed in the approximate model is responsible to the discrepancy. In addition, the wake structure is largely unaffected by the transport properties models.
Background: Depression is common in women during perimenopause and menopause. Complementary therapies such as acupuncture and Chinese herbal medicine (CHM) are often utilized by these women. However, the efficacy and safety of these treatments have not been systematically evaluated. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Nine English and Chinese databases were searched and search terms included perimenopause, menopause, depression, Chinese herbal medicine, acupuncture, RCTs, and their synonyms. Methodological quality was assessed using the Cochrane Risk of Bias Tool. Results: A total of 18 RCTs were identified (6 CHM, 11 acupuncture related therapies, 1 combination of CHM and acupuncture). For Hamilton Rating Scale of Depression (HRSD) and Kuppermans Index of Menopause, tuina-massage, combined therapy of CHM plus acupuncture showed significant benefits at end of treatment compared to antidepressants. Either CHM and acupuncture reduced HRSD scores, indicating less severe depression, showing comparable effects to antidepressants. Conclusion: CHM and acupuncture treatment in perimenopause and menopausal women resulted in reduced severity of depression. Results should be interpreted with caution given the small number of studies included in this review and further RCTs are warranted to validate findings from this review.
Objectives: Bupleurum chinense (BC; Radix Bupleuri) formulae are widely used in herbal medicine clinical practice for major depressive disorder (MDD). This study provides an up-to-date and comprehensive systematic review and meta-analysis of BC formula for MDD. Design: Randomized controlled trials were retrieved from English and Chinese databases, from their inceptions to March 2019. Included studies compared BC formula alone or as integrative medicine to selective serotonin reuptake inhibitor (SSRI) antidepressants. Studies included adults 18-65 years of age. People with other types of depression or physical comorbidities, such as poststroke depression, bipolar, and other mental or physical disorders, were excluded. Meta-analysis was performed using STATA software. Grading of Recommendations Assessment, Development, and Evaluation was also conducted to assess the quality of evidence. Results: Thirty studies compared BC formula to antidepressants and 25 studies compared BC formula plus antidepressants to antidepressants alone. BC formula was more effective than antidepressants at improving depression severity measured on the Hamilton Rating Scale for Depression (HRSD) (standardized mean difference [SMD] -0.35, 95% confidence interval [CI] -0.52 to -0.18, I2 = 81.2%). Integrative use of BC formula plus SSRIs was also superior to SSRIs alone at improving HRSD scores (SMD -1.03, 95% CI -1.43 to -0.62, I2 = 94.2%). However, heterogeneity of the included studies was high and quality was low. The total number and severity of adverse events in the BC formula groups were less than that in the antidepressant groups. Conclusions: BC formula alone or given as integrative medicine with antidepressants reduced depression severity. However, the evidence is low quality and at risk of bias. Well-designed studies are needed to validate the results we identified in this review.
To evaluate the diagnostic value of fiber tractography and diffusivity analysis generated from 3D diffusion-weighted (DW) sequences for preoperative assessment of benign peripheral nerve sheath tumors.MR imaging at 3 T was performed in 22 patients (mean age 41.9 ± 17.1y, 13 women) with histologically confirmed schwannomas (N = 18) and histologically confirmed neurofibromas (N = 11), including a 3D DW turbo spin echo sequence with fat suppression. Diffusion tensor parameters were computed and fiber tracks were determined. Evaluation was performed by two radiologists and one orthopedic surgeon blinded for final diagnosis. Mean diffusivity was computed to allow further assessment of tumor microstructure. Preoperative fascicle visualization was graded, fascicles were categorized regarding anatomical location and amount of fascicles surrounding the tumor. The agreement of imaging findings with intraoperative findings was assessed.On 78.3 % of the DTI images, the fascicle visualization was rated as good or very good. Tractography differences were observed in schwannomas and neurofibromas, showing schwannomas to be significantly more often located eccentrically to the nerve (94.8 %) than neurofibromas (0 %, P < 0.01). Fascicles were significantly more often continuous (87.5 %) in schwannomas, while in neurofibromas, none of the tracks was graded to be continuous (0 %, P = 0.014). A substantial agreement between fiber tracking and surgical anatomy was found regarding the fascicle courses surrounding the tumor (κ = 0.78). Mean diffusivity of schwannomas (1.5 ± 0.2 × 10−3 mm2/s) was significantly lower than in neurofibromas (1.8 ± 0.2 × 10−3 mm2/s; P < 0.001). The Youden index showed an optimal cutoff at 1.7 × 10−3 mm2/s (sensitivity, 0.91; specificity, 0.78; J = 0.69).Preoperative diffusion tensor imaging allowed to accurately differentiate between schwannomas and neurofibromas and to describe their location in relation to the nerve fascicles for preoperative planning.
•This systematic review provides up-to-date evidence of acupuncture and Chinese herbal medicine for postpartum depression.•We found Chinese herbal medicine improved depression symptoms and severity compared to antidepressants.•Acupuncture was neither superior nor inferior to sham or antidepressants.•Adverse events were similar to sham/placebo and less than antidepressants.•The full extent of the effect remains inconclusive due to poor quality extant randomized controlled trials.