Effect of Shi-Zhen-An-Shen herbal formula granule in the treatment of young people at ultra-high risk for psychosis: a pilot study.

Introduction: To date, there is no conclusive evidence for early interventions on ultra-high risk (UHR) for psychosis. The Chinese herbal medicine is confirmed to be beneficial in improving psychiatric symptoms and cognitive impairments for schizophrenia patients. However, the effect of Chinese herbal medicine on treating UHR patients remains unknown. Methods: Eighty UHR patients were recruited from the outpatient department. They were randomly assigned to receive either Shi-Zhen-An-Shen herbal formula granule (SZAS-HFG) combined with aripiprazole placebo or aripiprazole combined with SZAS-HFG placebo for a 12-week treatment. The psychiatric symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). The Trail Making Test part A (TMT-A), Brief Visuospatial Memory Test (BVMT), Hopkins Verbal Learning Test (HVLT), and Continuous Performance Test (CPT) were used to assess cognitive functions. we also employed the Global Assessment of Functioning (GAF) to evaluate social functioning. The linear mixed-effects models were performed to detect the difference in effectiveness between the two groups. Results: After 12-week treatment, both groups showed significant effects of time on SIPS, TMT-A, HVLT, BVMT, and GAF. There was a significant effect of group only on CPT. Moreover, we also found a significant interaction effect on GAF. Conclusion: SZAS-HFG can effectively alleviate psychosis symptoms, and improve cognitive impairments and overall functioning as well as aripiprazole.Clinical trial registration: Chinese Clinical Trial Registry, ChiCTR-IOR-17013513.

Protective Effects of Shi-Zhen-An-Shen Decoction on the Cognitive Impairment in MK801-Induced Schizophrenia Model.

BACKGROUND: Cognitive dysfunction is a core feature of schizophrenia that strongly correlates to the patients' difficulties in independent living and occupational functioning. Synaptic dysfunction may result in cognitive and behavioral changes similar to what have been identified in schizophrenia. Shi-Zhen-An-Shen Decoction (SZASD) is the empirical formula of traditional Chinese medicine adopted in treating psychiatric symptoms, especially the cognitive impairment in schizophrenia patients, with proven efficacy in the long term of clinical practice in Beijing Anding Hospital, Capital Medical University. However, the mechanisms of SZASD on the cognitive improvement in schizophrenia is still unclear. Here, we aim to investigate the underlying mechanisms of the impact of SZASD on the cognitive impairment in MK801-induced schizophrenia-like rats. METHODS: Six rat groups (n = 12 per group) were subjected to different treatments for 14 days. All the six groups were injected intraperitoneally with a given volume of 0.9% saline and MK801 (0.2 mg/kg) for consecutive 14 days for modelling. And the rats in the SZASD-treated groups and the clozapine-treated group were given SZASD (low, middle, and high doses) or clozapine, respectively, by intragastric administration. Then, we performed behavioral tests after the treatments, and the rats were sacrificed on the 19th day for biological analysis. RESULTS: Behavioral tests indicated that SZASD mitigated the aberrant motor activity and improved schizophrenia-like rats' spatial reference memory and sensory gating ability. Furthermore, SZASD significantly increased the expressions of PSD95, BDNF, and synapsin I in the hippocampus of MK801-induced schizophrenia-like rats. CONCLUSIONS: Our findings suggest that SZASD may ameliorate cognitive impairment by restoring the levels of synaptic proteins in the hippocampus.

The altered intrinsic functional connectivity after acupuncture at shenmen (HT7) in acute sleep deprivation.

Introduction: Accumulating evidence has shown that acupuncture could significantly improve the sleep quality and cognitive function of individuals suffering from insufficient sleep. Numerous animal studies have confirmed the effects and mechanisms of acupuncture on acute sleep deprivation (SD). However, the role of acupuncture on individuals after acute SD remains unclear. Methods: In the current study, we recruited 30 healthy subjects with regular sleep. All subjects received resting-state fMRI scans during the rested wakefulness (RW) state and after 24 h of total SD. The scan after 24 h of total SD included two resting-state fMRI sessions before and after needling at Shenmen (HT7). Both edge-based and large-scale network FCs were calculated. Results: The edge-based results showed the suprathreshold edges with abnormal between-network FC involving all paired networks except somatosensory motor network (SMN)-SCN between the SD and RW state, while both decreased and increased between-network FC of edges involving all paired networks except frontoparietal network (FPN)-subcortical network (SCN) between before and after acupuncture at HT7. Compared with the RW state, the large-scale brain network results showed decreased between-network FC in SMN-Default Mode Network (DMN), SMN-FPN, and SMN-ventral attention network (VAN), and increased between-network FC in Dorsal Attention Network (DAN)-VAN, DAN-SMN between the RW state and after 24 h of total SD. After acupuncture at HT7, the large-scale brain network results showed decreased between-network FC in DAN-VAN and increased between-network FC in SMN-VAN. Conclusion: Acupuncture could widely modulate extensive brain networks and reverse the specific between-network FC. The altered FC after acupuncture at HT7 may provide new evidence to interpret neuroimaging mechanisms of the acupuncture effect on acute SD.

Therapeutic Strategies for Resectable Stage-IIIA N2 Non-Small Cell Lung Cancer Patients: A Network Meta-Analysis.

Background: The National Comprehensive Cancer Network (NCCN) guidelines did not give an explicit comparison of the efficacy between surgery and radiotherapy in treating Stage-III N2 non-small cell lung cancer (NSCLC) patients, leaving a paucity for clinical reference. Through this study, we try to locate the optimum treatment strategy including surgical type for these patients. Methods: A systematic literature search was performed from PubMed, Cochrane Library, Embase, and Google Scholars. The endpoints were overall survival (OS), mean OS, and progression-free survival (PFS). The treatments comprised radiotherapy, lobectomy, and pneumonectomy. Network meta-analysis was carried out for calculating the odds ratio (OR) for binary variants. All the analyses implemented Stata 17.0 MP. Results: Eight clinical trials reporting 1756 patients met the inclusion criteria. Radiotherapy and surgery were equivalent in improving patients' OS (OR = 0.842, 95% confidence interval [CI]: [0.645, 1.099]). The mean OS of patients were similar in terms of radiotherapy, lobectomy, and pneumonectomy. Besides, radiotherapy and surgery had equivalent effects in improving PFS (OR = 0.896, 95% CI: [0.718, 1.117]). Conclusions: Since lobectomy and pneumonectomy following neoadjuvant treatments had equivalent efficacy in prolonging OS for patients with stage-IIIA N2 NSCLC compared with definitive radiotherapy, young patients with favorable performance status (0) should try surgery to pursue better prognosis while elderly patients with unfavorable PS or radiosensitive pathology types should accept definitive radiotherapy. More high-quality clinical trials are needed to support our findings.

Mangiferin, a natural glucoxilxanthone, inhibits mitochondrial dynamin-related protein 1 and relieves aberrant mitophagic proteins in mice model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease featured to mitochondrial dysfunction in neuronal cells. Dynamin-related protein 1 (Drp1) is an important regulator of mitochondrial fission and subsequent mitophagy. Mangiferin (MGF) is a glucosyl xanthone mainly derived from Mangifera indica L., possessing multifaceted properties, e.g., antioxidant, anti-inflammatory, and enhancement of cognitive ability. Besides, it can cross the blood-brain barrier, thereby exerting a neuroprotective effect. However, so far, MGF's effect in balancing mitochondrial homeostasis via regulation of Drp1 level and mitophagic pathway in PD remains rarely reported. PURPOSE: We aimed to investigate the neuroprotective effect of MGF against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and examine the possible mechanisms. METHODS: We utilized C57BL/6 mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Behavioral parameters, containing the open field test, balance beam, pole test, and rotarod test, assessed the locomotor activity; immunohistochemistry assessed the number of TH-positive neurons; transmission electron microscopy detected ultrastructural mitochondrial morphology in the dopaminergic neuron; complex I enzymatic activity microplate assay kit measured the mitochondrial complex I activity; ATP determination kit measured ATP levels in mitochondria isolated from cells or striatal tissues; western blot measured the levels of Drp1 and mitophagic proteins. RESULTS: We observed that MGF could mitigate motor deficiency and improve the expression of tyrosine hydroxylase in the substantia nigra of MPTP-induced PD mice. Furthermore, MGF not only ameliorated mitochondrial ultrastructure, but also improved mitochondrial ATP content. Within mitochondria, MGF could reduce Drp1 expression and reverse the expressions of mitophagic proteins, including PINK1, Parkin, NIX, BNIP3, FUNDC1, and p62. CONCLUSION: Present study indicates that MGF benefits mitochondrial networks by recovering mitochondrial ultrastructure and ATP contents, reducing mitochondrial Drp1, and modulating mitophagic proteins in the MPTP-induced PD mice model, which revealed a novel acting mechanism of MGF in PD's treatment.

Effects of Jie Yu Wan on Generalized Anxiety Disorder: A Randomized Clinical Trial.

Objective: To systematically assess the clinical efficacy of the Jie Yu Wan (JYW) formula in treating generalized anxiety disorder (GAD). Methods: A multicenter, prospective, double-blind, double-dummy, randomized controlled trial (RCT) was conducted at four hospitals in China. A total of one hundred thirty-three patients with GAD were enrolled from 2017 to 2019. This study aimed to evaluate the effects of a Traditional Chinese Medicine (TCM) JYW formula on GAD at eight weeks, with the use of Buspirone as the comparator. A stepwise dosing protocol was used (JYW: high dose 24 g/day, low dose 12 g/day; Buspirone: high dose 30 mg/day, low dose 15 mg/day) and the dose was adjusted depending on whether the treatment response of Hamilton Anxiety Scale (HAMA) score was less than or equal to 25% after one week. The primary outcome was a change in total score on the HAMA. The secondary outcomes included the Hamilton Depression Scale (HAMD), Clinical Global Impression (CGI) scale, and TCM Syndrome Scale. Adverse events were recorded using the Treatment Emergent Symptom Scale (TESS). Assessments were conducted at the baseline and 1, 2, 4, and 8 weeks. Results: A total of one hundred thirty-three participants were randomly assigned to the JYW group (n = 66) and the Buspirone group (n = 67). One hundred twenty-one patients (91%) completed at least one follow-up session. There were no significant differences between the two groups in terms of gender, age, disease course, HAMA, HAMD, CGI, and TCM Syndrome Scale scores at baseline (all P > 0.05). Repeated-measures analysis of variance revealed statistically significant time effects for the HAMA (P=0.002), HAMD (P = 0.018), and CGI (P=0.001) in both groups. Sensitivity analyses supported the credibility of the main results (P > 0.05). The group effect was not significant for the HAMA (P=0.43), HAMD (P=0.27), CGI (P=0.37), and TCM Syndrome Scale (P=0.86). Furthermore, there were no significant interaction effects between time and group in terms of the HAMA (P=0.47), HAMD (P=0.79), CGI (P=0.67), and TCM Syndrome Scale (P=0.69). After one week, 53 patients (80%) of the JYW group and 52 patients (78%) of the Buspirone group were adjusted to high doses. The interaction effect between time, group, and the dose was determined by repeated measures ANOVA test, and the HAMA score served as the outcome measure. The interaction effect between time and dose was statistically significant (P=0.04), which shows that high-dose JYW (24 g/day) was more effective in decreasing patients' HAMA scores than low-dose JYW (12 g/day), and Buspirone had the same effect, which means that high-dose Buspirone (30 mg/day) was more effective than low dose. (15 mg/day). Conclusions: The conclusion of this study supports that JYW and Buspirone can effectively alleviate the anxiety symptoms of GAD patients, which are both effective and safe for treatment of mild to moderate GAD. Besides, high-dose JYW or Buspirone are more effective than low-dose, which is of great importance in assisting clinical medication choice.

Canonical Chinese medicine formula Danzhi-Xiaoyao-San for treating depression: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Danzhi-Xiaoyao-San (DXS), as a canonical Chinese medicine formula, possessing the functions of the soothing liver, invigorating spleen, clearing heat, and cooling blood, has been widely used for the treatment of depression. AIM OF THE STUDY: This systematic review and meta-analysis of randomized controlled trials aimed to examine the efficacy of DXS in depression. MATERIALS AND METHODS: We performed a literature search in several databases, e.g., PUBMED, until August 2021 and conducted the meta-analysis using Review Manager 5.3 software. The random-effects model and fixed-effects model were used to synthetize extracted data. RESULTS: Finally, this meta-analysis showed that comparing with antidepressants, DXS exhibited similar effect to antidepressants in the clinical comprehensive effect [RR = 1.04, 95% CI (0.77, 1.40); P = 0.81] and decrease in Self-Rating Depression Scale scores [WMD = 0.89, 95% CI (-6.33, 8.11); P = 0.81], while lower effect in Hamilton Depression Scale scores [SMD = -0.29, 95% CI (-0.55, -0.03); P = 0.03]; Furthermore, DXS plus antidepressants can significantly improve the clinical comprehensive effect [RR = 1.23, 95% CI (1.17, 1.29); P < 0.00001] and decrease the Hamilton Depression Scale scores [SMD = 1.04, 95% CI (0.51, 1.58); P = 0.0001] than pure antidepressants. CONCLUSION: This systematic review and meta-analysis approved an efficient role of DXS in improving depression in clinical randomized controlled trials. However, further evidence from large samples and high-quality randomized controlled trials is needed to be investigated for a reliable conclusion about DXS in the treatment of depression.

Paeoniflorin: A neuroprotective monoterpenoid glycoside with promising anti-depressive properties.

BACKGROUND: Depression, as a prevalent and debilitating psychiatric disease, severely decreases the life quality of individuals and brings heavy burdens to the whole society. Currently, some antidepressants are applied in the treatment of severe depressive symptoms, while there are still some undesirable drawbacks. Paeoniflorin is a monoterpenoid glycoside that was firstly extracted from Paeonia lactiflora Pall, a traditional Chinese herb that is widely used in the Chinese herbal formulas for treating depression. PURPOSE: This review summarized the previous pre-clinical studies of paeoniflorin in treating depression and further discussed the potential anti-depressive mechanisms for that paeoniflorin to be further explored and utilized in the treatment of depression clinically. METHODS: Some electronic databases, e.g., PubMed and China National Knowledge Infrastructure, were searched from inception until April 2021. RESULTS: This review summarized the effective anti-depressive properties of paeoniflorin, which is related to its functions in the upregulation of the levels of monoaminergic neurotransmitters, inhibition of the hypothalamic-pituitary-adrenal axis hyperfunction, promotion of neuroprotection, promotion of hippocampus neurogenesis, and upregulation of brain-derived neurotrophic factor level, inhibition of inflammatory reaction, downregulation of nitric oxide level, etc. CONCLUSION: This review focused on the pre-clinical studies of paeoniflorin in depression and summarized the recent development of the anti-depressive mechanisms of paeoniflorin, which approves the role of paeoniflorin plays in anti-depression. However, more high-quality pre-clinical and clinical studies are expected to be conducted in the future.

Efficacy of Traditional Chinese Medicine Combined with Selective Serotonin Reuptake Inhibitors on the Treatment for Parkinson's Disease with Depression: A Systematic Review and Meta-Analysis.

Depression is a common neuropsychiatric symptom of Parkinson's disease (PD), resulting in a lower quality of life and cognitive impairment in PD patients. Traditional Chinese medicine (TCM) formulas have been widely used in neurodegenerative disease and neuropsychic disorders to improve life quality of patients in ethnomedicine. TCM formulas combined with selective serotonin reuptake inhibitors (SSRIs) also have a positive effect on depressed PD compared with SSRIs as reported by several clinical studies. However, the results are discordant and failed to be conclusive. We aim to evaluate the efficacy of TCM formulas combined with SSRIs for depressed PD in this systematic review. We searched literatures from PubMed, Web of Science, Medline, Embase, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang Database, and VIP Information Database before July 2020. We included randomized controlled trials investigating the efficacy of TCM formulas combined with SSRIs on depressed PD patients. This analysis was according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Eleven randomized clinical trials involving 861 subjects were enrolled in this analysis. The overall results showed that TCM formulas combined with SSRIs significantly improved the depression score [weighted mean difference (WMD): -4.920, 95% confidence interval (CI): (-5.999, -3.840); [Formula: see text]¡ 0.001] and had a statistical significance on Unified Parkinson's Disease Rating Scale II score [WMD: -1.209, 95% CI: (-1.561, -0.857); [Formula: see text] < 0.001]. Furthermore, we observed that Chai-Hu-Shu-Gan Powder combined with SSRIs had a significant improvement on the depressive symptom in PD compared to the SSRIs alone [WMD: -5.390, 95% CI: (-7.66, -3.11); [Formula: see text] < 0.001]. No severe side events were reported in these included trials. This systematic review provided the evidences that TCM formulas combined with SSRIs might be helpful and safe in the treatment of depression of PD, including Chai-Hu-Shu-Gan Powder. Also, more randomized double-blinded trials with reliable design are required in the future.