Effects of Banhabaekchulcheonma-Tang on Brain Injury and Cognitive Function Impairment Caused by Bilateral Common Carotid Artery Stenosis in a Mouse Model.

Vascular dementia (VD) is the second most prevalent dementia type, with no drugs approved for its treatment. Here, the effects of Banhabaekchulcheonma-Tang (BBCT) on ischemic brain injury and cognitive function impairment were investigated in a bilateral carotid artery stenosis (BCAS) mouse model. Mice were divided into sham-operated, BCAS control, L-BBCT (40 ml/kg), and H-BBCT (80 ml/kg) groups. BBCT's effects were characterized using the Y-maze test, novel object recognition test (NORT), immunofluorescence staining, RNA sequencing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses. The NORT revealed cognitive function improvement in the H-BBCT group, while the Y-maze test revealed no significant difference among the four groups. The CD68+ microglia and GFAP+ astrocyte numbers were reduced in the H-BBCT group. Furthermore, H-BBCT treatment restored the dysregulation of gene expression caused by BCAS. The major BBCT targets were predicted to be cell division cycle protein 20 (CDC20), Epidermal growth factor (EGF), and tumor necrosis factor receptor-associated factor 1 (TRAF1). BBCT regulates the neuroactive ligand-receptor interaction and neuropeptide signaling pathways, as predicted by KEGG and GO analyses, respectively. BBCT significantly improved cognitive impairment in a BCAS mouse model by inhibiting microglial and astrocyte activation and regulating the expression of CDC20, EGF, TRAF1, and key proteins in the neuroactive ligand-receptor interaction and neuropeptide signaling pathways.

Pharmacopuncture Effects on Insomnia Disorder: Protocol for a Multi-Site, Randomized, Acupuncture-Controlled, Clinical Trial.

Insomnia is a common health problem that can lead to various diseases and negatively impact quality of life. Pharmacopuncture is a new type of acupuncture that involves applying herbal medicine extracts to acupoints. Korean medicine doctors frequently use it to treat insomnia disorder. However, there is insufficient evidence to support the effectiveness and safety of pharmacopuncture for insomnia disorder. We designed a pragmatic randomized controlled trial to compare the effectiveness of pharmacopuncture and acupuncture for insomnia disorder. This multi-site, randomized, acupuncture-controlled trial will enroll 138 insomnia patients. The subjects will be randomly assigned to one of two groups, pharmacopuncture or acupuncture, at a 2:1 ratio. For 4 weeks, the participants will receive ten sessions of pharmacopuncture or acupuncture treatment and will be followed up for 4 weeks after the treatment ends. The Pittsburgh Sleep Quality Index score is the primary outcome measure. Insomnia severity index score, sleep parameters recorded using actigraphy and sleep diaries, physical symptoms associated with insomnia, emotions, quality of life, medical costs, and safety are the secondary outcome measures. The findings of this trial willprovide evidence that will be useful in clinical decision-making for insomnia treatment strategies.

Evaluation of the color stability of 3D printed resin according to the oxygen inhibition effect and temperature difference in the post-polymerization process.

The aim of this study was to determine the color stability of 3D printed resin according to the post-curing conditions (polymerization conditions and temperature). Specimens were post-polymerized under different conditions of oxygen inhibition, such as on glycerin immersion (GLY), medium-low vacuum environment (VA), and oxygen contact (CON, the control group), and temperature (35 °C, 60 °C, and 80 °C). The degree of conversion (DC), water sorption (Wsp) and solubility (Wsl), surface roughness (Ra) were measured. Additionally, surface free energy (SFE), pH values of colorants were measured. Grape juice (grape), coffee, and curry were used as the colorants, and distilled water (DW) was used as a control. And the color value was measured before and after immersion using a spectrophotometer. Then, Calculated the color change. For statistical methods, The Shapiro-Wilk test performed to check for normality revealed that the data presented a normal distribution (p>0.05). ΔE values were analyzed using three-way ANOVA. DC, Wsp, Wsl, SFE, and Ra were analyzed using two-way ANOVA. To confirm the linear correlation, Pearson's correlation coefficient was determined. The threshold for significance (p) was set at 0.05 (95% confidence interval) for all tests. DC was the highest at 80 °C in the GLY group (95.08 ± 4.88%). And Wsl decreased with increasing temperature, and was lowest at 80 °C in the GLY group (0.46 ± 0.30 um/mm3). After the colorants were immersed for 30 days, as the temperature increased, ΔE decreased in the GLY group but not in the VA and CON groups, and was the lowest at 80 °C in the GLY group: (DW, 0.95 ± 0.45 [mean± SD]; grape, 6.45± 0.69; coffee, 4.50± 0.56; curry, 9.37± 1.40). There was also a significant inverse relation between DC and ΔE. A significant inverse relation was found between Wsl and DC, and a significant positive correlation was found between Wsl and ΔE. Wsp, SFE, and Ra did not affect color stability. In the post-polymerization process, increasing the temperature and GLY were effective in reducing ΔE, which was lowest at 80 °C in the GLY group. It was also observed that a complex mechanism between the DC, Wsl of 3D printed resin affects ΔE of the resin.

The Cost-Effectiveness Analysis of Gamiguibi-Tang versus Hwangryunhaedok-Tang for Patients with Insomnia Disorder Based on a Randomized Controlled Trial.

(1) Insomnia is associated with poor quality of life and loss of productivity, and is a significant economic burden on society. Gamiguibi-tang (GGBT) is the most frequently prescribed herbal medicine for insomnia treatment. Hwangryunhaedok-tang (HHT) is used as an insured herbal medicine for insomnia in the Korean National Health Insurance (NHI) system. This study aims to evaluate the cost-effectiveness of GGBT versus HHT in patients with insomnia disorders based on clinical trial data; (2) Methods: The EuroQol five-dimension scale (EQ-5D) was used to estimate quality-adjusted life-years (QALY). Direct and non-direct medical costs and lost productivity costs were estimated. The cost-effectiveness of GGBT was compared with HHT treatments over six weeks from a societal perspective; (3) Results: A total of 81 patients who underwent GGBT (n = 56) and HHT (n = 25) treatment completed the clinical trial. The EQ-5D score improved significantly more in the GGBT than in the HHT group (0.02 vs. −0.03, p < 0.05). The QALYs for six weeks were slightly greater in GGBT (0.0997) than in the HHT group (0.0987); however, the total costs incurred were approximately 9% less in GGBT ($934) than in the HHT group ($1029). GGBT was found to be a more economically dominant treatment option compared to HHT for treating insomnia; (4) Conclusions: Among herbal medicines, GGBT may be a cost-effective option for treating insomnia from a societal perspective in Korea.

Traditional East Asian Herbal Medicine for Post-Stroke Insomnia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Post-stroke insomnia (PSI) is a highly prevalent complication after stroke. Current evidence of psychotropic drug use for PSI management is scarce and indicates harmful adverse events (AEs). Traditional East Asian herbal medicine is a widely used traditional remedy for insomnia. However, so far, no study has systematically reviewed the efficacy and safety of traditional east asian herbal medicine (HM) for PSI. Therefore, we perform meta-analysis to evaluate the effectiveness and safety of HM for PSI. After a comprehensive electronic search of 15 databases, we review the randomized controlled trials (RCTs) of HM use as monotherapy for PSI. Our outcomes were the Pittsburgh sleep quality index and total effective rate. In total, 24 RCTs were conducted with 1942 participants. HM showed statistically significant benefits in sleep quality. It also appeared to be safer than psychotropic drugs in terms of AEs, except when the treatment period was two weeks. The methods used for RCTs were poor, and the quality of evidence assessed was graded "low" or "moderate." The findings of this review indicate that the use of HM as a monotherapy may have potential benefits in PSI treatment when administered as an alternative to conventional medications. However, considering the methodological quality of the included RCTs, we were uncertain of the clinical evidence. Further, well-designed RCTs are required to confirm these findings.

Herbal medicine for post-stroke insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke insomnia (PSI) is a highly prevalent complication in patients with stroke. However, there has been no comprehensive systematic review assessing the efficacy and safety of herbal medicine (HM) on PSI. This protocol was developed to conduct a systematic review and meta-analysis to evaluate the evidence related to the efficacy and safety of HM on PSI. METHODS: We will perform a comprehensive electronic search, including Medline, EMBASE, CENTRAL, AMED, CINAHL, PsycARTICLES, and Chinese, Korean, and Japanese databases from their inception to November 2020. This systemic review will include only randomized controlled clinical trials of HM on PSI. The main outcome is the Pittsburgh Sleep Quality Index score. Two researchers will independently screen citations and abstracts, identify full-text articles for inclusion, extract data, and appraise the quality and risk of bias of included studies. A meta-analysis will be conducted using Review Manager 5.4. The evidence quality of each outcome will be appraised according to Grades of Recommendation, Assessment, Development, and Evaluation. RESULTS: This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-P (PRISMA-P) guidelines to ensure clarity and completeness of reporting in all phases of the systematic review. CONCLUSION: This study will provide evidence regarding the efficacy and safety of HM for the treatment of PSI. ETHICS AND DISSEMINATION: No ethical approval will be needed because data from previously published studies in which informed consent was obtained by primary investigators will be retrieved and analyzed. We will publish this systematic review in a peer-reviewed journal. OSF REGISTRATION DOI: 10.17605/OSF.IO/PEHQZ.

Corrigendum to "Acupuncture using pattern-identification for the treatment of insomnia disorder: a systematic review and meta-analysis of randomized controlled trials" [Integr Med Res 8 (2019) 216-226].

[This corrects the article DOI: 10.1016/j.imr.2019.08.002.].

Electroacupuncture for treatment-resistant insomnia: study protocol for a randomised, controlled, assessor-blinded, pilot clinical trial.

INTRODUCTION: A considerable number of insomnia patients experience sleep disturbance even with long-term use of hypnotic medication. Previous studies have indicated that electroacupuncture (EA) could be an efficacious treatment for managing insomnia. However, few trials have been conducted to evaluate the effectiveness and safety of EA for treatment-resistant insomnia. This pilot study aims to explore the feasibility and preliminary effectiveness and safety of EA as an adjunct treatment for treatment-resistant insomnia. METHODS AND ANALYSIS: This is a multicentre, randomised, usual care controlled and assessor-blinded pilot study protocol. Fifty patients presenting with sleep problems who have been taking hypnotic medication for more than 3 months will be randomly allocated to either an EA group or a usual care group at a 1:1 ratio. The EA group will undergo 12 EA treatment sessions twice a week for 6 weeks whereas the usual care group will not receive EA treatment. All the participants will receive a brochure containing educational information on sleep hygiene. The primary outcome will be the measured mean change of the total score of the Insomnia Severity Index from the baseline to week 7. The secondary outcome regarding sleep quality will be measured using the Pittsburgh Sleep Quality Index, a sleep diary and actigraphy. Moreover, we will assess the quality of life, the direct and indirect cost of treating insomnia for economic evaluation. After 4 weeks, the subjects will visit the research sites for a follow-up assessment. ETHICS AND DISSEMINATION: Ethical approval of this study protocol was established by the institutional review boards of the each involved study site. All potential subjects will be provided written informed consent. The results of this study will be accessible in peer-reviewed publications and be presented at academic conference. TRIAL REGISTRATION NUMBER: KCT0003235.

Effective reconstruction of functional organotypic kidney spheroid for in vitro nephrotoxicity studies.

Stable and reproducible kidney cellular models could accelerate our understanding of diseases, help therapeutics development, and improve nephrotoxicity screenings. Generation of a reproducible in vitro kidney models has been challenging owing to the cellular heterogeneity and structural complexity of the kidney. We generated mixed immortalized cell lines that stably maintained their characteristic expression of renal epithelial progenitor markers for the different lineages of kidney cellular compartments via the BMP7 signaling pathway from a mouse and a human whole kidney. These cells were used to generate functional and matured kidney spheroids containing multiple renal lineages, such as the proximal tubule, loop of Henle, distal tubules, and podocytes, using extracellular matrix and physiological force, named spheroid-forming unit (SFU). They expressed all apical and basolateral transporters that are important for drug metabolism and displayed key functional aspects of the proximal tubule, including protein endocytosis and increased gamma-glutamyltransferase activity, and cyclic AMP responded to external cues, such as parathyroid hormone. Following exposure, cells fluxed and took up drugs via proximal tubule-specific apical or basolateral transporters, and displayed increased cell death and expression of renal injury marker. Here, we developed a new differentiation method to generate kidney spheroids that structurally recapitulate important features of the kidney effectively and reproducibly using mixed immortalized renal cells, and showed their application for renal toxicity studies.

Acupuncture using pattern-identification for the treatment of insomnia disorder: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Insomnia symptoms are common, affecting almost 30% of the population of the population. Many use medications that may be ineffective and cause substantial harm. In complementary and alternative medicine, acupuncture is widely used to manage mental health problems. Acupuncture therapy emphasizes individualized treatment according to TCM pattern diagnosis. Although there are some systematic reviews that acupuncture has the benefit for insomnia, there is no systematic review on acupuncture using pattern identification. This review aimed for evaluating acupuncture efficacy using pattern-identification to treat insomnia. METHODS: We carried out a comprehensive review of randomized controlled trials (from 2000 to April 12, 2018), using PubMed, Cochrane CENTRAL, EMBASE, CINAHL, PsycINFO, CNKI, and 3 Korean (OASIS, NDSL, RISS4U) databases, comparing acupuncture using pattern identification (only) with medication in primary insomnia. Response rate and the Pittsburgh Sleep Quality Index (PSQI) were the primary outcomes. Risk of bias and publication biases were evaluated, and meta-analyses were conducted. RESULTS: Nineteen RCTs were included (11 manual acupuncture (1079 patients), 8 electro-acupuncture (442 patients)) of low quality. Meta-analyses of all studies reveled that acupuncture improved total effectiveness rate (Risk Ratio [RR] = 1.23, 95% confidence intervals [CIs]: 1.12-1.35, p < 0.00001; I2 = 80%) and PSQI (MD = -1.92, 95% CI: -2.41-1.42, p < 0.00001; I2 = 30%) compared to medication. Results of overall risk of bias assessments were unclear or high. CONCLUSIONS: Acupuncture using pattern identification led to significantly improved total effectiveness rate compared to medication. With regard to PSQI, as compared to the control group, acupuncture using pattern identification was similar to medication. However, this study has limitations of high risk of bias, not using a standardized pattern-diagnosis-treatment and not comparing with standarized acupuncture without pattern identification.

The Pilot Survey of the Perception on the Practice Pattern, Diagnosis, and Treatment on Korean Medicine Insomnia: Focusing on the Difference between Korean Medical Neuropsychiatry Specialists and Korean Medical General Practitioners.

INTRODUCTION: This study aims to investigate the clinical practice states on the diagnosis and treatment for insomnia between Korean medical general practitioners (KMGPs) and Korean medical neuropsychiatry specialists (KMNPSs). METHODS: We distributed questionnaires via email or in person to 1,017 KMGPs and via email to 165 KMNPSs. We collected and analyzed responses from 305 (30.00%) KMGPs and 53 (32.12%) KMNPSs. RESULTS: Most KMGPs and KMNPSs responded that the number of new patients visiting the clinic for treatment of insomnia was less than 10 per month (78.2%). Frequently utilized therapies for insomnia are acupuncture and herbal decoctions. Particularly acupoint GV20 and Guipi decoction were chosen with the highest response rate. There was no difference between KMNPSs and KMGPs in the traditional Korean medical diagnosis methods. However, KMNPSs utilized more various methods to diagnose, treat, and evaluate insomnia and educated more actively sleep hygiene compared to KMGPs. CONCLUSIONS: This survey showed how insomnia is currently diagnosed and treated in Korean medical care settings. Moreover, we identified some differences between KMNPSs and KMGPs. Further research is required to explore the underlying reasons for these discrepancies among KMDs and to improve the quality of Korean medical clinical practice in treating insomnia.

Current utilization and influencing factors of complementary and alternative medicine among children with neuropsychiatric disease: a cross-sectional survey in Korea.

BACKGROUND: Complementary and alternative medicine (CAM) is widespread but has various utilization rates according to country and the condition of patients. Generally, CAM is more frequently used in diseases that have no clear treatment method in conventional medicine. Therefore, a high utilization rate of CAM can be assumed in pediatric neurological diseases, but few studies have investigated the utilization of CAM in children with neuropsychiatric diseases. In particular, studies regarding the current use of CAM are scarce. METHODS: We conducted a survey of the parents or caregivers of patients who visited the pediatric rehabilitation clinic, pediatric neurology clinic, or pediatric psychiatry clinic at one university hospital from April to July 2011. We analyzed the factors that affect the utilization of CAM and other rehabilitation therapies. RESULTS: Among the 578 patients recruited, 258 patients have ever received CAM (51.5%), and the current CAM utilization rate was 19.0% (110 patients). Two hundred patients (34.6%) were currently receiving only other rehabilitation therapies, and 268 patients (46.4%) were currently receiving no type of therapy. The rate of current CAM usage was significantly high in epilepsy patients. The ORs of 1-6-year-old and 7-12-year-old children compared with 13-19-year-old children were 3.14 (95 % CI 1.31-7.53) and 3.34 (95% CI 1.64-6.79), respectively, and the OR of the group with longer disease duration (≥48 months) compared with the group with shorter disease duration was 3.36 (95% CI 1.71-6.59). Only the age and disease duration showed statistically significant differences between the patients who were administered CAM and those who received other rehabilitation therapies (p < 0.0001). CONCLUSIONS: CAM is preferred by patients under 13 years of age compared with patients aged 13-19 years, whereas other rehabilitation therapies are preferred by patients aged 1-6 years, followed by those aged 6-12 years and then by those aged 13-19 years. The patient's age and disease duration are the major factors influencing CAM use. Future studies should specify particular diseases, rather than combining all types of neuropsychiatric diseases, and include the socio-economic status of the parents.

Effects of Medicinal Herb Extracts on In vitro Ruminal Methanogenesis, Microbe Diversity and Fermentation System.

This study was aimed to evaluate the in vitro effects of medicinal herb extracts (MHEs) on ruminal fermentation characteristics and the inhibition of protozoa to reduce methane production in the rumen. A fistulated Hanwoo was used as a donor of rumen fluid. The MHEs (T1, Veratrum patulum; T2, Iris ensata var. spontanea; T3, Arisaema ringens; T4, Carduus crispus; T5, Pueraria thunbergiana) were added to the in vitro fermentation bottles containing the rumen fluid and medium. Total volatile fatty acid (tVFA), total gas production, gas profiles, and the ruminal microbe communities were measured. The tVFA concentration was increased or decreased as compared to the control, and there was a significant (p<0.05) difference after 24 h incubation. pH and ruminal disappearance of dry matter did not show significant difference. As the in vitro ruminal fermentation progressed, total gas production in added MHEs was increased, while the methane production was decreased compared to the control. In particular, Arisaema ringens extract led to decrease methane production by more than 43%. In addition, the result of real-time polymerase chain reaction indicted that the protozoa population in all added MHEs decreased more than that of the control. In conclusion, the results of this study indicated that MHEs could have properties that decrease ruminal methanogenesis by inhibiting protozoa species and might be promising feed additives for ruminants.

The past, present, and future of traditional medicine education in Korea.

Korea has kept the heritage of Korean traditional medicine (KM) during the 19th century harsh modernization, and has established a medical system in parallel with Western medicine. The purpose of this study was to review systematically the history and current system for educating highly qualified traditional medical doctors in Korea. KM produces 750 certified medical doctors every year with a 4-7-year curriculum in 12 universities and their affiliated hospitals. There are 22,074 clinicians along with 2474 clinical specialists in eight departments as of 2014. A national licensing examination and continuing medical education for KM are used for maintaining qualifications of KM doctors, and independent organizations are established for the evaluation of educational institutes. KM has thrived to establish an independent and competitive educational system for KM doctors, equivalent to Western medicine, and has regained a pivotal role for public health in Korea. This study would be useful for cultivating traditional medicine and establishing its educational system in the world.

Acupuncture for posttraumatic stress disorder: a systematic review of randomized controlled trials and prospective clinical trials.

To evaluate the current evidence for effectiveness of acupuncture for posttraumatic stress disorder (PTSD) in the form of a systematic review, a systematic literature search was conducted in 23 electronic databases. Grey literature was also searched. The key search terms were "acupuncture" and "PTSD." No language restrictions were imposed. We included all randomized or prospective clinical trials that evaluated acupuncture and its variants against a waitlist, sham acupuncture, conventional therapy control for PTSD, or without control. Four randomized controlled trials (RCTs) and 2 uncontrolled clinical trials (UCTs) out of 136 articles in total were systematically reviewed. One high-quality RCT reported that acupuncture was superior to waitlist control and therapeutic effects of acupuncture and cognitive-behavioral therapy (CBT) were similar based on the effect sizes. One RCT showed no statistical difference between acupuncture and selective serotonin reuptake inhibitors (SSRIs). One RCT reported a favorable effect of acupoint stimulation plus CBT against CBT alone. A meta-analysis of acupuncture plus moxibustion versus SSRI favored acupuncture plus moxibustion in three outcomes. This systematic review and meta-analysis suggest that the evidence of effectiveness of acupuncture for PTSD is encouraging but not cogent. Further qualified trials are needed to confirm whether acupuncture is effective for PTSD.

Neuroprotective Activity of Sibjeondaebo-tang on Aß Peptide-Induced Damages.

Background. Sibjeondaebo-tang (SJDBT) has been used to treat diverse disorders including neuropsychiatric disabilities in traditional Korean medicine. Objective. The present study aims to investigate the potential effects of SJDBT on neuroprotection against Aß peptide-induced damage using in vitro culture and in vivo rat brain systems. Materials and Methods. PC12 cell viability was analyzed by MTT assay, and neurite arborizations and caspase 3 protein signals in cultured PC12 cells and in vivo cortical neurons were analyzed by immunofluorescence staining. Phospho-Erk1/2 protein was analyzed by immunofluorescence staining and western blot analysis. Results. In PC12 cells, atrophied cell body and reduced neurite extension by Aß treatment were recovered by SJDBT treatment. Caspase 3 protein signals were increased in Aß-treated PC12 cells, but SJDBT treatment decreased apoptotic cell death. Caspase 3 activation in cortical neurons, which was induced similarly by Aß treatment, was reduced by SJDBT treatment. Furthermore, phospho-Erk1/2 protein levels, which had been decreased by Aß treatment, were elevated in the cortical neurons by SJDBT treatment. Conclusion. These data show that SJDBT may play a role in protecting from damages induced by Aß in neuronal tissue and further suggest that SJDBT can be explored as the potential therapeutic target for AD treatments in human.