Effectiveness and Safety of Fufang Danshen Dripping Pill (Cardiotonic Pill) on Blood Viscosity and Hemorheological Factors for Cardiovascular Event Prevention in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis.

Background and Objectives: Diabetes can cause various vascular complications. The Compounded Danshen-Dripping-Pill (CDDP) is widely used in China. This study aimed to analyze the effectiveness and safety of CDDP in the blood viscosity (BV) with type 2 diabetes mellitus (T2DM). Materials and Methods: We conducted a systematic search of seven databases from their inception to July 2022 for randomized controlled trials that used CDDP to treat T2DM. To evaluate BV, we measured low shear rate (LSR), high shear rate (HSR), and plasma viscosity (PV). Homocysteine and adiponectin levels were also assessed as factors that could affect BV. Results: We included 18 studies and 1532 patients with T2DM. Meta-analysis revealed that CDDP significantly reduced LSR (mean difference [MD] -2.74, 95% confidence interval [CI] -3.77 to -1.72), HSR (MD -0.86, 95% CI -1.08 to -0.63), and PV (MD -0.37, 95% CI -0.54 to -0.19) compared to controls. CDDP also reduced homocysteine (MD -8.32, 95% CI -9.05 to -7.58), and increased plasma adiponectin (MD 2.72, 95% CI 2.13 to 3.32). Adverse events were reported less frequently in the treatment groups than in controls. Conclusions: CDDP is effective in reducing BV on T2DM. However, due to the poor design and quality of the included studies, high-quality, well-designed studies are required in the future.

Two case reports of tapering sedative-hypnotic drugs through classical conditioning using herbal medicine (CARE-compliant).

RATIONALE: Sedative-hypnotic drugs (SHDs) used for insomnia are recommended for short-term use owing to concerns regarding abuse and dependence. Nevertheless, drug discontinuation is challenging owing to rebound insomnia that occurs when the SHD is ceased. Therefore, a strategy is required to reduce or discontinue SHDs, while minimizing rebound insomnia. PATIENT CONCERNS: The present report discusses the cases of a 72-year-old man and 27-year-old man with insomnia. Both patients had been taking SHDs for more than 2 months. DIAGNOSES: Both patients were diagnosed with primary insomnia. INTERVENTIONS AND OUTCOMES: After 2 weeks of classical conditioning (CC) using Hwangryunhaedok-tang (HHT), both patients succeeded in tapering SHD; the Korean version of the insomnia severity index of patient 1 dropped from 14 to 5, and that of patient 2 dropped from 28 to 11. In the final follow-up, the index dropped to 2 and 3, respectively. LESSONS: The CC, a concept emerging in psychology, could be a new strategy for tapering drugs. In this case, SHDs, which had been taken for a long time, were successfully reduced or discontinued through CC using HHT. Herbal medicine such as HHT is selected as a neutral stimulus for CC because the risk of rebound phenomenon is low as the compounds of herbal medicine have high structural similarities with human metabolites. Both patients in this study reported no particular challenges when HHT was discontinued. However, further studies are needed that will assist in tapering anticonvulsants or steroids as well as SHDs.

Effect of herbal medicine (Jodeungsan) on migraine: A double-blind randomized clinical trial.

Background: Migraine is a relatively common disease that has a significant effect on the daily activities of affected individuals. The purpose of this study was to explore the effects of herbal medicine (Jodeungsan, JDS) on migraine. Methods: Sixty-four patients with migraine were recruited and randomized to either the JDS or placebo group at a 1:1 ratio. The subjects received JDS or placebo daily for four weeks. The primary outcome was a change in the number of headache attack days (HADs), and the secondary outcome measures were the headache impact test (HIT), migraine-specific quality of life (MSQoL), the deficiency and excess pattern identification questionnaire (DEPIQ), the cold and heat pattern identification questionnaire (CHPIQ), and the blood stasis pattern questionnaire (BSPQ). Results: In all, 61 of the 64 patients took the investigational drugs for four weeks. The number of HADs did not significantly differ between the JDS and placebo groups at the end of the study. However, the HIT and MSQoL results showed significant improvement over the baseline in both groups. Conclusion: JDS did not have a significant effect on chronic migraine. Larger studies are needed to confirm this result. Trial registration: Clinical Research Information Service (https://cris.nih.go.kr/): KCT0003121.

Comparison of Metabolites and Gut Microbes between Patients with Ulcerative Colitis and Healthy Individuals for an Integrative Medicine Approach to Ulcerative Colitis-A Pilot Observational Clinical Study (STROBE Compliant).

Ulcerative colitis (UC) is an intractable disease associated with high morbidity and healthcare costs. Metabolites and gut microbes are areas of interest for mainstream and complementary and alternative medicine. We, therefore, aimed to contribute to the discovery of an integrative medicine for UC by comparing and analyzing gut microbes and metabolites in patients with UC and in healthy individuals. This was an observational case-control study. Blood and stool samples were collected from the participants, and metabolite and gut microbial studies were performed. Among metabolites, formate, glycolate, trimethylamine, valine, and pyruvate levels were significantly different between the two groups. Among gut microbes, the abundance of Bacteroidetes at the phylum level; Bacteroidia at the class level; Bacteroidales and Actinomycetales at the order level; Prevotellaceae, Acidaminococcaceae, and Leptotrichiaceae at the family level; and Prevotella, Roseburia, Paraprevotella, Phascolarctobacterium, Ruminococcus, Coprococcus, Clostridium_XIVB, Atopobium, and Leptotrichia at the genus level was also significantly different. Most of the metabolites and gut microbes significantly different between the two groups were involved in energy metabolism and inflammatory processes, respectively. The results of this study could be helpful for the identification of targets for integrative medicine approaches for UC.

Cupping Therapy for Migraine: A PRISMA-Compliant Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Migraine is a common reason for primary headache disorders. Cupping is a frequently used traditional intervention for controlling pain including migraine. There have been no systematic reviews on the clinical effects of cupping on migraine. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effectiveness of cupping therapy for migraine. The search strategy was built for the presence of related keywords, such as "migraine" and "cupping therapy", in the title and abstract of research articles indexed in the MEDLINE, EMBASE, CENTRAL, and other databases. The randomized controlled trials (RCTs) of cupping therapy for migraine were searched and selected from inception to May 2019. We searched eight databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials. The selection process and the quality assessment were performed by 2 authors independently. The meta-analysis was conducted and qualitative analysis was also performed. RESULTS: 218 studies were identified, and 6 RCTs were enrolled in this review. In comparison to drugs, wet cupping showed a higher total effective rate (TER). In the dry cupping plus acupuncture, the result of TER showed more effectiveness (RR 1.05, 95% CI 0.99 to 1.12, P=0.13) compared with acupuncture alone, but there was no statistically significant difference. In qualitative analysis, the results showed wet cupping plus drugs treatment could quickly relieve pain and significantly improve patients' quality of life and wet cupping could reduce headache pain. CONCLUSION: Cupping therapy could be effective for the treatment of migraine. However, the qualities of the evidence were low, so well-designed RCTs are needed to confirm the effectiveness of cupping. Systematic review registration: PROSPERO registration number is CRD42017054979.

Effect of Heat-killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome.

Non-viable bacteria, referred to as "paraprobiotics," have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.

Effect of a Synbiotic Containing Lactobacillus paracasei and Opuntia humifusa on a Murine Model of Irritable Bowel Syndrome.

The administration of a combination of probiotics and prebiotics is expected to be a promising strategy for improving irritable bowel syndrome (IBS) symptoms. This study aimed to investigate the efficacy of a synbiotic containing Lactobacillus paracasei and Opuntia humifusa extract for symptomatic improvement of IBS in a murine model and to evaluate the mechanism underlying the beneficial effects of this synbiotic. A total of 20 male Wistar rats aged 8 weeks with IBS induced by restraint stress were assigned into four groups and administered L. paracasei as a probiotic and O. humifusa extract as a prebiotic for 4 weeks. The primary outcome was stool consistency at week 4. To evaluate the mechanism underlying the beneficial effects of the synbiotic, fecal microbial analysis was conducted, and the serum corticosterone levels, tumor necrosis factor-α (TNF-α) levels in the colon tissue, and expression of tight junction proteins were investigated. All three treatment groups showed significantly lower scores for stool consistency than the control group at week 4 (all p < 0.001). When compared with the control group, the synbiotic groups showed a significantly greater abundance of L. paracasei in fecal microbial analysis, lower serum corticosterone levels, lower TNF-α levels in the colon tissue, and higher expression of tight junction proteins. This novel synbiotic containing L. paracasei and O. humifusa extract can improve the stool consistency in a murine model of IBS. It may be a promising treatment option for IBS, and human studies are warranted.

Development of Integrative Medicine Therapy for Gastrointestinal Autoimmune Diseases: A study protocol for a registry study.

BACKGROUND: Although the incidence of AD, including gastrointestinal AD, increases every year, there is no effective therapy for it yet. This causes high medical costs to be spent on the management of autoimmune patients every year. The aim of this study is to identify the characteristics related to the causes and symptoms of gastrointestinal autoimmune disease (AD) by collecting patients' information and to further contribute to the development of an integrative medicine therapy for gastrointestinal AD. METHODS/DESIGN: This study is a registry study of patients diagnosed with gastrointestinal AD. Subjects who voluntarily sign a written consent form after receiving a sufficient explanation will be assessed for compliance with the inclusion and exclusion criteria through a screening process on their first visit. A total of 35 subjects will be recruited; 15 will be assigned to the patient group, 10 to the control group, 8 to the caregiver group, and 2 to the medical staff group. The clinical information of the subjects will be evaluated through statistical analyses. As this study is a registry study, it will not test specific hypotheses. DISCUSSION: If this study identifies the significant characteristics of gastrointestinal AD patients, the results will be useful for the development of integrative medicine methods for the treatment of gastrointestinal AD. STUDY REGISTRATION: This study was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0003976, date of registration: May 23, 2019).

Difference in gait recovery rate of hemiparetic stroke patients according to paralyzed side: A cross-sectional study based on a retrospective chart review.

In Donguibogam, a representative encyclopedic source of knowledge on traditional Korean medicine, left-sided hemiparesis due to stroke is called "Tan" as a sort of "Heyol-Byeong," while right-sided hemiparesis due to stroke is called "Tan" as a sort of "Gi-Byeong." According to the theory of Donguibogam, diseases on the left or right side of the human body must be treated differently. Clinically, the symptoms caused by left and right hemisphere lesions in stroke patients differ, as the functions of the left and right hemispheres differ. Considering these facts, when treating patients in clinical practice, it may be useful to distinguish between diseases on the left or right side according to Donguibogam. This study set out to confirm whether side-dependent gait rehabilitation could be used to treat hemiparetic stroke patients. Gait was selected for analysis, as it is the most important factor in returning stroke patients to daily life.This study conducted a retrospective chart review of stroke patients who satisfied the following criteria: outpatient or inpatient at the Wonkwang University Korean Medicine Hospital in Gwangju (WKUGH) with hemiparesis due to stroke; aged between 19 and 85 years old; with a stroke onset within the past 6 months; having undergone gait analysis (GAITRite) more than twice between September 1, 2017 and June 30, 2018 at the WKUGH, with a minimum 2-week interval between the first and next gait analysis; right-handed stroke patient; able to walk unaided. The spatio-temporal parameters for analysis included the FAP, walking velocity, step length, stance time, and swing time as obtained with GAITRite.In the initial gait analysis, there was no significant difference between the 2 groups in all spatio-temporal parameters. However, in the follow-up gait analysis, the left hemiparesis group showed a significantly higher FAP and faster walking velocity than the right hemiparesis group.This study found a difference in the recovery rate between the left and right hemiparesis groups. Based on this, we suggest that a different treatment strategy for gait rehabilitation can be used according to the paralyzed side.This study was approved by the Institutional Review Board (IRB) of the Wonkwang University Korean Medicine Hospital in Gwangju (WKUGH), Republic of Korea (WKIRB 2018 - 25, November 28, 2018). This trial was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0002984).

Repurposing of ginseng extract as topoisomerase I inhibitor based on the comparative analysis of gene expression patterns.

Repositioning of plant extracts and chemical drugs can accelerate drug development. However, its success rate may depend on what the clue is for the repositioning. Recently, repositioning based on correction of unwarranted gene expression pattern has suggested the possibility of new drug development. Here, we designed a similar method for the repositioning of nutraceutical ginseng (Panax ginseng C.A.Mey.), which is one of the most validated natural therapeutic products for various diseases. We analyzed ginseng-induced gene expression profiles using the connectivity map algorithm, which is a database that connects diseases, chemical drugs, and gene expression. Ginseng was predicted to show the same effects as those of topoisomerase I inhibitors. In a subsequent in vitro assay, ginseng extract unwound coiled or supercoiled DNA, an effect comparable to that of the topoisomerase I inhibitor, camptothecin. Furthermore, ginseng extract induced synthetic lethality with suppression of the Werner syndrome gene. The collected data implicate ginseng as a candidate antitumor agent owing to its topoisomerase I inhibitory activity and further validate the usefulness of differentially expressed gene similarity-based repurposing of other natural products.

Comparison of recovery patterns of gait patterns according to the paralyzed side in Korean stroke patients: Protocol for a retrospective chart review.

INTRODUCTION: In Traditional Korean Medicine (TKM), diseases on the left or right side of the human body have been treated differently according to the theory of Donguibogam, which is an encyclopedic source for TKM. In the Wind chapter of Donguibogam, left hemiparesis due to stroke is called Tan, a sort of Hyeol-Byeong, and right hemiparesis due to stroke is called Tan, a sort of Gi-Byeong. As neuroscience develops, it has been shown that the functions of the left and right hemispheres differ, as do the symptoms caused by differently located lesions in the brain. In light of these recent findings and the theory of Donguibogam, it may be useful when treating patients in clinical practice to consider the side of the human body on which symptoms appear. The aim here is to establish whether side-dependent treatments are more effective in treating patients with symptoms on different sides of the body. Specifically, this exploratory study investigates changes in gait pattern among stroke patients with hemiparesis or hemiplegia during gait recovery. METHODS: To develop this protocol, a retrospective review of charts will be used to assess differences in gait recovery patterns among stroke patients with left or right hemiparesis, using gait analysis systems that include GAITRite, G-walk, and Treadmill. The data will be selected from gait analysis performed more than twice in the period from September 1, 2017 to June 31, 2018 at Wonkwang University Gwangju Hospital (WKUGH). RESULTS: The primary outcomes include spatiotemporal parameters obtained using GAITRite (FAP, velocity, step length, swing time, and stance time); symmetric parameters obtained using G-walk (tilt, obliquity, and pelvis rotation symmetry); and center of pressure (COP) area and velocity as measured by Treadmill. DISCUSSION: This will be the first study to analyze the gait recovery pattern of stroke patients according to the paralyzed side by comparing spatiotemporal, symmetric, and COP parameters using gait analysis systems. Like all retrospective studies, the present research was subject to certain limitations related to bias (selection bias, recall bias, misclassification bias, confounding value bias), difficulty in assessing temporal relationships, and small sample size. However, these limitations were of less significance here because gait parameters and body side of symptoms of hemiplegia or hemiparesis are relatively clear. CONCLUSION: If the use of gait analysis systems (GAITRite, G-walk, and Treadmill) confirms differences in gait recovery pattern among stroke patients according to the paralyzed side, the findings will provide essential evidence for differential treatment of stroke patients on that basis.

Banhabaekchulchunma-tang and chongsanggeontong-tang (herbal medicine) effect on migraine: A protocol for a systematic review of controlled trials.

BACKGROUND: Migraine is a common disease of primary headache, which it causes many kinds of secondary diseases or symptoms. The treatment drugs have sometimes shown side effects such as overuse headache, stroke, and cardiovascular disease. Therefore, the demand for complementary and alternative interventions for migraine has increased. Herbal medicines are a representative intervention to treat migraine traditionally. Among these herbal medicines, Banhabaekchulchunma-tang (BBT) and Chongsanggeontong-tang (CGT) have been most commonly used for migraine treatment in traditional clinical practice. However, to our knowledge, there has been no systematic review considering the efficacy and safety of BBT or CGT on migraine. This protocol aims to perform a systematic review for assessing the effectiveness and safety of BBT or CGT on Migraine. METHODS: This protocol was developed according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) and registered on the international prospective register of systematic reviews (PROSPERO). The randomized controlled clinical trials of BBT or CGT for migraine treatment will be searched in following 8 databases from their inception to December 2016: Medline, EMBASE, the Cochrane Central Register of Controlled Trials, OASIS, the Korean Traditional Knowledge Portal, the Korean Medical Database, DBPIA, and the China National Knowledge Infrastructure. Study selection, data extraction, assessment with risk of bias, and data analysis will be performed in order. In this study, headache pain intensity and the total treatment effective rate will be evaluated as primary outcomes. RESULTS AND CONCLUSION: we propose the current protocol to evaluate the effectiveness and safety of BBT or CGT for migraine systematically. ETHICS AND DISSEMINATION: This systematic review will not need ethical approval, because it does not involve human beings. We will publish this systematic review electronically in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018076171 for BBT and CRD42018085130 for CGT.

Heat-killed Lactobacillus casei confers broad protection against influenza A virus primary infection and develops heterosubtypic immunity against future secondary infection.

Lactic acid bacteria (LAB) are the common probiotics. Here, we investigated the antiviral protective effects of heat-killed LAB strain Lactobacillus casei DK128 (DK128) on influenza viruses. Intranasal treatment of mice with DK128 conferred protection against different subtypes of influenza viruses by lessening weight loss and lowering viral loads. Protection via heat-killed DK128 was correlated with an increase in alveolar macrophage cells in the lungs and airways, early induction of virus specific antibodies, reduced levels of pro-inflammatory cytokines and innate immune cells. Importantly, the mice that were protected against primary viral infection as a result of heat-killed DK128 pretreatment developed subsequent heterosubtypic immunity against secondary virus infection. For protection against influenza virus via heat-killed DK128 pretreatment, B cells and partially CD4 T cells but not CD8 T cells were required as inferred from studies using knockout mouse models. Our study provides insight into how hosts can be equipped with innate and adaptive immunity via heat-killed DK128 treatment to protect against influenza virus, supporting that heat-killed LAB may be developed as anti-virus probiotics.