Calcium homeostasis modulator 2 (Calhm2) as slowly activating membrane current channel in mouse B cells.

In mouse B lymphocytes, an unidentified slow-activating voltage-dependent current resembling the characteristics of the Calhm family ion channel (ICalhm-L) was investigated. RT-PCR analysis revealed the presence of Calhm2 and 6 transcripts, with subsequent whole-cell patch-clamp studies indicating that the ICalhm-L is augmented by heat, alkaline pH, and low extracellular [Ca2+]. Overexpression of Calhm2, but not Calhm6, in N2A cells recapitulated ICalhm-L. Moreover, Calhm2 knockdown in Bal-17 cells abolished ICalhm-L. We firstly identify the voltage-dependent ion channel function of the Calhm2 in the mouse immune cells. ATP release assays in primary mouse B cells suggested a significant contribution of Calhm2 for purinergic signaling at physiological temperature.

Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories.

Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.

An economic evaluation of pharmacopuncture versus usual care for chronic neck pain: a pragmatic randomized controlled trial.

BACKGROUND: This study aimed to evaluate the cost utility of pharmacopuncture in comparison with usual care for patients with chronic neck pain. METHODS: A 12-week, multicenter, pragmatic randomized controlled trial was conducted, and 101 patients suffering from chronic neck pain for more than six months were randomly placed into the pharmacopuncture and usual care groups to receive four weeks of treatment and 12 weeks of follow-up observations. The quality-adjusted life year (QALY) was calculated using EQ-5D and SF-6D. Concerning costs in 2019, a primary analysis was performed on societal perspective cost, and an additional analysis was performed on healthcare perspective cost. RESULTS: Compared to usual care, pharmacopuncture was superior as it showed a slightly higher QALY and a lower incremental cost of $1,157 from a societal perspective. The probability that pharmacopuncture would be more cost-effective at a willingness-to-pay (WTP) of $26,374 was 100%. Pharmacopuncture was also superior from a healthcare perspective, with a lower incremental cost of $26. The probability that pharmacopuncture would be more cost-effective at a WTP of $26,374 was 83.7%. CONCLUSIONS: Overall, pharmacopuncture for chronic neck pain was found to be more cost-effective compared to usual care, implying that clinicians and policy makers should consider new treatment options for neck pain. TRIAL REGISTRATION: Number NCT04035018 (29/07/2019) Clinicaltrials.gov; Number KCT0004243 (26/08/2019) Clinical Research Information Service.

IgGs from patients with amyotrophic lateral sclerosis and diabetes target CaVα2δ1 subunits impairing islet cell function and survival.

Patients with amyotrophic lateral sclerosis (ALS) often show hallmarks of type 2 diabetes mellitus (T2DM). However, the causal link between ALS and T2DM has remained a mystery. We now demonstrate that 60% of ALS patients with T2DM (ALS-T2DM) have sera that exaggerated K+-induced increases in cytosolic free Ca2+ concentration ([Ca2+]i) in mouse islet cells. The effect was attributed to the presence of pathogenic immunoglobulin Gs (IgGs) in ALS-T2DM sera. The pathogenic IgGs immunocaptured the voltage-dependent Ca2+ (CaV) channel subunit CaVα2δ1 in the plasma membrane enhancing CaV1 channel-mediated Ca2+ influx and [Ca2+]i, resulting in impaired mitochondrial function. Consequently, impairments in [Ca2+]i dynamics, insulin secretion, and cell viability occurred. These data reveal that patients with ALS-T2DM carry cytotoxic ALS-T2DM-IgG autoantibodies that serve as a causal link between ALS and T2DM by immunoattacking CaVα2δ1 subunits. Our findings may lay the foundation for a pharmacological treatment strategy for patients suffering from a combination of these diseases.

Association of temporomandibular disorders and tinnitus with health-related quality of life: A cross-sectional study using the Fifth Korea National Health and Nutrition Examination Survey.

BACKGROUND: Few studies have examined the associations of temporomandibular disorders (TMDs) and tinnitus with health-related quality of life on a national level. OBJECTIVE: We aimed to investigate the associations of TMDs, tinnitus and quality of life among the Korean population, aged 19 years or older. METHODS: Data were obtained from the fifth Korea National Health and Nutrition Examination Survey (2012; N = 5786). TMDs, tinnitus and health-related quality of life were assessed using self-report data from EuroQol-5 Dimension. Participants were divided into four groups: no TMD and no tinnitus, TMD present but no tinnitus, no TMD but tinnitus present and both TMD and tinnitus present. RESULTS: Among the participants, 21.88% had TMD, 24.93% had tinnitus, and 7.74% had both. The prevalence of most TMD and all types of tinnitus was higher among females than among males. The group with both TMD and tinnitus reported the highest percentage of problems in the usual activity, pain/discomfort and anxiety/depression dimensions. Moreover, the odds ratio (OR) for lower quality of life was significantly higher in the group with both TMD and tinnitus compared to the group without TMD and tinnitus: mobility (OR = 1.527, 95% confidence interval [CI]: 1.014-2.300), pain/discomfort (OR = 2.072, 95% CI: 1.570-2.735), anxiety/depression (OR = 1.692, 95% CI: 1.034-2.767), EQ-5D score (OR = 1.651, 95% CI: 1.121-2.431) and EQ-VAS (OR = 1.682, 95% CI: 1.246-2.269). CONCLUSION: The presence of both TMD and tinnitus has a considerable impact on HRQoL in the Korean population. In our study, the group with both TMD and tinnitus showed lower HRQoL than without TMD and tinnitus group. These results emphasise the need for a multilateral and comprehensive approach to address these disorders and provide baseline data for developing appropriate interventions.

Expenditure on complementary and alternative medicine and productivity losses in patients with primary dysmenorrhea: A survey of women in Korea.

In women with primary dysmenorrhea (PD), the use of complementary and alternative medicine (CAM) and productivity losses at both workplaces and schools have not been comprehensively assessed. In this study, researchers evaluated the disease burden in women with PD in patients' perspective in two categories: direct cost (the use of CAM and associated costs) and indirect cost (productivity losses). Women with PD aged 16-49 years were asked to fill an online survey in 2017. The survey consisted of 49 questions. CAM included traditional Korean medicines, over-the-counter products, dietary supplements, and traditional remedies. All costs were expressed in US dollars in this study. The survey data from 86 patients with PD were analyzed. The total mean annual cost per patient with PD was $4053, comprising direct costs ($1245) and indirect costs ($2807). PD causes considerable expenditure on CAM and impairs work productivity (especially in presenteeism).

Association between diabetes mellitus and anemia among Korean adults according to sex: a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey (2010-2016).

BACKGROUND: There are many conflicting opinions regarding the association between anemia and diabetes mellitus (DM), and the mechanism by which DM influences anemia remains uncertain. Therefore, we aimed to investigate the association between anemia and DM in Korean adults and to analyze the risk factors for anemia among these patients according to sex. METHODS: This retrospective cross-sectional survey was conducted using data from the Korea National Health and Nutrition Examination Survey V, VI, and VII between January 2010 and December 2016. In total, 25,597 Korean adults aged ≥19 years (10,117 men, 15,480 women) were included. Patients with a fasting blood sugar level of ≥126 mg/dL or who have been diagnosed with DM were classified as the DM group. Anemia was defined as hemoglobin levels of < 13 g/dL in men and < 12 g/dL in women. Logistic regression analysis was used to adjust for demographic characteristics and lifestyle-, disease-, and health-related factors. RESULTS: Approximately 11.3% of patients had DM. The prevalence of anemia was significantly higher in the DM group than in the non-DM group. After adjusting for confounding factors, the odds of the prevalence of anemia in men were higher in the DM group than in the non-DM group (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.42-2.50, p < 0.0001). When investigated according to the serum creatinine level, the association was significantly stronger among women (OR 42.63, 95% CI 17.25-105.36, p < 0.0001) than among men (OR 6.30, 95% CI 3.08-12.90, p < 0.0001). CONCLUSIONS: We found a strong association between DM and anemia that was more prominent among men than among women. We also determined that the serum creatinine level had a greater influence on DM and anemia in women than in men.

Soluble Prokaryotic Overexpression and Purification of Human GM-CSF Using the Protein Disulfide Isomerase b'a' Domain.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the colony-stimulating factor (CSF) family, which functions to enhance the proliferation and differentiation of hematopoietic stem cells and other hematopoietic lineages such as neutrophils, dendritic cells, or macrophages. These proteins have thus generated considerable interest in clinical therapy research. A current obstacle to the prokaryotic production of human GM-CSF (hGM-CSF) is its low solubility when overexpressed and subsequent complex refolding processes. In our present study, the solubility of hGM-CSF was examined when combined with three N-terminal fusion tags in five E. coli strains at three different expression temperatures. In the five E. coli strains BL21 (DE3), ClearColi BL21 (DE3), LOBSTR, SHuffle T7 and Origami2 (DE3), the hexahistidine-tagged hGM-CSF showed the best expression but was insoluble in all cases at each examined temperature. Tagging with the maltose-binding protein (MBP) and the b'a' domain of protein disulfide isomerase (PDIb'a') greatly improved the soluble overexpression of hGM-CSF at 30 °C and 18 °C. The solubility was not improved using the Origami2 (DE3) and SHuffle T7 strains that have been engineered for disulfide bond formation. Two conventional chromatographic steps were used to purify hGM-CSF from the overexpressed PDIb'a'-hGM-CSF produced in ClearColi BL21 (DE3). In the experiment, 0.65 mg of hGM-CSF was isolated from a 0.5 L flask culture of these E. coli and showed a 98% purity by SDS-PAGE analysis and silver staining. The bioactivity of this purified hGM-CSF was measured at an EC50 of 16.4 ± 2 pM by a CCK8 assay in TF-1 human erythroleukemia cells.

Forkhead box O1 (FOXO1) controls the migratory response of Toll-like receptor (TLR3)-stimulated human mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) can potently regulate the functions of immune cells and are being investigated for the management of inflammatory diseases. Toll-like receptor 3 (TLR3)-stimulated human MSCs (hMSCs) exhibit increased migration and chemotaxis within and toward damaged tissues. However, the regulatory mechanisms underlying these migratory activities are unclear. Therefore, we analyzed the migration capability and gene expression profiles of TLR3-stimulated hMSCs using RNA-Seq, wound healing, and transwell cell migration assay. Along with increased cell migration, the TLR3 stimulation also increased the expression of cytokines, chemokines, and cell migration-related genes. The promoter regions of the latter showed an enrichment of putative motifs for binding the transcription factors forkhead box O1 (FOXO1), FOXO3, NF-κB (NF-κB1), and RELA proto-oncogene and NF-κB subunit. Of note, FOXO1 inhibition by the FOXO1-selective inhibitor AS1842856 significantly reduced both migration and the expression of migration-related genes. In summary, our results indicate that TLR3 stimulation induces hMSC migration through the expression of FOXO1-activated genes.

Alterations in intracellular Ca2+ levels in human endometrial stromal cells after decidualization.

Calcium (Ca2+) is an important element for many physiological functions of the uterus, including embryo implantation. Here, we investigated the possible involvement of altered intracellular Ca2+ levels in decidualization in human endometrial stromal cells (hEMSCs). hEMSCs showed high levels of mesenchymal stem cell marker expression (CD73, CD90, and CD105) and did not express markers of hematopoietic progenitor cells (CD31, CD34, CD45, and HLA-DR). Decidualization is a process of ovarian steroid-induced endometrial stromal cell proliferation and differentiation. Several types of ion channels, which are regulated by the ovarian hormones progesterone and estradiol, as well as growth factors, are important for endometrial receptivity and embryo implantation. The combined application of progesterone (1 µM medroxyprogesterone acetate) and cyclic AMP (0.5 mM) for 6 days not only elevated inositol 1,4,5-triphosphate receptor (IP3R)-mediated Ca2+ release and IP3R expression, it also promoted ORAI and STIM expression as well as cyclopiazonic acid-induced Ca2+ release. Finally, intracellular Ca2+ levels and ion channel gene expression influenced hEMSC proliferation. These results suggest that cytosolic Ca2+ dynamics, mediated by specific ion channels, serve as an important step in the decidualization of hEMSCs.

miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells.

Though Cnidium officinale Makino (COM) was known to have anti-angiogenic, anti-oxidant, neuroprotective, and anti-cancer effects, the underlying anticancer mechanism of COM using endoplasmic reticulum (ER) stress and miRNA remained unclear until now. Thus, in the current study, the inhibitory mechanism of COM in lymphoma and multiple myeloma (MM) cells was elucidated. COM exerted cytotoxicity in U937 and U266 but not Raw264.7 cells. COM treatment increased the expression of ER stress-related proteins such as p-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic initiation factor (p-eIF2α), and activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). COM also cleaved poly (ADP-ribose) polymerase (PARP) in a dose-dependent manner in both cells. Also, reactive oxygen species (ROS) generation was elevated by COM treatment. Conversely, the apoptotic effect of COM treatment was blocked by N-acetyl-l-cysteine (NAC) pretreatment. Also, the pro-survival miRNA, miR-211 was decreased by COM treatment in U937 and U266 cells. miR-211 mimic attenuated COM-induced apoptosis. Taken together, these results support the scientific evidence that COM induces apoptosis via ROS generation/CHOP activation and miR-211 suppression in U937 and U266 cells.

Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia.

BACKGROUND: Microglia are resident myeloid cells in the CNS that are activated by infection, neuronal injury, and inflammation. Established BV2 microglial cell lines have been the primary in vitro models used to study neuroinflammation for more than a decade because they reduce the requirement of continuously maintaining cell preparations and animal experimentation models. However, doubt has recently been raised regarding the value of BV2 cell lines as a model system. METHODS: We used triplicate RNA sequencing (RNA-seq) to investigate the molecular signature of primary and BV2 microglial cell lines using two transcriptomic techniques: global transcriptomic biological triplicate RNA-seq and quantitative real-time PCR. We analyzed differentially expressed genes (DEGs) to identify transcription factor (TF) motifs (-950 to +50 bp of the 5' upstream promoters) and epigenetic mechanisms. RESULTS: Sequencing assessment and quality evaluation revealed that primary microglia have a distinct transcriptomic signature and express a unique cluster of transcripts in response to lipopolysaccharide. This microglial signature was not observed in BV2 microglial cell lines. Importantly, we observed that previously unidentified TFs (i.e., IRF2, IRF5, IRF8, STAT1, STAT2, and STAT5A) and the epigenetic regulators KDM1A, NSD3, and SETDB2 were significantly and selectively expressed in primary microglia (PM). Although transcriptomic alterations known to occur in BV2 microglial cell lines were identified in PM, we also observed several novel transcriptomic alterations in PM that are not frequently observed in BV2 microglial cell lines. CONCLUSIONS: Collectively, these unprecedented findings demonstrate that established BV2 microglial cell lines are probably a poor representation of PM, and we establish a resource for future studies of neuroinflammation.

Transcriptome sequencing of microglial cells stimulated with TLR3 and TLR4 ligands.

BACKGROUND: Resident macrophages in the CNS microglia become activated and produce proinflammatory molecules upon encountering bacteria or viruses. TLRs are a phylogenetically conserved diverse family of sensors that drive innate immune responses following interactions with PAMPs. TLR3 and TLR4 recognize viral dsRNA Poly (I:C) and bacterial endotoxin LPS, respectively. Importantly, these receptors differ in their downstream adaptor molecules. Thus far, only a few studies have investigated the effects of TLR3 and TLR4 in macrophages. However, a genome-wide search for the effects of these TLRs has not been performed in microglia using RNA-seq. Gene expression patterns were determined for the BV-2 microglial cell line when stimulated with viral dsRNA Poly (I:C) or bacterial endotoxin LPS to identify novel transcribed genes, as well as investigate how differences in downstream signaling could influence gene expression in innate immunity. RESULTS: Sequencing assessment and quality evaluation revealed that common and unique patterns of proinflammatory genes were significantly up-regulated in response to TLR3 and TLR4 stimulation. However, the IFN/viral response gene showed a stronger response to TLR3 stimulation than to TLR4 stimulation. Unexpectedly, TLR3 and TLR4 stimulation did not activate IFN-ß and IRF3 in BV-2 microglia. Most importantly, we observed that previously unidentified transcription factors (TFs) (i.e., IRF1, IRF7, and IRF9) and the epigenetic regulators KDM4A and DNMT3L were significantly up-regulated in both TLR3- and TLR4-stimulated microglia. We also identified 29 previously unidentified genes that are important in immune regulation. In addition, we confirmed the expressions of key inflammatory genes as well as pro-inflammatory mediators in the supernatants were significantly induced in TLR3-and TLR4-stimulated primary microglial cells. Moreover, transcriptional start sites (TSSs) and isoforms, as well as differential promoter usage, revealed a complex pattern of transcriptional and post-transcriptional gene regulation upon infection with TLR3 and TLR4. Furthermore, TF motif analysis (-950 to +50 bp of the 5' upstream promoters) revealed that the DNA sequences for NF-κB, IRF1, and STAT1 were significantly enriched in TLR3- and TLR4-stimulated microglia. CONCLUSIONS: These unprecedented findings not only permit a comparison of TLR3-and TLR4-stimulated genes but also identify new genes that have not been previously implicated in innate immunity.

RNA sequencing reveals distinct mechanisms underlying BET inhibitor JQ1-mediated modulation of the LPS-induced activation of BV-2 microglial cells.

BACKGROUND: Microglial cells become rapidly activated through interaction with pathogens, and their persistent activation is associated with the production and secretion of various pro-inflammatory genes, cytokines, and chemokines, which may initiate or amplify neurodegenerative diseases. Bromodomain and extraterminal domain (BET) proteins are a group of epigenetic regulators that associate with acetylated histones and facilitate the transcription of target genes. A novel synthetic BET inhibitor, JQ1, was proven to exert immunosuppressive activities by inhibiting the expression of IL-6 and Tnf-α in macrophages. However, a genome-wide search for JQ1 molecular targets is largely unexplored in microglia. METHODS: The present study was aimed at evaluating the anti-inflammatory function and underlying genes targeted by JQ1 in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells using two transcriptomic techniques: global transcriptomic biological duplicate RNA sequencing and quantitative real-time PCR. Associated biological pathways and functional gene ontology were also evaluated. RESULTS: With a cutoff value of P ≤ 0.01 and fold change ≥1.5 log2, the expression level of 214 and 301 genes, including pro-inflammatory cytokine, chemokine, and transcription factors, was found to be upregulated in BV-2 cells stimulated with LPS for 2 and 4 h, respectively. Among these annotated genes, we found that JQ1 selectively reduced the expression of 78 and 118 genes (P ≤ 0.01, and fold change ≥ 1.5, respectively). Importantly, these inflammatory genes were not affected by JQ1 treatment alone. Furthermore, we confirmed that JQ1 reduced the expression of key inflammation- and immunity-related genes as well as cytokines/chemokines in the supernatants of LPS-treated primary microglial cells isolated from 3-day-old ICR mice. Utilizing functional group analysis, the genes affected by JQ1 were classified into four categories related to biological regulation, immune system processes, and response to stimuli. Moreover, the biological pathways and functional genomics obtained in this study may facilitate the suppression of different key inflammatory genes through JQ1-treated BV-2 microglial cells. CONCLUSIONS: These unprecedented results suggest the BET inhibitor JQ1 as a candidate for the prevention or therapeutic treatment of inflammation-mediated neurodegenerative diseases.

Ethanol-related alterations in gene expression patterns in the developing murine hippocampus.

It is well known that consuming alcohol prior to and during pregnancy can cause harm to the developing fetus. Fetal alcohol spectrum disorder is a term commonly used to describe a range of disabilities that may arise from prenatal alcohol exposure such as fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related neurodevelopmental disorders, and alcohol-related birth defects. Here, we report that maternal binge alcohol consumption alters several important genes that are involved in nervous system development in the mouse hippocampus at embryonic day 18. Microarray analysis revealed that Nova1, Ntng1, Gal, Neurog2, Neurod2, and Fezf2 gene expressions are altered in the fetal hippocampus. Pathway analysis also revealed the association of the calcium signaling pathway in addition to other pathways with the differentially expressed genes during early brain development. Alteration of such important genes and dynamics of the signaling pathways may cause neurodevelopmental disorders. Our findings offer insight into the molecular mechanism involved in neurodevelopmental disorders associated with alcohol-related defects.

Long-term follow-up of inpatients with meniscus tears who received integrative Korean medicine treatment: A retrospective analysis and follow-up survey.

Evidence regarding the use of Korean medicine (KM) for the conservative treatment of meniscus tears remains lacking. We aimed to evaluate clinical effectiveness and long-term follow-up outcomes in patients undergoing integrative KM treatment for meniscus tears. We analyzed the electronic medical records (EMRs) of 86 patients with meniscus tears and administered a follow-up survey. Patients treated at 1 of 4 KM hospitals between June 1, 2015, and June 30, 2020, were reviewed. KM treatment comprised herbal medicine, acupuncture, pharmacopuncture, bee venom pharmacopuncture, Chuna therapy, and KM physiotherapy. The primary outcome was the numeric rating scale (NRS) score for knee pain; secondary outcomes were the Western Ontario and McMaster Universities Arthritis Index (WOMAC), EuroQol 5-dimension (EQ-5D) score, range of motion, and patient global impression of change. The NRS for knee pain was reduced by an average of 2.49 (95% confidence interval [CI]: 2.03-2.95) at discharge and 1.97 (95% CI: 2.03-2.95) at follow-up. The WOMAC decreased by an average of 15.52 (95% CI: 10.14-20.89) during hospital stay and 30.72 (95% CI: 24.58-36.87) at follow-up. The EQ-5D score increased by an average of 0.06 (95% CI: -0.14 to 0.02) at discharge and 0.19 (95% CI: -0.29 to -0.09) at follow up. KM treatment effectively reduced knee pain, improved knee joint function, and enhanced the quality of life in patients with a meniscus tear for a relatively long period after treatment.

Effectiveness and safety of hominis placental pharmacopuncture for chronic temporomandibular disorder: A multi-center randomized controlled trial.

Background: Hominis placental (HPP) extract has been approved by the Ministry of Food and Drug Safety in Korea for treating chronic liver diseases and postmenopausal syndrome. However, its efficacy and safety for treating chronic temporomandibular disorder (TMD) remains unclear. We aimed to assess the effectiveness and safety of HPP for treating chronic TMD compared with physical therapy (PT). Methods: This study is a 2-arm parallel, multi-center, randomized controlled trial. We enrolled 82 chronic TMD patients from 2 Korean medicine hospitals between December 2019 and January 2021. We included patients with chronic TMD and randomly assigned them to undergo HPP or PT. The primary outcome was the difference in the scores for temporomandibular joint (TMJ) pain at baseline and week 6. The secondary outcomes were the scores for TMJ pain and bothersomeness, TMJ range of motion, the Korean version of Beck's depression index-Ⅱ, jaw functional limitation scale (JFLS) score, patient global impression of change (PGIC) scores, EuroQoL 5-dimension 5-level score, and short form-12 health survey (SF-12) scores. Results: Compared with PT, HPP showed significantly superior effects on TMJ pain and bothersomeness, protrusive movement pain, JFLS (verbal, emotional, and global), SF-12, and PGIC scores at week 6 (P < 0.05). Compared with the PT group, the HPP group showed a significantly higher recovery rate (≥50 % reduction in the scores for TMJ pain at the 24-week follow-up). Conclusion: HPP was more effective than PT managing pain and improving function and quality of life. Our findings demonstrate the effectiveness and safety of HPP for TMD treatment. Trial registration: This study has been registered at clinicalTrials.gov (NCT04087005), Clinical Research Information Service (CRIS) (KCT0004437), and Ministry of Food and Drug Safety (No. 31886).

Safety and effectiveness of integrative Korean medicine for the management of patients sustaining injuries in traffic accidents during pregnancy: A retrospective chart review and questionnaire survey.

The number of traffic accidents (TAs) is rising each year, and the severity of injuries can vary. Many people experience limitations in activities of daily living following TAs, affecting their quality of life. In pregnant women, even simple injuries caused by a TA could lead to unfavorable obstetric outcomes. Thus, we conducted a retrospective chart review and follow-up questionnaire survey to assess the safety and effectiveness of integrative Korean medicine (KM) treatment for pregnant women injured in TAs. To assess integrative KM effectiveness, the numeric rating scale (NRS) for TA-related symptoms, neck disability index (NDI) score, Oswestry disability index (ODI) score, shoulder pain and disability index score, Western Ontario and McMaster Universities Arthritis Index score, EuroQol 5-dimension 5-level (EQ-5D-5L) score, and patient global impression of change score were investigated for pregnant women injured in TAs. Additionally, for safety evaluation, obstetric and neonatal outcomes, as well as symptoms related to pregnancy, were assessed. At the end of treatment and follow-up, there were significant reductions in NDI and ODI scores, as well as NRS for neck pain, lower back pain, and headache, compared to scores at baseline. EQ-5D-5L scores significantly increased. A follow-up of 50 patients showed no major differences in obstetric and neonatal outcomes compared to the typical outcomes that occur in pregnant women and neonates. Major improvements were observed in the symptoms of patients who underwent integrative KM treatment after being injured in TAs. The symptoms occurred at a rate similar to those in typical pregnant women, while causality with integrative KM treatment was assessed to be unlikely or unclear. Therefore, integrative KM treatment may be considered an alternative treatment option for pregnant women who currently have limited treatment options.

Long-Term Follow-Up of Inpatients with Rotator Cuff Tear Who Received Integrative Korean Medicine Treatment: A Retrospective Analysis and Questionnaire Survey.

CONTEXT: Rotator cuff tear is one of the most common causes of shoulder pain and has become a prominent disease most frequently treated by surgery. OBJECTIVES: To investigate the long-term therapeutic effect of integrative Korean medicine (KM) as a conservative treatment in treating rotator cuff tears. DESIGN: A multicenter observational study. SETTINGS: The settings involve four regional network KM hospitals. PATIENTS: The study participants are 288 patients aged 19-70 with rotator cuff tear identified by radiologist based on magnetic resonance imaging who received integrative KM treatment for the chief complaint of shoulder pain between 1 January 2015 and 31 March 2020. INTERVENTION: None. MAIN OUTCOMES: The primary outcome was the pain score in the affected shoulder, measured by the numeric rating scale (NRS). The secondary outcomes were Shoulder Pain and Disability Index (SPADI), 5-Level Quality of life: EuroQol 5-Dimension (EQ-5D-5L), Patient Global Impression of Change (PGIC), and range of motion (ROM) scores. RESULTS: Eligible patients for MCID achievement analysis for minimally clinical important change were 167, and 109 completed the follow-up survey. The mean NRS pain score in the affected shoulder was 5.80 ± 1.27 at admission, 3.50 ± 1.32 at discharge, and 3.83 ± 2.04 at follow-up.The mean SPADI score was 51.48 ± 20.18 at admission, 37.76 ± 19.23 at discharge, and 24.26 ± 21.80 at follow-up. The improvement at discharge (P-value < 0.001) and follow-up (P-value < 0.001) compared to those at admission was statistically significant. The results also presented a significant improvement in ROM for all motions at discharge after treatment (P-value < 0.001). The number of patients who achieved minimal clinically important difference in NRS was 116 (69.5%) at discharge and 71 (65.1%) at follow-up, and in SPADI was 82 (50.9%) at discharge and 77 (70.6%) at follow-up. CONCLUSION: The results of this study suggested that integrative KM treatment can help improve pain, functional impairment, QoL, and ROM in patients with a rotator cuff tear TRIAL REGISTRATION: NCT04566939.

Effectiveness and safety of motion-style acupuncture treatment using traction for inpatients with acute low back pain caused by a traffic accident: A randomized controlled trial.

BACKGROUND: Musculoskeletal symptoms, such as neck pain and low back pain (LBP) are common after a traffic accident (TA). While motion-style acupuncture treatment (MSAT) is effective in relieving pain, MSAT using traction (T-MSAT) has rarely been studied, and evidence for its efficacy and safety is lacking. To address this gap, this study aimed to assess the effectiveness and safety of T-MSAT for pain and functional disturbances in patients with acute LBP caused by a TA. METHODS: This two-armed, parallel, assessor blinded randomized controlled trial, conducted at Jaseng Hospital of Korean Medicine, included 100 patients with acute LBP occurring within 1 week of a TA. The participants were randomly allocated (1:1 ratio) to receive either combined T-MSAT and integrative Korean medicine treatment (IKMT) or only conventional IKMT, applied for 3 consecutive days after admission. The primary outcome was the difference between numerical rating scale (NRS) scores for LBP at baseline and after treatment completion on day 4 after admission. RESULTS: At the primary endpoint, the difference in NRS scores for LBP between the T-MSAT and control groups was 0.94 (95% confidence interval [CI] 0.40-1.48). The T-MSAT group showed a significantly lower NRS score for LBP than the control group. Differences in visual analogue scale (VAS) scores between the T-MSAT and control groups were significant at baseline and discharge. The area under the curve of the VAS score showed a significant difference (-46.86 [95% CI -85.13 to -8.59]), indicating faster pain reduction in the T-MSAT group than in the control group. Recovery (30% pain reduction) was achieved more rapidly in the T-MSAT group than in the control group (log-rank test P = .005). Meanwhile, the NRS, VAS, Oswestry disability index, and quality of life scores at discharge or at the 12-week follow-up showed no significant difference. The rates of mild adverse events (AEs) were comparable between the groups. No severe AEs were reported, and none of the AEs were associated with the clinical trial. CONCLUSIONS: T-MSAT combined with IKMT is a safe treatment that can effectively and quickly reduce initial pain in patients with LBP.