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Abstract Breast cancer categorized into hormone receptor-positive (HR+), HER2-positive (HER2+), and triple-negative (TNBC) subtypes, exhibits varied outcomes based on the number of tumor-infiltrating lymphocytes (TILs). To explore the divergent roles of TIL levels across different subtypes, we employed single-cell RNA sequencing on 31 patients with breast cancer. HR+ breast cancer with high TIL levels (TIL-high) revealed increased SPP1+ macrophages, increased SPP1 expression in other monocytes/macrophages (mono/macro) subgroups, and enriched pathways associated with extracellular matrix (ECM) remodeling in mono/macro. Moreover, cell–cell interaction analyses revealed enhanced SPP1, MIF, and FN1 signaling in the interaction between SPP1+ macrophages and T-cells in TIL-high HR+ breast cancer. Spatial transcriptomics data highlighted the close proximity of SPP1+ macrophages, CD8+ T-cells, and CD4+ T-cells in TIL-high HR+ breast cancer. Our findings unveil the novel influence of SPP1+ macrophages on T-cells in TIL-high HR+ breast cancer, potentially explaining the poor prognosis and offering insights for targeted interventions.

Abstract Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.

Abstract Background Foot ulcers are a major complication of diabetes mellitus that increase morbidity and mortality in patients with diabetes, affect their quality of life, and increase the overall social burden. A considerable number of patients with diabetic foot ulcers (DFUs) require amputations every year. Methods This nation population–based study included 1 923 483 patients with diabetes who underwent regular health screening through the National Health Insurance Service during January 2009 and December 2012. We investigated the association between changes in physical activity (PA) status and the incidence of lower extremity amputation (LEA). Based on changes in PA status, participants were categorized into four groups: “remained inactive,” “remained active,” “active‐to‐inactive,” and “inactive‐to‐active.” Results Regular PA is an independent factor associated with a decreased risk of LEA in patients with diabetes. During the follow‐up period, 0.23% (n = 4454) of the patients underwent LEA. Compared with the “remained inactive” group, the “remained active” group were at the lowest risk of LEA (adjusted hazard ratio 0.5888; 95% confidence interval 0.524–0.66). A protective effect of regular PA against LEA was observed in the “remaining active” group. Conclusions Our findings suggest a protective role of PA against LEA in individuals with diabetes. This highlights the importance of recommending appropriate levels of PA for patients with diabetes. The study also showed a dose–response relationship, indicating that engaging in vigorous‐intensity PA was most beneficial, and higher amounts of PA may provide additional benefits.

Abstract Athletes are at high risk of dehydration, fatigue, and cardiac disorders due to extreme performance in often harsh environments. Despite advancements in sports training protocols, there is an urgent need for a non‐invasive system capable of comprehensive health monitoring. Although a few existing wearables measure athlete's performance, they are limited by a single function, rigidity, bulkiness, and required straps and adhesives. Here, an all‐in‐one, multi‐sensor integrated wearable system utilizing a set of nanomembrane soft sensors and electronics, enabling wireless, real‐time, continuous monitoring of saliva osmolality, skin temperature, and heart functions is introduced. This system, using a soft patch and a sensor‐integrated mouthguard, provides comprehensive monitoring of an athlete's hydration and physiological stress levels. A validation study in detecting real‐time physiological levels shows the device's performance in capturing moments (400–500 s) of synchronized acute elevation in dehydration (350%) and physiological strain (175%) during field training sessions. Demonstration with a few human subjects highlights the system's capability to detect early signs of health abnormality, thus improving the healthcare of sports athletes.

Abstract Dysphagia is more common in conditions such as stroke, Parkinson's disease, and head and neck cancer. This can lead to pneumonia, choking, malnutrition, and dehydration. Currently, the diagnostic gold standard uses radiologic imaging, the videofluoroscopic swallow study (VFSS); however, it is expensive and necessitates specialized facilities and trained personnel. Although several devices attempt to address the limitations, none offer the clinical‐grade quality and accuracy of the VFSS. Here, this study reports a wireless multimodal wearable system with machine learning for automatic, accurate clinical assessment of swallowing behavior and diagnosis of silent aspirations from dysphagia patients. The device includes a kirigami‐structured electrode that suppresses changes in skin contact impedance caused by movements and a microphone with a gel layer that effectively blocks external noise for measuring high‐quality electromyograms and swallowing sounds. The deep learning algorithm offers the classification of swallowing patterns while diagnosing silent aspirations, with an accuracy of 89.47%. The demonstration with post‐stroke patients captures the system's significance in measuring multiple physiological signals in real‐time for detecting swallowing disorders, validated by comparing them with the VFSS. The multimodal electronics can ensure a promising future for dysphagia healthcare and rehabilitation therapy, providing an accurate, non‐invasive alternative for monitoring swallowing and aspiration events.

Background: Although several studies have reported the effectiveness of acupuncture treatment for adhesive capsulitis (AC), research on pharmacopuncture therapy for AC remains limited. We compared the effectiveness and safety of pharmacopuncture and physiotherapy for AC. Methods: This pragmatic, randomized, controlled, parallel-group pilot study enrolled patients with limitations of shoulder movement and a numeric rating scale (NRS) score for shoulder pain ≥5 randomized (1:1) to the pharmacopuncture therapy (PPT) and physiotherapy (PT) groups. Treatment sessions were administered twice weekly for 6 weeks, and the participants were followed up for 13 weeks after randomization. The primary outcome was the NRS score for shoulder pain, and the secondary outcomes were the visual analog scale (VAS), Shoulder Pain and Disability Index (SPADI), range of motion (ROM), patient global impression of change (PGIC), EuroQol 5-Dimension 5-Level (EQ-5D-5L), and Short Form 12 Health Survey (SF-12) scores. The intention-to-treat (ITT) analysis was set as the primary analysis. Results: Among 50 participants, for the primary endpoint (week 7) the PPT group showed a significantly superior improvement in NRS, VAS, SPADI, ROM for flexion, ROM for abduction, and EQ-5D-5L scores. The ROM for extension, ROM for adduction, physical component summary, and patient global impression of change were significantly better in the PPT than in the PT group, and these effects were sustained until week 13. Conclusion: In this pilot study, PPT showed better effects than PT, confirming the feasibility of a follow-up main study. Trial registration: Clinicaltrials.gov (NCT05292482) and cris.nih.go.kr (KCT0007198).

Abstract. Recent research has demonstrated that chronic pain, resulting from peripheral nerve injury, leads to various symptoms, including not only allodynia and hyperalgesia but also anxiety, depression, and cognitive impairment. These symptoms are believed to arise due to alterations in gene expression and neural function, mediated by epigenetic changes in chromatin structure. Emerging evidence suggests that acupuncture can modulate DNA methylation within the central nervous system, contributing to pain relief and the mitigation of comorbidities. Specifically, acupuncture has been shown to adjust the DNA methylation of genes related to mitochondrial dysfunction, oxidative phosphorylation, and inflammation pathways within cortical regions, such as the prefrontal cortex, anterior cingulate cortex, and primary somatosensory cortex. In addition, it influences the DNA methylation of genes associated with neurogenesis in hippocampal neurons. This evidence indicates that acupuncture, a treatment with fewer side effects compared with conventional medications, could offer an effective strategy for pain management.

Electrocardiogram (ECG) monitoring has recently been an important indicator of cardiac health diagnosis. In the past, ECG could be measured under limited conditions in hospitals with 12‐lead electrode systems. Recently, portable and wearable devices have offered continuous, real‐time monitoring of ECG signals in real life. However, developing wearable ECG sensors that provide low‐motion artifacts and high‐quality signals during exercise conditions is still challenging. Herein, this review reports a systematic summary of the key characteristics, properties, and requirements of flexible wearable ECG devices for the early diagnosis of heart dysfunction in dynamic motions, including exercise. In addition, the recent progress in controlling sensor adhesion and novel materials for designing dry electrodes are discussed to improve ECG signal quality in exercise. Finally, various aspects of electrode developmental challenges and limitations are reviewed, and research directions for future studies are discussed.

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).

Background and purpose: This parallel, single-center, pragmatic, randomized controlled study aimed to investigate the effectiveness and safety of motion style acupuncture treatment (MSAT; a combination of acupuncture and Doin therapy) to reduce pain and improve the functional disability of patients with acute low back pain (aLBP) due to road traffic accidents. Materials and Methods: Ninety-six patients with aLBP admitted to the Haeundae Jaseng Hospital of Korean Medicine in South Korea due to traffic accidents were treated with integrative Korean medicine (IKM) with additional 3-day MSAT sessions during hospitalization (MSAT group, 48 patients) or without (control group, 48 patients), and followed up for 90 days. Results: The mean numeric rating scale (NRS) scores of low back pain (LBP) of the MSAT and control groups were both 6.7 (95% confidence interval [CI]: 6.3, 7.1) at baseline. After completing the third round of all applicable treatment sessions (the primary endpoint in this study), the mean NRS scores of the MSAT and control groups were 3.76 (95% CI: 3.54, 3.99) and 5.32 (95% CI: 5.09, 5.55), respectively. The difference in the mean NRS score between the two groups was 1.56 (95% CI: 1.25, 1.87). Conclusion: IKM treatment combined with MSAT can reduce pain and improve the range of motion of patients with aLBP. Trial registration: This trial is registered at ClinicalTrial.gov (NCT04956458).

Abstract The age and stroke-associated decline in musculoskeletal strength degrades the ability to perform daily human tasks using the upper extremities. Here, we introduce an intelligent upper-limb exoskeleton system that utilizes deep learning to predict human intention for strength augmentation. The embedded soft wearable sensors provide sensory feedback by collecting real-time muscle activities, which are simultaneously computed to determine the user’s intended movement. Cloud-based deep learning predicts four upper-limb joint motions with an average accuracy of 96.2% at a 500–550 ms response rate, suggesting that the exoskeleton operates just by human intention. In addition, an array of soft pneumatics assists the intended movements by providing 897 newtons of force while generating a displacement of 87 mm at maximum. The intent-driven exoskeleton can reduce human muscle activities by 3.7 times on average compared to the unassisted exoskeleton.

Abstract Background This study, utilizing the claims data from the Health Insurance Review and Assessment Service of Korea, aimed to examine the 10-year (2010–2019) trends in various types of lumbar spine surgeries performed on patients diagnosed with lumbar herniated intervertebral disc (HIVD), and the current status of opioid prescriptions, as well as the duration of postoperative hospital stays based on the type of surgery performed. Method This retrospective cross-sectional study examined patients with one or more national health insurance claims carrying a primary or secondary diagnosis of HIVD (ICD-10 codes: M511, M518, M519) over a 10-year period (2010–2019). From the patients undergoing lumbar spine surgery, we selected those who did not require reoperation within 30 days following the initial lumbar surgery. Our final study sample comprised patients who underwent only one type of surgery. Results Among the patients diagnosed with HIVD and subsequently undergoing lumbar surgery between 2010 and 2019, a slight downward trend was observed in those undergoing open discectomy (OD); however, OD persistently accounted for the highest proportion over the 10 years. Percutaneous endoscopic lumbar discectomy (PELD) demonstrated a consistent upward trend from 2016 to 2018. When inspecting trends, we noted a consistent escalation over the decade in the postoperative opioid prescription rates of strong opioids (50.7% in 2010 to 77.8% in 2019) and tramadol (50.9% in 2010 to 76.8% in 2019). Analyzing these trends by surgery type, spinal fusion exhibited a slightly higher rate of opioid prescriptions than other lumbar surgeries. Regarding the length of postoperative hospital stays, patients undergoing PELD recorded the shortest stay (7.04 ± 6.78 days), while spinal fusion necessitated the longest (20.14 ± 12.18 days). Conclusion This study analyzed the trends in types of lumbar spine surgeries, opioid analgesic prescriptions, and length of hospital stays over 10 years (2010–2019) among patients with HIVD in Korea. Our data and findings provide valuable evidence that may prove beneficial for clinicians and researchers involved in HIVD-related practices.

Abstract Objective The Synkinesis Assessment Questionnaire (SAQ) is a reliable tool to assess synkinesis symptoms; however, it is yet to be validated in Korea. Thus, this study aimed to translate and validate the Korean SAQ. Methods This validation study was set in a clinic in Seoul, Korea, that provides general integrative medicine services. A total of 100 participants with facial palsy were enrolled. Participants completed the SAQ, House–Brackmann grade (HB grade), Sunnybrook Facial Grading System (SB), and Facial Disability Index (FDI). The forward–backward translation method was followed. Of the 100 participants, 31 underwent a second assessment for test–retest reliability. Internal consistency and test–retest reliability were evaluated using Cronbach's alpha coefficient. The construct validity of the Korean version of the SAQ was tested using Spearman's rank correlation coefficient. Results The internal consistency score for the SAQ was 0.789, and the test–retest reliability score was 0.787. According to Spearman's rank correlation coefficient, the SAQ correlations to the synkinesis subdomain of SB score, total SB score, HB grade, and physical function domain in the FDI score were 0.366 (p

Highlights This article summarizes the recent advances in wireless, batteryless, implantable electronics for continuous physiological monitoring. The critical factors that affect the design of implantable electronics for biosensing are discussed. The recent progress of material research for developing various implantable devices is summarized. This article reviews various biomedical applications of implantable devices for human healthcare.

The choice of treatment for lumbar spinal stenosis (LSS) depends on symptom severity. When severe motor issues with urinary dysfunction are not present, conservative treatment is often considered to be the priority. One such conservative treatment is epidural injection, which is effective in alleviating inflammation and the pain caused by LSS-affected nerves. In this study, Shinbaro2 (Sh2), pharmacopuncture using natural herbal medicines for patients with disc diseases, is introduced as an epidural to treat LSS in a rat model. The treatment of primary sensory neurons from the rats’ dorsal root ganglion (DRG) neurons with Sh2 at various concentrations (0.5, 1, and 2 mg/mL) was found to be safe and non-toxic. Furthermore, it remarkably stimulated axonal outgrowth even under H2O2-treated conditions, indicating its potential for stimulating nerve regeneration. When LSS rats received epidural injections of two different concentrations of Sh2 (1 and 2 mg/kg) once daily for 4 weeks, a significant reduction was seen in ED1+ macrophages surrounding the silicone block used for LSS induction. Moreover, epidural injection of Sh2 in the DRG led to a significant suppression of pain-related factors. Notably, Sh2 treatment resulted in improved locomotor recovery, as evaluated by the Basso, Beattie, and Bresnahan scale and the horizontal ladder test. Additionally, hind paw hypersensitivity, assessed using the Von Frey test, was reduced, and normal gait was restored. Our findings demonstrate that epidural Sh2 injection not only reduced inflammation but also improved locomotor function and pain in LSS model rats. Thus, Sh2 delivery via epidural injection has potential as an effective treatment option for LSS.

Abstract 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.

Abstract Many patients in Korea use Korean Medicine (KM) after spine surgery, but related research is lacking. Therefore, this retrospective cohort study aimed to analyze factors affecting the use and costs of KM using nationally representative data from the National Health Insurance Service-National Sample Cohort, South Korea. Patients who underwent spinal surgery for spinal diseases from 2011 to 2014 were followed up for 5 years, and their medical care was described. The association between patient and spinal surgery characteristics and the use of KM was analyzed. A two-part model was used to analyze factors affecting the use of KM in patients undergoing spinal surgery. Of 11,802 patients who underwent spinal surgery, 11,367 who met the inclusion criteria were included. Overall, 55.5% were female, 32.3% were aged ≥ 70 years, and 50.2% received KM treatment during the follow-up period. Open discectomy was the most common surgical procedure performed (58.6%), and 40.2% of surgeries were performed because of lumbar disc disorder. Female sex, older age, high Charlson Comorbidity Index score, and use of KM before surgery were associated with increased KM use and expenditure after surgery. In conclusion, patient characteristics, rather than surgical characteristics, appeared to be more strongly associated with the use of KM after surgery, particularly prior experience with KM use. This study is significant in that it analyzed the entire spine surgery to provide a comprehensive view of the use of KM after spine surgery and analyzed the impact of various factors related patients and surgical characteristics on KM use. The results of this study may be useful to patients with spinal diseases, clinicians, and policymakers.

Intervertebral disc degeneration (IDD) progresses owing to damage and depletion of nucleus pulposus (NP) cells. Cytoprotection mitigates oxidative stress, nutrient deprivation, and mechanical stress, which lead to cell damage and necrosis. We aimed to examine the protective effect of Raphanus sativus Linne (RSL), common radish, against oxidative stress by H2O2 in human NP cells and whether the RSL extracts can inhibit triggering receptor expressed on myeloid cells 2 (TREM2), an inducer of apoptosis and degeneration in NP cells. We administered hydrogen peroxide (H2O2) to cultured human NP cells treated with RSL extracts. We used immunoblotting and quantitative PCR to investigate expression of the apoptosis-associated proteins in cultured cells. RSL significantly enhanced cell survival by suppressing the activation of cleaved caspase-3 and Bax. In contrast, RSL extract increased Bcl2 concentration to downregulate apoptosis. Additionally, RSL treatment notably enhanced the mRNA levels of ACAN and Col2a1 while significantly reducing those of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, key genes involved in NP degeneration. While H2O2 elevated TREM2 expression, causing disc degeneration, RSL downregulated TREM2 expression. Thus, our findings imply that RSL supports human NP cells under oxidative stress and regulates the pathways underlying disc degeneration, particularly TREM2, and that RSL extracts may potentially prevent IDD.

Abstract While a wide range of treatments, including medical therapies and surgery, are used to manage endometriosis, the characteristics and treatment status of patients who received these treatments have not been investigated in Korea. This study analyzed the Korean Health Insurance Review & Assessment Service—National Patient Sample (HIRA-NPS) data from 2010 to 2019 with 7530 patients diagnosed with endometriosis. Annual trends in the types of visit and surgery, medication prescriptions and associated costs were investigated. The analysis showed that surgery slightly decreased among the types of utilized healthcare services (2010: 16.3, 2019: 12.7), dienogest prescription rapidly increased due to national health insurance coverage from 2013 (2013: 12.1, 2019: 36.0), and the use of gonadotrophin-releasing hormone analogues decreased (2010: 33.6, 2019: 16.4). There was no significant change in total and outpatient costs per person over time. Regarding endometriosis treatment, conservative treatment mainly based on prescribed medications has been gradually replacing surgery. Particularly, the listing of dienogest for national health insurance coverage might have affected the trend. However, there were no significant changes in terms of total and medication costs per person.

Abstract Augmented reality (AR) is a computer graphics technique that creates a seamless interface between the real and virtual worlds. AR usage rapidly spreads across diverse areas, such as healthcare, education, and entertainment. Despite its immense potential, AR interface controls rely on an external joystick, a smartphone, or a fixed camera system susceptible to lighting. Here, an AR‐integrated soft wearable electronic system that detects the gestures of a subject for more intuitive, accurate, and direct control of external systems is introduced. Specifically, a soft, all‐in‐one wearable device includes a scalable electrode array and integrated wireless system to measure electromyograms for real‐time continuous recognition of hand gestures. An advanced machine learning algorithm embedded in the system enables the classification of ten different classes with an accuracy of 96.08%. Compared to the conventional rigid wearables, the multi‐channel soft wearable system offers an enhanced signal‐to‐noise ratio and consistency over multiple uses due to skin conformality. The demonstration of the AR‐integrated soft wearable system for drone control captures the potential of the platform technology to offer numerous human–machine interface opportunities for users to interact remotely with external hardware and software.

Osteoarthritis is the most prevalent type of degenerative arthritis. It is characterized by persistent pain, joint dysfunction, and physical disability. Pain relief and inflammation control are prioritised during osteoarthritis treatment Mume Fructus (Omae), a fumigated product of the Prunus mume fruit, is used as a traditional medicine in several Asian countries. However, its therapeutic mechanism of action and effects on osteoarthritis and articular chondrocytes remain unknown. In this study, we analyzed the anti-osteoarthritis and articular regenerative effects of Mume Fructus extract on rat chondrocytes. Mume Fructus treatment reduced the interleukin-1β-induced expression of matrix metalloproteinase 3, matrix metalloproteinase 13, and a disintegrin and metalloproteinase with thrombospondin type 1 motifs 5. Additionally, it enhanced collagen type II alpha 1 chain and aggrecan accumulation in rat chondrocytes. Furthermore, Mume Fructus treatment regulated the inflammatory cytokine levels, mitogen-activated protein kinase phosphorylation, and nuclear factor-kappa B activation. Overall, our results demonstrated that Mume Fructus inhibits osteoarthritis progression by inhibiting the nuclear factor-kappa B and mitogen-activated protein kinase pathways to reduce the levels of inflammatory cytokines and prevent cartilage degeneration. Therefore, Mume Fructus may be a potential therapeutic option for osteoarthritis.

This study aimed to investigate the changes in lymph node surgery types and prescription patterns of postoperative medications for pain management in patients with breast cancer using national health insurance claim data from South Korea. The study population comprised patients with at least one record of a principal diagnosis of breast cancer (ICD-10 code: C50) from the national health insurance claim database between 2010 and 2019. Patients who underwent mastectomy or lumpectomy only once were selected for the analysis. Patients who underwent axillary lymph node dissection (ALND) with mastectomy or lumpectomy on the day of surgery were included in the ALND group, whereas those who underwent sentinel lymph node biopsy (SLNB) were included in the SLNB group. Prescription records of opioids before, after and on the date of breast cancer surgery were collected and categorized according to the opioid type. Multivariate logistic regression modeling was used to compare postoperative opioid prescriptions. The proportion of those undergoing ALND among 3,080 patients decreased consistently after 2014, while the proportion undergoing SLNB increased. Although the rate of pain medication prescription on the day of surgery was similar between the two groups, the rate of prescription of postoperative pain medication and anticancer agents was lower in the SLNB group than in the ALND group. Logistic regression modeling showed that the SLNB group had lower odds of receiving opioids than did the ALND group (Odds ratio (OR) = 0.727, Confidence Interval (CI) = 0.546-0.970). A consistent trend was observed when the model was adjusted for neoadjuvant chemotherapy and the use of preoperative pain medications (OR = 0.718, CI = 0.538-0.959). To manage postoperative pain and prevent chronic pain with minimal side effects, sufficient discussion among clinicians, patients, and other healthcare professionals is imperative, along with adequate treatment planning.

Immune responses must be strictly regulated to prevent autoimmune and infectious diseases and to protect against infectious agents. As people age, their immunity wanes, leading to a decrease in lymphocyte production in bone marrow and thymus and a decline in the efficacy of mature lymphocytes in secondary lymphoid organs. This study explores the immune-boosting potential of Yookgong-dan (YGD) in enhancing the immune system by activating immune cells. In our in vitro experiments, cyclophosphamide (Cy) treatment led to a significant decrease in primary splenocyte viability. However, subsequent treatment with YGD significantly improved cell viability, with doses ranging between 1 and 25 μg/mL in Cy-treated splenocytes. Flow cytometry analysis demonstrated that the Cy group exhibited reduced positivity of CD3+ T cells and CD45+ leukocytes compared to the blank group. In contrast, treatment with YGD led to a notable, dose-responsive increase in these immune cell types. In our in vivo experiments, YGD was orally administered to Cy-induced immunosuppressed mice at 20 and 100 mg/kg doses for 10 days. The results indicated a dose-dependent elevation in immunoglobulin (Ig)G and IgM levels in the serum, emphasizing the immunostimulatory effect of YGD. Furthermore, the Cy-treated group showed decreased T cells, B (CD19+) cells, and leukocytes in the total splenocyte population. Yet, YGD treatment resulted in a dose-dependent reversal of this pattern, suggesting its ability to counter immunosuppression. Notably, YGD was found to effectively stimulate T (CD4+ and CD8+) lymphocyte subsets and natural killer cells, along with enhancing Th1/Th2 cytokines in immunosuppressed conditions. These outcomes correlated with the modulation of BCL-2 and BAX expression, which are critical for apoptosis. In conclusion, YGD has the potential to bolster immune functionality through the activation of immune cells, thereby enhancing the immune system's capacity to combat diseases and improve overall health and wellness.

Objectives Fibromyalgia treatment trends vary globally; however, the trend in South Korea has not been investigated yet. This study aimed to analyse the fibromyalgia treatment trends in South Korea.Design Retrospective, observational study using serial cross-sectional data.Setting The National Patient Samples of the Korean Health Insurance Review & Assessment Service from 2011 to 2018 were used.Participants A total of 31 059 patients with fibromyalgia were included in this study. The basic characteristics of the patients were stratified by sex, age and comorbidity. A patient was considered to have a condition if it was recorded as a principal diagnosis at least once in a year.Primary and secondary outcome measures Trends in the types of medical visits and prescribed treatments were investigated and the values are presented as rates per 100 patients. The types of pharmacological treatment were presented according to the existing clinical guidelines. Additionally, combination prescription trends and associated characteristics were investigated.Results Of the patients, 66.2% were female. Visits to internal medicine departments showed the most significant increase (2011: 11.34; 2018: 21.99; p

Abstract Biometric locking systems offer a seamless integration of an individual's physiological characteristics with secure authentication. However, they suffer from limitations such as false positive and negative authentication, environmental interference, and varying disadvantages across multiple authentication methods. To address these limitations, this study develops a soft smart biopatch for a continuous cardiac biometric wearable device that can continuously gather novel biometric data from an individual's heart sound for authentication with minimal error (less than 0.5%). The device is designed to be discreet and user‐friendly, and it employs soft biocompatible materials to ensure comfort and ease of use. The patch system incorporates a miniaturized microphone to monitor sounds over long periods and multiple dimensions, enhancing the reliability of the biometric data. Furthermore, the use of machine‐learning algorithms has enabled the creation of unique identification keys for individuals based on the continuous monitoring properties of the low‐cost device. These advantages make it more effective and efficient than traditional biometric systems, with the potential to enhance the security of mobile devices and door locks.

Real world data (RWD) is increasingly used to investigate health outcomes and treatment efficacy in the field of integrative medicine. Due to the fact that the majority of RWDs are not intended for research, their secondary use in research necessitates complex study designs to account for bias and confounding. To conduct a robust analysis of RWD in integrative medicine, a comprehensive study design process that reflects the characteristics of integrative therapies is necessary. In this paper, we present a guide for designing comparative effectiveness RWE research in integrative medicine. We discuss key factors to consider when selecting RWDs for research on integrative medicine. We provide practical steps for developing a research question, formulating the PICOT objectives (population, intervention, comparator, outcome, and time horizon), and selecting and defining covariates with a summary table. Specific study designs are depicted with corresponding diagrams. Finally, data analysis procedures are introduced. We hope this article clarifies the importance of RWE research design and related processes in order to improve the rigor of RWD studies in the field of integrative medicine research.

Spinal cord injury (SCI) is a devastating event that often results in the inflammatory condition of glial scar tissue formation, impeding neural regeneration and recovery. Reducing the inflammatory response and inhibiting glial formation are promising strategies for improving SCI outcomes. Here, we introduce a new role for Shinbaro2 (Sh2), known for its anti-inflammatory and pain-reducing effects, in ameliorating glial scars formed in the damaged spinal cord and promoting axon growth after SCI. Sh2 was applied at various concentrations to cultivate primary spinal cord neurons. Concentrations of 1 and 2 mg/mL effectively enhanced cell viability and axonal outgrowth in spinal cord neurons subjected to hydrogen peroxide or laceration injury. Sh2 helped reduce neuroinflammation by increasing anti-inflammatory M2 macrophages (arginase 1) and decreasing inflammatory cells, ultimately reducing lesion size. In scar formation, Sh2 inhibited the expression of β-catenin and nestin in reactive astrocytes in the injured spinal cord. Moreover, Sh2 suppressed the expression of chondroitin sulfate proteoglycans and SOX9, which are involved in scar formation. Furthermore, Sh2 promoted the sprouting of serotonergic axons and the growth of neurofibrillary tangles, enhancing motor function recovery in SCI. These findings highlight the potential of Sh2 as an SCI therapeutic intervention, offering hope for neural and functional restoration in individuals with this debilitating condition.

Abstract Background Plantar fasciitis (PF) is the most common cause of heel pain in adults, and the number of patients and medical expenses are increasing annually. However, studies on this condition are lacking. There is a need to investigate universally administered PF treatment and the associated costs. Therefore we analyzed the South Korean Health Insurance Review and Assessment Service data to investigate the distribution and healthcare usage of patients with PF. Methods A cross-sectional retrospective observational design was used in this study. Patients diagnosed with PF (ICD-10 code M72.2) between January 2010 and December 2018 in South Korea, of whom 60,079 had used healthcare at least once, were included in the study. We assessed healthcare usage and cost due to PF, treatment method, and visit route. All statistical analyses were performed with descriptive statistics using SAS 9.4 version. Results The number of treated cases of PF and patients with PF was 11,627 cases and 3,571 patients in 2010, respectively, which increased annually to 38,515 cases and 10,125 patients by 2018, respectively. The 45-54-year-old age group had the highest number of patients; the patient population was predominantly women. Physical therapy was used frequently in Western medicine (WM) institutions, where > 50% of the medicines prescribed to outpatients were analgesics. In contrast, acupuncture therapy was most commonly used in Korean medicine (KM) institutions. A high percentage of patients who visited a KM institution, followed by a WM institution, and then returned to the same KM institution had visited the WM institution for radiological diagnostic examination. Conclusion This study analyzed nine years of period data from a patient sample of claims data from the Health Insurance Review and Assessment Service to examine the current status of health service use for PF in Korea. We obtained information on the status of WM/KM institution visits for PF treatment, which could be useful for health policymakers. Study findings regarding treatments often used in WM/KM, the frequency of treatments, and their costs could be used as basic data by clinicians and researchers.

Background : Adhesive capsulitis is a progressive, idiopathic disorder that significantly impacts individuals̓ daily lives and increases their medical burden. Pharmacopuncture therapy, which combines acupuncture techniques with herbal medicine, involves injecting herbal extracts into specific acupoints. This study aims to determine the effectiveness and safety of pharmacopuncture therapy in comparison to physiotherapy (PT) for treating adhesive capsulitis. Methods : This research protocol outlines a two-arm, parallel, multi-center, pragmatic randomized controlled trial. Fifty participants will be randomly allocated to either the pharmacopuncture therapy or PT group, and they will receive 12 sessions of their respective therapies over a 6-week period. The primary outcome measure is the numeric rating scale for shoulder pain. Secondary outcomes include the visual analog scale score for shoulder pain, Shoulder Pain and Disability Index, Patients̓ Global Impression of Change score, Short Form-12 Health Survey Version 2 score, and EuroQol-5 Dimension. Statistical analysis will be conducted based on the intention-to-treat principle. Discussion: This trial may offer high-quality and reliable clinical evidence for evaluating the effectiveness and safety of pharmacopuncture therapy compared to PT in the treatment of adhesive capsulitis. Furthermore, this study will serve as a valuable guideline for practitioners when making clinical decisions and managing adhesive capsulitis.

Background and Objective: The aim of this study was to analyze trends in surgical and non-surgical service utilization for common shoulder disorders in Korea from 2010 to 2019. Methods and Materials: This retrospective, cross-sectional, descriptive study utilized National Patient Sample data from the Health Insurance and Review Assessment Service (HIRA) of Korea. These data constitute a 2% sample out of the entire Korean population and include data for a variety of parameters instrumental for health care research. Patients with at least one medical service use for rotator cuff syndrome or tear, impingement syndrome, or adhesive capsulitis between January 2010 and December 2019 were included. Trends in healthcare utilization by disorder type, patient demographics, seasonal service use, and treatment details were examined. Results: There was an upward trend in the total number of patients and costs for shoulder disorders, from 35,798 patients and USD 5,485,196 in 2010 to 42,558 and USD 11,522,543 in 2019, respectively. The number of patients aged ≥60 and hospital visits increased. March had the highest number of claims. Physical therapy was the most common non-surgical procedure, while nerve block claims more than doubled. Opioid prescription rates also tripled. Surgical treatments were dominated by shoulder rotator cuff repair and acromioplasty. Conclusions: There was a significant increase in healthcare utilization for shoulder disorders, marked by rising costs and patient numbers. The use of nerve blocks and opioids notably increased. These data are valuable for clinicians, researchers, and policymakers.

Abstract Recent advances in soft sensors and flexible electronics offer various applications in detecting physical, electrical, and chemical signals. However, there are still technical barriers in current mechanical, electrical, and material properties for enhanced signal sensing. When measuring signals from the human skin, minimizing the skin‐sensor contact impedance is still challenging while maximizing sensitivity through optimized materials and soft electronics. Here, this review summarizes recent advances in materials, manufacturing, and integration technologies to develop ultrathin soft sensors for monitoring various human physiological signals. The enhancements in soft and compliant structures and mechanical properties are critical to making reliable wearable electronic systems. This article shares the details of soft sensors, integration processes, manufacturing methods, and their applications to target physical, electrical, and chemical signals. In addition, the limitations and current trends in developing multifunctional sensors, self‐powered devices, and integration with external stimuli systems are discussed.

Abstract Purpose National big data pertaining to the status of common respiratory diseases is essential to devising appropriate policies to promote proper treatment and prevention of respiratory diseases amid the prolonged coronavirus disease 2019 (COVID‐19) pandemic. The aim of this study is to investigate the prevalence of common respiratory diseases and their association with sociodemographic characteristics, comorbidities, and medical history using 11 years (2008–2018) of the Korea National Health and Nutrition Examination Survey (KNHANES) data, ultimately to present foundational data for policy decision making and disease prevention measures. Methods Among the participants of the KNHANES survey (2008–2018), 93 028 adults aged ≥40 years who underwent a lung function test were included in this cross‐sectional study. The participants were divided into four groups: Asthma, chronic obstructive pulmonary disease (COPD), asthma + COPD, and no respiratory disease. Their data were analyzed for demographic factors, health behavior, and disease‐related factors. Multiple logistic regression was used to calculate the odds ratio (OR) adjusted for sex, age, household income, educational level, occupation, body mass index (BMI), smoking status, alcohol consumption, physical activity, and comorbidities. Results Of all participants, 1.83%, 12.63%, and 1.27% had only asthma, only COPD, and asthma + COPD, respectively. With respect to the patients with asthma who also had asthma + COPD, the OR of asthma + COPD was 5.272 in underweight patients and 6.479 in patients aged ≥70 years. Meanwhile, a high association between COPD and asthma + COPD was found in female patients, whereas asthma was more highly associated with asthma + COPD in male patients. Conclusion The study confirmed that old age, sex, smoking status, BMI, previous history of atopic dermatitis, and lung cancer were independent risk factors for asthma, COPD, and asthma + COPD. The present study demonstrated the need for a multidisciplinary integrative approach to respiratory diseases, and the findings could be used for developing policies for the treatment of COVID‐19 and respiratory diseases and the prevention of infectious diseases.

Abstract In this retrospective cross-sectional observational study, the medical service utilization of post-stroke sequelae patients was examined using a national patient sample. The Korean Health Insurance Review and Assessment Service-National Patients Sample database was used to investigate the medical service utilization of 19,562 patients, diagnosed with post-stroke sequelae of cerebrovascular disease (I69) in Korea between January 2016 and December 2018. We compared the demographic characteristics, diagnosis code subtypes, frequency of healthcare utilization, medical costs, and comorbidities of standard care (SC) and Korean medicine (KM) users. Overall, patients aged ≥ 65 years accounted for the highest percentage, and utilization of medical services increased among patients aged ≥ 45 years. Outpatient care was higher among SC (79.23%) and KM (99.38%) users. Sequelae of cerebral infarction accounted for the highest percentage of diagnosis subtypes. Physical therapy and rehabilitation therapy were most frequent in SC, whereas injection/procedure and acupuncture were most frequent in KM. Cerebrovascular circulation/dementia drugs were prescribed most frequently in SC. Circulatory, digestive, endocrine, and metabolic disorders were the most common comorbidities in SC, whereas musculoskeletal and connective tissue disorders were most common in KM. Overall, SC and KM users showed differences in the number of medical service claims, cost of care, and comorbidities. Our findings provide basic research data for clinicians, researchers, and policy makers.

Background The present study investigates whether modifiable behavioral factors of current cigarette smoking, heavy alcohol consumption, and regular exercise are associated with risk of lower extremity amputation (LEA) in diabetic patients. Methods A total of 2,644,440 diabetic patients (aged ≥20 years) was analyzed using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios (HRs) for the behavioral factors with risk of LEA under adjustment for potential confounders. Results The risk of LEA was significantly increased by current cigarette smoking and heavy alcohol consumption (HR, 1.436; 95% confidence interval [CI], 1.367 to 1.508 and HR, 1.082; 95% CI, 1.011 to 1.158) but significantly decreased with regular exercise (HR, 0.745; 95% CI, 0.706 to 0.786) after adjusting for age, sex, smoking, alcohol consumption, exercise, low income, hypertension, dyslipidemia, body mass index, using insulin or oral antidiabetic drugs, and diabetic duration. A synergistically increased risk of LEA was observed with larger number of risky behaviors. Conclusion Modification of behaviors of current smoking, heavy alcohol intake, and exercise prevents LEA and can improve physical, emotional, and social quality of life in diabetic patients.

Recent advances in sensors and electronics have enabled electrooculogram (EOG) detection systems for capturing eye movements. However, EOG signals are susceptible to the sensor's skin‐contact quality, limiting the precise detection of eye angles and gaze. Herein, a two‐camera eye‐tracking system and a data classification method for persistent human–machine interfaces (HMIs) are introduced. Machine‐learning technology is used for a continuous real‐time classification of gaze and eye directions, to precisely control a robotic arm. In addition, a deep‐learning algorithm for classifying eye directions is developed and the pupil center‐corneal reflection method of an eye tracker for gaze tracking is utilized. A supervisory control and data acquisition architecture that can be universally applied to any screen‐based HMI task are used by the system. It is shown in the study that the classification algorithm using deep learning enables exceptional accuracy (99.99%) with the number of actions per command (≥64), the highest performance compared to other HMI systems. Demonstrating real‐time control of a robotic arm captures the unique advantages of the precise eye‐tracking system for playing chess and manipulating dice. Overall, this paper shows the HMI system's potential for remote control of surgery robots, warehouse systems, and construction tools.

Obesity is a well-established risk factor for various malignancies and emerging evidence suggests that adipokines play a pivotal role in linking excess adiposity to tumorigenesis. Adipokines are bioactive molecules secreted by adipose tissue and their altered expression in obesity contributes to a pro-inflammatory, pro-angiogenic, and growth-promoting microenvironment conducive to tumorigenesis. Leptin, a key adipokine, activates survival and proliferative signaling pathways whereas adiponectin exhibits tumor-suppressive effects by inducing apoptosis and cell cycle arrest. Visfatin has also been documented to promote tumor growth, angiogenesis, migration, and invasion. Moreover, emerging studies suggest that adipokines, such as resistin, apelin, and chemerin, which are overexpressed in obesity, may also possess oncogenic functions. Despite advancements in our understanding of the roles of individual adipokines in cancer, the intricate interplay and crosstalk between adipokines, tumor cells, and the tumor microenvironment remain complex and multifaceted. This review highlights the evolving knowledge of how adipokines contribute to obesity-related tumorigenesis, shedding light on the potential of targeting adipokine signaling pathways as a novel therapeutic approach for obesity-associated cancers. Further research on the specific mechanisms and interactions between adipokines and tumor cells is crucial for a comprehensive understanding of obesity-associated cancer pathogenesis.

Objective This study used 2010–2018 Health Insurance Review and Assessment Service National Patient Sample data to analyse the distribution and healthcare utilisation of patients with migraine in South Korea.Design Retrospective, observational study using serial cross-sectional data.Participants Patients with primary diagnosis of G43, a Korean Standard Classification of Diseases-10 code for migraine, were included in the analysis. The exclusion criteria were missing code information; code for dental, health centre or psychiatry; institution type specified as nursing hospital, psychiatric hospital, dental hospital, midwifery centre or health centre; blank entries for total cost or days of care. 453 246 records of patients and 117 157 patients corresponding to those records were identified.Outcome measures Primary outcome measures were medical service utilisation status, treatment methods and drug use status associated with migraine.Results Cases and patients of migraine increased from 48 846 and 19 468 (2010) to 52 729 and 20 802 (2018), respectively, increases of 7.95% and 6.85%, respectively, compared with 2010. Total cost of care increased from $921 857.88 (2010) to $1 711 219.60 (2018). The most common age range of patients was 45–54 years, with 2.69 times more female than male patients. In Western medicine hospitals, subcutaneous or intramuscular injection therapy was used frequently, while in Korean medicine hospitals, acupuncture therapy was used. Among Western medicine outpatients, more than 50% of the therapeutics prescribed for acute migraine were simple analgesics or non-steroidal anti-inflammatory drugs. The number of prescriptions for the prevention of episodic migraine increased from 13 600 cases (2010) to 20 546 cases (2018), representing the steepest increase in drug utilisation.Conclusions Treatments frequently used in Western and Korean medicine hospitals and their frequency of use and costs were identified. The findings of this study can be used as a basis for relevant health policy decisions.

Background: Since evidence-based medicine has been pursued in complementary and alternative medicine, the clinical practice guideline (CPG) has become a key factor in providing standardized and validated practices in Korean Medicine (KM). We aimed to review the current status and characteristics of the development, dissemination, and implementation of KM-CPGs. Methods: We searched KM-CPGs and relevant publication via web-based databases. We organized the searching results focused on the year of publications and the development programs to show which and how KM-CPGs have been development. We also reviewed the manuals for KM-CPG development to introduce concise characteristics of the KM-CPGs published in Korea. Results: The KM-CPGs have been developed according to manuals and standard templates for developing evidence-based KM-CPGs. First, CPG developers reviews the previously published CPGs for a clinical condition of interest and plans the CPG development. After finalizing the key clinical questions, the evidence is searched, selected, appraised, and analyzed following the internationally standardized methods. The quality of the KM-CPGs is controlled by a tri-step appraisal process. Second, the CPGs were submitted for the appraisal of the KM-CPG Review and Evaluation Committee. The committee evaluates the CPGs according to the AGREE II tool. Finally, the Steering Committee of the KoMIT project reviews the entire process of developing the CPGs and confirms it for public disclosure and dissemination. Conclusion: Evidence-based KM from research to practice can be achieved with the attention and effort of multidisciplinary entities such as clinicians, practitioners, researchers, and policymakers for the CPGs.

Background: Traffic injuries include acute low back pain (LBP) needing active treatment to prevent chronicity. This two-armed, parallel, assessor-blinded, randomized controlled trial evaluated the effectiveness and safety of progressive loading–motion style acupuncture treatment (PL-MSAT) for acute LBP following traffic accidents. Methods: Based on an effect size of 1.03, 104 participants were recruited and divided in a 1:1 ratio into PL-MAST and control groups using block randomization. Both groups underwent integrative Korean medicine treatment (IKMT) daily; only the PL-MSAT group underwent three PL-MSAT sessions. The outcomes were assessed before and after the treatment sessions and at 1 and 3 months post-discharge. The primary outcome was the difference in the numeric rating scale (NRS) for LBP. The secondary outcomes included a visual analog scale for LBP, leg pain status, the Oswestry disability index, lumbar active range of motion (ROM), quality of life, Patient Global Impression of Change, and Post-Traumatic Stress Disorder Checklist adverse events. Results: In the modified intention-to-treat analysis, 50 and 51 participants were included in the PL-MSAT and control groups. On Day 4, the mean LBP NRS score was 3.67 (3.44–3.90) in the PL-MSAT group, indicating a significantly lower NRS 0.77 (0.44–1.11) compared to 4.44 (4.20–4.68) for the control group (p < 0.001). The PL-MSAT group exhibited greater ROM flexion (−5.31; −8.15 to −2.48) and extension (−2.09; −3.39 to −0.80). No significant differences were found for the secondary outcomes and follow-ups. Conclusions: Compared with IKMT alone, PL-MSAT plus IKMT showed significantly better outcomes for reducing pain and increasing the ROM in acute LBP.

Epidural administration is the leading therapeutic option for the management of pain associated with lumbar spinal stenosis (LSS), which is characterized by compression of the nerve root due to narrowing of the spinal canal. Corticosteroids are effective in alleviating LSS-related pain but can lead to complications with long-term use. Recent studies have focused on identifying promising medications administered epidurally to affected spinal regions. In this study, we aimed to investigate the effectiveness of harpagoside (HAS) as an epidural medication in rats with LSS. HAS at various concentrations was effective for neuroprotection against ferrous sulfate damage and consequent promotion of axonal outgrowth in primary spinal cord neurons. When two concentrations of HAS (100 and 200 μg/kg) were administered to the rat LSS model via the epidural space once a day for 4 weeks, the inflammatory responses around the silicone block used for LSS were substantially reduced. Consistently, pain-related factors were significantly suppressed by the epidural administration of HAS. The motor functions of rats with LSS significantly improved. These findings suggest that targeted delivery of HAS directly to the affected area via epidural injection holds promise as a potential treatment option for the recovery of patients with LSS.

Prior studies exploring the effectiveness of traditional Korean medicine (TKM) treatment for facial palsy have mainly focused on Bell’s palsy, and there are few studies on the effectiveness of TKM treatments for traumatic facial palsy following mandibular fracture. The patient was a 24-year-old Korean man with left-sided facial paralysis following a left mandibular fracture. Surgery was performed for the fracture and the facial palsy was treated using conventional medicine (CM) treatments for approximately 3 months, but there was no improvement observed in the patient’s condition. Subsequently, the patient underwent an integrative Korean medicine treatment regimen consisting of acupuncture, pharmacopuncture, cupping, moxibustion, and herbal medication for a duration of 2 months. After 2 months of treatments, the House–Brackmann facial grading scale changed from Ⅴ to II and Yanagihara’s unweighted grading score increased from 9 to 34. This case presentation and previous studies of traumatic facial palsy using TKM treatment show that TKM treatment may be considered a complementary or alternative treatment method to CM treatment in patients with traumatic facial palsy. PROSPERO registration number: CRD42023445051.

As primary outcomes differ among clinical lumbar disc herniation (LDH) studies, this study aimed to explore outcomes reflecting real-world patient experiences through an exploratory questionnaire survey. Those diagnosed with LDH having radiating leg pain in South Korea in November of 2022 (N = 500) were administered a questionnaire including basic characteristics, disease onset, symptoms and severity, priority symptoms for improvement, and important treatment factors. Outcome measures included the identification of priority symptoms and disabilities. Most common symptoms were numbness in the leg (N = 435, 87.0%) and back pain (N = 406, 81.2%); most common disabilities were discomfort in sitting (N = 323, 64.6%) and lifting (N = 318, 63.6%). The highest priority symptom was back pain (N = 242, 48.4%). A satisfactory degree of symptom improvement was a decrease of at least 3 points on the numeric rating scale. The majority of respondents preferred improvement in disability over pain (N = 270, 55.8%), a stable effect over a rapid effect (N = 391, 78.2%), and safety over treatment efficacy (N = 282, 56.4%). Safety (N = 129, 25.8%) and cost (N = 111, 22.2%) were the most important treatment factors. Improvements in back pain, leg pain, sitting, and sleeping were prioritized, and safety, stable treatment effect, and functional recovery were desired. Clinical trials for LDH should be designed to reflect this real-world patient need. Further study to examine the patients’ symptoms and needs in details is needed.

This study aims to analyze the types and cost of infertility care provided in a clinical setting to examine the changes of healthcare utilization for infertility after the 2017 launch of assisted reproductive technology (ART) health insurance coverage in South Korea. Health Insurance Review Assessment-National Patient Sample data from 2016 and 2018 were analyzed comparatively. Data related to receiving medical service under the International Classification of Diseases 10th revision code N97 (female infertility) or N46 (male infertility) at least once were analyzed, including patients' characteristics and healthcare utilization (type of healthcare facility and treatment approach). Between 2016 and 2018, the percentage of patients aged 30-34 receiving infertility care dropped; the percentages of patients in older age groups increased. The number of female patients remained comparable, whereas the number of male patients increased by 23%. Average visits per patient increased by about 1 day from 2016 to 2018. Total annual infertility care claim cost increased from $665,391.05 to $3,214,219.48; the per-patient annual cost increased from $114.76 to $522.38. The number of claims and cost of treatment and surgery increased markedly, as did the number of claims and cost of gonadotropins. With its focus on health insurance coverage of ART and results demonstrating increases in medical services, medications, cost, and patient utilization, this study reveals the significant effects of national health policies on the treatment, cost, and management of infertility.

Lumbar spinal stenosis (LSS) is defined as spinal canal narrowing, resulting in the compression of the nerves traversing the lower back into the leg. Inflammation is the most common cause of LSS. Elevated iron stores are often associated with chronic inflammation resulting in nerve damage-induced pain. Macrophage polarization to either the M1 (inflammatory) or M2 (anti-inflammatory) type is essential for regulating host defenses and promoting tissue repair. However, the precise role of macrophage polarization in iron release or retention in LSS pathophysiology remains elusive. Melittin, a component of bee venom, modulates iron metabolism-related macrophage polarization and is beneficial in LSS. We treated primary peritoneal macrophages with melittin and assessed macrophage polarization by immunofluorescence staining. Melittin (100 and 250 µg/kg) effects on iron deposition-induced macrophage polarization were also evaluated using immunochemistry, real-time PCR, and flow cytometry in an LSS rat model. Locomotor function was assessed using the Basso–Beattie–Bresnahan (BBB) locomotor rating scale, ladder scoring, and von Frey test for up to 3 weeks. Melittin induced M2 polarization of iron-insulted primary macrophages in vitro and increased the proportion of M2 macrophages in the damaged spinal cord in vivo. Moreover, melittin attenuated iron overload-induced M1 polarization by regulating iron metabolism-related genes in rats with LSS. In conclusion, melittin improves locomotor recovery and stimulates axonal growth following LSS. Additionally, it promotes functional recovery in LSS rat models by regulating macrophage iron metabolism, thereby activating M2 macrophages, suggesting its potential application in LSS treatment.

Abstract Background There has been little investigation on how guidelines for allergic rhinitis (AR) treatment are applied in current clinical practice. We aimed to analyze prescription trends and patterns for AR treatment according to patient characteristics over a 9-year period in Korea. Methods We used cross-sectional data from the Korean Health Insurance Review & Assessment Service National Patient Sample from 2010 to 2018. We analyzed 1,719,194 patients with AR as the principal diagnosis. Prescription rates of antihistamines, steroids, and other drugs; combination prescriptions; and first-choice prescriptions were analyzed. Results The prescription rate of first-generation antihistamines decreased over the years (2010: 29.13; 2018: 23.41). By contrast, the prescription rate of systemic steroids (2010: 23.60; 2018: 28.70), nasal steroids (2010: 9.70; 2018: 14.67), and leukotriene receptor antagonists (LTRAs) (2010: 11.13; 2018: 26.56) increased. The prescription rate of steroids was lower in patients aged 0–5 years and ≥ 65 years than in other age groups and that of LTRAs was the highest in patients aged 0–5 years. The rate of combination prescribing antihistamines and nasal steroids increased (2010: 7.99; 2018: 12.09). The rate of first-choice prescriptions with antihistamines and nasal steroids also increased (2010: 4.72; 2018: 7.24). Conclusions The results confirmed a decrease in antihistamine prescriptions, especially with first-generation, and an increase in steroid and LTRA prescriptions in patients with AR in Korea. Regarding prescription patterns, steroids were increasingly prescribed in combination with antihistamines. However, the trend was opposite in the 0–5 years and ≥ 65 years groups.

Female menopause is a hormone deficiency phenomenon that causes hot flashes, vaginal dryness, depression, nervous tension, insomnia, obesity, and bone loss. There are various hormone replacement therapy (HRT)-based menopausal treatments, but they are accompanied by side effects such as endometrial cancer and hyperplasia. To confirm the menopausal improvement effect of Polygonatum sibiricum (PS), we prepared an ovariectomized animal model, administered 17β-estradiol (E2) and PS, and analyzed various menopausal symptoms. PS restored vaginal epithelium thickness, by increasing the expression of estrogen receptors ERα (ESR1) and ERβ (ESR2), and increased serotonin concentration by reducing serotonin receptor 1 A (5-HT1A) and glucocorticoid receptor (Gr) expression. In addition, PS suppressed obesity by increasing HDL-C and decreasing LDL-C levels and improved the osteoporosis induced by ovariectomy. In particular, by controlling Hand2, Fgf2, and Faf9 expression through PR, the antiproliferative signal was suppressed in uterine epithelium, thereby reducing the risk of side effects of the administration of E2 alone. These results demonstrate that PS alleviates menopausal symptoms without causing endometrial hyperplasia.

Background and Objectives: This study aimed to investigate osteoporosis-related treatments and the overall anticancer drug treatment tendencies, with a focus on selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), in Korean patients with breast cancer from 2010 to 2019. Materials and Methods: Data were obtained from the Health Insurance Review and Assessment Service. Patients with breast cancer (International Classification of Diseases, 10th Revision code: C50) as a principal diagnosis at least once from 2010 to 2019 were included. Those with osteoporosis (M80, M81, or M82) as a principal or sub-diagnosis or those who received osteoporosis treatment at least once were categorized as the osteoporosis-related treatment group, and others as the non-osteoporosis-related treatment group. The trends of drug prescriptions and treatment costs in patient groups were evaluated using descriptive statistics. Results: Among all included patients, those aged 45–54 years (40.20%) without osteoporosis treatment and those aged 55–64 years (34.11%) with osteoporosis treatment were the most common. SERM was the most commonly prescribed anticancer drug (29.20%) in the entire patient group, followed by AIs (20.83%). Patients without osteoporosis treatment had the highest prescription rate of SERM (31.48%), and those with osteoporosis treatment had a higher prescription rate of AIs (34.28%). Additionally, SERM and AIs were prescribed most frequently before and after the age of 55 years, respectively, regardless of the presence of treatment. Conclusions: This study found that osteoporosis-related treatment and patient age were associated with anticancer drug prescriptions. The present findings would help clinicians and researchers in the clinical diagnosis and treatment of breast cancer.

Background and Objectives: This retrospective, cross-sectional, and descriptive study used claims data from the Korean Health Insurance Review and Assessment Service (HIRA) between 2010 and 2019 to analyze the trend of surgical service utilization in patients with lumbar spinal stenosis (LSS). Materials and Methods: The national patient sample data provided by the HIRA, which consisted of a 2% sample of the entire Korean population, was used to assess all patients who underwent decompression or fusion surgery at least once in Korea, with LSS as the main diagnosis from January 2010 to December 2019. An in-depth analysis was conducted to examine the utilization of surgical services, taking into account various demographic characteristics of patients, the frequency of claims for different types of surgeries, reoperation rates, the specific types of inpatient care associated with each surgery type, prescribed medications, and the overall expense of healthcare services. Results: A total of 6194 claims and 6074 patients were analyzed. The number of HIRA claims for patients increased from 393 (2010) to 417 (2019) for decompression, and from 230 (2010) to 244 (2019) for fusion. As for the medical expenses of surgery, there was an increase from United States dollar (USD) 867,549.31 (2010) to USD 1,153,078.94 (2019) for decompression and from USD 1,330,440.37 (2010) to USD 1,780,026.48 (2019) for fusion. Decompression accounted for the highest proportion (65.8%) of the first surgeries, but more patients underwent fusion (50.6%) than decompression (49.4%) in the second surgery. Across all sex and age groups, patients who underwent fusion procedures experienced longer hospital stays and incurred higher medical expenses for their inpatient care. Conclusion: The surgical service utilization of patients with LSS and the prescribing rate of opioids and non-opioid analgesics for surgical patients increased in 2019 compared to 2010. From mid-2010 onward, claims for fusion showed a gradual decrease, whereas those for decompression showed a continuously increasing trend. The findings of this study are expected to provide basic research data for clinicians, researchers, and policymakers.

This study aimed to analyze the trends in conservative treatment and associated medical costs for lumbar intervertebral disc disorders with radiculopathy in Korea. This population-based cross-sectional study included patients aged ≥ 20 years with at least one “intervertebral disc disorder with radiculopathy” claim (Korean Standard Classification of Diseases (KCD)-7 code: M511) who sought treatment from tertiary, general, or Korean Medicine hospitals or clinics between 2010 and 2019 and whose data were extracted from the Korean Health Insurance Review and Assessment Service National Patients Sample database. Intervention frequency, ratio, and medical costs, including medication, were analyzed. The number of patients with lumbar intervertebral disc disorders and radiculopathy undergoing conservative treatment increased by >30%, and medical costs increased from USD 3,342,907 to USD 5,600,456 during the 10-year period. The non-surgical treatments mainly used were medication and physiotherapy, and the most commonly prescribed medication was non-opioid analgesics. Meanwhile, the number of patients who used nerve plexus and root and ganglion nerve blocks showed the most significant increase. In conclusion, the number of patients with radiculopathy who received nerve blocks, particularly nerve plexus and root and ganglion nerve blocks, and related expenditure increased, implying a gradual shift in medical decisions from systemic pain reduction to specific and targeted pain treatments. Future studies and clinical practice guidelines may require further inspection of real-world practice to advise optimal treatment choices for an effective treatment plan.

Many updated clinical research results have been published since the Korean Medicine Clinical Practice Guidelines (KMCPGs) for temporomandibular disorders (TMDs) were published in 2018. Therefore, it is necessary to update the existing clinical practice guidelines (CPGs). This study presents updated recommendations for TMD treatment based on current research data published up to February 2020. The draft version of the level of evidence and grade of recommendation was determined through an assessment of the risk of bias and a meta-analysis of selected literature based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The final guidelines were derived using the Delphi method. Eighteen recommendations were derived for eight items of Korean medicine treatment for TMDs. Compared with previous Korean medicine CPGs for TMDs, the grades of seven recommendations, including acupuncture, pharmacopuncture, and Chuna manual therapy, were increased. The grades of the two recommendations have been changed. Six new recommendations were added to fully reflect clinical reality. Acupuncture, pharmacopuncture, and Chuna manual therapy are recommended for TMD patients in clinical practice. Concurrent conventional conservative therapy with Korean medicine or a combination of Korean medicines should be considered in clinical practice in patients with temporomandibular disorders.