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Purpose Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin–stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients.Materials and Methods A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study.Results The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis.Conclusion In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH.

Background: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD’s effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of GCD based on salvianolic acid B content. Methods: The neuroprotective effects of GCD based on the salvianolic acid B content were evaluated by measuring infarct volume 24 h after permanent middle cerebral artery occlusion in an in vivo stroke model. For the experimental group, each GCD was administered immediately before surgery. The control groups were administered distilled water and aspirin (30 mg/kg) in the same way. The salvianolic acid B content in five types of Salviae Miltiorrhizae Radix (two Chinese and three Korean regions) based on different cultivation regions was analyzed by high-performance liquid chromatography. Results: Three samples met the Korean and Chinese Pharmacopeia standards for salvianolic acid B. However, two samples did not. GCDs with high salvianolic acid B showed marked neuroprotective effects compared to the control groups, whereas GCDs with low salvianolic acid B did not. Conclusions: The salvianolic acid B content of Salviae miltiorrhizae Radix affects the neuroprotection effect of GCD. Stable, raw Salviae miltiorrhizae Radix is essential for GCD homogenization.

Background. Kami Guibi-tang (KGT), a traditional Korean herbal medicine is mainly used to treat insomnia and nervousness. Acetylcholinesterase inhibitors (AChEIs) are the main treatments for mild Alzheimer’s disease (AD), a degenerative brain disease. However, currently no drug can fundamentally treat AD or reverse the advanced cognitive decline. This clinical study explored the efficacy and safety of adding KGT to AChEI for cognitive function in mild AD. Methods. This was a pilot study for a larger randomized, double-blind, placebo-controlled trial. Participants between 55–90 years diagnosed with mild AD were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea. They were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary outcome was treatment efficacy, as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D). Changes in SNSB subscores were assessed as secondary outcomes. Safety parameters, including adverse events and abnormalities in blood tests, electrocardiograms, and brain magnetic resonance imaging were also monitored. Results. Between March 2018 and November 2020, seven participants each in the KGT group and the placebo group completed the 24-week trial. There were no significant changes in SNSB-D total or subindex scores for either group ( p = 0.69 and 0.63, respectively), and no significant differences were observed between them ( p = 0.71 ). No adverse events related to KGT were reported. We also compared and analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment (aMCI) using protocol of this study. The aMCI group showed a significant improvement in the total SNSB-D score, especially in the memory domain, compared to the mild AD group ( p = 0.04 and 0.02, respectively). The Korean Mini-Mental State Exam and Korean Instrumental Activities of Daily Living scores also significantly improved in the aMCI group ( p = 0.01 and 0.02, respectively). Conclusions. Compared to placebo, adding KGT to AChEI did not significantly improve cognitive function in SNSB in patients with mild AD. We suggest that KGT would have a positive effect on patients with early stages of cognitive impairment such as aMCI. The findings could assist design larger, longer-term clinical trials of KGT use in elderly patients with mild AD. This study was registered in the Korean Clinical Trial Registry on December 26, 2017, with the CRIS approval number KCT0002904.

Objectives: Parkinson’s disease (PD) patients experience various non-motor symptoms, among which constipation is the second most common after anosmia. However, there are no clear guidelines or effective treatment for constipation in PD.Methods: To investigate the efficacy of Majainhwan (MH) on constipation in patients with PD, we conducted a retrospective chart review study of PD or Parkinsonism patients with constipation who received outpatient or inpatient treatment and whose previous laxatives were replaced by MH from August 2016 to July 2019.Results: In this study, a total of 68 patients’ medical records were reviewed. Among the 44 outpatients with MH treatment, “effective” results were observed in 86.4% patients. Similarly, among the 24 inpatients, “effective” results were noted in 95.8% patients. The adverse effect was "diarrhea" reported in five cases.Conclusion: Based on these findings, we could suggest that MH is relatively safe and may be effective in the treatment of constipation in patients with PD.

The most common definition of postherpetic neuralgia is the presence of pain more than a month after the onset of the eruption of zoster. This case report suggests the effect of Korean medicine on postherpetic neuralgia. An 85-year-old male patient with postherpetic neuralgia was treated with a combination of Korean medical remedies. Kyung Hee Gongjin-dan and Hyangbujapalmul-tang-gagam were applied for 23 days. The Numerical Rating Scale was used to measure pain intensity. The Barthel Index and Beck Depression Inventory were used for the functional assessment and depression evaluation, respectively. After treatment, the patient’s pain intensity decreased. Additionally, the patient’s independence increased during activity, and the severity of their depression decreased. Thus, this case suggests that a combination of Korean medicine treatments might be effective for postherpetic neuralgia. In particular, it shows that Kyung Hee Gongjin-dan and Hyangbujapalmul-tang-gagam can be therapeutic options in the treatment of postherpetic neuralgia.

This case report determines the effects of Korean medicine treatment on a pontine hemorrhage with a cavernous malformation. In this study, Korean medicine treatments, such as herbal medicine, acupuncture, electro-acupuncture, and moxibustion, were administered for 30 days. During the hospitalization period, evaluations were performed using the Scott and Kraft Scale, eye movement, 9-gaze photography, the House-Brackmann grading system, and Yanagihara’s unweighted grading system on days 1, 12, and 30. The Scott and Kraft Scale increased from -4 to -2, while eye movement increased from 43.1% to 72.3%. The House-Brackmann grading system improved from 4 to 2, and Yanagihara’s unweighted grading system increased from 13 to 31. We also discovered that the movement of the left eye was improved by 9-gaze photography. Our findings suggest that Korean medicine treatment has potential effects on esotropia and facial palsy caused by a pontine hemorrhage with a cavernous malformation.

Objectives: To investigate the effects of acupuncture at GV20 and EX-HN1 on cerebral blood flow (CBF) velocity and cerebrovascular reactivity (CVR) in the middle cerebral arteries (MCA) and anterior cerebral arteries (ACA) and to compare the effects to acupuncture at GV20.Methods: The study was a randomized, crossover trial that included 10 healthy men aged 20 to 29 years who underwent acupuncture treatment four times with a washout period of one week. The CBF velocity and CVR were measured by transcranial Doppler sonography (TCD) on both MCAs at the first and second visits, and both ACAs at the third and fourth visits. Participants were randomly assigned to one of two groups (A and B) before the first and third visits. Group A received two phases of acupuncture intervention at a single GV20 point and a combination of GV20 and EX-HN1 acupoints. Group B received the same interventions, but in the reverse order.Results: The increase in CO2 reactivity was significantly higher for the combination acupoints of GV20 and EX-HN1 than for the GV20 single acupoint in both MCAs (Right: 136 to 178, p=0.017; Left: 127 to 191, p=0.017) and ACAs (Right: 133 to 158, p=0.013; Left: 122 to 168, p=0.025). No significant change was noted in the corrected velocity at PETCO2 40 mmHg, blood pressure, or heart rate.Conclusions: The findings suggest that improvement of the CBF in the MCA and ACA after GV20 acupuncture increases when acupuncture is also performed at EX-HN1. These results clinically support the combined use of EX-HN1 and GV20 to treat disorders of MCA and ACA circulation.

Objectives: This study was designed to investigate the clinical effectiveness of Ikgibohyeol-tang(Yìqìbǔxuè-tāng) granules and Deer antler granules on fatigue symptoms.Methods: This is a 39-patient case series from a retrospective chart review of outpatients who were treated with Ikgibohyeol-tang granules and Deer antler granules at a Kyung Hee University Korean Medicine Hospital (Seoul) between 1st, January 2015 to 1st, August 2021. We reviewed the patients who complained of fatigue and analyzed changes in the degree of discomfort with fatigue and accompanying symptoms and HRV (Heart Rate Variability) score before and after treatment.Results: After taking Ikgibohyeol-tang granules and Deer antler granules, the degree of discomfort with fatigue and accompanying symptoms decreased significantly compared to before taking them. After treatment, Autonomic nervous system activity, Stress resistance, Heart Stability increased, and Stress index, Degree of fatigue decreased significantly.Conclusions: This study showed subjective symptoms and objective indicator (HRV score) were improved by taking Ikgibohyeol-tang granules and Deer antler granules.

Objectives: Bee venom (BV) is a widely used therapy in Traditional East Asian Medicine (TEAM). We previously reported that BV was clinically effective for treating Parkinson’s disease, that phospholipase A2 (PLA2) was the main component of BV, and that it induced regulatory T cells (Tregs) by binding CD206 on dendritic cells (DCs). Therefore, we aimed to reconfirm our findings in human blood samples and investigate the relationship between CD206+ DCs and clinical syndrome differentiation in TEAM.Methods: We surveyed 100 subjects with questionnaires on cold-heat patternization and obtained their blood samples. The obtained human peripheral blood monocytes (hPBMCs) were washed with phosphate-buffered saline (PBS). After resuspension with ex vivo media, numbers of cells were counted. Tregs were counted after culturing the samples in a 37℃ CO2 incubator for 72 h.Results: We divided the subjects into a relatively high CD206+ group or a relatively low CD206+ group. The heat factor scores of high CD206+ group were significantly higher than that of low CD206+ group (high vs low: 239.2 ± 54.1 vs 208.4 ± 55.1, p=0.023). After culturing with PLA2, Tregs increased in the high CD206+ group but decreased in the low CD206+ group.Conclusion: In this study, we reconfirm that CD206+ DCs induced Treg differentiation by incubating human blood samples with PLA2 and that they showed an association with syndrome differentiation, especially with heat patterns, in TEAM. A heat pattern in TEAM might be one indication for PLA2 therapy because its score was elevated in the high CD206+ group.

Objectives: This study examined the effectiveness of Korean medical treatment for two patients complaining of discomfort after receiving Pfizer COVID-19 vaccine.Methods: The patients were hospitalized for 50 days and 12 days, respectively. They were treated with herbal medicine, acupuncture, electroacupuncture, and moxibustion. We used the Numerical Rating Scale (NRS) on numbness in extremities and headache, Manual Muscle Testing Grading System (MMT), Criteria for Sweating Categorization, and 36-Item Short Form Health Survey (SF-36) to evaluate the clinical effects of the treatment.Results: In Case 1, headache improved from peak NRS 9 and average NRS 7 on admission day to both NRS 3 on discharge. The SF-36 score was also increased, suggesting that the quality of life was improved. In Case 2, numbness in the extremities improved from NRS 8 on the day before admission to NRS 2 on discharge, and general condition also improved.Conclusions: This study suggests that Korean medicine can be an effective treatment for patients who experience long-lasting discomfort after being vaccinated with COVID-19, but with no abnormal findings in the examination.

This work reports the case of a middle cerebral artery infarction patient with hyperhidrosis and left upper extremity paresthesia whose condition improved following Korean medicine treatment. The patient was hospitalized for 10 days and treated with herbal medicine, mainly Hwanggigyeji-tang, and acupuncture, electroacupuncture, and moxibustion. The hyperhidrosis was clinically classified and the patient’s subjective discomfort in this regard was also checked. A subjective percentage of strength and sensation in the left extremity was evaluated to assess the clinical effects of the treatment. After treatment, the hyperhidrosis classification improved from Grade 3 to Grade 0, and the patient’s subjective discomfort was greatly improved and continued for the two weeks after discharge. In addition, subjective strength and sensation improved by 20% and 5%, respectively, compared to time of admission. These results suggest that Korean medicine is effective in treating paresthesia after stroke and long-lasting hyperhidrosis.

Objective: The purpose of this case study is to report the effectiveness of Baliao acupoints electro-acupuncture treatment on a neurogenic overactive bladder induced by stroke.Method: A patient suffering from middle cerebral artery infarction was diagnosed with a neurogenic overactive bladder and treated by Korean medicine, including electro-acupuncture on Baliao acupoints six times per week. The evaluation was performed by monitoring urinary frequency and using the Korean versions of the Overactive Bladder Symptom Score (OABSS) and Urinary Incontinence Quality of Life (I-QoL).Results: After 27 days of electro-acupuncture treatment, the OABSS score improved from 6 to 3. The I-QoL total score improved from 60 to 87. The patient also showed a decrease in nocturia frequency.Conclusion: This case suggests that electro-acupuncture on Baliao acupoints can be effective for overactive bladders due to supra-pontine lesions.

Objectives: This study aimed to examine the safety, effects on proliferation of hair papilla cells, and anti-inflammatory and antioxidant mechanisms of Artemisia sieversiana Ehrh. ex Willd. (AS) extract.Methods: Safety tests through purity testing, acute toxicity tests, and repeated toxicity tests were performed using AS extract (ASE) which had been dried for over two years. Cell culture and proliferation tests were conducted; VEGF (vascular endothelial growth factor), bFGF (basic fibroblast growth factor), and EGF (epidermal growth factor) and protein expression analyses were performed for mechanistic evaluation; and inhibitory effects of ASE on the RNA expression of testosterone, 5α-reductase, and aromatase was assessed. The anti-inflammatory and antioxidant efficacy of ASE was confirmed by measuring the levels of nitric oxide, inflammatory mediators (TNF-α and PGE2), inflammatory cytokines (IL-1β, IL-6, and IL-8), and chemokine MCP-1.Results: The safety of ASE was confirmed. The mechanism of cell proliferation in human hair follicle dermal papilla cells involved the promotion of VEGF, bFGF, and EGF expression. ASE decreased mRNA expression of testosterone, 5α-reductase, and aromatase-1 in a concentration-dependent manner. PGE2 and TNF-α production by inflammatory mediators was also significantly decreased in a concentration-dependent manner, and inflammatory cytokine and chemokine expression was inhibited.Conclusions: ASE is suggested to promote papillary cell growth at the cellular level, to suppress expression of various enzymes involved in hair cycle and cell death, and to inhibit hair loss through anti-androgen, anti-inflammatory, and antioxidant effects.

This study examined the effectiveness of Korean medical treatment in a patient with persistent drug-induced parkinsonism after drug discontinuation. The changes in symptoms were assessed using the unified parkinson's disease rating scale (UPDRS), postural instability-gait disturbance (PIGD) score, and the 20 m gait time and steps. After 22 days of hospitalization, the UPDRS, PIGD score, and 20 m gait time and steps showed clinically significant improvement. The improvement persisted after discharge. This study indicated that Korean medical treatment could be an effective alternative therapy for treating persistent drug-induced parkinsonism after drug discontinuation.

Poststroke fatigue (PSF) is reported to occur in 30%–72% of all patients with stroke. PSF not only is a symptom of stroke but has also been reported to adversely affect the prognosis of patients with stroke. However, no treatment has had a significant effect on PSF. In East Asian countries, several herbal medicines have been used to treat stroke, with Buyang Huanwu Tang (BHT) being the most common. This review aimed to evaluate the efficacy and safety of BHT for PSF. A literature search was conducted on MEDLINE, CENTRAL, Scopus, CiNii, CNKI, OASIS, NDSL, and KTKP databases for randomized controlled trials that evaluated the effects and safety of BHT on PSF. Six studies (n = 427) were included. The overall methodological quality of these studies was relatively low. In the adjunctive BHT group, the meta-analysis indicated statistically significant improvements in the Fatigue Severity Scale score (mean difference −1.49, 95% CI [−2.25, −0.73]) and total clinical efficacy rate (risk ratio 0.11, 95% CI [0.03, 0.41]) compared to those in the nonherbal group. Adverse events were only reported in one study, and no serious adverse events occurred. BHT administration might be effective in the treatment of PSF. We were unable to draw definitive conclusions owing to the limitations of the included studies. The trial is registered with CRD42019130178 in PROSPERO.

Objectives: The LI11 (Quchi) acupuncture point has always been included in the Seven acupoints for stroke; however, additional LI11 acupuncture research is needed. In this study, the effect of LI11 acupuncture on cerebral blood flow of the anterior cerebral arteries (ACA) and middle cerebral arteries (MCA) was investigated.Method: This study included 10 healthy young male subjects. Cerebral blood flow velocity and cerebrovascular reactivity were measured using transcranial Doppler sonography. Changes in hyperventilation-induced carbon dioxide (CO2) reactivity and modified ACA and MCA blood flow velocity at 40 mmHg (CV40), blood pressure, and heart rate were observed before and after LI11 acupuncture treatment.Results: A statistically significant increase in contralateral anterior cerebral artery CO2 reactivity (p=0.036) and decrease in contralateral middle cerebral artery CV40 (p=0.047) were observed. No significant difference in mean blood pressure was shown. A statistically significant increase in heart rate occurred after LI11 acupuncture; however, it was not clinically significant as there were negligible changes in the heart rhythm.Conclusions: LI11 acupuncture treatment could improve cerebral blood flow velocity. These results might be explained by regulating endothelium-dependent vessel dilation in the anterior cerebral artery region.Trial registration: This trial has been registered with Clinical Research Information Service, a service of the Korea Centers for Disease Control and Prevention: KCT0004494 (retrospectively registered). https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=15359

Objectives: This study considered the effectiveness of Korean medicine for the treatment of eyelid edema post craniotomy.Methods: The patient was diagnosed with Taeumin-one of the four constitution types in Korean medicine-and treated with herbal medicines: Cheongsimyeunja-tang, Chungpyesagan-tang, and Hwangryunhaedok-tang pharmacoacupuncture treatment. The severity of eyelid edema was assessed using Kara and Gokalan’s scale, daily imaging of the patient’s eyelids, and the ratio of the length of the left eye to that of the right.Results: Following treatment, the Kara and Gokalan score decreased from 3 to 0. The changes in the ratios were 29% and 50%, respectively. The visual field defect due to edema in the left eye was also repaired.Conclusion: This study suggests that Korean medical treatment could be an effective option for treating eyelid edema following craniotomy.

Objective: This study investigated the effectiveness of bee venom acupuncture for a diabetic neuropathy patient.Methods: A diabetic neuropathy patient received twenty-one bee venom acupuncture treatments for a total of 99 days. The Neuropathy Pain Scale (NPS) was used to evaluate the weekly peak pain during the treatment period.Results: After the treatments, the NPS scores improved, and the frequencies of peak pain decreased.Conclusions: This clinical case indicates that bee venom acupuncture combined with Korean medicine may be effective for treating diabetic neuropathy patients.

Objective: This study examined the effectiveness of Korean medical treatment for an 81-year-old female patient with pontine infarction complaining of discomfort in both legs.Methods: The patient was hospitalized for 45 days and treated with herbal medicine (mainly Bohyulanshin-tang [補血安神湯], pharmacopuncture, acupuncture, electroacupuncture, and moxibustion). We used the International Restless Legs Scale (IRLS) and Numerical Rating Scale (NRS) and checked the duration of the symptoms to evaluate the clinical effects of the treatment.Results: After 45 days of hospitalization, the IRLS score decreased from 33 to 19, with the lowest score of 8 recorded on the twenty-seventh day after discharge. The NRS score and the duration of symptoms also improved, and the treatment effect continued following discharge.Conclusions: This study suggests that Korean medical treatment may be effective for the treatment of restless legs.

Purpose To evaluate the effectiveness of Kami Guibi‐tang (KGT) in the treatment of mild cognitive impairment (MCI) using magnetic resonance imaging (MRI) on brain metabolites, neurotransmitter, and cerebral blood flow (CBF). Methods We randomly allocated a total of 30 MCI patients to a KGT (N = 16) or a placebo (N = 14) group and performed MRI scans before and after 24 weeks of treatment. The participants underwent brain magnetic resonance spectroscopy and MRI scans to obtain brain metabolites using Point‐RESolved Spectroscopy (PRESS) single‐voxel spectroscopy, gamma‐aminobutyric acid (GABA) neurotransmitter using Mescher–Garwood PRESS, and CBF using pseudocontinuous arterial spin labeling sequences using a 3.0 Tesla MRI system. We analyzed metabolite and neurotransmitter levels and CBF using repeated‐measure analysis of variance to evaluate between‐subject group effect, within‐subject treatment condition effect, and interaction of group by condition (group x condition). Results The GABA+/creatine (Cr) ratio values were not significantly different between the before and after treatment conditions. The glutamate complex/Cr ratio difference before and after treatment was lower in the KGT group than in the placebo group, but was not statistically significant (p = 0.077). The result of region of interest–based CBF measurement showed that CBF values were significantly lower after treatment at Cluster 2 for the KGT group (p = 0.003) and the placebo group (p = 0.011), at hippocampus for the KGT group (p = 0.004) and the placebo group (p = 0.008), and at the fusiform gyrus for the KGT group (p = 0.002). Furthermore, the absolute CBF difference before and after treatment in the fusiform gyrus was significantly lower in the KGT group than in the placebo group (p = 0.024). Conclusions Although a KGT treatment of 24 weeks showed some significant impact on the level of CBF, the Korean version of the mini‐mental state examination score was not significantly different between before and after treatment conditions, indicating that there was no memory function improvement after treatment in amnestic MCI patients. Therefore, further studies should be performed with a relatively larger population and extending the duration of the KGT treatment.

ObjectivesParkinson's disease (PD) is a neurodegenerative disease in which patients are suffering various symptoms. Previous experimental studies suggested that herbal medicine Ukgansan (UGS) could be beneficial for PD. The aim of this pilot clinical trial was to evaluate the efficacy of UGS for improving clinical symptoms in patients with PD.MethodsSixty patients with idiopathic PD were randomly assigned to receive either UGS plus acupuncture or acupuncture alone for 6 weeks. During the trial, all anti-parkinsonian medications were maintained. Subjects were evaluated for various clinical assessments of PD, including the Movement Disorder Society-Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39), until 12 weeks.ResultsIn MDS-UPDRS between the groups, no significant time x group interaction was found. In the subgroup analysis of participants with anxiety, a significant time x group interaction was found in the PDQ-39 domain of mobility (P = 0.007), activities of daily living (P = 0.042), and the PDQ-39 summary index (P = 0.048). In addition, post-hoc analysis in participants with anxiety showed a significant decrease in the domains of mobility (P = 0.001) and activities of daily living (P = 0.013) at week 7. There were no adverse events associated with UGS.ConclusionThe additional administration of UGS has the potential to significantly improve the quality of life of PD patients with anxiety. In order to create more definitive evidence, clinical trials with more rigorous methodologies should be conducted in future.Clinical trial registrationhttp://cris.nih.go.kr, identifier: KCT0003444.