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Purpose: We analyzed the characteristics of patients with refractive accommodative esotropia (RAET) who required glasses for stable alignment after a myopic shift.Methods: We retrospectively analyzed the medical records of patients diagnosed with RAET at the initial visit, and who had developed a myopic shift in both eyes over the 5-year follow-up period. To evaluate clinical factors associated with the persistence of esotropia after myopia, the enrolled patients were divided into two groups; patients with RAET who needed glasses for stable alignment after a myopic shift (unstable group) and patients with RAET whose esotropia resolved after a myopic shift (stable group).Results: A total of 55 patients met the inclusion criteria. The mean follow-up period was 13.8 ± 5.7 years (5-27 years). Spherical equivalent (SE) refractive errors at the initial visit were +3.1 ± 1.6 diopters (D) (+1.00 to +7.25 D) and -1.5 ± 0.9 D (-4.38 to -0.5 D) at the last visit. Of the 55 RAET patients, 24 were included in the unstable group and 31 were included in the stable group. No significant differences in gender, age at diagnosis, SE refractive error, or angle of esotropia with glasses were observed between the two groups. However, significantly more patients failed the Lang I test or had anisometropia over 1.5 D at the last visit, and the duration between the onset of esotropia and prescribing glasses was significantly longer in the unstable group than in the stable group.Conclusions: Glasses may be needed for stable alignment even after a myopic shift in RAET patients with long durations of misalignment, poor stereopsis, and anisometropia.

In treating constipation, pharmacotherapy is known to cause various adverse drug reactions. This therapy includes the use of laxatives, which may not be safe for the treatment of elderly patients. Traditional Korean Medicine has been widely used for a long time to treat various gastrointestinal symptoms, such as constipation. A 70-year-old male patient had no history of constipation, but complained of constipation with abdominal distention and inability to pass stool occurring after the initiation of pharmacotherapy after his stroke. The patient was diagnosed with post-stroke constipation that lasted for more than 1 month. Acupuncture, electroacupuncture, and moxibustion were performed for 3 weeks. Each session was performed for 15 min. In addition, herbal medications were administered for 15 days. As a result, the Numeric Rating Scale score for abdominal distention and inability to pass stool reduced and most of the constipation-related discomfort improved. This case report demonstrates that integrative traditional Korean medicine can be effective for the treatment of post-stroke constipation in elderly patients.

Balance in time perspectives has been gaining interest in South Korea since it is considered as a precondition for an individual’s mental health and happiness. However, measuring the time perspective with the Swedish Zimbardo Time Perspective Inventory (S-ZTPI) – which consists of 64 items, including a Future Negative dimension – creates difficulties in practical use due to its length. The aim of the present study is to develop and validate a South Korean short version of the Swedish Zimbardo Time Perspective Inventory (KS-S-ZTPI) in a total sample of 725 adults in South Korea. The factor structure of this inventory was investigated, and the validity and reliability of the inventory were analyzed. Exploratory Factor Analysis (EFA) was first performed along with a Confirmatory Factor Analysis (CFA) to identify internal consistency. The results showed that the KS-S-ZTPI, containing 16 items, supported a four-factor model: “Past Negative,” “Past Positive,” “Present Hedonistic,” and “Future” time perspectives. Finally, the correlations with depression, anxiety, life satisfaction, and self-esteem were examined to evaluate convergent and discriminant validity. The results showed that “Past Negative” and “Present Hedonistic” time perspectives were negatively associated with self-esteem but positively associated with depression and anxiety. On the other hand, “Past Positive” and “Future” time perspectives were positively associated with self-esteem and life satisfaction, but negatively associated with depression and anxiety. Considering these results, implications and suggestions are discussed.

It would be a very challenging task for mobile robot to track a person walking ahead on hilly terrains with a 2D lidar sensor instead of a 3D lidar or a rotating 2D lidar sensor. But it is clear that the 2D lidar based method is much more efficient in terms of computational costs and sensor cost only. For successful leader-following of the mobile robot with the 2D lidar sensor on such hilly roads, it is necessary to develop a classifier capable of recognizing a specific body part of the leader differently from other parts. In this study, the Mahalanobis distance kernel based on two features extracted from the leader’s torso profiles is used to construct the elliptical decision boundaries for the classification problem. In addition, based on that classifier, the roll and pitch angle of the 2D lidar sensor are controlled to continuously track the leader’s body part and to estimate the relative distance between the leader and the robot. As a result, even when the leader walks along paths with flat-to-hill transitions in day and night, the mobile robot successfully follows the leader with 80 % detection rate by stable pitching not exceed 1° of the 2D lidar sensor for keeping the torso inside its field of view. The proposed approach will be useful to improve the performances of multi-sensor based leader detection system using not only lidar sensor but also vision sensor with switching control scheme.

AIM: To compare the changes in excyclotorsion after inferior oblique (IO) recession in patients with primary and secondary inferior oblique overaction (IOOA). METHODS: We retrospectively analyzed the data obtained from patients with IOOA who underwent graded IO recession. The patients were followed up for at least 3mo after surgery. Fundus photographs were taken pre- and postoperatively, and the sum of the angles of torsion in both eyes was used to analyze changes in excyclotorsion. Patients were divided into two groups: those diagnosed with primary IOOA were enrolled in the 1'IOOA group, and those diagnosed with secondary IOOA caused by superior oblique palsy (SOP) were enrolled in the 2'IOOA group. Excyclotorsion before and after surgery were compared between the two groups. RESULTS: A total of 78 patients were enrolled in this study: 34 eyes in the 1'IOOA group and 44 eyes in the 2'IOOA group. In the 78 patients, torsional angle significantly decreased from 15.31°±7.40° to 12.11°±6.53° after IO recession (P

This review aimed to comprehensively assess the efficacy and safety of oral East Asian herbal medicine (EAHM) for overall peripheral neuropathy (PN). In addition, an Apriori algorithm-based association rule analysis was performed to identify the core herb combination, thereby further generating useful hypotheses for subsequent drug discovery. A total of 10 databases were searched electronically from inception to July 2021. Randomized clinical trials (RCTs) comparing EAHM with conventional analgesic medication or usual care for managing PN were included. The RCT quality was appraised using RoB 2.0, and the random effects model was used to calculate the effect sizes of the included RCTs. The overall quality of evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation. By analyzing the constituent herb data, the potential association rules of core herb combinations were explored. A total of 67 RCTs involving 5753 patients were included in this systematic review. In a meta-analysis, EAHM monotherapy and combined EAHM and western medicine therapy demonstrated substantially improved sensory nerve conduction velocity, motor nerve conduction velocity, and response rate. Moreover, EAHM significantly improved the incidence rate, pain intensity, Toronto clinical scoring system, and Michigan diabetic neuropathy score. The evidence grade was moderate to low due to the substantial heterogeneity among the studies. Nine association rules were identified by performing the association rule analysis on the extraction data of 156 EAHM herbs. Therefore, the constituents of the herb combinations with consistent association rules were Astragali Radix, Cinnamomi Ramulus, and Spatholobi Calulis. This meta-analysis supports the hypothesis that EAHM monotherapy and combined therapy may be beneficial for PN patients, and follow-up research should be conducted to confirm the precise action target of the core herb.

Background: Peripheral neuropathy (PN) is one of the most common medical problems encountered. Since the pathophysiology and symptom manifestation characteristics of PN are very diverse, it is difficult to provide an appropriate treatment. East Asian herbal medicine (EAHM) has long contributed to the treatment of neurological and pain disorders. The goal of this systematic review is to measure the efficacy and safety of EAHM for PN and to identify core herb patterns. In order to derive a more conservative result, a random effect model will be applied regardless of the significance of heterogeneity. Methods: We will search 10 databases to identify suitable studies. There will be no restrictions regarding language or publication date. Primary outcomes will be nerve conduction velocity and response rate. Secondary outcomes will be any objective tool that can measure the efficacy of EAHM, and adverse events will be included. We will perform a meta-analysis of trials with the same intervention and outcome with comparator in a similar population. Meanwhile, in order to explore significant potential correlation in herb preparation, association rule analysis based on the Apriori algorithm will be performed on the collected composition data of herbal medicines. Results: This study will provide scientific evidence for the treatment of EAHM for PN. Conclusions: Based on the results of this review, it is expected that the efficacy and safety of EAHM for PN can be confirmed. In addition, through additional analysis using data mining techniques, it will be possible to present a core herb pattern related to this research topic.

During constipation, indigestible foods, such as probiotics, prebiotics, and dietary fiber, may improve the bowel environment and activity. In this randomized, double-blind, and placebo-controlled study, the effects of ID-HWS1000, composed of

Oleic acid (OA) is released from brain phospholipids after cerebral ischaemia; however, its role in ischaemic injury remains unknown. We hypothesised that OA has neuroprotective effects after cerebral ischaemia, which may be exerted through peroxisome proliferator-activated receptor gamma (PPAR-γ) activation, since OA is an endogenous ligand of PPAR-γ. The effects of OA administration were evaluated in rodent models of middle cerebral artery occlusion (MCAO), photothrombosis, and four-vessel occlusion (4-VO). We determined the time window of therapeutic opportunity and examined the ability of the PPAR-γ antagonist GW9662 to reverse OA’s protective effects after MCAO. We found that OA administration decreased the MCAO-induced infarct volume and functional deficits, photothrombosis-induced infarct volume, and 4-VO-induced hippocampal neuronal death. Additionally, OA was highly efficacious when administered up to 3 h after MCAO. Pre-treatment with GW9662 abolished the inhibitory effects of OA on the infarct volume and immunoreactivity of key inflammatory mediators in the ischaemic cortex. Our results indicate that OA has neuroprotective effects against transient and permanent focal cerebral ischaemia, as well as global cerebral ischaemia. It may have therapeutic value for the ischaemic stroke treatment with a clinically feasible therapeutic window. The OA-mediated neuroprotection might be attributable to its anti-inflammatory actions through PPAR-γ activation.

Musk of musk deer has been one of the most precious traditional medicinal materials for treatment of stroke, but trading is prohibited. Musk of muskrat, Ondatra zibethicus, is an accessible substitute for musk of musk deer. However, neuroprotective effects of the musk of muskrat on stroke model are so far unclear. Aim of the study is to determine neuroprotective effects of the musk of muskrat on focal cerebral ischemia. The protective effects against focal cerebral ischemia were evaluated using a model of middle cerebral artery occlusion (90-minute occlusion followed by 24-hour reperfusion). Musk of muskrat was collected from scent bag of muskrat and orally administered at doses of 100 and 300 mg/kg twice at times of 0 and 90 min after occlusion. The effects on sensorimotor dysfunction were investigated by using balance beam test and rotarod test after brain ischemia. The expression of cyclooxygenase-2 (COX-2) was investigated by immunohistochemistry. Oral administration of musk at 300 mg/kg significantly reduced (p

This paper describes the optimal design of a 3-DOF redundant planar parallel kinematic mechanism (PKM) based finishing cut stage to improve the surface roughness of FDM 3D printed sculptures. First, to obtain task-optimized and singularity minimum workspace of the redundant PKM, a weighted grid map based design optimization was applied for a task-optimized workspace without considering the redundancy. For the singularity minimum workspace, the isotropy and manipulability of the end effector of the PKM were carefully modeled under the previously obtained redundancy for optimality. It was confirmed that the workspace size increased by 81.4%, and the internal singularity significantly decreased. To estimate the maximum rated torque and torsional stiffness of all active joints and prevent an undesired end effector displacement of more than 200 μμm, a kinematic stiffness model composed of active and passive kinematic stiffness was derived from the virtual work theorem, and the displacement characteristic at the end effector was examined by applying the reaction force for the PLA surface finishing as an external force acting at the end effector. It was confirmed that the displacement of the end effector of a 1-DOF redundant PKM was not only less than 200 μμm but also decreased from 40.9% to 67.4% compared to a nonredundant actuation.

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions. We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1&beta, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1&beta, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA.

Background: This systematic review and meta-analysis aim to assess the effectiveness of Dangguijagyag-san (DJS) for primary dysmenorrhea (PD) and to update the previous reviews. Methods: We searched for randomized controlled trials (RCTs) of DJS for PD from inception to April 2019. The search databases were the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Oriental Medicine Advanced Searching Integrated System, Korean Traditional Knowledge Portal, Korean Medical Database, National Digital Science Library, and the China National Knowledge Infrastructure. The selection of studies, the extraction of data, and the quality assessment with risk of bias tool were performed by 2 authors independently. To analyze the data, the meta-analysis was conducted and qualitative analysis was also performed. Results: Total 2766 studies were identified, and 14 RCTs were enrolled in this review. According to the type of interventions, the analysis was performed in 4 groups. In comparison to western medication, DJS showed a higher total effective rate (TER) (RR 1.16, 95% CI 1.08–1.24) and a higher effect in reducing the pain (MD = −0.86, 95% CI −1.56–−0.16). Compared with placebo, DJS was superior to placebo in reducing pain (MD = −1.1, 95% CI −2.04 –−0.16) and also in reducing the consumption of the rescue medication during menstrual period (MD = −2.3, 95% CI −3.58–−1.02). Compared with other herbal medicines, the subgroup analysis showed that DJS applied with PD of differentiated patterns had a higher total effective rate (TER) (RR 1.21, 95% CI 1.03–1.43, P=.02). DJS with moxibustion as an adjuvant therapy was also more effective than western medication (RR 1.47, 95% CI 1.23–1.76). Conclusion: DJS may be effective for the treatment of PD. However, the quality of the evidence is relatively low, so larger-scale and well-designed RCTs are needed to confirm the effects of DJS. Systematic review registration: PROSPERO registration number is CRD42019130768.

Classification of foot&ndash, ground contact phases, as well as the swing phase is essential in biomechanics domains where lower-limb motion analysis is required, this analysis is used for lower-limb rehabilitation, walking gait analysis and improvement, and exoskeleton motion capture. In this study, sliding-window label overlapping of time-series wearable motion data in training dataset acquisition is proposed to accurately detect foot&ndash, ground contact phases, which are composed of 3 sub-phases as well as the swing phase, at a frequency of 100 Hz with a convolutional neural network (CNN) architecture. We not only succeeded in developing a real-time CNN model for learning and obtaining a test accuracy of 99.8% or higher, but also confirmed that its validation accuracy was close to 85%.

Background Adverse events of endocrine therapy reduce the breast cancer patient's quality of life and adversely affect treatment compliance. Method A 50-year-old breast cancer patient complained of several symptoms such as hot flush, hyperhidrosis, urinary frequency, and depression. These symptoms occurred after taking tamoxifen. The adverse events induced by tamoxifen were assessed using both World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality categories and the Naranjo probability scale. Traditional Korean herbal medicine was used to treat vasomotor symptoms and vulvovaginal symptoms. And acupuncture was used to manage musculoskeletal symptoms. Results As a result of traditional Korean medicine treatment for 25 days, symptoms and quality of life improved significantly, and improvement was estimated in the Menopause Rating Scale and Menopause-Specific Quality of Life. Conclusion This case report suggests that traditional Korean medicine interventions might have improved the adverse events of tamoxifen in breast cancer patients.

Osteoarthritis (OA), being the most prominent degenerative joint disease is affecting millions of elderly people worldwide. Although Andrographis paniculata is an ethnic medicine with a long history of being used as analgesic agent, no study using a monosodium iodoacetate (MIA) model has investigated its potential activities against OA. In this study, experimental OA was induced in rats with a knee injection of MIA, which represents the pathological characteristics of OA in humans. A. paniculata extract (APE) substantially reversed the loss of hind limb weight-bearing and the cartilage damage resulted from the OA induction in rats. Additionally, the levels of serum pro-inflammatory cytokines, such as IL-1&beta, IL-6, and TNF-&alpha, as well as the concentration of matrix metalloproteinases, including MMP-1, MMP-3, MMP-8, and MMP-13 were decreased by APE administration. Acetic acid-induced writhing responses in mice which quantitatively measure pain were significantly reduced by APE. In vitro, APE inhibited the generation of NO and downregulated the expression of IL-1&beta, IL-6, COX-2, and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The above results suggest the potential use APE as a therapeutic agent against OA.

Osteoarthritis (OA) is a chronic inflammatory joint disease that affects millions of elderly people around the world. The conventional treatments for OA consisting of nonsteroidal anti-inflammatory drugs and steroid have negative health consequences, such as gastrointestinal, renal, and cardiac diseases. This study has evaluated the Commiphora extract mixture (HT083) on OA progression as an alternative treatment in animal models. The root of P. lactiflora and the gum resin of C. myrrha have been in use as traditional medicines against many health problems including bone disorders since ancient time. The extracts of P. lactiflora root and C. myrrha gum resin were mixed as 3:1 for their optimal effects. Male Sprague-Dawley rats were injected with monosodium iodoacetate (MIA) into the knee joints to induce the symptoms identical to human OA. HT083 substantially prevented the loss of weight-bearing inflicted with MIA in rats. The MIA-induced cartilage erosion as well as the subchondral bone damage in the rats was also reversed. In addition, the increase of serum IL-1&beta, concentration, a crucial pro-inflammatory cytokine involved in OA progression was countered by HT083. Furthermore, HT083 significantly reduced the acetic acid-induced writhing response in mice. In vitro, HT083 has shown potent anti-inflammatory activities by inhibiting the production of NO and suppressing the interleukin -1&beta, interleukin -6, cyclooxygenase-2, and inducible nitric oxide synthase expression in lipopolysaccharide -stimulated RAW 264.7 cells. Given its potent analgesic and anti-inflammatory activities in MIA rats and acetic acid-induced writhing in mice, HT083 should be further studied in order to explain its mechanism of actions in alleviating OA pain and inflammation.

Introduction Rapid globalization has produced a growing demand for the chronic care management of overseas populations living in medically underserved areas. This study investigated the utilization pattern of telehealth counselling among overseas Koreans with high blood pressure, and evaluated the relationships between mobile self-monitoring application and blood pressure reduction. Methods A global chronic management programme consisting of lifestyle modification and self-monitoring blood pressure was launched to provide a telehealth counselling service for Koreans with high blood pressure living in Vietnam from August 2016 to December 2017. During the first telehealth session, doctors educated patients on lifestyle modifications using a mobile self-monitoring application and checked the change of blood pressure in a follow-up telehealth visit. We examined utilization patterns and compared the blood pressure change among the mobile self-monitoring group versus the control group using Wilcoxon signed rank tests. Results A total of 234 patients with systolic blood pressure of more than 130 mmHg or diastolic blood pressure of more than 80 mmHg were registered, installed the mobile app and were provided with automated blood pressure devices with the telehealth counselling service by Korean doctors. A follow-up telehealth counselling session was provided at three months. Only 15% (36/234) received two or more telehealth counselling sessions. Significant differences were found in the mean change of systolic blood pressure at three months in the monitoring group and the non-monitoring group (−16.0 vs. −5.7, p = 0.008). Discussion In this unique telehealth study, a mobile self-monitoring application was associated with significantly reducing systolic blood pressure levels in three months. Encouraging patients via a mobile application that includes a self-monitoring function might have the potential for self-managing chronic diseases, especially in resource-limited environments.

Background To evaluate the effects of Huang Bai (Phellodendron amurense) on growth and maturation in adolescent female rats. Methods Female Sprague–Dawley rats (28 days old; n = 72) were divided into six daily treatment groups: control (distilled water), Huang Bai (100 and 300 mg/kg), recombinant human GH (rhGH; 20 μg/kg), estradiol (1 μg/kg), and triptorelin (100 μg). Body weight, food intake, and vaginal opening were measured daily from postnatal day (PND) 28 to PND 43. Tetracycline (20 mg/kg) was injected on PND 41. After sacrifice on PND 43, the ovaries and uterus were weighed, and the tibias were fixed in 4% paraformaldehyde. Decalcified and dehydrated tibias were sectioned at a thickness of 40 μm, and sectioned tissues were examined with a fluorescence microscope. Insulin-like growth factor (IGF)-1 and bone morphogenetic protein (BMP)-2 were detected using immunohistochemistry. Results Relative to controls, body weight was higher in the triptorelin group. Bone growth rate increased in the Huang Bai 100 mg/kg (354.00 ± 31.1 μm/day), rhGH (367.10 ± 27.11 μm/day), and triptorelin (374.50 ± 25.37 μm/day) groups. Expression of IGF-1 and BMP-2 in the hypertrophic zone was higher in all experimental groups. Vaginal opening occurred earlier in the estradiol group (PND 33.58 ± 1.62) than in controls and later in the triptorelin group (PND > 43). Ovarian and uterine weights were lower in the oestradiol and triptorelin groups. However, Huang Bai had nonsignificant effects on vaginal opening and the weights of ovaries and the uterus. Conclusions Huang Bai stimulated bone growth by upregulating IGF-1 and BMP-2 in the growth plate. However, it had no effect on pubertal development. Electronic supplementary material The online version of this article (10.1186/s13020-017-0156-7) contains supplementary material, which is available to authorized users.

Astragalus extract mixture HT042 is a standardized functional food granted by the Korean FDA for promoting “Children’s Height Growth”. In this study, we determined whether HT042 affects circulatory Insulin-like growth factor-1 (IGF-1) after administration and investigated whether Growth hormone (GH), Growth hormone-releasing hormone receptor (GHRH-R), and Growth hormone secretagogue receptor (GHS-R) mRNAs are expressed in the pituitary, and whether Growth hormone-releasing hormone (GHRH) and Somatostatin (SST) are expressed in the hypothalamus. We also evaluated the growth effect of HT042 on endochondral bone formation. Male Sprague-Dawley rats in the control and HT042 groups were orally administered a single dose of the control and HT042, respectively, and those in the recombinant human GH (rhGH) group were subcutaneously injected with rhGH. Tetracycline was injected intraperitoneally 72 h prior to sacrifice to decide endochondral bone formation. To determine the endocrine or paracrine/autocrine mechanism, we evaluated the expression of local BMP-2 and IGF-1, an immunohistochemical study after HT042 administration. It was confirmed that the growth-promoting effect of HT042 can be contributed to the increase in serum IGF-1, which can be stimulated by GH secretion. Administration of HT042 modulated the activity of GHRH-R and GHR-S in the pituitary gland and promoted GH secretion, thereby changing longitudinal growth through GH/IGF-1 mediation. Results for GHRH and SST expression demonstrated that the hypothalamus can be influenced and mediated by HT042 through a complex neuroendocrine regulatory system. In addition, it was confirmed by oral administration for 10 days that HT042 increased bone formation in cartilage, which is important for height growth. The effect of HT042 could be owing to upregulation of local Bone morphogenetic protein-2 (BMP-2) and IGF-1 expression in the growth plate, which could be regarded as a GH-dependent autocrine/paracrine pathway, as well as circulatory IGF-1.

HT042 is a standardized functional food ingredient approved by Korean Food and Drug Administration with a claim ‘HT042 can help height growth of children’. We aimed to evaluate the safety and efficacy of HT042 on height growth in children with mild short stature. A multicenter, randomized, double-blind, placebo-controlled parallel study was performed on children aged 6–8 years with height ranked below the 25th percentile. In 129 children, height gain was significantly higher in HT042 group than placebo group after 24 weeks (mean difference, 0.29 cm; 95% CI, 0.01 to 0.57 cm; p = 0.027). The difference was elevated when the efficacy analysis was restricted to children below the 10th percentile (mean difference, 0.45 cm; 95% CI, 0.04 to 0.87 cm; p = 0.031). Because bone age advancement was lower in HT042 group, height standard deviation score gain for bone age was higher in HT042 group and the difference was significant in children below the 10th percentile (mean difference, 0.20 score; 95% CI, 0.00 to 0.39 points; p = 0.045). Serum IGF-1 and IGFBP-3 levels were significantly increased compared with baseline within HT042 group, but group difference was not significant. HT042 supplementation helped to increase height growth in children without skeletal maturation and was more effective in much shorter children. The effects might be mediated by increases in serum IGF-1 and IGFBP-3 levels. Copyright © 2017 John Wiley & Sons, Ltd.

Background The roots of Pueraria lobata and Scutellaria baicalensis, herbal medicines with a long history of widespread use, have been traditionally prescribed in combination to treat stroke, diabetes, and acute infectious diarrhea in East Asia. Nevertheless, toxicological data on these herbs and their combination are limited. This study investigated the acute and 13-week subchronic toxicity of root extract of P. lobata and S. baicalensis (HT047) for stroke treatment in male and female Sprague-Dawley rats. Methods In the acute toxicity study, HT047 was administered orally at a single dose of 5000 mg/kg. In the subchronic toxicity study, HT047 was administered orally at repeated daily doses of 800, 2000, and 5000 mg/kg/day for 13 weeks, followed by a 4-week recovery period. Results In the acute toxicity study, there were no deaths or toxicologically significant changes in clinical signs, body weight, and necropsy findings. In the subchronic toxicity study, HT047 at all doses caused no death and no treatment-related adverse effects on food consumption; organ weight; ophthalmologic, urinalysis, and hematological parameters; and necropsy findings of both rat sexes. There were some treatment-related alterations in clinical signs, body weight, and serum biochemistry and histopathological parameters; however, these changes were not considered toxicologically significant because they were resolved during the recovery period or resulted from the pharmacological effects of P. lobata and S. baicalensis. Conclusions The oral approximate lethal dose (the lowest dose that causes mortality) of HT047 was greater than 5000 mg/kg in male and female rats. The oral no-observed-adverse-effect level of HT047 was greater than 5000 mg/kg/day in rats of both sexes, and no target organs were identified. The present findings support the safety of an herbal extract of P. lobata and S. baicalensis as a therapeutic agent for stroke and further confirm the safety of the combined use of P. lobata and S. baicalensis in clinical practice.

Background.Paeonia extract mixture HT074 is a standardized multiherbal mixture comprising extracts fromInula britannicaflowers andPaeonia lactifloraroots, which are used to treat digestive disorders in traditional Korean medicine. This study was focused on elucidating the underlying mechanisms of the gastroprotective effects of HT074 in different gastric ulcer models.Methods.Gastric lesions were induced in rats by an HCl/EtOH solution, water immersion-restraint stress (WIRS), and indomethacin. Gastric secretions were studied in pylorus-ligated rats, while mucus secretions were assessed by measuring alcian blue-binding capacity of mucus in the rat model of HCl/EtOH-induced gastric ulcer. Additionally, the involvement of nitric oxide (NO) and sulfhydryl compounds in HT074-mediated mucosal protection was elucidated using their inhibitors, i.e.,NG-nitro- L-arginine methyl ester hydrochloride (L-NAME) andN-ethylmaleimide (NEM), respectively. Furthermore, the effects on indomethacin-induced cell death and prostaglandin E2(PGE2) levels were assessed in AGS cells.Results.Oral administration of HT074 significantly decreased gastric lesions induced by HCl/EtOH, WIRS, and indomethacin. Furthermore, it significantly decreased the volume, acidity, and total acidity of gastric juice in pylorus-ligated rats and increased the alcian blue-stained gastric mucus in HCl/EtOH-induced gastric ulcer in rats. Pretreatment with NEM abolished the gastroprotective effects of HT074, while L-NAME did not. In AGS cells, HT074 significantly reduced indomethacin-induced cell death and increased the PGE2levels.Conclusions.These findings suggest that HT074 has gastroprotective effects against various ulcerogens, including HCl/EtOH, immersion stress, and NSAIDs. These effects are attributed to the inhibition of gastric secretions and preservation of the gastric mucosal barrier by increased mucus production, which is partially mediated through endogenous sulfhydryl compounds and PGE2. Based on these findings, we propose that HT074 may be a promising therapeutic agent for gastritis and gastric ulcer.

Background: Pathologists reviewing breast tissue slides must identify the presence of many salient features within each slide, including invasive and in situ breast cancer as well as various forms of atypia. In breast pathology particularly, the large volume of slides poses significant challenges for workload management and pathologist productivity (Johnson et al. 2019). The shift to a digital workflow in pathology, augmented by machine learning algorithms, has the potential to increase the efficiency, and productivity of pathologists by identifying cancer and pre-cancerous lesions in digitized slides. While there has been extensive work using machine learning algorithms to detect breast cancer metastasis in lymph nodes (Liu et al. 2018; Steiner et al. 2018), almost no research has been done on using such systems to detect breast cancer in biopsies and excisions. Methods: We created and assessed Paige Breast Alpha, a machine learning system for the detection of breast cancer in hematoxylin and eosin (H&E) stained whole slide images (WSIs) of glass slides. The system is a binary classifier, intended to draw a pathologist’s attention to concerning features. Concerning features (the positive category) consisted of invasive breast cancer, in situ breast cancer, and various forms of atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, etc. ). The deep learning system is based on the method proposed in Campanella et al. (2019). It learns directly from diagnosis using multiple instance learning, without the need for pixel-wise annotations. Paige Breast Alpha was trained on 17354 images from 3378 patients, and was assessed on 7921 images from 2443 patients. All slides were scanned on a Leica Aperio AT2. Results: For detecting invasive or in situ cancer at the part level, the system achieved an overall sensitivity of 97.3% and a specificity of 98.0% in biopsies and 96.1% sensitivity and 91.5% specificity in excisions. Each part had between 1—10 slides. Conclusions: We hypothesized that a machine learning system trained to detect predefined types of breast cancer and pre-cancerous lesions could be applied to a range of breast biopsy and resection WSIs to detect for the presence of these lesions. Herein we showed that the presence of these predefined features can be detected with high accuracy. Future studies are being initiated to assess the potential benefits of such a system when used by a pathologist. Additional systems are under development that would have the capability of subtyping the lesion present, in addition to acting as an overall binary classifier. Citation Format: Matthew G Hanna, Patricia Raciti, Ran Godrich, Adam Casson, Julian Viret, Donghun Lee, Matthew Lee, Alican Bozkurt, Jillian Sue, Belma Dogdas, Brandon Rothrock, Leo Grady, Christopher Kanan, Thomas Fuchs. Clinical-grade detection of breast cancer in biopsies and excisions using machine learning [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD6-03.

Oxaliplatin is a platinum derivative chemotherapeutic drug widely used against cancers, but even a single treatment can induce a severe allodynia that requires treatment interruption and dose diminution. The rhizome of Zingiber officinale roscoe (Z. officinale, ginger), has been widely used in traditional medicine to treat various diseases causing pain, however, its effect against oxaliplatin-induced neuropathic pain has never been assessed. In mice, a single oxaliplatin (6 mg/kg, i.p.) treatment induced significant cold and mechanical allodynia. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. Water extracts of Z. officinale (100, 300, and 500 mg/kg, p.o.) significantly attenuated both cold and mechanical allodynia induced by oxaliplatin. Intrathecal pre-treatment with the antagonist 5-HT1A (NAN-190, i.t., 1 &mu, g), but not with the antagonist 5-HT2A (ketanserin, i.t., 1 &mu, g), significantly blocked the analgesic effect of Z. officinale against both cold and mechanical allodynia. However, 5-HT3 antagonist (MDL-72222, i.t., 15 &mu, g) administration only blocked the anti-allodynic effect of Z. officinale against cold allodynia. Real-time PCR analysis demonstrated that Z. officinale significantly increased the mRNA expression of the spinal 5-HT1A receptor that was downregulated after oxaliplatin injection. These results suggest that Z. officinale may be a viable treatment option for oxaliplatin-induced neuropathic pain.

Purpose: Authors analyzed long-term surgical outcomes of infantile esotropia and the occurrence of associated strabismus, inferior oblique overaction (IOOA), and dissociated vertical deviation (DVD). Clinical factors related to the occurrence of IOOA and DVD in patients with infantile esotropia were also evaluated. Methods: Medical records of patients with infantile esotropia, who underwent surgery between 1995 and 2008, were reviewed retrospectively. Included patients were followed for at least 10 years. The incidence and age at development of IOOA and DVD were analyzed. To evaluate predisposing factors for developing IOOA or DVD, patients were divided into two groups: those with infantile esotropia only (group A) and those who developed IOOA or DVD (group B). Results: A total of 122 patients were enrolled and mean follow-up period was 16.0 years (range: 10–32 years). The mean number of surgeries was 1.7 (range: 1–5), and 64 (52.5%) patients achieved optimal horizontal alignment (esotropia

Background Korean cosmetics are widely exported throughout Asia. Cosmetics exploiting traditional Korean medicine lead this trend; thus, the traditional medicinal literature has been invaluable in terms of cosmetic development. We sought candidate medicinal herbs for skincare. Methods We used data mining to investigate associations between medicinal herbs and skin-related keywords (SRKs) in a classical text. We selected 26 SRKs used in the Donguibogam text; these referred to 626 medicinal herbs. Using a term frequency-inverse document frequency approach, we extracted data on herbal characteristics by assessing the co-occurrence frequencies of 52 medicinal herbs and the 26 SRKs. Results We extracted the characteristics of the 52 herbs, each of which exhibited a distinct skin-related action profile. For example Ginseng Radix was associated at a high-level with tonification and anti-aging, but Rehmanniae Radix exhibited a stronger association with anti-aging. Of the 52 herbs, 46 had been subjected to at least one modern study on skincare-related efficacy. Conclusions We made a comprehensive list of candidate medicinal herbs for skincare via data mining a classical medical text. This enhances our understanding of such herbs and will help with discovering new candidate herbs.

Allium macrostemon (AM) may affect bone growth by regulating bone formation and resorption. To examine the effect of AM on bone growth, 48 rats were divided into four administration groups in which either distilled water, AM (100 and 300 mg/kg), or recombinant human growth hormone (rhGH, 20 &mu, g/kg) was administered for 10 days. On day 9, all animals were intraperitoneally injected with tetracycline hydrochloride (20 mg/kg), and 48 h after the injection, the rats were sacrificed. Their tibial sections were photographed to measure bone growth. Antigen-specific immunohistochemistry was performed to detect insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2). The food intake of the AM 100 mg/kg group was higher, however, the food intake of the AM 300 mg/kg group was less than that of the control group. The rhGH and AM 100 mg/kg groups showed greater rates of bone growth (359.0 &plusmn, 23.7 and 373.1 &plusmn, 28.0 &mu, m/day, respectively) compared with the control group. IGF-1 and BMP-2 in the AM and rhGH groups were highly expressed. Indigestion at higher doses of AM led to nonsignificant bone growth in spite of increased IGF-1 and BMP-2 expression. Therefore, a suitable amount of AM could increase bone growth.

Background: The increasing prevalence of osteoarthritis among the old population worldwide is a great concern. Two of the biggest complaints of OA patients are joint pain and inflammation. Currently, people are relying on non-steroidal anti-inflammatory drugs (NSAIDs) and steroids to control pain and inflammation. However, long-term use of these pharmaceutical drugs has negative health consequences in the elderly, including gastro-intestinal, respiratory, and renal diseases. Natural products are receiving more attention than ever as alternative treatments against OA for their efficacies and safety. The root of Paeonia lactiflora Pal and the gum resin of Commiphora myrrha have been used as analgesics and anti-inflammatory agents since ancient time. A new herbal formula composed of P. lactiflora root and C. myrrha gum resin extracts, known as HT083, has shown promising antinociceptive and anti-inflammatory effects in a rodent model of OA. We design this study to investigate the safety and the efficacy of HT083 to prevent OA in patients with mild OA. Methods: This is a randomized, double-blind, and placebo-controlled study. A total of 100 eligible participants will be divided into two groups and will be given HT083 and a placebo for 12 weeks in 1:1 ratio. Treatment results will be assessed using a visual analog scale (VAS), Korean-Short Form health survey-36 score (SF-36), personal evaluation, and laboratory analysis. Discussion: This trial is expected to provide clinical evidence on the effectiveness and the safety of HT083 as a natural treatment for mild OA. Trial registration: Korean Clinical Research Information Service (CRIS) number KCT0004925 Registered on 2020.04.16.

Purpose To evaluate the changes in esodeviation after inferior oblique (IO) recession in patients with refractive accommodative esotropia and IO overaction. Methods Graded IO recession was performed in 68 patients who were diagnosed with refractive accommodative esotropia with IO overaction. The patients were followed for at least 3 months after surgery and the angle of esodeviation with correction was evaluated at distance and near at each follow-up evaluation. The patients were divided into two groups: patients who underwent unilateral IO recession (UIO-Rec) and patients who underwent bilateral IO recession (BIO-Rec). The change in esodeviation after surgery was compared between the two groups. Results A total of 68 patients were enrolled in this study, with 38 patients in the UIO-Rec group and 30 in the BIO-Rec group. In the UIO-Rec group, there was no statistically significant difference in esodeviation before and after surgery. In the BIO-Rec group, esodeviation at distance increased significantly 1 day postoperatively (p = 0.033). However, esodeviation returned to the preoperative value one week after surgery (p = 0.665). Changes in esodeviation at distance were significantly greater in the BIO-Rec group than in the UIO-Rec group one day after surgery (p = 0.044). Conclusions Bilateral IO-weakening surgery induced a transient increase in esodeviation in patients with refractive accommodative esotropia. However, we found no evidence that well-controlled esotropia with corrected hyperopia became decompensated after IO-weakening surgery, as induced esodeviation was minor and temporary.

Statins are mainstay anti-lipidaemic treatments for preventing cardiovascular diseases but also known to increase coronary artery calcification (CAC). However, underlying relationship between statin and CAC is still unclear. This study explored the mediating role of five statin-related biochemical factors [i.e., low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and high sensitivity C-reactive protein levels]. Seoul Metabolic Syndrome cohort study includes 1370 participants suspected of metabolic syndrome. For causal mediation analysis, the dataset for 2016 including 847 participants with coronary computed tomography without any missing value were analysed using the Mediation package in R software. This study identified a causal mediation mechanism of HDL-cholesterol among the five biochemical factors. It implied that statin treatment increases the HDL-cholesterol level, leading to decreasing the probability of CAC score > 0. Estimated values of interest in HDL-cholesterol mediation were (1) average causal mediation effect, -0.011 with 95% CI [-0.025, -0.003], (2) average direct effect, 0.143 with 95% CI [0.074, 0.219], and total effect, 0.132 with 95% CI [0.063, 0.209]. Its mediation effect was maintained regardless of statin intensity. Sensitivity analysis also provided a robustness of the results under potential existence of a confounder between HDL-cholesterol and CAC. This study suggests a potential causal pathway between statin and CAC (the positive association of statin on CAC) through HDL-cholesterol as an inhibitor.

Ethnopharmacological relevance According to traditional Korean medicine theory in which children's growth retardation is attributed to blood deficiency, Siwu decoction (SWD), a representative treatment for blood deficiency, was chosen as a sample. Aim of the study: To evaluate the effects of SWD on chondrocyte proliferation of growth plate in adolescent female rats. Materials and methods Female adolescent rats were allocated to one of the following four groups; SWD 100 and 300 mg/kg, recombinant human growth hormone, and vehicle for 4 days. Tetracycline was intraperitoneally injected at 48 h before sacrifice to obtain a band exhibiting fluorescence by binding newly formed bone. Bromodeoxyuridine was injected at day 2–4 to mark proliferating chondrocytes. To evaluate possible mechanisms of SWD, expressions of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate were examined by immunohistochemistry. Results Treatment with SWD significantly increased the number of BrdU-positive chondrocytes and the new bone formation in the proximal growth plate of tibia compared to the vehicle treated control group. SWD also increased the expression of IGF-1 and BMP-2 in the proliferative and hypertrophic zones of the growth plate. Conclusions SWD 300 mg/kg stimulates chondrocyte proliferation and new bone formation in the growth plate. Immunohistochemical studies indicate that the effects of SWD may be due to upregulation of local IGF-1 and BMP-2 expression in the growth plate, which may be considered as a GH-dependent paracrine-autocrine pathway.

Analytical methods of aflatoxins (AFs: B1, B2, G1 and G2) in herbal medicines (HMs) and health functional foods (HFFs) were optimized, which were used to analyze the representative samples that were directly collected from the users (total 2348 examinees) of HMs and HFFs. Two analytical methods, trifluoroacetic acid and Kobra cell derivatization methods, were compared; The latter was selected based on high linearity and sensitivity. The limits of detection of AFs using the Kobra cell method were 0.07–0.32 ng g−1. Recoveries of AFs using various matrixes such as solid, semi-solid, liquid samples and CRM were 81.81–119.87%. The Z-score and linearities of calibration curves were 0.53 and 0.9996–0.9999, respectively. Among 241 samples, only Angelica gigas NAKAI extract products (2 products) were detected to have 7.93 and 5.70 ng g−1 of aflatoxin G2.

Nipples are protected by nipple splints after reconstructing or reshaping them using various materials. We have devised a nipple splint using textile-like thermoplastic tape, which is made out of knitted hybrid fabric, is latex-free, and keeps its position well beneath a brassiere with simple taping. Its conformation is readily modifiable according to each patient's breast shape, if it is soaked into hot water. A patient who underwent nipple reconstructive surgery had this thermoplastic cast applied for a month, and the contour of the nipple was well preserved without reports of skin irritation or pressure sores developing on the areola.