Evaluation of Genotoxicity of SU-Eohyeol Pharmacopuncture Using an In Vitro Chromosome Aberration Test in Chinese Hamster Lung Cell.

Objectives: This study was conducted to evaluate the safety of SU-Eohyeol pharmacopuncture (SUEP) by assessing its potential to cause chromosomal abnormalities in Chinese hamster lung cells (CHL/IC). Methods: A dose-curve was conducted to determine the highest dose of SUEP. Doses of 10, 5, 2.5, 1.25, 0.625, and 0.313% were used, and no cytotoxicity or SUEP precipitation was observed. SUEP doses of 10, 5, and 2.5%, with positive and negative controls, were used in a chromosome aberration test. Results: In this study, the frequency of abnormal chromosomal cells in the SUEP group did not show a statistically significant difference from that of the negative control group in short-term treatments with and without metabolic activation and the continuous treatment without metabolic activation. Compared with the negative control group, the positive control group had a significantly higher frequency of cells with structural chromosomal abnormalities. This test's results satisfied all conditions for determining the results. Conclusion: SUEP did not induce chromosomal aberrations under the conditions of this study. Other toxicity evaluations, safety studies in humans, and various clinical trials are required to evaluate the safety and efficacy of SUEP.

Single-Dose Intramuscular Toxicity Study of SU-Eohyeol Pharmacopuncture in Rats.

Objectives: This toxicological study was performed to assess for potential toxicity and to determine the approximate lethal dose of SU-Eohyeol pharmacopuncture (SUEP) following a single intramuscular injection of SUEP into male and female Sprague-Dawley (SD) rats. Methods: The groups in our experiment consisted of an experimental group treated with SUEP at a dose of 1.0 mL/animal and a control group injected with a normal saline solution, and five male and female rats were placed in each group. Each animal was administered a single intramuscular injection. We monitored all rats for clinical signs and body weight changes for 14 days after administration. At the end of the observation period, the rats were euthanized and autopsied, and localized tolerance examinations were conducted at the site of administration of the test substance. Results: There were no deaths in either sex in the SUEP-treated group. There was no significant difference between the SUEP-treated group and the control group in the clinical signs and weight changes among the rats. In addition, no significant SUEP-related changes were observed on autopsy findings or local tolerance examinations at the injection site by histopathological examination. Conclusion: Our results suggest that the approximate lethal dose of a single intramuscular administration of SUEP in female and male rats under the conditions of this study is greater than 1.0 mL/animal. To determine the safety of the use of SUEP in Korean medical clinical practice, additional toxicity studies will be needed.

Effect of Taraxaci Herba on Bone Loss in an OVX-Induced Model through the Regulation of Osteoclast Differentiation.

Bone is a dynamic tissue that maintains homeostasis with a balance of osteoclasts for bone resorption and osteoblasts for bone formation. Women are deficient in estrogen after menopause, which promotes bone resorption due to excessive activity of osteoclasts, leading to osteoporosis. TH (also known as dandelion) is native to warm regions and has traditionally been used to treat gynecological diseases and inflammation. Menopause is a major cause of osteoporosis as it causes abnormal activity of osteoclasts, and various studies have shown that anti-inflammatory drugs have the potential to treat osteoporosis. We analyzed the effect of TH on osteoclast differentiation and the relevant mechanisms using RANKL. After administration of TH in a menopause-like rat model in which ovariectomy of the was rats carried out, changes in bone microstructure were analyzed via micro-CT, and the antiosteoporosis effect of TH was verified by a histological analysis. In addition, the pharmacological effects of TH in an animal model of osteoporosis were compared and analyzed with osteoporosis medications (17ß-estradiol (E2) and alendronate (ALN)). TH significantly inhibited the initial osteoclast differentiation via the NFATc1/c-Fos mechanism. In addition, bone density in the femur of osteoporotic rats was increased, and the expression of osteoclast-related factors in the serum and tissues was controlled. The results of this study provide objective evidence of the inhibitory effect of TH on osteoclastogenesis and OVX-induced bone loss.

A Single-Center Retrospective Study on the Effects of Korean Medicine in 342 Traffic Accident Cases.

OBJECTIVES: In South Korea, traffic accident victims can be treated under automobile insurance coverage. Korean medicine (KM) clinics have reported the largest number of automobile insurance fee claims among medical institutions. This study investigated the status of the KM automobile insurance system in a single KM clinic. METHODS: We retrospectively surveyed the medical charts of 342 traffic accident patients treated at the Jisung KM clinic between January 2009 and June 2017. RESULTS: Most of the patients were men and in their 30s. The most common method of locating the clinic was an internet search. The most common traffic accident type was collision between vehicles (83.63%), with 70.76% of patients visiting during the most acute phase. The major disease codes included S434, M4836, F072, S0600, and S3350. The most frequent treatment period was within 1 month of the accident, and most patients received 10 or fewer treatments. The mean treatment duration and number of treatments were 37.68 ± 45.11 days and 11.68 ± 10.63 treatments, respectively. The initial pain numerical rating scale (NRS), 7.32 ± 0.96, decreased to 3.57 ± 1.40 at the end of treatment, with a symptom improvement score of 1.87 ± 0.60. Regarding sex, age, disease duration, location at the time of the accident, presence of additional and psychological symptoms, and chuna, there were statistically significant differences in treatment duration and number of treatments. A higher number of treatments and the longer treatment duration was associated with a higher initial NRS, lower post-treatment NRS, and better improvement score. Since the introduction of traffic accident (TA) pharmacopuncture, the rate of use of a single type of pharmacopuncture increased; however, no significant differences in treatment duration and number, NRS before and after treatment, and improvement score were observed between treatment groups before and after TA pharmacopuncture. No adverse reactions were observed for any treatment. CONCLUSION: This study confirmed the previous findings of a high treatment effect of KM under automobile insurance. We also observed significant correlations based on a detailed medical status, which may explain the increasing use of KM in the automobile insurance system. Additional multi-center studies in different regions are needed.

Suppression of Unwanted ZZ Interactions in a Hybrid Two-Qubit System.

Mitigating crosstalk errors, whether classical or quantum mechanical, is critically important for achieving high-fidelity entangling gates in multiqubit circuits. For weakly anharmonic superconducting qubits, unwanted ZZ interactions can be suppressed by combining qubits with opposite anharmonicity. We present experimental measurements and theoretical modeling of two-qubit gate error for gates based on the cross resonance interaction between a capacitively shunted flux qubit and a transmon, and demonstrate the elimination of the ZZ interaction.

Herbal medicine for the management of idiopathic trigeminal neuralgia: A protocol for a systematic review of controlled trials.

BACKGROUND: Trigeminal neuralgia is an oral facial pain that is limited to one or more parts of the trigeminal nerve. As it becomes chronic, it can seriously affect the quality of life of most patients, and it is expected to increase in incidence in modern aging society. The objective of this systematic review protocol is to provide methods for evaluating the effectiveness and safety of herbal medicines for idiopathic trigeminal neuralgia (ITN). METHODS: A total of 14 databases will be searched for studies uploaded from inception to the present date that investigated the treatment of ITN. These databases are MEDLINE, EMBASE, AMED, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, PsycARTICLES, four Korean databases, two Chinese databases, and two Japanese databases. We will include randomized controlled trials (RCTs) assessing herbal medicine decoctions used to treat any type of ITN. All RCTs of decoctions or modified decoctions with any type of form of herbal medicine will be eligible for inclusion. The methodological quality of randomized controlled trials will be analyzed using the Cochrane Collaboration tool to assess risk of bias, and the confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. ETHICS AND DISSEMINATION: The results of this systematic review will be published in a peer-reviewed journal and disseminated electronically and in print. To inform and guide healthcare practices, the review will be updated. TRIAL REGISTRATION NUMBER: PROSPERO CRD42020129667.

Pharmacopuncture for the management of musculoskeletal diseases: A protocol for systematic review.

BACKGROUND: Musculoskeletal disorders are the main reason for people to seek counseling and use of complementary and alternative medicine. Although pharmacopuncture is used to treat various diseases in traditional medicine, it is most often applied to treat musculoskeletal conditions. Here, we will review systematically the clinical evidence for the effectiveness and safety of pharmacopuncture for musculoskeletal diseases. METHODS: A total of 13 databases will be searched for studies uploaded from January 2014 to December 2018 that investigated the treatment of musculoskeletal diseases. These databases are MEDLINE, EMBASE, AMED, Cochrane Library, CINAHL, 4 Korean databases, 2 Chinese database, and 2 Japanese databases. The methodological quality of randomized controlled trials will be analyzed using the Cochrane Collaboration tool to assess risk of bias, and the confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal and disseminated electronically and in print. To inform and guide healthcare practices, the review will be updated. REGISTRATION NUMBER: CRD42019148795.

Genotoxicity Evaluation of Capsaicin-Containing (CP) Pharmacopuncture, in an In Vivo Micronucleus Test.

OBJECTIVES: Capsaicin-containing (CP) pharmacopuncture was developed to treat neuropathic pain. This study was conducted to assess the toxicity of CP extract for pharmacopuncture, using a micronucleus test. METHODS: First, a dose range finding study was conducted. Then an in vivo micronucleus test was performed to determine the induction of micronuclei in mouse bone marrow cells after intramuscular administration of CP twice with a 24-hour interval to 8-week-old ICR mice. A high dose of 0.2 mL/animal was selected, and this was sequentially diluted by applying a geometric ratio of 2 to produce two lower dose levels (0.1 and 0.05 mL/animal). In addition, negative and positive control groups were set up, and an HPLC analysis was conducted to confirm the capsaicin content of CP. RESULTS: The incidence of micro-nucleated polychromatic erythrocytes in polychromatic erythrocytes in the CP-treated group was similar to that in the negative-control group, while that in the positive-control group was significantly greater. In addition, the ratio of polychromatic erythrocytes to total erythrocytes in the CP treatment group and the positive control group was not significantly different from the negative control group. In the HPLC analysis, capsaicin in the CP was identified through a comparison with the retention time of the capsaicin standard of 27 min. CONCLUSION: CP did not show any indication of any potential to induce micronuclei formation in bone marrow cells of ICR mice under the conditions of this study. Further toxicity studies are necessary to ensure the safety of the use of CP in clinical practice.

Preparation of Optically Active Apoverbenone and Verbenone from Nopinone by Use of the Sulfenylation-Dehydrosulfenylation Method. Stability and Reactivity Attributable to Absolute Configuration at the Sulfur Atom in Sulfoxides.

Apoverbenone (4) and verbenone (5) in optically active forms are potentially useful compounds as the chiral source in enantioselective synthesis. Starting with (+)-nopinone (1), readily available from (-)-beta-pinene, (+)-apoverbenone (4a) and (+)-verbenone (5a) were prepared in synthetically satisfactory overall yields, using commonly the sulfenylation-dehydrosulfenylation method directed toward construction of an enone function. This methodology could be applicable to preparation of their enantiomers (-)-4b and (-)-5b on starting with (-)-nopinone. While configuration of the phenylsulfinyl group in sulfoxides 10a,b, and 18a,b were assigned by their (1)H NMR spectra and NOE correlations, absolute configurations at the sulfur atom were performed by comparison in (1)H NMR spectra with their homologues whose absolute configurations are well-defined, that is, 10a with 13a, 10b with 13b, 18a with 19b, and 18b with 19a. As a result, it was proved that, in 3-(phenylsulfinyl)nopinones, thermodynamic stability of isomers is dependent on absolute configuration at the sulfur center; that is, the trans-isomer 10a possesses an R(s)-phenylsulfinyl group and the cis-isomer 10b possesses an S(s)-phenylsulfinyl group, and it was proved that, in (4R)-4-methyl-3-(phenylsulfinyl)nopinones, both cis-isomers 18a,b are stable, irrelevant with absolute configurations at the sulfur atom. In elimination of phenylsulfenic acid from sulfoxides 10 and 18, the use of purified sulfoxides was essential, because the competing Pummerer reaction proceeded to give 3-(phenylthio)verbenone (11) as a byproduct, when acidic contaminants were present. The sulfoxides 10a,b and 18a provided smoothly 4a and 5a, respectively, in a syn elimination manner, whereas 18b gave a mixture of decomposed products as a major part, probably because of instability of 18b to heat as well as because of its conformational requirement.