Influence of Feeding Time on a Non-steroidal Anti-inflammatory Drug-induced Small Intestinal Injury Mouse Model.

BACKGROUND/AIM: Non-steroidal anti-inflammatory drugs (NSAIDs), the most widely used pharmaceuticals, induce various adverse effects, including gastrointestinal injuries, such as ulcers and bleeding. Animal models of NSAID-induced small intestinal injury (NSI) have been extensively employed for the development of preventive and therapeutic agents. However, some experimental variations related to feeding times have been observed following NSI induction. This study aimed to investigate the impact of feeding time on an NSI mouse model. MATERIALS AND METHODS: The mice were divided into eight groups: normal, sham, and model groups (with feeding times of 2 h, 6 h, 10 h, 14 h, 18 h, and 22 h; n=10 in each group). The mice were fasted for 18 h before the injection of indomethacin (15 mg/kg, subcutaneously), except for the normal group. Food supply was halted at specific time points (2 h, 6 h, 10 h, 14 h, 18 h, and 22 h); however, the normal and sham groups were continuously fed throughout the experiment. The length of the small intestine was measured, and histological analysis was performed 24 h after induction. RESULTS: Up to 14 h after induction, NSI, indicated by small intestine shortening, remained consistent, with a reduction in length of approximately 10-20%. However, feeding for more than 14 h significantly exacerbated NSI, both anatomically and histologically. CONCLUSION: The ulcerative changes observed in the small intestine 14 h after indomethacin injection may be closely associated with the influence of food on NSI.

Research status of east Asian traditional medicine treatment for chronic cough: A scoping review.

BACKGROUND: When patients continue to experience cough despite conventional treatment, East Asian traditional medicine (EATM) including herbal medicine and/or acupuncture has been frequently used. Previous systematic reviews of EATM treatment for chronic cough have been conducted mainly on herbal medicine, targeting patients with conditions that cause cough. In clinical practice, EATM interventions are not limited to herbal medicine, and considering that chronic cough is often caused by two or more conditions or unspecific causes, a comprehensive investigation is clinically relevant. We examined the current research status of EATM for chronic cough. METHODS: Based on Arksey and O'Malley's scoping review methodological framework, a total of six English, Chinese, Korean, and Japanese electronic databases were searched on August 2022. Any clinical studies on EATM targeting chronic cough patients (regardless of their cause) were included. RESULTS: Among 474 included studies, the study designs were mainly randomized controlled trials (72.4%), and the population was evenly distributed between children and adults. The cause of cough was not reported in most studies (56.1%). The common cause of cough was upper airway cough syndrome and post-respiratory infection (9.5%, each), followed by mixed cause (7.6%), nonspecific cause (5.9%), and gastroesophageal reflux disease (4.0%). EATM was conducted for a mean of 19.1 days, and herbal medicine was the most common (80.6%). Conventional medication was frequently used as a control (81.2%). For outcomes, the total effective rate was the most frequently utilized (94.3%), followed by cough severity (53.8%). EATM treatment showed positive outcomes in most studies. CONCLUSIONS: In future EATM studies, it is necessary to either specify the cause of chronic cough or to report that the study was targeting nonspecific chronic cough. In addition, high-quality studies assessing the efficacy of EATM with placebo control treatment should be conducted, using validated evaluation tools.

The Effectiveness and Safety of Chuna Manual Therapy Adjuvant to Western Medicine in Patients with Chronic Obstructive Pulmonary Disease: A Randomized, Single-Blind, Investigator-Initiated, Pilot Trial.

Recently, non-pharmacological treatments are gaining increasing importance for improving the quality of life in patients with chronic obstructive pulmonary disease (COPD). This pilot study aimed to evaluate the feasibility of conducting extensive research on Chuna manual therapy (CMT). This study investigated the effectiveness and safety of CMT adjuvant to Western medicine (WM) in patients with COPD. Forty patients with COPD were randomized into two groups in a 1:1 ratio: experimental (CMT plus WM) and control (WM only) groups. The CMT intervention was administered once a week for eight weeks. The primary outcome measured was the 6-min walk distance (6MWD). Secondary outcomes measured were: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), assessments using the modified Medical Research Council (mMRC) scale and Visual Analog Scale (VAS) for dyspnea, the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and the EuroQoL five-dimensional questionnaire (EQ-5D). The mean differences in FEV1 (L) between Weeks 1 and 8 were statistically significant between the groups (p = 0.039). Additionally, the experimental group showed improved 6MWD, mMRC, VAS for dyspnea, CAT, SGRQ (total), and EQ-VAS scores than the control group. However, the differences between the two groups were not statistically significant. No adverse events were observed during this trial. CMT has the potential to alleviate symptoms, improve quality of life, and delay the decline in lung function in patients with COPD. The results of this pilot study could lead to large-scale clinical trials in the future.

Understanding experiences of cancer-related fatigue in patients with lung cancer after their cancer treatment: a qualitative content analysis.

PURPOSE: Cancer-related fatigue (CRF) is an important symptom affecting the quality of life of patients with lung cancer. However, research on the characteristics of CRF in lung cancer and their relationship to cancer treatment is limited. We aimed to explore the unique features of CRF in patients with lung cancer, and investigate the influencing factors. METHODS: Semi-structured interviews were conducted with 21 adult patients with lung cancer until data saturation was reached. The collected data were analyzed using qualitative content analysis. An inductive coding process and deductive content analysis incorporating the established CRF domains were employed. Patient data from electronic medical records were used for data triangulation. RESULTS: The analysis revealed five themes of CRF: (1) energy depletion, the double burden of illness and treatment, and daily life impediments; (2) feeling down and anxious; (3) neurovascular disturbances and changes in sensory perception; (4) cognitive impairment; and (5) personal and social isolation. CRF tended to improve over time, except for persistent emotional fatigue beyond 6 months. Patients who underwent surgery followed by adjuvant cancer treatment exhibited the most diverse CRF symptoms. The concurrent chemoradiation therapy group experienced significant physical fatigue, whereas the radiosurgery group reported distinct emotional fatigue. Certain factors, such as exercise, can serve as both alleviating and aggravating factors for CRF. CONCLUSION: Tailored interventions that take into account the multidimensional symptoms of CRF and patient characteristics are crucial. These findings will guide healthcare professionals when implementing patient-centered symptom management and patient education.

Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis.

Objectives: Chronic cough is a frequent condition worldwide that significantly impairs quality of life. Herbal medicine (HM) has been used to treat chronic cough due to the limited effectiveness of conventional medications. This study aimed to summarize and determine the effects of HM on patients with chronic cough. Methods: A comprehensive search of 11 databases was conducted to find randomized controlled clinical trials (RCTs) that reported the effects of HM for patients with chronic cough on 16 March 2023. The primary outcome was cough severity, and the secondary outcomes included cough-related quality of life, cough frequency, total effective rate (TER), and cough recurrence rate. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and the certainty of the evidence for effect estimates was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations tool. Results: A total of 80 RCTs comprising 7,573 patients were included. When HM was used as an alternative therapy to conventional medication, there were inconsistent results in improving cough severity. However, HM significantly improved cough-related quality of life and TER and significantly lowered the cough recurrence rate compared with conventional medication. When used as an add-on therapy to conventional medication, HM significantly improved cough severity, cough-related quality of life, and TER and significantly lowered the recurrence rate. In addition, HM had a significantly lower incidence of adverse events when used as an add-on or alternative therapy to conventional medication. The subgroup analysis according to age and cause of cough also showed a statistically consistent correlation with the overall results. The certainty of the evidence for the effect of HM was generally moderate to low due to the risk of bias in the included studies. Conclusion: HM may improve cough severity and cough-related quality of life, and lower the cough recurrence rate and incidence of adverse events in patients with chronic cough. However, due to the high risk of bias and clinical heterogeneity of the included studies, further high-quality placebo-controlled clinical trials should be conducted using a validated and objective assessment tool. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418736, CRD42023418736.

Effects of herbal medicines (Eunkyosan/Yin qiao san and Samsoeum/Shen su yin) for treating the common cold: A randomized, placebo-controlled, multicenter clinical trial.

Background: Eunkyosan (EKS) and Samsoeum (SSE), which are called Yin qiao san and Shen su yin in Chinese, are commonly used herbal medicines for the common cold in East Asian countries. This study aimed to evaluate the effectiveness and safety of EKS and SSE for treating the common cold. Methods: A randomized, patient-assessor-blind, placebo-controlled, parallel, and multicenter clinical trial was conducted. Adult participants who had one or more cold within 48 h before screening, were randomly allocated to EKS, SSE, or placebo groups. The recruitment goal was planned to be 375 participants. They took an EKS, SSE, or placebo, thrice daily for up to 8 days. The primary outcome was the change in the total score of the Wisconsin Upper Respiratory Symptom Scale-21-Korean version (WURSS-21-K) on day 6 compared to the baseline. The secondary outcomes included visual analog scale (VAS) scores and the duration of symptoms was assessed throughout the trial. Results: A total of 128 participants were enrolled and 44, 42, and 42 were allocated to the EKS, SSE, and placebo groups, respectively. This study was prematurely terminated due to the COVID-19 pandemic, and we were unable to recruit all the planned participants (n = 375). EKS showed significant clinical effectiveness over the placebo group in the treatment of the common cold, as assessed by the total, symptom, and quality of life scores of WURSS-21-K and VAS, whereas SSE showed significant improvement over the placebo group in terms of WURSS-21-K symptom score. No severe adverse events were reported. Conclusions: Although EKS and SSE demonstrated statistically significant clinical effectiveness and safety in patients with the common cold, we failed to recruit our pre-planned number of participants. Future definitive full-scale studies are needed to confirm these results. Trial registration: ClinicalTrials. gov, registration number: NCT04073511. Registered on 29 August 2019.

Efficacy and Safety of Yukmijihwang-Tang in the Treatment of Cough-Variant Asthma: Study Protocol for a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

BACKGROUND: Cough-variant asthma (CVA), a precursor of typical asthma, is the main cause of chronic cough. We hypothesize that yukmijihwang-tang (YJT), which has been used for chronic cough in traditional medicine and has been reported to have an anti-inflammatory effect, could be an adjuvant to asthma treatment. METHODS: We plan a randomized, double-blind, placebo-controlled, multicenter, phase 2 trial to investigate the efficacy and safety of YJT in CVA patients. A total of 60 patients with CVA will be recruited and randomly assigned to either a high-dose YJT group, standard-dose YJT group, or control group (placebo) in a 1:1:1 allocation ratio after a 2-week run-in period. For the run-in period, only inhaled corticosteroids (ICSs) will be used, and the investigational drug will be administered once a day with concomitant ICS for 6 weeks. Data will be collected at baseline, week 3, and week 6, and the primary outcome measure will be the mean cough symptom score (CSS) change before and after medication. The secondary outcome measures will include the Leicester cough questionnaire-Korean version (LCQ-K) score, eosinophil count and eosinophil cationic protein level, pulmonary function test, and the number of uses of rescue medication, and so on. CONCLUSION: This study aimed to evaluate the efficacy and safety of YJT in concomitant treatment with ICS in patients with CVA and to determine the optimal dosage of YJT. The results are expected to provide evidence for the use of YJT as an adjuvant treatment for CVA.Cough-Variant-Asthma (CVA), eine Frühform von typischem Asthma, ist die Hauptursache von chronischem Husten. Unserer Vermutung nach könnte Yukmijihwang-Tang (YJT), das in der traditionellen Medizin zur Behandlung von chronischem Husten eingesetzt wird und das Berichten zufolge einen entzündungshemmenden Effekt hat, unterstützend in der Asthma-Therapie wirken.en: Wir planen eine randomisierte, doppelblinde, placebokontrollierte, multizentrische Phase-2-Studie, um die Wirksamkeit und Sicherheit von YJT bei Patienten mit CVA zu untersuchen. Insgesamt werden 60 CVA-Patienten für die Studie rekrutiert und nach einer zweiwöchigen Run-in-Phase randomisiert im Verhältnis 1:1:1 einer Gruppe mit hochdosiertem YJT, einer Gruppe, die YJT in der Standarddosierung erhält oder einer Kontrollgruppe (Placebo) zugewiesen. Während der Run-in-Phase werden nur inhalative Corticosteroide (ICS) verwendet, und das Prüfpräparat wird über 6 Wochen einmal täglich gleichzeitig mit den ICS angewendet. Die Datenerhebung erfolgt bei Studienbeginn, in Woche 3 sowie in Woche 6, und das primäre Zielkriterium ist die Änderung des mittleren Hustenscores (cough symptom score, CSS) vor und nach der Anwendung der Medikamente. Zu den sekundären Zielkriterien gehören der Score des Leicester Hustenfragebogens - koreanische Version (LCQ-K), die Eosinophilenzahl und der Spiegel an eosinophilem kationischen Protein, Lungenfunktionstests sowie die Anzahl der Anwendungen von Bedarfsmedikation usw.Ziel dieser Studie ist es, die Wirksamkeit und Sicherheit von YJT bei gleichzeitiger Behandlung mit ICS bei Patienten mit CVA zu bewerten und die optimale YJT-Dosis zu ermitteln. Es wird erwartet, dass die Ergebnisse Belege für die Anwendung von YJT als adjuvante Therapie bei CVA liefern werden.WHO International Clinical Trials Registry Platform, Clinical Research Information Service (CRIS), KCT0006994, registriert am 10. Februar 2022, https://cris.nih.go.kr/cris/search/detailSearch.do/21743.

Characteristics and difference of respiratory diseases in Korean adults aged ≥40 years: A cross-sectional study.

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

Therapeutic Potential of Chungsangboha-tang for the Treatment of Asthma: A Review of Preclinical and Clinical Studies.

In traditional Korean medicine, Chungsangboha-tang (CSBHT) and its modified forms are used to treat various respiratory disorders, including asthma. This study aimed to identify research trends, clarify the effectiveness of CSBHT and related prescriptions, and lay a foundation for future research. We conducted a literature review using PubMed, Embase, Google Scholar, Oriental Medicine Advanced Searching Integrated System, National Digital Science Links, Korean Medical Database, Wanfang Data, and Chinese National Knowledge Infrastructure databases. We analyzed 25 studies, including 5 in vitro studies, 6 animal studies, and 14 human studies. Many studies evaluated the efficacy of CSBHT and its related prescriptions, including experimental studies on its effectiveness in asthma. The main mechanism of action involves the anti-inflammatory effect caused by the regulation of various immune cells, cytokines, and chemokines. In addition, clinical trials on asthma reported the benefits of CSBHT and its related prescriptions. However, there has been no randomized controlled study of clinical trials on the clinical effectiveness of CSBHT in asthma. Therefore, large-scale randomized controlled studies should be conducted in the future.

Rosa laevigata Attenuates Allergic Asthma Exacerbated by Water-Soluble PM by Downregulating the MAPK Pathway.

Exposure to water-soluble particulate matter (WPM) containing heavy metals can cause severe inflammatory responses and trigger and exacerbate the onset of asthma. As a follow-up study of Rosa laevigata (RL), this study analyzed the therapeutic effects and mechanisms of oral and intratracheal administration of RL and demonstrated anti-inflammatory effects in asthma models. Worse T-helper cell type 2 (Th2)-related inflammatory and pro-inflammatory responses were observed after simultaneous challenge with ovalbumin (OVA) and WPM. To establish a model of asthma exacerbated by WPM, BALB/c mice were sensitized with OVA + aluminum hydroxide and challenged with OVA + WPM. To confirm the therapeutic efficacy of RL, it was administered both orally and intratracheally. Histopathological analysis of H&E staining confirmed that oral and intratracheal administration of RL alleviated inflammatory cell infiltration in the airways aggravated by OVA + WPM. RL effectively reduced the number of inflammatory cells obtained from the bronchoalveolar lavage fluid. In addition, enzyme-linked immunosorbent assay (ELISA) and multiplex analysis of serum samples confirmed that the administration of RL reduced the levels of immuno-globulin E (IgE), Th2-related cytokines, and pro-inflammatory cytokines. Furthermore, real-time PCR analysis of lung tissue samples confirmed that the release of MUC5AC (Mucin 5AC, Oligomeric Mucus/Gel-Forming) and pro-inflammatory cytokines was reduced by RL, and western blotting confirmed that the administration of RL reduced the phosphorylation of ERK and p38 in the MAPK pathway. In conclusion, oral and intratracheal administration of RL appears to have an anti-asthmatic effect by reducing the secretion of Th2-related cytokines, pro-inflammatory cytokines, and IgE by downregulating the MAPK pathway. Thus, RL has further demonstrated potential for development as an oral and inhaled therapeutic for asthma symptoms exacerbated by WPM exposure.

Efficacy and Safety of Bojungikgi-Tang for Persistent Allergic Rhinitis: A Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

Background: Allergic rhinitis (AR) is a common disease, and conventional medications are often insufficient for treatment. Bojungikgi-tang (BJIGT) is an herbal medicine widely used in traditional medicine and has anti-inflammatory and immunoregulatory effects. We hypothesize that BJIGT would improve nasal symptoms in patients with persistent AR (PAR). Methods: This is a randomized, double-blind, placebo-controlled, phase II trial. A total of 105 patients, identified with perennial allergens, with a history of PAR and a mean total nasal symptom score (TNSS) ≥ 5 during the run-in period will be recruited from Daejeon Korean Medicine Hospital. Participants will be randomly assigned to a high-dose BJIGT group, standard-dose BJIGT group, or control group (placebo) in a 1 : 1 : 1 allocation ratio after a week run-in period. The treatment medication will be taken three times per day for 4 weeks. The primary outcome measure is the mean change in the TNSS before and after medication. The secondary outcome measures include the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, total IgE and eosinophil count, overall assessment of AR, pattern identification questionnaire for AR, and Sasang constitution. Discussion. The aim of this study is to investigate the efficacy and safety of BJIGT in the treatment of PAR and to determine the suitable dosage of BJIGT. Therefore, we planned a randomized, controlled, phase II trial of two different doses of BJIGT compared with placebo, and the results of this study are expected to provide evidence for the use of BJIGT as a treatment of PAR. Trial Registration. The National Clinical Trial Registry Clinical Research Information Service, CRIS, KCT0006616, https://cris.nih.go.kr/cris/search/detailSearch.do/20706.

Efficacy and Safety of Ojeok-San Plus Saengmaek-San for Gastroesophageal Reflux-Induced Chronic Cough: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial.

Introduction: Gastroesophageal reflux-induced chronic cough (GERC) is one of the most common etiologies of chronic cough. Despite the growing prevalence and interest in GERC, no effective treatment is currently available. In our study, we used a combination of herbal medicines, Ojeok-san (OJS) plus Saengmaek-san (SMS), for the treatment of GERC. Methods: We conducted a pilot, randomized, placebo-controlled, parallel-arm, single-center clinical trial to assess the feasibility of our study protocol, as our study is the first herbal medicine trial for GERC. All enrolled participants were randomly assigned to either the intervention or placebo group in a 1:1 ratio and were administered trial drugs three times a day for 6 weeks, with an evaluation visit performed every 2 weeks for their efficacy and safety assessment until the follow-up visit (week 8). We evaluated the severity and frequency of cough, cough-specific quality of life, airway hypersensitivity, and reflux-related gastrointestinal symptoms, as well as pattern identification, to investigate the complex mechanisms of reflux cough syndrome. Results: A total of 30 participants were enrolled, and 25 completed the study at Kyung Hee University Korean Medicine Hospital from 26 December 2018 to 31 May 2021. OJS plus SMS significantly improved the cough diary score (CDS), cough visual analog scale, Korean version of the Leicester Cough Questionnaire, Hull Airway Reflux Questionnaire, and Gastrointestinal Symptom Rating Scale after the treatment compared to the baseline. Notably, OJS plus SMS showed significant efficacy in the daytime and total CDS compared with the placebo. Only one adverse event was observed during the trial, and no serious adverse events occurred. Additionally, we achieved successful results in feasibility outcomes by exceeding the ratio of 80%. Conclusion: We confirmed the feasibility of our trial design and demonstrated the potential of OJS plus SMS in relieving the severity of cough and GI symptoms in GERC patients with safe and successful feasibility results. We anticipate that our study results will be used as the basis for further large-scale, well-designed, confirmatory trials to evaluate the safety and efficacy of OJS plus SMS in GERC. Clinical Trial Registration: [https://cris.nih.go.kr], identifier WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003115].

Herbal Medicine Compared to Placebo for Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by irreversible airflow limitation. Many COPD patients use complementary and alternative modalities, including herbal medicines (HMs). This systematic review investigated the effectiveness and safety of HM in managing COPD symptoms compared to placebo. Nine electronic databases were searched to identify relevant randomized controlled trials (RCTs) up to February 12, 2021. The Cochrane risk of bias tool was used to assess the methodological qualities of the included studies. Primary outcomes were lung function parameters and exercise capacity. A meta-analysis was conducted to determine the effect size for homogeneous outcomes. Fourteen studies were included. There was low to very low quality evidence that HM significantly improved forced expiratory volume in 1 â€Šs (FEV1) (L), FEV1 (%) and 6-minute walk distance, as well as moderate quality evidence that HM significantly improved forced vital capacity (FVC) (L) compared to placebo. However, according to low quality evidence, there was no significant difference in FEV1/FVC (%) or vital capacity (L) between the groups. Low to moderate evidence suggests that HM has the potential to help improve some respiratory functions, COPD symptoms, and some aspects of quality of life in COPD patients compared to placebo. However, these findings are challenged by the poor methodological quality of the included studies, the heterogeneity of HMs used, and potential publication bias. Therefore, the findings could be significantly influenced by further larger, more rigorous RCTs on this topic. Moreover, it may also be recommended to develop standardized HMs focused on some individual herbs that are frequently used or expected to play an important role in patients with COPD, and to elucidate the underlying mechanisms.

Modified Protocol to Enable the Study of Hemorrhage and Hematoma in a Traumatic Brain Injury Mouse Model.

To date, many studies using the controlled cortical impact (CCI) mouse model of traumatic brain injury (TBI) have presented results without presenting the pathophysiology of the injury-core itself or the temporal features of hemorrhage (Hrr). This might be owing to the removal of the injury-core during the histological procedure. We therefore developed a modified protocol to preserve the injury-core. The heads of mice were obtained after perfusion and were post-fixed. The brains were then harvested, retaining the ipsilateral skull bone; these were post-fixed again and sliced using a cryocut. To validate the utility of the procedure, the temporal pattern of Hrr depending on the impacting depth was analyzed. CCI-TBI was induced at the following depths: 1.5 mm (mild Hrr), 2.5 mm (moderate Hrr), and 3.5 mm (severe Hrr). A pharmacological study was also conducted using hemodynamic agents such as warfarin (2 mg/kg) and coagulation factor VIIa (Coa-VIIa, 1 mg/kg). The current protocol enabled the visual observation of the Hrr until 7 days. Hrr peaked at 1-3 days and then decreased to the normal range on the seventh day. It expanded from the affected cortex (mild) to the periphery of the hippocampus (moderate) and the brain ventricle (severe). Pharmacological studies showed that warfarin pre-treatment produced a massively increased Hrr, concurrent with the highest mortality rate and brain injury. Coa-VIIa reduced the side effects of warfarin. Therefore, these results suggest that the current method might be suitable to conduct studies on hemorrhage, hematoma, and the injury-core in experiments using the CCI-TBI mouse model.

Comparative Effectiveness of Western and Eastern Manual Therapies for Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Manual therapy (MT) is considered a promising adjuvant therapy for chronic obstructive pulmonary disease (COPD). Comparing the effectiveness among different Western and Eastern MTs being used for the management of COPD could potentially facilitate individualized management of COPD. This systematic review attempted to estimate the comparative effectiveness of Western and Eastern MTs for COPD patients using a network meta-analysis (NMA) methodology. METHODS: Nine electronic databases were comprehensively searched for relevant randomized controlled trials (RCTs) published up to February 2021. Pair-wise meta-analysis and NMA were conducted on the outcomes of COPD, which included lung function and exercise capacity. RESULTS: The NMA results from 30 included RCTs indicated that the optimal treatment for each outcome according to the surface under the cumulative ranking curve was massage, acupressure, massage, and tuina for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and 6 min walking distance, respectively. CONCLUSIONS: MTs such as massage, acupressure, and tuina have shown comparative benefits for lung function and exercise capacity in COPD. However, the methodological quality of the included studies was poor, and the head-to-head trial comparing the effects of different types of MTs for COPD patients was insufficient. Therefore, further high-quality RCTs are essential.

The effectiveness and safety of Chuna manual therapy adjuvant to Western medicine in patients with chronic obstructive pulmonary disease: Study protocol for a randomized, single-blind, investigator-initiated, pilot trial.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) management, greater emphasis has been placed on symptomatic improvement and enhanced quality of life in patients. Manual therapy among respiratory rehabilitation programs has received much attention recently, with the publication of numerous studies. In South Korea, a method known as Chuna Manual Therapy (CMT) has been applied in the management of COPD patients and in clinical practice, but the clinical basis for safety and effectiveness is yet to be established. Therefore, rigorously designed randomized controlled trials are required. We aimed to evaluate the feasibility of assessing the add-on effect and safety of CMT administered with standard Western medicine therapy for the treatment of COPD. METHODS: This is a randomized, single-blind, single-center clinical pilot trial. Patients with COPD receiving standard drug therapy are randomly divided into an experimental group (n = 20) and a control group (n = 20) at a 1:1 ratio. The experimental group receives CMT adding to the standard medical therapy once a week for 8 weeks. The control group receives only the standard drug treatment. The trial is conducted with an outcome assessor and statistician blinding. The primary outcome is the 6-minute walk test. The secondary outcomes include the pulmonary function test, the Modified Medical Research Council, visual analog scale for dyspnea, COPD assessment test, quality of life using the St. George's respiratory questionnaire, EuroQOL five dimensions questionnaire, and Korean pattern identification questionnaire. Adverse events are also be evaluated. CONCLUSIONS: The results of this study will provide the feasibility of a large-scale clinical trial to establish high-quality clinical evidence of CMT for COPD. TRIAL REGISTRATION: Korean Clinical Trial Registry (http://cris.nih.go.kr; registration number: KCT0006119).

Long-term progression-free survival in a patient with advanced non-small-cell lung cancer treated with low-dose gefitinib and traditional herbal medicine: A case report.

RATIONALE: Gefitinib is a first-line palliative chemotherapy drug used to treat advanced non-small-cell lung cancer (NSCLC) in patients who have an epidermal growth factor receptor (EGFR) mutation. However, approximately two-thirds of NSCLC patients with EGFR-tyrosine kinase inhibitor experience dermatological toxicity. Cutaneous toxicity is usually not life threatening but can necessitate modification or discontinuation of medication in severe cases. In this case, despite a reduction in the dose of gefitinib due to side effects, combined treatment with modified Bojungikki-tang (BJKIT) increased progression-free survival (PFS) in an advanced NSCLC patient. PATIENT CONCERNS: An 83-year-old Asian woman presented with chief complaints of chronic cough, dyspnea, weight loss, and anorexia. DIAGNOSES: The patient was diagnosed with stage IV NSCLC (T2aN3M1), adenocarcinoma with metastasis to the lymph node, brain, and bone based on image scan and biopsy. An EGFR deletion was detected in exon 19. INTERVENTIONS: The patient was treated with gefitinib (250 mg/d) and traditional herbal medicine, modified Bojungikki-tang (BJIKT). However, after 1 year of combination therapy, gefitinib was tapered down to once per week while modified BJIKT was maintained. OUTCOMES: A partial response was achieved, but after 3 months severe papulopustular skin rashes developed and became aggravated with time. Thus, the gefitinib dose was reduced. However, the PFS has been maintained for approximately 78 months. LESSONS: Despite the reduction in gefitinib dose due to side effects, the combined treatment of gefitinib and the modified BJIKT has maintained a PFS of over 78 months, indicating that modified BJIKT enhanced the anti-cancer effect of gefitinib in a patient with advanced NSCLC harboring the EFGR mutation, and may have delayed acquired resistance, the main limitation on the efficacy of gefitinib. Further investigations including clinical trials are needed to confirm these effects.

Effectiveness and safety of herbal medicine for cancer-related fatigue in lung cancer survivors: A systematic review and meta-analysis.

Approximately half of lung cancer patients (LCP) receiving chemotherapy are experiencing cancer-related fatigue (CRF). In East Asia, herbal medicines (HMs) have been used as tonics due to their anti-fatigue effect. This systematic review evaluated the effectiveness and safety of HMs for CRF in LCP. We comprehensively searched 12 electronic medical databases to search randomized controlled trials (RCTs) and quasi-RCTs investigating HMs for CRF in LCP, published up to September 2019. The primary outcome was the fatigue severity. Secondary outcomes included patients' quality of life (QOL), activities of daily life (ADL), and incidence of adverse events. Cochrane's risk of bias tool assessed the methodological quality of included RCTs. The risk ratio or mean difference was estimated with 95% confidence intervals by performing a meta-analysis. Twelve RCTs with 861 participants were included. Compared to conventional medicine alone, HM combined with conventional medicine significantly improved fatigue level, QOL, and ADL. As monotherapy, HM significantly improved ADL compared with megestrol. No serious HM-related adverse events were reported. Limited evidence suggests that HM could be effective and safe for CRF in LCP. However, further high-quality RCTs are needed to confirm these findings owing to the small number and low methodological quality of the included studies.

A consensus guideline of herbal medicine for coronavirus disease 2019.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which originated in Wuhan, Hubei Province, China in late December 2019, is the cause of ongoing pandemic. We analyzed the symptoms of SARS-CoV-2, a classification of the Chinese medicine dialectic and treatment regimen, and promptly enacted the recommendation of Korean medicine preparations in herbal medicine covered under domestic medical insurance benefits depending on the circumstances in our country. METHOD: The clinical practice guideline (CPG) for the treatment of SARS-CoV-2 was developed based on consensus from a group of experts. RESULTS: Two kinds of herbal medicines (HM) were recommended for the prevention of SARS-CoV-2; Youngyopaedoc-san plus Bojungikgitang, and Youngyopaedoc-san plus Saengmaek-san. Two herbal preparations were recommended for people with a history of exposure to SARS-CoV-2; Youngyopaedoc-san plus Bulhwangeumjeonggi-san, and Youngyopaedoc-san plus Bojungikgi-tang. Three herbal preparations were recommended for mildly symptomatic COVID-19 patients; Youngyopaedoc-san plus Galgunhaegui-tang was recommended for those without pneumonia with wind-warmth disease invading the lungs; Sosiho-tang plus Bulhwangeumjeonggi-san was recommended for those with dampness-heat disease in the lungs. For the recovery stage, Samchulkunbi-tang plus Saengmaek-san, or Samchulkunbi-tang plus Chungseuiki-tang was recommended. CONCLUSION: The CPG was developed to guide the use of Korean herbal medicine in the treatment of SARS-CoV-2, and it is expected that this will be the basis for providing proper treatment of similar infectious diseases in the future.