Background and Objectives: This study aimed to investigate the protective effect of polydeoxyribonucleotide (PDRN) against skin flap necrosis in a murine skin flap model.Materials and Method Twenty mice with rectangular skin flaps on the dorsum were randomly divided into the PDRN (n=10) and pentobarbital sodium (PBS) (n=10) injection groups. PDRN (8 mg/kg) was subdermally injected at 12 different points immediately after the operation. After 7 days, the flap perfusions were evaluated using a laser speckle contrast imaging (LSCI) system, and specimens were collected for immunohistochemistry analysis. Results: The percentage of survival area relative to the total flap area was significantly higher in the PDRN group (60.87%±7.63%) than in the PBS group (45.23%±10.72%) (p<0.05). The mean LSCI perfusion signal of the distal part of the skin flap in the PBS group was 0.57±0.12, and that in the PDRN group was 0.74±0.13 (p<0.05). The PDRN group had a significantly lower interleukin 1 beta expression than the PBS group and higher vascular endothelial growth factor α expression than the PBS group (p<0.05). Conclusion These findings suggest that subdermally injected PDRN is more effective in enhancing flap survival during necrosis.

Background: This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. Methods: In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. Results: The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. Conclusion Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Background: The importance of animal welfare is being recognized worldwide. Recently, the increasing demand for enhanced laboratory animal welfare has led to clinically featured transformations of animal research institutes. This study aims to describe the process and findings of veterinary medical check-ups and its influence on laboratory dogs and pigs welfare. Regular medical checkups were conducted by the attending veterinarian twice a year to ensure the health and welfare of dogs and pigs in our animal research institute. Based on the findings from the medi‑ cal checkup, we assessed the current health of dogs and pigs,providing reasonable treatments to prevent the risk of complications. Results: Blood tests and physical examinations revealed clinically relevant findings. Some of these findings were due to insufficient postoperative care after invasive surgical experiments and the remaining were predictable side effects after surgical experiments. However, one finding involved severe gum bleeding due to retained deciduous teeth.This animal was euthanized because it was judged to reach the humane endpoint. Majority of the dogs and pigs at our animal research institute were considered to be healthy, based on the comprehensive results of the medical checkups. Conclusions Regular medical checkups by the attending veterinarian established enhanced animal welfare, ensur‑ ing the accuracy and reproducibility of animal studies. This pioneering veterinary animal care program can serve as a potential advanced guideline for animal research institutes to improve dogs and pigs welfare.

Purpose: We investigated whether the use of a phosphodiesterase-5 inhibitor (PDE5i) after robot assited radical prostatectomy has a survival benefit over non-use patients because there are controversial results on the association between PDE5i use and survival outcomes for prostate cancer patients in literature. Materials and Methods: We designed a retrospective, matched, large-sample cohort study of 5,545 patients who underwent robot assisted radical prostatectomy (RARP) during 2013–2021 in a single institute. The exclusion criteria was patients who were aged >70 years at surgery, American Society of Anesthesiologists (ASA) physical status classification grade 4 or 5, history of other malignancies, patients who started PDE5i 6 months after survery and patients with follow up period less than 24 months after surgery. Among the 1,843 included patients, 1,298 were PDE5i users, and 545 were PDE5i non-users. We performed propensity score matching (PSM) of PDE5i users (n=529) with non-users (n=529) by adjusting for the variables of age, Gleason grade group, pathological T stage, preoperative ASA physical status grade, and International Index of Erectile Function score. Results: There were no significant difference in patient characteristics according to PSM. Kaplan–Meier curve revealed the difference of overall survival for PDE5i users and non-users (clustered log-rank test p<0.05). In a stratified Cox regression analysis, PDE5i use after RARP was associated with improved overall survival and reduced risk of death (hazard ratio 0.43; confidence interval 0.24–0.79; p=0.007). The limitation of this study was that the indication for the prescription of PDE5i was not given. Conclusions PDE5i administration after RARP were associated with overall survival of patients with prostate cancer. A further randomized control trial may reveal whether routine use of PDE5i after prostatectomy can improve survival of prostate cancer patient.

Background: Danshen has been widely used in oriental medicine to improve body function. The purpose of this study is to investigate the effect of water-soluble Danshen extract (DE) on weight loss and on activation proteins involved in mitochondrial biogenesis in brown adipose tissue (BAT) in obese mice. Methods: BAT was isolated from 7-week-old male Sprague-Dawley rats, and expression of proteins related to mitochondrial biogenesis was confirmed in both brown preadipocytes and mature brown adipocytes treated with DE. For the in vivo study, low-density lipoprotein receptor knock out mice were divided into three groups and treated for 17 weeks with: standard diet; high fat diet (HFD); HFD+DE. Body weight was measured every week, and oral glucose tolerance test was performed after DE treatment in streptozotocin-induced diabetic mice. To observe the changes in markers related to thermogenesis and adipogenesis in the BAT, white adipose tissue (WAT) and liver of experimental animals, tissues were removed and immediately frozen in liquid nitrogen. Results: DE increased the expression of uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in brown preadipocytes, and also promoted the brown adipocyte differentiation and mitochondrial function in the mature brown adipocytes. Reactive oxygen species production in brown preadipocytes was increased depending on the concentration of DE. DE activates thermogenesis in BAT and normalizes increased body weight and adipogenesis in the liver due to HFD. Browning of WAT was increased in WAT of DE treatment group. Conclusion DE protects against obesity and activates mitochondrial function in BAT.

The kainic acid-induced seizure mouse model is widely used in epilepsy research. In this study, we applied kainic acid to the subcutaneous injections of three different sources of DBA/2 mice to compare and evaluate the seizure response. The three mouse sources consisted of DBA/2Kor1 (Korea FDA source), DBA/2A (USA source), and DBA/2 (Japan source), and were purchased from different vendors. To compare the responses of DBA/2 mice to kainic acid injections, we examined the survival rate, seizure phenotype scoring, and behavioral changes. We also evaluated brain lesions using histopathological analysis. Following the administration of kainic acid, almost half of the cohort survived, and the seizure phenotype displayed a moderate level of sensitivity (2 ~ 4 out of 6). In the histopathologic analysis, there was no change in morphological features, and levels of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) increased in the kainic acid-treated groups. However, there was no difference in the neuronal nuclei (NeuN) expression level. All the data showed that the responses in the kainic acid-treated group were similar across the three strains. In conclusion, our results suggest that the three sources of DBA/2 mice (DBA/2Kor1, DBA/2A, and DBA/2B) have similar pathological responses to kainic acid-induced seizures.

Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.

The kainic acid-induced seizure mouse model is widely used in epilepsy research. In this study, we applied kainic acid to the subcutaneous injections of three different sources of DBA/2 mice to compare and evaluate the seizure response. The three mouse sources consisted of DBA/2Kor1 (Korea FDA source), DBA/2A (USA source), and DBA/2 (Japan source), and were purchased from different vendors. To compare the responses of DBA/2 mice to kainic acid injections, we examined the survival rate, seizure phenotype scoring, and behavioral changes. We also evaluated brain lesions using histopathological analysis. Following the administration of kainic acid, almost half of the cohort survived, and the seizure phenotype displayed a moderate level of sensitivity (2 ~ 4 out of 6). In the histopathologic analysis, there was no change in morphological features, and levels of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) increased in the kainic acid-treated groups. However, there was no difference in the neuronal nuclei (NeuN) expression level. All the data showed that the responses in the kainic acid-treated group were similar across the three strains. In conclusion, our results suggest that the three sources of DBA/2 mice (DBA/2Kor1, DBA/2A, and DBA/2B) have similar pathological responses to kainic acid-induced seizures.

Botulinum-toxin A (BoNT/A) is a widely used not only for cosmetics but also for various experimental purposes including muscle-related research. In this study, we applied BoNT/A to mouse muscle of three different sources to compare and evaluate the biological and pathological response. The three different mouse sources consist of Korl: ICR (Korea FDA source), A:ICR (USA source) and B:ICR (Japan source) which were purchased from each different vendors. To compare the responses of ICR mice with BoNT/A muscle injection, we examined the body weight, hematological and serum biochemistry analysis. Also, we evaluated the muscle change by histopathological analysis and gene expression patterns of muscle-related target by qPCR. The body weight gain was decreased in the BoNT/ A-treated group compared with the control group. In clinical pathologic analysis and gene expression patterns, the data showed that the responses in the BoNT/A-treated group were similar compared with the control group. Decreased muscle fiber was observed in BoNT/A-treated group compared with control group, while Korl:ICR showed a little low response with the other mouse sources. In conclusion, our results suggest that three different sources ICR mice (Korl:ICR, A:ICR and B:ICR) have a similar biological and pathological responses in BoNT/A muscle injection.

BACKGROUND: Endotracheal intubation in patients with compromised cervical vertebrae and limited mouth opening is challenging, however, there are still limited options available. Among devices used for managing difficult airways, the Clarus Video System (CVS) might have considerable promise due to its semi-rigid tip. We evaluated the performance of CVS in patients with simulated difficult airways. METHODS: Philadelphia cervical collars were applied to 74 patients undergoing general anesthesia. The degree of simulated difficult airway was assessed by observing laryngeal view using McCoy laryngoscope; modified Cormack and Lehane grade (MCL) ≥ 3a (high-grade group, n = 38) or ≤ 2b (low-grade group, n = 36). Subsequently, patients were intubated using CVS by a blinded practitioner. We evaluated total time to intubation, intubation success rate, and conditions of intubation. RESULTS: Intubation took significantly longer time for the high-grade group than that for the low-grade group (38.2 ± 25.9 seconds vs. 27.9 ± 6.2 seconds, time difference 10.3 seconds, 95% confidence interval: 1.4–19.2 seconds, P < 0.001). However, CVS provided similar high intubation success rates for both groups (97.4% for the high-grade and 100% for the low-grade group). During intubation, visualization of vocal cords and advancement into the glottis for the high-grade group were significantly more difficult than those for the low-grade group. CONCLUSIONS: Although intubation took longer for patients with higher MCL laryngeal view grade, CVS provided high intubation success rate for patients with severely restricted neck motion and mouth opening regardless of its MCL laryngeal view grade.
Anesthesia, General ; Cervical Vertebrae ; Female ; Glottis ; Humans ; Intubation ; Intubation, Intratracheal* ; Laryngoscopes ; Mouth ; Neck ; Vocal Cords