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BACKGROUND/AIMS: The impact of coronavirus disease 2019 (COVID-19) on the management of colorectal cancer (CRC) may worse in elderly population, as almost all COVID-19 deaths occurred in the elderly patients. This study aimed to evaluate the impact of COVID-19 on CRC management in the elderly population. METHODS: The numbers of patients who underwent colonoscopy, who visited hospitals or operated for CRC in 2020 and 2021 (COVID-19 era) were compared with those in 2019, according to 3 age groups (≥70 years, 50-69 years, and ≤49 years), based on the nationwide, population-based database (2019-2021) in South Korea. RESULTS: The annual volumes of colonoscopy and hospital visits for CRC in 2020 were more significantly declined in the old age group than in the young age group (both P

Abstract Background High-grade serous ovarian cancer (HGSOC), which is known for its heterogeneity, high recurrence rate, and metastasis, is often diagnosed after being dispersed in several sites, with about 80% of patients experiencing recurrence. Despite a better understanding of its metastatic nature, the survival rates of patients with HGSOC remain poor. Methods Our study utilized spatial transcriptomics (ST) to interpret the tumor microenvironment and computed tomography (CT) to examine spatial characteristics in eight patients with HGSOC divided into recurrent (R) and challenging-to-collect non-recurrent (NR) groups. Results By integrating ST data with public single-cell RNA sequencing data, bulk RNA sequencing data, and CT data, we identified specific cell population enrichments and differentially expressed genes that correlate with CT phenotypes. Importantly, we elucidated that tumor necrosis factor-α signaling via NF-κB, oxidative phosphorylation, G2/M checkpoint, E2F targets, and MYC targets served as an indicator of recurrence (poor prognostic markers), and these pathways were significantly enriched in both the R group and certain CT phenotypes. In addition, we identified numerous prognostic markers indicative of nonrecurrence (good prognostic markers). Downregulated expression of PTGDS was linked to a higher number of seeding sites (≥ 3) in both internal HGSOC samples and public HGSOC TCIA and TCGA samples. Additionally, lower PTGDS expression in the tumor and stromal regions was observed in the R group than in the NR group based on our ST data. Chemotaxis-related markers (CXCL14 and NTN4) and markers associated with immune modulation (DAPL1 and RNASE1) were also found to be good prognostic markers in our ST and radiogenomics analyses. Conclusions This study demonstrates the potential of radiogenomics, combining CT and ST, for identifying diagnostic and therapeutic targets for HGSOC, marking a step towards personalized medicine.

Summary: Background: In an interim analysis of this phase 2 trial, adding the GX-188E vaccine to pembrolizumab resulted in manageable toxicity with antitumor activities in patients with recurrent or advanced cervical cancer. Here, we report the final safety and efficacy results after a long-term follow-up at the study's completion. Methods: This open-label, single-arm, phase II trial was conducted in nine hospitals in South Korea (ClinicalTrials.gov identifier, NCT03444376). Eligible patients were aged ≥18 years with recurrent or advanced inoperable cervical cancer, Eastern Cooperative Oncology Group Performance status of 0 or 1, and positivity for HPV 16/18, who failed the available standard-of-care therapy. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, 19, and 46 and intravenous 200 mg pembrolizumab every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the objective response rate (ORR) within 24 weeks. Findings: Between June 19, 2018, and December 24, 2021, 65 patients were enrolled and received at least one dose of the study treatment. Sixty patients received combination treatment with GX-188E and pembrolizumab and underwent efficacy analysis. After a median follow-up of 14.72 months, the confirmed ORR was 35.0% (95% CI, 23.1–48.4). Five patients (8.3%) had a complete response, and 16 (26.7%) had a partial response. In addition, patients with PD-L1-positive and PD-L1-negative tumors had an ORR of 38.9% (95% CI, 23.1–56.5) and 29.2% (95% CI, 12.6–51.1), respectively. The median duration of response of all the patients was 12.3 months (95% CI, 5.3–not reached [NR]). For those with PD-L1-positive tumors, it was 12.3 months (95% CI, 3.5–NR), and for those with PD-L1-negative tumors, it was NR (95% CI, 2.4–NR). The median progression-free survival of the 60 patients was 4.4 months (95% CI, 2.1–8.3), and the median overall survival was 23.8 months (95% CI, 14.0–NR). 22 (33.8%) of 65 patients had treatment-related adverse events (TRAEs) of any grade and four (6.2%) had grade 3–4 TRAEs. No treatment-related deaths occurred. Interpretation: The GX-188E vaccine combined with pembrolizumab in recurrent or advanced HPV-positive cervical cancer was safe and showed a promising overall survival and clinical response rate. This combination therapy might provide a new potential treatment option for patients with recurrent or advanced cervical cancer. Funding: National Cancer Center Onco-Innovation Unit, Korea.

Abstract Background Sigmoid sinus diverticulum/dehiscence (SSD) is one of the treatable causes of venous pulsatile tinnitus. It can be diagnosed using temporal bone computed tomography (CT) or magnetic resonance angiography/venography (MRA). In cases where patients find their symptoms intolerable, surgical treatment is typically preferred. Here, we have presented a novel surgical technique involving sigmoid sinus re‐roofing and have analyzed its feasibility. Methods Between January 2020 and July 2023, approximately 150 patients with pulsatile tinnitus were evaluated at two different tertiary hospitals. Of these, 12 patients were diagnosed with SSD, and seven underwent surgical treatment. Five patients were treated with tailored reroofing (TRR) of the sigmoid sinus and two with transmastoid resurfacing (MRS) of the sigmoid sinus. We compared the Korean tinnitus handicap inventory (K‐THI) score, pure tone audiogram (PTA) threshold, and CT findings before and a month after surgeries for these two techniques. The operation time was also analyzed. Results In TRR cases, the K‐THI score reduced from 55.0 ± 31.4 preoperatively to 4.0 ± 3.0 postoperatively, and the SSD was well‐repositioned and covered by a bone chip postoperatively. In MRS cases, the K‐THI score reduced from 41.0 ± 9.9 preoperatively to 15.0 ± 21.2 postoperatively, and the SSD was well‐covered with bone cement postoperatively. The average surgical time of five TRR and two MRS cases were 77.5 ± 32.5 and 174.0 ± 75.0 min, respectively. No complications were noted. Conclusions Despite the insufficient number of cases, we noted that TRR requires a reasonable amount of time, involves a smaller incision, and may provide favorable outcomes compared to conventional MRS in cases of pulsatile tinnitus associated with SSD. Level of evidence IV.

Background and Objectives: Postoperative nausea and vomiting (PONV) is a common issue for females undergoing gynecological surgeries, including those assisted by robotic systems. Despite available prophylactic measures, the incidence of PONV remains high, negatively impacting recovery and increasing healthcare costs. This study evaluates whether preoperative gum chewing reduces the need for anti-emetic drugs in females undergoing robot-assisted laparoscopic surgery for benign ovarian mass. Materials and Methods: This prospective, single-blinded, randomized controlled trial enrolled 92 adult females scheduled for robot-assisted laparoscopic surgery to treat benign ovarian mass. Following exclusions, the remaining participants were randomly assigned to either a gum-chewing group or a no-gum-chewing group. The gum-chewing group chewed sugar-free gum for 15 min in the holding area before surgery. The primary outcome measured was the need for anti-emetics to control PONV during the first hour in the post-anesthesia care unit (PACU). Secondary outcomes included the number of anti-emetic requests. No preemptive anti-emetics were administered during surgery. Results: Out of the initial 92 patients, 88 were included in the final analysis, with 44 in each group. The incidence of PONV requiring anti-emetics in the PACU was significantly lower in the gum-chewing group (79.5%) compared to the no-gum-chewing group (95.5%). Additionally, the number of anti-emetic requests was higher in the no-gum-chewing group. No postoperative complications such as tooth or jaw pain/injury or gastric content regurgitation were reported. Conclusions: Preoperative gum chewing for 15 min immediately before surgery significantly reduced the incidence of PONV in females undergoing robot-assisted laparoscopic surgery for benign ovarian mass. This simple, non-pharmacological intervention improved patient comfort and reduced the need for anti-emetic medications without any adverse effects. Further studies are needed to confirm these findings and to develop guidelines for incorporating preoperative gum chewing into clinical practice.

Abstract Background Denosumab (DMB) is a bone antiresorptive agent used to treat osteoporosis or metastatic cancer of the bones. However, denosumab-associated osteonecrosis of the jaw (DRONJ) has become a common complication in cancer patients. The prevalence of osteonecrosis of the jaw (ONJ) in cancer patients is estimated to be similar for both bisphosphonate-related cases (1.1 to 1.4%) and denosumab-related cases (0.8 to 2%), with the addition of adjunctive therapy with anti-angiogenic agents reportedly increasing its prevalence to 3%. (Spec Care Dentist 36(4):231–236, 2016). The aim of this study is to report on DRONJ in cancer patients treated with DMB (Xgeva®, 120mg). Case presentation In this study, we identified four cases of ONJ among 74 patients receiving DMB therapy for metastatic cancer. Of the four patients, three had prostate cancer and one had breast cancer. Preceding tooth extraction within 2 months of the last DMB injection was found to be a risk factor for DRONJ. Pathological examination revealed that three patients had acute and chronic inflammation, including actinomycosis colonies. Among the four patients with DRONJ referred to us, three were successfully treated without complications and had no recurrence following surgical treatment, while one did not follow up. After healing, one patient experienced a recurrence at a different site. Sequestrectomy in conjunction with antibiotic therapy and cessation of DMB use proved to be effective in managing the condition, and the ONJ site healed after an average 5-month follow-up period. Conclusion Conservative surgery, along with antibiotic therapy and discontinuation of DMB, was found to be effective in managing the condition. Additional studies are needed to investigate the contribution of steroids and anticancer drugs to jaw bone necrosis, the prevalence of multicenter cases, and whether there is any drug interaction with DMB.

Background The depth of double-lumen endobronchial tube (DLT) is reportedly known to be directly proportional to height and several height-based recommendations have been suggested. This retrospective study was designed to find out the difference between calculated depths using height-based formulae and realistic depths in clinical practice of DLT placement by analyzing pooled data from patients intubated with left-sided DLT. Methods The electronic medical records of adults, intubated with DLT from February 2018 to December 2020, were reviewed. Data retrieved included age, sex, height, weight, and size and depth of DLT. The finally documented DLT depth (depth final, DF) was compared with the calculated depths, and the relationship between height and DF was also evaluated. A questionnaire on endobronchial intubation method was sent to anesthesiologists. Results A total of 503 out of 575 electronic records of consecutive patients were analyzed. Although the relationship between height and DF was shown to have significant correlation (Spearman’s rho = 0.63, P < 0.001), DF was shown to be significantly greater than calculated depths (P < 0.001). Despite 57.1% of anesthesiologists have knowledge of clinical recommendations to anticipate size and depth of DLT, no one routinely utilizes those recommendations. Conclusions Anesthesiologists tend to place DLTs in a deeper position than expected when depths are calculated using height-based recommendations. Although such discrepancies may not be clinically meaningful, efforts are needed to standardize the methods of endobronchial intubation to prevent potential complications associated with malposition.

AbstractIn this study, the α-amylase inhibitory activity, α-glucosidase inhibitory activity, pancreatic lipase inhibitory activity, and Xanthine Oxidase inhibitory activity of the fruiting body extracts of 5 varieties of Agaricus bisporus (AB) were confirmed. First, the α-amylase inhibitory activity of AB12, AB13, AB18, AB34, and AB40 methanol extracts was lower than that of acarbose, a positive control, in all concentration ranges. The α-glucosidase inhibitory activity of the AB40, AB13, and AB12 methanol extracts at the extract concentration of 1.0 mg/mL was 80.5%, 81.3%, and 78.5%, respectively, similar to that of acarbose, a positive control. The pancreatic lipase inhibitory activity of the methanol extract of Agaricus bisporus fruiting body was significantly lower than that of the positive control orlistat in the concentration range of 50 ∼ 1.000 (mg/mL). The Xanthine Oxidase inhibitory activity was 0.5 ∼ 8.0 mg/mL of each extract, which was significantly lower than that of the positive control allopurinol in the same concentration range. However, the Xanthine Oxidase inhibitory activity of AB13 and AB40 at 8.0 mg/mL was about 70%, which was higher than that of other mushrooms. In conclusion, five kinds of Agaricus bisporus fruiting bodies seem to have inhibitory effects on enzymes such as α-amylase, α-glucosidase, pancreatic lipase, and Xanthine Oxidase that degrade starch and protein. In particular, it has an inhibitory effect and a reduction effect on xanthine oxidase that causes gout, so it is expected that it can be developed and used as a food or health supplement with health functional properties through future research.

In October 2022, common Asian cowpea (Vigna nakashimae) powdery mildew disease was investigated at Yesan-gun, Chungcheongnam-do, Korea (36°40’12.7′ N,126°51’36.4′ E). The disease mainly occurred on the front of the leaves, and weak powdery mildew disease occurred on the back side of leaf. The chasmothecia was identified on the back side of the leaf. Analysis of the internal transcribed spacer rDNA sequence and 28S large subunit sequence, along with the morphological characteristics of the anamorph and teleomorph of the causal fungus identified as Podosphaera xanthii. This is the first time in Korea to report common Asian cowpea (Vigna nakashimae) powdery mildew disease caused by Podospaera xanthii.

Abstract Discrimination of ovarian tumors is necessary for proper treatment. In this study, we developed a convolutional neural network model with a convolutional autoencoder (CNN-CAE) to classify ovarian tumors. A total of 1613 ultrasound images of ovaries with known pathological diagnoses were pre-processed and augmented for deep learning analysis. We designed a CNN-CAE model that removes the unnecessary information (e.g., calipers and annotations) from ultrasound images and classifies ovaries into five classes. We used fivefold cross-validation to evaluate the performance of the CNN-CAE model in terms of accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). Gradient-weighted class activation mapping (Grad-CAM) was applied to visualize and verify the CNN-CAE model results qualitatively. In classifying normal versus ovarian tumors, the CNN-CAE model showed 97.2% accuracy, 97.2% sensitivity, and 0.9936 AUC with DenseNet121 CNN architecture. In distinguishing malignant ovarian tumors, the CNN-CAE model showed 90.12% accuracy, 86.67% sensitivity, and 0.9406 AUC with DenseNet161 CNN architecture. Grad-CAM showed that the CNN-CAE model recognizes valid texture and morphology features from the ultrasound images and classifies ovarian tumors from these features. CNN-CAE is a feasible diagnostic tool that is capable of robustly classifying ovarian tumors by eliminating marks on ultrasound images. CNN-CAE demonstrates an important application value in clinical conditions.

Background Postpartum hemorrhage (PPH) is a major cause of maternal mortality and the risk factors for PPH differ among studies. In this large-scale study, we investigated whether the anesthetic method used was associated with PPH after cesarean section. Methods We extracted data on cesarean sections performed between January 2008 and June 2013 from the National Health Insurance Service database. The anesthetic methods were categorized into general, spinal and epidural anesthesia. To compare the likelihood of PPH among deliveries using different anesthetic methods, crude and adjusted odds ratios (ORs) and 95% confidence intervals were calculated using logistic regression analysis. Results Data from 330,324 cesarean sections were analyzed, and 21,636 cases of PPH were identified. Univariate analysis showed that general and epidural anesthesia increased the risk of PPH compared to spinal anesthesia. The OR for PPH was highest for morbidly adherent placenta, followed by placenta previa, placental abruption, and hypertension. When other clinical covariates were controlled for, general and epidural anesthesia still remained significant risk factors for PPH compared to spinal anesthesia. Conclusions This study showed that general and epidural anesthesia elevated the risk of PPH compared to spinal anesthesia during cesarean section. Since we could not consider the potential bias of group differences in indications, more in-depth clinical trials are needed to validate our findings. Obstetric factors such as placental abnormalities had high odds ratios and thus are more important than the choice of anesthetic method, which should be based on the patient’s clinical condition and institutional resources.

Laccase is an enzyme that plays an important role in fungi, including lignin degradation, stress defense, and formation of fruiting bodies. Auricularia auricula-judae is a white-rot fungus in the Basidiomycota phylum, capable of delignifying wood. In this study, seven genes belonging to the laccase family were identified through de novo sequencing, containing Cu-Oxidase, Cu-Oxidase_2, and Cu-Oxidase_3 domains. Subsequently, the physical characteristics, phylogenetic relationships, protein secondary structure, and tertiary structure of the laccase family (AaLac1–AaLac7) were analyzed. Prediction of N-glycosylation sites identified 2 to 10 sites in the laccase family, with AaLac7 having the highest number of sites at 10. Sequence alignment and analysis of the laccase family showed high consistency in signature sequences. Phylogenetic analysis confirmed the relationship among laccases within the family, with AaLac3–AaLac4 and AaLac5–AaLac6 being closely positioned on the tree, exhibiting high similarity in tertiary structure predictions. This study identified and analyzed laccase family genes in Auricularia auricula-judae using de novo sequencing, offering a simple method for identifying and analyzing the laccase family in organisms with unknown genetic information. [ABSTRACT FROM AUTHOR]

Abstract Background Exosomal miRNAs regulate gene expression and play important roles in several diseases. We used exosomal miRNA profiling to investigate diagnostic biomarkers of epithelial ovarian cancer (EOC). Methods In total, 55 individuals were enrolled, comprising healthy (n = 21) and EOC subjects (n = 34). Small mRNA (smRNA) sequencing and real-time PCR (RT-PCR) were performed to identify potential biomarkers. Receiver operating characteristic (ROC) curves were conducted to determine biomarker sensitivity and specificity. Results Using smRNA sequencing, we identified seven up-regulated (miR-4732-5p, miR-877-5p, miR-574-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7f-5p) and two down-regulated miRNAs (miR-1273f and miR-342-3p) in EOC patients when compared with healthy subjects. Of these, miR-4732-5p and miR-1273f were the most up-regulated and down-regulated respectively, therefore they were selected for RT-PCR analysis. Plasma derived exosomal miR-4732-5p had an area under the ROC curve of 0.889, with 85.7% sensitivity and 82.4% specificity in distinguishing EOC patients from healthy subjects (p

Abstract Melanoma is a disease with a high recurrence rate and poor prognosis; therefore, the need for targeted therapeutics is steadily increasing. Oligodendrocyte transcription factor2 (Olig2) is a basic helix-loop-helix transcription factor that is expressed in the central nervous system during embryonic development. Olig2 is overexpressed in various malignant cell lines such as lung carcinoma, glioma and melanoma. Olig2 is known as a key transcription factor that promotes tumor growth in malignant glioma. However, the role of Olig2 in melanoma is not well characterized. We analyzed the role of Olig2 in apoptosis, migration, and invasion of melanoma cells. We confirmed that Olig2 was overexpressed in melanoma cells and tissues. Reduction of Olig2 increased apoptosis in melanoma cells by increasing p53 level and caspase-3/-7 enzyme activity. In addition, downregulation of Olig2 suppressed migration and invasion of melanoma cells by inhibiting EMT. Reduction of Olig2 inhibited expression of MMP-1 and the enzyme activity of MMP-2/-9 induced by TGF-β. Moreover, Olig2 was involved in the downstream stages of MEK/ERK and PI3K/AKT, which are major signaling pathways in metastatic progression of melanoma. In conclusion, this study demonstrated the crucial roles of Olig2 in apoptosis, migration, and invasion of melanoma and may help to further our understanding of the relationship between Olig2 and melanoma progression.

Objective: Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods: This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 μM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results: A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 μM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 μM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion: The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage. [ABSTRACT FROM AUTHOR]

Background and Objectives: Postoperative nausea and vomiting (PONV) is a common issue for females undergoing gynecological surgeries, including those assisted by robotic systems. Despite available prophylactic measures, the incidence of PONV remains high, negatively impacting recovery and increasing healthcare costs. This study evaluates whether preoperative gum chewing reduces the need for anti-emetic drugs in females undergoing robot-assisted laparoscopic surgery for benign ovarian mass. Materials and Methods: This prospective, single-blinded, randomized controlled trial enrolled 92 adult females scheduled for robot-assisted laparoscopic surgery to treat benign ovarian mass. Following exclusions, the remaining participants were randomly assigned to either a gum-chewing group or a no-gum-chewing group. The gum-chewing group chewed sugar-free gum for 15 min in the holding area before surgery. The primary outcome measured was the need for anti-emetics to control PONV during the first hour in the post-anesthesia care unit (PACU). Secondary outcomes included the number of anti-emetic requests. No preemptive anti-emetics were administered during surgery. Results: Out of the initial 92 patients, 88 were included in the final analysis, with 44 in each group. The incidence of PONV requiring anti-emetics in the PACU was significantly lower in the gum-chewing group (79.5%) compared to the no-gum-chewing group (95.5%). Additionally, the number of anti-emetic requests was higher in the no-gum-chewing group. No postoperative complications such as tooth or jaw pain/injury or gastric content regurgitation were reported. Conclusions: Preoperative gum chewing for 15 min immediately before surgery significantly reduced the incidence of PONV in females undergoing robot-assisted laparoscopic surgery for benign ovarian mass. This simple, non-pharmacological intervention improved patient comfort and reduced the need for anti-emetic medications without any adverse effects. Further studies are needed to confirm these findings and to develop guidelines for incorporating preoperative gum chewing into clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background Pain assessment and management are important in postoperative circumstances as overdosing of opioids can induce respiratory depression and critical consequences. We aimed this study to check the reliability of commonly used pain scales in a postoperative setting among Korean adults. We also intended to determine cut-off points of pain scores between mild and moderate pain and between moderate and severe pain by which can help to decide to use pain medication. Methods A total of 180 adult patients undergoing elective non-cardiac surgery were included. Postoperative pain intensity was rated with a visual analog scale (VAS), numeric rating scale (NRS), faces pain scale revised (FPS-R), and verbal rating scale (VRS). The VRS rated pain according to four grades: none, mild, moderate, and severe. Pain assessments were performed twice: when the patients were alert enough to communicate after arrival at the postoperative care unit (PACU) and 30 min after arrival at the PACU. The levels of agreement among the scores were evaluated using intraclass correlation coefficients (ICCs). The cut-off points were determined by receiver operating characteristic curves. Results The ICCs among the VAS, NRS, and FPS-R were consistently high (0.839–0.945). The pain categories were as follow: mild ≦ 5.3 / moderate 5.4 ~ 7.1 /severe ≧ 7.2 in VAS, mild ≦ 5 / moderate 6 ~ 7 / severe ≧ 8 in NRS, mild ≦ 4 / moderate 6 / severe 8 and 10 in FPS-R. The cut-off points for analgesics request were VAS ≧ 5.5, NRS ≧ 6, FPS-R ≧ 6, and VRS ≧ 2 (moderate or severe pain). Conclusions During the immediate postoperative period, VAS, NRS, and FPS-R were well correlated. The boundary between mild and moderate pain was around five on 10-point scales, and it corresponded to the cut-off point of analgesic request. Healthcare providers should consider VRS and other patient-specific signs to avoid undertreatment of pain or overdosing of pain medication.

Abstract Acquisition of recurrent/metastatic potential by a tumor cell defines a critical step in malignant progression. However, understanding of metastatic progression at the molecular level is scarce for cervical carcinomas (CES). In this study, we performed genomic, transcriptomic, and viral profiling of five pairs of primary (CES‐P) and matched recurrent/metastatic tumors (CES‐R/M) with high risk human papillomavirus. Whole exome sequencing revealed mutation features of CES‐R/M including elevated mutation burdens and prevalent copy number alterations compared to their matched CES‐P. A relative deficit of APOBEC‐related mutation signatures accompanying the transcriptional downregulation of APOBEC3A was observed for CES‐R/M. Mutations in genes encoding epigenetic regulators were commonly observed as CES‐R/M‐specific alterations. Immunoprofiling and gene set analysis revealed CES‐Ps were enriched with transcripts representing activated anticancer immunity such as interferon‐gamma pathway, while CES‐R/M exhibited upregulation of genes involved in epithelial‐mesenchymal transition and angiogenesis. Viral capture sequencing revealed that integration sites remained enriched in viral E1 protein domain during malignant progression. Moreover, we found transcriptional upregulation of POSTN and downregulation of APOBEC3A were associated with unfavorable clinical outcomes in CES. Comprehensive genomic and transcriptomic profiling of a rare cohort including CES‐R/M identified metastases‐specific features to advance the molecular understanding into CES metastatic progression with potential clinical implications.

Abstract Background Combined spinal-epidural anesthesia (CSEA) can be performed with either a single-space technique or a double-space technique for cesarean section. We performed a double-blind randomized controlled study to compare the effect of the double-space technique with that of the single-space technique on sensory block level and side effects. Methods Parturients undergoing elective cesarean section under regional anesthesia were randomized to receive CSEA with either the double-space technique (double group, n = 20) or the single-space technique (single group, n = 20). In the double group, an epidural catheter was inserted at the L1–2 interspace, and dural puncture was performed at the L3–4 interspace. In the single group, the procedure was performed at the L3–4 interspace using the needle-through-needle technique. Results There were no differences in time to readiness or intraoperative level of sensory block between the two groups. The postoperative sensory level was maintained at a higher level in the double group than in the single group (1 h postoperatively, P = 0.029; 6 h postoperatively, P = 0.016). There was no difference between the two groups in terms of side effects. The parturient satisfaction scores 48 h postoperatively were significantly different between groups (9.5 in the double group vs. 8 in the single group, P = 0.004). Conclusions We conclude that there were no differences in intraoperative variables between the double-space technique and the single-space technique for CSEA. However, double-space CSEA for cesarean section may be beneficial for controlling postoperative pain and improving parturient satisfaction. Trial registration The study was retrospectively registered at https://cris.nih.go.kr under the trial ID KCT0002514. Date of registration: October 27, 2017.

Context Methyl lucidone (ML) from the dried fruit of Lindera erythrocarpa Makino (Lauraceae) exhibits cytotoxic effects in various cancer cell lines. However, its effects on ovarian cancer cells remain unknown. Objective This study evaluates the mechanism of ML-induced apoptosis, cell cycle distribution in ovarian cells. Materials and methods The cytotoxic effect of ML (2.5–80 µM) on OVCAR-8 and SKOV-3 cells was evaluated by MTS assay for 24 and 48 h. Apoptosis and cell cycle arrest were analysed by flow cytometry. PCR, western blot analyses were performed to examine the related signalling pathways. Results ML induced significant cellular morphological changes and apoptosis in ovarian cancer cells, leading to an antiproliferative effect (IC50 = 33.3–54.7 µM for OVCAR-8 and 48.8-60.7 µM for SKOV-3 cells). Treatment with ML induced cleavage of caspase-3/9 and PARP and release of cytochrome c from the mitochondria. Moreover, ML downregulated the expression of Bcl-2 and Bcl-xL and induced cell cycle arrest in the G2/M phase. Additionally, ML suppressed the expression of cyclin-A/B and promoted that of the cyclin-dependent kinase inhibitors p21 and p27. The expression of death receptors was not altered. Interestingly, ML also inhibited the activity of PI3K/Akt and NF-κB. Discussion and conclusions ML caused G2/M phase arrest and apoptosis in ovarian cancer cells by activating intrinsic apoptotic pathways and suppressing the PI3K/Akt survival pathway. ML may be a potential anticancer agent to suppress ovarian cancer proliferation; thus, to improve the survival rate of cancer patients.

Complex regional pain syndrome (CRPS) is a condition associated with neuropathic pain that causes significant impairment of daily activities and functioning. Nuclear factor kappa B (NFκB) is thought to play an important role in the mechanism of CRPS. Recently, exosomes loaded with super-repressor inhibitory kappa B (Exo-srIκB, IκB; inhibitor of NFκB) have been shown to have potential anti-inflammatory effects in various inflammatory disease models. We investigated the therapeutic effect of Exo-srIκB on a rodent model with chronic post-ischemia pain (CPIP), a representative animal model of Type I CRPS. After intraperitoneal injection of a vehicle, Exo-srIκB, and pregabalin, the paw withdrawal threshold (PWT) was evaluated up to 48 h. Administration of Exo-srIκB increased PWT compared to the vehicle and pregabalin, and the relative densities of p-IκB and IκB showed significant changes compared to the vehicle 24 h after Exo-srIκB injection. The levels of several cytokines and chemokines were reduced by the administration of Exo-srIκB in mice with CPIP. In conclusion, our results showed more specifically the role of NFκB in the pathogenesis of CRPS and provided a theoretical background for novel treatment options for CRPS.

This study was conducted to confirm the expression patterns of genes involved in stress resistance by comparing the expression patterns of genes expressed after sodium chloride (NaCl) treatment in Pleurotus ostreatus (PO) cultivation. To confirm this, as a result of checking different gene expressions for the untreated group and the NaCl 1% and 2% treated group, a total of 12,460 gene expression differences were confirmed. There were 275 and 397 genes with increased expression in the 2.0% and 1.0% NaCl treated group and 400 and 247 genes with reduced expression in the 1.0% and 2.0% NaCl treated group, respectively. Among the genes whose expression was confirmed in DEG, qRT-PCR was performed on six genes to confirm the expression pattern of the genes affecting the mycelium structure. The DEG results showed that a putative aldo-keto reductase of akor3, Alpha-1,4 glucan phosphorylase of PLEOSDRAFT_1058949, and heme-thiolate peroxidase of HTP1 were up-regulated and that glycoside hydrolase family 92 protein of PLEOSDRAFT_1063499 were down-regulated, and the qRT-PCR showed the same results. However, hydrophobin of Hydph16 and pleurotolysin B of plyB were up-regulated in the qRT-PCR results while down-regulated in the DEG results. From the above results, it is judged that NaCl ultimately inhibits growth by inhibiting the formation of the skeleton constituting the mycelium and the physiological activity within the cell.

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs. [ABSTRACT FROM AUTHOR]