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Abstract Hepatitis B virus (HBV) infection is a major health problem, causing thousands of deaths each year worldwide. Although current medications can often inhibit viral replication and reduce the risk of liver carcinoma, several obstacles still hinder their effectiveness. These include viral resistance, prolonged treatment duration, and low efficacy in clearing viral antigens. To address these challenges in current HBV treatment, numerous approaches have been developed with remarkable success. Among these strategies, small-interfering RNA (siRNA) stands out as one of the most promising therapies for hepatitis B. However, naked siRNAs are vulnerable to enzymatic digestion, easily eliminated by renal filtration, and unable to cross the cell membrane due to their large, anionic structure. Therefore, effective delivery systems are required to protect siRNAs and maintain their functionality. In this review, we have discussed the promises of siRNA therapy in treating HBV, milestones in their delivery systems, and products that have entered clinical trials. Finally, we have outlined the future perspectives of siRNA-based therapy for HBV treatment. Graphical Abstract

Purpose Several studies demonstrated that obesity and underweight were negatively associated with outcomes of breast cancer. However, the results are still controversial, and the impact of body mass index (BMI) on distant metastasis-free survival (MFS), which might directly affect mortality, was less well evaluated. Our study aimed to verify the prognostic effect of BMI in breast cancer. Methods A retrospective analysis of 504 patients with stage I–III breast cancer who underwent surgery from January 2005 to December 2013 was performed. The patients were divided into three groups according to preoperative BMI: underweight

Effective treatment of failed back surgery syndrome (FBSS) remains challenging despite urgent medical attention requirements. Depression is a contributing factor to the development and poor prognosis of FBSS, and vice versa. We report the case of a patient with FBSS and major depressive disorder (MDD) treated with graded exercise combined with motion-style acupuncture therapy (MSAT). A 53-year-old male veteran who had undergone lumbar discectomy and laminectomy with instrumented fusion was admitted to the hospital with re-current back pain and radiative pain in the left leg. The effects of failed surgery triggered MDD as a comorbidity. After a six-week routine treatment without remarkable improvement, a three-week program of graded exercise with MSAT was applied. The numeric rating scale (NRS) and short form-36 (SF-36) were used to assess low back pain with radiating leg pain, and daily functioning levels, respectively. The voluntary walking distance of the patients was measured. To analyze the therapeutic effects and other applications of the intervention, we surveyed clinical trials using MSAT or graded exercise therapy (GET). Three weeks of graded exercise with MSAT reduced physical and mental functional disabilities (SF-36, physical component: 15.0 to 37.2, mental component: 21.9 to 30.1) as well as the intensity of low back pain and/or radiative leg pain (NRS: 50 to 30). Furthermore, as the therapeutic intensity gradually increased, there was a significant corresponding increase in daily walking distance (mean daily walking distance, the first week vs. baseline, second, and third week, 3.05 ± 0.56: 2.07 ± 0.79, 4.27 ± 0.96, and 4.72 ± 1.04 km, p = 0.04, p = 0.02, and p = 0.003, respectively). Three randomized controlled trials of GET were included, all showing statistically significant antidepressant effects in the diseased population. Graded exercise with MSAT may be an effective rehabilitative therapy for patients with FBSS and MDD who have impaired daily routines.

We report a case about successful surgical treatment of a granular cell tumor in the ascending colon. A 36-year-old man underwent screening colonoscopy. An endoscopic examination revealed a 10-mm yellowish and hemispheric mass in the ascending colon, and lower endoscopic ultrasonography revealed a hypoechoic-to-isoechoic mass invaded the submucosal layer. The mass was suspected to be a colonic carcinoid tumor. Based on the preoperative evaluation, endoscopic complete resection was considered difficult. Therefore, the lesion was removed via laparoscopic right hemicolectomy. Histological examination revealed that the tumor consisted of nests of polygonal cells with abundant granular eosinophilic cytoplasm. Immunohistochemical staining revealed diffuse positivity for S100 and CD68. Therefore, the tumor was diagnosed as a granular cell tumor. We suggest that surgical resection should be considered if it is located in the thin-walled ascending colon prone to perforation, difficult to rule out malignant tumor due to submucosal invasion, or to remove endoscopically.

Introduction: The purpose of this study was to compare the transcriptomes of poorly cohesive carcinoma (PCC; diffuse-type) and well-differentiated tubular adenocarcinoma (WD; intestinal-type) using gastric cancer (GC) tissues and cell lines and to evaluate the prognostic role of HIV-1 Tat Interactive Protein 2 (HTATIP2). Materials and Methods: We performed next-generation sequencing with 8 GC surgical samples (5 WD and 3 PCC) and 3 GC cell lines (1 WD: MKN74, and 2 PCC: KATOIII and SNU601). Immunohistochemistry was used to validate HTATIP2 expression. We performed functional analysis by HTATIP2 overexpression (OE). Kaplan-Meier survival plots and the PrognoScan database were used for survival analysis. Results: The genes with significantly reduced expression in PCC versus WD (in both tissues and cell lines) were HTATIP2, ESRP1, GRHL2, ARHGEF16, CKAP2L, and ZNF724. According to immunohistochemical staining, the HTATIP2-OE group had significantly higher number of patients with early GC (EGC) (T1) ( P = .024), less lymph node (LN) metastasis ( P = .008), and low TNMA stage ( P = .017) than HTATIP2 underexpression (UE) group. Better survival rates were confirmed in the HTATIP2 OE group by Kaplan-Meir survival and PrognoScan analysis. In vitro, HTATIP2-OE in KATO III cells caused a significant decrease in cancer cell migration and invasion. Decreased Snail and Slug expression in HTATIP2 OE cells suggested that epithelial-mesenchymal transition is involved in this process. Conclusion: HTATIP2 might be a good prognostic marker and a candidate target for GC treatment.

Purpose: Pegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. Materials and methods: This was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. Results: Pegfilgrastim administration reduced FN by 11.8–1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. Conclusion: The use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.

Abstract Background Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. Findings This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. Conclusions The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( https://cris.nih.go.kr ).

Ectopic thymic neoplasm, particularly ectopic thymic carcinoma, is a rare disease that presents as a neck mass. Here, we present a case of ectopic thymic squamous carcinoma in a 65-year-old man who presented with persistent hoarseness. After fine needle aspiration cytology, the patient underwent total thyroidectomy with lymph node dissection. The final histopathological examination revealed the ectopic thymic squamous carcinoma. The patient was discharged without any postoperative complications. The patient received adjuvant radiation therapy and did not progress during the 1-year follow-up period.

Previous studies reported that Bifidobacterium animalis ssp. lactis HY8002 (HY8002) improved intestinal integrity and had immunomodulatory effects. Lactobacillus plantarum HY7717 (HY7717) was screened in vitro from among 21 other lactic acid bacteria (LAB) and demonstrated nitric oxide (NO) production. The aims of this study were to investigate the individual and combined ex vivo and in vivo effects of LAB strains HY8002 and HY7717 at immunostimulating mice that have been challenged with an immunosuppressant drug. The combination of HY8002 and HY7717 increased the secretion of cytokines such as interferon (IFN)-γ, interleukin (IL)-12, and tumor necrosis factor (TNF)-α in splenocytes. In a cyclophosphamide (CTX)-induced immunosuppression model, administration of the foregoing LAB combination improved the splenic and hematological indices, activated natural killer (NK) cells, and up-regulated plasma immunoglobulins and cytokines. Moreover, this combination treatment increased Toll-like receptor 2 (TLR2) expression. The ability of the combination treatment to upregulate IFN-γ and TNF-α in the splenocytes was inhibited by anti-TLR2 antibody. Hence, the immune responses stimulated by the combination of HY8002 and HY7717 are associated with TLR2 activation. The preceding findings suggest that the combination of the HY8002 and HY7717 LAB strains could prove to be a beneficial and efficacious immunostimulant probiotic supplement. The combination of the two probiotic strains will be applied on the dairy foods including yogurt and cheese.

Small intestinal malignant tumor accounts for about 3% of all malignant tumors in the gastrointestinal tract, among which 13% are leiomyosarcoma (LMS). In addition, epithelioid LMS is of very rare occurrence. As small intestinal malignant tumors are initially asymptomatic and nonspecific, diagnosis is often delayed, and this can lead to large tumor at the time of detection and lead to intussusception. We observed ileocolonic intussusception in an 80-year-old male patient who was admitted to the hospital with a complaint of abdominal pain and palpable mass on right lower quadrant. The laparoscopic ileocecectomy was performed by the emergency operation because of obstruction. The pathologic examination revealed that the epithelioid LMS developed in the terminal ileum was the leading point of intussusception. To the best of our knowledge, laparoscopic surgery for ileocolonic intussusception with epithelioid LMS has not yet been reported.

Lysosomes are intracellular acidic organelles with catabolic functions that contribute to the activation of autophagy. Although autophagy abnormality is associated with defects in lysosomal acidification during the progression of nonalcoholic fatty liver disease (NAFLD), the mechanisms of control of lysosomal acidification are not well understood at the molecular level. Thus, we aimed to elucidate the role of the orphan nuclear receptor retinoic acid–related orphan receptor α (RORα) in lysosomal acidification and autophagic flux, particularly in nutrition‐enriched hepatocytes. First, lysosomal acidity was much lower in the hepatocytes obtained from hepatocyte‐specific RORα‐deleted (RORα‐LKO) mice, whereas the infusion of an adenovirus encoding RORα in wild‐type hepatocytes increased lysosomal acidity, as determined by LysoSensor. Second, the lysosomal translocation of the mechanistic target of rapamycin was increased and immature cathepsin D was accumulated in the liver of RORα‐LKO mice. Third, the accumulation of LC3‐II, p62/sequestosome 1 (SQSTM1), and neighbor of BRCA1 gene 1 (NBR1) was increased in the livers of RORα‐LKO mice, indicating an impaired autophagic flux in the livers. Consistently, the number of autolysosomes containing mitochondria and lipid droplets was dramatically reduced in the RORα‐deleted hepatocytes. Finally, we found that RORα induced the transcription of genes involved in lysosomal function, such as Atp6v1g1, a vacuolar H+‐ATPase (v‐ATPase) subunit, which were largely down‐regulated in the livers of mice with high‐fat diet–induced NAFLD and patients with hepatitis. Conclusion: Targeting RORα may be a potential therapeutic strategy to restore lysosomal acidification, which inhibits the progression of NAFLD.

Here, we show that Lactiplantibacillus plantarum LP158 (LP158), Lactobacillus helveticus HY7804 (HY7804), and Lacticaseibacillus paracasei LPC226 (LPC226) isolated from raw milk alleviate non-alcoholic fatty acid disease (NAFLD) in a C57BL/6 mouse model. Lactic acid bacteria (LAB) were screened for their ability to inhibit fatty acid accumulation in palmitic acid (PA)-treated HepG2 cells, and three strains were selected based on the results. We also investigated hemolytic activity and antibiotic resistance of the three strains. LP158, HY7804, and LPC226 suppressed expression of mRNA encoding genes related to lipogenesis, and increased expression of genes related to β-oxidation, in a PA-induced HepG2 cell model. Moreover, when LP158, HY7804, and LPC226 were administered at 109 CFU/kg/day for 8 weeks to mice with dietary-induced NAFLD, they all modulated blood biochemistry markers and reduced steatosis in liver tissue. Also, all three strains significantly reduced expression of mRNA encoding lipogenesis genes (Fasn, Acaca, and Srebp-1c) and inflammatory factors (Tnfα and Ccl-2) and fibrosis factors, and increased expression of a β-oxidation gene (Acox1) in the liver. In particular, HY7804 showed the strongest effects both in vitro and in vivo. Therefore, HY7804, LP158, and LPC226 can be proposed as potential supplements that can improve NAFLD through anti-steatosis, anti-inflammatory, and anti-fibrotic effects.

Bezafibrate, a fibrate drug used as a lipid-lowering agent to treat hyperlipidemia, is a pan-agonist of peroxisome proliferator-activated receptor alpha. It can enhance mitochondrial fatty acid oxidation, oxidative phosphorylation, and mitochondrial biogenesis. After ovulation, oocytes may get arrested at the metaphase II (MII) stage until fertilization beyond optimal timing, which is termed as post-ovulatory aging. Post-ovulatory aging is a disease that degrades DNA, mitochondria, and oxidative system, and has a negative impact on embryo development and quality; however, the impact of bezafibrate during post-ovulatory aging has not been fully defined. In the present study, we assessed the ability of bezafibrate to prevent the progression of aging in in vitro conditions as well as the underlying mechanisms in pigs. An appropriate concentration of this drug (50 μM) was added, and then oxidative stress, reactive oxygen species downstream, mitochondrial biogenesis, and mitochondrial function were analyzed via immunofluorescence staining and real-time polymerase chain reaction. Bezafibrate significantly alleviated reactive oxygen species and ameliorated glutathione production simultaneously in oocytes and embryos. Moreover, it diminished H2A.X and attenuated CASPASE 3 expression produced by oxidative stress in oocytes and embryos. Furthermore, bezafibrate remarkably improved the mitochondrial function and blastocyst quality as well as markedly reduced the mitochondria/TOM20 ratio and mtDNA copy number. The elevated PARKIN level indicated that mitophagy was induced by bezafibrate treatment after post-ovulatory aging. Collectively, these results suggest that bezafibrate beneficially affects against porcine post-ovulatory oocyte aging in porcine by its antioxidant property and mitochondrial protection.

Abstract Background The aim of this multicenter cohort study was to compare the clinical courses between open and laparoscopic Petersen’s hernia (PH) reduction. Method We retrospectively collected the clinical data of patients who underwent PH repair surgery after gastrectomy for gastric cancer from 2015–2018. Forty patients underwent PH reduction operations that were performed by six surgeons at four hospitals. Among the 40 patients, 15 underwent laparoscopic PH reduction (LPH), and 25 underwent open PH reduction (OPH), including 4 patients who underwent LPH but required conversion to OPH. Results We compared the clinical factors between the LPH and OPH groups. In the clinical course, we found no differences in operation times or intraoperative bowel injury, morbidity, or mortality rates between the two groups (p > 0.05). However, the number of days on a soft fluid diet (OPH vs. LPH; 5.8 vs. 3.7 days, p = 0.03) and length of hospital stay (12.6 vs. 8.2 days, p = 0.04) were significantly less in the LPH group than the OPH group. Regarding postoperative complications, the OPH group had a case of pneumonia and sepsis with multi-organ failure, which resulted in mortality. In the LPH group, one patient experienced recurrence and required reoperation for PH. Conclusion Laparoscopic PH reduction was associated with a faster postoperative recovery period than open PH reduction, with a similar incidence of complications. The laparoscopic approach should be considered an appropriate strategy for PH reduction in selected cases.

Abstract Background We aimed to identify whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are more useful predictors after initial intention to treat than at the time of diagnosis. Methods We collected the medical data of 533 patients. The results of the peripheral blood sampling before the primary treatments were labeled as initial cohort, and those obtained between 24 and 36 months after initial treatment were defined as the 2nd cohort. Delayed metastasis has been defined as distant metastasis 2 years after treatment, and survival outcome was estimated and compared across groups. Results Median follow-up duration was 74 months (24–162 months), and 53 patients experienced delayed metastasis. In univariate analysis, metastasis-free survival, patient age at diagnosis, tumor size, axillary lymph node metastasis, HER-2 status, initial NLR and PLR, and 2nd NLR and PLR were found to be significantly associated with delayed metastasis. However, in multivariate analysis, only the 2nd NLR and PLR were found to be significantly associated with delayed metastasis, excluding initial NLR and PLR. Metastasis-free survival was analyzed through the pattern changes of NLR or PLR. The results revealed that patients with continued low NLR and PLR values at pre- and post-treatment (low initial values and 2nd values) showed a significantly better prognosis than those with a change in value or continued high NLR and PLR. Conclusions We identified that patients with persistent high NLR and PLR after initial treatment have significant worse prognosis in terms of late metastasis. Therefore, these results suggest that NLR and PLR are more useful in predicting prognosis post-treatment.

Nitric oxide (NO)-induced protein S-nitrosylation triggers mitochondrial dysfunction and was related to cell senescence. However, the exact mechanism of these damages is not clear. In the present study, to investigate the relationship between in vitro aging and NO-induced protein S-nitrosylation, oocytes were treated with sodium nitroprusside dihydrate (SNP), and the resultant S-nitrosylated proteins were detected through biotin-switch assay. The results showed that levels of protein S-nitroso thiols (SNO)s and expression of S-nitrosoglutathione reductase (GSNOR) increased, while activity and function of mitochondria were impaired during oocyte aging. Addition of SNP, a NO donor, to the oocyte culture led to accelerated oocyte aging, increased mitochondrial dysfunction and damage, apoptosis, ATP deficiency, and enhanced ROS production. These results suggested that the increased NO signal during oocyte aging in vitro, accelerated oocyte degradation due to increased protein S-nitrosylation, and ROS-related redox signaling.

Intestinal microbiota mediate the development and regulation of the intestinal immune system either directly or indirectly. Particularly, Bifidobacterium spp. play an important role in regulating the intestinal immunity and intestinal barrier. We demonstrated that Bifidobacterium animalis ssp. lactis HY8002, selected from eight Bifidobacterium strains by in vitro experimentation, had exceptional resistance to digestive tract conditions and high adhesion to intestinal epithelial cells and a positive effect on immunoglobulin A (IgA) secretion by Peyer’s patch cells. Moreover, HY8002 restored the expression of tight junction-related genes, initially reduced by lipopolysaccharide treatment, to normal levels in human intestinal epithelial cells. Notably, HY8002 restored kanamycin-induced reduction in Peyer’s patch cell numbers, serum and fecal IgA levels, and zonula occludens 1 and Toll-like receptor 2 levels in the mouse small intestine. In addition, HY8002 restores microbiome composition disturbed by kanamycin, and these microbiome changes have been found to correlate with TLR2 levels in the small intestine. Moreover, the ability of HY8002 to enhance IgA in Peyer’s patch cells and ZO-1 levels in intestinal epithelial cells was significantly inhibited by a TLR2 blocking antibody, which suggests that the HY8002 improve intestinal barrier function via TLR2. Finally, whole-genome sequencing of HY8002 revealed that it did not possess any known virulence factors. Therefore, HY8002 is a promising, functional probiotic supplement to improve intestinal barrier function by improving intestinal immunity and microbiota balance.

Introduction: The aim of this study was to perform a clinicopathologic analysis of PHLPP1 expression in gastric cancer patients and analyze AKT activity with chemotherapy drug treatment in cancer subtypes. Materials and Methods: Surgically resected gastric cancer tissue specimens were obtained from 309 patients who underwent gastrectomy, and PHLPP1 expression was validated by tissue microarray analysis with immunohistochemistry. We assessed whether PHLPP1 selectively dephosphorylates Ser473 of AKT in an in-vitro study. Results: We found that the PHLPP1 overexpression (OE) group showed significantly greater proportions of differentiated subtype samples and early T stage samples, lower lymph node metastasis, and lower TNM stage than the PHLPP1 underexpression (UE) group. The overall survival of the PHLPP1-OE group was significantly higher (53.39 ± 0.96 months) than that of the PHLPP1-UE group (47.82 ± 2.57 months) ( P = .01). In vitro analysis, we found that the PHLPP1-OE group showed a significant decrease in relative AKT S-473 levels in both cell lines (MKN-74 and KATO-III). We found that treatment with chemotherapy drugs decreased the activity of Ser473 in the MKN-74 cell line with PHLPP1 OE, but it did not affect the activity of Ser473 in KATO-III cells. Conclusion: We found that patients who overexpressed PHLPP1 showed low recurrence and good prognosis. PHLPP1 was found to work by lowering the activity of AKT Ser473 in gastric cancer. Additionally, we found a clue regarding the mechanism of chemotherapeutic drug resistance in a cell line of signet ring cell origin and will uncover this mechanism in the future.

Purpose Whether subtotal or total colectomy with primary anastomosis (PA) is safer than Hartmann procedure (HP) for left-sided colon cancer obstruction or perforation remains controversial. The purpose of this study was to compare postoperative morbidity, mortality, and defecation frequency between PA and HP for left-sided colon cancer obstruction or perforation. Methods This retrospective study enrolled 54 patients from January 2014 to February 2018 who underwent emergency surgery due to left-sided colon cancer obstruction or perforation. Results PA was carried out in 20 patients while HP was performed for 34 patients. Thirty-day mortality did not show significant difference between the two groups (15.0% vs. 14.7%, P=1.000). No anastomotic leakage occurred in PA group while three (8.8%) cases of stump leakage occurred in HP group. Stoma repair was performed for 13 cases (44.8%) and stoma reformation was performed for one case in HP group (7.7%). Stoma related complications occurred in five cases (17.24%). For patients after stoma repair, defecation frequency at 3 months after operation was 2.91±2.88 times per day in PA group and 2.86±2.63 times per day in HP group. At 1 year after operation, defecation frequency was changed to 1.40±1.12 times per day in PA group and 1.17±0.39 times per day in HP group. Conclusion Primary ileosigmoid or ileorectal anastomosis for left-sided colon cancer obstruction or perforation is safe, and shows similar outcome of defecation frequency compared to HP.

Introduction: There have been few studies about gene differences between patients with diffuse-type gastric cancer and those with intestinal-type gastric cancer. The aim of this study was to compare the transcriptomes of signet ring cell gastric cancer (worst prognosis in diffuse-type) and well-differentiated gastric cancer (best prognosis in intestinal-type); NUDC was identified, and its prognostic role was studied. Materials and Methods: We performed next-generation sequencing with 5 well-differentiated gastric cancers and 3 of signet ring cell gastric cancer surgical samples. We performed gene enrichment and functional annotation analysis using the Database for Annotation, Visualization and Integrated Discovery bioinformatics resources. Immunohistochemistry was used to validate NUDC expression. Results: Overall, 900 genes showed significantly higher expression, 644 genes showed lower expression in signet ring cell gastric cancer than in well-differentiated gastric cancers, and there was a large difference in adhesion, vascular development, and cell-to-cell junction components between the 2 subtypes. We performed variant analysis and found 52 variants and 30 cancer driver genes, including NUDC. We analyzed NUDC expression in gastric cancer tissue and its relationship with prognosis. Cox proportional hazard analysis identified T stage, N stage, and NUDC expression as independent risk factors for survival ( P < 0.05). The overall survival of the NUDC-positive group was significantly higher (53.2 ± 0.92 months) than that of the NUDC-negative group (44.6 ± 3.7 months) ( P = 0.001) in Kaplan-Meier survival analysis. Conclusion: We found 30 cancer driver gene candidates and found that the NUDC-positive group showed significantly better survival than the NUDC-negative group via variant analysis.

Abstract Background While extended cholecystectomy is recommended for T2 gallbladder cancer (GBC), the role of hepatic resection for T2 GBC is unclear. This study aimed to identify the necessity of hepatic resection in patients with T2 GBC. Methods Data of 81 patients with histopathologically proven T2 GBC who underwent surgical resection between January 1999 and December 2017 were enrolled from a retrospective database. Of these, 36 patients had peritoneal-side (T2a) tumors and 45 had hepatic-side (T2b) tumors. To identify the optimal surgical management method, T2 GBC patients were classified into the hepatic resection group (n = 44, T2a/T2b = 20/24) and non-hepatic resection group (n = 37, T2a/T2b = 16/21). The recurrence pattern and role of hepatic resection for T2 GBC were then investigated. Results Mean age of the patients was 69 (range 36–88) years, and the male-to-female ratio was 42:39 (male, 51.9%; female, 48.1%). Hepatic-side GBC had a higher rate of recurrence than peritoneal-side GBC (44.4% vs. 8.3%, p = 0.006). The most common type of recurrence in T2a GBC was para-aortic lymph node recurrence (n = 2, 5.6%); the most common types of recurrence in T2b GBC were para-aortic lymph node recurrence (n = 7, 15.6%) and intrahepatic metastasis (n = 6, 13.3%). Hepatic-side GBC patients had worse survival outcomes than peritoneal-side GBC patients (76.0% vs. 96.6%, p = 0.041). Hepatic resection had no significant treatment effect in T2 GBC patients (p = 0.272). Multivariate analysis showed that lymph node metastasis was the only significant prognostic factor (p = 0.002). Conclusions Hepatic resection is not essential for curative treatment in T2 GBC, and more systemic treatments are needed for GBC patients, particularly for those with T2b GBC.

Purpose We investigated the long-term oncologic outcomes of laparoscopic gastrectomy (LG) and open gastrectomy (OG) for advanced gastric cancer (AGC) with a 5-year follow-up period. Methods Clinical data of 180 patients (109 LG and 71 OG) who underwent radical D2 gastrectomy for AGC at Gyeongsang National University Hospital between 2007 and 2009 were included. Survivals and predictors of these outcomes were analyzed. Results The mean follow-up period was 54.3 months. Recurrence was observed in 68 patients (37.8%). The 5-year disease-free survival (DFS) rate was 52.2% for all patients, 39.4% in the OG group, and 60.6% in the LG group. The 5-year DFS rates for OG and LG with respect to pathological stage were stage I, 87.5% and 84.2%, respectively (P=0.684); stage II, 55.0% and 77.3%, respectively (P=0.032); and stage III, 23.3% and 34.8%, respectively (P=0.265). The 5-year overall survival (OS) rate was 52.8% for all patients, 40.8% in the OG group, and 60.6% in the LG group. The 5-year OS rates for OG and LG with respect to pathological stage were stage I, 87.5% and 84.2%, respectively (P=0.753); stage II, 55.0% and 77.3%, respectively (P=0.034); and stage III, 25.6% and 34.8%, respectively (P=0.302). For survival, TMN cancer stage was statistically independent prognostic factors. Conclusion Our analysis revealed that LG for AGC had acceptable long-term oncologic outcomes comparable to the outcomes of conventional OG. Cancer stage was independent risk factors associated with survival.

Purpose This study was designed to retrospectively identify prognostic factors of survival among breast cancer patients with 10 or more metastatic lymph nodes (LNs). Methods The study included 58 patients with 10 or more metastatic LNs who received standard treatment from January 2005 to December 2015. To identify the prognostic factors, we analyzed the difference of disease-free survival (DFS) according to clinicopathologic factors. Results The 5-year DFS and overall survival rates in all patients were 55% and 69%, respectively. Tumor size, number of metastatic LNs and ratio of metastatic to total LNs were associated with poorer prognosis. DFS was significantly poorer in patients with >15 than ≤15 metastatic LNs (hazard ratio [HR], 4.60; 95% confidence interval [CI], 1.38–15.32) and with LN ratio >0.64 than ≤0.64 (HR, 26.13; 95% CI, 3.16–215.80) A scoring system based on these factors was significantly prognostic of survival outcomes. Conclusion This study identified factors of survival in breast cancer patients with extensive LN metastasis. Patients with unfavorable factors may require modified management to improve their clinical outcomes.

The regulation of M1/M2 polarization in liver macrophages is closely associated with the progression of nonalcoholic steatohepatitis (NASH); however, the mechanism involved in this process remains unclear. Here, we describe the orphan nuclear receptor retinoic-acid-related orphan receptor α (RORα) as a key regulator of M1/M2 polarization in hepatic residential Kupffer cells (KCs) and infiltrated monocyte-derived macrophages. RORα enhanced M2 polarization in KCs by inducing the kruppel-like factor 4. M2 polarization was defective in KCs and bone-marrow-derived macrophages of the myeloid-specific RORα null mice, and these mice were susceptible to HFD-induced NASH. We found that IL-10 played an important role in connecting the function of M2 KCs to lipid accumulation and apoptosis in hepatocytes. Importantly, M2 polarization was controlled by a RORα activator, JC1-40, which improved symptoms of NASH. Our results suggest that the M2-promoting effects of RORα in liver macrophages may provide better therapeutic strategies against NASH.

An accurate method for detecting vital signs obtained from a Doppler radar sensor is proposed. A Doppler radar sensor can remotely obtain vital signs such as heartbeat and respiration rate, but the vital signs obtained by using the sensor do not show clear peaks like in electrocardiography (ECG) because of the operating characteristics of the radar. The proposed peak detection algorithm extracts the vital signs from the raw data. The algorithm shows the mean accuracy of 96.78% compared to the peak count from the reference ECG sensor and a processing time approximately two times faster than the gradient-based algorithm. To verify whether heart rate variability (HRV) analysis similar to that with an ECG sensor is possible for a radar sensor when applying the proposed method, the continuous parameter variations of the HRV in the time domain are analyzed using data processed with the proposed peak detection algorithm. Experimental results with six subjects show that the proposed method can obtain the heart rate with high accuracy but cannot obtain the information for an HRV analysis because the proposed method cannot overcome the characteristics of the radar sensor itself.

Cervical lymph node metastasis is common in patients with papillary thyroid carcinoma (PTC). Salmonella species are rarely reported as causative agents in focal infections of the head and neck. The cooccurrence of lymph node metastasis from PTC and a bacterial infection is rare. This report describes a 76-year-old woman with a cervical lymph node metastasis from PTC and Salmonella infection of the same lymph node. The patient presented with painful swelling in her left lateral neck region for 15 days, and neck ultrasonography and computed tomography showed a cystic mass along left levels II–IV. The cystic mass was suspected of being a metastatic lymph node; modified radical neck dissection was performed. Histopathological examination confirmed the presence of PTC in the resected node and laboratory examination of the combined abscess cavity confirmed the presence of Salmonella Typhi. Following antibiotic sensitivity testing of the cultured Salmonella Typhi, she was treated with proper antibiotics. Cystic lesions in lymph nodes with metastatic cancer may indicate the presence of cooccurring bacterial infection. Thus, culturing of specimen can be option to make accurate diagnosis and to provide proper postoperative management.

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) secrete various beneficial molecules, which have anti-apoptotic activity and cell proliferation. However, the effect of hUCB-MSCs in melanogenesis is largely unclear. In this study, we show that conditioned media (CM) derived from hUCB-MSCs inhibit melanogenesis by regulating microphthalmia-associated transcription factor (MITF) expression via the ERK signalling pathway. Treatment of hUCB-MSC-CM strongly inhibited the alpha-melanocyte stimulating hormone-induced hyperpigmentation in melanoma cells as well as melanocytes. Treatment of hUCB-MSC-CM induced ERK1/2 activation in melanocytes. In addition, inhibition of ERK1/2 suppressed the anti-pigmentation activity of the hUCB-MSC-CM in melanocytes and in vitro artificial skin models. We also found that the expression of MITF was appreciably diminished while expression of phosphorylated MITF, which leads to its proteasomal degradation, was increased in cells treated with hUCB-MSC-CM. These results suggested that hUCB-MSC-CM significantly suppresses melanin synthesis via MITF degradation by the ERK pathway activation.

A series of etching experiments on light trapping structure have been carried out by glass etching. The block structure provides long light traveling path and a constant distance between the cathode and anode electrodes regardless of the block height, which results in higher efficiency of the block textured solar cell. In terms of etching profile of the glass substrate, the addition of NH4F resulted in the smooth and clean etching profile, and the steep slope of the block was obtained by optimizing the composition of etching solution. For a higher HF concentration, a more graded slope was obtained and the addition of HNO3 and NH4F provided steep slope and clean etching profile. The effects of the block textured glass were verified by a comparison of the solar cell efficiency. For the textured solar cell, the surface was much rougher than that of the plain glass, which also contributes to the improvement of the efficiency. We accomplished block shaped light trapping structure for the first time by wet etching of the glass substrate, which enables the high efficiency thin film solar cell with the aid of the good step coverage deposition.

Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear. This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1- stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1- stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 µM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression. Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cells (VSMCs) under biophysical stress play an active role in the progression of vascular inflammation, but the precise mechanisms are unclear. This study examined the cellular expression of monocyte chemoattractant protein 1 (MCP-1) and its related mechanisms using cultured rat aortic VSMCs stimulated with mechanical stretch (MS, equibiaxial cyclic stretch, 60 cycles/ min). When the cells were stimulated with 10% MS, MCP-1 expression was markedly increased compared to those in the cells stimulated with low MS intensity (3% or 5%). An enzyme-linked immunosorbent assay revealed an increase in HMGB1 released into culture media from the cells stimulated with 10% MS compared to those stimulated with 3% MS. A pretreatment with glycyrrhizin, a HMGB1 inhibitor, resulted in the marked attenuation of MCP-1 expression in the cells stimulated with 10% MS, suggesting a key role of HMGB1 on MCP-1 expression. Western blot analysis revealed higher PDGFR-α and PDGFR-β expression in the cells stimulated with 10% MS than 3% MS-stimulated cells. In the cells deficient of PDGFR-β using siRNA, but not PDGFR-α, HMGB1 released into culture media was significantly attenuated in the 10% MS-stimulated cells. Similarly, MCP-1 expression induced in 10% MS-stimulated cells was also attenuated in cells deficient of PDGFR-β. Overall, the PDGFR-β signaling plays a pivotal role in the increased expression of MCP-1 in VSMCs stressed with 10% MS. Therefore, targeting PDGFR-β signaling in VSMCs might be a promising therapeutic strategy for vascular complications in the vasculatures under excessive biophysical stress. [ABSTRACT FROM AUTHOR]