TNF receptor 2 knockout mouse had reduced lung cancer growth and schizophrenia-like behavior through a decrease in TrkB-dependent BDNF level.

The relationship between schizophrenia (SCZ) and cancer development remains controversial. Based on the disease-gene association platform, it has been revealed that tumor necrosis factor receptor (TNFR) could be an important mediatory factor in both cancer and SCZ development. TNF-α also increases the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) in the development of SCZ and tumor, but the role of TNFR in mediating the association between the two diseases remains unclear. We studied the vital roles of TNFR2 in the progression of tumor and SCZ-like behavior using A549 lung cancer cell xenografted TNFR2 knockout mice. TNFR2 knockout mice showed significantly decreased tumor size and weight as well as schizophrenia-like behaviors compared to wild-type mice. Consistent with the reduced tumor growth and SCZ-like behaviors, the levels of TrkB and BDNF expression were significantly decreased in the lung tumor tissues and pre-frontal cortex of TNFR2 knockout mice. However, intravenous injection of BDNF (160 µg/kg) to TNFR2 knockout mice for 4 weeks increased tumor growth and SCZ-like behaviors as well as TrkB expression. In in vitro study, significantly decreased cell growth and expression of TrkB and BDNF by siTNFR2 transfection were found in A549 lung cancer cells. However, the addition of BDNF (100 ng/ml) into TNFR2 siRNA transfected A549 lung cancer cells recovered cell growth and the expression of TrkB. These results suggest that TNFR2 could be an important factor in mediating the comorbidity between lung tumor growth and SCZ development through increased TrkB-dependent BDNF levels.

The application of enhanced recovery after surgery protocol after distal gastrectomy for patients with gastric cancer: a prospective randomized clinical trial.

BACKGROUND: This study aimed to evaluate the clinical outcomes and efficacy of enhanced recovery after surgery (ERAS) protocol in patients undergoing distal gastrectomy for gastric cancer (GC). METHODS: Patients were randomly assigned to the ERAS group (EG) and the conventional care group (CG) by stratified randomization according to age and sex. The primary endpoint was adjusted postoperative hospital stay, calculated using discharge criteria developed to evaluate recovery. Nutritional data and quality of life (QoL) (European Organisation for Research and Treatment of Cancer [EORTC] C30 and STO22) during the perioperative period were also analyzed. RESULTS: We enrolled 198 eligible patients with GC for the study between June 2017 and January 2019. A total of 147 patients were finally enrolled in this study (full analysis set) and were assigned to EG (n = 71) and CG (n = 76). First flatus was faster significantly in EG (3.6 ± 1.5 vs 4.1 ± 1.2 days, P = .019). EG showed a faster start of the sips and soft diet than CG (1.3 ± 0.7 vs 3.1 ± 0.4 days, P < .001; 2.4 ± 0.9 vs 5.2 ± 0.7 days, P < .001) according to the protocol. The recorded hospital stay was not significantly different; however, adjusted hospital stay was significantly shorter in EG than in CG (6.5 ± 3.1 vs 7.8 ± 2.1 days, P = .005). There was no difference in morbidity, and no mortality occurred in both groups. EG did not show significant superiority in nutritional outcome and QoL improvement, except for pain scale in EORTC-STO22. CONCLUSION: The application of the ERAS protocol could reduce the adjusted hospital stay without an increase in postoperative complications. There was no significant difference in long-term nutritional outcome and QoL of the 2 groups.

Comparison between the mesenteric fixation method (MEFIX) and conventional methods at preventing the occurrence of Petersen's hernia: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Petersen's hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien-Dindo classification grade III due to Petersen's hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. METHODS: This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen's defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen's hernia within 3 years after laparoscopic or robotic gastrectomy. DISCUSSION: This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen's defect without increased postoperative complications compared to the conventional method. TRIAL REGISTRATION: ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.

10-Year Clinical Follow-Up after Decompression of Lipofibromatous Hamartoma of the Median Nerve in a 3-Year-Old Patient: Case Report and Review of the Literature.

Lipofibromatous hamartoma, first reported in 1953, is a rare, slowly progressive soft tissue tumor, the characteristics of which include the enlargement of the affected nerve via the epineurial and perineurial proliferation of adipose and fibrous tissues. Out of 200 previously reported cases of lipofibromatous hamartoma of the median nerve, there have been approximately 25 pediatric cases under the age of 18. Herein, we report a case of lipofibromatous hamatoma of the median nerve in a 3-year-old female patient who was surgically decompressed via carpal tunnel release and epineurolysis. The patient was followed-up on an outpatient clinic basis annually with sonographic evaluations, and the postoperative 10th-year follow-up did not show recurrence or any deficits in motor and sensory functions.

Diagnostic performance of F-18 FDG PET or PET/CT for detection of recurrent gastric cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis investigated the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) or PET/computed tomography (PET/CT) for the detection of disease recurrence after curative resection of gastric cancer. METHODS: The PubMed and Embase databases, from the earliest available date of indexing through November 30, 2019, were searched for studies evaluating the diagnostic performance of F-18 FDG PET or PET/CT to detect recurrent disease after gastric cancer surgery. RESULTS: Across 17 studies (1,732 patients), the pooled sensitivity for F-18 FDG PET or PET/CT was 0.82 (95% confidence interval [CI], 0.74-0.88) with heterogeneity of I2=76.5 (p<0.001), and the specificity was 0.86 (95% CI, 0.78-0.91) with heterogeneity of I2=94.2 (p<0.001). Likelihood ratio (LR) tests gave an overall positive LR of 6.0 (95% CI, 3.6-9.7) and negative LR of 0.2 (95% CI, 0.14-0.31). The pooled diagnostic odds ratio was 29 (95% CI, 13-63). The summary receiver operating characteristic curve indicates that the area under the curve was 0.91 (95% CI, 0.88-0.93). CONCLUSION: The current meta-analysis showed good sensitivity and specificity of F-18 FDG PET or PET/CT for detecting recurrent disease after curative resection of gastric cancer despite heterogeneity in ethnicity, recurrence rate, histology, and interpretation method.

Protaetia Brevitarsis-Derived Protein Hydrolysate Reduces Obesity-Related Colitis Induced by High-Fat Diet in Mice through Anti-Inflammatory Pathways.

Ulcerative colitis is an inflammatory bowel disease characterized by inflammation in the mucosal and submucosal layers of the colon. Obesity is closely related to the occurrence and progression of colitis. The most plausible mechanism linking obesity and colitis is an excessive adipogenesis-related inflammatory response, which causes mucosal dysfunction. Obesity and colitis are linked by several etiologic mechanisms, including excessive adipogenesis, lipotoxicity, pro-inflammatory adipokines/cytokines, macrophage polarization, oxidative stress, endoplasmic reticulum (ER) stress, and gut microbiota. These low-grade enteric inflammations cause mucosal layer damage, especially goblet cell dysfunction through mucin 2 (MUC2) misfolding, ultimately leading to colitis. Inhibiting the inflammatory response can be the most effective approach for treating obesity-related colitis. We focused on the anti-inflammatory effects of polyphenols in Protaectia brevitas larvae. The P. brevitas was prepared as a low molecular protein hydrolysate (PHPB) to increase the concentration of anti-inflammatory molecules. In the current study, we investigated the anti-inflammatory effect of PHPB in an obesity-induced colitis mouse model. Compared with the high-fat diet (HFD) group, the group treated with PHPB exhibited reduced body/organ/fat weight, appetite/food intake inhibition, hypolipidemic effect on ectopic fat, and anti-adipogenic mechanism through the AMPK signaling pathway. Furthermore, we observed attenuated expression of PPARγ and C/EBPα, inhibition of pro-inflammatory molecules, stimulation of anti-inflammatory molecules, probiotic-like effect against obesogenic gut microbiota, inhibition of macrophage polarization into M1, suppression of oxidative/ER stress, and reduction of Muc2 protein misfolding in colon. These diverse anti-inflammatory responses caused histological and functional recovery of goblet cells, eventually improving colitis. Therefore, our findings suggest that the protein hydrolysate of Protaetia brevitarsis can improve obesity-related colitis through its anti-inflammatory activities.

Occupational exposure to polycyclic aromatic hydrocarbons in Korean adults: evaluation of urinary 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, and 2-hydroxyfluorene using Second Korean National Environmental Health Survey data.

Background: Polycyclic aromatic hydrocarbons (PAHs) are occupational and environmental pollutants generated by the incomplete combustion of organic matter. Exposure to PAHs can occur in various occupations. In this study, we compared PAH exposure levels among occupations based on 4 urinary PAH metabolites in a Korean adult population. Methods: The evaluation of occupational exposure to PAHs was conducted using Second Korean National Environmental Health Survey data. The occupational groups were classified based on skill types. Four urinary PAH metabolites were used to evaluate PAH exposure: 1-hydroxypyrene (1-OHP), 2-naphthol (2-NAP), 1-hydroxyphenanthrene (1-OHPHE), and 2-hydroxyfluorene (2-OHFLU). The fraction exceeding the third quartile of urinary concentration for each PAH metabolite was assessed for each occupational group. Adjusted odds ratios (ORs) for exceeding the third quartile of urinary PAH metabolite concentration were calculated for each occupational group compared to the "business, administrative, clerical, financial, and insurance" group using multiple logistic regression analyses. Results: The "guard and security" (OR: 2.949; 95% confidence interval [CI]: 1.300-6.691), "driving and transportation" (OR: 2.487; 95% CI: 1.418-4.364), "construction and mining" (OR: 2.683; 95% CI: 1.547-4.655), and "agriculture, forestry, and fisheries" (OR: 1.973; 95% CI: 1.220-3.191) groups had significantly higher ORs for 1-OHP compared to the reference group. No group showed significantly higher ORs than the reference group for 2-NAP. The groups with significantly higher ORs for 1-OHPHE than the reference group were "cooking and food service" (OR: 2.073; 95% CI: 1.208-3.556), "driving and transportation" (OR: 1.724; 95% CI: 1.059-2.808), and "printing, wood, and craft manufacturing" (OR: 2.255; 95% CI: 1.022-4.974). The OR for 2-OHFLU was significantly higher in the "printing, wood, and craft manufacturing" group (OR: 3.109; 95% CI: 1.335-7.241) than in the reference group. Conclusions: The types and levels of PAH exposure differed among occupational groups in a Korean adult population.

Prevalence of feline chronic gingivostomatitis in feral cats and its risk factors.

OBJECTIVES: This study investigated the prevalence of feline chronic gingivostomatitis in urban feral cats in South Korea and analysed its risk factors. METHODS: Three hundred and forty-five feral cats that visited the hospital for neutering using a trap-neuter-return approach were screened for feline chronic gingivostomatitis based on clinical criteria. In addition, we determined if body weight, sex and the presence of tongue lesions are risk factors for feline chronic gingivostomatitis. The difference in severity due to the presence or absence of risk factors, and the relationship between gross findings and histopathological lesions, were analysed by grading lesion severity. RESULTS: Feline chronic gingivostomatitis was diagnosed in 92 cats. Disease prevalence did not significantly differ with body weight and sex but was significantly related to tongue lesions. CONCLUSIONS AND RELEVANCE: The prevalence of feline chronic gingivostomatitis in urban feral cats in South Korea was 26.6%. It was significantly more prevalent in cats that had tongue lesions. Severity was also significantly associated with tongue lesions. Feline chronic gingivostomatitis may be associated with an infectious agent that causes tongue lesions.

Laparoscopic gastric wedge resection and spleen-preserving distal pancreatectomy performed on a 6-cm gastric desmoid tumour with pancreatic invasion.

Desmoid tumours are rare tumours originating from fibroblasts, and are characterised by local infiltration and no metastasis. When complete resection is possible, surgical resection is considered a first-line treatment. In the case of large desmoid tumours, it is mainly performed by laparotomy, not laparoscopy. We report a case of a 43-year-old female patient presenting with a hypodense mass of approximately 5 cm in the posterior wall of the gastric antrum on computed tomography. There was no history of familial adenomatous polyposis, trauma or abdominal surgery. The patient underwent laparoscopic gastric wedge resection and spleen-preserving distal pancreatectomy without peri-operative complications. Pathological analysis revealed a desmoid tumour, which originated from the stomach and invaded the pancreas. Despite the large size and the locally infiltrative characteristics of these tumours, laparoscopic surgery can be an optimal treatment option due to its advantages.

Conservative Treatment in Two Patients With Spontaneous Hepatic Artery Dissection.

BACKGROUND: Spontaneous dissection of the hepatic artery is a rare finding for which there is no specific treatment algorithm. Even though endovascular treatment and surgery have been used to treat other visceral artery dissections, these approaches can be challenging in the case of hepatic artery dissection because it is difficult to access the hepatic artery. CASE SUMMARY: 2 patients with spontaneous dissection of the hepatic artery were admitted due to epigastric pain. Although the liver function test results were normal, and there were no complications such as bleeding, shock, or ischemia in other organs, a subsequent computed tomography scan directly revealed the spontaneous dissection of the hepatic artery in both patients. The patients were treated with anticoagulants without surgery. Because it is difficult to perform surgery or endovascular treatment on the hepatic artery, we focused on preventing the progression of hepatic artery dissection and the formation of a new thrombus in the dissection. CONCLUSION: Considering the risk of surgical treatment for the hepatic artery and the condition of the patients, medical treatment with anticoagulants may be considered as an initial treatment and provide more benefits than surgical treatment.

Retrospective Case Control Study: Clinical and Computer Tomographic Fusion and Subsidence Evaluation for Single Level Uniportal Endoscopic Posterolateral Approach Transforaminal Lumbar Interbody Fusion Versus Microscopic Minimally Invasive Transforaminal Interbody Fusion.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: Assessment of difference in clinical and computer tomographic outcomes between the 2 cohorts. METHODS: Computer tomographic evaluation by Bridwell's grade, Kim's stage, Kim's subsidence grade and clinical evaluation by VAS, ODI and McNab's criteria on both cohorts. RESULTS: 33 levels of Endo-TLIF and 22 levels of TLIF were included, with a mean follow up of 14.3 (10-24) and 22.9 (13-30) months respectively. Both Endo-TLIF and TLIF achieved significant improvement of pain and ODI at post-operative 4 week, 3 months and at final follow up with VAS 4.39 ± 0.92, 5.27 ± 1.16 and 5.73 ± 1.21in Endo-TLIF and 4.55 ± 1.16, 5.05 ± 1.11 and 5.50 ± 1.20 in TLIF respectively and ODI at post-operative 1 week, 3 months and final follow up were 43.15 ± 6.57, 49.27 ± 8.24 and 51.73 ± 9.09 in Endo-TLIF and 41.73 ± 7.98, 46.18± 8.46 and 49.09 ± 8.98 in TLIF respectively, P < 0.05. Compared to TLIF, Endo-TLIF achieved better VAS with 0.727 ± 0.235 at 3 months and 0.727 ± 0.252 at final follow up and better ODI with 3.88 ± 1.50 at 3months and 3.42 ± 1.63 at final follow up, P < 0.05. At 6 months radiological evaluation comparison of the Endo-TLIF and TLIF showed significant with more favorable fusion rate in Endo-TLIF of -0.61 ± 0.12 at 6 months and -0.49 ± 0.12 at 1 year in Bridwell's grading and 0.70 ± 0.15 at 6 months and 0.56 ± 0.14 at 1 year in Kim's stage.There is less subsidence of 0.606 ± 0.18 at 6 months and -0.561 ± 0.20 at 1 year of Kim's subsidence grade, P < 0.05. CONCLUSION: Application of single level uniportal endoscopic posterolateral lumbar interbody fusion achieved better clinical outcomes and fusion rate with less subsidence than microscopic minimally invasive transforaminal lumbar interbody fusion in mid-term evaluation for our cohorts of patients.

Plant Alkaloid Tetrandrine Is a Nuclear Receptor 4A1 Antagonist and Inhibits Panc-1 Cell Growth In Vitro and In Vivo.

The orphan nuclear receptor 4A1 (NR4A1) is highly expressed in human pancreatic cancer cells and exerts pro-oncogenic activity. In a previous study, we demonstrated that fangchinoline (FCN), a natural inhibitor of nuclear NR4A1, induces NR4A1-dependent apoptosis in human pancreatic cancer cells. In this study, we evaluated FCN and its structural analogs (berbamine, isotetrandrine, tetrandrine, and tubocurarine) for their inhibitory effects on NR4A1 transactivity, and confirmed that tetrandrine (TTD) showed the highest inhibitory effect in pancreatic cancer cells. Moreover, in a tryptophan fluorescence quenching assay, TTD directly bound to the ligand binding domain (LBD) of NR4A1 with a KD value of 10.60 µM. Treatment with TTD decreased proliferation and induced apoptosis in Panc-1 human pancreatic cancer cells in part through the reduced expression of the Sp1-dependent anti-apoptotic gene survivin and induction of ROS-mediated endoplasmic reticulum stress, which are the well-known NR4A1-dependent proapoptotic pathways. Furthermore, at a dose of 25 mg/kg/day, TTD reduced tumor growth in an athymic nude mouse xenograft model bearing Panc-1 cells. These data show that TTD is an NR4A1 antagonist and that modulation of the NR4A1-mediated pro-survival pathways is involved in the antitumor effects of TTD.

Comparative Clinical and Radiographic Cohort Study: Uniportal Thoracic Endoscopic Laminotomy With Bilateral Decompression by Using the 1-Block Resection Technique and Thoracic Open Laminotomy With Bilateral Decompression for Thoracic Ossified Ligamentum Flavum.

BACKGROUND: Symptomatic thoracic myelopathy secondary to thoracic ossified ligamentum flavum (OLF) often requires decompression spinal surgery. OBJECTIVE: To compare clinical and radiological outcomes in uniportal endoscopic vs open thoracic decompression for thoracic OLF. METHODS: Retrospective evaluation of patients who underwent uniportal thoracic endoscopic unilateral laminotomy with bilateral decompression (TE-ULBD) by using the one-block resection technique compared with thoracic open laminotomy (TOL) with bilateral decompression. Radiological outcomes in MRI scan and clinical charts were evaluated. RESULTS: Thirty-five levels of TE-ULBD were compared with 24 levels of TOL. The overall complication rate of TOL was 15% while TE-ULBD was 6.5%. Both TOL and TE-ULBD cohort had significantly improved their visual analog scale (VAS), Oswestry Disability Index, and Japanese Orthopaedic Association (JOA) myelopathy score after operation. Comparative analysis of TE-ULBD performed statistically and significantly better than TOL in improvement of final VAS and JOA scores. The mean difference ± standard deviation of VAS and JOA improvement in final follow-up when compared with preoperative state of TE-ULBD and TOL was 0.717 ± 0.131 and 1.03 ± 0.2, respectively, P < .05. The mean Hirabayashi recovery rates were 94.5% (TE-ULBD) and 56.8% (TOL). There was no statistical difference in change in preoperative and final Oswestry Disability Index and MRI volume at upper endplate, middisk, and lower endplate canal cross-sectional area. CONCLUSION: Uniportal TE-ULBD achieved significantly improved pain and neurological recovery with sufficient spinal canal decompression, as compared with thoracic open laminectomy for patients with myelopathy secondary to OLF in our cohort.

Antiobesity and Hepatoprotective Effects of Protein Hydrolysates Derived from Protaetia brevitarsis in an Obese Mouse Model.

Background: Obesity induced by excessive nutrients can cause fatty liver and metabolic dysfunction, which leads to hepatic dysfunction and local/systemic inflammatory responses. Previously, we analyzed the antioxidant, antilipotoxicity, and anti-inflammatory effects of protein hydrolysates in vitro. The aim of the present study is to investigate the antiobesity and hepatoprotective effects of protein hydrolysates derived from Protaectia brevitas (PHPB) in an obese mouse model. Methods: For this in vivo study, 40 mice were included and divided into four groups: (1) normal diet group, (2) high-fat-diet (ctrl(-)) group, (3) high-fat-diet and silymarin-treated (ctrl(+)) group, and (4) high-fat-diet and PHPB-treated group. After 6 weeks of treatment, body weight and the amount of daily food intake were observed. Moreover, the major organs and blood of animals were collected for the analysis of serum chemistry, histopathological examination, and obesity- and inflammation-related gene expressions. Results: The body weight and the amount of daily food intake significantly decreased in the PHPB-treated group compared with those in the ctrl(-) group. The levels of serum ALT, AST, ALP, creatinine, blood urea nitrogen, glucose, bilirubin, total cholesterol, TG, low-density lipoprotein, IL-6, TNF-α, and IGF-1 significantly reduced in the PHPB-treated group, whereas the serum free fatty acid, albumin, high-density lipoprotein, and adiponectin concentrations increased. In the analysis of weight of the liver, kidney, lungs, spleen, and fat tissues (from epididymal, perirenal, and mesentery tissues), the PHPB-treated group showed decreased values compared with the ctrl(-) group. In the histopathological analysis, the PHPB-treated group showed significantly reduced macrovesicular fatty change and inflammatory cell infiltration in the liver, and the size of the adipocyte in the epididymis also significantly decreased. The obesity- and inflammation-related gene (IL-6, TNF-α, IGF-1, leptin, AP2/FABP4, AMPK-α2, ß3AR, and PPAR-γ) expressions in the liver and epididymal adipose tissue were reduced in the PHPB-treated group. Conclusions: Overall, the results of this study suggest that the protein hydrolysates that derived from Protaectia brevitas produce antiobesity and hepatoprotective effects via anti-inflammatory activities.

Comparison of intermaxillary fixation techniques for mandibular fractures with focus on patient experience.

BACKGROUND: Intermaxillary fixation (IMF) is a technique that allows for the reduction and stabilization of mandibular fractures. Several methods of IMF, such as self-tapping screws or arch bars, have been developed. This study aimed to validate the usefulness of IMF with a self-tapping screw compared to IMF with arch bars with focus on the patients' perspective. METHODS: We retrospectively reviewed the medical records of all patients who were treated for mandibular fractures at our hospital between August 2014 and February 2021. A total of 57 patients were enrolled in this study. Thirteen patients were excluded from the analysis: three patients were lost to follow-up, and 10 patients did not undergo IMF. Finally, 44 patients were analyzed, of which 31 belonged to the arch bar group, and 13 belonged to the screw group. Patient discomfort and pain during IMF application and removal were analyzed using a patient self-assessment questionnaire. The surgeon also assessed oral hygiene, IMF stability, and occlusion. RESULTS: We applied IMF to 34 men (77%) and 10 women (23%). The mean age of the patients was 37.3 years. The most common fracture site was the angle (30%), followed by the parasymphysis (25%), the body (23%), the condyle (11%), and the ramus (11%). Patient discomfort and oral hygiene were statistically favorable in the screw group. The IMF application time was statistically shorter in the screw group (p< 0.001). IMF stability was not statistically different between the two groups. The pain score during IMF removal was lower in the screw group (p< 0.001). CONCLUSION: Compared to arch bars, IMF screws provide more comfort during the IMF period, help maintain favorable oral hygiene, and have a shorter application time. From the patient's perspective, IMF screws are an excellent alternative to conventional arch bars when applicable.

Actual 3-Year Survival After Reduced-Port Laparoscopic Distal Gastrectomy for Gastric Cancer (RpLDG): a Propensity Score Matching Analysis.

BACKGROUND: Total laparoscopic distal gastrectomy for early gastric cancer has been widely accepted; however, reduced-port laparoscopic distal gastrectomy has not gained the same popularity because of technical difficulties and oncologic safety issues. This study aimed to analyze the oncologic safety and short-term surgical outcomes of patients who underwent reduced-port laparoscopic distal gastrectomy (RpLDG) for gastric cancer. METHODS: Consecutive patients who underwent surgical treatment between January 2016 and May 2018 were included in this study. Of the 833 patients enrolled, 158 underwent RpLDG and were propensity-matched with 158 patients who underwent conventional port laparoscopic distal gastrectomy (CpLDG). The groups were compared in terms of short-term outcomes and disease-free and overall survival rates. RESULTS: The RpLDG group had shorter operation times (161.8 min vs. 189.0 min, p < 0.00) and shorter postoperative hospital stays (7.6 days vs. 9.1 days, p = 0.04) compared to the CpLDG group. Estimated blood loss was lower in the RpLDG group than in the CpLDG group (52.6 mL vs. 73.7 mL, p < 0.00), while hospital costs incurred by the RpLDG group were lower than those of the CpLDG group (10,033.7 vs. 11,016.8 USD, p < 0.00). No statistical differences were found regarding overall morbidity and occurrence of surgical complications of grade III or higher, as defined by the Clavien-Dindo classification. Furthermore, no significant differences between RpLDG and CpLDG were found in 3-year disease-free (99.4% vs. 98.1%; p = 0.42) and 3-year overall survival rates (98.7% vs. 96.8%; p = 0.25). CONCLUSION: Patients who underwent RpLDG had better short-term surgical outcomes than those who underwent CpLDG in terms of operation time, estimated blood loss, duration of hospital stay, and hospital costs. The oncologic safety of RpLDG was satisfactory.

Exposure to polycyclic aromatic hydrocarbons and serum total IgE in the Korean adults: the Third Korean National Environmental Health Survey (2015-2017).

Background: Polycyclic aromatic hydrocarbons (PAHs) have become common pollutants with industrial development. Although the effect of exposure to PAHs on allergic disease in humans has been evaluated, evidence of an association is sparse. The association between PAH exposure and serum total immunoglobulin E (IgE) levels was evaluated in Korean adults. Methods: In total, this study included 3,269 participants in the Third Korean National Environmental Health Survey (2015-2017). Four urinary PAH metabolites were used to assessed exposure to PAHs: 1-hydroxypyrene, 1-hydroxyphenanthrene, 2-naphthol, and 2-hydroxyfluorene. The analyses were performed on 3 cutoff levels (100 IU/mL, 114 IU/mL, and 150 IU/mL) set as the total IgE elevation. Prevalence of total IgE elevation by PAH exposure group and general characteristics (age, sex, BMI, smoking, alcohol drinking, and occupation) were analyzed using the Rao-Scott χ2 test. Multiple logistic regression analyses were conducted to calculate adjusted odds ratios (ORs) for total IgE elevation by PAH exposure groups. Results: Total IgE elevation differed significantly by age, sex, smoking status, alcohol drinking status, and occupation. For 2-hydroxyfluorene, the fourth quartile showed a significant association with IgE elevation compared to the first quartile in the analyses of cutoff-level 100 IU/mL (OR: 1.372, 95% confidence interval [CI]: 1.007-1.869) and 114 IU/mL (OR: 1.643, 95% CI: 1.167-2.312). In the analysis of cutoff-level 150 IU/mL, the adjusted ORs of the third and fourth quartile of 2-hydroxyfluorene were significantly higher than the first quartile (3rd quartile: OR: 1.478, 95% CI: 1.034-2.113; 4th quartile: OR: 1.715, 95% CI: 1.161-2.534). However, there were no significant positive associations for the other metabolites. Conclusions: This study implied that PAHs exposure is associated with total IgE elevation in Korean adults. More research is needed to confirm the effect of exposure to PAHs on serum IgE and allergic diseases.

The relationship between working hours and the intention to quit smoking in male office workers: data from the 7th Korean National Health and Nutrition Examination Survey (2016-2017).

BACKGROUND: The intention to quit smoking is one of the most important factors in smoking cessation. Long working hours is also a constant issue, and many studies have shown an association between the working hours and diseases, including cardiovascular and gastrointestinal diseases. This study evaluated the relationship between working hours and the intention to quit smoking among Korean male office workers, and blue collar workers for comparison. METHODS: This study was based on the Seventh Korea National Health and Nutrition Examination Survey (2016-2017). A total of 1,389 male workers were smokers, and then office workers and blue collar workers were selected. Logistic regression was used to calculate the odds ratio (OR) for the intention to quit smoking according to smoking-related characteristics and working hours after adjusting for age group, body mass index (kg/m2), marital status, household income (quartile), educational level, drinking, exercise, smoking-related characteristics (smoking initiation age, smoking amount, and attempt to quit smoking more than 1day in the past year) and working hours. RESULTS: The percentage of workers who had the intention to quit smoking in 6 months was higher in office workers (38.9% for office workers and 29.4% for blue collars, p = 0.017). Blue collar workers had higher percentages of workers who worked more than 52 hours per week (19.8% for office workers and 38.9% for blue collar workers, p < 0.001). Logistic regression analysis showed that working > 52 hours per week was significantly associated with a lower intention to quit smoking within 6 months among male office workers (OR = 0.30, 95% confidence interval = 0.14-0.66). CONCLUSIONS: Working more than 52 hours per week was positively related with a lower intention to quit smoking among currently smoking male office workers. Further studies are needed considering more work-related variables such as job stress and physical load.

Transcriptome analysis upon potassium usnate exposure reveals ATF3-induced apoptosis in human gastric and colon cancer cells.

BACKGROUND: Potassium usnate (KU), a water-soluble form of usnic acid, shows anticancer activity. However, the underlying mechanisms have not been fully elucidated. PURPOSE: We aimed to identify the pathways involved in anticancer effects of KU in human gastric cancer (GC) and colorectal cancer (CRC) cells using RNA-sequencing (RNA-seq) based transcriptome analysis. STUDY DESIGN: We analyzed the cytotoxic effects of KU to identify the common molecular events in GC and CRC cells upon KU exposure using unbiased approaches. METHODS: Cell viability assays and western blot experiments were used to examine apoptotic changes, cell cycle arrest, and endoplasmic reticulum (ER) stress-induced cellular responses in KU-treated cells. Total RNA from KU-treated human GC and CRC cells was prepared for RNA-seq analysis. Gene ontology term and gene set enrichment analyses were used to identify the key mediators of the cytotoxic effects of KU. The expression of ER stress-induced apoptotic markers was evaluated using quantitative reverse-transcription PCR and western blot analysis. Chromatin immunoprecipitation assays for ATF3 and H3K27ac, and ATF3 knockdown were employed to verify the underlying molecular mechanisms. The inhibitory effect of KU on tumor growth in vivo was validated with metastatic tumor nodule formations in a mouse liver model. RESULTS: KU exerted cytotoxicity in human GC and CRC cells through the activation of the ER stress-induced apoptotic pathway. KU stimulated ATF3 expression, an important mediator of molecular events of apoptosis. ATF3 binds to the promoter region of ATF3, CHOP, GADD34, GADD45A, DR5, and PUMA genes and subsequently promoted apoptotic events. Knockdown of ATF3 significantly reduced the expression of ATF3 target genes and the cytotoxic effects of KU. The intraperitoneal injection of KU induced ATF3 and the apoptosis of implanted colon cancer cells, resulting in reduced metastatic tumor growth in the mouse livers. CONCLUSION: KU exerts cytotoxic effects in human GC and CRC cells by triggering ER stress-induced apoptosis via an ATF3 dependent pathway.

BET Bromodomain Inhibition Blocks an AR-Repressed, E2F1-Activated Treatment-Emergent Neuroendocrine Prostate Cancer Lineage Plasticity Program.

PURPOSE: Lineage plasticity in prostate cancer-most commonly exemplified by loss of androgen receptor (AR) signaling and a switch from a luminal to alternate differentiation program-is now recognized as a treatment resistance mechanism. Lineage plasticity is a spectrum, but neuroendocrine prostate cancer (NEPC) is the most virulent example. Currently, there are limited treatments for NEPC. Moreover, the incidence of treatment-emergent NEPC (t-NEPC) is increasing in the era of novel AR inhibitors. In contradistinction to de novo NEPC, t-NEPC tumors often express the AR, but AR's functional role in t-NEPC is unknown. Furthermore, targetable factors that promote t-NEPC lineage plasticity are also unclear. EXPERIMENTAL DESIGN: Using an integrative systems biology approach, we investigated enzalutamide-resistant t-NEPC cell lines and their parental, enzalutamide-sensitive adenocarcinoma cell lines. The AR is still expressed in these t-NEPC cells, enabling us to determine the role of the AR and other key factors in regulating t-NEPC lineage plasticity. RESULTS: AR inhibition accentuates lineage plasticity in t-NEPC cells-an effect not observed in parental, enzalutamide-sensitive adenocarcinoma cells. Induction of an AR-repressed, lineage plasticity program is dependent on activation of the transcription factor E2F1 in concert with the BET bromodomain chromatin reader BRD4. BET inhibition (BETi) blocks this E2F1/BRD4-regulated program and decreases growth of t-NEPC tumor models and a subset of t-NEPC patient tumors with high activity of this program in a BETi clinical trial. CONCLUSIONS: E2F1 and BRD4 are critical for activating an AR-repressed, t-NEPC lineage plasticity program. BETi is a promising approach to block this program.