Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: 5-year Results of the SENORITA Trial.

OBJECTIVE: This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for EGC in terms of 5-year long-term oncologic outcomes. SUMMARY BACKGROUND DATA: The oncological safety of LSNNS for early gastric cancer (EGC) has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of the phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial), did not show the non-inferiority of LSNNS relative to LSG. METHODS: The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is non-inferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set (FAS). Disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the FAS of both LSG (n=269) and LSNNS (n=258). RESULTS: The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer-related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, ten recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and one by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups. CONCLUSION: The 5-year DFS, DSS and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.

Feasibility of Regional Lymphadenectomy for Stomach-Preserving Surgery in Early Gastric Cancer Omitting Sentinel Node Navigation: A Post Hoc Analysis of the SENORITA Trial.

BACKGROUND: Sentinel node navigation (SNN) has been known as the effective treatment for stomach-preserving surgery in early gastric cancer; however, SNN presents several technical difficulties in real practice. OBJECTIVE: This study aimed to evaluate the feasibility of regional lymphadenectomy omitting SNN, using the post hoc analysis of a randomized controlled trial. METHODS: Using data from the SENORITA trial that compared laparoscopic standard gastrectomy with lymphadenectomy and laparoscopic SNN, 237 patients who underwent SNN were included in this study. Tumor location was divided into longitudinal and circumferential directions. According to the location of the tumor, the presence or absence of lymph node (LN) metastases between sentinel and non-sentinel basins were analyzed. Proposed regional LN stations were defined as the closest area to the primary tumor. Sensitivities, specificities, positive predictive values, and negative predictive values (NPV) of SNN and regional lymphadenectomy were compared. RESULTS: Metastasis to non-sentinel basins with tumor-free in sentinel basins was observed in one patient (0.4%). The rate of LN metastasis to non-regional LN stations without regional LN metastasis was 2.5% (6/237). The sensitivity and NPV of SNN were found to be significantly higher than those of regional lymphadenectomy (96.8% vs. 80.6% [p = 0.016] and 99.5% vs. 97.2% [p = 0.021], respectively). CONCLUSIONS: This study showed that regional lymphadenectomy for stomach-preserving surgery, omitting SNN, was insufficient; therefore, SNN is required in stomach-preserving surgery.

Artificial Intelligence for Assessment of Endotracheal Tube Position on Chest Radiographs: Validation in Patients From Two Institutions.

BACKGROUND. Timely and accurate interpretation of chest radiographs obtained to evaluate endotracheal tube (ETT) position is important for facilitating prompt adjustment if needed. OBJECTIVE. The purpose of our study was to evaluate the performance of a deep learning (DL)-based artificial intelligence (AI) system for detecting ETT presence and position on chest radiographs in three patient samples from two different institutions. METHODS. This retrospective study included 539 chest radiographs obtained immediately after ETT insertion from January 1 to March 31, 2020, in 505 patients (293 men, 212 women; mean age, 63 years) from institution A (sample A); 637 chest radiographs obtained from January 1 to January 3, 2020, in 302 patients (157 men, 145 women; mean age, 66 years) in the ICU (with or without an ETT) from institution A (sample B); and 546 chest radiographs obtained from January 1 to January 20, 2020, in 83 patients (54 men, 29 women; mean age, 70 years) in the ICU (with or without an ETT) from institution B (sample C). A commercial DL-based AI system was used to identify ETT presence and measure ETT tip-to-carina distance (TCD). The reference standard for proper ETT position was TCD between greater than 3 cm and less than 7 cm, determined by human readers. Critical ETT position was separately defined as ETT tip below the carina or TCD of 1 cm or less. ROC analysis was performed. RESULTS. AI had sensitivity and specificity for identification of ETT presence of 100.0% and 98.7% (sample B) and 99.2% and 94.5% (sample C). AI had sensitivity and specificity for identification of improper ETT position of 72.5% and 92.0% (sample A), 78.9% and 100.0% (sample B), and 83.7% and 99.1% (sample C). At a threshold y-axis TCD of 2 cm or less, AI had sensitivity and specificity for critical ETT position of 100.0% and 96.7% (sample A), 100.0% and 100.0% (sample B), and 100.0% and 99.2% (sample C). CONCLUSION. AI identified improperly positioned ETTs on chest radiographs obtained after ETT insertion as well as on chest radiographs obtained of patients in the ICU at two institutions. CLINICAL IMPACT. Automated AI identification of improper ETT position on chest radiographs may allow earlier repositioning and thereby reduce complications.

Identification of maximal tumor size associated with negligible lymph node metastasis for endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND AND AIMS: When treating undifferentiated-type early gastric cancer (UD-EGC) that is limited to the mucosa (clinically T1a), endoscopic submucosal dissection (ESD) can be considered if the tumor is 2 cm or less and is not ulcerated. However, there is insufficient evidence to determine the relationships between tumor size and oncological safety of ESD in UD-EGC. METHODS: The pathology reports of Korean patients who were diagnosed with UD-EGC (n = 5286) were retrospectively reviewed. The cumulative incidence of lymph node metastasis (LNM) according to tumor size was evaluated in subgroups. The tumor-size cut-off was identified as the upper limit of the 95% confidence interval (CI) of cumulative LNM incidence that did not exceed 1.0%. RESULTS: We identified 1516 patients with non-ulcerated T1a tumors ≤2 cm in size. Among patients without lymphatic invasion, 1.5% (95% CI 0.91-2.16%) had LNM. In patients with poorly differentiated tubular adenocarcinoma (PD), LNM increased from 0 to 0.74% based on a tumor size of 1.0 cm. Regardless of tumor size, smaller percentages of undifferentiated-type (UD) and poorly cohesive carcinoma (PCC) patients experienced LNM than did those with PD. In non-ulcerated mucosal cancer without lymphatic invasion and tumor size ≤0.9 cm, no LNM was observed in patients with UD (95% CI 0-0.53%), PCC (95% CI 0-0.59%), or PD (95% CI 0-0.86%) histologic type. CONCLUSION: In patients diagnosed with non-ulcerated T1a UD-EGC, ESD can be performed if the tumor size is 0.9 cm or less, regardless of histologic type.

Mood Disorder Severity and Subtype Classification Using Multimodal Deep Neural Network Models.

The subtype diagnosis and severity classification of mood disorder have been made through the judgment of verified assistance tools and psychiatrists. Recently, however, many studies have been conducted using biomarker data collected from subjects to assist in diagnosis, and most studies use heart rate variability (HRV) data collected to understand the balance of the autonomic nervous system on statistical analysis methods to perform classification through statistical analysis. In this research, three mood disorder severity or subtype classification algorithms are presented through multimodal analysis of data on the collected heart-related data variables and hidden features from the variables of time and frequency domain of HRV. Comparing the classification performance of the statistical analysis widely used in existing major depressive disorder (MDD), anxiety disorder (AD), and bipolar disorder (BD) classification studies and the multimodality deep neural network analysis newly proposed in this study, it was confirmed that the severity or subtype classification accuracy performance of each disease improved by 0.118, 0.231, and 0.125 on average. Through the study, it was confirmed that deep learning analysis of biomarker data such as HRV can be applied as a primary identification and diagnosis aid for mental diseases, and that it can help to objectively diagnose psychiatrists in that it can confirm not only the diagnosed disease but also the current mood status.

Predictive Value of KLASS-02-QC Assessment Score on KLASS-02 Surgical Outcomes: Validation of Surgeon Quality Control and Standardization for D2 Lymphadenectomy.

OBJECTIVE: The aim of this study was to audit the 22 items and assessed each item's predictive value on surgical outcomes. BACKGROUND: The KLASS-02 trial revealed that the oncologic outcomes of laparoscopic distal gastrectomy are not inferior to open distal gastrectomy in patients with advanced gastric cancer. The surgeons participating in this trial were chosen based on the assessment scores from the KLASS-02-QC trial, which used 22 items for standardization of D2 lymphadenectomy and quality control. METHODS: We reviewed proficiency scores (PSs) for 22 items for 20 surgeons who participated in KLASS-02. The surgeons were divided into 2 groups according to PS, and the perioperative outcomes of 924 patients enrolled in KLASS-02 were compared between groups. Each item's predictive value for perioperative outcome was then assessed using multivariable regression models. RESULTS: Of the total 924 patients, 529 were operated on by high-score surgeons (high PS) and 395 were operated on by low-score surgeons (low-PS). High-PS group had less intraoperative blood loss, longer operation times, and fewer complications, major complications, reoperations, and shorter first flatus and hospital stay than low-PS group ( P =0.006, P <0.001, P <0.001, P <0.001, P =0.042, P =0.013, and P <0.001, respectively). Some items used in KLASS-02-QC predicted perioperative outcomes, such as intraoperative blood loss, major complications, reoperation, and hospital stay. CONCLUSIONS: Although this study only analyzed data associated with qualified surgeons, the 22 items effectively assessed the surgeons based on PS. A high score was associated with longer operation times, but better perioperative outcomes.

Standard follow-up after curative surgery for advanced gastric cancer: secondary analysis of a multicentre randomized clinical trial (KLASS-02).

BACKGROUND: The benefit of regular follow-up after curative resection for gastric cancer is controversial as there is no evidence that it will improve survival. This study assessed whether regular follow-up leads to improved survival in patients after surgery for gastric cancer. METHODS: A secondary analysis was undertaken of patients who participated in an RCT of laparoscopic versus open distal gastrectomy for advanced gastric cancer between November 2011 and April 2015. Depending on whether patients were compliant with the initial trial follow-up protocol or not, they were analysed as having had either regular or irregular follow-up. Clinicopathological characteristics, recurrence patterns, detection, treatments, and survival were compared between the groups. RESULTS: The regular and irregular follow-up groups comprised 712 and 263 patients respectively. Disease recurrence within 36 months was more common in the regular group than in the irregular group (17.0 versus 11.4 per cent; P = 0.041). Recurrence patterns did not differ between the groups. The 3-year recurrence-free survival rate was worse in the regular than in the irregular group (81.2 versus 86.5 per cent; P = 0.031). However, the 5-year overall survival rate was comparable (84.5 versus 87.5 per cent respectively; P = 0.160). Multivariable analysis revealed that type of follow-up was not an independent factor affecting 5-year overall survival. CONCLUSION: Regular follow-up after radical gastrectomy was not associated with improved overall survival.

Determining the precise extent of sentinel basins during laparoscopic gastrectomy for early gastric cancer.

PURPOSE: By analyzing sentinel basin dissection (SBD) data from the SEntinel Node ORIented Tailored Approach (SENORITA) trial, we sought to determine the precise extent of the sentinel basin (SB) without a tracer. MATERIALS AND METHODS: This study investigated SB length in patients (n = 25) who underwent laparoscopic SBD for early gastric cancer (EGC) in the SENORITA trial. SB length along the greater curvature (GC) and lesser curvature (LC) was measured intraoperatively before performing SBD. RESULTS: In all 25 cases, along the LC of the stomach, the lengths of the SB were 3.7 cm [2.0-5.0] (median [min-max]) proximally and 3.0 cm [2.3-5.5] distally; along the GC side, the lengths of the SB were 6.8 cm [3.5-11.0] proximally and 7.0 cm [3.8-9.5] distally from the tumors. The SB length at the GC or LC side was not significantly different between subgroups categorized by tumor depth, size, and longitudinal location. When tumors were located at the anterior wall of the stomach, the length of the proximal SB (10.0 cm [9.0-11.0]) at the GC side was the longest. In cases with several sentinel lymph nodes (SLNs), the lengths of the SB at the GC side were significantly longer than those with fewer SLNs. However, the lengths of the SB were similar on the LC side regardless of the number of SLNs. CONCLUSIONS: This pilot study had some limitations of a small number of enrolled patients, the lack of research on the specific station of SLNs, and the inaccurate indication for sentinel node navigation surgery (SNNS) without tracer. Nevertheless, the present study which reported the extents of SBs might be the first step towards simplifying procedures in laparoscopic SNNS for stomach preservation in EGC.

Soil potentially toxic element pollution at different urbanization intensities: Quantitative source apportionment and source-oriented health risk assessment.

Potentially toxic element (PTE) pollution of urban soils has become the focus of social concern, but the differences of the sources, pollution levels and source-oriented human health risks (HHR) of PTE in urban soils among different urban intensity areas is rarely known. This study explored a comprehensive scheme that combined positive matrix factorization model and source-oriented assessment to quantitatively assess the priority pollution sources and HHR in urban soils from areas with different urbanization intensities. All the average values for PTE concentrations, except for Cr, were higher than their corresponding background values. The contributions made by the four sources (atmospheric deposition, agricultural activities, traffic activities, and natural sources) were relatively similar (22.29-29.89%) in the low urbanization intensity (LUI) area, whereas traffic activities and atmospheric deposition made the greatest contributions in the medium urbanization intensity (MUI) (29.12%) and the high urbanization intensity (HUI) (38.97%) areas, respectively. The geo-accumulation index results revealed that Cd was the most polluting element and the HUI area had the highest pollution levels. The content-oriented assessment of HHR demonstrated that the non-carcinogenic risks were acceptable, but the carcinogenic risks were unacceptable. According to the source-oriented HHR assessment, among the anthropogenic activities, atmospheric deposition contributed the most to carcinogenic risk of children in all areas, and atmospheric deposition, traffic activities and agricultural activities contributed the most to the carcinogenic risk of adults in HUI, MUI and LUI, respectively. This suggest that control measures need to be tailored to the appropriate urbanization intensity to effectively curb PTE pollution caused by anthropogenic activities.

A Three-Year Longitudinal Study of Risk Factors for Suicidality in North Korean Defectors.

BACKGROUND: This longitudinal study examined risk factors for future suicidality among North Korean defectors (NKDs) living in South Korea. METHODS: The subjects were 300 NKDs registered with a regional adaptation center (the Hana Center) in South Korea. Face-to-face interviews were conducted using the North Korean version of the World Health Organization's Composite International Diagnostic Interview to diagnose mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Subjects were also asked about sociodemographic and clinical factors at baseline. At follow-up after three years, the NKDs (n = 172 respondents) were asked to participate in an online survey, responding to self-questionnaires about suicidality. Logistic regression analyses were used to explore associations between baseline variables and future suicidality among NKDs. RESULTS: Thirty (17.4%) of the 172 survey respondents reported suicidality at follow-up. The presence of health problems over the past year, any prior suicidality at baseline, a higher score on a trauma-related scale, and a lower score on a resilience scale at baseline were associated with greater odds of suicidality at follow-up after adjusting for age, sex, and educational level. Of all mental disorder categories, major depressive disorder, dysthymia, agoraphobia, and social phobia were also associated with significantly increased odds of suicidality at follow-up after adjusting for age, sex, educational level, and prior suicidality at baseline. CONCLUSION: Resilience, a previous history of suicidality, and the presence of lifetime depressive disorder and anxiety disorder should be given consideration in mental health support and suicide prevention in NKDs.

Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis.

Studies have shown that diabetes is associated with the occurrence of neurodegenerative diseases and cognitive decline. However, there is currently no effective treatment for diabetes-induced cognitive dysfunction. The superior efficacy of liraglutide (LIRA) for cognitive impairment and numerous neurodegenerative diseases has been widely demonstrated. This study determined the effects of LIRA on diabetic cognitive impairment and on the levels of oxidative stress, lipid peroxidation, iron metabolism and ferroptosis in the hippocampus. Mice were injected daily with liraglutide (200 µg/kg/d) for 5 weeks. LIRA could repair damaged neurons and synapses, and it increased the protein expression levels of PSD 95, SYN, and BDNF. Furthermore, LIRA significantly decreased oxidative stress and lipid peroxidation levels by downregulating the production of ROS and MDA and upregulating SOD and GSH-Px in the serum and hippocampus, and the upregulation of SOD2 expression was also proven. The decreased levels of TfR1 and the upregulation of FPN1 and FTH proteins observed in the LIRA-treated db/db group were shown to reduce iron overload in the hippocampus, whereas the increased expression of Mtft and decreased expression of Mfrn in the mitochondria indicated that mitochondrial iron overload was ameliorated. Finally, LIRA was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4; simultaneously, the damage to the mitochondria observed by TEM was also repaired. For the first time, we proved in the T2DM model that ferroptosis occurs in the hippocampus, which may play a role in diabetic cognitive impairment. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetic cognitive disorders and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.

Clinicopathologic and genomic characteristics of mucinous gastric adenocarcinoma.

BACKGROUND: Mucinous gastric adenocarcinoma (MGC) is a rare but distinctive histologic subtype of gastric cancer (GC). The clinico-pathologic and genomic characteristics of MGC have not been well evaluated. METHODS: We collected individual data from five cohorts targeting the microsatellite instability (MSI) of GC (n = 5089) to evaluate the clinico-pathologic characteristics of MGC. In addition, public genomic databases were used for genomic analysis. The characteristics of MGC were compared with those of non-mucinous GC (NMGC). RESULTS: MGC (n = 158, 3.1%) showed distinctive characteristics in terms of age, sex, and TNM stage compared to NMGC (n = 4931). MGC was frequently associated with MSI-high (OR: 2.24, 95% confidence interval [CI] 1.44-3.40, p < 0.001), while mutually exclusive to the Epstein-Barr virus type. The prognosis of MGC was better than that of NMGC (adj.HR: 0.731, 95% CI 0.556-0.962, p = 0.025). There was no clear benefit from postoperative chemotherapy in MGC. TP53 was the main driver mutation in the MGC without recurrent variants. MGC was related to high expression of GPR120 and B3GNT6 and moderate regulation of epithelial-mesenchymal transition (EMT)-up signature with a high EMT-down signature, and those characteristics was related to favorable prognosis of GC (log-rank p = 0.044, p < 0.001, p < 0.001, respectively). MSI-H of MGC was associated with low cancer-associate fibroblasts but high CD274 (PD-L1) expression compared to microsatellite stable MGC, suggesting that immune checkpoint inhibitors may be useful for the MSI-H of MGC. CONCLUSION: MGC could be a surrogate for performing MSI but not the EBV test in GC. Further, its genetic characteristics lead to a favorable prognosis for MGC.

A preoperative risk prediction model for high malignancy potential gastrointestinal stromal tumors of the stomach.

BACKGROUND: Gastric gastrointestinal stromal tumors (GISTs) exhibit various degrees of aggression and malignant potential. However, no systematic preoperative evaluation strategy to predict the malignancy potential of gastric GISTs has yet been developed. This study aimed to develop a reliable and easy-to-use preoperative risk-scoring model for predicting high malignancy potential (HMP) gastric GISTs. METHODS: The data of 542 patients with pathologically confirmed gastric GISTs who underwent resection were reviewed. Multivariate logistic regression analysis was used to identify significant predictors of HMP. The risk-scoring system (RSS) was based on the predictive factors for HMP, and its performance was validated using a split-sample approach. RESULTS: A total of 239 of 542 (44.1%) surgically resected gastric GISTs had HMP. Multivariate analysis demonstrated that tumor size, location, and surface changes were independent risk factors for HMP. Based on the accordant regression coefficients, the presence of surface ulceration was assigned 1 point. Tumor sizes of 4-6 cm and > 6 cm were assigned 2 and 5 points, respectively. Two points were assigned to cardia or fundus locations. A score of 3 points was the optimal cut-off value for HMP prediction. HMP were found in 19.8% and 82.7% of the low and high-risk groups of the RSS, respectively. The area under the receiver-operating characteristic curve for predicting HMP was 0.81 (95% confidence interval (CI) 0.75-0.86). Discrimination was good after validation (0.75, 95% CI 0.69-0.81). CONCLUSION: This simple RSS could be useful for predicting the malignancy potential of gastric GISTs and may aid preoperative clinical decision making to ensure optimal treatment.

Work-family conflict and job stress among seafarers: the moderating role of job satisfaction.

Work-family conflict (WFC) is not only prevalent among seafarers but also may cause their job stress. The objective of this research is to investigate the relationship between WFC and job stress, examining the moderating role of job satisfaction, which plays in this relationship. A cross-sectional survey was conducted in Yangshan Port, Shanghai, China, from August to October 2019. Seafarers working on merchant vessels participated in the present study. Hierarchical linear regression analyses were employed to test the moderating role of job satisfaction. The results demonstrated that WFC was positively associated with job stress. Job satisfaction played a moderating role in the association of WFC with job stress. The findings show that job satisfaction was a crucial factor to reduce seafarers' job stress. Managers should therefore enhance organizational investment and support in job satisfaction to reduce seafarers' job stress.

Comparative Metabolomic Analysis of Moromi Fermented Using Different Aspergillus oryzae Strains.

Aspergillus oryzae (A. oryzae) is an important starter in the fermentation of koji and moromi. However, the effect of different A. oryzae strains on the quality of moromi has rarely been studied. For this reason, this study analyzed the physicochemical properties, enzyme activity, sensory quality, and metabolite profiles of moromi samples fermented using two strains (A. oryzae KCCM12012P (moromi-1) and KCCM12804P (moromi-2)), which were newly isolated from fermented soy foods, and compared them to those of a commercialized A. oryzae strain (control). Amino-type nitrogen contents of moromi-1 and moromi-2 samples were higher than that of control moromi, and their amylase and protease activities were also higher. Moreover, metabolite profiles of moromi were significantly altered according to strains. In particular, the levels of many amino acids, peptides, nucleotides, and acidic compounds were altered, which resulted in changes in the sensory quality of moromi. Although volatile compounds were not investigated, the results suggested that the quality of moromi was significantly different for newly isolated strains, especially A. oryzae KCCM12804P, and they were superior to the commercial strain in terms of taste-related substances. Therefore, these strains could be used as good starters to produce moromi and soy sauce with good sensory quality.

Banxia-Houpu decoction diminishes iron toxicity damage in heart induced by chronic intermittent hypoxia.

CONTEXT: Obstructive sleep apnoea (OSA) causes chronic intermittent hypoxia (CIH), which results in mitochondrial dysfunction and generates reactive oxygen species (ROS) in the heart. Excessive free iron could accelerate oxidative damage, which may be involved in this process. Banxia-Houpu decoction (BHD) was reported to improve the apnoea hypopnoea index in OSA patients, but the specific mechanism was still unclear. OBJECTIVE: To investigate whether BHD could reduce CIH-induced heart damage by regulating iron metabolism and mitochondrial function. MATERIALS AND METHODS: C57BL/6N mice were randomly divided into control, CIH and BHD groups. Mice were exposed to CIH (21 - 5% O2, 20 times/h, 8 h/d) and administered BHD (3.51, 7.01 and 14.02 g/kg, intragastrically) for 21 d. Cardiac and mitochondrial function, iron levels, apoptosis and mitophagy were determined. RESULTS: BHD (7.01 g/kg) significantly improved cardiac dysfunction, pathological change and mitochondrial structure induced by CIH. BHD increased the Bcl-2/Bax ratio (1.4-fold) and inhibited caspase 3 cleavage in CIH mice (0.45-fold). BHD activated mitophagy by upregulating Parkin (1.94-fold) and PINK1 (1.26-fold), inhibiting the PI3K-AKT-mTOR pathway. BHD suppressed ROS generation by decreasing NOX2 (0.59-fold) and 4-HNE (0.83-fold). BHD reduced the total iron in myocardial cells (0.72-fold) and mitochondrial iron by downregulating Mfrn2 (0.81-fold) and MtFt (0.78-fold) proteins, and upregulating ABCB8 protein (1.33-fold). Rosmarinic acid, the main component of Perilla Leaf in BHD, was able to react with Fe2+ and Fe3+ in vitro. DISCUSSION AND CONCLUSIONS: These findings encourage the use of BHD to resist cardiovascular injury and provide the theoretical basis for clinical treatment in OSA patients.

Effects of alternating pressure air mattresses on pressure injury prevention: A systematic review of randomized controlled trials.

BACKGROUND: Pressure injury (PI) is a significant health problem among inpatients that affects their health, quality of life, and expenses. AIM: This systematic review aimed to compare effects of alternating pressure air mattresses (APMs) with other types of supporting surfaces as a tool for PI prevention. METHODS: The literature published between 2009 and 2020 was searched using the databases PubMed, EMBASE, CINAHL, and Cochrane. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses process was followed, including independent study selection and data extraction. Quality appraisal was conducted using the Cochrane Risk of Bias Tool (RoB 2.0). RESULTS: A total of six randomized controlled trials (RCTs) were analyzed. The incidence of hospital-acquired PIs at stage 1 or higher was reported in the APM group from 0.3% to 25%. In one study, APMs were found to be less effective than static air mattresses (SAMs); in contrast, two studies found no difference. In one study, the APM was reported to be more effective than the viscoelastic foam mattress (VFM). On the contrary, in a more recent study, the APM was reported to be less effective than the VFM, and there was no difference compared with high-specification foam mattresses in another study. Using the RoB 2.0 tool, one study was evaluated at "low risk of bias," another as "some concern," and four as "high risk." LINKING EVIDENCE TO ACTION: There is insufficient evidence to suggest that APM is more effective in preventing PIs than other supporting surfaces. Evidence to date suggests that APM can be used in patients at risk for PIs. It is important to change position regardless of the type of support surface used. Highly controlled RCTs with low risk of bias are needed to provide strong evidence for identifying the most effective PI prevention support surfaces.

Adjuvant Chemotherapy vs. Surgery Alone for pT3N0M0 Gastric Cancer.

BACKGROUND: As both the role and clinical application of adjuvant chemotherapy (CTx) for pT3N0M0 gastric cancer after curative gastrectomy have fluctuated chronologically, the oncological benefit of adjuvant CTx in patients should be elucidated. METHODS: Between 2000 and 2018, 1083 patients underwent radical gastrectomy for pT3N0M0 gastric cancer and were subsequently divided into two groups: the surgery-alone group (n = 471) and the adjuvant CTx group (n = 612). Chronological changes in adjuvant CTx and various chemotherapeutic regimens were evaluated and disease-free survival was compared between the two groups. Risk factors for tumor recurrence were also analyzed. RESULTS: The proportion of patients in the surgery-alone group was more than 60% until 2001, whereas in the CTx group this increased to over 80%, especially after publication of the American Joint Committee on Cancer (AJCC) 7th edition staging manual. The main chemotherapeutic agents were tegafur-uracil (UFT) and 5-fluorouracil with leucovorin until 2008, whereas tegafur/gimeracil/oteracil (TS-1) has been the main agent since 2009. The 5-year disease-free survival was 89.2% in the surgery-alone group and 89.9% in the CTx group, which was not significantly different (p = 0.694). In multivariate analysis, larger tumor size (≥ 4.5 cm) and venous invasion were significant risk factors for tumor recurrence. In addition, adjuvant CTx did not improve the oncological outcome, even in the large tumor size group (p = 0.760) and the venous invasion group (p = 0.753). CONCLUSIONS: As adjuvant CTx did not show any oncological benefit in pT3N0M0 gastric cancer in this large-scale study, it might be unnecessary for these patients after curative gastrectomy.

Microsatellite Instability and Effectiveness of Adjuvant Treatment in pT1N1 Gastric Cancer: A Multicohort Study.

BACKGROUND: Microsatellite status is a prognostic biomarker in advanced gastric cancer. This retrospective study aimed to investigate the usefulness of microsatellite status in predicting prognosis and response to adjuvant treatment in pT1N1 gastric cancer. PATIENTS AND METHODS: Among 875 patients who underwent radical gastrectomy for pT1N1 gastric cancer at two tertiary hospitals, 838 with available microsatellite instability (MSI) data were included and classified into two groups according to microsatellite status: microsatellite stable (MSS) and MSI-high (MSI-H). Recurrence-free survival rate and risk factors for tumor recurrence were analyzed. RESULTS: Of 838 gastric cancer patients, 100 (11.9%) were MSI-H and 307 (36.6%) received adjuvant treatment. During median follow-up of 70 months, 42 (5.0%) patients experienced gastric cancer recurrence; hematogenous recurrences were the most common (45.2%). Recurrence-free survival was similar in the MSS and MSI-H groups (p = 0.27), and adjuvant treatment did not show an oncological benefit over surgery alone for pT1N1 gastric cancer (p = 0.53). On univariate analysis, age, operation period, and Lauren classification were significantly associated with tumor recurrence, while adjuvant treatment and MSI status were not associated with tumor recurrence. On multivariate analysis, MSI status was not associated with tumor recurrence, and adjuvant treatment worsened the tumor recurrence risk [hazard ratio (HR) 2.373, 95% confidence interval (CI) 1.125-5.006, p = 0.023). CONCLUSION: MSI status may not be a prognostic factor for tumor recurrence or a predictor of response to adjuvant treatment in pT1N1 gastric cancer patients. Considering that the effect of adjuvant treatment to decrease the risk of tumor recurrence is not clear, it may not be indicated in pT1N1 patients.

[Expression of TGF-ß in bladder neck contracture after transurethral enucleation and resection of the prostate].

OBJECTIVE: To explore the role of transforming growth factor-ß (TGF-ß) in bladder neck contracture (BNC) after transurethral enucleation and resection of the prostate (TUERP). METHODS: This study included 300 BPH patients undergoing TUERP, aged 51－89 (69.19 ± 8.43) years, with the prostate volume of 14.4－355.8 (63.18 ± 47.63) ml and preoperative IPSS of 15－35 (26.07 ± 5.9), QOL score of 3－6 (4.43 ± 0.67), PSA content of 0.17－23.16 (2.94 ± 3.77) ug/L, urinary leukocyte increase in 50 cases, post-void residual urine volume (PVR) of 0－440 (83.53 ± 86.85) ml, and maximum urinary flow rate (Qmax) of 2.3－14.5 (7.77 ± 3.47) ml/s. During TUERP, we collected the tissues from the bladder neck at 5 and 7 o'clock as well as the BPH tissue and the tissue from the residual prostate for HE staining, immunohistochemistry (the SP method) and examination of the infiltration degree of inflammatory cells and expressions of TGF-ß1 and TGF-ß3. During the 6－24 months follow-up, 6 of the patients were confirmed with BNC based on the clinical symptoms and the results of uroflowmetry and cystoscopy, and underwent transurethral bladder neck incision and detection of the expressions of TGF-ß1 and TGF-ß3 in the bladder neck tissue with BNC. RESULTS: The bladder neck tissue without BNC was mainly composed of smooth muscle and fibrous tissues with local infiltration of inflammatory cells, and the residual prostate tissue primarily comprised fibrous and muscle tissues, mixed with a little prostatic epithelial tissue. The bladder neck tissue with BNC, compared with that harvested during the initial TUERP, exhibited significantly increased expression of TGF-ß1 (ï¼»68.20 ± 10.88ï¼½% vs ï¼»36.14 ± 7.62ï¼½%, P < 0.05), decreased expression of TGF-ß3 (ï¼»8.55 ± 4.73ï¼½% vs ï¼»20.77 ± 8.69ï¼½%, P < 0.05), and enhanced infiltration of inflammatory cells (P < 0.05). The bladder neck tissue without BNC, in comparison with the BPH tissue, showed dramatically up-regulated expressions of TGF-ß1 (ï¼»27.05 ± 8.21ï¼½% vs ï¼»1.61 ± 0.69ï¼½%, P < 0.001) and TGF-ß3 (ï¼»14.09 ± 4.19ï¼½% vs ï¼»0.32 ± 0.11ï¼½%, P < 0.001) and increased infiltration of inflammatory cells (P < 0.05). CONCLUSIONS: After TUERP, the expression of TGF-ß1 is increased, that of TGF-ß3 decreased and the infiltration of inflammatory cells enhanced in the bladder neck tissue with BNC, which suggests that BNC may be related to the expression of TGF-ß and that BNC after TUERP could be prevented by regulating the expression of TGF-ß.