BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma.

Interaction between programmed death-1 (PD-1) ligand 1 (PD-L1) on tumor cells and PD-1 on T cells allows tumor cells to evade T cell-mediated immune surveillance. Strategies targeting PD-1/PD-L1 have shown clinical benefits in a variety of cancers. However, limited response rates in hepatocellular carcinoma (HCC) have prompted us to investigate the molecular regulation of PD-L1. Here, we identify B cell lymphoma-2-associated transcription factor 1 (BCLAF1) as a key PD-L1 regulator in HCC. Specifically, BCLAF1 interacts with SPOP, an E3 ligase that mediates the ubiquitination and degradation of PD-L1, thereby competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Furthermore, we determined an SPOP-binding consensus (SBC) motif mediating the BCLAF1-SPOP interaction on BCLAF1 protein and mutation of BCLAF1-SBC motif disrupts the regulation of the SPOP-PD-L1 axis. In addition, BCLAF1 expression was positively correlated with PD-L1 expression and negatively correlated with biomarkers of T cell activation, including CD3 and CD8, as well as with the level of immune cell infiltration in HCC tissues. Besides, BCLAF1 depletion leads to a significant reduction of PD-L1 expression in vitro, and this reduction of PD-L1 promoted T cell-mediated cytotoxicity. Notably, overexpression of BCLAF1 sensitized tumor cells to checkpoint therapy in an in vitro HCC cells-Jurkat cells co-culture model, whereas BCLAF1-SBC mutant decreased tumor cell sensitivity to checkpoint therapy, suggesting that BCLAF1 and its SBC motif serve as a novel therapeutic target for enhancing anti-tumor immunity in HCC.

Genetic Diversity, Heteroplasmy, and Recombination in Mitochondrial Genomes of Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa.

Genetic variants of mitochondrial DNA at the individual (heteroplasmy) and population (polymorphism) levels provide insight into their roles in multiple cellular and evolutionary processes. However, owing to the paucity of genome-wide data at the within-individual and population levels, the broad patterns of these two forms of variation remain poorly understood. Here, we analyze 1,804 complete mitochondrial genome sequences from Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa. Extensive heteroplasmy is observed in D. obtusa, where the high level of intraclonal divergence must have resulted from a biparental-inheritance event, and recombination in the mitochondrial genome is apparent, although perhaps not widespread. Global samples of D. pulex reveal remarkably low mitochondrial effective population sizes, <3% of those for the nuclear genome. In addition, levels of population diversity in mitochondrial and nuclear genomes are uncorrelated across populations, suggesting an idiosyncratic evolutionary history of mitochondria in D. pulex. These population-genetic features appear to be a consequence of background selection associated with highly deleterious mutations arising in the strongly linked mitochondrial genome, which is consistent with polymorphism and divergence data suggesting a predominance of strong purifying selection. Nonetheless, the fixation of mildly deleterious mutations in the mitochondrial genome also appears to be driving positive selection on genes encoded in the nuclear genome whose products are deployed in the mitochondrion.

Diagnosis and Treatment Strategy of Nasogenic Olfactory Dysfunction.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

US LI-RADS in surveillance for recurrent hepatocellular carcinoma after curative treatment.

OBJECTIVES: To investigate the performance of US LI-RADS in surveillance for recurrent hepatocellular carcinoma (RHCC) after curative treatment. MATERIALS AND METHODS: This study enrolled 644 patients between January 2018 and August 2018 as a derivation cohort, and 397 patients from September 2018 to December 2018 as a validation cohort. The US surveillance after HCC curative treatment was performed. The US LI-RADS observation categories and visualization scores were analyzed. Four criteria using US LI-RADS or Alpha-fetoprotein (AFP) as the surveillance algorithm were evaluated. The sensitivity, specificity, and negative predictive value (NPV) were calculated. RESULTS: A total of 212 (32.9%) patients in derivation cohort and 158 (39.8%) patients in validation cohort were detected to have RHCCs. The criterion of US-2/3 or AFP ≥ 20 µg/L had higher sensitivity (derivation, 96.7% vs 92.9% vs 81.1% vs 90.6%; validation, 96.2% vs 90.5% vs 80.4% vs 89.9%) and NPV (derivation, 95.7% vs 93.3% vs 88.0% vs 91.8%; validation, 94.6% vs 89.4% vs 83.6% vs 89.0%), but lower specificity (derivation, 35.9% vs 48.2% vs 67.6% vs 51.9%; validation, 43.5% vs 52.7% vs 66.1% vs 54.0%) than criterion of US-2/3, US-3, and US-3 or AFP ≥ 20 µg/L. Analysis of the visualization score subgroups confirmed that the sensitivity (89.2-97.6% vs 81.0-83.3%) and NPV(88.4-98.0% vs 80.0-83.3%) of score A and score B groups were higher than score C group in criterion of US-2/3 in both two cohorts. CONCLUSIONS: In the surveillance for RHCC, US LI-RADS with AFP had a high sensitivity and NPV when US-2/3 or AFP ≥ 20 µg/L was considered a criterion. CLINICAL RELEVANCE STATEMENT: The criterion of US-2/3 or AFP ≥ 20 µg/L improves sensitivity and NPV for RHCC surveillance, which provides a valuable reference for patients in RHCC surveillance after curative treatment. KEY POINTS: • US LI-RADS with AFP had high sensitivity and NPV in surveillance for RHCC when considering US-2/3 or AFP ≥ 20 µg/L as a criterion. • After US with AFP surveillance, patients with US-2/3 or AFP ≥ 20 µg/L should perform enhanced imaging for confirmative diagnosis. Patients with US-1 or AFP < 20 µg/L continue to repeat US with AFP surveillance. • Patients with risk factors for poor visualization scores limited the sensitivity of US surveillance in RHCC.

Ecological model of health behaviour of hypertensive stroke patients at the end of recovery period.

AIMS AND OBJECTIVES: This study aimed to construct a structural equation model guided by the ecological model to explore the factors influencing health behaviour among hypertensive stroke patients 6 months post-stroke. BACKGROUND: Health behaviour is important for recurrence prevention in hypertensive stroke patients. Moreover, previous studies have indicated that health behaviour at the end of the recovery period is of particular concern. The ecological model provides an integrated perspective for explaining the factors influencing health behaviour. DESIGN: A cross-sectional study guided by the STROBE. METHODS: A total of 121 hypertensive stroke patients were included to assess stroke knowledge, health belief, depression, family function, chronic illness resource and health behaviour. A structural equation model was used to explore the health behaviour's factors and pathways. RESULTS: In the final ecological model, sex, education level, depression and chronic illness resource directly affected health behaviour. Stroke knowledge directly affected health behaviour and indirectly affected health behaviour through health belief and chronic illness resource. Family function indirectly affected health behaviour through health belief, depression and chronic illness resource. Health belief affected health behaviour indirectly through depression and chronic illness resource. CONCLUSIONS: Hypertensive stroke patients' health behaviour is jointly and interactively influenced by stroke knowledge, health belief, depression, family function and chronic illness resource. In particular, chronic illness resource is an important mediator of health behaviour. RELEVANCE TO CLINICAL PRACTICE: For clinical practitioners, health behaviour of men and patients with low educational levels should be specifically focused on. Additionally, it is necessary to provide stroke knowledge, establish health beliefs, control depression emotion and improve family function. Furthermore, chronic illness resources should be improved particularly due to its important mediating role. PATIENT OR PUBLIC CONTRIBUTION: Participants completed demographic and disease-related questionnaires during hospitalisation and completed other questionnaires when returning to hospital at 6 months follow-up.

Shear-wave elastography combined with contrast-enhanced ultrasound algorithm for noninvasive characterization of focal liver lesions.

PURPOSE: To establish shear-wave elastography (SWE) combined with contrast-enhanced ultrasound (CEUS) algorithm (SCCA) and improve the diagnostic performance in differentiating focal liver lesions (FLLs). MATERIAL AND METHODS: We retrospectively selected patients with FLLs between January 2018 and December 2019 at the First Affiliated Hospital of Sun Yat-sen University. Histopathology was used as a standard criterion except for hemangiomas and focal nodular hyperplasia. CEUS with SonoVue (Bracco Imaging) and SCCA combining CEUS and maximum value of elastography with < 20 kPa and > 90 kPa thresholds were used for the diagnosis of FLLs. The diagnostic performance of CEUS and SCCA was calculated and compared. RESULTS: A total of 171 FLLs were included, with 124 malignant FLLs and 47 benign FLLs. The area under curve (AUC), sensitivity, and specificity in detecting malignant FLLs were 0.83, 91.94%, and 74.47% for CEUS, respectively, and 0.89, 91.94%, and 85.11% for SCCA, respectively. The AUC of SCCA was significantly higher than that of CEUS (P = 0.019). Decision curves indicated that SCCA provided greater clinical benefits. The SCCA provided significantly improved prediction of clinical outcomes, with a net reclassification improvement index of 10.64% (P = 0.018) and integrated discrimination improvement of 0.106 (P = 0.019). For subgroup analysis, we divided the FLLs into a chronic-liver-disease group (n = 88 FLLs) and a normal-liver group (n = 83 FLLs) according to the liver background. In the chronic-liver-disease group, there were no differences between the CEUS-based and SCCA diagnoses. In the normal-liver group, the AUC of SCCA and CEUS in the characterization of FLLs were 0.89 and 0.83, respectively (P = 0.018). CONCLUSION: SCCA is a feasible tool for differentiating FLLs in patients with normal liver backgrounds. Further investigations are necessary to validate the universality of this algorithm.

A Multifluorination Strategy Toward Wide Bandgap Polymers for Highly Efficient Organic Solar Cells.

Creating new electron-deficient unit is highly demanded to develop high-performance polymer donors for non-fullerene organic solar cells (OSCs). Herein, we reported a multifluorinated unit 4,5,6,7-tetrafluoronaphtho[2,1-b : 3,4-b']dithio-phene (FNT) and its polymers PFNT-F and PFNT-Cl. The advantages of multifluorination: (1) it enables the polymers to exhibit low-lying HOMO (≈-5.5 eV) and wide band gap (≈2.0 eV); (2) the short interactions (F⋅⋅⋅H, F⋅⋅⋅F) endow the polymers with properties of high film crystallinity and efficient hole transport; (3) well miscibility with NFAs that leads to a more well-defined nanofibrous morphology and face-on orientation in the blend films. Therefore, the PFNT-F/Cl : N3 based OSCs exhibit impressive FF values of 0.80, and remarkable PCEs of 17.53 % and 18.10 %, which make them ranked the best donor materials in OSCs. This work offers new insights into the rational design of high-performance polymers by multifluorination strategy.

Efficient synthesis and evaluation of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives as antiproliferative agents.

Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized, and evaluated for antiproliferative activities. SAR studies revealed that inserting an amino linkage between 6­aryl group and [1,2,4]triazolo[4,3-a]pyridine core led to amuch broaderantitumorspectrum, and the most promising compound 8 l exerted potent andbroad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC50 values in the micromolar range of 5.98-12.58 µM, which were more active than the positive control 5-FU. The mechanism investigation illustrated that 8 l dose-dependently caused cell cycle arrest at the G2/M phase, and induced cell apoptosis in HeLa cells. Consequently, these findings suggest the 6-arylamino-[1,2,4]triazolo[4,3-a]pyridines afford significant potential for the discovery of a new highly efficient anticancer agents.

Preoperative prognostic value of alfa-fetoprotein density in patients with hepatocellular carcinoma undergoing radiofrequency ablation.

OBJECTIVES: To examine the prognostic value of preoperative alfa-fetoprotein (AFP) density and other clinical factors in patients undergoing percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: From January 2010 to December 2018, a total of 543 patients undergoing RFA for HCC meeting the Milan criteria were included at our institution. AFP density was calculated as absolute AFP pre-ablation divided by the total volume of all HCC lesions. The survival rates according to AFP density were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazards regression analyses were used to assess predictors of overall survival (OS) and progression-free survival (PFS). RESULTS: The Kaplan-Meier 1-, 3-, and 5-year OS rates were 98.8%, 88.5%, and 70.4%, respectively, for the low AFP density group, and 98.3%, 74.9%, and 49.4%, respectively, for the high AFP density group. The corresponding PFS rates were 78.9%, 56.7%, and 40.9% (low AFP density group), and 63.6%, 40.8%, and 27.5% (high AFP density group). High AFP density was associated with significantly reduced PFS and OS (both p < 0.001). Multivariate analysis suggested that AFP density was a predictor of OS and PFS. CONCLUSIONS: Serum AFP density may serve as a promising predictor of survival in patients with HCC undergoing RFA. High AFP density could identify patients who might be prone to recurrence or progression and need close surveillance.

Identification of the origin of tumor in vein: comparison between CEUS LI-RADS v2017 and v2016 for patients at high risk.

OBJECTIVES: To compare the diagnostic performance of the Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Report and Data System (LI-RADS) v2016 and v2017 in identifying the origin of tumor in vein (TIV). METHODS: From April 2014 to December 2018, focal liver lesions (FLLs) accompanied by TIV formation in patients at high risk for hepatocellular carcinoma (HCC) were enrolled. Histologic evaluation or composite imaging reference standard were served as the reference standard. Each case was categorized according to the CEUS LI-RADS v2016 and v2017, respectively. Diagnostic performance of CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV was validated via sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value. RESULTS: A total of 273 FLLs with TIV were analyzed finally, including 266 HCCs and 7 non-HCCs. In v2016, when adopting all TIV as LR-5V, the accuracy and PPV in identifying the originated tumor were both 97.4%. In v2017, when assigning TIV according to contiguous FLLs CEUS LI-RADS category, the accuracy and PPV were 61.9% and 99.4% in subclass of LR-5 as the diagnostic criteria of HCC, and 64.1% and 99.4% in subclass of LR-4/5 as the criteria of HCC diagnosis. There were significant differences in diagnostic accuracy between CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV (p < 0.001). CONCLUSIONS: CEUS LI-RADS v2016 could be better than v2017 in identifying the originated tumor of TIV.

Research Progress on the SERPINE1 Protein and Chronic Inflammatory Diseases of the Upper Respiratory Tract: A Literature Review.

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases.

Inter-reader agreement of CEUS LI-RADS among radiologists with different levels of experience.

OBJECTIVES: To investigate the inter-reader agreement of contrast-enhanced ultrasound (CEUS) of Liver Imaging Reporting and Data System version 2017 (LI-RADS v2017) categories among radiologists with different levels of experience. MATERIALS AND METHODS: From January 2014 to December 2014, a total of 326 patients at high risk of hepatocellular carcinoma (HCC) who underwent CEUS were included in this retrospective study. All lesions were classified according to LI-RADS v2017 by six radiologists with different levels of experiences: two residents, two fellows, and two specialists. Kappa coefficient was used to assess consistency of LI-RADS categories and major features among radiologists with different levels of experience. The diagnostic performance of HCC was described by accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC). RESULTS: Inter-reader agreement among radiologists of different experience levels was substantial agreement for arterial phase hyperenhancement, washout appearance, and early or late washout. Inter-reader agreement for LI-RADS categories was moderate to substantial. When LR-5 was used as criteria to determinate HCC, the AUC of LI-RADS for HCC was 0.67 for residents, 0.72 for fellows, and 0.78 for specialist radiologists. When compared between residents and specialists, accuracy, sensitivity, and AUC were significantly different (all p < 0.05). However, there were no significant differences in specificity, PPV, and NPV between the two groups. CONCLUSION: CEUS LI-RADS showed good diagnostic consistency among radiologists with different levels of experience, and consistency increased with experience levels. KEY POINTS: • The inter-reader agreement for LI-RADS categories was moderate to substantial agreement (κ, 0.60-0.80). • When compared between residents and specialists, accuracy, sensitivity, and AUC showed significantly different (all p < 0.05). However, there were no significant differences for specificity, PPV, and NPV between these two groups. • Among the radiologists with more than 1 year of experience, there was no significant difference in the diagnostic performance of HCC, suggesting that CEUS LI-RADS is a good standardized categorization system for high-risk patients.

Percutaneous thermal ablation of hepatic tumors: local control efficacy and risk factors for artificial ascites failure.

OBJECTIVE: To investigate the risk factors affecting the technical failure of artificial ascites (AA) formation and to evaluate the local control efficacy of percutaneous thermal ablation assisted by the AA for hepatic tumors. METHODS: A total of 341 patients with 362 hepatic tumors who underwent thermal ablation assisted by AA were reviewed retrospectively. The technical success of AA, the volume of liquid, and local efficacy after ablation were assessed. Predictive factors for the technical failure of AA formation and local tumor progression (LTP) were analyzed using univariate and multivariate analysis. RESULTS: The technical success rate of AA formation was 81.8% (296/362). The amount of fluid was higher when the tumor was located in the left lobe of the liver than when it was located in the right lobe (median 950 ml versus 700 ml, p < 0.001). Previous hepatic resection (OR: 12.63, 95% CI: 2.93-54.45, p < 0.001), ablation (OR: 6.48, 95% CI: 1.36-30.92, p = 0.019) and upper-abdomen surgery (OR: 11.34, 95% CI: 1.96-65.67, p = 0.007) were the independent risk factors of AA failure. In the AA success group, the complete ablation rate was higher and the LTP rate was lower than that in the AA failure group (98.7 versus 92.4%, p = 0.012; 8.8 versus 21.2%, p = 0.004). Multivariate analysis identified AA failure (p = 0.004), tumor size (>3.0 cm) (p = 0.002) and metastatic liver tumor (p = 0.008) as independent risk factors for LTP. CONCLUSION: History of hepatic resection, ablation and upper abdomen surgery were significant predictive factors affecting the technical failure of AA formation. Successful introduction of AA before thermal ablation can achieve better local tumor control efficacy.

Preoperative prediction of tumour deposits in rectal cancer by an artificial neural network-based US radiomics model.

OBJECTIVE: To develop a machine learning-based ultrasound (US) radiomics model for predicting tumour deposits (TDs) preoperatively. METHODS: From December 2015 to December 2017, 127 patients with rectal cancer were prospectively enrolled and divided into training and validation sets. Endorectal ultrasound (ERUS) and shear-wave elastography (SWE) examinations were conducted for each patient. A total of 4176 US radiomics features were extracted for each patient. After the reduction and selection of US radiomics features , a predictive model using an artificial neural network (ANN) was constructed in the training set. Furthermore, two models (one incorporating clinical information and one based on MRI radiomics) were developed. These models were validated by assessing their diagnostic performance and comparing the areas under the curve (AUCs) in the validation set. RESULTS: The training and validation sets included 29 (33.3%) and 11 (27.5%) patients with TDs, respectively. A US radiomics ANN model was constructed. The model for predicting TDs showed an accuracy of 75.0% in the validation cohort. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and AUC were 72.7%, 75.9%, 53.3%, 88.0% and 0.743, respectively. For the model incorporating clinical information, the AUC improved to 0.795. Although the AUC of the US radiomics model was improved compared with that of the MRI radiomics model (0.916 vs. 0.872) in the 90 patients with both ultrasound and MRI data (which included both the training and validation sets), the difference was nonsignificant (p = 0.384). CONCLUSIONS: US radiomics may be a potential model to accurately predict TDs before therapy. KEY POINTS: • We prospectively developed an artificial neural network model for predicting tumour deposits based on US radiomics that had an accuracy of 75.0%. • The area under the curve of the US radiomics model was improved than that of the MRI radiomics model (0.916 vs. 0.872), but the difference was not significant (p = 0.384). • The US radiomics-based model may potentially predict TDs accurately before therapy, but this model needs further validation with larger samples.

Quercetin Promotes Diabetic Wound Healing via Switching Macrophages From M1 to M2 Polarization.

BACKGROUND: For patients with diabetes mellitus, excessive and long-lasting inflammatory reactions at the wound site commonly lead to the delayed refractory wound healing. The polarization of macrophages in terms of M1 and M2 phenotypes is closely related to the production of inflammatory cytokines. Quercetin is traditionally recognized to have anti-inflammatory effect; however, whether quercetin modulates macrophage polarization from M1 to M2 and thus promotes diabetic wound healing remain unknown. MATERIALS AND METHODS: Wounded male diabetic rats were equally divided into five groups: model group, solvent control group (10% DMSO), and three drug groups treated with quercetin (Q) at concentrations of 10 mg/mL (Q-LD [low dose]), 20 mg/mL (Q-MD [medium dose]), and 40 mg/mL (Q-HD [high dose]), respectively. The anti-inflammatory effect of quercetin on diabetic wounds was observed. Immunohistochemistry and quantificational real-time polymerase chain reaction were applied to test the changes in macrophage polarization and inflammatory responses. RESULTS: The wound contraction was fastest in Q-HD group. Hematoxylin and eosin (H&E) and Masson's trichrome staining revealed that fibroblast distribution and collagen deposition in quercetin-treated groups were significantly higher than those in the model group. Immunohistochemistry tests showed more CD206-positive cells and less iNOS-positive cells in quercetin-treated groups. Furthermore, the levels of proinflammatory factors in quercetin-treated groups were lower than those in the model group, whereas the levels of the anti-inflammatory factors and angiogenesis-related factors were relatively higher. CONCLUSIONS: In short, quercetin inhibits inflammatory reactions via modulating macrophage polarization switching from M1 to M2 phenotype, thereby accelerating the diabetic wound repair.

Impact of the systematic use of the volume-viscosity swallow test in patients with acute ischaemic stroke: a retrospective study.

BACKGROUND: Dysphagia is common after stroke. Patients with dysphagia have a higher risk of stroke-associated pneumonia (SAP) and poor outcomes. Early detection of dysphagia is necessary to identify and manage patients at high risk of aspiration. The aim of the study was to assess the impact of the systematic administration of the volume-viscosity swallow test (V-VST) in patients with acute ischaemic stroke. METHODS: This was a retrospective observational study that enrolled patients with acute ischaemic stroke in two consecutive time periods: pre-V-VST, when the 30-mL water-swallowing test (WST) was systematically administered, and V-VST, when all patients underwent the WST and the V-VST test was systematically administered if the patient failed the WST. RESULTS: Two hundred and 42 patients were enrolled. The mean age of the participants was 68.8 ± 10.88 years, 61.2% were male, and the median National Institutes of Health Stroke Scale score was 3 (IQR, 1-6). A total of 147 patients were enrolled during the pre-V-VST period and 95 were enrolled during the V-VST period. There was a significant difference in the occurrence of SAP (21.8% vs. 10.5%, p = 0.024) and the rate of nasogastric tube feeding (25.9% vs. 14.7%, p = 0.040) between the two groups, and no differences were found in the length of hospital stay (p = 0.277) or the total cost of hospitalization (p = 0.846). CONCLUSIONS: The V-VST was a better clinical screening tool, and it can also provide detailed suggestions regarding dietary modifications to prevent aspiration and SAP.

Thermal ablation versus hepatic resection for the treatment of liver metastases from gastrointestinal stromal tumors: a retrospective study.

Objective: The study aimed to compare effectiveness and safety of thermal ablation and hepatic resection in patients with liver metastases of gastrointestinal stromal tumors (GISTs).Method: A total of 55 patients (27 in the ablation group and 28 in the surgery group) with liver metastases were included. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier's survival estimate curves. Univariate and multivariate regression analyses were carried out to identify potential prognostic factors.Results: The median OS was 102.0 months in the ablation group and 117.0 months in the surgery group (p = .875). The 1-, 3- and 5-year OS rates were 100%, 88.9% and 74.1% in the ablation group and 92.8%, 82.1% and 78.6% in the surgery group, respectively. The 1-, 3- and 5-year PFS rates were 48.1%, 25.9% and 18.5% in the ablation group and 67.8%, 64.3% and 64.3% in the surgery group, respectively. Multivariate analysis showed that preoperative tyrosine kinase inhibitor (TKI) treatment (progressive disease, PD) (HR, 13.985; 95% CI, 1.791-109.187; p = .012) was the only significant independent prognostic factor for OS. Tumor number (HR, 1.318; 95% CI, 1.021-1.702; p = .034) was identified as an independent predictor for PFS in multivariate analysis. There were fewer postoperative complications (18.5% vs. 78.6%, p = .001) and shorter lengths of hospital stay (8.0 vs. 16.5 days, p = .001) in the ablation group.Conclusion: Compared with resection, thermal ablation offered comparable OS for liver metastases of GISTs. Furthermore, thermal ablation had the advantages of fewer complications and shorter lengths of hospital stay.

A modified subclassification to evaluate the survival of patients with N3 gastric cancer: an international database study.

BACKGROUND: The eighth TNM classification for gastric cancer categorizes N3 as N3a and N3b in the final pathologic stage. The cutoff for N3a/N3b is defined as 15 metastatic lymph nodes, but the rationale for this cutoff remains unclear. This study aimed to determine the optimal N3a/N3b cutoff and evaluate its prognostic significance. METHODS: An international database was constructed by combining data from patients with N3 gastric cancer and complete five-year follow-up data from the Surveillance, Epidemiology, and End Results program database (n = 1833) and the Fujian Medical University Union Hospital database (n = 920) (total n = 2753). A log-rank test was performed to determine the optimal N3a/N3b cutoff, and its prognostic significance was confirmed in a two-step multivariate analysis and compared to that of the eighth TNM. RESULTS: A cut-point analysis performed at each metastatic lymph node number identified the greatest survival difference between N3a and N3b at 13 metastatic lymph nodes (χ2 = 157.671, P = 3.65 × 10- 36). In patients with 14-15 metastatic lymph nodes, prognoses were significantly worse than those in patients with 7-13 metastatic lymph nodes (P < 0.001) but similar to those in patients with > 15 metastatic lymph nodes (P = 0.078). Therefore, patients with 14-15 metastatic lymph nodes were incorporated into a modified N3b classification. In the two-step multivariate analysis, the eighth N3 classification fell out of the model, while the modified N3 classification remained intact (HR 1.51, P < 0.001). Further analyses demonstrated that the modified TNM classification had superior homogeneity, discriminatory ability, and gradient monotonicity compared to the eighth TNM classification. CONCLUSIONS: For improved prognostic stratification, we recommend adjusting the cutoff for subclassification of N3 gastric cancer to 13 metastatic lymph nodes.

Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells.

Damulin B, a dammarane-type saponin from steamed Gynostemma pentaphyllum, exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. In vitro, human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer.

Bibliometric Study of the Comorbidity of Pain and Depression Research.

Background: Comorbid pain and depression occur with high prevalence in clinical observations, and published academic journals about them have been increasing in number over time. However, few studies used the bibliometric method to analyze the general aspects of scientific researches on the comorbidity of pain and depression. The aim of this study is to systematically provide global scientific research in the comorbidity of pain and depression from 1980 to 2018. Methods: The published papers were searched between 1980 and 2018 in Web of Science. Publications related to comorbid pain and depression research were included. The language was restricted to English, and no species limitations were specified. Results: A total of 2,519 papers met the inclusion criteria in our study. The results revealed that the publications had a significant growth over time in the comorbidity of pain and depression research (P < 0.001) by linear regression analyses. The United States had the largest number of publications and citations and the highest value of H-index. According to subject categories of Web of Science, research areas of the 2,519 papers mainly focused on clinical neurology (28.78%), neurosciences (22.9%), and psychiatry (22.23%). In accordance with types of pain, headache (19.09%) was the most popular topic in the included papers on comorbid pain and depression research. Conclusions: The findings provide useful information for pain and depression researchers to detect new areas related to collaborators, cooperative institutions, popular topics, and research frontiers.