An investigative meta-analysis on the effectiveness and safety of integrating VEGF/VEGFR inhibitors with PD-1/PD-L1 inhibitors in cases with R/M HNSCC.

OBJECTIVES: Exploration into the use of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors alongside programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has been undertaken for treating recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). We conducted a meta-analysis to provide a more precise assessment of the efficacy and safety of this integrated approach in managing R/M HNSCC. METHODS: A systematic exploration encompassing PubMed, Embase, the Cochrane Library, and Web of Science databases was undertaken to figure out relevant studies. It was attempted to analyze critical endpoints, such as overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) utilizing a random-effects model. RESULTS: Eleven studies, encompassing 413 patients, were analyzed. The combined data revealed an ORR of 41 % (95 % CI: 34-49 %), a DCR of 67 % (95 % CI: 51-83 %), a median PFS of 5.87 months (95 % CI: 3.90-7.85), and a median OS of 9.63 months (95 % CI: 6.78-12.49). Furthermore, the rates for 1-year PFS and OS were 45 % (95 % CI: 27-64 %) and 65 % (95 % CI: 49-81 %), respectively. The occurrence of grade 3 or higher adverse events related to the drugs was 20 % (95 % CI: 10-30 %). Subgroup analysis within the tyrosine kinase inhibitor (TKI) group revealed an ORR of 47 % (95 % CI: 39 %-55 %) and a DCR of 67 % (95 % CI: 46 %-88 %). CONCLUSIONS: In summary, combining VEGF/VEGFR inhibitors with PD-1/PD-L1 inhibitors shows considerable effectiveness with manageable side effects in cases with R/M HNSCC. SYSTEMATIC REVIEW REGISTRATION: Registered with the International Prospective Register of Systematic Reviews, identifier CRD42023486345.

EGFR Oncogenic Mutations in NSCLC Impair Macrophage Phagocytosis and Mediate Innate Immune Evasion Through Up-Regulation of CD47.

INTRODUCTION: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved. METHODS: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models. RESULTS: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models. CONCLUSIONS: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC.

Immobilization of arsenic in different contaminated soils by zero-valent iron-embedded biochar: Effect of soil characteristics and treatment conditions.

Although zero-valent iron-embedded biochar (ZVI-BC) has been proposed as an effective amendment for arsenic (As)-contaminated soils, the impacts of soil characteristics and treatment conditions on the remediation process remained poorly understood. Herein, the immobilization of As in four As-contaminated soils (i.e., smelting soil, storage soil, agricultural soil, and mining soil) by ZVI-BC under different amendment dosages, cultivation temperatures, and soil moisture contents were investigated. ZVI-BC showed high As immobilization capacity in all four soils via forming the AsFe co-precipitation, and the liable As was reduced by 82.4-97.0 % with a 2 % (w/w) amendment. The higher temperature could raise the concentration of liable As in all four soils, especially for the storage soil, in which liable As at 35 °C was almost 3 times of that at 25 °C after 50-days treatment, because the elevated temperature enhanced the destruction of the generated AsFe coprecipitation as well as the desorption of As in soils. Too much soil moisture was unfavorable for the As immobilization after 50-days treatment. Flooding tended to inhibit the community diversity of As-detoxicated bacteria, e.g., Halomonas, Bryobacter, and Anaerolinea, thus resulting in the release of liable As. According to the correlation analysis, the crucial influencing factor for As immobilization was different in four soils, which was determined by the soil properties and proportion of liable As. Our study indicates that ZVI-BC is an effective amendment for As immobilization under various conditions, and the biogeochemical processes of As-associated Fe minerals determine the As immobilization during amendment.

Unraveling nonlinear and interaction effects of various determinants on bus gaseous emissions.

Urban transit buses equipped with large-displacement engines operate on circular routes several times throughout the day, emitting large amounts of environmentally hazardous exhaust. Hence, understanding the intricate associations between bus emissions and multiple contributors is beneficial for creating sustainable transportation systems, while previous studies focusing on statistical methods fail to unravel them. This paper innovatively leverages the bagged decision tree approach to delineate such complex relationships based on the data collected from CNG-fueled and diesel-powered buses. Relative importance indicates that velocity appears to be the primary factor and is therefore selected as the research objective. Results suggest that the effects of different contributors on bus emissions present nonlinear patterns. More specifically, the influence of speed on CO, CO2, and NOx exhaust generally reveals an increasing-stabilizing tendency while that of HC represents a decreasing-stabilizing mode. Besides, the phenomenon of synergies between determinants is also prevalent, for instance, buses within high-speed and large-slope conditions tend to produce more emissions. These findings can provide nuanced guidance for policy-making and bus route planning issues in consideration of environmental protection and pollution mitigation.

Clinical observation of pulmonary lymphoepithelioma-like carcinoma.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) of the lung is a rare type of non-small cell lung cancer (NSCLC), and researches of it are still not enough. METHODS: In this study, we retrospectively analyzed 36 patients with LELC diagnosed in the Fifth Affiliated Hospital of Sun Yat-sen University and Zhaoqing First People's Hospital from January 2014 to June 2021, to investigate the clinical manifestations, tumor markers, treatment, and prognosis of LELC. Clinical data including age, gender, smoking history, family history of cancers, Epstein-Barr virus (EBV) encoding RNA (EBER) status, gene mutations, programmed death-ligand 1 (PD-L1) expression, treatment, and prognosis. RESULTS: There was a total of 36 participants in this study, 16 males and 20 females, the median age was 57 years (37-76 years). A total of 22 cases (61.1%) were advanced (stage III and IV), and EBER was 94.4% positive. Most patients were treated with surgery, platinum chemotherapy, or radiotherapy. At the time of 31 June 2021, 33 participants had survived, and the longest survival time was 72 months. Lung LELC was more common in old participants (≥59 years) and was not associated with smoking history. Expression of PD-L1 was positive in the majority (27 cases, 75%) and participants with positive PD-L1 expression tended to have longer progression-free survival (PFS) and overall survival (OS) time than those with negative PD-L1 expression. CONCLUSIONS: Pulmonary LELC usually occurs in non-smoking patients and is associated with EBV infection. Common treatments for tumors include multimodal therapy. The expression of PD-1 may be related to the prognosis of LELC, but more studies are needed to support further optimization of the treatment of LELC.

Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer.

BACKGROUND: The role of caudal-related homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the mRNA (message RNA) expression of CDX2 in NSCLC, and to determine its relationship with miR-744 (microRNA744) and its potential as a biomarker of NSCLC. METHODS: MiR-744 is overexpressed in A549, H460, and H1299 cell lines. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression. A chromatin immunoprecipitation (ChIP) essay was performed to determine the CDX2 binding sites. We then conducted a luciferase reporter essay to analyze interaction between MiR-744 and 3'UTRs (the 3' untranslated sequences). The migration and Boyden chamber method were used to study cell mobility. RESULTS: In this study, we found that ectopic CDX2 increased the expression of miR-744, while the attenuation of CDX2 reduced the expression of miR-744 by qRT-PCR. Chromatin immunoprecipitation experiments confirmed that CDX2 directly binds to the promoter of miR-744. The luciferase reporter assay further verified the binding sites of -347 to -358 bp in the most likely promoter like sequence of miR-744. CDX2-induced up-regulation of miR-744 can significantly promote the migration and invasion of NSCLC cells, while overexpression CDX2 is sufficient to rescue the migration and invasion capacity of these cells following knockdown of miR-744. CONCLUSIONS: In summary, our results confirmed for the first time the regulatory mechanism of CDX2 on miR-744 transcription and provided a potential mechanism for CDX2 as an oncogene in lung cancer.

Estimating gaseous pollutants from bus emissions: A hybrid model based on GRU and XGBoost.

In urban areas, traffic-related contamination is one of the main contributors to environmental deterioration, and the pollution from public transit buses is a major component. To mitigate these impacts, it is essential to estimate bus emissions and analyze their characteristics. This paper proposes a hybrid model based on gated recurrent unit (GRU) and extreme gradient boosting (XGBoost), termed GRU-XGB, to predict gaseous pollutants from bus emissions (CO, CO2, HC, NOX) under real conditions. On-road experimental data collected from CNG-fueled and diesel-powered buses in Zhenjiang was used as a case study to verify the model's effectiveness. A comparison between the proposed and other state-of-the-art models reveals that GRU-XGB performs best for all evaluation metrics on both microscopic and aggregative levels, with an average correlation coefficient above 0.98 and an average MAPE lower than 9%. Moreover, the results of estimation errors analysis suggest that the real conditions of bus stations are more complicated than those of intersections and road sections. In most cases, however, the emission factors produced from intersections are proven to be the highest. Furthermore, operating patterns are shown to be the most significant factors, with relative importance equal to 45.09% and 71.68% for CNG and diesel buses, respectively. Besides, the results also indicate that humidity has little impact on this issue, while the influence of temperature is obvious, with relative importance equal to 17.56% and 9.41% for CNG and diesel buses, separately. Such findings can provide theoretical guidance for both emission estimation and environmental protection. Also, it is applicable for the management of accurate monitoring from an urban-level and can be integrated into emission simulation tools.

Treatment Patterns and Survival of Patients With Advanced Non-Small Cell Lung Cancer Guided by Comprehensive Genomic Profiling: Real-World Single-Institute Study in China.

Although the National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology guidelines recommend comprehensive genomic profiling of lung adenocarcinoma, it has not been widely applied in Chinese hospitals. This observational study aimed to determine real-world evidence of whether comprehensive genomic profiling can benefit the survival of patients with lung cancer. We investigated the frequency of genomic alterations, treatment strategies, and clinical outcomes in 233 patients with advanced non-small cell lung carcinoma who were routinely screened using a 508-gene panel. The most prevalent drivers were mutations of EGFR (51%), KRAS (9%), PIK3CA (7%), ALK (7%), MET (6%), and BRAF (5%). Mutations in tumor suppressor genes included TP53, KEAP1, RB1, PTEN, and APC. Median overall survival (OS) was significantly shorter among patients harboring KRAS (mutant, n = 17; WT, n = 154) and TP53 (mutant, n = 103; WT n =68) mutations (11.3 vs. 24.0 months; P = 0.16 and 18.7 vs. 28.7 months; P = 0.018, respectively). The OS was longer among patients with tumors harboring EGFR (P = 0.069) and ALK (P = 0.51) mutations. Most patients (65.4%) with the driver gene-positive (EGFR, ALK, and ROS1) tumors were received TKI treatment, whereas those with driver gene wild tumors (53.1%) chose platinum-based therapy. Univariate and multivariate analyses associated a shorter OS among patients with tumors harboring concomitant TP53 and EGFR mutations. These findings provide additional evidence from real-world on the potential importance of targeted therapies as a treatment option in NSCLC patients harboring clinically actionable mutation.

Factors for peripherally inserted central catheters care delay in cancer patients during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. The public health systems have consequently been placed under tremendous pressure. Peripherally inserted central catheters (PICCs) are widely used in patients with cancers. Little is known about the provision of PICCs care amongst cancer patients during this pandemic. METHODS: We studied 156 cancer patients with PICCs treated at the Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University between January 2020 and March 2020. Their clinical characteristics, social features, psychological characteristics, and PICCs care situations were analyzed. The chi-squared (χ2) test or Fisher's exact test were used for univariate analyses. Multivariate logistic regression analyses were performed using stepwise variable selection. Differences were evaluated using a two-tailed test, and P<0.05 was considered statistically significant. RESULTS: Of 156 patients, 57 (36.5%) experienced delays of PICCs care, and 12 (21.1%) suffered from complications including infection, thrombosis, and mechanical failure. Univariate analysis detected that the increased risk of PICCs care delay was associated with older age (≥30), lower level of education (<9 years), working, taking public transport to the hospital, anxiety about COVID-19, lower social support rating scale (SSRS) score (<30). Multivariate analysis detected level of education, being employed or not, mode of transport, and SSRS score were independent predictive factors for the delay in PICCs care. CONCLUSIONS: Physical aspects, social factors, and psychological status commonly influenced patients' health care seeking behaviors such as PICCs maintenance. An increase in effort is required from patients' families and society to assure optimal care for cancer patients during this pandemic.

Strong sorption of two fungicides onto biodegradable microplastics with emphasis on the negligible role of environmental factors.

Microplastics have attracted much attention in recent years because they are able to interact with other pollutants including pesticides, with implications for the potential risks to biota. However, the sorption behavior of pesticides on microplastics, especially on biodegradable microplastics which are promising alternatives to conventional polymers, has been insufficiently studied. In this study, triadimefon and difenoconazole were selected as model triazole fungicides, and their sorption behavior on a typical biodegradable microplastics (PBS: polybutylene succinate) and two conventional polyethylene (PE) and polyvinyl chloride (PVC) microplastics was investigated with batch experiments in an aqueous solution. PBS presented the highest sorption capacity for triadimefon (104.2 ± 4.8 µg g-1) and difenoconazole (192.8 ± 2.3 µg g-1), which was 1.8- and 1.3-fold that on PE and 4.4- and 7.4-fold that of PVC, respectively. The results of sorption kinetic and isotherm modeling were better fit by a pseudo-second order model and linear model, respectively. More importantly, the effects of environmental factors (pH, salinity and dissolved organic matter) on the sorption behavior were investigated. Fungicide sorption on PBS was generally not affected by salinity, pH or dissolved organic matter. However, in contrast, salinity and dissolved organic matter both significantly decreased sorption on PE and PVC. The results showed that not only the sorption capacities of biodegradable microplastics but also their responses to environmental factors are quite different from those of conventional microplastics. This finding highlights the importance of the role played by biodegradable microplastics in the accumulation and transportation of organic pollutants.

Clinical observation of Pemetrexed first-line treatment in advanced non-squamous lung cancer or non-small cell lung cancer without driver-mutations: a phase 2, single-arm trial.

BACKGROUND: Non-dominant population, which means patients with advanced non-squamous lung cancer or non-small cell lung cancer (NSCLC) without driver-mutations, who are excluded from clinical studies because of specific baseline conditions refractory to multiple treatments, have poor outcomes. We assessed the activity of pemetrexed first-line treatment for a non-dominant population, explore the safety and efficacy of pemetrexed therapy. METHODS: We did this two-phased, single-arm trial at two sites at the Fifth Affiliated Hospital of Sun Yat-sen University and Guangxi medical university cancer hospital. Pemetrexed 500 mg/m2, static drops on day 1; 21 days for a cycle, each treatment for at least two cycles and up to six cycles. Efficacy was assessed every two cycles. RESULTS: We counted the July 21, 2018 to 2020 on May 31, first diagnosed with IIIb-IV period (American Joint Committee on Cancer eighth edition) no drive genes, non-squamous cell carcinomas, 30 patients with non-small cell lung cancer, the follow-up to July 31, 2020, median follow-up time was 12 months. Most were elderly patients with poor general conditions (96.7% of patients had ECOG scores of 2-3) (median age 66 years). Median duration of maintenance treatment was 6 months. Median progression-free survival was 6.5 months. Median overall survival was 12 months. Patients with performance status =0-2 had a significantly higher median overall survival time (16 months) compared with patients with performance status =3 who had a median overall survival time of 7 months (P=0.001). Most treatment-related adverse events were grade 1 or grade 2. CONCLUSIONS: This study is the first to investigate the survival benefit and toxicity tolerance of pemetrexed treatment in non-dominant population in the real world, providing a new therapeutic possibility for those who failed to be enrolled in clinical studies.

The impact of the COVID-19 pandemic on lung cancer patients.

BACKGROUND: The coronavirus disease (COVID-19) poses an unprecedented challenge to health and epidemic prevention system, especially the healthcare of patients with cancer. We sought to study the impact of COVID-19 on lung cancer patients in our center. METHODS: We initiated a retrospectively study to analyze the impact of COVID-19 on lung cancer patients in our center, who were accepted for routine anticancer treatment before the epidemic and planned to return to hospital in January and February of 2020. RESULTS: A total of 161 cases of lung cancer were included in the final analysis. As of April 15, 95 patients had delayed their return visit, and 47 cases were finally designated as having delayed admission during the epidemic and having to discontinue or delay their regular anticancer treatments. Of these 47 delayed patients, 33 were evaluated for tumor status using a computed tomography scan, 6 of these 33 cases (18.18%) were diagnosed as progressive disease (PD), and 5 cases did not return for visit. CONCLUSIONS: This is the first study investigating impact of COVID-19 on non-COVID-19 lung cancer patients during the pandemic. The study demonstrates the significant impact of the COVID-19 crisis on oncological care, indicating the need for appropriate change of treatment decisions and continued follow-up and psycho-oncological support during this pandemic.

Electro-enhanced leaching method for the mobilization of Cr(VI) in contaminated groundwater aquifer.

Removal of hexavalent chromium [Cr(VI)] from soils and water has been widely studied for its high toxicity. Although leaching method is viewed as an effective approach to eliminate Cr(VI) and some studies attempted to enhance leaching performance via the external electric field, there is little knowledge about the influential factor in electro-leaching system on Cr(VI) removal performance. In this study, an electro-leaching technology was developed for removing Cr(VI) from groundwater aquifer to comprehensively discuss the correlation between the operational parameters and Cr(VI) removal efficiency. When the applied voltage was 20 V and the initial Cr(VI) concentration was 40 mg/kg, Cr(VI) removal efficiency achieved 99.9% in 120 min in the electro-leaching system, 15% higher than the system without the electric field. Cr(VI) removal efficiencies increased with the voltage demonstrating the significant enhancement of the electro-leaching method in removing Cr(VI). When Cr(VI) concentration climbed to 120 mg/kg, Cr(VI) removal efficiency remained above 85%. The effects of different voltages, Cr(VI) concentrations, pollutant distribution and salt content of leaching solution on the leaching effect were also investigated. Meanwhile, the relationship between the current intensity change and the amount of removed Cr(VI) during the electro-leaching process was first investigated, and the relevant model was fitted. There is a quadratic linear correlation between the amount of current change and the amount of removed Cr(VI). This novel electro-enhanced leaching method can effectively remove Cr(VI) from contaminated groundwater aquifer by enhancing the migration of charged contaminant ions during the leaching process, and it is worthy of further study of heavy metal remediation.

Cr(VI) removal from soils and groundwater using an integrated adsorption and microbial fuel cell (A-MFC) technology.

Remediation of hexavalent chromium [Cr(VI)] has been widely studied for its high mobility and toxicity. As Cr(VI) migrates in natural environment, both soils and groundwater are contaminated simultaneously. In the present study, a novel reactor combining adsorption and microbial fuel cell (A-MFC) using Platanus acerifolia leaves was developed for removing Cr(VI) from groundwater and soils. When initial Cr(VI) concentration was 50 mg/L, the adsorption efficiency of A-MFC achieved 98% after 16 h. Afterwards, the leaves were used for fabricating an MFC-integrated leaching reactor. The A-MFC significantly improved the overall Cr(VI) removal efficiency through leaching and 40% of Cr(VI) in the soil column was removed. The electrical voltage and current of A-MFC reactor achieved averagely 343 mV and 141 µA to maintain the system operation without extra energy supply. This novel A-MFC reactor is an environmentally friendly technology which achieved efficient Cr(VI) removal from groundwater and soils using natural materials, proving the concept that integrated self-remediation of Cr(VI) in contaminated soil and groundwater with natural material and energy.

Diagnostic value of circulating microRNAs for liver cirrhosis: a meta-analysis.

Circulating microRNAs are potential biomarkers for various diseases including liver cirrhosis. We designed a meta-analysis to evaluate the diagnostic value of circulating microRNAs for liver cirrhosis patients. Eligible studies were identified by searching PubMed, Embase, and the Cochrane Library up to July 1, 2017. The diagnostic sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic (AUROC) curve were analyzed using a random or fixed effects models based on the between-study heterogeneities. Thirteen studies from 7 articles with 627 patients and 418 healthy controls were included in this meta-analysis. All studies had high quality assessment scores. The pooled sensitivity, specificity, PLR, NLR, DOR and AUROC were 0.83 (95% CI: 0.80-0.86), 0.89 (95% CI: 0.86-0.92), 6.41 (95% CI: 3.93-10.44), 0.22 (95% CI: 0.14-0.33), 35.18 (95% CI: 15.90-77.81) and 0.93 (95% CI: 0.91-0.95), respectively. In conclusion, circulating microRNAs may serve as potential noninvasive biomarkers of liver cirrhosis.

Expression and clinical value of programmed cell death-ligand 1 (PD-L1) in diffuse large B cell lymphoma: a retrospective study.

BACKGROUND: The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis. METHODS: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical (IHC) assay. The expression of anaplastic lymphoma kinase (ALK), CD5, CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus (EBV)-encoded RNAs (EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis. RESULTS: Of the 204 patients, 100 (49.0%) were PD-L1-positive in tumor cells and 44 (21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype (P = 0.02 and P = 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment (P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression (r = - 0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival (OS) rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells (P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS (P < 0.01). CONCLUSIONS: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.

Transient Elastography (FibroScan) Performs Better Than Non-Invasive Markers in Assessing Liver Fibrosis and Cirrhosis in Autoimmune Hepatitis Patients.

BACKGROUND Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that can lead to severe fibrosis and cirrhosis. Transient elastography (TE, FibroScan) can assess the fibrotic stages of chronic liver diseases by liver stiffness measurement (LSM). Studies on the diagnostic accuracy of FibroScan for the detection of fibrosis in AIH patients are still limited. MATERIAL AND METHODS This study enrolled 108 AIH patients who underwent liver biopsies. Using the METAVIR scoring system as the reference, Spearman's rank correlation was performed to explore the relationship between the markers and stages of fibrosis. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic accuracy. The optimal LSM cut-off values for predicting the stages of fibrosis were calculated. RESULTS LSM was superior to other non-invasive markers in differentiating the stages of fibrosis in AIH patients. AUROC value of LSM was 0.885 for stage F2, 0.897 for stage F3, and 0.878 for stage F4. The optimal LSM cut-off value was 6.27 kPa for stage F2, 8.18 kPa for F3, and 12.67 kPa for F4. CONCLUSIONS FibroScan is a valuable non-invasive method for the evaluation of liver fibrosis of AIH patients.

The Effect of Prophylactic Lamivudine plus Adefovir Therapy Compared with Lamivudine Alone in Preventing Hepatitis B Reactivation in Lymphoma Patients with High Baseline HBV DNA during Chemotherapy.

Prophylactic antiviral therapy is essential for lymphoma patients with high baseline HBV DNA who undergo cytotoxic chemotherapy. However, there are limited data on the optimal options. The present study was designed to compare the efficacy of prophylactic lamivudine (LAM) with lamivudine plus adefovir dipivoxil (LAM+ADV) in preventing hepatitis B virus (HBV) reactivation in lymphoma with, pre-chemotherapy HBV DNA load ≥2000 IU/ml. We retrospectively analyzed the medical records of 86 lymphoma patients with baseline HBV DNA load ≥2000 IU/ml during chemotherapy and received LAM or LAM+ADV as prophylaxis between January 1, 2008 and November 30, 2014 at Sun Yat-sen University Cancer Center, China. Sixty-five patients received LAM and 21 received LAM+ADV. The rate was significantly lower in the LAM+ADV group compared with the LAM group for HBV reactivation (23.8% vs 55.4%; p = 0.012), while no difference was observed between the two groups in patients for HBV-related hepatitis (21.3% vs 33.3%; p = 0.349), and chemotherapy disruption (10.9% vs 19.0%; p = 0.337). In a multivariate analysis of factors associated with HBV reactivation in these patients, LAM+ADV treatment and HBeAg negative were the independent protective factors. Therefore, LAM+ADV should be considered for antiviral prophylaxis in lymphoma patients with pre-chemotherapy HBV DNA load ≥2000 IU/ml. Further study is warranted to confirm these findings.

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma: a retrospective study.

BACKGROUND: In patients with diffuse large B-cell lymphoma (DLBCL), central nervous system (CNS) relapse is uncommon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the efficacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction. METHODS: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat-sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathecal chemotherapy prophylaxis (methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R-CHOP set in particular, the Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Differences were evaluated using a two-tailed test, and P < 0.05 was considered significant. RESULTS: At a median follow-up of 46 months, 25 (4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3-year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R-CHOP group (P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much benefit in terms of preventing CNS relapse. Bone involvement [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.38-12.77], renal involvement (HR = 3.85, 95% CI 1.05-14.19), alkaline phosphatase (ALP) >110 U/L (HR = 3.59, 95% CI 1.25-10.34), serum albumin (ALB) <35 g/L (HR = 3.63, 95% CI 1.25-10.51), treatment with rituximab (HR = 0.34, 95% CI 0.12-0.96), and a time to complete remission ≤ 108 days (HR = 0.22, 95% CI 0.06-0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement (HR = 4.44, 95% CI 1.08-18.35), bone marrow involvement (HR = 11.70, 95% CI 2.24-60.99), and renal involvement (HR = 10.83, 95% CI 2.27-51.65) were independent risk factors for CNS relapse in the R-CHOP set. CONCLUSIONS: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemotherapy prophylaxis alone was not sufficient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R-CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma.

BACKGROUND: We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I. RESULTS: The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis. CONCLUSION: Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC.