Cuprotosis clusters predict prognosis and immunotherapy response in low-grade glioma.

Cuprotosis, an emerging mode of cell death, has recently caught the attention of researchers worldwide. However, its impact on low-grade glioma (LGG) patients has not been fully explored. To gain a deeper insight into the relationship between cuprotosis and LGG patients' prognosis, we conducted this study in which LGG patients were divided into two clusters based on the expression of 18 cuprotosis-related genes. We found that LGG patients in cluster A had better prognosis than those in cluster B. The two clusters also differed in terms of immune cell infiltration and biological functions. Moreover, we identified differentially expressed genes (DEGs) between the two clusters and developed a cuprotosis-related prognostic signature through the least absolute shrinkage and selection operator (LASSO) analysis in the TCGA training cohort. This signature divided LGG patients into high- and low-risk groups, with the high-risk group having significantly shorter overall survival (OS) time than the low-risk group. Its predictive reliability for prognosis in LGG patients was confirmed by the TCGA internal validation cohort, CGGA325 cohort and CGGA693 cohort. Additionally, a nomogram was used to predict the 1-, 3-, and 5-year OS rates of each patient. The analysis of immune checkpoints and tumor mutation burden (TMB) has revealed that individuals belonging to high-risk groups have a greater chance of benefiting from immunotherapy. Functional experiments confirmed that interfering with the signature gene TNFRSF11B inhibited LGG cell proliferation and migration. Overall, this study shed light on the importance of cuprotosis in LGG patient prognosis. The cuprotosis-related prognostic signature is a reliable predictor for patient outcomes and immunotherapeutic response and can help to develop new therapies for LGG.

The clinical characteristics of 1894 cases of upper respiratory papillomatosis: A single-center retrospective analysis.

BACKGROUND: With advancements in medicine and economy, it would be expected that there will be changes in the clinical characteristics of upper respiratory papillomatosis. The aim of this study was to examine the current clinical characteristics of upper respiratory papillomatosis, as there are no recent data in the literature. METHODS: The medical records of 1894 patients with upper respiratory papillomatosis were retrospectively reviewed. Data extracted included clinical features, laryngoscopy images, and surgical procedure data. RESULTS: The upper frequency of upper respiratory papillomatosis in the oropharynx was 69.1 %, and in the larynx was held 28.9 %. The overall postoperative relapse rate was 2.4 %. The relapse rate of laryngeal papillomatosis was 6.5 %. Approximately 2.6 % of cases were in children. All postoperative recurrences in children were laryngeal, and the recurrence rate was 30.4 %. CONCLUSION: The oropharynx has the highest frequency of upper respiratory papillomatosis. The larynx, however, has the highest rate of postoperative recurrence. Compared to adults, children are more likely to experience a postoperative recurrence.

Automatic Shrimp Fry Counting Method Using Multi-Scale Attention Fusion.

Shrimp fry counting is an important task for biomass estimation in aquaculture. Accurate counting of the number of shrimp fry in tanks can not only assess the production of mature shrimp but also assess the density of shrimp fry in the tanks, which is very helpful for the subsequent growth status, transportation management, and yield assessment. However, traditional manual counting methods are often inefficient and prone to counting errors; a more efficient and accurate method for shrimp fry counting is urgently needed. In this paper, we first collected and labeled the images of shrimp fry in breeding tanks according to the constructed experimental environment and generated corresponding density maps using the Gaussian kernel function. Then, we proposed a multi-scale attention fusion-based shrimp fry counting network called the SFCNet. Experiments showed that our proposed SFCNet model reached the optimal performance in terms of shrimp fry counting compared to CNN-based baseline counting models, with MAEs and RMSEs of 3.96 and 4.682, respectively. This approach was able to effectively calculate the number of shrimp fry and provided a better solution for accurately calculating the number of shrimp fry.

Metabolic Footprinting-Based DNA-AuNP Encoders for Extracellular Metabolic Response Profiling.

Metabolic footprinting as a convenient and non-invasive cell metabolomics strategy relies on monitoring the whole extracellular metabolic process. It covers nutrient consumption and metabolite secretion of in vitro cell culture, which is hindered by low universality owing to pre-treatment of the cell medium and special equipment. Here, we report the design and a variety of applicability, for quantifying extracellular metabolism, of fluorescently labeled single-stranded DNA (ssDNA)-AuNP encoders, whose multi-modal signal response is triggered by extracellular metabolites. We constructed metabolic response profiling of cells by detecting extracellular metabolites in different tumor cells and drug-induced extracellular metabolites. We further assessed the extracellular metabolism differences using a machine learning algorithm. This metabolic response profiling based on the DNA-AuNP encoder strategy is a powerful complement to metabolic footprinting, which significantly applies potential non-invasive identification of tumor cell heterogeneity.

Strontium ranelate enriched Ruminococcus albus in the gut microbiome of Sprague-Dawley rats with postmenopausal osteoporosis.

BACKGROUND: Gut microbiome is critical to our human health and is related to postmenopausal osteoporosis (PMO). Strontium ranelate (SrR) is an anti-osteoporosis oral drug that can promote osteoblast formation and inhibit osteoclast formation. However, the effect of SrR on gut microbiome has been rarely studied. Therefore, we investigated the effect of oral SrR on gut microbiome and metabolic profiles. RESULTS: In this study, we used ovariectomized (OVX) Sprague-Dawley rats to construct a PMO model and applied oral SrR for 6 weeks. The relative abundance of intestinal microbiome was investigated by 16S rRNA metagenomic sequencing. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to analyze changes in metabolites of intestinal contents. Results demonstrated that 6-week oral SrR alleviated osteoporosis and significantly changed the composition of the gut microbiome and metabolic profiles of OVX rats. Ruminococcus, Akkermansia and Oscillospira were significantly enriched in the gut of OVX rats after 6-week oral SrR. Especially, the species R. albus showed the greatest importance by a random forest classifier between OVX and OVX_Sr group. The enrichment of R. albus in the gut was positively correlated with bone mineral density and the accumulation of lycopene and glutaric acid, which also significantly elevated after oral SrR. CONCLUSIONS: We discovered that oral SrR can improve bone health while stimulate the accumulation of gut microbe R. albus and metabolites (lycopene and glutaric acid). The results suggested possible connections between oral SrR and the gut-bone axis, which may provide new insight into the treatment/prevention of osteoporosis.

Impact of sex on treatment-related adverse effects and prognosis in nasopharyngeal carcinoma.

BACKGROUND: In nasopharyngeal cancer (NPC), women have a lower incidence and mortality rate than men. Whether sex influences the prognosis of NPC patients remains debatable. We retrospectively examined the influence of sex on treatment-related side effects and prognosis in NPC. METHODS: Clinical data of 1,462 patients with NPC treated at the Southern Hospital of Southern Medical University from January 2004 to December 2015 were retrospectively examined. Statistical analysis was performed to assess differences in overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival(LRFS), and progression-free survival(PFS), as well as treatment-related adverse effects, including myelosuppression, gastrointestinal responses, and radiation pharyngitis and dermatitis, between men and women. RESULTS: Women had better 5-year OS (81.5% vs. 87.1%, P = 0.032) and DMFS (76.2% vs. 83.9%, P = 0.004) than men. Analysis by age showed that the prognoses of premenopausal and menopausal women were better than those of men, whereas prognoses of postmenopausal women and men were not significantly different. Additionally, women had a better prognosis when stratified by treatment regimen. Furthermore, chemotherapy-related adverse effects were more severe in women than in men; however, the incidences of radiation laryngitis and dermatitis were not significantly different between the sexes. Logistic regression analysis revealed that the female sex was an independent risk factor for severe myelosuppression and gastrointestinal reactions. CONCLUSIONS: Chemotherapy-related side effects are more severe but the overall prognosis is better in women with NPC than in men with NPC. Patients may benefit from a personalized treatment approach for NPC. TRIAL REGISTRATION: This study was approved by the Medical Ethics Committee of Nanfang Hospital of the Southern Medical University (NFEC-201,710-K3).

Teacher feedback-based collaborative testing improves students' knowledge gaps of parasitology.

Collaborative testing has been demonstrated the ability to improve students' performance, enhance students' learning, and aid in knowledge retention in many different courses. However, this examination mode lacks the process of teacher feedback. Herein, a short teacher feedback from was added immediately after the collaborative testing to improve the students' performance. A parasitology class of 121 undergraduates was randomized into two groups: group A and group B. Collaborative testing was carried out at the end of theoretical teaching. During the test, students would first answer questions as individuals for 20 minutes. Then, students from group A answered the same questions in groups (5 students in each group) for 20 minutes, while the group-testing duration was only 15 minutes in group B. Immediately after the group testing, teachers conducted a 5-minute feedback about the morphology identification according to the analysis of the answers by group B. Four weeks later, a final test was conducted in an individual test. The total scores and scores for each examination content were analyzed. The results showed that there was no significant difference in the final exam scores between both groups (t = -1.278, P = 0.204). However, the morphological and diagnostic test results of the final examination in group B were significantly higher than those of the midterm examination, while there was no significant change in group A (t = 4.333, P = 0.051). The results confirmed that the teacher feedback after the collaborative testing can effectively make up for the students' knowledge gaps.NEW & NOTEWORTHY This study found that collaborative group testing is helpful for teachers to grasp students' knowledge gaps more easily and the teacher feedback after the collaborative group testing can effectively make up for the knowledge gaps of students.

Combination of smoking and Epstein-Barr virus DNA is a predictor of poor prognosis for nasopharyngeal carcinoma: a long-term follow-up retrospective study.

BACKGROUND: This retrospective study was performed to determine the prognostic potential of smoking and its combination with pre-treatment plasma Epstein-Barr virus (EBV) DNA levels in patients with nasopharyngeal carcinoma (NPC). METHODS: Medical records of 1080 non-metastatic NPC patients who received intensity-modulated radiotherapy were reviewed. Male patients were categorized as never and ever smokers, and the smoking amount, duration, and cumulative consumption were used to evaluate dose-dependent effects. Survival outcomes were assessed using Kaplan-Meier survival analysis and the multivariate Cox regression analysis. Propensity score matching (PSM) was constructed. RESULTS: The 5-year overall survival (OS) was worse for ever smokers than never smokers, and significantly decreased with the increase of smoking amount, duration, and cumulative consumption. Compared with never smokers, the multivariate-adjusted hazard ratio (HR) of death was higher in ever smokers (HR = 1.361, P = 0.049), those smoked ≥20 cigarettes/day (HR = 1.473, P = 0.017), those smoked for ≥30 years (HR = 1.523, P = 0.023), and those cumulative smoked for ≥30 pack-years (HR = 1.649, P = 0.005). The poor prognostic effects of smoking was also confirmed in the PSM analysis. The combination of cumulative smoking consumption and pre-treatment EBV DNA levels was proven to be an independent poor prognostic factor for male NPC, and the risk of death, progression, and distant metastases gradually increased with both factors (P < 0.001). CONCLUSIONS: Combination of smoking and pre-treatment EBV DNA levels as a predictor of poor prognosis could further improve the risk stratification and prognostication for NPC.

Epstein-Barr virus (EBV) encoded microRNA BART8-3p drives radioresistance-associated metastasis in nasopharyngeal carcinoma.

Radiotherapy plays an important role in the treatment of nasopharyngeal carcinoma (NPC), however, 20% of patients with NPC exhibit unusual radioresistance. Patients with radioresistance are at risk of recurrence, so it is imperative to explore the mechanism of resistance to radiotherapy. In the past, studies on the mechanism of radioresistance have been restricted to DNA damage and related cell cycle remodeling or apoptosis. So far, no studies have explored the relationship between radioresistance and metastasis. Through the analysis of clinical samples, we observed that the metastasis rate of recurrent NPC was much higher than that of primary patients. In vitro and in vivo experiments showed that NPC cells with acquired radioresistance exhibited a stronger ability for invasion and metastasis. Mechanistically, we found that the Epstein-Barr virus (EBV)-encoded miRNA BART8-3p was increased in patients with NPC, and its expression was positively correlated with adverse prognostic factors, such as radioresistance. Besides this, miR-BART8-3p promoted the epithelial-mesenchymal transition, invasion, and metastasis of radioresistant NPC cells by targeting and inhibiting their PAG1 host gene. These findings suggested a novel role for EBV-miR-BART8-3p in promoting NPC radioresistance-associated metastasis and highlighted its potential value as a prognostic indicator or therapeutic target.

Survival benefit of induction chemotherapy for locally advanced nasopharyngeal carcinoma: prognosis based on a new risk estimation model.

BACKGROUND: Although the National Comprehensive Cancer Network (NCCN) Guidelines recommend CCRT+AC and IC + CCRT as level 2A evidence for treatment of the locoregionally advanced NPC (II-IVa), IC + CCRT+AC could also be an alternative but it is seldom used because of the low completion rates. This article aimed to compare the effectiveness of the three radiotherapy regimens using a large-scale retrospective study. METHODS: This retrospective single center analysis enrolled 1812 diagnosed NPC patients at Nanfang Hospital from January 2005 to December 2015 and only 729 patients met the inclusion criteria and were analyzed. Patients without distant metastasis, age of 18-70 years, Karnofsky scores of at least 70,stage III-IVb, and adequate adequate bone marrow, liver and renal function. Were enrolled. Adverse events and other categorical variables were compared by Pearson chi-square test or Fishier exact test. Time-to-event data were described with the Kaplan-Meier curves, time-to-event intervals compared with the log-rank test. We did multivariable analyses with the Cox proportional hazards model to test the independent signifi cance of diff erent factors. Cox proportional hazards model was used to estimate the ß regression coeffi cient, p value, and hazard ratio and its 95% CI for each of the selected risk predictors. RESULTS: The median follow-up time was 47 months. Kaplan-Meier analyses revealed no significant differences among three groups in 3-year failure-free survival (FFS, P = 0.225), 3-year overall survival (OS, P = 0.992), 3-year locoregional failure-free survival (LFFS, P = 0.549), and 3-year distant failure-free survival (DFFS, P = 0.174). Stratified survival analysis based on the risk scoring model revealed no differences in FFS, OS, LFFS, and DFFS between IC + CCRT and CCRT+AC groups for low-risk patients, however, the 3-year OS (88.3% vs. 77.6%, P = 0.049) and 3-year DFFS (84.0% vs.66.8%, P = 0.032) were respectively significantly better in IC + CCRT group compared with CCRT+AC group for high-risk patients. CONCLUSIONS: Compared with CCRT+AC, IC + CCRT lowers distant metastasis rate and improves OS among patients with locally advanced NPC in high risk group.

LSTM-DDPG for Trading with Variable Positions.

In recent years, machine learning for trading has been widely studied. The direction and size of position should be determined in trading decisions based on market conditions. However, there is no research so far that considers variable position sizes in models developed for trading purposes. In this paper, we propose a deep reinforcement learning model named LSTM-DDPG to make trading decisions with variable positions. Specifically, we consider the trading process as a Partially Observable Markov Decision Process, in which the long short-term memory (LSTM) network is used to extract market state features and the deep deterministic policy gradient (DDPG) framework is used to make trading decisions concerning the direction and variable size of position. We test the LSTM-DDPG model on IF300 (index futures of China stock market) data and the results show that LSTM-DDPG with variable positions performs better in terms of return and risk than models with fixed or few-level positions. In addition, the investment potential of the model can be better tapped by the reward function of the differential Sharpe ratio than that of profit reward function.

Red- and Far-Red-Emitting Zinc Probes with Minimal Phototoxicity for Multiplexed Recording of Orchestrated Insulin Secretion.

Zinc biology, featuring intertwining signaling networks and critical importance to human health, witnesses exciting opportunities in the big data era of physiology. Here, we report a class of red- and far-red-emitting Zn2+ probes with Kd values ranging from 190 nM to 74 µM, which are particularly suitable for real-time monitoring the high concentration of Zn2+ co-released with insulin during vesicular secretory events. Compared to the prototypical rhodamine-based Zn2+ probes, the new class exploits morpholino auxochromes which eliminates phototoxicity during long-term live recording of isolated islets. A Si-rhodamine-based Zn2+ probe with high turn-on ratio (>100), whose synthesis was enabled by a new route featuring late-stage N-alkylation, allowed simultaneous recording of Ca2+ influx, mitochondrial signal, and insulin secretion in isolated mouse islets. The time-lapse multicolor fluorescence movies and their analysis, enabled by red-shifted Zn2+ and other orthogonal physiological probes, highlight the potential impact of biocompatible fluorophores on the fields of islet endocrinology and system biology.

CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection.

BACKGROUND & AIMS: Although CD8+T cell exhaustion hampers viral control during chronic HBV infection, the pool of CD8+T cells is phenotypically and functionally heterogeneous. Therefore, a specific subpopulation of CD8+T cells should be further investigated. This study aims to dissect a subset of CD8+T cells expressing C-X-C motif chemokine receptor 5 (CXCR5) in chronic HBV infection. METHODS: The frequency of CXCR5+CD8+T cells and the levels of C-X-C motif chemokine ligand 13 (CXCL13), a chemokine of CXCR5, were measured in patients with chronic HBV infection. C57BL/6, interleukin (IL)-21 receptor- or B cell-deficient mice were hydrodynamically injected with pAAV-HBV1.2 plasmids. Phenotype and functions of peripheral and intrahepatic CXCR5+ and CXCR5-CD8+T cells were assessed. RESULTS: CXCR5+CD8+T cells were partially exhausted but possessed a stronger antiviral ability than the CXCR5- subset in patients with chronic HBV infection; moreover, CXCR5+CD8+T cells were associated with a favorable treatment response in patients with chronic hepatitis B (CHB). High levels of CXCL13 from patients with CHB facilitated the recruitment of intrahepatic CXCR5+CD8+T cells, and this subpopulation produced high levels of HBV-specific interferon (IFN)-γ and IL-21. Notably, PD1 (programmed death 1) blockade and exogenous IL-21 enhanced the production of IFN-γ. More strikingly, mice injected with CXCR5+CD8+T cells showed remarkably decreased expression of HBsAg. Additionally, an impaired production of HBV-specific IFN-γ from intrahepatic CXCR5+CD8+T cells was observed in IL-21 receptor- or B cell-deficient mice. CONCLUSION: CXCL13 promotes the recruitment of CXCR5+CD8+T cells to the liver, and this subpopulation improves viral control in chronic HBV infection. The identification of this unique subpopulation may contribute to a better understanding of CD8+T cell functions and provide a potential immunotherapeutic target in chronic HBV infection. LAY SUMMARY: Exhaustion of CD8+ T cells is an important factor in the development of chronic hepatitis B virus (HBV) infection. CD8+ T cells expressing the receptor CXCR5 are partially exhausted, but have potent antiviral activity, as they produce high levels of HBV-specific cytokines in chronic HBV infection. Increased expression of CXCL13 within the liver facilitates the recruitment of CXCR5+CD8+T cells and establishes effective immune control of HBV infection.

Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade.

BACKGROUND: Substantial clinical and preclinical evidence have indicated the association between amide-linked local anesthesia and the long-term outcomes of cancer patients. However, the potential effects of local anesthesia on cancer recurrence are inconclusive and the underlying mechanisms remain poorly understood. METHODS: We systematically examined the effects of three commonly used local anesthetics in melanoma cells and analyzed the underlying mechanisms focusing on small GTPases. RESULTS: Ropivacaine and lidocaine but not bupivacaine inhibited migration and proliferation, and induced apoptosis in melanoma cells. In addition, ropivacaine and lidocaine but not bupivacaine significantly augmented the in vitro efficacy of vemurafenib (a B-Raf inhibitor for melanoma with BRAF V600E mutation) and dacarbazine (a chemotherapeutic drug). Mechanistically, ropivacaine but not bupivacaine decreased the activities of Ras superfamily members with the dominant inhibitory effects on RhoA and Ras, independent of sodium channel blockade. Rescue studies using constitutively active Ras and Rho activator calpeptin demonstrated that ropivacaine inhibited migration mainly through RhoA whereas growth and survival were mainly inhibited through Ras in melanoma cells. We further detected a global reduction of downstream signaling of Ras and RhoA in ropivacaine-treated melanoma cells. CONCLUSION: Our study is the first to demonstrate the anti-melanoma activity of ropivacaine and lidocaine but not bupivacaine, via targeting small GTPases. Our findings provide preclinical evidence on how amide-linked local anesthetics could affect melanoma patients.

Anesthetic Management of Patients with COVID 19 Infections during Emergency Procedures.

OBJECTIVES: The aim of the present study was to prevent cross-infection in the operating room during emergency procedures for patients with confirmed or suspected 2019 novel coronavirus (2019-nCoV) by following anesthesia management protocols, and to document clinical- and anesthesia-related characteristics of these patients. DESIGN: This was a retrospective, multicenter clinical study. SETTING: This study used a multicenter dataset from 4 hospitals in Wuhan, China. PARTICIPANTS: Patients and health care providers with confirmed or suspected 2019-nCoV from January 23 to 31, 2020, at the Wuhan Union Hospital, the Wuhan Children's Hospital, The Central Hospital of Wuhan, and the Wuhan Fourth Hospital in Wuhan, China. INTERVENTIONS: Anesthetic management and infection control guidelines for emergency procedures for patients with suspected 2019-nCoV were drafted and applied in 4 hospitals in Wuhan. MEASUREMENTS AND MAIN RESULTS: Cross-infection in the operating rooms of the 4 hospitals was effectively reduced by implementing the new measures and procedures. The majority of patients with laboratory-confirmed 2019-nCoV infection or suspected infection were female (23 [62%] of 37), and the mean age was 41.0 years old (standard deviation 19.6; range 4-78). 10 (27%) patients had chronic medical illnesses, including 4 (11%) with diabetes, 8 (22%) with hypertension, and 8 (22%) with digestive system disease. Twenty-five (68%) patients presented with lymphopenia, and 23 (62%) patients exhibited multiple mottling and ground-glass opacity on computed tomography scanning. CONCLUSIONS: The present study indicates that COVID 19-specific guidelines for emergency procedures for patients with confirmed or suspected 2019-nCoV may effectively prevent cross-infection in the operating room. Most patients with confirmed or suspected COVID 19 presented with fever and dry cough and demonstrated bilateral multiple mottling and ground-glass opacity on chest computed tomography scans.

High spatiotemporal resolution and low photo-toxicity fluorescence imaging in live cells and in vivo.

Taking advantage of high contrast and molecular specificity, fluorescence microscopy has played a critical role in the visualization of subcellular structures and function, enabling unprecedented exploration from cell biology to neuroscience in living animals. To record and quantitatively analyse complex and dynamic biological processes in real time, fluorescence microscopes must be capable of rapid, targeted access deep within samples at high spatial resolutions, using techniques including super-resolution fluorescence microscopy, light sheet fluorescence microscopy, and multiple photon microscopy. In recent years, tremendous breakthroughs have improved the performance of these fluorescence microscopies in spatial resolution, imaging speed, and penetration. Here, we will review recent advancements of these microscopies in terms of the trade-off among spatial resolution, sampling speed and penetration depth and provide a view of their possible applications.

Loss of IP3 Receptor-Mediated Ca2+ Release in Mouse B Cells Results in Abnormal B Cell Development and Function.

Intracellular calcium (Ca2+) mobilization after engagement of the BCR has been proposed to play an important role in B cell development and function. BCR activation causes an initial Ca2+ release from the endoplasmic reticulum that is mediated by inositol 1,4,5-trisphosphate receptor (IP3R) and then triggers store-operated Ca2+ entry once endoplasmic reticulum Ca2+ store is depleted. Store-operated Ca2+ entry has been shown to regulate B cell function but is dispensable for B cell development. By contrast, the function of IP3R-mediated Ca2+ release in B cells remains to be determined. In this study, we generated a B cell-specific IP3R triple-knockout (IP3R-TKO) mouse model and revealed that loss of IP3Rs increased transitional B cell numbers and reduced recirculating mature B cell numbers in bone marrow. In the peripheral tissues, the numbers of conventional B2 B cells and B1 B cells were both significantly decreased in IP3R-TKO mice. Ablation of IP3Rs also dramatically reduced BCR-mediated B cell proliferation and survival. Furthermore, T cell-dependent and T cell-independent Ab responses were altered in IP3R-TKO mice. In addition, deletion of IP3Rs reduced IL-10-producing regulatory B cell numbers and led to defects in NFAT activation, which together resulted in decreased IL-10 secretion. Taken together, our study demonstrated for the first time, to our knowledge, that IP3R-mediated Ca2+ release plays an essential role in regulating B cell development, proliferation, Ab production, and B cell regulatory function in vivo.

Retrospective study comparing anti-EGFR monoclonal antibody plus cisplatin-based chemoradiotherapy versus chemoradiotherapy alone for stage II-IVb nasopharyngeal carcinoma and prognostic value of EGFR and VEGF expression.

OBJECTIVES: The benefits of adding anti-EGFR therapy to conventional chemoradiotherapy (CRT) for nasopharyngeal carcinoma (NPC) remain uncertain, possibly because only a subgroup of patients show better outcome. To address this issue, we compared the efficacy of CRT plus cetuximab (CTX) or nimotuzumab (NTZ) to CRT alone for stage II-IVb NPC and examined possible prognostic indicators, including tumour EGFR and VEGR expression levels. DESIGN, SETTING AND PARTICIPANTS: This retrospective study enrolled 1812 patients at initial NPC diagnosis at Nanfang Hospital Affiliated to Southern Medical University between January 2005 and December 2015. The cetuximab or nimotuzumab plus CRT group (CRT+NTZ/CTX) and the conventional chemoradiotherapy group (CRT) were matched by propensity scoring at 1:5, yielding 282 patients at clinical stage II-IVb with 47 in the CRT+NTZ/CTX group and 235 in the CRT group. MAIN OUTCOME MEASURES: The endpoints of the present study were locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS). Immunohistochemistry (IHC) was used to investigate EGFR and VEGF expression levels in 31 patients of the CRT+NTZ/CTX group. RESULTS: There were no significant differences in LRFS, DMFS and OS, haematologic toxicity reactions, and gastrointestinal reactions between CRT+NTZ/CTX and CRT groups. There was a positive correlation between EGFR and VEGF expression levels. Among CRT+NTZ/CTX patients, those with high EGFR and VEGF expression levels exhibited better DMFS. CONCLUSIONS: Addition of anti-EGFR to cisplatin-based CRT appears to benefit only a subset of stage II-IVb NPC patients, those with elevated EGFR and VEGF expression levels.

Ropivacaine inhibits the migration of esophageal cancer cells via sodium-channel-independent but prenylation-dependent inhibition of Rac1/JNK/paxillin/FAK.

The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival. We further demonstrate that ropivacaine significantly decreases activities of GTPases including RhoA, Rac1 and Ras, and inhibits prenylation in esophageal cancer cells. In addition, the inhibitory effects of ropivacaine on GTPases activities and migration are abolished in the presence of geranylgeraniol and farnesol, demonstrating that ropivacaine inhibits GTPases activities via prenylation inhibition. Finally, we demonstrate that ropivacaine-inhibited esophageal cancer cell inhibition occurs independently of sodium channel but via suppressing Rac1/JNK/paxillin/FAK pathway. Our work demonstrates the potent anti-migratory effect of ropivacaine in esophageal cancer by attenuating prenylation-dependent migratory signalling events. These findings provide significant insight into the potential mechanisms by which local anaesthetics may negatively affect metastasis.

Incidence of paragonimiasis in Chongqing China: a 6-year retrospective case review.

Paragonimiasis is an important infectious disease in Chongqing, China. However, no epidemiological surveys of paragonimiasis have been carried out in Chongqing since it became a municipality in 1997. We conducted a retrospective case review of 683 patients who were referred to our laboratory and diagnosed as having paragonimiasis during 2010-2015. Patients were diagnosed with paragonimiasis based on immunodiagnostic tests in addition to clinical and laboratory findings. Patient data extracted from the epidemiologic form were analysed. The majority of patients were distributed on the east side of the Wujiang River, which belongs to the Three Gorges Reservoir region. Consumption of raw or undercooked freshwater crab or crayfish in the family Cambaridae was the main reason for infection. Notably, more than 50·0% of patients were diagnosed between March and July, indicating that serious clinical symptoms only appear approximately 6 months post-infection. Paragonimiasis remains a public health issue in Chongqing, and an epidemiological study of Paragonimus in the Three Gorges region is strongly recommended.