[Clinicopathological Features and Prognosis of Patients Newly Diagnosed With Lung Adenocarcinoma With Both EGFR Mutation and C-MET Amplification].

Objective To explore the clinicopathological features and prognosis of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification.Methods The pathological sections were reviewed.EGFR mutation was detected by amplification refractory mutation system-quantitative real-time polymerase chain reaction,and C-MET amplification by fluorescence in situ hybridization.The clinicopathological features and survival data of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification were analyzed retrospectively.Results In 11 cases of EGFR mutation combined with C-MET amplification,complex glands and solid high-grade components were observed under a microscope in 10 cases except for one case with a cell block,the tissue structure of which was difficult to be evaluated.The incidence of lung adenocarcinoma in the patients with EGFR mutation combined with C-MET amplification at clinical stage Ⅳ was higher than that in the EGFR mutation or C-MET amplification group (all P<0.001),whereas the difference was not statistically significant between the EGFR mutation group and C-MET amplification group at each clinical stage (all P>0.05).There was no significant difference in the trend of survival rate between EGFR gene group and C-MET amplification group (χ2=0.042,P=0.838),while the survival of the patients with EGFR mutation combined with C-MET amplification was worse than that of the patients with EGFR mutation (χ2=246.72,P<0.001) or C-MET amplification (χ2=236.41,P<0.001).Conclusions The patients newly diagnosed with lung adenocarcinoma with EGFR mutation plus C-MET amplification demonstrate poor histological differentiation,rapid progress,and poor prognosis.The patients are often in the advanced stage when being diagnosed with cancer.Attention should be paid to this concurrent adverse driving molecular event in clinical work.With increasing availability,the inhibitors targeting C-MET may serve as an option to benefit these patients in the near future.

24-h Urinary Calcium Excretion and Renal Outcomes in Hospitalized Patients with and without Chronic Kidney Disease.

This study investigated the impact of 24-h urinary calcium excretion (UCaE) on renal function decline in hospitalized patients with and without chronic kidney disease (CKD). This study enrolled 3815 CKD patients in stages 1-4 and 1133 non-CKD patients admitted to the First Center of the Chinese PLA General Hospital between January 2014 and July 2022. The primary outcome for CKD patients was a composite of CKD progression, defined as a 40% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease. Annual eGFR change was the secondary outcome. For non-CKD patients, the primary outcome was an eGFR decline of ≥20% or CKD incidence, while annual eGFR change was the secondary outcome. The association between UCaE and kidney function decline was assessed using Cox proportional hazards and generalized linear models. Primary outcomes were observed in 813 CKD patients and 109 non-CKD patients over a median follow-up of 3.0 and 4.1 years, respectively. For CKD patients, every 1-mmol/d increase in UCaE was associated with a 15% decreased risk of CKD progression. The hazard ratio (HR) was 0.85, with a 95% confidence interval (CI) of 0.77-0.93. For non-CKD patients, the risk of renal function decline decreased by 11%. The multivariate models indicated that there was an annual decrease in eGFR in both CKD and non-CKD patients, with a reduction of 0.122 mL/min/1.73 m2/year (p < 0.001) and 0.046 mL/min/1.73 m2/year (p = 0.004), respectively, for every 1-mmol/d increase in UCaE. CKD experiences a decrease in 24-h UCaE as early as stage 1, with a significant decline in stage 4. CKD and non-CKD patients with lower UCaE levels are at an increased risk of renal decline, regardless of other variables.

Optical trapping of two different microparticles by a double-tapered fiber probe.

We theoretically and experimentally study the optical trapping of two different microparticles by a double-tapered optical fiber probe (DOFP) which is fabricated by the interfacial etching method. A SiO2 microsphere and a yeast, or two SiO2 microspheres with different diameters, are trapped. We calculate and measure the trapping forces on the two microparticles, discuss the impacts of the geometrical size and refractive index on the trapping forces. Both the theoretical calculation and experimental measurements indicate that if the two particles have the same refractive index, the larger the second particle is, the larger the trapping force is. Whereas, if the two particles have the same geometrical size, the smaller the refractive index is, the lager trapping force is. Trapping and manipulation of different multiple microparticles by a DOFP enhance the application of optical tweezers, especially in biomedical engineering and material science.

A novel prognostic model for patients with colon adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is a highly heterogeneous disease, which makes its prognostic prediction challenging. The purpose of this study was to investigate the clinical epidemiological characteristics, prognostic factors, and survival outcomes of patients with COAD in order to establish and validate a predictive clinical model (nomogram) for these patients. Methods: Using the SEER (Surveillance, Epidemiology, and End Results) database, we identified patients diagnosed with COAD between 1983 and 2015. Disease-specific survival (DSS) and overall survival (OS) were assessed using the log-rank test and Kaplan-Meier approach. Univariate and multivariate analyses were performed using Cox regression, which identified the independent prognostic factors for OS and DSS. The nomograms constructed to predict OS were based on these independent prognostic factors. The predictive ability of the nomograms was assessed using receiver operating characteristic (ROC) curves and calibration plots, while accuracy was assessed using decision curve analysis (DCA). Clinical utility was evaluated with a clinical impact curve (CIC). Results: A total of 104,933 patients were identified to have COAD, including 31,479 women and 73,454 men. The follow-up study duration ranged from 22 to 88 months, with an average of 46 months. Multivariate Cox regression analysis revealed that age, gender, race, site_recode_ICD, grade, CS_tumor_size, CS_extension, and metastasis were independent prognostic factors. Nomograms were constructed to predict the probability of 1-, 3-, and 5-year OS and DSS. The concordance index (C-index) and calibration plots showed that the established nomograms had robust predictive ability. The clinical decision chart (from the DCA) and the clinical impact chart (from the CIC) showed good predictive accuracy and clinical utility. Conclusion: In this study, a nomogram model for predicting the individualized survival probability of patients with COAD was constructed and validated. The nomograms of patients with COAD were accurate for predicting the 1-, 3-, and 5-year DSS. This study has great significance for clinical treatments. It also provides guidance for further prospective follow-up studies.

Divergent responses in the gut microbiome and liver metabolome to ammonia stress in three freshwater turtles.

Ammonia is a common pollutant in aquaculture system, and toxic to all aquatic animals. However, different aquatic animals exhibit diverse physiological responses to high-level ammonia exposure, potentially indicating their divergent resistance to ammonia stress. In this study, juveniles of three freshwater turtles (Mauremys reevesii, Pseudemys nelsoni and Trachemys scripta elegans) were exposed to different concentrations of ammonia (0, 0.3 and 3.0 mg/L) for 30 days, and their swimming, growth performance, gut microbiota, and hepatic metabolites were measured to evaluate the interspecific difference in physiological responses to ammonia stress. Despite no differences in swimming ability, growth rate, and gut microbial diversity, observable changes in microbial community composition and hepatic metabolite profiles were shown in ammonia-exposed turtles. A relatively higher abundance of potentially pathogenic bacteria was found in M. reevesii than in the other two species. Moreover, microbial compositions and metabolic responses differed significantly among the three species. M. reevesii was, out of the three tested species, the one in which exposure to ammonia had the greatest effect on changes in bacterial genera and hepatic metabolites. Conversely, only a few metabolites were significantly changed in T. scripta elegans. Integrating these findings, we speculated that native M. reevesii should be more vulnerable to ammonia stress compared to the invasive turtle species. Our results plausibly reflected divergent potential resistance to ammonia among these turtles, in view of differential physiological responses to ammonia exposure at environmentally relevant concentrations.

Comparison of the Effectiveness of Transnasal Humidified Rapid Insufflation Ventilator Exchange (THRIVE) with Facemask Pre-Oxygenation in 40 Patients ≥65 Years of Age Undergoing General Anaesthesia During Gastrointestinal Surgery for Intestinal Obstruction.

BACKGROUND In this study, we aimed to compare the effectiveness of transnasal humidified rapid insufflation ventilator exchange (THRIVE) with facemask pre-oxygenation in 40 patients ≥65 years of age undergoing general anesthesia during gastrointestinal surgery for intestinal obstruction. MATERIAL AND METHODS Patients with gastrointestinal obstruction were randomized to either a facemask group (group M, n=20) or THRIVE group (group T, n=20). During pre-oxygenation, the 2 groups used a facemask (100% oxygen, 6 L/min) and THRIVE (100% oxygen, 40 L/min) to supply oxygen, respectively. Induction of anesthesia was performed in both groups using facemasks and without mechanical or assisted ventilation. The intubation occurred after myorelaxant action began. When the peripheral oxygen saturation (SpO2) dropped below 95%, or 480 s after administration of muscle relaxants, mechanical ventilation was initiated immediately. The primary outcome was arterial partial pressure of oxygen (PaO2) at 5 min after pre-oxygenation. A secondary outcome was time to SpO2 of 95% during apnea, with a cut-off time of 480 s. RESULTS PaO2 at 5 min after pre-oxygenation was (261.5±30.9) mmHg for group M and (446.1±84.4) mmHg for group T (P<0.001). Based on survival analysis, the median time-to-event in group T was 480 s (95% CI 415.7 s - upper limit unknown) and 240 s (95% CI 225.9-254.1 s) in group M (P<0.001). CONCLUSIONS In elderly patients undergoing rapid sequence induction, pre-oxygenation with THRIVE could improve oxygenation and extend safe apnea time, compared with facemask pre-oxygenation.

San-Zhong-Kui-Jian-Tang Exerts Antitumor Effects Associated With Decreased Cell Proliferation and Metastasis by Targeting ERK and the Epithelial-Mesenchymal Transition Pathway in Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive cancer whose 5-year survival rate remains poor. San-Zhong-Kui-Jian-Tang (SZKJT), a Chinese herbal formula, has long been used in clinical practice as adjuvant therapy in cancers. However, its therapeutic effects and molecular mechanisms in OSCC remain unclear. METHODS: We investigated the potential therapeutic effects and molecular mechanism of SZKJT in OSCC in tumor cell lines and in tumor xenograft mice and evaluated combined SZKJT and cisplatin treatment efficacy. In vitro-cultured OSCC cells were administered SZKJT at different doses or SZKJT plus cisplatin, and cell proliferation, colony formation assays, and cell cycle analysis were used to assess the effects on cancer cell proliferation and apoptosis. We also analyzed the effects of SZKJT on oral cancer cell line migration, the regulation of mitogen-activated protein kinase (MAPK) signaling, and epithelial-mesenchymal transition (EMT)-associated genes. The antitumor effects of SZKJT plus cisplatin were also tested in vivo using a tumor-bearing NOD/SCID mice model. RESULTS: The results showed that SZKJT effectively inhibited OSCC cell proliferation, induced cell cycle S phase arrest, and induced cell apoptosis. SZKJT also inhibited cell migration by modulating the MAPK signaling and epithelial-mesenchymal transition (EMT) pathway. Further exploration suggested that SZKJT affects OSCC by modulating ERK pathway; downregulating vimentin, fibronectin, and Oct-4; and upregulating E-cadherin. In vivo, SZKJT significantly inhibited tumor growth, and SZKJT and cisplatin exerted synergistic antitumor effects in model animals. CONCLUSIONS: SZKJT exerts antitumor effects in OSCC cells. Additionally, SZKJT and cisplatin exhibit synergy in OSCC treatment. These findings support the clinical usage of Chinese herbal formulas as adjuvant therapy with chemotherapy in cancer treatment.

The effect of varying inhaled oxygen concentrations of high-flow nasal cannula oxygen therapy during gastroscopy with propofol sedation in elderly patients: a randomized controlled study.

BACKGROUND: Despite evidence that high-flow nasal cannula oxygen therapy (HFNC) promotes oxygenation, its application in sedated gastroscopy in elderly patients has received little attention. This study investigated the effect of different inhaled oxygen concentrations (FiO2) of HFNC during sedated gastroscopy in elderly patients. METHODS: In a prospective randomized single-blinded study, 369 outpatients undergoing regular gastroscopy with propofol sedation delivered by an anesthesiologist were randomly divided into three groups (n = 123): nasal cannula oxygen group (Group C), 100% FiO2 of HFNC group (Group H100), and 50% FiO2 of HFNC (Group H50). The primary endpoint in this study was the incidence of hypoxia events with pulse oxygen saturation (SpO2) ≤ 92%. The secondary endpoints included the incidence of other varying degrees of hypoxia and adverse events associated with ventilation and hypoxia. RESULTS: The incidence of hypoxia, paradoxical response, choking, jaw lift, and mask ventilation was lower in both Group H100 and Group H50 than in Group C (P < 0.05). Compared with Group H100, Group H50 showed no significant differences in the incidence of hypoxia, jaw lift and mask ventilation, paradoxical response, or choking (P > 0.05). No patients were mechanically ventilated with endotracheal intubation or found to have complications from HFNC. CONCLUSION: HFNC prevented hypoxia during gastroscopy with propofol in elderly patients, and there was no significant difference in the incidence of hypoxia when FiO2 was 50% or 100%. TRIAL REGISTRATION: This single-blind, prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20201102-04) and registered in the China Clinical Trial Center (20/10/2021, ChiCTR2100052144) before patients enrollment. All patients signed an informed consent form.

Gut Microbial Composition and Liver Metabolite Changes Induced by Ammonia Stress in Juveniles of an Invasive Freshwater Turtle.

As the most common pollutant in aquaculture systems, the toxic effects of ammonia have been extensively explored in cultured fish, molluscs, and crustaceans, but have rarely been considered in turtle species. In this study, juveniles of the invasive turtle, Trachemys scripta elegans, were exposed to different ammonia levels (0, 0.3, 3.0, and 20.0 mg/L) for 30 days to evaluate the physiological, gut microbiomic, and liver metabolomic responses to ammonia in this turtle species. Except for a relatively low growth rate of turtles exposed to the highest concentration, ammonia exposure had no significant impact on the locomotor ability and gut microbial diversity of turtles. However, the composition of the microbial community could be altered, with some pathogenic bacteria being increased in ammonia-exposed turtles, which might indicate the change in their health status. Furthermore, hepatic metabolite profiles via liquid chromatography-mass spectrometry revealed extensive metabolic perturbations, despite being primarily involved in amino acid biosynthesis and metabolism. Overall, our results show that ammonia exposure causes gut dysbacteriosis and disturbs various metabolic pathways in aquatic turtle species. Considering discrepant defense mechanisms, the toxic impacts of ammonia at environmentally relevant concentrations on physiological performance might be less pronounced in turtles compared with fish and other invertebrates.

[Clinicopathological Characteristics of Lymphadenitis Caused by Talaromyces marneffei Diagnosed by Core Needle Biopsy].

Objective To analyze the clinicopathological characteristics of lymphadenitis caused by Talaromyces marneffei (TM).Method s The clinical data,pathological features,pathogen examination,and treatment of 15 cases of TM-caused lymphadenitis were analyzed retrospectively.Results The 15 cases included 14 males and 1 females,who were aged 26-67 years,with an average age of (49.1±11.87) years.The 15 cases,including 13 cases of acquired immunodeficiency syndrome and 2 cases of diabetes mellitus,were accompanied by superficial lymph node enlargement in the neck and supraclavicular,axillary,and inguinal regions.The structure of cord-like lymph node tissue punctured by thick needle was completely or partially replaced by inflammatory lesions. Under microscope,8 cases showed mainly diffuse infiltration of phagocytes with pathogens;5 cases presented mainly extensive coagulation necrosis with a small amount of pathogens and nuclear debris;2 cases were characterized by small nodular hyperplasia of fibroblasts,formation of granulomatous structure,and scattered distribution of a few multinucleated giant cells.The pathogens were relatively consistent in size and shape,which were round,oval or sausage-shaped and clustered like mulberry.Diastase periodic acid-Schiff staining and hexamine silver staining highlighted the bacterial structure with transverse septum.TM growth was detected in the blood,alveolar lavage fluid,sputum or lymph node extract fungal culture of the 15 patients.Owing to the adequate antifungal treatment in time,these 15 patients were discharged after their conditions were improved.Conclusion Lymphadenitis is one of the major manifestations of the systemic invasion of TM at the late stage,which is tended to be misdiagnosed.Through core needle biopsy of lymph node,it can be diagnosed as soon as possible to avoid delayed treatment and improve the cure rate.

Association between the Platelet-Derived Growth Factor/Platelet-Derived Growth Factor Receptor System and Risk of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

This research examines the association between the platelet-derived growth factor/platelet-derived growth factor receptor (PDGF/PDGFR) system and rheumatoid arthritis (RA) susceptibility through a comprehensive search of the PubMed database to study the expression of the PDGF/PDGFR system in RA. Review Manager software version 5.3 was used for statistical analysis. Six eligible studies published in the English language were included, including 108 rheumatoid arthritis cases and 85 controls with the corresponding 126 and 97 tests, respectively, relating the expression of the PDGF/PDGFR system to the risk of RA. The overall results indicated a significant association between the PDGF/PDGFR system expression and RA (OR = 5.25, 95% CI: 3.00-9.18, p < 00001), RA patients in Asian countries (OR = 4.13, 95% CI = 2.04-8.39, p < 0.0001) and in Western countries (OR = 9.18, 95% CI = 2.04-8.39, p = 0.03), and only PDGF expression in RA patients (OR = 5.28, 95% CI = 2.73-10.21, p < 0.00001). Thus, only the PDGFR expression was insignificantly associated with RA susceptibility (OR = 9.25, 95% CI = 0.63-136.30, p = 0.11). Hence, the PDGF/PDGFR system most likely contributes to susceptibility to RA.

Radiation-Induced Metabolic Shifts in the Hepatic Parenchyma: Findings from 18F-FDG PET Imaging and Tissue NMR Metabolomics in a Mouse Model for Hepatocellular Carcinoma.

PURPOSE: By taking advantage of 18F-FDG PET imaging and tissue nuclear magnetic resonance (NMR) metabolomics, we examined the dynamic metabolic alterations induced by liver irradiation in a mouse model for hepatocellular carcinoma (HCC). METHODS: After orthotopic implantation with the mouse liver cancer BNL cells in the right hepatic lobe, animals were divided into two experimental groups. The first received irradiation (RT) at 15 Gy, while the second (no-RT) did not. Intergroup comparisons over time were performed, in terms of 18F-FDG PET findings, NMR metabolomics results, and the expression of genes involved in inflammation and glucose metabolism. RESULTS: As of day one post-irradiation, mice in the RT group showed an increased 18F-FDG uptake in the right liver parenchyma compared with the no-RT group. However, the difference reached statistical significance only on the third post-irradiation day. NMR metabolomics revealed that glucose concentrations peaked on day one post-irradiation both, in the right and left lobes-the latter reflecting a bystander effect. Increased pyruvate and glutamate levels were also evident in the right liver on the third post-irradiation day. The expression levels of the glucose-6-phosphatase (G6PC) and fructose-1, 6-bisphosphatase 1 (FBP1) genes were down-regulated on the first and third post-irradiation days, respectively. Therefore, liver irradiation was associated with a metabolic shift from an impaired gluconeogenesis to an enhanced glycolysis from the first to the third post-irradiation day. CONCLUSION: Radiation-induced metabolic alterations in the liver parenchyma occur as early as the first post-irradiation day and show dynamic changes over time.

Gastrodin alleviates perioperative neurocognitive dysfunction of aged mice by suppressing neuroinflammation.

Perioperative neurocognitive disorder (PND) is a common complication of elderly patients after surgery and lacks effective prevention and treatment measures. We investigated the effect and mechanism of gastrodin (GAS), a natural plant ingredient, on postoperative cognition induced by laparotomy in aged mice. Male aged (18 months) mice were subjected to laparotomy and orally treated with GAS (25, 50, and 100 mg/kg) 3 weeks before surgery and 1 week after surgery. In addition, some male aged (18 months) mice were subjected to viral vector or GSK-3ß expression virus injection followed by laparotomy with or without 100 mg/kg GAS treatment. GAS improved learning and memory in aged mice after surgery. Surgery increased the levels of pro-inflammatory factors (TNF-α, IL-1ß and IL-6) and decreased the level of an anti-inflammatory factor (IL-10) in the mouse hippocampus, and these changes were reversed by GAS treatment. GAS also suppressed the activation of microglia. GAS inhibited the phosphorylation of GSK-3ß and Tau. Furthermore, surgery induced more serious cognitive dysfunction, inflammatory factors, activation of microglia, and phosphorylation of GSK-3ß and Tau in GSK-3ß overexpressing aged mice. The improvement of learning and memory, the reduction of inflammation and microglia activation, and the suppression of GSK-3ß and Tau phosphorylation by GAS were prevented when GSK-3ß was overexpressed in aged mice subjected to surgery. Our finding suggested that GAS exerts neuroprotective effects in aged mice subjected to laparotomy by suppressing neuroinflammation and GSK-3ß and Tau phosphorylation. Thus, these findings suggest that GAS may be a promising agent for PND.

[Ultrasound assessment of gastric insufflation in obese patients receiving transnasal humidified rapid-insufflation ventilatory exchange during general anesthesia induction].

OBJECTIVE: To assess the effect of transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) on gastric insufflation during general anesthesia induction in obese patients. METHODS: Ninety obese patients (BMI 30-39.9 kg/m2) undergoing laparoscopic cholecystectomy under general anesthesia were randomized into 3 groups (n=30) to receive facemask pre- oxygenation followed by face mask ventilation (FMV) after administration of anesthetics (Group M), oxygenation with THRIVE (Group T), or pre-oxygenation with facemask combined with THRIVE followed continuous oxygenation with both FMV and THRIVE after administration of anesthetics (Group M+T). The patients in the latter two groups received continuous oxygen via THRIVE during tracheal intubation. All the patients received real-time ultrasound monitoring of the gastric antrum, and positive gastric insufflation (GI+) was defined by the presence of comet-tail artifacts. The cross-sectional area of the gastic antrum (CSA-GA) was measured by ultrasound before and after pre-oxygenation and after intubation. The patients' SpO2, PaO2, and PaCO2 at admission (T1), 5 min after pre-oxygenation (T2), 5 min after medication (T3), and immediately after intubation (T4) were recorded, and the incidence of postoperative adverse events was assessed. RESULTS: The incidence of gastric insufflation was significantly higher in Group M and Group M+T than in Group T (P < 0.05). The CSA-GA was significantly greater at T4 than at T1 in Group M and Group M+T and in their GI+s ubgroups. The GI+ subgroups in Group M and Group M+ T had significantly larger CSA-GA at T4 than the GI- subgroups (P < 0.05). CSA-GA did not vary significantly during anesthesia induction in Group T (P>0.05). The incidence of grade Ⅰ gastric distension was lower but grade Ⅱ gastric distention was higher in Group M and Group M+T than in Group T (P < 0.05). Group M showed significantly greater variations of PaO2 at T3 and T4 than Group T and Group M+T (P < 0.05). CONCLUSIONS: Ultrasound monitoring of the comet tail sign and the changes of CSA-GA in the gastric antrum is feasible and reliable for detecting gastrointestinal airflow, and in obese patients, the application of THRIVE for induction of anesthesia can ensure the oxygenation level without further increasing gastric insufflation.

Cotargeting CHK1 and PI3K Synergistically Suppresses Tumor Growth of Oral Cavity Squamous Cell Carcinoma in Patient-Derived Xenografts.

Oral cavity squamous cell carcinomas (OSCCs) are aggressive tumors, and their recurrence leads to poor prognosis and reduced survival rates. This study aimed to identify therapeutic targets and to evaluate the efficacy of targeted inhibitors in OSCC patient-derived xenograft (PDX) models. Herein, we reported that OSCC PDXs recapitulated the genomic signatures of their paired primary tumors and the expression of CHEK1, PIK3CA, and PIK3CD was significantly upregulated in OSCC. The antitumor efficacy of CHK1 inhibitors (PF477736, AZD7762, LY2606368) and PI3K inhibitors (BYL719, GDC0941, GSK1059615) was investigated in OSCC cell lines and PDX models. Targeting either CHK1 or PI3K effectively inhibited cell proliferation and colony formation by inducing cell cycle arrest and apoptosis in in vitro cell-based assays. Cisplatin-based chemotherapy combined with CHK1 inhibitor treatment synergistically inhibited cell proliferation by suppressing CHK1 phosphorylation and inducing PARP cleavage. Furthermore, compared with monotherapy, cotreatment with CHK1 and PI3K inhibitors exerted synergistic anticancer effects by suppressing CHK1, AKT, and 4E-BP1 phosphorylation. In summary, our study identified CHK1 and PI3K as promising targets, especially in a dual treatment strategy combining a CHK1 inhibitor with cisplatin or a PI3K inhibitor as a novel therapeutic approach for OSCC patients with aberrant cell cycle regulation and PI3K signaling activation.

Nuclear Magnetic Resonance Metabolomics Biomarkers for Identifying High Risk Patients with Extranodal Extension in Oral Squamous Cell Carcinoma.

Extranodal extension (ENE) is an independent adverse prognostic factor in oral squamous cell carcinoma (OSCC), and is difficult to identify preoperatively. We aimed to discover biomarkers for high risk patients with ENE. Tandem tissue, plasma, and urine samples of 110 patients with OSCC were investigated through 600-MHz nuclear magnetic resonance (NMR) metabolomics analysis. We found that the levels of creatine, creatine phosphate, glycine, and tyramine in plasma significantly decreased in stage IV ENE positive OSCC compared with stage IV ENE negative OSCC. To understand the underlying mechanism behind the alteration of plasma metabolites, our tissue analysis revealed that the carnitine level significantly increased in tumors but significantly decreased in the adjacent normal tissue in advanced stage OSCC, in addition to decreased levels of alanine and pyruvate in tumor tissues. The global metabolomics analysis on tumor tissues also showed that stage IV tumors with an ENE positive status demonstrated higher levels of aspartate, butyrate, carnitine, glutamate, glutathione, glycine, glycolate, guanosine, and sucrose but lower levels of alanine, choline, glucose, isoleucine, lactate, leucine, myo-inositol, O-acetylcholine, oxypurinol, phenylalanine, pyruvate, succinate, tyrosine, valine, and xanthine than tumors with an ENE negative status. We concluded that metabolomics alterations in tumor tissues correspond to an increase in the tumor stage and are detectable in plasma samples. Metabolomic alterations of OSCC can serve as potential diagnostic markers and predictors of ENE in patients with stage IV OSCC.

Sweroside eradicated leukemia cells and attenuated pathogenic processes in mice by inducing apoptosis.

Acute myeloid leukemia (AML), characterized by extremely heterogeneous molecular and biologic abnormalities, is an aggressive hematologic malignancy, hampering the research and development of effective targeted treatment modalities. Sweroside (SWE), an iridoid glycoside, is isolated from Lonicera japonIca. It has diverse biological activities, but little is known in human leukemia. Here, our study showed the potential of sweroside as an effective agent against human leukemia using in vitro and in vivo approaches. Sweroside treatment obviously reduced the cell viability in human leukemia cell lines and primary human leukemia cells. S and G2/M cell-cycle arrest were induced by sweroside, associated with the down-regulation of Cyclin D1, cyclin-dependent kinase 4 (CDK4), CDC2 and CDC25 as well as the up-regulation of p53 and p21. In addition, apoptosis was highly induced by sweroside both in vitro and in vivo through enhancement of cleaved Caspase-3 and poly (ADP-ribosyl) transferase (PARP). Consistently, anti-apoptotic molecule of B cell CLL/lymphoma 2 (Bcl-2) was impeded by sweroside, while pro-apoptotic signal of Bcl-2-associated X protein (Bax) was elevated. In vivo, HL-60-bearing tumor growth was considerably inhibited by sweroside, which was related to proliferation suppression and apoptosis induction. Our study highlighted the therapeutic potential of sweroside, and provided new insights into the molecular mechanism of sweroside chemosensitization in human leukemia.

Identification of Four ATP-Binding Cassette Transporter Genes in Cnaphalocrocis medinalis and Their Expression in Response to Insecticide Treatment.

The ATP-binding cassette (ABC) transporters belong to a superfamily of genes involved in the transport of specific molecules across lipid membranes, as well as insecticide resistance, present in all living organisms. In this study, we combined the Cnaphalocrocis medinals transcriptome database with a bioinformatics approach to identify four C. medinals ABCs (CmABCs), including CmABCG1, CmABCG4, CmABCC2 and CmABCC3. Tissue expression analysis showed that these genes had a tissue-specific expression pattern. CmABCG1 had significantly higher expression in the haemolymph and head compared to the other tissues. The expression of CmABCG4, CmABCC2 and CmABCC3 was highest in the midgut, followed by expression in the fat body. The developmental stage expression analysis showed that CmABCG1, CmABCG4, CmABCC2 and CmABCC3 were mainly expressed in adults. The transcription of CmABCG1, CmABCG4 and CmABCC2 was significantly induced by chlorpyrifos. Taken together, the results of our study provided useful information for understanding of the detoxification system of C. medinalis.

[Abnormal Expression and Clinical Significance of B Lymphocyte Stimulating Factor in B Cell-derived Malignant Hematologic Diseases].

OBJECTIVE: To explore the expression and clinical significance of B cell lymphocyte stimulating factor (BLyS) in B cell-derived malignant hematological diseases. METHODS: Fifty-seven cases of newly diagnosed B cell-derived hematologic malignancies were admitted and treated in our hospital from March 2015 to 2016 July. including 17 cases of multiple myeloma(MM) (A group) and 40 cases of B cell non-Hodgkin's lymphoma(B-NHL) (B group), 30 healthy volunteers were enrolled in control group(C group). The BLyS level in peripheral blood of A,B and C groups was detected by ELISA kit; for patient with hematologic malignancies, the BLyS level was detected again after chemotherapy and was compared with level before chemotherapy. RESULTS: The BLyS level in patients with B cell-derived hematologic malignancies significantly increased, as compared with healthy volanteers(P<0.05). After chemotherapy, the BLyS level in patients all significantly dicreased (P<0.05); the BLyS level in peripheral blood of DLBCL and FL patients was significantly higher than that in patients with B-NHL of other types(P<0.05); the BLyS level in peripheral blood of patients at III-IV stage was significantly higher than that in patients at I-II stage. CONCLUSION: The BLyS expression in B cell derived hematologic malignancies significantly increases, moreover the its expression level in B-NHL patients at different stages and histologic types is different, suggesting that detection of BLyS expression level in patients in vivo possesses a certain guiding role for diagnosis, staging and treatment of B cell-derived hematologic malignancies.

Association between tumor necrosis factor-α gene polymorphisms and diffuse large B-cell lymphoma in Chinese Han population: evidence from two center case-control study and a meta-analysis.

OBJECTIVES: The tumor necrosis factor-α (TNF-α) gene, which plays crucial roles in tumorigenesis, is reported to be an independent marker for cancer. This study aims to examine the association between the TNF-α G308A polymorphism and DLBCL risk based on the two center case-control studies and meta-analysis. METHODS: In the current study, we performed a two centers case-control study to investigate the effect of the TNF-α G308A polymorphism on DLBCL risk in Chinese Han population. A meta-analysis including 10 published datasets along with current dataset, including 111 comparisons containing 34,041 cases and 42,730 controls were enrolled, was next performed to further confirm the association after literature search was conducted and relevant studies were identified from PubMed, Embase, and Web of Science. RESULTS: The TNF-α -308A allele was associated with a significantly increased DLBCL risk in the two independent patient case-control studies and additionally for pooled analysis from the two sets (P<0.05 for both). The result of meta-analysis further demonstrated that the A allele of -308A was significantly correlated with DLBCL risk under the allelic model (OR=1.35, 95% CI=1.27-1.44) without heterogeneity by fixed-effects model analysis (Q=17.30, P=0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis. CONCLUSION: This study suggested that -308A polymorphism may be associated with the susceptibility of DLBCL in a Chinese population. The further meta-analysis provides additional evidence supporting the above result that the risk allele of the -308A polymorphism may increase DLBCL risk.