Mechanisms of Dangua Fang in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.

OBJECTIVE: To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics. METHODS: Sprague-Dawley rats with normal glucose levels were randomly divided into three groups, including a conventional diet control group (Group A), high-fat-high-sugar diet model group (Group B), and DGR group (Group C, high-fat-high-sugar diet containing 20.5 g DGR). After 10 weeks of intervention, the fasting blood glucose (FBG), 2 h blood glucose [PBG; using the oral glucose tolerance test (OGTT)], hemoglobin A1c (HbA1c), plasma total cholesterol (TC), and triglycerides (TG) were tested, and the livers of rats were removed to calculate the liver index. Then, hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis followed by database search and bioinformatics analysis. Finally, cell experiments were used to verify the results of phosphoproteomics. Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4 (MAP4k4) and phosphorylated adducin 1 (ADD1) were detected using western blotting. RESULTS: DGR effectively reduced PBG, TG, and the liver index (P < 0.05), and significantly decreased HbA1c, TC, and hepatic portal TG (P < 0.01), showed significant hematoxylin and eosin (HE) staining, red oil O staining, and Masson staining of liver tissue. The total spectrum was 805 334, matched spectrum was 260 471, accounting for accounting 32.3%, peptides were 19 995, modified peptides were 14 671, identified proteins were 4601, quantifiable proteins were 4417, identified sites were 15 749, and quantified sites were 14659. Based on the threshold of expression fold change ( > 1.2), DGR up-regulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins, and down-regulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins, which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism. Therefore, DGR improved biological tissue processes, including information storage and processing, cellular processes and signaling, and metabolism. The metabolic functions regulated by DGR mainly include energy production and conversion, carbohydrate transport and metabolism, lipid transport and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism. In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies. CONCLUSION: DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders, thereby regulating glycolipid metabolism through a multi-target and multi-method process.

Bioconjugation of nanozyme and natural enzyme to enable a one-step cascade reaction for the detection of metabolites.

Nanozyme, with enzyme-mimicking activity and excellent stability, has attracted extensive attention. However, some inherent disadvantages, including poor dispersion, low selectivity, and insufficient peroxidase-like activity, still limit its further development. Therefore, an innovative bioconjugation of a nanozyme and natural enzyme was conducted. In the presence of graphene oxide (GO), histidine magnetic nanoparticles (H-Fe3O4) were first synthesized by a solvothermal method. The GO-supported H-Fe3O4 (GO@H-Fe3O4) exhibited superior dispersity and biocompatibility because GO was the carrier and possessed outstanding peroxidase-like activity because of the introduction of histidine. Furthermore, the mechanism of the peroxidase-like activity of GO@H-Fe3O4 was the generation of •OH. Uric acid oxidase (UAO) was selected as the model natural enzyme and covalently linked to GO@H-Fe3O4 with hydrophilic poly(ethylene glycol) as a linker. UAO could specifically catalyze the oxidation of uric acid (UA) to generate H2O2, and subsequently, the newly produced H2O2 oxidized the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB under the catalysis of GO@H-Fe3O4. Based on the above cascade reaction, the GO@H-Fe3O4-linked UAO (GHFU) and GO@H-Fe3O4-linked ChOx (GHFC) were used for the detection of UA in serum samples and cholesterol (CS) in milk, respectively. The method based on GHFU exhibited a wide detection range (5-800 µM) and a low detection limit (1.5 µM) for UA, and the method based on GHFC exhibited a wide detection range (4-400 µM) and a low detection limit (1.13 µM) for CS. These results demonstrated that the proposed strategy had great potential in the field of clinical detection and food safety.

Bioconjugation of nanozyme and natural enzyme for ultrasensitive detection of cholesterol.

When nanozymes are used in biological analysis, higher activity can improve the detection sensitivity, and better selectivity can eliminate other interference. To improve the specificity and sensitivity, we fabricated an innovative bioconjugated nanozyme with natural enzyme (BNNZ), in which natural ChOx was immobilized onto histidine-modified Fe3O4 (His-Fe3O4) with hydrophilic poly(ethylene glycol) (PEG) as a linker. ChOx could specifically catalyze the oxidation of cholesterol to generate H2O2 molecule, and then the newly formed H2O2 oxidized the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue ox-TMB by peroxidase-like His-Fe3O4. According to the above cascade reaction, the BNNZ-based colorimetric strategy was proposed for the detection of cholesterol. Wherein, natural enzymes specifically catalyzed substrates, which endowed BNNZ with excellent specificity for target molecules; meanwhile, the introduction of histidine on His-Fe3O4 effectively increased the peroxidase-like activity of BNNZ, which provided a guarantee for sensitivity. Furthermore, BNNZ after reaction could be rapidly separated by an external magnetic field without interfering with colorimetric quantitative detection. The proposed strategy exhibited excellent sensitivity with limit of detection of 0.446 µM and was successfully used for the detection of cholesterol in spiked human serum sample with recovery and relative standard deviation in the range of 97.9-103.5% and 2.5-4.0%, respectively. This work indicates that the bioconjugation of nanozyme and natural enzyme may be a universal strategy for synthesis of high-performance enzyme-nanozyme systems, and the new-type BNNZ will be widely used in biological detection and disease treatment.

Fabrication of self-healing magnetic nanoreceptors for glycoprotein via integrating boronate-affinity-oriented and sequential surface imprinting.

Molecularly imprinted polymers (MIPs) as artificial receptors have been widely applied in various fields. However, construction of MIPs for precise recognition of glycoprotein still remains a rather challenging task. To overcome this problem, we first fabricated boronate-affinity-oriented and sequential-surface imprinting magnetic nanoparticles (BSIMN) through integrating the boronate-affinity-oriented and sequential surface imprinting. The boronate-affinity-oriented immobilization of glycoprotein template endowed the BSIMN with homogeneous imprinted cavities. In addition, the polydopamine (PDA) imprinted layer was introduced by self-polymerization of dopamine in the first imprinting process, and then the phenylboronic acid (PBA) imprinted layer was introduced by boronate-affinity interaction in the second imprinting process. Surprisingly, the PBA imprinted layer possessed self-healing property due to the presence of pH-dependent boronate-affinity interaction between two imprinted layers. Therefore, the fabricated BSIMN exhibited excellent selectivity toward glycoprotein templates. To quantitatively detect glycoproteins in biological samples, the BSIMN was linked with hydrophilic rhodamine B-loaded/boronic acid-modified graphene oxide (HRBGO), which could selectively label glycoprotein and output amplified signal. In quantitative analysis, target glycoproteins were firstly captured by BSIMN and then specifically labeled by HRBGO; subsequently, the releasing agent was added to release numerous rhodamine B from HRBGO, and the corresponding fluorescence signal was used for further quantitative analysis. The proposed strategy showed ultrahigh sensitivity for ovalbumin, carcinoembryonic antigen and alpha fetoprotein with limit of detection of 4.5 fg mL-1, 3.6 fg mL-1 and 4.2 fg mL-1, respectively, and was successfully applied in determination of these glycoproteins in serum samples.

Construction of PEGylated boronate-affinity-oriented imprinting magnetic nanoparticles for ultrasensitive detection of ellagic acid from beverages.

Molecularly imprinted polymers (MIPs) can exhibit antibody-level affinity for target molecules. However, the nonspecific adsorption of non-imprinted regions for non-target molecules limits the application range of MIPs. Herein, we fabricated PEGylated boronate-affinity-oriented ellagic acid-imprinting magnetic nanoparticles (PBEMN), which first integrated boronate-affinity-oriented surface imprinting and sequential PEGylation for small molecule-imprinted MIPs. The resultant PBEMN possess higher adsorption capacity and faster adsorption rate for template ellagic acid (EA) molecules than the non-PEGylated control. To prove the excellent performance, the PBEMN were linked with hydrophilic boronic acid-modified/fluorescein isothiocyanate-loaded graphene oxide (BFGO), because BFGO could selectively label cis-diol-containing substances by boronate-affinity and output ultrasensitive fluorescent signals. Based on a dual boronate-affinity synergy, the PBEMN first selectively captured EA molecules by boronate-affinity-oriented molecular imprinted recognition, and then the EA molecules were further labeled with BFGO through boronate-affinity. The PBEMN linked BFGO (PBPF) strategy provided ultrahigh sensitivity for EA molecules with a limit of detection of 39.1 fg mL-1, resulting from the low nonspecific adsorption of PBEMN and the ultrasensitive fluorescence signal of BFGO. Lastly, the PBPF strategy was successfully employed in the determination of EA concentration in a spiked beverage sample with recovery and relative standard deviation in the range of 96.5 to 104.2% and 3.8 to 5.1%, respectively. This work demonstrates that the integration of boronate-affinity-oriented surface imprinting and sequential PEGylation may be a universal tool for improving the performance of MIPs.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

Enhancer of zeste homolog 2 contributes to apoptosis by inactivating janus kinase 2/ signal transducer and activator of transcription signaling in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a prevalent worldwide health problem featured by relapsing, chronic gastrointestinal inflammation. Enhancer of zeste homolog 2 (EZH2) is a critical epigenetic regulator in different pathological models, such as cancer and inflammation. However, the role of EZH2 in the IBD development is still obscure. AIM: To explore the effect of EZH2 on IBD progression and the underlying mechanism. METHODS: The IBD mouse model was conducted by adding dextran sodium sulfate (DSS), and the effect of EZH2 on DSS-induced colitis was assessed in the model. The function of EZH2 in regulating apoptosis and permeability was evaluated by Annexin V-FITC Apoptosis Detection Kit, transepithelial electrical resistance analysis, and Western blot analysis of related markers, including Zona occludens 1, claudin-5, and occludin, in NCM460 and fetal human colon (FHC) cells. The mechanical investigation was performed by quantitative reverse transcription-polymerase chain reaction, Western blot analysis, and chromatin immunoprecipitation assays. RESULTS: The colon length was inhibited in the DSS-treated mice and was enhanced by the EZH2 depletion in the system. DSS treatment caused a decreased histological score in the mice, which was reversed by EZH2 depletion. The inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, and interleukin-1ß, were induced in the DSS-treated mice, in which the depletion of EZH2 could reverse this effect. Moreover, the tumor necrosis factor-α treatment induced the apoptosis of NCM460 and FHC cells, in which EZH2 depletion could reverse this effect in the cells. Moreover, the depletion of EZH2 attenuated permeability of colonic epithelial cells. Mechanically, the depletion of EZH2 or EZH2 inhibitor GSK343 was able to enhance the expression and the phosphorylation of janus kinase 2 (JK2) and signal transducer and activator of transcription in the NCM460 and FHC cells. Specifically, EZH2 inactivated JAK2 expression by regulating histone H3K27me3. JAK2 inhibitor TG101348 was able to reverse EZH2 knockdown-mediated colonic epithelial cell permeability and apoptosis. CONCLUSION: Thus, we concluded that EZH2 contributed to apoptosis and inflammatory response by inactivating JAK2/ signal transducer and activator of transcription signaling in IBD. EZH2 may be applied as a potential target for IBD therapy.

College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer.

BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

Chemotherapy in Combination With Radiotherapy for Definitive-Intent Treatment of Stage II-IVA Nasopharyngeal Carcinoma: CSCO and ASCO Guideline.

PURPOSE: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other healthcare providers on definitive-intent chemoradiotherapy for patients with stage II-IVA nasopharyngeal carcinoma (NPC). METHODS: The Chinese Society of Clinical Oncology (CSCO) and ASCO convened an expert panel of radiation oncology, medical oncology, surgery, and advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. Outcomes of interest included survival, distant and locoregional disease control, and quality of life. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 108 relevant studies to inform the evidence base for this guideline. Five overarching clinical questions were addressed, which included subquestions on radiotherapy (RT), chemotherapy sequence, and concurrent, induction, and adjuvant chemotherapy options. RECOMMENDATIONS: Evidence-based recommendations were developed to address aspects of care related to chemotherapy in combination with RT for the definitive-intent treatment of stage II to IVA NPC.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Clinical and electrophysiological features of patients with coexistence of epilepsy and narcolepsy / 中华神经科杂志

Objective:To describe the electroclinical features of the coexistence of epilepsy and narcolepsy.Methods:The electroencephalography database was searched using the terms “epilepsy” and “narcolepsy” over a four-year period from January 2016 to December 2019 in the Xijing Hospital. The clinical and electrophysiological characteristics of patients with coexistence of epilepsy and narcolepsy were studied.Results:Five patients with comorbidity for epilepsy and narcolepsy were found, of which three patients were female, two patients were male. The age at epilepsy onset and narcolepsy onset was 2-12 years and 8-17 years, respectively. There were two patients with juvenile myoclonic epilepsy, one with sleep-related hypermoter epilepsy, one with epilepsy with retardation of brain development, one with symptomatic epilepsy with cognitive decline. All the patients had narcolepsy with cataplexy, which followed the onset of epilepsy by three months to eight years. All the patients accepted 24 h video electroencephalography monitoring and multiple sleep latency test. Interictal epileptic discharges were found, mean sleep latency was<8 min, and two or more sleep onset rapid eye movement periods were recorded. Duloxetine hydrochloride can effectively improve the drowsiness and catalepsy symptoms of narcolepsy, and seizures did not worsen in patients using duloxetine hydrochloride.Conclusions:Both generalized and focal epilepsy can occur in narcolepsy with cataplexy. Duloxetine hydrochloride may be safe and effective in treating narcolepsy in patients with epilepsy.

Seizure clusters / 中华神经科杂志

Seizure cluster (SC) is a common clinical phenomenon in patients with epilepsy, which was reported to be associated with post-ictal psychosis, status epilepticus, and increased risk of death, with a negative impact on the quality of life of patients and caregivers, but the diagnostic criteria, management principles and pathogenesis of SC are still unclear."seizure cluster" "acute repitetive seizures" and "cluster seizures" were used to search the relevant literatures in the databases of "Pubmed" "Wanfang Medicine" and "China Knowledge Network" from 1990 to 2019. The definitions, prevalence, risk factors, consequences, possible mechanism, and current management methods of seizure clusters were summaried in this article, to help health care professionals and patients gain a clearer understanding of SC.

Research on the electro-clinical aspects of epilepsy patients with breach rhythm / 中华神经科杂志

Objective:To investigate the clinical characteristics and electroencephalogram (EEG) of epilepsy patients with breach rhythm, improve clinical understanding of breach rhythm and avoid over-interpretation.Methods:Twelve epilepsy patients with breach rhythm who visited the Department of Neurology, Xijing Hospital, the Air Force Military Medical University from January 2016 to January 2017 were collected retrospectively. The clinical data, including etiology, clinical manifestations, EEG features and prognosis were summarized, and outpatient and telephone follow-up was performed for at least three years.Results:The clinical data of 12 patients with epilepsy with breach rhythm were collected, including eight males and four females, aged 36-78 years. After analysis, it was found that brain trauma was the most common cause of breach rhythm. Among them, two cases of skull defect were not repaired, eight cases were repaired with skull titanium mesh, one case was repaired with skull polymethylmethacrylate, and one case was repaired with skull polyetheretherketone. The distribution of the breach rhythm in 12 patients was consistent with the abnormal area of the skull. The breach rhythm can be expressed as high amplitude and fast frequency, or low amplitude and slow frequency and appear individually (similar to sharp waves, spikes). On the basis of pleomorphic slow waves, 10 patients were mixed with sharp waves and spike waves, and imaging confirmed that they had brain damage in corresponding parts. All of the 12 patients had a history of seizures, with tonic-clonic seizures and (or) focal seizures being the most common. Three patients with breach rhythm had no clinical seizures for more than five years, and had been taking antiepileptic drugs for epileptic spikes on EEG, and they were given reduction and discontinuation of the drugs and were seizure-free for three years during follow up.Conclusions:Skull repair is a common cause of breach rhythm, and repair materials with different resistances cause different waveforms and frequencies. Breach rhythm, epileptiform discharge and other pathological slow-wave activities can exist at the same time. Breach rhythm is a benign variant phenomenon which needs no special treatment.

Preoperative platelet-lymphocyte ratio is a superior prognostic biomarker to other systemic inflammatory response markers in non-small cell lung cancer.

Systemic inflammatory response markers are associated with poor survival in many types of malignances. This study aimed to evaluate the prognostic value of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein (CRP) in patients with non-small cell lung cancer (NSCLC).We retrospectively evaluated 254 NSCLC patients who underwent radical surgery between January 2012 and April 2014 in the Sichuan Provincial Cancer Hospital. The cut-off values of NLR, PLR, LMR, and CRP were determined according to the receiver operating characteristic curve, and the correlation of NLR, PLR, LMR, and CRP with prognosis was analyzed based on the cut-off value.The cut-off value for NLR, PLR, LMR, and CRP were 3.18, 122, 4.04, and 8.8, respectively. Univariate analysis showed that age (P = .022), tumor-node-metastasis (TNM) stage (P < .001), T stage (P = .001), and N stage (P < .001) were significantly correlated with disease-free survival (DFS), while age (P = .011), TNM stage (P < .001), T stage (P = .008), N stage (P < .001), and PLR (P = .001) were significantly correlated with overall survival (OS). In multivariate analysis, age (hazard ratio [HR]: 1.564, 95% confidence interval [CI]: 1.087-2.252, P = .016) and TNM stage (HR: 1.704, 95% CI: 1.061-2.735, P = .027) remained independent risk factors affecting DFS, while age (HR: 1.721, 95% CI: 1.153-2.567, P = .008), TNM stage (HR: 2.198, 95% CI: 1.263-3.824, P = .005), and PLR (HR: 1.850, 95% CI: 1.246-2.746, P = .002) were independent risk factors affecting OS.The preoperative PLR is superior to NLR, LMR, and CRP as a biomarker for evaluating the prognosis of patients undergoing curative surgery for NSCLC.

Comprehensively investigating the expression levels and the prognostic role of transforming growth factor beta-induced (TGFBI) in glioblastoma multiforme.

BACKGROUND: Transforming growth factor beta-induced (TGFBI) protein has been found expressed in several cancer types, and expression levels of TGFBI can affect the cancer patients' outcomes, but the role of TGFBI in glioblastoma multiforme (GBM) remains obscure. METHODS: The TGFBI expression levels in GBM were performed via Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN databases. Further, the mutations types of TGFBI were analyzed by using the cBioportal dataset. LinkedOmics selected correlated genes, kinases, and microRNA (miRNA) targets of TGFBI. GEPIA conducted the prognostic value of TGFBI and correlated genes. Then, the relationship between TGFBI and immune infiltrates was performed by Tumor Immune Estimation Resource (Timer). We compared the TGFBI protein expression levels in GBM and control samples through the Human Protein Atlas (HPA). Finally, the GSCAlite was used to achieve the drugs, and molecules target the TGFBI and significantly correlated genes. RESULTS: TGFBI is significantly overexpressed in GBM, but the clinical features do not have considerable influence on TGFBI expression levels. Overexpression of TGFBI acts as an adverse biomarker of GBM. The enrichment function of TGFBI showed that the main biological functions, including extracellular matrix (ECM) organization, angiogenesis, leukocyte migration, T cell activation, cell cycle G2/M phase transition, and growth factor binding. About the significant correlated genes, overexpression of mitogen-activated protein kinase 13 (MAPK13) [Log-rank P=0.08 HR (high) =1.4], myosin IG (MYO1G) [Log-rank P=0.06 HR (high) =1.4], plasminogen activator urokinase receptor (PLAUR) [Log-rank P=0.03 HR (high) =1.5], thrombomodulin (THBD) [Log-rank P=0.028 HR (high) =1.5] indicated the poor prognosis of GBM. Further, TGFBI had a significant association with dendritic cell (DC) infiltrates (cor =0.516, P=9.00e-30). The higher the DC infiltration, the shorter survival of GBM. TGFBI protein expression levels were not significantly different in GBM and normal tissue. Finally, TGFBI is associated with resistance to belinostat, LAQ824, CAY10603, CUDC-101, methotrexate, 5-fluorouracil, and navitoclax. CONCLUSIONS: In the present study, we showed TGFBI was overexpressed in GBM, and TGFBI is associated with DC cell infiltrates. Overexpression of TGFBI and high DC infiltration might be an adverse biomarker of GBM. Finally, TGFBI is associated with tumor multi-drug resistance.

Clinical and electrophysiological study of propriospinal myoclonus / 中华神经科杂志

Objective:To discuss the clinical and electrophysiological characteristics of propriospinal myoclonus (PSM).Methods:The clinical and electrophysiological characteristics of four patients diagnosed as PSM in the Electroencephalography Monitoring Center, Department of Neurology, Xijing Hospital, the Air Force Military Medical University from April 2018 to July 2019 were studied. All patients were accorded with diagnostic criteria of PSM that international classification of sleep disorders-3 edition recommended and were followed up.Results:There were three males and one female in the four patients. The age of onset was ranged from 43 to 55 years. The course was from eight months to three years, and the follow-up time was from three months to one year. The clinical features of the four patients were characteristically paroxysmal tic or shaking of the neck, trunk or limbs, with short duration and great frequency. All patients accepted 24-hour video electroencephalography monitoring. No epileptic discharge was recorded during the monitoring. The burst activity of deltoid, quadriceps or rectus abdominis muscle was monitored by surface electromyography at the onset of myoclonus. All patients were treated with clonazepam. Three patients had an obvious curative effect and one patient had no effect.Conclusions:The clinical manifestation of PSM is similar to seizures. There is no epileptic discharge, and only the burst activity of muscles is monitored at the onset. Most patients have significant effect on clonazepam.

Inhibition of ZIP4 reverses epithelial-to-mesenchymal transition and enhances the radiosensitivity in human nasopharyngeal carcinoma cells.

ZIP4 is a zinc transporter involved in epithelial cell morphology and migration in various cancers. In the epithelial-to-mesenchymal transition (EMT), epithelial cells transition into mesenchymal cells. The EMT plays a crucial role in invasiveness and metastasis during tumorigenesis. The aim of this study was to investigate the role of ZIP4 in the invasiveness and radiosensitivity of human nasopharyngeal carcinoma (NPC). In this study, results from 99 human patients with NPC showed that ZIP4 expression levels significantly correlated with a higher TN (tumor, lymph node) classification, as well as shorter overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Forced overexpression of ZIP4 promoted the migration and invasion of C666-1 cells through regulation of the EMT process. In contrast, ZIP4 silencing by lentivirus-mediated shRNA inhibited the EMT and metastasis of C666-1 cells in vitro and in vivo. Importantly, protein microarray analyses showed that downregulation of ZIP4 in C666-1 cells resulted in the decreased abundance of phosphoinositide 3-kinase (PI3K) p85 (Tyr607), phosphorylated (p)-Akt (Ser473), phosphorylated (p)-Akt (Thr308), and phosphorylated glycogen synthase kinase 3ß (pGSK3ß; Ser9). These data suggest that ZIP4 induces the EMT and promotes migration and invasion via the PI3K/Akt signaling pathway in NPC. Moreover, ZIP4 silencing significantly enhanced radiation-induced apoptosis and growth inhibition of human C666-1 cells in vitro and enhanced the antitumor activity of ionizing radiation (IR), leading to tumor growth inhibition in vivo. These results demonstrate that ZIP4 is a novel prognostic factor for malignant NPC progression. More importantly, targeting ZIP4, along with radiotherapy, may be an effective new treatment for NPC.

Recognition of the breach rhythm / 中华神经科杂志

Breach rhythm was firstly described in 1979, and is considered as a rare benign variant of electroencephalogram. The etiology, electroencephalogram features and evaluation of breach rhythm, and so on, are discussed in this article.

Primary undifferentiated pleomorphic sarcoma of the thyroid: A case report and review of the literature.

RATIONALE: Primary undifferentiated pleomorphic sarcoma is extremely rare in the thyroid, and can be easily misdiagnosed as anaplastic thyroid cancer. PATIENT CONCERNS: We present a case of a 71-year-old woman who presented with a rapidly growing painless mass in the neck. DIAGNOSES-INTERVENTIONS-OUTCOMES: Computed tomography showed a large hypointense mass with hyperdense areas involving whole of the right lobe of thyroid gland and fine-needle aspiration cytology found a few atypical cells. Surgical exploration was performed subsequently and frozen section showed malignant tumor. Therefore, a total thyroidectomy, central, and bilateral lateral neck dissection were performed and adjuvant radiotherapy of 60 Gy was administered. The patient was alive and had no recurrence at 6-month follow-up. LESSONS: Although primary undifferentiated pleomorphic sarcoma in the thyroid is extremely rare, patients who presented with a rapidly growing painless mass in the neck should be considered and it is essential to excise the tumor completely as soon as possible.

Prognostic value of neutrophil-to-lymphocyte ratio for nasopharyngeal carcinoma: A meta-analysis.

BACKGROUND: The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) for nasopharyngeal carcinoma (NPC) remains controversial. This study was designed to provide a more accurate assessment of the prognostic value, based on a meta-analysis. METHODS: A comprehensive search for relevant studies published before June 2016 was performed using the PubMed, Cochrane Library, and Web of Science databases. The correlations of NLR with overall survival (OS) and progression-free survival (PFS) were evaluated for NPC. Hazard ratios (HRs) and associated 95% confidence intervals (CIs) were calculated to estimate the effects. RESULTS: Six studies with a total of 4359 NPC patients were included in this meta-analysis. The pooled results showed that, among patients with NPC, elevated pretreatment NLR was associated with poorer OS (HR = 1.74, 95% CI = 1.45-2.10) and PFS (HR = 1.48, 95% CI = 1.30-1.69). Subgroup analyses indicated that the use of different cut-off values for NLR (<3 or ≥3) did not affect the consistent prognostic value of NLR for OS or PFS. No significant heterogeneity or publication bias was observed among the included studies for OS or PFS (P > .05). CONCLUSIONS: This meta-analysis indicates that elevated pretreatment NLR might be a valuable predicative biomarker of poor prognosis for patients with NPC.

New Evidence and Perspectives on the Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

Portal vein tumor thrombosis (PVTT) is an intractable condition but common phenomenon in hepatocellular carcinoma (HCC). HCC patients with PVTT may have worse liver function, a higher chance of comorbidity related to portal hypertension, lower tolerance to treatment and poorer prognoses. In Western guidelines, patients are offered palliative treatment with sorafenib or other systemic agents because HCC with PVTT is grouped together with metastatic HCC during the planning of its management. In recent years, various treatment options have become available for patients with HCC and PVTT. Therapy has also shifted toward evidence-based treatment. However, policies for the management of HCC with PVTT have not been established. This comprehensive literature review aims to present current and available management options for patients with HCC and PVTT. Evidence is mainly based on studies published after 2010.