Prognostic significance of platelet­to­albumin ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: a retrospective study of 858 cases.

BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Prognostic significance of the novel nutrition-inflammation marker of lymphocyte-C-reactive protein ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy.

Background: Recent studies indicate that the novel lymphocyte-C-reactive protein ratio (LCR) is strongly associated with the survival of various tumors, but its prognostic value in nasopharyngeal carcinoma (NPC) is understudied. This study aimed to explore the relationship between LCR and overall survival (OS) in NPC and develop a predictive model. Methods: A total of 841 NPC patients who received concurrent chemoradiotherapy (CCRT) between January 2010 and December 2014 were retrospectively enrolled and randomly divided into a training cohort (n = 589) and a validation cohort (n = 252), and 122 patients between January 2015 and March 2015 were included as an additional validation cohort. Univariate and multivariate Cox analyses were performed to identify variables associated with OS and construct a predictive nomogram. The predictive accuracy of the nomogram was evaluated and independently validated. Results: The LCR score differentiated NPC patients into two groups with distinct prognoses (HR = 0.53; 95% CI: 0.32-0.89, P = 0.014). Multivariate analysis showed that age, T stage, N stage, EBV-DNA status, and LCR score were independently associated with OS, and a predictive nomogram was developed. The nomogram had a good performance for the prediction of OS [C-index = 0.770 (95% CI: 0.675-0.864)]. and outperformed the traditional staging system [C-index = 0.589 (95% CI: 0.385-0.792)]. The results were internally and additionally validated using independent cohorts. Conclusion: The pretreatment LCR could independently predict the overall survival in NPC patients. A novel LCR-based prognostic model of an easy-to-use nomogram was established, and it outperformed the conventional staging system in terms of predictive power. Further external verification remains necessary.

A single center retrospective study assessing the prognostic significance of pre-treatment neutrophil/lymphocyte ratio in locally advanced nasopharyngeal carcinoma.

Background: In light of the growing evidence suggesting the impact of inflammatory parameters on the survival of individuals with cancer, this research assessed the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) in individuals diagnosed with locally advanced nasopharyngeal carcinoma (NPC) prior to undergoing intensity-modulated radiation therapy (IMRT). Methods: A total of 163 individuals diagnosed with locally advanced NPC treated with IMRT at our hospital between January 2012 and December 2017 were included in this research. For each patient, the absolute counts of neutrophils and lymphocytes were recorded, and the NLR was calculated at the first diagnosis. To determine the optimal cut-off values for NLR, receiver operating characteristic (ROC) curve analysis was conducted. The effects of the determined cut-off value on local failure-free survival (LFFS), overall survival (OS), progression-free survival (PFS), and distant failure-free survival (DFFS) were evaluated employing the Cox regression model. Results: The median follow-up duration for the individuals in this study was 15 months (ranging from 6 to 79 months). According to the determined NLR cut-off value of 3.27, individuals were classified into two groups (high NLR and low NLR). Individuals in the high-NLR group had remarkably poorer 3-year OS (62.8% vs. 91.7%), PFS (51.4% vs. 82.4%), and DFFS (70.7% vs. 89.6%) compared to the low-NLR group. Furthermore, the outcomes of univariate and multivariate survival analyses revealed that NLR served as an independent predictor of DFFS (HR: 2.81, 95% CI: 1.195-6.608, P=0.018), OS (HR: 3.1, 95% CI: 1.211-7.935, P=0.018), and PFS (HR: 2.21, 95% CI: 1.133-4.292, P=0.02). Conclusions: Elevated NLR exhibited a significant correlation with reduced OS, DFFS, and PFS. These findings suggest that NLR holds promise as a cost-effective and reliable marker for the prediction of clinical outcomes among patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Furthermore, incorporating NLR into clinical decision-making regarding LANPC treatment strategies may contribute to a more targeted approach aimed at reducing the risk of distant failure.

The Disorazole Z Family of Highly Potent Anticancer Natural Products from Sorangium cellulosum: Structure, Bioactivity, Biosynthesis, and Heterologous Expression.

Myxobacteria serve as a treasure trove of secondary metabolites. During our ongoing search for bioactive natural products, a novel subclass of disorazoles termed disorazole Z was discovered. Ten disorazole Z family members were purified from a large-scale fermentation of the myxobacterium Sorangium cellulosum So ce1875 and characterized by electrospray ionization-high-resolution mass spectrometry (ESI-HRMS), X-ray, nuclear magnetic resonance (NMR), and Mosher ester analysis. Disorazole Z compounds are characterized by the lack of one polyketide extension cycle, resulting in a shortened monomer in comparison to disorazole A, which finally forms a dimer in the bis-lactone core structure. In addition, an unprecedented modification of a geminal dimethyl group takes place to form a carboxylic acid methyl ester. The main component disorazole Z1 shows comparable activity in effectively killing cancer cells to disorazole A1 via binding to tubulin, which we show induces microtubule depolymerization, endoplasmic reticulum delocalization, and eventually apoptosis. The disorazole Z biosynthetic gene cluster (BGC) was identified and characterized from the alternative producer S. cellulosum So ce427 and compared to the known disorazole A BGC, followed by heterologous expression in the host Myxococcus xanthus DK1622. Pathway engineering by promoter substitution and gene deletion paves the way for detailed biosynthesis studies and efficient heterologous production of disorazole Z congeners. IMPORTANCE Microbial secondary metabolites are a prolific reservoir for the discovery of bioactive compounds, which prove to be privileged scaffolds for the development of new drugs such as antibacterial and small-molecule anticancer drugs. Consequently, the continuous discovery of novel bioactive natural products is of great importance for pharmaceutical research. Myxobacteria, especially Sorangium spp., which are known for their large genomes with yet-underexploited biosynthetic potential, are proficient producers of such secondary metabolites. From the fermentation broth of Sorangium cellulosum strain So ce1875, we isolated and characterized a family of natural products named disorazole Z, which showed potent anticancer activity. Further, we report on the biosynthesis and heterologous production of disorazole Z. These results can be stepping stones toward pharmaceutical development of the disorazole family of anticancer natural products for (pre)clinical studies.

Genome-Guided Discovery of the Myxobacterial Thiolactone-Containing Sorangibactins.

In this study, an unprecedented myxobacterial siderophore termed sorangibactin was discovered by heterologous expression of a coelibactin-like nonribosomal peptide synthetase (NRPS) gene cluster from the Sorangiineae strain MSr11367 in the host Myxococcus xanthus DK1622. De novo structure elucidation uncovered a linear polycyclic structure consisting of an N-terminal phenol group, an oxazole, tandem N-methyl-thiazolidines, and an unusual C-terminal γ-thiolactone moiety. Except for the unprecedented oxazoline dehydrogenation to form an oxazole, which we show to be catalyzed by a cytochrome P450-dependent enzyme, other tailoring steps were found necessary for efficient downstream processing. The unusual thioesterase (TE) domain is proposed to select homocysteine or methionine for offloading involving an intramolecular γ-thiolactone formation. Its active site comprises a rare cysteine, which was found essential for product formation by point mutation to alanine or serine, which both abolished its activity. This unusual release mechanism and the resulting rare thiolactone structure can serve as a starting point for detailed biochemical investigations.

The prognostic significance of human ovarian aging-related signature in breast cancer after surgery: A multicohort study.

Background: Recent studies have shown that ovarian aging is strongly associated with the risk of breast cancer, however, its prognostic impact on breast cancer is not yet fully understood. In this study, we performed a multicohort genetic analysis to explore its prognostic value and biological features in breast cancer. Methods: The gene expression and clinicopathological data of 3366 patients from the The Cancer Genome Atlas (TCGA) cohort, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort and the GSE86166 cohort were analyzed. A total of 290 ovarian aging-related genes (OARGs) were included in the establishment of the prognostic model. Furthermore, functional mechanisms analysis, drug sensitivity, and immune cell infiltration were investigated using bioinformatic methods. Results: An eight OARG-based signature was established and validated using independent cohorts. Two risk subgroups of patients with distinct survival outcomes were identified by the OARG-based signature. A nomogram with good predictive performance was developed by integrating the OARG risk score with clinicopathological factors. Moreover, the OARG-based signature was correlated with DNA damage repair, immune cell signaling pathways, and immunomodulatory functions. The patients in the low-risk subgroup were found to be sensitive to traditional chemotherapeutic, endocrine, and targeted agents (doxorubicin, tamoxifen, lapatinib, etc.) and some novel targeted drugs (sunitinib, pazopanib, etc.). Moreover, patients in the low-risk subgroup may be more susceptible to immune escape and therefore respond less effectively to immunotherapy. Conclusions: In this study, we proposed a comprehensive analytical method for breast cancer assessment based on OARG expression patterns, which could precisely predict clinical outcomes and drug sensitivity of breast cancer patients.

Prognostic value of nasopharynx tumour volume in local-regional advanced nasopharyngeal carcinoma.

BACKGROUND: To investigate the prognostic value of pretreatment primary gross tumor with (GTVp) and without retropharyngeal lymph nodes (GTVnx) for predicting survival outcomes in patients with local-regional advanced nasopharyngeal carcinoma (NPC) after intensity-modulated radiation therapy (IMRT). METHODS: From Jan 2012 to Dec 2017, 148 patients with local-regional advanced NPC who had undergone definitive radiotherapy were identified. GTVnx volume and retropharyngeal lymph nodes (GTVrLNs) volume were measured based on registration of MRI with contrast-enhanced CT images. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate prognostic analyses was performed by using the Cox proportional hazard model. Receiver operating characteristic (ROC) curves were used to identify the cut-off point and assess the prognostic value for GTVnx, GTVp and GTVrLNs. RESULTS: The median follow-up time for the entire group was 27 months (ranging 7 to 80 months). The 3-year overall survival (OS) rate was 85%, and the 3-year local failure-free rate (LFFR), distant failure-free rate (DFFR) and disease-free survival (DFS) rates were 93%, 81%, and 73%, respectively. A positive correlation between GTVnx or GTVp volume and T stage was observed (both P<0.001). The 3-year LFFR, OS, and DFS rate, but not for DMFS, in NPC patients with GTVnx ≤42.7 cm3 was significantly better than those with >42.7 cm3 (all P<0.05). Multivariate analysis indicated that GTVnx volume (P=0.041) was the only independent prognostic factor for LFFR, while age and AJCC stage were two independent prognostic factors for OS. CONCLUSIONS: The GTVnx is an independent prognostic factor for local control, while the prognostic value of GTVrLNs is limited. Physicians are recommended to distinguish between GTVnx and retropharyngeal lymph nodes (RLN) involvement when assessing the risk for local recurrence in advanced NPC.

Survival impact of delaying postoperative chemoradiotherapy in newly-diagnosed glioblastoma patients.

BACKGROUND: Maximal safe resection followed by adjuvant chemoradiotherapy (CRT) with temozolomide (TMZ) is the standard treatment for newly diagnosed glioblastoma multiforme (GBM) patients. Time of initiation of postoperative adjuvant therapy has been demonstrated to impact on prognosis. For GBM patients, the optimal interval between definitive surgery and CRT is still uncertain. Current study aims to find whether the delayed initiation of CRT after surgery has a negative impact on patients' outcome. METHODS: Sixty-six consecutively patients with newly-diagnosed GBM treated with surgery and adjuvant CRT from April 2014 to September 2019 at Ruijin Hospital School of Medicine Shanghai Jiaotong University were retrospectively reviewed. The impact of postoperative time from surgery to adjuvant treatment on patient's overall survival (OS) and progression-free survival (PFS) were evaluated by univariate Log-rank test and multivariate Cox regression analysis. Factors including age, Karnofsky performance status (KPS), maximum diameter of primary tumor, extent of resection, isocitrate dehydrogenase (IDH) mutation status and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also analyzed in Cox regression model. RESULTS: The median OS for patients who started CRT less than 6 weeks (n=48) and more than 6 weeks (n=18) were 26.6 months (95% CI: 18.3-34.9) and 15.7 months (95% CI: 9.2-22.3) (P=0.001). The median PFS for the short interval group was 16.3 months (95% CI: 14.7-18.0) and for the long interval group was 9.1 months (95% CI: 4.7-13.4) (P=0.006). On multivariate Cox regression analysis, high KPS and initiation of CRT less than 6 weeks were two independent prognostic factors for better OS and PFS (all P<0.05). CONCLUSIONS: Initiation of adjuvant CRT beyond 6 weeks contributed to worse survival in GBM patients, therefore CRT should be initiated within 6 weeks after surgery.

Single-Stranded DNA-Binding Protein and Exogenous RecBCD Inhibitors Enhance Phage-Derived Homologous Recombination in Pseudomonas.

The limited efficiency of the available tools for genetic manipulation of Pseudomonas limits fundamental research and utilization of this genus. We explored the properties of a lambda Red-like operon (BAS) from Pseudomonas aeruginosa phage Ab31 and a Rac bacteriophage RecET-like operon (RecTEPsy) from Pseudomonas syringae pv. syringae B728a. Compared with RecTEPsy, the BAS operon was functional at a higher temperature indicating potential to be a generic system for Pseudomonas. Owing to the lack of RecBCD inhibitor in the BAS operon, we added Redγ or Pluγ and found increased recombineering efficiencies in P. aeruginosa and Pseudomonas fluorescens but not in Pseudomonas putida and P. syringae. Overexpression of single-stranded DNA-binding protein enhanced recombineering in several contexts including RecET recombination in E. coli. The utility of these systems was demonstrated by engineering P. aeruginosa genomes to create an attenuated rhamnolipid producer. Our work enhances the potential for functional genomics in Pseudomonas.

The maximum diameter of cervical lymph node was not a prognostic factor for local-regional advanced nasopharyngeal carcinoma treated with intensity modified radiotherapy.

BACKGROUND: Cervical lymph node metastasis was an important prognostic factor. However, the prognosis of the maximum diameter of cervical lymph nodes before treatment has always been controversial. The aim of this study was to analyze the relationship between treatment outcomes and the maximum diameter of lymph nodes (Dmax) in loco-regional advanced nasopharyngeal carcinoma (NPC) after intensity modified radiotherapy. METHODS: From Jan. 2012 to Dec. 2017, 163 patients with locally advanced NPC treated with intensity modified radiotherapy were retrospectively analyzed. The T-stage distribution was 6.7% in T1, 23.3% in T2, 38.7% in T3, and 31.3% in T4. The N-classifications were 6.1% in N0, 23.3% in N1, 47.9% in N2, and 22.7% in N3. TNM stages were III 51.5% and IVa 48.5%. All patients received intensity modified radiotherapy to the nasopharynx and neck. The dose was 66-70.4 Gy, 2-2.2 Gy per fraction over 6-7 weeks to the primary tumor and lymph nodes and 54-60 Gy to clinical target volumes (CTVs). One hundred fifty patients were received induction chemotherapy and/or concurrent chemotherapy. The maximum diameter of the lymph node is measured on the axial or coronal MRI image. RESULTS: The median follow-up time was 31 months (range, 6.1-79.3 months). Six cases developed neck recurrence and 9 cases developed nasopharynx recurrence. The lymph nodes diameter was 0-12 cm, median 2.9 cm. Three-year overall survival (OS) rate was 77.8%. Three-year local failure-free rate (L-FFR), distant failure-free rate (D-FFR) and disease-free survival (DFS) rate were 88.1%, 77.6% and 63.9% respectively. Multivariate analysis showed Dmax was not a prognostic factor for OS, L-FFR, D-FFR, DFS. Both uni- and multivariate analyses demonstrated that N-classification and age is the significant prognostic factor for predicting OS while the maximum diameter of lymph nodes, T-classification, N-classification and AJCC-classification are the significant prognostic factor for predicting OS in univariate analyses in local-regional advanced NPC. CONCLUSIONS: The maximum diameter of the lymph nodes was not a prognostic factor for local-regional advanced NPC treated with intensity modulated radiotherapy.

Patterns of local failure in patients with high-grade glioma after postoperative radiotherapy with or without chemotherapy.

BACKGROUND: To retrospectively analyze the failure patterns of postoperative adjuvant chemoradiotherapy for high-grade glioma (HGG) under the new WHO classification, particularly focusing on relationship of recurrence pattern and molecular subtypes. METHODS: This retrospective study was conducted in Ruijin Hospital of Shanghai Jiaotong University from April 2014 to April 2018. A total of 56 patients diagnosed as WHO III-IV were included. Patients, who underwent pathological typing according to the 2016 WHO Classification of Tumors of the Central Nervous (CNCS), including tumor grade and IDH status. We collected the basic data. The initial relapsed T1 enhancement MRI imaging was transferred and fused to the original treatment planning CT. The tumors were classified as in-field, marginal, or out-field if greater than 80%, 20-80%, or less than 20% of the recurrent volume fell within the 95% isodose line, respectively. RESULTS: The median overall survive was 22.0 months (95% CI: 16.7-27.2). The 1-, 2-, and 3-year survival rates were 85.8%, 43.9%, and 28.8%, respectively. Thirty-three (58.9%) patients progressed with a median progression survival of 15.9 (95% CI: 12.9-19.0) months. Of 33 patients experienced recurrence, 22 (66.7%) had in-field recurrence within a 9.3-month median period (range, 3-32.7 months), and 3 patients (9.1%) were respectively marginal recurrence occurred at 5.9, 6.4, and 15 months, and 6 patients (18.2%) developed out-field progression at a median of 16.1 (4.5-27.1) months, and 2 patients developed both in- and out-field recurrence (6.1%) at 3.2, 4.7 months, respectively. There were16 cases of WHO III, 40 cases of WHO IV, 13 cases of IDH mutation (IDHmt), 30 cases of wildtype (wt) and 13 cases of NOS. The incidence of recurrence of IDHmt (4 cases, 30%) was significantly lower than that of IDHwt (19 cases, 63.3%) and IDH NOS (10 cases, 76.9%) (P=0.001). Local recurrence (in the field and margin) of radiotherapy was 16 cases (84.2%) of IDHwt and 2 cases (50%) of IDHmt type (P=0.05). CONCLUSIONS: In this study, we highlighted the importance of genomic research on identifying local failure patterns and providing recommendations of target delineation for HGG treatment. IDHwt HGG had a higher probability of in-field recurrence after radiotherapy, and RTOG target delineation guide was appropriate, while EORTC guidelines were recommended to IDHmt HGG. Further investigations in prospective randomized clinical trials were warranted to confirm our results.

Enhanced Heterologous Spinosad Production from a 79-kb Synthetic Multioperon Assembly.

Refactoring biosynthetic pathways for enhanced secondary metabolite production is a central challenge for synthetic biology. Here we applied advanced DNA assembly methods and a uniform overexpression logic using constitutive promoters to achieve efficient heterologous production of the complex insecticidal macrolide spinosad. We constructed a 79-kb artificial gene cluster in which 23 biosynthetic genes were grouped into 7 operons, each with a strong constitutive promoter. Compared with the original gene cluster, the artificial gene cluster resulted in a 328-fold enhanced spinosad production in Streptomyces albus J1074. To achieve this goal, we applied the ExoCET DNA assembly method to build a plasmid from 13 GC-rich fragments with high efficiency in one step. Together with our previous direct cloning and recombineering tools, we present new synthetic biology options for refactoring large gene clusters for diverse applications.

Absorption and metabolism characteristics of pristimerin as determined by a sensitive and reliable LC-MS/MS method.

In this research, a sensitive and reliable LC-MS/MS method was developed and applied to determine the concentration of pristimerin in rat plasma, cell incubation media and metabolism incubation mixtures. The absolute oral bioavailability of pristimerin is 28.4% at a dose of 1 mg·kg(-1), and the bioavailability was poor. The bidirectional transport of pristimerin across Caco-2 cells was studied in vitro. A markedly higher transport of pristimerin across Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated that P-gp might be involved in the transport of pristimerin in intestine. The phase I and phase II metabolic stability was also investigated using human liver microsomes (HLM) and S9 fractions, respectively. Pristimerin was stable in S9 fractions but metabolized in HLM with a half-life of 20.4 min, which indicated that pristimerin could be mainly metabolized by phase I enzymes. In conclusion, the absolute oral bioavailability of pristimerin in plasma, transport across Caco-2 cell monolayers, and metabolic stability in HLM and S9 fractions were systematically investigated by using a sensitive and reliable LC-MS/MS method.

Involvement of both cervical lymph nodes and retropharyngeal lymph nodes has prognostic value for N1 patients with nasopharyngeal carcinoma.

BACKGROUND: The N1 definition of 2010 UICC/AJCC staging system for nasopharyngeal carcinoma (NPC) covers quite a large range of nodal pattern. The objective of this research is to investigate prognostic value of lymph nodes related factors including involvement of both cervical lymph nodes (CLNs) and retropharyngeal lymph nodes (RLNs) or not, size and number of cervical lymph nodes (CLNs) in N1 patients with NPC. METHODS: 142 newly diagnosed non-metastatic N1 patients with NPC, staged according to the 2010 AJCC staging system for NPC were retrospectively enrolled. All patients had undergone contrast-enhanced magnetic resonance imaging (MRI), and received radiotherapy, with or without chemotherapy as their primary treatment. RESULTS: The median follow-up was 48 months. The 5-year local recurrence-free survival (LFS), nodal recurrence-free survival (NFS), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) of the whole group were 82.3%, 83.0%, 81.0%, 82.1%, 75.3% and 89.8%, respectively. In univariate analysis, patients with both CLNs and RLNs involvement showed a significant lower DMFS, PFS and LRFS than the rest patients (p=0.004 p=0.003 and p=0.034, respectively). Neither size nor number of CLNs affected the survival. In multivariate analysis, involvement of both CLNs and RLNs was an independent prognostic factor for DMFS and PFS (p=0.019, p=0.019), but there was no enough evidence confirming its prognostic value for LRFS (p=0.051). CONCLUSIONS: For N1 patients with NPC, involvement of both RLNs and CLNs may be a potentially prognostic factor for distant metastasis and disease progression. The N stage for N1 patients with involvement of both cervical lymph nodes and retropharyngeal lymph nodes might need to be deliberated.

Using neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy for nasopharyngeal carcinoma with intracranial invasion to protect critical normal tissue.

PURPOSE: To investigate the feasibility of neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy (IMRT) for intracranial invasion nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From June 2007 to January 2012, 32 patients with intracranial invasion NPC treated with TPF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, 5-FU 2500 mg/m2 every 3 weeks for 3 cycles) neoadjuvant chemotherapy, and replanning IMRT with concurrent chemotherapy were retrospectively studied. The first IMRT plan for each patient was generated based on the original planning CT scan acquired before the start of treatment. Because of tumor shrinkage during radiotherapy, modified gross tumor volume of primary tumor (GTV-P) and high risk clinical target volume (CTV-H), and a new plan was generated and used to complete the course of IMRT. The DVHs of IMRT plan with or without replanning were compared. RESULTS: There weren't statistically significant differences in the V95, D-mean, D-95, and D-99 to the modified PTVGTV-P and PTVCTV-H with and without replanning IMRT. Replanning reduced the doses to the brain stem, optic nerve, optic chiasm and temporal lobe. Objective responses were 100.0% 3 months after completion of radiotherapy. Acute toxicities were well tolerated, except for the relatively high incidence of neutropenia. The 2-year local control rates and distant-metastasis free survival were 88.2% (95% CI, 72.9% to 100.0%) and 89.6% (95% CI, 75.9% to 100.0%). CONCLUSION: Neoadjuvant chemotherapy and replanning IMRT according to tumor shrinkage during the treatment is essential to ensure safe doses to normal tissues, and produces encouraging outcome for intracranial invasion NPC.

[Epidemiology and etiology of hand-foot-and-mouth disease in Hainan, 2010].

To reveal the epidemiological and pathogenic characteristics of Hand-foot-and-mouth disease (HFMD) in Hainan province in 2010, epidemiology data of HFMD reporting cases were analyzed, clinical specimens from 1346 HFMD cases were collected for enterovirus (EV) detection. Viral isolation was performed for EV nucleic acid positive samples. Complete VP1 encoding region of EV71 were sequenced and analyzed with Sequencher (version 5.0) and MEGA software (version 5.0). The epidemiology data showed that all 18 prefectures in Hainan had reporting cases during 2010, with higher incidence in the northeast; and the children less than 4 years old accounted for the majority of the suffered; the epidemic reached peak during September to October, which was different from other Provinces in China. The laboratory results indicated that EV71 and CA16 were identified as the major causative pathogens in Hainan in 2010, however, EV71 infection was absolutely dominant among severe and fatal cases. In addition, some HFMD cases were identified associated with other serotypes of EV infections. Molecular epidemiological analysis showed that all the EV71 strains belonged to C4a evolutionary branch, which is the dominant evolutionary branch in China in recent years, and at least three transmission chains existed. This study has an important information in clarifying the characteristics of epidemics and transmission of HFMD in Hainan, and to provide the guidance for HFMD prevention and control in the future.

Development and optimization of baicalin-loaded solid lipid nanoparticles prepared by coacervation method using central composite design.

The objective of this study was to design and optimize a novel baicalin-loaded solid lipid nanoparticles (SLNs) carrier system composed of a stearic acid alkaline salt as lipid matrix and prepared as per the coacervation method in which fatty acids precipitated from their sodium salt micelles in the presence of polymeric nonionic surfactants. A two-factor five-level central composite design (CCD) was introduced to perform the experiments. A quadratic polynomial model was generated to predict and evaluate the independent variables with respect to the dependent variables. The composition of optimal formulation was determined as 0.69% (w/v) lipid and 26.64% (w/w) drug/lipid ratio. The results showed that the optimal formulation of baicalin-loaded SLN had entrapment efficiency (EE) of 88.29%, particle size of 347.3 nm and polydispersity index (PDI) of 0.169. The morphology of nanoparticles was found to be nearly spherical in shape by scanning electron microscopy (SEM) observation. The differential scanning calorimetry (DSC) analysis indicated that the drug incorporated into SLN was not in an amorphous form but in a crystalline state. The C(max), MRT, AUMC(0→∞) and AUC(0→∞) values of SLN were approximately 1.6-fold, 1.9-fold, 5.0-fold and 2.6-fold greater than that of reference preparation, respectively.

Treatment outcome of nasopharyngeal carcinoma with retropharyngeal lymph nodes metastasis only and the feasibility of elective neck irradiation.

OBJECTIVE: To investigate the outcome of nasopharyngeal carcinoma (NPC) with retropharyngeal lymph nodes (RLNs) metastasis only and evaluate the feasibility of elective neck irradiation. MATERIALS AND METHODS: This is a retrospective study of 119 newly diagnosed non-metastatic NPC patients with RLNs metastasis only. All of them received definitive radiotherapy. Eighty nine patients received elective neck irradiation to levels II, III, VA and the rest received whole neck irradiation, including levels II-V. RESULTS: The median follow-up was 36.6 months. The 5-year local recurrence-free survival (LFS), nodal recurrence-free survival (NFS), distant metastasis-free survival (DMFS) and overall survival (OS) was 81.4%, 92.7%, 91.8%, and 93.6%, respectively. Four patients developed nodal relapse and only one was out-of-field relapse. No significant difference of nodal recurrence was observed between elective neck irradiation and whole neck irradiation. IMRT or three-dimensional conformal radiotherapy (3D-CRT) showed a trend of improving regional control, compared with conventional two-dimensional radiotherapy (2D-RT) (p=0.074). In 2D-RT, a higher dose (>5600 cGy) to the upper neck showed a benefit of regional control(p=0.006). Multivariate analysis demonstrated that only the dose of upper neck was an independent prognostic factor of NFS. CONCLUSIONS: Elective irradiation to levels II, III, VA was not inferior to whole neck irradiation for NPC patients with RLNs metastasis only. However, more evidences are needed to confirm the result. IMRT showed a trend of improving regional control. A higher dose of prophylactic radiation may be required for upper neck region in patients with RLNs metastasis.

[Study on the extraction of total alkaloid from folium nelumbinis with ultrasonic wave technology optimized by central composite design and response surface method].

OBJECTIVE: To optimize the extracting process of Folium Nelumbinis by central composite design and response surface method. METHODS: Independent variables were ethanol concentration, solvents ratio and pH,dependent variable was extracting rate of alkaloid. Composite design and response surface method were used to optimize the extracting process. Resultant model was used to predict the response in the optimal region. RESULTS: The optimum extraction conditions were 80% aqueous ethanol, 75 fold solvent, pH value 5. CONCLUSION: The optimum process is simple and more convenient for extracting Folium Nelumbinis. The observed and predicted values are close to each other.