Effects of hemoglobin variants HbJ Bangkok, HbE, HbG Taipei, and HbH on analysis of glycated hemoglobin via ion-exchange high-performance liquid chromatography.

BACKGROUND: To explore the effects of HbJ Bangkok, HbE, HbG Taipei, and α-thalassemia HbH on the results of HbA1c assessment using ion-exchange high-performance liquid chromatography (IE-HPLC). METHODS: We enrolled five patients in which the results of the IE-HPLC HbA1c assay were inconsistent with the average levels of FBG. We performed hemoglobin capillary (Hb) electrophoresis using whole-blood samples. We also sequenced the genes encoding Hb using dideoxy-mediated chain termination and analyzed HbA1c using borate affinity HPLC (BA-HPLC) and turbidimetric inhibition immunoassay (TINIA). RESULTS: Two patients had the HbJ Bangkok variant. Hb genotypes of these patients were ß41-42 /ßJ Bangkok and ßN /ßJ Bangkok , and the content of HbJ Bangkok was 93.9% and 52.4%, respectively. The remaining three patients had the following: HbE (ßN /ßE Hb genotype, 23.6% HbE content), HbG Taipei (ßN /ßG Taipei Hb genotype, 39.4% HbG Taipei content), and α-thalassemia HbH (6.1% HbH content, 2.8% Hb Bart's content). In the patients with ß-thalassemia and HbJ Bangkok variants, the presence of the variants interfered with the results of HbA1c analyses using IE-HPLC and TINIA; in the remaining four patients, there was interference with the results of HbA1c IE-HPLC but not with the TINIA assay. There was no interference with BA-HPLC HbA1c results. CONCLUSIONS: HbJ Bangkok, HbE, HbG Taipei Hb, and α-thalassemia HbH disease cause varying degrees of interference with the analysis of HbA1c using IE-HPLC. In these patients, we suggest using methods free from such interference for the analysis of HbA1c and other indicators to monitor blood glucose levels.

Percutaneous liver biopsy: retrospective study of primary and secondary hepatic lymphoma in twenty-one patients.

BACKGROUND: Hepatic lymphoma (HL) is categorized as primary and secondary hepatic lymphoma (PHL and SHL). This disorder can present as hepatic mass or mass-like lesion. Chemotherapy often is the first line treatment for patients with HL. Thus, an accurate pre-management histological diagnosis is essential to potentially improve clinical outcomes. The present study was to explore the prevalence of HL in ultrasound guided liver biopsies for hepatic mass or mass-like lesions, to investigate HL associated clinicopathological features, to raise the awareness of early recognition and proper diagnosis of this entity, and to assess specimen adequacy in needle core biopsy. METHODS: Twenty-one cases of HL were enrolled. Clinical and pathological characteristics were evaluated, quality of biopsies was assessed and pertinent literature was reviewed. RESULTS: HL was diagnosed in 0.94% of 2242 liver biopsy cases with ambiguous clinical presentation, laboratory tests and image studies. There were two cases of PHL (0.09%), and nineteen cases of SHL (0.85%). Histopathologically, diffuse large B-cell lymphoma was the most common type, followed by B-cell lymphoma not otherwise specified, T-cell lymphoma, Hodgkin's lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Additionally, three lymphocytic infiltration patterns were documented microscopically. The nodular infiltration was the most common type. CONCLUSIONS: HL is a rare entity and histopathology along with ancillary tests remains the only way to make the diagnosis. Clinicians' awareness of this entity and early liver biopsy are essential in patient management.

[Association of polymorphisms in signal transducer and activator of transcription 4 gene and the susceptibility to unexplained recurrent spontaneous abortions].

OBJECTIVE: To investigate the association between the polymorphisms of signal transducer and activator of transcription 4 (STAT4) gene and the susceptibility to unexplained recurrent spontaneous abortion(URSA). METHODS: PCR-restriction fragment length polymorphism (PCR-RFLP) was used to detect genotype 3 loca (rs7574865 G/T, rs10181656 C/G and rs16833431 C/T) polymorphism of STAT4 in 246 URSA cases (URSA group) and 183 normal controls (control group) . RESULTS: (1)The frequencies of rs7574865 were genotype G/G of 36.2% (89/246) in URSA group and 46.4% (85/183) in control group, genotype G/T of 47.2% (116/246) in URSA group and 45.4% (83/183) in control group, and genotype T/T of 16.7% (41/246) in URSA group and 8.2% (15/183) in control group, which reached statistical difference (P < 0.05). The frequencies of rs10181656 were genotype CC of 36.6% (90/246) in URSA group and 46.4% (85/183) in control group, genotype C/G of 48.0% (118/246) in URSA group and 44.8% (82/183) in control group, and genotype G/G of 15.4% (38/246) in URSA group and 8.7% (16/183) in control group, which reached statistical difference (P < 0.05). The carriers of rs7574865 T allele and rs10181656 G allele increased the risk of URSA (OR = 1.51, 1.44, all P < 0.05).(2) There was no different distribution in 3 genotypes (C/C, C/T, T/T) and 2 alleles (C and T) of rs16833431 C/T between URSA patients and normal controls (P = 0.43,0.48). (3) Timated haplotype frequency distribution of rs7574865 G/T and rs10181656 C/G showed haplotype G-T conferring the susceptibility to URSA (OR = 1.49, P < 0.01), but haplotype C-G could provide protection on URSA (OR = 0.68, P < 0.01). CONCLUSION: Polymorphisms of STAT4 gene might confer the susceptibility to URSA by altering STAT4 function and (or) its expression.

Long-term survival of gastric mixed neuroendocrine-non-neuroendocrine neoplasm: Two case reports.

BACKGROUND: Gastric mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), which consists of neuroendocrine and non-neuroendocrine components, is quite rare. Until now, most data on gastric MiNEN come from clinical cases, without large-scale retrospective studies or controlled clinical trials. Consequently, no consensus regarding the origin, molecular characteristics, or appropriate treatment of MiNEN has been reached so far. We conducted chemotherapy of irinotecan plus cisplatin (IP regimen) and surgery in two patients with gastric MiNEN, which had never been used in treating this kind of tumor, leading to their long-term survival for more than 3 and 7 years, respectively. CASE SUMMARY: We present two patients (one male and one female) with gastric MiNEN, with the primary manifestation of recurrent upper abdominal pain. After they were referred to our hospital, a diagnosis of gastric MiNEN was defined with the help of CT scan, and histopathological and immunohistochemical examinations on the samples of gastrointestinal endoscopy or radical surgery. The male patient (case 1) were found to have metastases in the reginal lymph nodes and the left liver. He received four cycles of IP regimens first, then the gastrectomy and partial left liver resection, followed by additional two cycles of IP chemotherapy. The female patient (case 2) underwent a laparoscopic gastrectomy, and received six cycles of IP regimen. She was found to have metastatic lesions in the right lung 2 years after that, and underwent video-assisted thoracoscopic surgery (VATS) of the lower lobe of the right lung. The two patients have now survived for more than 3 years and 7 years, respectively, without any evidence of recurrence or metastases. CONCLUSION: IP regimen, combined with curative-intent surgery if feasible, could be considered as the priority in the choice of front-line chemotherapy for gastric MiNEN.

Epstein-Barr virus-associated leiomyosarcoma of the larynx in an adult patient with human immunodeficiency virus infection: Case report and review of the literature.

We investigated the clinical features, treatment, and prognosis of laryngeal leiomyosarcoma (LLMS) and Epstein-Barr virus-associated (EBV-associated) LMS. We report a case of EBV-associated LLMS in an adult patient with HIV infection. We also conducted a review of the English-language literature on LLMS and EBV-associated leiomyosarcoma. To the best of our knowledge, 62 cases of LLMS and EBV-associated leiomyosarcoma have been reported to date. Of patients with LLS, 18.9% had distant metastases and 17.0% had local recurrence. The overall 5-year survival rate was 64.0%. Distant metastases affected the survival of patients with LLMS (p = 0.04). EBV-positive patients had a low survival rate (p = 0.01). Among patients with EBV-associated LMS, 8.2% had distant metastases and recurrence and the overall 5-year survival rate was 50.0%. EBV-associated LLMS is rare. The EBV infection might be a poor prognostic factor of LLMS.

Shape dependence of gold nanoparticles on in vivo acute toxicological effects and biodistribution.

The toxicity and biodistribution in vivo of various morphologies of Au nanoparticles (AuNPs) were studied by using KM mice. The quantitative analysis of Au in each tissue of mice was done by using the Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Sphere-shaped AuNPs displayed the best biocompatibility, compared with rod- and cube-shaped of AuNPs, and rod-shaped AuNPs was more toxic than cube-shaped AuNPs. In vivo biodistribution study revealed all AuNPs were preferentially accumulated in organ of liver and spleen. The findings from this study thus revealed that the toxicity and biodistribution in vivo of AuNPs are shape dependent.

[Study on association of functional polymorphisms in Foxp3 gene with the susceptibility to unexplained recurrent spontaneous abortion].

OBJECTIVE: To investigate the association between the functional polymorphisms of Foxp3 gene and unexplained recurrent spontaneous abortion (URSA). METHODS: PCR-restriction fragment length polymorphism (rs3761548, rs2294021) and PCR with sequence-specific primers (rs2232365, rs5902434) were used to detect four polymorphisms of Foxp3 in 146 URSA cases and 112 normal controls. RESULTS: (1) The frequencies of rs3761548A/C were 10.3%, 22.3% in genotype C/C, 38.4%, 40.2% in genotype A/C and 51.4%, 37.5% in genotype A/A between URSA patients and normal controls; the frequencies of rs2232365A/G were 5.5%, 15.2% in genotype A/A, 47.9%, 50.0% in genotype A/G, 46.6%, 34.8% in genotype G/G between URSA patients and normal controls; they all reached statistical difference (P < 0.05). The carriers of rs3761548A allele and rs2232365G allele increased the risk of URSA (OR = 1.73, 1.61;all P < 0.05). (2) There was no difference in the genotypic distribution of rs5902434del/ATT polymorphism between cases and controls (P = 0.10), but the frequency of del allele in URSA was statistically increased than that of controls (71.2%, 62.5%;OR = 1.49, P = 0.04). (3) There was no different distribution in 3 genotypes (C/C, T/C, T/T) and 2 alleles (T and C) of rs2294021T/C between URSA patients and normal controls (P = 0.18 and 0.08). (4) Estimated haplotype frequency distribution of rs5902434del/ATT, rs3761548A/C and rs22323565A/G showed haplotype del-A-G conferring the susceptibility to URSA (OR = 2.51, P < 0.01) but haplotype del-C-G and ATT-A-A could provide protection on URSA (OR = 0.18, 0.22; all P < 0.01). CONCLUSION: Functional polymorphisms of Foxp3 gene could probably confer the susceptibility to URSA, by altering Foxp3 function and (or) its expression.

[Amino-terminal pro-brain natriuretic peptide and brain natriuretic peptide measurements under various detection conditions in patients with chronic heart failure].

OBJECTIVE: To find the potential interference factors for the detection of NT-proBNP and BNP in patients with chronic heart failure. METHODS: EP15-A2 issued by Clinical and Laboratory Standards Institute (CLSI) was employed to compare the precision and accuracy of commercial NT-proBNP and BNP analyzer electrochemiluminescence immunoassay system Cobas E601 and chemiluminescence system ADVIA Centaur. Moreover, NT-proBNP and BNP were detected in different time interval and in different interfered sampling conditions (haematolysis, choloplania, lipemia). NT-proBNP and BNP of 203 patients with heart failure or heart failure complicated with acute cerebral infarction were analyzed to find the deviation caused by patients' endogenous factors. RESULTS: The precision and accuracy were comparable for NT-proBNP and BNP detection using Cobas E601 and ADVIA Centaur (total-CV below 2.9% and 3.5%, the deviation from definite value below 2.38% and 3.91%). The most suitable sample type for NT-proBNP and BNP detection was serum and EDTA-anticoagulant plasma. The detection results of NT-proBNP and BNP were comparable for at least 120 min post sampling and not affected by Hb (2 g/L), DB (428 µmol/L) and chyle (2000 FIU). NT-proBNP was significantly higher in heart failure patients complicated with cerebral infarction (P = 0.003) than in heart failure patients. BNP was significantly higher in heart failure grade III patients complicated with cerebral infarction (P < 0.01). CONCLUSIONS: Cobas E601 and ADVIA Centaur supplied satisfactory detection of NT-proBNP and BNP in patients with chronic heart failure with strong anti-interference capacity. The diagnostic value of NT-proBNP and BNP for chronic heart failure should be analyzed objectively in the presence of complicating diseases.

[Effect of C/EBPalpha on the monocytic differentiation of HL60 cells induced by NSC67657].

OBJECTIVE: To figure out the function of C/EBPalpha in the monocytic differentiation of HL60 cells induced by a new steroidal drug NSC67657. METHODS: The differentiation of HL60 cells was induced by NSC67657, and the cell surface antigen CD14 expression was detected by flow cytometry. The gene and protein expressions of CCAAT enhancer binding protein alpha (C/EBPalpha) before and after the induction of cell differentiation were determined by RT-PCR and Western blot. Eukaryotic expressing vector pDsRed-ICAT was constructed and transfected into HL60 cells, and its expression was verified. The effect of C/EBPalpha overexpression in HL60 cells was assessed by MTT assay, Wright's staining and flow cytometry before and after NSC67657 transfection. RESULTS: HL60 cells could be induced into monocytes by 10 micromol/L ATRA within 5 days, and the coverage of CD14 positive cells reached 93.9% after 5 days of drug treatment. The eukaryotic expressing vector was successfully constructed, and over 90% positive clones were obtained after screening by G418 and electrotransfection. The results of proliferative analysis, chemical staining, ultrastructural observation, and CD11b detection confirmed that HL60 cells could be induced into granulocytic differentiation by overexpression of C/EBPalpha protein. Moreover, in the drug treatment group, transfected cells could not be induced into monocytic differentiation, and their granulocytic differentiation was also inhibited. CONCLUSION: The monocytic differentiation of HL60 cells induced by NSC67657 may not be via the regulation by C/EBPalpha protein-mediated signal transduction. However, the overexpression of CEBPalpha may inhibit the process of NSC67657-induced monocytic differentiation in HL60 cells.

[Regulation and mechanism of Notch signaling pathway in small cell lung cancer].

OBJECTIVE: To investigate the status of Notch signaling pathway in small cell lung cancer (SCLC). METHODS: Expression plasmids of pEFBOS-NIC-MYC and pEFBOS-neo were transfected into NCI-H446 cells. Stably transfected cell lines were selected and their growth rates were examined by MTT method. Expression of downstream genes along the Notch signaling pathway were studied by RT-PCR. Protein expression of euroendocrine markers of CgA and NSE were detected by Western blot analysis and immunocytochemistry. RESULTS: The expression of HES1 was increased in the pEFBOS-NIC-MYC group, but the expression of hASH in the pEFBOS-NIC-MYC group was decreased significantly. The transfected cells with pEFBOS-NIC-MYC plasmid showed a significantly slower growth rate compared with that of two control groups (P < 0.05, Student's t-test). Immunocytochemistry of NSE showed that PUs in the NIC transfected group, sham group and negative control group were 7.21 ± 0.59, 28.25 ± 1.46, 30.57 ± 1.31 respectively, the former one was smaller than the values of the latter two significantly (P < 0.01). Western blot analysis showed the grave scales of CgA in NIC transfected group and sham group to be 0.54 ± 0.03 and 0.99 ± 0.05 respectively (grave scales of the negative control was set as 1.00), the former one significantly smaller than that of the other two groups (P < 0.01). The grave scales of NSE in the NIC transfected group and sham group were 0.43 ± 0.02 and 1.07 ± 0.09 respectively (grave scales of the negative control was set as 1.00) and the former one was significantly smaller than the other two groups (P < 0.01). CONCLUSION: Notch signaling pathway regulates SCLC cells through its inhibitory effect on hASH1 transcription via HES1 along with an expression inhibition of neuroendocrine markers in SCLC.

[Effects of herba ephedrae, honey-fried herba ephedrae and maxingshigan decoction on autonomic activities of mice].

OBJECTIVE: To discuss the significance of processing and complex prescription with Herba Ephedrae, the effects of Herba Ephedrae, Honey-fried Herba Ephedrae and Maxingshigan decoction on autonomic activities in mice were compared. METHODS: 110 female Kunming mice were divided into 11 groups, namely normal saline group (NS), ephedrine group (E), high dose Herba Ephedrae group (MH-H), moderate dose Herba Ephedrae group (MH-M), low dose Herba Ephedrae group (MH-L) ,high dose Honey-fried Herba Ephedrae group (ZMH-H), moderate dose Honey-fried Herba Ephedrae group (ZMH-M),low dose Honey-fried Herba Ephedrae group (ZMH-L), high dose Maxingshigan decoction group (MX-H), moderate dose Maxingshigan decoction group (MX-M) and low dose Maxingshigan decoction group (MX-L). The numbers of autonomic activity in 15 minutes before intragastric administration (ig), and after ig 0.5, 1, 2, 3, 4 h were determined. RESULTS: There was interaction between time and groups. There were very significant differences between before ig and all time-points after ig (P < 0.01). 30 minutes after ig,there were significant differences between E and NS,E and ZMH-L,E and MX-L (P < 0.05). 1 h after ig, there were significant differences between MX-M and NS (P < 0.05). 3 h after ig, there were significant differences between MX-M and MH-L (P < 0.05). 30 minutes after ig, both ZMH-L and MX-L could reduce the number of autonomic activity in some extent compare with MH-L. 1 h or 2 h after ig, ZMH-L could reduce the number of autonomic activity in some extent compare with MH-L 4 h after ig, MX-L could reduce the number of autonomic activity in some extent compare with MH-L. CONCLUSION: Under the condition of this study, regarding autonomic activity as index, both ZMH-L and MX-L can reduce center stimulation in some extent.

Radiomics Analysis on Multiphase Contrast-Enhanced CT: A Survival Prediction Tool in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Patients with HCC receiving TACE have various clinical outcomes. Several prognostic models have been proposed to predict clinical outcomes for patients with hepatocellular carcinomas (HCC) undergoing transarterial chemoembolization (TACE), but establishing an accurate prognostic model remains necessary. We aimed to develop a radiomics signature from pretreatment CT to establish a combined radiomics-clinic (CRC) model to predict survival for these patients. We compared this CRC model to the existing prognostic models in predicting patient survival. This retrospective study included multicenter data from 162 treatment-naïve patients with unresectable HCC undergoing TACE as an initial treatment from January 2007 and March 2017. We randomly allocated patients to a training cohort (n = 108) and a testing cohort (n = 54). Radiomics features were extracted from intra- and peritumoral regions on both the arterial phase and portal venous phase CT images. A radiomics signature (Rad-signature) for survival was constructed using the least absolute shrinkage and selection operator method in the training cohort. We used univariate and multivariate Cox regressions to identify associations between the Rad- signature and clinical factors of survival. From these, a CRC model was developed, validated, and further compared with previously published prognostic models including four-and-seven criteria, six-and-twelve score, hepatoma arterial-embolization prognostic scores, and albumin-bilirubin grade. The CRC model incorporated two variables: The Rad-signature (composed of features extracted from intra- and peritumoral regions on the arterial phase and portal venous phase) and tumor number. The CRC model performed better than the other seven well-recognized prognostic models, with concordance indices of 0.73 [95% confidence interval (CI) 0.68-0.79] and 0.70 [95% CI 0.62-0.82] in the training and testing cohorts, respectively. Among the seven models tested, the six-and-12 score and four-and-seven criteria performed better than the other models, with C-indices of 0.64 [95% CI 0.58-0.70] and 0.65 [95% CI 0.55-0.75] in the testing cohort, respectively. The CT radiomics signature represents an independent biomarker of survival in patients with HCC undergoing TACE, and the CRC model displayed improved predictive performance.

[Expression and significance of CD147 and E-cadherin in human gastric carcinoma].

OBJECTIVE: To investigate the expression of CD147 and E-cadherin in gastric carcinoma and their correlation with clinicopathological features. METHODS: The expression of CD147 and E-cadherin in gastric cancer tissue chip (TC) was detected by in situ hybridization (ISH) and immunohistochemistry in 220 cases of gastric carcinoma and 31 cases with normal gastric mucosa. RESULTS: The expression rates of CD147 mRNA, E-cadherin mRNA and E-cadherin protein were 50.5%, 17.7% and 15.5%, respectively. The CD147 expression was negatively correlated with E-cadherin expression. There was a significant relationship between CD147 mRNA expression and tumor diameter, TNM stage, invasion depth, vessel invasion, lymph node and distant metastasis. The E-cadherin mRNA expression was closely related with TNM stage, invasion depth and vascular invasion. There was a significant relationship between E-cadherin protein expression and tumor diameter, TNM stage and vascular invasion. The mean survival time in cases with CD147-positive expression was shorter than that in negative cases, while E-cadherin was in an opposite relationship. CONCLUSION: In gastric carcinoma, up-regulation of CD147 and down-regulation of E-cadherin are in a negative correlation. The examination of both these two factors together is useful for predicting the invasion and metastasis of gastric cancer, therefore, can be used as a significant marker to direct clinic therapy and estimation of prognosis.

[Inhibitory effects of Notch1 overexpression on proliferation and neuroendocrine marker expression in a small cell lung cancer cell line].

OBJECTIVE: To investigate the effects of Notch1 signal activation on proliferation and neuroendocrine marker expression in small cell lung cancer cells. METHODS: The active form of Notch1 (NIC) was over-expressed in NCI-H446 cells by constitutive transfection and a stable transfected cell line was established. Proliferation of NCI-H446 cells was analysed by MTT assay on 6 successive days. Expression of neuroendocrine markers (CgA, NSE) was observed by immunohistochemistry and Western blot analysis. Statistical analysis was conducted to compare the results in cells with NIC transfected and those in control groups. RESULTS: MTT assay showed that absorbance (A) of cells overexpressing Notch1 was significantly depressed compared with that of the control cells (P<0.05). Immunohistochemistry of CgA showed that PUs in the NIC transfected group, sham group and negative control group were 8.81 +/- 0.77, 38.10 +/- 1.55, 38.97 +/- 0.80, respectively, the former one was significantly smaller than that of the latter two (P<0.01). Immunohistochemistry of NSE showed that PUs in the NIC transfected group, sham group and negative control group were 7.21 +/- 0.59, 28.25 +/- 1.46, 30.57 +/- 1.31, respectively, the former one was significantly smaller than that in the latter two (P<0.01). Western blot analysis showed that the gray scales of CgA in the NIC transfected group and sham group were 0.54 +/- 0.03 and 0.99 +/- 0.05, respectively, (gray scale of the negative control set as 1.00), the former one was significantly smaller than that of the other two groups (P<0.01). The gray scales of NSE in the NIC transfected group and sham group were 0.43 +/- 0.02 and 1.07 +/- 0.09, respectively (gray scale of the negative control set as 1.00), the former one was significantly smaller than that of the other two groups (P<0.01). CONCLUSION: Notch1 may behave as a tumor suppressor in small cell lung cancer. Notch1 signal activation can inhibit the proliferation and neuroendocrine marker expression in small cell lung cancer cells, suggesting that Notch1 gene could be a new target for small cell lung cancer treatment and probable relief of paraneoplastic syndrome.

[Study on the expression and significance of Galectin-3 and CDC25B mRNA in human gastric carcinoma].

OBJECTIVE: To study the expression of Galectin-3 and CDC25B mRNA in gastric carcinoma and their correlation with clinical-pathological features and the survival time. METHODS: Tissue microarray (TMA) technique and in situ hybridization were used to detect the expression of Galectin-3 and CDC25B mRNA in 220 gastric carcinoma specimens and 31 normal gastric mucosa samples. RESULTS: In situ hybridization results revealed that from the 220 cases, the positive expression rate of Galectin-3 and CDC25B mRNA were 58.6% and 54.1%, respectively. There was significant relationship between the Galectin-3 mRNA expression and tumor diameter, advanced TNM stage, invasion depth, vessel invasion, lymph node and distant metastasis. There was significant relationship between CDC25B mRNA expression and tumor diameter, advanced TNM stage, vessel invasion, lymph node and distant metastasis. In addition, there was apositive relationship of Galectin-3 and CDC25B mRNA expression. Finally, the mean survival time in cases with Galectin-3 and CDC25B mRNA positive expression was significantly shorter than those without Galectin-3 and CDC25B expression. CONCLUSION: The expression of Galectin-3 and CDC25B mRNA appears to act as a promoting factor in the onset and development of gastric cancer. It can be used as a marker of prognosis of gastric carcinoma in clinical practice.

Diffusion-weighted imaging volume and diffusion-weighted imaging volume growth in acute stroke: associations with fluid-attenuated inversion recovery hyperintensities-diffusion-weighted imaging mismatch and functional outcome.

PURPOSE: This study assessed the association between diffusion-weighted imaging (DWI) volume and fluid-attenuated inversion recovery vascular hyperintensity (FVH)-DWI mismatch, functional outcome in patients with acute stroke patients receiving endovascular therapy, as well as the value of DWI volume in predicting functional outcome with stroke patients. METHODS: In 38 stroke patients who received endovascular therapy, FVH-DWI mismatch, DWI volume on admission, DWI volume on follow-up, DWI volume growth, the functional outcome at 3 months [modified Rankin scale (mRS)], and other clinical data were collected. Statistical analysis was performed to compare the associations with the above variables and predict functional outcome after stroke. RESULTS: Compared with no FVH-DWI mismatch group (n = 15), FVH-DWI mismatch group (n = 23) had a smaller DWI volume on admission (t = -2.980; P = 0.008), smaller DWI volume on follow-up (t = -2.911; P = 0.009), lower DWI volume growth (t = -2.328; P = 0.031). The 3-month outcome (1.87 ± 0.92) in patients with FVH-DWI mismatch was better than that (2.93 ± 1.62) of patients with no FVH-DWI mismatch (t = -2.307; P = 0.032). Spearman's rank correlation analysis revealed that FVH-DWI mismatch (r = 0.327; P = 0.045), DWI volume on admission (r = 0.414; P = 0.010), DWI volume on follow-up (r = 0.486; P = 0.002), and DWI volume growth (r = 0.467; P = 0.003) were positively correlated with mRS at 3 months. ROC analysis showed when the optimal cutoff value of DWI volume on admission was 33.50, the sensitivity and specificity for predicting functional outcome was 60 and 95.65%, respectively. CONCLUSIONS: Evaluating DWI volume on admission, DWI volume on follow-up as well as DWI volume growth comprehensively may be useful in predicting the functional outcome of acute stroke patients after thrombectomy.

Validation of the 8th edition of AJCC/UICC staging system for nasopharyngeal carcinoma: Results from a non-endemic cohort with 10-year follow-up.

OBJECTIVES: This study aimed to validate the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for nasopharyngeal carcinoma (NPC) in non-endemic region. MATERIALS AND METHODS: We recruited 607 patients with histology-proven, previously untreated, non-metastatic NPC treated by intensity-modulated radiotherapy (IMRT) at our center. Harrell's concordance index (c-index) and Akaike information criterion (AIC) were applied to compare the prognostic discrimination between the 7th and 8th edition staging system. RESULTS: For T category, the local recurrence-free survival (LRFS) Kaplan-Meier curves of T1, T2 and T3 were well separated in the 8th edition; however, LRFS did not significantly differ between T3 and T4 (P = 0.166). Moreover, the 7th edition achieved higher c-index (0.702 [95% CI, 0.618-0.787] vs. 0.685 [95% CI, 0.604-0.767]) and lower AIC (766.1 vs. 770.8) than 8th edition for LRFS. With regard to N category, the 8th edition achieved higher c-index (0.796 [95% CI, 0.749-0.843] vs. 0.751 [95% CI, 0.696-0.805]) and lower AIC (1439.4 vs. 1471.9) for distant metastasis-free survival. In terms of overall stage, the 8th edition also had higher c-index (0.798 [95% CI, 0.753-0.844] vs. 0.721 [95% CI, 0.672-0.770]) and lower AIC (1963.9 vs. 2007.2) compared with the 7th edition for overall survival. Furthermore, interval validation by bootstrapping the sample randomly for ~100-1000 times also validated above findings. CONCLUSION: The 8th edition of AJCC/UICC TNM staging system achieved significantly better prognostic discrimination than the 7th edition with regard to N category and overall stage but not T category.

Isolation, characterization and gene modification of fetal neural stem/progenitor cells from cynomolgus monkey.

Successful isolation and expansion of neural stem/progenitor cells from cynomolgus monkey (cm-NSPCs), may not only help to increase our understanding of NSPCs, but also provide an important translational tool for preclinical trials. Here we initially isolated NSPCs from aborted fetal cynomolgus monkey brain, and expanded them in adherent culture system. Then we demonstrated that cultured cm-NSPCs were almost bipolar cells proliferated in clump-like structure, expressed typical markers for NSPCs, and could differentiate into neurons, astrocytes, and oligodendrocytes. After transduction with lentivirus, 70-80% of cm-NSPCs expressed enhanced green fluorescent protein and the stemness was unaffected. This study provided basis for obtaining large numbers of cm-NSPCs, and efficient transduction of them with exogenous genes, which would facilitate cell-based therapies in nonhuman primate models, and might help to investigate the mechanism of central nervous system development and/or controlling neural regeneration.

Mathematical models for the proliferation of neural stem/progenitor cells in clonogenic culture.

Neurospheres are free-floating heterogeneous spheroid structures maintained in culture and have been used for in vitro expansion of neural stem/progenitor cells. But the growth characteristics and proliferation kinetics of cell population in neurospheres are poorly understood. Using clonogenic culture and immunocytochemistry, we observed the growth dynamics of cell populations in neurospheres and identified key parameters relating to the growth dynamics of cells in neurospheres, including the fraction of dividing cells, cell cycle duration, time delay of first division, and survival rate of cells. Based on these parameters, we established two mathematical models that describe kinetic features of neural stem/progenitor cells under clonogenic conditions. These models provide a powerful tool to explain and predict the experimental outcome and clarify the cell growth characteristics of neural stem/progenitor cells.

Establishment and characterization of two new human embryonic stem cell lines, SYSU-1 and SYSU-2.

BACKGROUND: Human embryonic stem cells can propagate indefinitely in vitro and are able to differentiate into derivatives of all three embryonic germ layers. The excitement surrounding human embryonic stem cells lies largely in their potential to produce specialized cells that can be used for transplant therapies. However, further investigation requires additional cell lines with varying genetic background. Therefore, efforts to derive and establish more human embryonic stem cell lines are highly warranted. METHODS: Surplus embryos (blastocysts) from donors were used to isolate the inner cell mass by immunosurgery. All cells were cultured continuously on irradiated murine embryonic fibroblasts feed layer and likely human embryonic stem cell colonies were subsequently characterized by cell surface marker staining, karyotyping and teratoma formation. RESULTS: Two human embryonic stem cell lines (SYSU-1 and SYSU-2) were established from surplus embryos. The two lines express several pluripotency markers including alkaline phosphatase, SSEA-4, Tra-1-60, Oct-4, Nanog and Rex-1. They remain in undifferentiated state with normal karyotype after prolonged passages and can form embryoid bodies in vitro and teratoma in vivo. CONCLUSION: Two new human embryonic stem cell lines have been established from surplus embryos. They can be used to understand selfrenewal and differentiating mechanisms and provide more choices for regenerative medicine.