Characteristic features of primary testicular lymphoma and survival trends: a multicenter clinical study.

OBJECTIVES: To retrospectively investigate the clinical characteristics, prognosis, treatment, and therapy outcome of Chinese patients with primary testicular lymphoma (PTL). METHODS: we collected data of 49 PTL patients from four hospitals over 13 years. The median age was 63 years old. We described the clinical characteristics of the patients including the laterality, serum lactate dehydrogenase (LDH), pathology classification, stage, International prognostic index (IPI) scores and more. RESULTS: Complete remission (CR) was achieved in 34 patients and partial remission (PR) in 3 patients; Progressive disease (PD) was detected in 11 patients, and 10 patients died. The average progression-free survival (PFS) of all patients was 43.92 months, and the average overall survival (OS) was 47.55 months. The Ann Arbor stage, IPI score, and LDH were associated with OS, while Ann Arbor stage, IPI score, LDH, and histotype were significantly associated with PFS. Chemotherapy and radiotherapy following orchiectomy was associated with a significantly longer PFS. CONCLUSION: Most patients can achieve CR after induced therapy or orchiectomy. However, there are many associated prognostic factors.

Dual-signal amplified electrochemical biosensor based on eATRP and PEI for early detection of lung cancer.

Carcinoembryonic antigen (CEA), a lung cancer marker with high sensitivity and specificity, plays vital roles in the early diagnosis of lung cancer. In this paper, an electrochemical biosensor for highly sensitive detection of CEA was constructed, which based on dual signal amplification of electrically mediated atom transfer radical polymerization (eATRP) and polyethyleneimine (PEI) for the first time. Firstly, CEA was captured in a specific recognition manner with CEA aptamer 1 (Apt1), which self-assembled on the electrode via "Au-S" bond. After that, CEA aptamer 2-PEI (Apt2-PEI) was recognized by CEA to form an Apt-antigen-Apt sandwich structure. Next, multiple initiation sites were introduced for the eATRP reaction by the amide reaction. Finally, numerous electroactive monomers, ferrocene methacrylate (FMMA), were grafted onto the modified electrode by eATRP. Under the optimized conditions, there was a wide linear detection range of 10-3 âˆ¼ 102 ng·mL-1, and the limit of detection (LOD) was 70.17 fg·mL-1. Compared to other reported sensors, this electrochemical biosensor used a simpler and more environmentally friendly eATRP, and the use of PEI increased the electron transfer rate. Moreover, the biosensor showed superior analytical performance in the clinical serums and has great promise for early lung cancer diagnosis applications.

Synthesis and Structure Elucidation of Two Essential Metal Complexes: In-Vitro Studies of Their BSA/HSA-Binding Properties, Docking Simulations, and Anticancer Activities.

Imidazole and tetrazole derivatives are widely used as clinical drugs since they possess a variety of pharmaceutical function. Zinc and iron are essential trace elements of the human body, with less toxicity and good biocompatibility. In this paper, two new essential metal mononuclear complexes [M(H2tmidc)2(H2O)2]·2H2O (M = Zn (1), Fe (2)) were synthesized through the reaction of 2-((1H-tetrazol-1-yl)methylene)-1H-imidazole-4,5-dicarboxylic acid (H3tmidc) and ZnSO4·7H2O or FeSO4·7H2O. The crystal structures were determined by means of the X-ray single crystal diffraction technique. Results from fluorescence investigations show that both complexes could interact with BSA as well as HSA through the static quenching mechanism. van der Waals forces and hydrogen bonds play important roles in the interaction of complexes and BSA/HSA since both ΔH and ΔS values are negative. The results of molecular docking are consistent with those in experimental studies. Furthermore, the anticancer activity of H3tmidc and both complexes against Eca-109 were preliminarily evaluated and the results show that both complexes have better anticancer activity than the corresponding ligand H3tmidc.

Rapid Genetic Diagnosis of Citrin Deficiency by Multicolor Melting Curve Analysis.

Citrin deficiency caused by SLC25A13 genetic mutations is an autosomal recessive disease, and four prevalent mutations including c.851_854del, c.1638_1660dup, IVS6+5G>A, and IVS16ins3kb make up >80% of total pathogenic mutations within the Chinese population. However, suitable assays for detection of these mutations have not yet been developed for use in routine clinical practice. In the current study, a real-time PCR-based multicolor melting curve analysis (MMCA) was developed to detect the four prevalent mutations in one closed-tube reaction. The analytical and clinical performances were evaluated using artificial templates and clinical samples. All four mutations in the test samples were accurately genotyped via their labeling fluorophores and Tm values, and the standard deviations of Tm values were indicated to be <0.2°C. The limit of detection was estimated to be 500 diploid human genomes per reaction. The MMCA assay of 5,332 healthy newborns from southern China identified a total of 107 SLC25A13-mutation carriers, indicating a carrier rate of 2%. The genotypes of 107 carriers and 112 random non-carriers were validated using direct sequencing and Long-range PCR with 100% concordance. In conclusion, the assay developed in this study may potentially serve as a rapid genetic diagnostic tool for citrin deficiency.

A multicentre retrospective study of primary breast diffuse large B-cell and high-grade B-cell lymphoma treatment strategies and survival.

Objectives: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) and primary breast high-grade B-cell lymphoma (PB-HGBCL) are rare extranodal aggressive B-cell lymphomas with distinct characteristics. Reliable data regarding appropriate treatment of these specific entities are lacking due to their rarity.Methods: We reviewed 36 patients diagnosed at four Chinese medical centres between January 2008 and December 2018. Data regarding clinicopathological features, therapeutic evaluation and central nervous system (CNS) relapse were collected, and overall survival (OS) and progression-free survival (PFS) were calculated.Results: Among the 36 patients, there were 29 PB-DLBCL patients and 7 PB-HGBCL patients. The 5-year OS for PB-DLBCL and PB-HGBCL was 75.9% and 28.6%, respectively. The 5-year PFS for PB-DLBCL and PB-HGBCL was 69.0% and 14.3%, respectively. The R-DAEPOCH regimen was significantly more effective in PB-DLBCL patients than the R-CHOP regimen (5-year OS: 78.9% vs 62.5%, P=0.024; 5-year PFS: 73.7% vs 50.0%, P=0.037) but resulted in more severe myelosuppression (P=0.025). The rate of CNS relapse was 17.2% in PB-DLBCL patients and 28.6% in PB-HGBCL patients; the difference was not significant (P=0.602). The R-DAEPOCH regimen did not predominantly reduce CNS recurrence as expected (P=0.616). The Cox proportional hazards model revealed that risk stratification and triple expression were independent prognostic factors.Conclusion: Current treatments, including more intensive chemotherapy regimens, achieve good control of the disease. Novel drugs combined with cellular immunotherapy initially show promising therapeutic effects, and more clinical trials are required to confirm these effects further.

Effect of Electron Irradiation Fluence on InP-Based High Electron Mobility Transistors.

In this paper, the effect of electron irradiation fluence on direct current (DC) and radio frequency (RF) of InP-based high electron mobility transistors (HEMTs) was investigated comprehensively. The devices were exposed to a 1 MeV electron beam with varied irradiation fluences from 1 × 1014 cm-2, 1 × 1015 cm-2, to 1 × 1016 cm-2. Both the channel current and transconductance dramatically decreased as the irradiation fluence rose up to 1 × 1016 cm-2, whereas the specific channel on-resistance (Ron) exhibited an apparent increasing trend. These changes could be responsible for the reduction of mobility in the channel by the irradiation-induced trap charges. However, the kink effect became weaker with the increase of the electron fluence. Additionally, the current gain cut-off frequency (fT) and maximum oscillation frequency (fmax) demonstrated a slightly downward trend as the irradiation fluence rose up to 1 × 1016 cm-2. The degradation of frequency properties was mainly due to the increase of gate-drain capacitance (CGD) and the ratio of gate-drain capacitance and gate-source capacitance (CGD/CGS). Moreover, the increase of Ron may be another important factor for fmax reduction.

Prognostic significance of stromal SMYD3 expression in colorectal cancer of TNM stage I-III.

BACKGROUND: SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferases and it promotes progression of many kinds of cancers including lung cancer, ovarian cancer and gastric cancer. In colorectal cancer (CRC), SMYD3 is proved to stimulate the proliferation of cancer cells, but the clinical significance of SMYD3 in CRC has not been elucidated. METHODS: In our study, we detected the expression of SMYD3 in CRC samples in TNM stage I-III with immunohistochemistry. The correlation between the expression of SMYD3 and the clinicopathological factors was analyzed with Chi-square test. The survival curve was displayed by Kaplan-Meier test and the statistical difference of subgroups was analyzed with log-rank test. Independent prognostic factors were identified by the Cox proportional hazards regression model. RESULTS: The percentage of high SMYD3 expression and low expression accounts for 47.98% and 52.02% respectively. High expression of SMYD3 was significantly associated with advance T stage (P=0.006) and lower survival rates (P=0.010), and it could be identified as an independent prognostic factor indicating unfavorable prognosis of patients with CRC (P=0.032, HR=1.98, 95% CI=1.06-3.70). CONCLUSIONS: SMYD3 high-expression is a high risk for poorer prognosis of CRC in TNM stage I-III. Our findings suggested that detecting SMYD3 may help stratify patients by risk more preciously and help make the individual treatment strategy.

Intraoperative sentinel lymph node mapping guides laparoscopic-assisted distal gastrectomy for distal gastric cancer.

AIMS: The aim of this retrospective study is to explore the effects of sentinel lymph node (SLN) mapping guided laparoscopic-assisted distal gastrectomy (LADG) for distal gastric cancer. METHODS: Two hundred patients were enrolled in this study. One hundred and one patients undergoing SLN guided LADG were designated as the SLN group. Ninety-nine patients having conventional LADG with D1 or D2 lymph node dissection were designated as the control group. Intraoperative and postoperative indicators such as the number of lymph nodes dissected, intraoperative and postoperative conditions, flow cytometry analysis of T lymphocyte subsets and natural killer (NK) cells, survival rates, recurrence rates and postoperative complications were investigated between these two groups. RESULTS: The number of lymph nodes dissected in the SLN group was significantly lesser than that in the control group. Furthermore, in the SLN group, the patients achieved better immunization status, improved intraoperative and postoperative conditions and decreased postoperative complications. There were no significant differences were found in the positive lymph nodes detected, the distance between proximal and distal cutting edge, postoperative survival or recurrence rates. CONCLUSIONS: SLN guided LADG for gastric cancer is a safe and effective method and could achieve an equal clinical effect as traditional laparoscopic D1 or D2 radical operation with less operation trauma and better recovery.

Expression of matrix metalloproteinase-9, cyclooxygenase-2 and vascular endothelial growth factor are increased in gastrointestinal stromal tumors.

This study is to investigate the expression of matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST). Immunohistochemistry was performed to detect the expression of MMP-9, COX-2 and VEGF. The expression of MMP-9, COX-2 and VEGF was compared among different clinicopathological features of GIST. Spearman rank correlation analysis was conducted to analyze the correlation among MMP-9, COX-2 and VEGF. The positive expression rates of MMP-9, COX-2 and VEGF were 76.9%, 84.6% and 82.7%. The expression levels of MMP-9, COX-2 and VEGF were significantly different among the clinicopathological features of growth pattern, tumor diameter, metastasis, mitotic count and central necrosis (P < 0.05). Their expression levels were higher in GIST tissues with higher levels of malignancy, tumor size, metastasis, mitotic count and central necrosis. However, their expression levels were not significantly different among age, gender, primary tumor site or CD117 expression. Additionally, there were positive correlations between COX-2 and VEGF (r = 0.612, P < 0.01), between COX-2 and MMP-9 (r = 0.592, P < 0.05), and between MMP-9 and VEGF (r = 0.690, P < 0.01). MMP-9, COX-2 and VEGF expression levels are increased in GIST tissues and related with clinicopathological features of GIST.

Expression and clinical significance of fibroblast growth factor 1 in gastric adenocarcinoma.

BACKGROUND: The clinical significance of fibroblast growth factor 1 (FGF1) has been revealed in several cancers, including ovarian cancer, breast cancer, and bladder cancer. However, the clinical significance of FGF1 in gastric adenocarcinoma has not been explored. PATIENTS AND METHODS: In our experiments, we systematically evaluated FGF1 expression in 178 cases of gastric adenocarcinoma with immunohistochemistry, and subsequently analyzed the correlation between FGF1 expression and clinicopathologic features. Moreover, FGF1 expression in tumor tissue and corresponding adjacent tissue was detected and compared by real-time polymerase chain reaction. The Kaplan-Meier method and the Cox-regression model were used with univariate and multivariate analysis, respectively, to evaluate the prognostic value of FGF1 in gastric adenocarcinoma. RESULTS: Higher FGF1 expression rate is 56.7% (101/178) in gastric adenocarcinoma. FGF1 expression in gastric adenocarcinoma was significantly higher than adjacent tissue (P<0.0001). Expression of FGF1 is significantly associated with lymph node invasion (P<0.001), distant metastasis (P=0.013), and differentiation (P=0.015). Moreover, FGF1 overexpression was closely related to unfavorable overall survival rate (P=0.021), and can be identified to be an independent unfavorable prognostic factor (P=0.004). CONCLUSION: FGF1 is an independent prognostic factor, indicating that FGF1 could be a potential molecular drug target in gastric adenocarcinoma.

[Association between G-protein beta3 subunit (GNB(3)) gene C825T polymorphism, hypertension, insulin resistance and obesity].

OBJECTIVES: To investigate the relationship between G-protein beta(3) subunit (GNB(3)) gene polymorphism and essential hypertension, insulin resistance and obesity. METHODS: Fasting plasma glucose (FPG), fasting insulin (Ins), lipid profile, and fibrinogen (Fib) were determined by convenient methods and the polymorphism of GNB(3) was detected by PCR-RFLP and sequencing in 376 individuals 187 first generation offsprings of hypertensives and 189 first generation offsprings of nonhypertensives in Daqing, China. The relationship between GNB(3) polymorphism and hypertension, insulin resistance was analyzed by univariate correlation analysis, and multivariate regression analysis with SAS software package. RESULTS: (1) The frequency of CT/TT genotype of GNB(3) C825T was significantly higher in the first generation offsprings of the hypertensives than in the first generation offsprings of nonhypertensives (0.78:0.69, P = 0.06). (2) The insulin sensitivity index [IAI = 1/(FPG x FINS)] in the CT and TT genotype groups was significantly lower than that in the group with CC genotype. The blood pressure and BMI were significantly higher than those of the CC genotype. (3) IAI was correlated negatively with SBP in CT/TT genotype group (r = -0.3519, P = 0.0001), whereas this correlation was not significant in the CC genotype group (r = -0.0055, P = 0.931). The patients were divided into 2 groups according to the median of IAI. In the group with the IAL higher than the median (LnIAI = -5.0016 +/- 0.1830) the SBP of the CT/TT genotype carriers was significantly higher than that of the CC genotype carriers (146 +/- 1.84 mm Hg vs 132 +/- 5.19 mm Hg, P < 0.05). In the group with the IAI lower than the median [IAI(2) = -4.1625 +/- 0.3716] the SBP of the CT/TT genotype carriers was not significantly different from that of the CC genotype carriers (136 +/- 2.4 mm Hg vs 133 +/- 2.0 mm Hg, P > 0.05). The comparison of diastolic pressure showed the similar result. (4) IAI had negatively correlation with SBP in CT/TT genotype carriers without hypertensive family history after controlling age and sex (r = -0.4864 P = 0.001), however, such correlation was not found in CC genotype carriers. CONCLUSION: CT and TT genotype of GNB(3) C825T was correlated with insulin sensitivity, blood pressure, and BMI. GNB(3) C825T gene enhances the hypertensive effect of insulin resistance.

[Is insulin resistance a common pathway for hereditary and environmental factors-induced hypertension?].

OBJECTIVE: To investigate whether insulin resistance is the common route for hereditary and environmental factors to cause hypertension. METHODS: 93 hypertensives with family history of hypertension, 94 hypertensives without family history of hypertension and 99 normal tensives without family history of hypertension as well as their spouse, and one child in each family were enrolled in the present study. Insulin sensitivity was calculated from fasting plasma glucose (FPG) and insulin (FINS) with the formula insulin sensitivity index (ISI) = 1/(FPG x FINS) and insulin resistance index (Homa-IR) = (FPG x FINS)/22.5. The contribution of insulin resistance to blood pressure elevation was investigated by multivariate regression analysis. RESULTS: Subjects with essential hypertension, regardless of the presence or absence of family history of hypertension, were more insulin resistant. Multivariate regression analysis demonstrated that insulin resistance contributed to 17% of mean blood pressure (MBP) elevation, whereas taken FPG + total cholesterol (TC) + high density lipoprotein (HDL) together it explained only 9% of MBP changes in the indicator group. When family history of hypertension was included as a independent variable in the analysis, it became the most important factor instead of insulin resistance in the model and contributed to 30% of the changes of MBP, while contribution of insulin resistance was significantly reduced as to explain only 7% of the changes of MBP. CONCLUSIONS: Insulin resistance is a common route for hereditary and environmental factors to induce hypertension. It is suggested that improving insulin sensitivity may play an important role in the management of essential hypertension.

[Relationship between calpain-10 gene polymorphism, hypertension and plasma glucose].

OBJECTIVE: To detect the association among calpain-10(CAPN-10) gene polymorphism, hypentension and hyperglycemia. METHODS: 378 individuals in the present study were the second generation offsprings of 187 hypentensives and 19 1 nonhypertensives. Fasting plasma glucose (FPG), insulin, triglyceride and fibrinogen were determined. The polymorphism of UCSNP-43 and UCSNP-44 of CAPN 10 gene were analysed with PCR-SSCP method. RESULTS: (1)The frequency of G/G geno type of UCSNP-43 was higher in the second generation offsprings of the hypertensives than that in the nonhypertensive controls(86.6%, 75.4%, P < 0.05). (2) The frequenncy of G/G genotype of UCSNP-43 was higher in the hypertensive parents of the second generation offsprings in the hypertensive groups than that in the normotensive parent of the second generation offsprings of the nonhypertensive control groups (OR = 2.84, P = 0.01). After adjustment of age, sex and body mass index (BMI), the frequency of G/G genotype in the highest FPG-quartiles (FPG 5.42 +/- 0.1mmol/L) was much more than that in the lowest FPG quartiles (FPG 4.09 +/- 0.3 mmol/L) with OR of 3.32. CONCLUSIONS: Polymorphism of UCSNP-43 in CAPN-10 gene might be one of the genetic factors contributing to hypertension and diabetes mellitus in the population in Daqing city. It may be a predictor of type 2 diabetes mellitus (T2DM) in the decendents of hypertensives.