Efficacy and Safety of Fruquintinib Combined with Sintilimab in Treatment of Advanced Microsatellite Stable Colorectal Cancer / 肿瘤防治研究

Objective To investigate the clinical efficacy and safety of fruquintinib combined with sintilimab in the treatment of advanced microsatellite stable (MSS) colorectal cancer. Methods A retrospective study of 44 patients with MSS colorectal cancer treated with fruquintinib and sintilimab was conducted.The patients were divided into the fruquintinib alone (n=22) and fruquintinib combined with sintilimab (n=22) groups.The treatment regimen was as follows: The patients in the fruquintinib alone group consumed oral fruquintinib capsules at 5 mg/d once for three consecutive weeks with a one week stop in 28 day cycles.The patients in the fruquintinib combined sintilimab group were injected intravenously with sintilimab (200 mg) once per three weeks, and fruquintinib was used in the same manner as the fruquintinib alone group. Results The objective response rate (ORR) of the fruquintinib alone group was 9.09%, the disease control rate (DCR) of the fruquintinib alone group was 45.45%.The ORR of the fruquintinib combined with sintilimab group was 18.18%, and the DCR was 63.64%.The median PFS of the fruquintinib alone and fruquintinib combined with sintilimab groups were 4.4 months (IQR: 2.1-8.2) and 6.7 months (IQR: 3.9-12.6), respectively (χ2=4.372, P=0.037).Most of the adverse reactions during the treatment of the two groups were grades 1-2.In addition, no significant difference in the incidence of adverse reactions was found between two groups (P > 0.05). Conclusion Compared with fruquintinib alone, fruquintinib combined with sintilimab in the treatment of patients with MSS colorectal cancer after the failure of standard treatment has better clinical efficacy, and adverse drug reactions can be controlled.

Prenatal diagnosis of Down syndrome using cell-free fetal DNA in amniotic fluid by quantitative fluorescent polymersase chain reaction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amniotic fluid (AF) supernatant contains cell-free fetal DNA (cffDNA) fragments. This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis, which could be combined with simple quantitative fluorescent polymerase chain reaction (QF-PCR) to provide an ancillary method for the prenatal diagnosis of trisomy 21 syndrome.</p><p><b>METHODS</b>AF supernatant samples were obtained from 27 women carrying euploid fetuses and 28 women carrying aneuploid fetuses with known cytogenetic karyotypes. Peripheral blood samples of the parents were collected at the same time. Short tandem repeat (STR) fragments on chromosome 21 were amplified by QF-PCR. Fetal condition and the parental source of the extra chromosome could be determined by the STR peaks.</p><p><b>RESULTS</b>The sensitivity of the assay for the aneuploid was 93% (26/28; confidence interval, CI: 77%-98%) and the specificity was 100% (26/26; CI: 88%-100%). The determination rate of the origin of the extra chromosome was 69%. The sensitivity and the specificity of the assay in the euploid were 100% (27/27).</p><p><b>CONCLUSIONS</b>Trisomy 21 can be prenatally diagnosed by the QF-PCR method in AF supernatant. This karyotype analysis method greatly reduces the requirement for the specimen size. It will be a benefit for early amniocentesis and could avoid pregnancy complications. The method may become an ancillary method for prenatal diagnosis of trisomy 21.</p>

Detection of the effect of bortezomib with arsenic trioxide different concentration on the cell cycle and apoptosis of Raji cells by flow cytometry / 白血病·淋巴瘤

Objective To investigate the effect of bortezomib with arsenic trioxide different concentration on the cell cycle and apoptosis of Raji cells. Methods Flow cytometry analysis showed that the relative number of cells in different phases and the percentages of cells calculated in G1 and S phase of the cell cycle and apoptosis were assessed after treatment with As2O3 and BOR or in combination with BOR in different concentration at indicated time (24 h, 48 h, 72 h). Results Flow cytometric analysis showed that the cell cycle was arrested at G1 phase, the number of cells G1 period increased significantly, and S phase decreased on Raji cells after As2O3 treatment. The relationship between the cellular DNA contents and the concentration of As2O3 showed a dose-and time-dependent manner (P ＜0.0001). But it was found that BOR had no effect on Raji cell cycle, but, in two drugs combination, cell apoptosis rate significantly increased from 16.98 % to 45.84 %. Conclusion The results show that As2O3 exerted variable and definite effects on lymphoma Raji cells, which indicated that As2O3 might induce apoptosis and arrest cell cycle. The combination of two drugs had a effective and synergistic effect on apoptosis.

Expression of glyoxalase Ⅰ and its effect on cell proliferation and apoptosis in endometrial carcinoma / 中华妇产科杂志

Objective To examine the expressions of glyoxalase Ⅰ (GLO-Ⅰ ) in endometrial cancer tissues and cell lines and to investigate the roles of GLO-Ⅰ on proliferation and apoptosis in endometrial cancer cells. Methods Immunohistochemistry, western blot and RT-PCR were used to investigate the expressions of GLO-Ⅰ protein and mRNA in endometrial cancer tissues and Ishikawa cell lines ;enzyme activity of GLO-Ⅰ in normal endometrium, endometrial cancer and paraneoplastic tissue samples was detected with spectrophotometer; proliferation and apoptosis of Ishikawa cell before and after RNA interference (RNAi) procedure were detected by the methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. Results (1)There were significant differences of GLO-Ⅰ expression between normal endometrium (0/19) and endometrial cancer tissues ( 76%, 22/29 ); these were also significant differences of enzyme activity of GLO-Ⅰ among normal endometrium, paraneoplastic and endometrial cancer tissues( 1.1,0.8 vs 92.3 IU/mg; P <0.01 ). Enzyme activity of GLO-Ⅰ in fresh normal endometrium and paraneoplastic tissues was weak, while that of fresh endometrial cancer tissues was as high as 92. 3 IU/mg in average. (2)The expression of GLO-Ⅰ mRNA in Ishikawa cell transfected with GLO-Ⅰ siRNA was significantly lower than that in negative group (0.25 ± 0.06 vs 0.93 ± 0.10, P < 0.0l ), and the similar results that in the expression of GLO-Ⅰ protein (0.38 ±0.06 vs 0.94 ±0.13, P <0.01 ). (3) Proliferation in Ishikawa cell was significantly inhibited after silencing RNA expression of GLO-Ⅰ ( P = 0.028 ). The apoptosis rate of cells transfected with GLO- Ⅰ siRNA was significantly higher than that of negative control group and blank control group [ ( 6.7 ± 0.8 ) % vs ( 1.2 ± 0.4) %, ( 1.4 ± 0.4 ) %; P < 0.01 ]. Conclusion The expression and enzyme activity of GLO- Ⅰ is significantly increased in endometrial cancer, which could promote abnormal proliferation and inhibit apoptosis in endometrial cancer cells.

Inhibitory effects of antisense Snail on invasion and migration of ovarian carcinoma cells / 中华妇产科杂志

Objective To investigate the inhibitory effects of Snail—— a zinc finger transcription factor, anti-sense plasmid on the invasion of ovary carcinoma cell lines in vitro. Methods Four human ovarian carcinoma cell lines ES-2,OVCAR3,HO8910,HO8910PM were analyzed for the expression of Snail and E-cadherin mRNA by RT-PCR.Then anti-Snail plasmid transfection was introduced into HO8910 cells using lipofectin 2000 reagent to investigate the inverse correlation between E-cadherin and Snail expression, and the inhibitory effects of anti-sense Snail were also detected by Transwell motility assay and Matrigel invasion assay. Results The results demonstrated the presence of Snail mRNA in ES-2,HO8910,HO8910PM detected by RT-PCR. By contrast, E-cadherin mRNA was only detected in OVCAR3 by RT-PCR.The inverse relationships were further observed by transient transfection of anti-sense Snail into HO8910 cells, which showed the down-regulated expression of Snail and the re-expression of E-cadherin. The Snail mRNA levels were 0.897?0.005,0.865?0.010,0.338?0.014 after 0,24,48 h of transfection and that of E-cadherin were 0,0.130?0.001,0.217?0.005 respectively, the difference was significant between different time points (P

Correlation of Helicobacter Pylori Infection in Liver Cirrhosis of Different Syndrome Patterns with Blood Ammonia Level / 广州中医药大学学报

Objective To explore the correlation of helicobacter pylori(HP) infection in liver cirrhosis(LC) of different syndrome patterns with blood ammonia level.Methods Two hundred and seventeen LC patients were divided into Hp-positive group and Hp-negative group.The patients were classified into 6 syndrome patterns: liver-Qi stagnation,internal accumulation of water-dampness,stagnation of damp-heat,deficiency of liver and kidney yin,deficiency of spleen and kidney yang,and blood-stasis blocking collaterals.Parameters of blood ammonia level,hepatic function and blood coagulation function were observed in LC patients with different syndrome patterns.Results The Hp infection rate in 217 LC patients was 40.1%,the difference being insignificant in the patients with different syndrome patterns and hepatic function grading.The percentage was in a decreasing sequence in syndrome patterns of stagnation of damp-heat,internal accumulation of water-dampness,blood-stasis blocking collaterals,deficiency of liver and kidney yin,liver-Qi stagnation,deficiency of spleen and kidney yang.The difference of blood ammonia level was significant between Hp-positive group and Hp-negative group(P0.05).Conclusion Hp infection is an important factor of inducing the increase of blood ammonia level in LC.Blood ammonia level increases in LC patients after Hp infection,especially in patients with blood-stasis blocking collaterals.The hepatic function grading is corrected with blood ammonia level,the worse the hepatic function,the higher the blood ammonia level.