Analysis of a child with holoprosencephaly due to variant of SIX3 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a child with holoprosencephaly.@*METHODS@#Genomic DNA of the child was extracted and subjected to whole exome sequencing. Suspected variant was verified by Sanger sequencing of her family members.@*RESULTS@#Cranial MRI suggested lobulated holoprosencephaly with partial absence of corpus callosum. Genetic testing revealed that she has carried a heterozygous c.517C>G (p.His173Asp) variant of the SIX3 gene, for which both of her parents were of wild type. Based on the American College of Medical Genetics and Genomics guidelines, the c.517C>G variant of SIX3 gene was predicted to be pathogenic (PS2+PM1+PM2+PM5+PP3).@*CONCLUSION@#The SIX3 gene c.517C>G variant probably underlay the multiple malformations in this child. Above finding has enabled her definite diagnosis.

Simultaneous Determination of 7 Effective Components in Yao Medicine Yueli Yaomi Spray by QAMS / 中国药房

OBJECTIVE：To establish QAMS method for simultaneou s determination of 7 effective components in Yao medicine Yueli yaomi spray ，such as α-cyperone，α-pinene，β-pinene，limonene，β-elemene，caryophyllene oxide and ligustilide ， so as to provide method reference for the quality control of the preparation. METHODS ：GC method was adopted. The determination was performed on DB- 1701P capillary column ，using nitrogen as carrier gas. The temperature of the hydrogen flame ion detector was 240 ℃. The temperature was programmed ，the inlet temperature was 240 ℃，the injection volume was 1 μL and the split ratio was 20 ∶ 1. Using limonene as internal reference ，the relative correction factors of other 6 components were calculated，the contents of them were calculated with relative correction factors ，and then compared with the results of internal standard method （using naphthalene as internal standard ）. RESULTS ：The mass concentration linear range of α-cyperone， α-pinene，β-pinene，limonene，β-elemene，caryophyllene oxide and ligustilide were 0.008 9-1.110 0，0.028 3-3.540 0，0.020 5- 2.560 0，0.023 0-2.880 0，0.016 3-2.035 0，0.013 1-1.640 0，0.008 3-1.040 0 mg/mL（all r＞0.999 0）；the limits of quantification were 0.005 6，0.013 1，0.011 4，0.018 6，0.010 8，0.008 9，0.004 5 mg/mL；the detection limits were 0.001 9，0.004 1，0.003 7， 0.006 2，0.003 5，0.002 9，0.001 5 mg/mL；RSDs for precision ，stability（24 h），and repeatability tests were all less than 2％ （n＝5 or n＝6）； the average recoveries were 98.48％ ， 014） 101.37％，97.96％，99.80％，102.79％，97.77％，102.14％， and RSDs were all lower than 2％（n＝9），respectively. The average relative correction factors of α-cyperone，α-pinene， β-pinene，β-elemene，caryophyllene oxide and ligustilide were 1.045 8，0.621 0，0.488 5，0.382 9，0.708 9，0.956 9 respectively，and the RSDs were all lower than 2％（n＝6）. There wa s no statistical significance in contents of 7 components between QAMS method and internal standard method （P＞0.05）. CONCLUSIONS ：The established QAMS method is simple ， accurate，stable and reproducible ，and can be used for simultaneous determination for 7 components in Yueli yaomi spray.

Efficacy observation of lenalidomide and rituximab in treatment of relapsed/refractory B-cell non-Hodgkin lymphoma / 白血病·淋巴瘤

Objective To evaluate the safety and efficacy of lenalidomide plus rituximab in treatment of the patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Methods The clinical data of the patients with relapsed/refractory B-NHL after the varieties of treatment methods in Peking Union Medical College Hospital between January 2015 and December 2017 were retrospectively analyzed. All the patients were treated with R2 regimen: oral lenalidomide (25 mg/d for day 1-day 21) and rituximab (375 mg/m2 of intravenous infusion on day 1, 28-day of each cycle); the efficacy was evaluated after three cycles. After this induction phase, the patients achieving complete response (CR), partial response (PR), or stable disease (SD) were given R2 regimen until the end of 8 cycles. The major end point was overall response rate (ORR) defined as CR + PR. Secondary end point included 1-year progression free survival (PFS), 1-year overall survival (OS) and grade 3-4 adverse events. T cell and B cell subsets of 7 patients at baseline were measured, and T cell and B cell subsets of 13 patients with good efficacy were dynamically observed. Results A total of 49 patients who received 1-4 chemotherapy regimens were included. The ORR after the R2 treatment for 3 courses was 65% (32/49). Thirty-six patients (9 cases of CR, 22 cases of PR, 5 cases of SD) were enrolled in R2 maintenance treatment. The median follow-up time was 13 months, 1-year PFS rate was 61% and 1-year OS rate was 84% . The most common adverse event was bone marrow suppression, including grade 3-4 neutropenia (27% ), grade 3-4 thrombocytopenia (6% ) and grade 4 anemia (4% ), most of which could be controlled by prolonging interval cycles or reduced lenalidomide dosage. The decreased number of CD19+B cell after treatment could be seen in 13 patients who obtained good efficacy under the dynamic observation. Conclusion Lenalidomide plus rituximab is well tolerated and highly active in the treatment of relapsed/refractory B-NHL.

Expression and prognostic value of CARD11 in diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To determine the CARD11 expression and its prognostic value in diffuse large B cell lymphoma (DLBCL).</p><p><b>METHODS</b>This retrospective study included previously untreated patients diagnosed with DLBCL from January 2007 to December 2012. Formalin-fixed, paraffin-embedded blocks of these patients were collected. Tissue microarray was built and expression of CARD11 was examined immunohistochemically. Subtype of DLBCL was determined by Hans algorithm (CD10, BCL6, MUM1). The pattern of CARD11 was further studied and their correlation with outcome was analyzed.</p><p><b>RESULTS</b>79 patients with DLBCL were enrolled and two reactive lymph nodes were used as control. The positive rate of high CARD11 expression in DLBCL was 65.33%, which showed no significant associations with patients' characteristics. Positive CARD11 expression was associated with an inferior event free survival (EFS)(2- year EFS: 52.03%vs 86.12%,P=0.036). Even in patients with a high international prognostic index (IPI, 3-5 points), this difference still remained significant (Median EFS not reached vs 557 days,P=0.033).</p><p><b>CONCLUSION</b>DLBCL patients with high CARD11 expression had a shorter EFS compared with low level of CARD11. This difference remained significant when patients were in high IPI (3-5 points), which might indicate the value of CARD11 in stratification of high-risk DLBCL patients.</p>

Association between fasting plasma glucose in early pregnancy and diagnosis of gestational diabetes mellitus / 中华围产医学杂志

Objective To explore the relevance between fasting plasma glucose (FPG) level in early pregnancy and gestational diabetes mellitus (GDM). Methods Clinical data of 5299 singletonpregnant women accepted antenatal examination and delivered in the Department of Obstetrics and Gynecology, Peking University First Hospital from January 1, 2008 to December 31, 2009 were retrospectively analyzed. Results (1) The pregnant women were divided into 3 groups according to their FPG levels at early stage of gestation: Group A, FPG ＜5. 1 mmol/L (n= 4565); Group B,FPG≥5.1, but ＜5.8 mmol/L (n=701); Group C, FPG≥5.8 mmol/L, but ＜7.0 mmol/L(n=33). The incidence of GDM in Group A, B and C was 10. 69% (488/4565), 26. 11% (183/701)and 54. 55% (18/33). (2) The incidences of large for gestational age (LGA), cesarean section,premature birth, preeclampsia, neonatal hyperbilirubinemia, neonatal hypoglycemia, neonatal polycythemia, and neonatal infection were compared between Group A and B. The cesarean section rate [54. 63% (282/518)]and neonatal hypoglycemia rate [1.54% (8/518)]of those who were not diagnosed as GDM in middle and late term in Group B were higher than those of Group A [49.03%(1999/4077) and 0. 61% (25/4077)] (P＜0. 05); while there were no differences between the other six index of Group A and Group B (P＞0. 05). The prognosis of the GDM patients who did not accept gestational glucose management in two groups were similar (P＞0. 05), so did the prognosis of the GDM patients who accepted gestational glucose management in two groups. After combining the patients of the two groups who were not diagnosed as GDM as a new group, they were compared with those who did not accept gestational glucose management of the two groups (Group A2 and B2)respectively. The incidence of LGA rate of the new group was lower than that of Group A2 (12. 00%va 4. 94 %, x2=21. 4159, P＜0. 05) and Group B2 (18. 39 % vs 4. 94%, x2 = 28. 7189, P＜0. 05).Cesarean section rate of the new group was lower than that of Group A2 (57. 78% vs 49.64%,x2 =5. 6806,P＜0.05) and Group B2 (66. 67% vs 49.64%, x2 =9. 9003, P＜0. 05). And there were no differences between the other six index between the new group and the other two groups (P＞0. 05). Conclusions The diagnosis criteria of GDM set as FPG≥5.1 mmol/L at early stage of gestation, recommended by International Association of Diabetes and Pregnancy Study Group, is not applicable in China yet. Oral glucose tolerance test in middle and late term is still the most important diagnostic tool for GDM.