[Efficacy and safety analysis of venetoclax combined with hypomethylating agents for the treatment of higher-risk myelodysplastic syndromes in the real world].

Objective: To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) . Methods: From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis. Results: ①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five naïve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions: There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

[Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center].

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

[Metagenomic next-generation sequencing of plasma for the identification of bloodstream infectious pathogens in severe aplastic anemia].

Objective: To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection. Methods: From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy. Results: ①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion: mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.

Philippine pediatric COVID-19 living clinical practice guidelines as of March 2022

Executive Summary@#The Coronavirus disease 2019 (COVID-19) pandemic has triggered a global crisis and has affected millions of people worldwide. With the evolution of the different variants of concern, the incidence of COVID- 19 in the pediatric population has risen. The Surveillance and Analysis of COVID-19 in Children Nationwide (SALVACION) Registry, developed by the Pediatric Infectious Disease Society of the Philippines (PIDSP) and the Philippine Pediatric Society (PPS), has reported 3,221 cases as of March 31, 2022, with 90.4% requiring hospitalization and 36.2% with moderate to critical disease severity. Given the magnitude of the impact of COVID-19, with most of the clinical recommendations available designed towards adult patients, there was an urgent need for clinicians, public health officials and the government to also prioritize evidence-based clinical practice guidelines for the pediatric population. Hence, the development of the Philippine Pediatric COVID-19 Living Clinical Practice Guidelines was conceptualized. This independent project, funded and supported by the PPS and PIDSP, aimed to formulate up-to-date, evidence-based recommendations on the treatment, diagnosis, infection prevention and control of COVID-19 in children. Following the standard CPG development process outlined in the DOH Manual for CPG Development and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, 15 evidence summaries and 24 recommendations were generated by 12 consensus panelists representing their specific health organizations and institutions.

[A case of diabetic retinopathy with coagulation factor â § and â « deficiency].

The patient was a 48-year-old male with a previous history of diabetes mellitus and hypertension. The patient had persistent bleeding after vitrectomy of the left eye, and the patient was examined for abnormal coagulation factor Ⅷ combined with Ⅻ. This case suggests that we need effective control of blood glucose and blood pressure in patients undergoing vitrectomy in clinical work, and adequate examination of coagulation function. Patients with coagulation factor deficiency should be treated with plasma transfusion to supplement coagulation factors before performing the necessary surgical treatment to prevent severe bleeding.

[Relationship between micronutrients supplementation during periconceptional period and serum concentration of vitamin E in the 1st trimester of gestational period].

OBJECTIVE: To explore the association of maternal periconceptional folic acid or multiple micronutrients supplementation during periconceptional period and the serum vitamin E (Vit.E) concentration in the 1st trimester of gestational period. METHODS: A retrospective cohort study was conducted based on the prenatal health care system and clinical laboratory information system. Totally, 22 171 pregnant women who had their prenatal health care and gave birth in Tongzhou Maternal & Child Health Hospital of Beijing from Jan. 2016 to Dec. 2018 were recruited. The usage patterns of nutritional supplements [folic acid (FA) or multiple micronutrients (MM)] during periconceptional period were independent variables, and serum Vit.E concentration and serum Vit.E concentration≥11.2 mg/L in the 1st trimester of gestational period were outcome variables for generalized linear regression model and Logistic regression model, respectively, to analyze the relationships between the independent and outcome variables. RESULTS: The range of the serum Vit.E concentration in the 1st trimester of gestational period was 5.2-24.0 mg/L, and the median concentration was 10.1 (8.8-11.6) mg/L; the excess rate of the serum Vit.E of those who took MM supplementation was 0.3%, and the rates for the groups of FA only or no nutritional supplements used were both 0.1%. Compared with women without nutritional supplement or the women taking FA, the women who took MM had higher serum Vit.E levels in the 1st trimester of gestational period (both P < 0.05). The women taking FA or MM initiated before the conception showed that the serum Vit.E concentration in the 1st trimester of gestational period was higher than that after the conception (P < 0.05), and the serum Vit.E concentration of women who took regularly was higher than that of irregular taking (P < 0.05); with taking compliance elevated, the serum Vit.E concentration of the two groups of women taking FA or MM increased (P < 0.05). The risk of serum Vit.E concentration≥11.2 mg/L among the women taking MM was higher than that of the women without nutritional supplements or taking FA only [odds ratio (OR)=1.36, 95% confidence interval (95%CI): 1.21-1.53; OR=1.39, 95%CI: 1.31-1.48)]; women who took FA or MM showed a lower risk for serum Vit.E concentration≥11.2 mg/L of taking it after the conception than before, the ORs (95%CI) were 0.86 (95%CI: 0.77-0.96) and 0.88 (95%CI: 0.81-0.95), respectively; the women taking the two supplements regularly had higher risk for serum Vit.E concentration≥11.2 mg/L than irregular taking, the ORs (95%CI) were 1.16 (95%CI: 1.05-1.29) and 1.13 (95%CI: 1.04-1.22) for FA and MM users, respectively; with the compliance increasing, the women taking MM had a higher risk of serum Vit.E levels≥11.2 mg/L in the 1st trimester [OR (95%CI) was 1.10 (1.07-1.14)], but for FA users, the OR (95%CI) was 1.04(1.00-1.08). CONCLUSION: Vit.E nutritional status in women in early gestational period in Beijing was generally good, and the excess rate of serum Vit.E was higher in women who took MM during periconceptional period than those without nutritional supplement or taking FA only, suggesting that women need to consider their own Vit.E nutritional status to choose the type of nutritional supplements during periconceptional period, so as to avoid related health hazards.

[Risk factors for leukemia transformation in patients with myelodysplastic syndromes].

Objective: To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) . Methods: From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done. Results: The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age (P<0.001) , bone marrow blast percentage (P<0.001) , bone marrow fibrosis (P=0.046) , WHO classification (P<0.001) , IPSS-R (P<0.001) and IPSS-R karyotype group (P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference (P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation (P=0.034) , DNMT3A mutation (P=0.026) , NRAS mutation (P=0.027) and NPM1 mutation (P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups (HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation (HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation (HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion: Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

[Prognostic factors of cyclosporine A combined with danazol with or without thalidomide in myelodysplastic syndrome treatment with low-percentage bone marrow blasts].

Objective: To explore the outcome of cyclosporine A (CsA) combined with danazol with or without thalidomide regimen for myelodysplastic syndrome (MDS) with low-percentage bone marrow blasts and predictive factors for treatment response. Methods: Data of 115 subjects who were newly diagnosed with primary MDS with low-percentage bone marrow blasts and were treated with CsA combined with danazol with or without thalidomide from December 2011 to December 2019 in our center were collected. Their clinical features, efficacy, and predictive factors of efficacy were retrospectively analyzed. A model for predicting this response was developed. Results: A total of 55 subjects responded (47.8%) , including 11 complete responses and 44 hematologic improvements. Fifty-two patients (52/105, 49.5%) achieved erythrocyte response; 35 (35/86, 40.7%) , platelet response; and 14 (14/40, 35%) , neutrophil response. Of 29 subjects (24.1%) , 7 who were red blood cell (RBC) transfusion-dependent became independent of transfusion. The median response duration was 20 months (range, 3-84 months) . In the univariate analysis, patients <0 years had a higher response rate than those ≥60 years (52.5% vs 22.2%, P=0.018) . Contrarily, the response rate was substantially decreased in patients with RBC transfusion dependence compared with those without RBC transfusion dependence (24.1% vs 55.8%, P=0.003) , as well as in patients with the mutated U2AF1 compared with those with the wild-type U2AF1 (26.1% vs 53.2%, P=0.020) . In multivariable analyses, age <0 years (OR=4.302, 95% CI 1.245-14.820, P=0.021) , RBC transfusion dependence (OR=3.774, 95% CI 1.400-10.177, P=0.009) , and U2AF1 mutation (OR=3.414, 95% CI 1.168-9.978, P=0.025) were significantly correlated with response. Variables that independently predicted the response were combined to generate the predictive model. According to the model, the overall response rates of patients with 0, 1, 2, and 3 risk factors were 65%, 30%-35%, 10%-15%, and 3%, respectively. Conclusion: CsA combined with danazol with or without thalidomide regimen could improve cytopenia symptoms in patients with MDS with low-percentage bone marrow blasts. At age <60 years, no transfusion dependence of RBC and wild-type U2AF1 mutation is a favorable prognostic factor.

[The observation of secretogranin â ¢ in the peripheral blood and vitreous of patients with diabetic retinopathy].

Objective: To study the expression levels of secretogranin Ⅲ (SCG3) in the peripheral blood and vitreous of patients with diabetic retinopathy (DR). Methods: Cross-sectional research. A total of 77 patients (41 men and 36 women, 77 eyes) received vitrectomy in Tianjin Medical University Eye Hospital from May to December 2018, with an average age of (60.75±11.34) years. According to the blood glucose level, diabetes history and fundus status, all the patients were divided into the DR group and the non-diabetic group. According to the patients' blood lipids and body mass index (BMI), patients were further divided into subgroups of high blood lipids, normal blood lipids, high BMI and normal BMI. All patients were tested with eye examinations, height and weight to calculate the BMI, and blood lipid levels in the peripheral blood. The vitreous was collected during the vitrectomy surgery, and the levels of SCG3 in the vitreous and peripheral blood were analyzed by ELISA. All the data were analyzed statistically with Wilcoxon rank sum test. Results: There were 43 patients in the DR group, among whom 25 had hyperlipidemia, 18 had normal blood lipids, 22 had a high BMI, and 21 had a normal BMI. There were 34 patients in the non-diabetic group, among whom 13 had hyperlipidemia, 21 had normal blood lipids, 17 had a high BMI, and 17 had a normal BMI. The level of SCG3 in the DR group [6.02 (4.34, 11.76) ng/ml] was higher than that in the non-diabetic group [4.30 (3.20, 10.78) ng/ml] (Z=-2.339, P =0.019). The level of SCG3 in the hyperlipidemia subgroup of the DR patients [7.94 (5.33, 13.51) ng/ml] was higher than that in the normal blood lipid subgroup of the non-diabetic patients [4.04 (3.12, 7.77) ng/ml] (Z=-3.473, P=0.001), and higher than that in the DR patients without hyperlipidemia [4.45 (3.71, 9.14) ng/ml] (Z=-2.511, P=0.012). The level of SCG3 in the DR patients with a high BMI [7.12 (4.56, 13.12) ng/ml] was higher than that in the non-diabetic patients with a normal BMI [3.53 (3.16, 4.38) ng/ml] (Z=-3.767, P =0.000). The level of SCG3 in the DR patients with a normal BMI [5.72 (4.10, 11.60) ng/ml] was higher than that in the non-diabetic patients with a normal BMI (Z=-2.862, P = 0.004). SCG3 in the plasma was rare or can not be detected. Conclusions: The concentration of SCG3 in the vitreous increase in DR patients. However, SCG3 can not be detected in the healthy vascular system. (Chin J Ophthalmol, 2020, 56: 933-937).

[Relationship between serum vitamin E concentration in first trimester and the risk of developing hypertension disorders complicating pregnancy].

OBJECTIVE: To investigate the incidence of hypertension disorders complicating pregnancy (HDCP) and vitamin E (VE) nutritional status among pregnant women in Beijing, and to determine the relationship between serum VE concentration in the first trimester of pregnancy and the risk of developing HDCP. METHODS: A retrospective cohort study was performed including 22 283 cases of pregnant women who underwent singleton deliveries in Tongzhou Maternal & Child Health Hospital of Beijing from January 2016 through December 2018 and received tests of serum VE concentrations in the first trimester of pregnancy. Nonconditional Logistic regression model was used to analyze the association between serum VE concentration levels and the risk of developing HDCP. RESULTS: The total incidence of HDCP was 5.4%, with the incidence of gestational hypertension around 2.1% and the incidence of preeclampsia-eclampsia around 3.3%. The median concentration of serum VE in early pregnancy was 10.1 (8.8-11.6) mg/L, and 99.7% of the participants had normal serum VE concentrations. The incidence of gestational hypertension and that of preeclampsia-eclampsia had been annually increasing in three years; a linear-by-linear association had also been observed between the serum VE concentrations and the years of delivery. According to the results of the univariable and the multivariable Logistic regression analyses, higher risks of developing HDCP had been observed among women with higher serum VE concentrations. Compared to those with serum VE concentrations in interquartile range (P25-P75) of all the participants, the women whose serum VE concentrations above P75 were at higher risks to be attacked by HDCP (OR = 1.34, P < 0.001), gestational hypertension (OR = 1.39, P = 0.002), or preeclampsia-eclampsia (OR = 1.34, P = 0.001), as suggested by the results of the multivariable Logistic regression model analyses. In addition, the women with serum VE concentrations of 11.2 mg/L or above had a significantly higher risk of developing HDCP than those whose serum VE concentrations of P40-P60 of all the participants, and this risk grew higher as serum VE concentrations in the first trimester of pregnancy increased. CONCLUSION: Women in Beijing are at good nutritional status. From January 2016 to December 2018, the incidence of HDCP increased with serum VE concentration level, and serum VE concentration of 11.2 mg/L is an indicator of an increased risk of developing HDCP, suggesting that pregnant women should take nutritional supplements containing VE carefully.

[Effect of exogenous gonadotropin dosage on embryo aneuploidy rate and pregnancy outcome in patients of preimplantation genetic test].

Objective: To investigate the effect of gonadotropin (Gn) on embryo aneuploidy rate and pregnancy outcome during preimplanptation genetic testing for aneuploidy (PGT-A) cycles. Methods: The clinical data of patients undergoing PGT-A cycle at the First Medical Center of the PLA General Hospital from January 1, 2013 to May 31, 2019 were retrospectively analyzed. Patients were divided into younger patient group (<35 years old) and elder patient group (≥35 years old) by maternal age, then divided into two groups in line with Gn dosage (≤2 250 U, >2 250 U), and into four groups by number of oocytes retrieved (1-5, 6-10, 11-15 and ≥16 oocytes). The embryo aneuploidy rate and pregnancy outcome between the groups were compared. Logistic regression was used to analyze the relationship between the cumulative amount of Gn, embryo aneuploidy rate and live-birth rate. Results: A total of 402 cycles (338 patients) and 1 883 embryos were included in the study. (1) In the younger patients, the aneuploidy rate was 52.5% (304/579) in the group of Gn≤2 250 U and 48.6% (188/387) in the group of Gn>2 250 U, with no significant difference between them (P=0.232). In the elderly patients, the difference in embryo aneuploidy rate between the two Gn group [57.9% (208/359) versus 60.6% (319/526)] was not statistically significant (P=0.420). (2) The embryonic aneuploidy rate in different protocol of ovary stimulation was analyzed,in the younger group, the embryonic aneuploidy rate in patients using antagonist long protocol was 50.3% (158/314), it was 50.0% (121/242) in agonist long protocol, 52.1% (207/397) in agonist short protocol and 6/13 in luteal phase protocol, no statistical difference was found in above groups (P=0.923); in the elder group, embryonic aneuploidy rate was 60.8% (191/314) in antagonist protocol, 58.4% (132/226) in agonist long protocol, 59.2%(199/336) in agonist short protocol, 5/9 in luteal phase protocol, respectively,no significant difference was found (P=0.938). (3) In the younger patients, the aneuploidy rate in 1-5 oocytes group, 6-10 oocytes group, 11-15 oocytes group and ≥16 oocytes group was 37.9% (11/29), 54.0% (94/174), 52.5% (104/198) and 50.1% (283/565) respectively, no significant difference was found between the groups (P=0.652); while in the elder patients, the difference between aneuploidy rate in each retrieved oocytes group [73.6% (89/121), 57.5% (119/207), 56.3% (108/192), 57.8% (211/365)] was statistically significant (P=0.046). (4) Logistic regression analysis of age, cumulative dosage of Gn, number of oocytes obtained, and embryo aneuploidy rate showed that there was no association between the amount of Gn and embryo aneuploidy rate (P>0.05); the increase in maternal age would increase the risk of aneuploidy rate of embryos, which was statistically significant (OR=1.031, 95%CI: 1.010-1.054, P=0.004); the increase in oocytes retrived would significantly decrease the risk of aneuploidy (OR=0.981, 95%CI: 0.971-0.991, P<0.01). (5) There was no significant difference in biochemical pregnancy rate [55.6% (80/144) versus 52.1% (63/121)], clinical pregnancy rate [50.0% (72/144) versus 47.9% (58/121)] and live-birth rate [46.5% (67/144) versus 40.5% (49/121)] between different Gn dosage groups (P=0.613, P=0.738, P=0.324). The logistic regression analysis showed that the maternal age, the cumulative dosage of Gn, the number of oocytes obtained, and the ovarian stimulation protocol had no effect on the live-birth rate (all P>0.05). Conclusions: In PGT-A cycle, the dosage of Gn has no association with the embryo aneuploidy rate and pregnancy outcome. In the patients ≥35 years old, the increase in number of oocytes obtained may decrease the risk of aneuploidy. Age is an important factor affecting the embryo aneuploidy in PGT-A cycle.

Oncogene miR-934 promotes ovarian cancer cell proliferation and inhibits cell apoptosis through targeting BRMS1L.

OBJECTIVE: Ovarian cancer is a common malignant cancer among women. Increasing studies have demonstrated that microRNAs function as important regulation factors in the progression of ovarian cancer. MATERIALS AND METHODS: Human ovarian cancer cell lines HO8910 and OVCAR-3 were transfected with miR-934 inhibitor and corresponding negative control (inhibitor control). Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) and TUNEL assay, respectively. The expression levels of proliferation/apoptosis-related genes and BRMS1L were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting. Furthermore, the association between miR-934 and BRMS1L was investigated through luciferase reporter assays. RESULTS: MiR-934 was significantly increased in ovarian cancer cell lines, whereas BRMS1L was significantly decreased. Downregulated miR-934 remarkably inhibited cell proliferation and induced cell apoptosis. Meanwhile, miR-934 could influence the expression levels of Ki67, Cyclin D1, Caspase3, and Bcl-2. In addition, BRMS1L was identified as a target gene of miR-934. CONCLUSIONS: Oncogene miR-934 promotes ovarian cancer cell proliferation and inhibits cell apoptosis through targeting BRMS1L. MiR-934 and BRMS1L may be novel biomarkers or therapeutic targets for ovarian cancer in the future.

[Long term clinical observation on postoperative microstructural change of macula lutea in treatment of idiopathic macular epiretinal membrane].

Objective: To evaluate the relationship between the structure of macular region and prognosis after vitrectomy in idiopathic macular epiretinal membrane patients. Methods: Retrospective case series study. The cases of 74 idiopathic macular epiretinal membrane patients (31 female patients, 43 male patients, aged 68.1±6.9) who received surgery treatment in our hospital during January 2013 and December were collected and analyzed. Ophthalmic routine examination and optical coherence tomography (OCT) have been conducted for all patients prior to operation. All eyes underwent vitecrtomy and macular epiretinal membrane peeling. During the 12 months follow up, the preoperative and postoperative data including best corrected visual acuity (BCVA), foveal thickness, changes of morphology in ellipsoid zone were observed and analyzed. All the patients were divided into two groups, continuous group (52 patients) and discontinuous group (22 patients), based on the preoperative continuity status of ellipsoid zone. The data of preoperative macular retinal thickness, the relationship between age and course of the disease, preoperative BCVA and postoperative BCVA were analyzed statistically with repeated ANOVA method. The postoperative BCVA were analyzed statistically with t test mtehod, based on the different grouping of continuity status of ellipsoid zone. Results: The preoperative LogMar BCVA, and the postoperative LogMAR BCVA of 1 month, 3 month, 6 month and 12 month after operation were 0.59±0.26, 0.63±0.34, 0.46±0.22, 0.45±0.23, 0.41±0.23 (F=25.122, P<0.05) respectively. The preoperative foveal thickness, and the postoperative foveal thickness of 1 month, 3 month, 6 month and 12 month after operation were (468.12±73.07), (371.57±57.09), (320.57±65.88), (294.85±69.36), (283.5±66.56)µm (F=8.802, P<0.05), the difference between the figures are of statistical significance. The postoperative BCVA of continuous group (0.34±0.27) improved significantly, as compared to the BCVA of discontinuous group (0.62±0.24) (t=-4.209, P<0.05). There is no obvious relationship between the degree of preoperative macular edema and postoperative visual function (r=0.015, P> 0.015). Seven patients still have macular edema one year after surgery. Conclusion: The postoperative visual function in patients with idiopathic macular epiretinal membrane has negative correlation with preoperative thickness of fovea, and has positive correlation with continuity of ellipsoid zone. (Chin J Ophthalmol, 2018, 54: 258-262).

A method for tracing exogenous DNA uptake in live spermatozoa and embryos.

Sperm-mediated gene transfer(SMGT) is a simple method for producing transgenic animals. Due to the lack of repeatability in spermatozoa binding and internalization of exogenous DNA, the efficiency of SMGT is still low. Considering this point, the present work aims to develop a method for evaluating the spermatozoa capacity of binding exogenous DNA after co-incubation with DNA. The main approach is using a Cy5-labelled DNA to trace the exogenous DNA and assess the ability of spermatozoa to take up exogenous DNA. Using this technique, we found that the percentage of spermatozoa that are binding and uptaking DNA is higher at concentration of 10 µg/mL and 100 µg/mL than 5 µg/mL, 1 µg/mL and 0 µg/mL after incubation with Cy5-DNA for 30min at 37oC. After fertilization, the DNA fluorescence signal was also detected in zygotes in groups where spermatozoa were incubated with 10 µg/mL and 100 µg/mL of Cy5-DNA. These results showed a simple and convenient method to trace the exogenous DNA in spermatozoa and zygote when compared to conventional methods of labeling DNA during fertilization, resulting in a real-time observation of the exogenous DNA in spermatozoa and zygote.

CUL4B promotes gastric cancer invasion and metastasis-involvement of upregulation of HER2.

Cullin 4B (CUL4B) is a scaffold protein overexpressed in several solid malignancies. It is known to silence tumor suppressor through post-transcriptional manner. However, its clinical significance and underlying molecular mechanisms in gastric cancer (GC) remain largely unknown. In this study, we found that CUL4B was significantly overexpressed in GC tissues and its overexpression was correlated with lymph node metastasis and poor prognosis. Through gain- and loss-of-function experiments, we showed that CUL4B promotes GC cell invasion and epithelial-mesenchymal transition (EMT) in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, we identified HER2 as a downstream target gene of CUL4B in GC. CUL4B unregulated HER2 expression via transcriptionally repressing miR-125a. Intriguingly, HER2 inhibitors significantly reversed CUL4B-induced EMT in vitro and partially blocked GC metastasis in tumor xenografts with CUL4B overexpression. Finally, we suggested the involvement of the PI3K/AKT pathway in CUL4B-induced HER2 upregulation in GC. In all, we proposed a model for a CUL4B-miR-125a-HER2 oncoprotein axis, which provided novel insight into how HER2 was activated and contributed to GC progression and metastasis.

A rapid review of needs assessment tools for post-treatment cancer survivors.

Relevant, comprehensive and psychometrically rigorous needs assessment tools are needed to ensure appropriate care is delivered to cancer survivors who have completed treatment. The aim of this rapid review was to identify and describe needs assessment tools that are used in cancer survivors post-treatment, assess their psychometric properties and describe their use in clinical care. The electronic databases Medline, Cochrane Library, CINAHL and PsycINFO were searched. Six studies were identified that described five needs assessment tools used in cancer survivors post-treatment. None of these tools covered all domains of unmet need nor demonstrated adequate evidence of all recommended criteria of validity and reliability. Few had been evaluated for use in a clinical environment. Out of the five tools, the Survivor Unmet Needs Survey (SUNS) showed the strongest psychometric properties. There is little empirical evidence available to guide recommendations on the most appropriate process of conducting needs assessment with cancer survivors once they have completed treatment.

Effect of the acrosome reaction on the efficiency of sperm-mediated DNA transfer.

Sperm-mediated gene transfer (SMGT) is based on the ability of spermatozoa to bind exoge- nous DNA and transfer it into oocytes by fertilization. However, SMGT is still undergoing opti- mization to improve its efficiency to produce transgenic animals. The acrosome reaction is neces- sary for spermatozoa to carry the exogenous DNA into oocytes. In this study, the effect of the acrosome reaction on the efficiency of spermatozoa carrying exogenous DNA was evalua- ted. The results showed that the efficiency of the acrosome reaction was significantly higher (p⟨0.05) after incubation with 50 µmol/L progesterone compared to incubation without proges- terone. It was significantly higher (p⟨0.05) in the 20, 40, and 60 min of progesterone treatment groups than in the 0 min treatment group. The spermatozoa were further incubated with cyanine dye Cy5 labeled DNA (Cy5-DNA) for 30 min at 37°C, and positive fluorescence signals were detected after the acrosome reaction was induced by progesterone at concentrations of 0 and 50 µmol/L for 40 min. The percentage of positive Cy5-DNA signals in spermatozoa was 96.61±2.06% and 97.51±2.03% following exposure to 0 and 50 µmol/L progesterone, respective- ly. The percentage of partial spermatozoa heads observed following combination with Cy5-DNA was 39.73±3.03% and 56.88±3.12% following exposure to 0 and 50 µmol/L progesterone, respec- tively. The ratio of positively stained spermatozoa combined with exogenous DNA showed no reduction after the acrosome reaction. These results suggest that the acrosome reaction might not be the key factor affecting the efficiency of SMGT.