[Breast ultrasound optimization process analysis based on breast cancer screening for 1 501 753 rural women in China].

Objective: To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening. Methods: The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children's public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated. Results: A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area (P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area (P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area (P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area (P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area (P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area (P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions: The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.

[Epidemiological characteristics of HIV infected pregnant women and exposed infants in Guangdong province, 2014-2017].

Objective: To analyze the epidemiological characteristics of HIV-infected pregnant women and exposed infant in Guangdong province and identify the factors associated with infant HIV infection through mother-to-child transmission. Methods: National Information System for Prevention of mother-to-child HIV Transmission and Early Infant Diagnosis Information Management Platform were used to collect the individual information about HIV-infected pregnant women and exposed infants who were delivered in Guangdong from January 1, 2014 to December 31 in 2017. The differences in pregnant women's demographic data, history of pregnancy and childbirth, the utilization of mother-to-child transmission prevention services and early infant diagnosis between the infected HIV exposed infants and uninfected HIV exposed infants were compared, and univariate and multivariate logistic regression analyses were conducted to identify the factors associated with mother-to-child HIV transmission. Results: Among 349 HIV infected pregnant women, the proportions of the pregnant women whose HIV infection status were confirmed before pregnancy, during pregnancy and at or after childbirth were 30.4% (106/349), 49.6% (173/349) and 20.0% (70/349) respectively. The proportions of those with sexual partners whose HIV infection status were unknown and those receiving no antiviral treatment were 39.5% (138/349) and 13.2% (46/349) respectively. Among the HIV exposed infants, the mother-to-child transmission rate was 4.2%(15/353), the HIV exposed infants had the first or second early diagnosis tests within 44 (P(25)-P(75): 42-50) days and 96 (P(25)-P(75): 92-106) days after birth, respectively. Univariate logistic regression analysis indicated that the risk for mother-to-child HIV transmission increased in those whose HIV infection status were confirmed at or after childbirth compared with before pregnancy (OR=5.72, 95%CI: 1.52-21.61) and in the group that antiviral treatment was given to either mothers or infants compared with the group that antiviral treatment was given to both mothers and infants (OR=33.56, 95%CI: 9.04-124.55), while there was lower mother-to-child HIV transmission risk in artificial feeding group compared with breast feeding group (OR=0.07, 95%CI: 0.01-0.76). Conclusion: The risk of mother-to-child HIV transmission in Guangdong can be effectively reduced by the measures of early diagnosis, antiviral treatment and artificial feeding as well as the improvement of mother-to-child transmission prevention service.

Bioengineering of coagulation factor VIII for efficient expression through elimination of a dispensable disulfide loop.

BACKGROUND: Heterologous expression of factor VIII (FVIII) is about two to three orders of magnitude lower than similarly sized proteins. Bioengineering strategies aimed at different structural and biochemical attributes of FVIII have been successful in enhancing its expression levels. OBJECTIVE: Disulfide bonds are vital to the proper folding, secretion and stability of most secretory proteins. In an effort to explore additional targeted bioengineering approaches, the role of disulfide bonds in FVIII secretion and function was probed in this study. METHODS AND RESULTS: Single and paired cysteine mutants were generated by substituting with serine or glycine residues and analyzed by transient transfection into COS-1 and CHO cells. Seven of the eight disulfide bonds in FVIII were found to be indispensable for proper secretion and function. However, elimination of the disulfide bond formed by C1899 and C1903 within the conserved A3 domain improved the secretion of FVIII. The addition of the C1899G/C1903G mutations to a previously described FVIII variant, 226/N6, with high secretion efficiency increased its secretion by 2.2-fold. Finally, the addition of the A1-domain mutation, F309S, in conjunction with the disulfide mutation had an additive effect, resulting in a net improvement in secretion of between 35 and 45-fold higher than wild-type FVIII in CHO cells. CONCLUSION: Such combined targeted bioengineering strategies may facilitate more efficient production of recombinant FVIII and contribute toward low-cost factor replacement therapy for hemophilia A.

Most factor VIII B domain missense mutations are unlikely to be causative mutations for severe hemophilia A: implications for genotyping.

BACKGROUND & OBJECTIVE: The factor VIII (FVIII) B domain shares very little amino acid homology with other known proteins and is not directly necessary for procoagulant activity. Despite this, missense mutations within the B domain have been reported in patients with hemophilia A. Given that the B domain is dispensable for secretion and function of FVIII, we hypothesized that these mutations should not be causative of hemophilia A in these patients. METHODS: Plasmid vectors containing B domain missense mutations that were reported to be associated with moderate/severe hemophilia A (T751S, D826E, V993L, H1047Y, T1353A, N1441K, L1462P, E1579D, A1591S, P1641L and S1669L) were analyzed for their effect on synthesis and secretion compared with FVIII wild-type (WT) following transient transfection into COS-1 and CHO cells in vitro. Further, H1047Y, N1441K and E1579D mutants were expressed in vivo in a hemophilia A mouse model by hydrodynamic tail-vein injection. RESULTS: FVIII activity and antigen levels for all mutants expressed into the conditioned media of COS-1 and CHO cells were similar to FVIII WT. Also, plasma expression of these mutants was similar to FVIII WT in hemophilia A mice. An in vivo tail clip bleeding assay also demonstrated that blood loss from hemophilia A mice expressing FVIII WT, H1047Y, N1441K and E1579D was similar. CONCLUSIONS: We conclude that most missense mutations within the FVIII B domain would be unlikely to lead to severe hemophilia A and that the majority of such missense mutations represent polymorphisms or non-pathologic mutations.

[Multiplication of the shrimp baculovirus HHNBV with primary cell cultures from lymphoid organ of Penaeus chinensis].

The hypodermal and hematopoietic necrosis baculovirus HHNBV has been confirmed to be the causative agent for the explosive epidermic disease of farmed shrimp Penaeus chinensis since 1993. The virus was isolated and multiplied successfully in the primary cell cultures from the lymphoid organ of the shrimp. A cell monolayer was formed in three days in the medium MPS and could be maintained for 1-3 months as the medium replaced every 4-5 days. The cytopathic effect occurred in 5 days after inoculation of the tissue extract from the diseased shrimp. The transmission electron microscopy showed many rod-shaped virions of HHNBV in the nuclei of infected cells.