Signal transducer and activator of transcription 6 mediates skeletal muscle cell injury in septic mice by regulating ferroptosis / 中华危重病急救医学

Objective:To explore the effect of signal transducer and activator of transcription 6 (STAT6) on ferroptosis in skeletal muscle cells in sepsis model and its potential mechanism.Methods:Twenty-four 8-week-old male specific pathogen free Kunming mice were divided into normal control group, sham group, sepsis model group and STAT6 inhibitor pretreatment group according to random number table method with 6 mice in each group. A mouse sepsis model was reproduced by cecal ligation and perforation (CLP). In the sham group, the skin of mice was sutured after exposing the cecum tissue. In the STAT6 inhibitor pretreatment group, 10 mg/kg AS1517499 was injected intraperitoneally 1 hour before model reproduction. The sham group and the model group were intraperitoneally injected with the same volume of normal saline. Mice in the normal control group did not receive any operation or drug intervention. The mice were sacrificed 24 hours after model reproduction, and the muscle tissue of hind limb was obtained under sterile condition. Hematoxylin-eosin (HE) staining was used to observe the histopathology with optical microscope, and mitochondrial morphological changes were observed by transmission electron microscopy after double staining with uranium acetate lead citrate. The ferroptosis marker proteins expressions of chitinase-3-like protein 1 (CHI3L1), cyclooxygenase-2 (COX-2), acyl-CoA synthetase long-chain family member 4 (ACSL4), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPx4) were detected by Western blotting.Results:Under the optical microscope, the morphology and structure of skeletal muscle tissues in the normal control and sham groups were normal. In the model group, the structure of skeletal muscle tissues was loose, the muscle fiber became smaller and atrophic, inflammatory cell infiltration and even muscle fiber loss were found. Compared with the model group, the structure of skeletal muscle tissues was tight and skeletal muscle atrophy was improved in the STAT6 inhibitor pretreatment group. The ultrastructure of skeletal muscle cell in the normal control and sham groups was normal under transmission electron microscope. The ultrastructure characteristics of skeletal muscle in the model group showed that cell membrane was broken and blister, mitochondria became smaller and membrane density increased, the mitochondrial crista decreased or disappeared, the mitochondrial outer membrane was broken, and the nucleus was normal in size but lacked chromatin condensation. Compared with the model group, the STAT6 inhibitor pretreatment group had a significant improvement in the ultrastructure of muscle cells. Compared with the normal control and sham groups, the protein expressions of CHI3L1, COX-2, ACSL4 and FTH1 in the muscle of the model group were significantly increased, while the protein expression of GPx4 was decreased significantly, indicating that the skeletal muscle cells in the mouse sepsis model showed characteristic mitochondrial injury and abnormal expression of ferroptosis markers. Compared with the model group, the protein expressions of CHI3LI, COX-2, ACSL4 and FTH1 in the STAT6 inhibitor pretreatment group were significantly decreased [CHI3L1 protein (CHI3L1/GAPDH): 0.70±0.08 vs. 0.97±0.09, COX-2 protein (COX-2/GAPDH): 0.61±0.03 vs. 0.83±0.03, ACSL4 protein (ACSL4/GAPDH): 0.75±0.04 vs. 1.02±0.16, FTH1 protein (FTH1/GAPDH): 0.49±0.06 vs. 0.76±0.13, all P < 0.05], while the protein expression of GPx4 was significantly increased (GPx4/GAPDH: 1.14±0.29 vs. 0.53±0.03, P < 0.05). Conclusions:Sepsis can induce ferroptosis in skeletal muscle cells of mice. STAT6 may mediate ferroptosis in mouse skeletal muscle cells by regulating the expressions of COX-2, ACSL4, FTH1 and GPx4, thereby inducing skeletal muscle cell injury in sepsis.

Effect of screening and treatment of syphilis among pregnant women on prevention of intrauterine syphilis transmission in Nantong City, 2012-2019 / 中华围产医学杂志

Objective:To evaluate the intrauterine transmission of syphilis in Nantong City, Jiangsu Province from 2012 to 2019, after the introduction of a nationwide policy for preventing intrauterine transmission of syphilis in China in 2011.Methods:This study enrolled all live birth deliveries ( n=455 561) in Nantong from January 2012 to December 2019. The screening, infection rates, anti-syphilis treatment, intrauterine transmission of syphilis, and outcomes of infants with congenital syphilis were retrospectively analyzed using χ 2 test for trend, adjusted χ 2 test, or Fisher's exact test. Results:Except for three women, the remaining 455 558 subjects were all screened for syphilis antibody with a total screening rate of nearly 100%, among which prenatal screening accounted for 96.4% (439 125/455 561) and intrapartum screening for 3.6% (16 433/455 561). In total, 796 (0.17%) women were diagnosed with syphilis during pregnancy, and the prevalence increased from 0.13% (85/64 229) in 2012 to 0.24% (110/45 517) in 2019 (χ 2trend=48.985, P<0.001). The prevalence among women underwent intrapartum screening was significantly higher than those underwent prenatal screening [0.50% (82/16 433) vs 0.16% (714/439 125), χ 2=102.769, P<0.001]. Out of the women with syphilis, 716 (89.9%) received anti-syphilis therapy with 695 cases using penicillin, 16 cases using ceftriaxone and five using erythromycin/azithromycin, while the remaining 80 (10.1%) did not. Intrauterine transmission of syphilis occurred in 14 infants with a transmission rate of 1.8% (14/796). The reported rate of congenital syphilis in all live infants was 0.03‰ (14/460 552). The intrauterine transmission rate in women receiving treatment during pregnancy was significantly lower than that in the untreated women [0.4% (3/716) vs 13.8% (11/80), χ2=66.499, P<0.001]. For the untreated women, the intrauterine transmission rate increased with the rising titers of non-specific syphilis antibody ( χ2trend=5.338, P=0.021). Among infants with congenital syphilis, no obvious adverse outcomes occurred in three infants born to treated mothers, whereas the rates of preterm birth and neonatal death were 7/11 and 2/11 in those born to untreated mothers. Conclusions:Since the implementation of the policy against intrauterine transmission of syphilis, the reported rate of congenital syphilis is 3/100 000 live-birth in Nantong City, reaching the national target of below 15/100 000. Screening and treatment in the first trimester are critical for preventing intrauterine transmission of syphilis. Increased prenatal syphilis screening rate can help further reduction of the intrauterine transmission of syphilis.

Effects of different feeding patterns on mother-to-child transmission of HBV infections in pregnant women with high viral loads after antiviral medication during pregnancy: A prospective cohort study / 中华围产医学杂志

Objective:To study the influence of different feeding patterns on mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with high viral loads who received antiviral medication during pregnancy to the day of delivery.Methods:This prospective cohort study was conducted in Beijing You'an Hospital. From January 1, 2019, to March 31, 2020, and 574 pregnant women with positive hepatitis B surface antigen (HBsAg) and HBV DNA>2×10 5 IU/ml were enrolled. All participants received tenofovir, telbivudine, lamivudine, or propofol tenofovir from 24-28 weeks of gestation and discontinued on the day of delivery, and their neonates were postnatally given routine passive-active immunoprophylaxis. Based on the feeding patterns, the subjects were divided into three groups: breastfeeding ( n=257), bottle-feeding ( n=241) and mixed feeding groups ( n=76). The follow-up data were obtained from liver functions and HBV DNA level of the mothers at 6-8 weeks postpartum and HBV serological markers of infants at 7-12 months. One-way ANOVA, Student-Newman-Keuls, Chi-square test or Fisher exact test, and repeated measures ANOVA were used to analyze the data. Results:The average maternal HBV DNA levels before antiviral treatment did not differ significantly between the three groups [(7.90±0.67), (7.82±0.70), (7.83±0.70) log 10 IU/ml, F=0.912, P>0.05]. HBV DNA level before delivery in the mixed feeding group was slightly lower than that in the breastfeeding and bottle-feeding group [(3.87 ±1.08) vs (4.21±1.17) and (4.30±1.28) log 10 IU/ml, q= 3.052 and 3.831, both P<0.05], while the comparison between the latter two groups showed no significant differences ( P>0.05). After delivery, HBV DNA level in the bottle-feeding group was slightly lower than that in the breastfeeding group [(7.42±0.93) vs (7.69±0.90) log 10 IU/ml, q=4.583, P<0.05]. Among 580 infants (including six pairs of twins), only one bottle-fed infant (0.4%, 1/243) was infected with HBV through MTCT, and none in the breastfeeding or mixed feeding group ( P=0.553). Conclusions:For pregnant women with high viral loads of HBV who have received antiviral medication during pregnancy, although HBV DNA level will rebound after discontinuation upon delivery, breastfeeding is recommended considering it does not increase the risk of MTCT.

Effects of chitinase-3-like protein 1 on the expression of inflammatory damage-related molecules in mouse skeletal muscle satellite cells induced by lipopolysaccharide / 中华危重病急救医学

Objective:To explore the potential mechanism of chitinase-3-like protein 1 (CHI3L1) involved in skeletal muscle stem cell injury induced by sepsis.Methods:Six different concentrations of lipopolysaccharide (LPS) were used to stimulate mouse skeletal muscle satellite cells cultured in vitro. Enzyme linked immunosorbent assay (ELISA) and cell counting kit-8 (CCK-8) were used to determine the optimal concentration. The overexpression and interference vectors of CHI3L1 were constructed to transfect skeletal muscle satellite cells, and the transfection efficiency was verified by polymerase chain reaction (PCR) and Western blotting. The cells were randomly divided into blank control group (cells without any intervention), model group (LPS-stimulated untransfected cells), overexpressing CHI3L1 group (LPS-stimulated cells transfected with CHI3L1 plasmid), overexpressing CHI3L1 control group [LPS-stimulated cells transfected with negative control (NC) plasmid], CHI3L1 interference group [LPS-stimulated cells transfected with CHI3L1 small interfering RNA (siRNA)], CHI3L1 interference control group (LPS-stimulated cells transfected with CHI3L1-siRNA NC). The levels of extracellular caspase-1 and interleukin-1β (IL-1β) were detected by ELISA. The protein expressions of intracellular IL-1β, signal transducer and activator of transcription 3 (STAT3), protein kinase B (Akt) and phosphorylated Akt (p-Akt) were detected by Western blotting. Results:According to the results of CCK-8 and ELISA, the best concentration of 5 mg/L LPS was selected for the subsequent experiment. The transfection was validated by PCR and Western blotting. Compared with the blank control group, the levels of extracellular IL-1β, caspase-1 and the protein expressions of intracellular Akt, p-Akt, and IL-1β were significantly increased in the model group [IL-1β (ng/L): 11.22±0.55 vs. 8.63±0.63, caspase-1 (pmol/L): 9.47±0.22 vs. 8.65±0.15, Akt/GAPDH: 1.36±0.12 vs. 1.06±0.15, p-Akt/GAPDH: 0.78±0.07 vs. 0.09±0.01, IL-1β/GAPDH: 1.38±0.12 vs. 0.18±0.03, all P < 0.05]. Compared with the model group and the overexpressing CHI3L1 control group, the levels of extracellular IL-1β, caspase-1 and the protein expressions of intracellular p-Akt and IL-1β were significantly increased in the overexpressing CHI3L1 group [IL-1β(ng/L): 14.93±0.97 vs. 11.22±0.55, 9.38±0.40, caspase-1 (pmol/L): 10.35±0.03 vs. 9.47±0.22, 8.46±0.24, p-Akt/GAPDH: 1.21±0.04 vs. 0.78±0.07, 0.63±0.04, IL-1β/GAPDH: 1.87±0.08 vs. 1.38±0.12, 1.51±0.17, all P < 0.05]. Compared with the model group and the CHI3L1 interference control group, the levels of extracellular IL-1β, caspase-1 and the protein expressions of intracellular p-Akt and IL-1β were significantly decreased in the CHI3L1 interference group [IL-1β(ng/L): 8.98±0.73 vs. 11.22±0.55, 10.44±0.65, caspase-1 (pmol/L): 7.61±0.63 vs. 9.47±0.22, 8.37±0.38, p-Akt/GAPDH: 0.50±0.04 vs. 0.78±0.07, 0.94±0.06, IL-1β/GAPDH: 0.77±0.02 vs. 1.38±0.12, 1.13±0.07, all P < 0.05]. Conclusions:CHI3L1 may mediate the damage of skeletal muscle stem cells in sepsis by increasing the expression of caspase-1 and IL-1β. CHI3L1 may be involved in the regulation of Akt signaling pathway in skeletal muscle stem cells, but has no significant effect on STAT3 signaling pathway.

How to obtain evidence of vertical transmission in viral infected pregnant women: Reflection on COVID-19 epidemic / 中华围产医学杂志

During the COVID-19 epidemic, there have been many misconceptions concerning vertical transmission between the mother and fetus/baby, which has caused much discussion and controversy. However, there is no strong evidence to indicate that this novel coronavirus could be vertically transmitted from infected mothers to their fetuses/infants. Several easily confused concepts are clarified in this paper, including vertical transmission, intrauterine transmission, mother-to-infant transmission, intrapartum or postpartum transmission. Well-designed protocols and a disciplined research team are essential for both basic and clinical research, in order to contribute to obtaining more scientific evidence for better understanding of the characteristics of this novel coronavirus. Proper handling and disposal of the body fluids and tissue are critical for safety. We highlight the significant value of relevant research, and suggest future research directions, such as investigating the impact of COVID-19 in different trimesters. Furthermore, China has the most experience of treating pregnant women exposed to the COVID-19 virus, and it would be a great service to the rest of the world, for all centers in China to collaborate to report this collective experience.

Comments on 2019 Chinese practice guideline for the prevention and treatment of hepatitis B virus mother-to-child transmission / 中华肝脏病杂志

Recently, the Society of Infectious Diseases of Chinese Medical Association and Chinese GRADE Center jointly released the "2019 Chinese practice guideline for the prevention and treatment of hepatitis B virus mother-to-child transmission" . We concerned several issues in the Guideline, including the improper citation of some references, no recommendations for some key strategies for the prevention of hepatitis B virus mother-to-child transmission, insufficient or even lack of evidence for some recommendations and others. Based on the principle of academic contention, we present in this article our comments on the Guideline to discuss these issues with the Guideline’s authors and readers.

Comments on“2019 Chinese practice guideline for the prevention and treatment of hepatitis B virus mothertochild transmission” / 临床肝胆病杂志

Recently, the Society of Infectious Diseases of Chinese Medical Association and Chinese GRADE Center jointly released the “2019 Chinese practice guideline for the prevention and treatment of hepatitis B virus mothertochild transmission”. We concerned several issues in the Guideline, including the improper citation of some references, no recommendations for some key strategies for the prevention of hepatitis B virus mothertochild transmission, insufficient or even lack of evidence for some recommendations and others. Based on the principle of academic contention, we present in this article our comments on the Guideline to discuss these issues with the Guideline’s authors and readers.

How to obtain evidence of vertical transmission of coronavirus according to serological test of specific IgM and IgG antibodies / 中华围产医学杂志

Whether 2019 novel coronavirus can be vertically transmitted to fetuses is a major concern, while how to obtain evidence of vertical transmission in viral infected pregnant women is the key. Virological and serological evidence is valuable to clarify this issue. However, longitudinal follow-up of infants for at least 3-6 months after birth and dynamic changes of specific antibodies of the mothers is essential when serological results are used to confirm or exclude vertical transmission.

Vertical transmission in COVID-19 pregnant women / 中华围产医学杂志

During the COVID-19 epidemic, there have been many misconceptions concerning vertical transmission between the mother and fetus/baby, which has caused much discussion and controversy. However, there is no strong evidence to indicate that this novel coronavirus could be vertically transmitted from infected mothers to their fetuses/infants. Several easily confused concepts are clarified in this paper, including vertical transmission, intrauterine transmission, mother-to-infant transmission, intrapartum or postpartum transmission. Well-designed protocols and a disciplined research team are essential for both basic and clinical research, in order to contribute to obtaining more scientific evidence for better understanding of the characteristics of this novel coronavirus. Proper handling and disposal of the body fluids and tissue are critical for safety. We highlight the significant value of relevant research, and suggest future research directions, such as investigating the impact of COVID-19 in different trimesters. Furthermore, China has the most experience of treating pregnant women exposed to the COVID-19 virus, and it would be a great service to the rest of the world, for all centers in China to collaborate to report this collective experience.

Real-world efficacy of immunoprophylaxis against mother-to-infant transmission of hepatitis B virus based on puerperant population / 中华围产医学杂志

Objective To assess the efficacy of immunoprophylaxis against mother-to-infant transmission of hepatitis B virus (HBV) in a real-world setting since the implementation of charge-free hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in China. Methods The screening rate and the prevalence of hepatitis B surface antigen (HBsAg) in 61 790 puerperants, and the administration of combined immunoprophylaxis in infants of HBsAg-positive mothers in Rugao City of Jiangsu Province from July 1, 2011 to June 30, 2016 were retrospectively analyzed. HBV infection status of infants born to HBV infected mothers was followed up after 7 months of age. HBsAg-positive infants and their mothers were followed up again for HBV markers in April 2018. Fisher's exact test and Cochran-Armitage trend test were used to statistically analyze the differences between groups and various years, respectively. Results All 61 790 puerperants were screened for HBsAg and the prenatal screen rate was 98.6% (60 937/61 790) with an increasing trend over time (χ2trend=750.908, P<0.001). HBsAg-positive puerperants accounted for 5.5% (3 397/61 790) with a decreasing trend over time (χ2trend=32.667, P<0.001). In total, 778 offspring (399 boys and 379 girls) of 759 HBsAg-positive mothers were followed up at (13.7±6.9) months of age, among which 751 (96.5%) were administered and 25 (3.2%) were probably administered standard combined immunoprophylaxis after birth, and the rest two (0.3%) were not. Fourteen infants (1.8%) were HBsAg positive and all born to mothers with positive hepatitis B e antigen (HBeAg). None of the 538 infants born to HBeAg-negative mothers was HBsAg-positive. HBsAg-positive rate in infants born since 2013 was lower than those in 2011 and 2012 (χ2trend=13.352, P=0.000 3). Eleven HBsAg-positive mothers and their children were followed up again 4–5 years later in April 2018. HBV DNA levels of all mothers were within the range of (7.34–28.2)×107 IU/ml except one case of spontaneous HBeAg seroconversion. One out of the 11 infected children also had HBeAg seroconversion. Phylogenetic analysis of HBV S gene showed that the 11 pairs of mothers and children were all infected with HBV of genotype C. Conclusions The implementation of charge-free HBIG and hepatitis B vaccine for newborns achieves fruitful results in Rugao city as the mother-to-infant transmission of HBV in the real-world had been further reduced to a similar level reported in literature survey.

Screening and identification of hepatitis B surface antigen binding to lactoferrin in human milk / 中华围产医学杂志

Objective Human milk of mothers with positive hepatitis B surface antigen (HBsAg) contains hepatitis B virus (HBV). However, breastfeeding does not increase the risk of mother-to-infant transmission of HBV. Previous investigations demonstrated that breast milk has a property of binding with HBsAg. This study aimed to identify the component in human milk that can bind to HBsAg. Methods This study was performed in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, from June 2015 to February 2017. Human milk samples from two postpartum women with negative HBV markers and two control samples of cow milk and goat milk were analyzed by Far-Western blot, in which highly purified recombinant yeast HBsAg was used to bind with whey proteins. Based on the results of mass-spectrum analysis, competition inhibition test was used to confirm the functioning component. Results Far-Western blot showed remarkable protein bands at the relative molecular weight of about 80 000 in both lanes of human milk, but none in the lane of cow or goat milk. Mass-spectrum analysis of the protein band indicated there were proteins sharing 28.4%-93.4% homology in amino acid sequences with five proteins with the highest homology to lactoferrin (93.4%). Further Far-Western blot with purified recombinant lactoferrin showed that lactoferrin could bind to the recombinant HBsAg. Competition inhibition test suggested that the purified recombinant lactoferrin inhibited the binding of HBsAg to its antibody in a dose-dependent manner. Conclusions This study confirms the capability of lactoferrin in human milk to combine with HBsAg, suggesting that lactoferrin can bind to HBV. Further study on whether lactoferrin can inhibit the infectivity of HBV would be valuable to clarify the reason for not increasing the risk of mother-to-infant transmission of HBV by breastfeeding.

Maternal infection and breastfeeding / 中华围产医学杂志

Breast milk is the best food for infants. However, worrying about the transmission of pathogens to their offspring, mothers who have ongoing infections are usually hesitated on breastfeeding, or even unwillingly give up breastfeeding. This article summarized some basic knowledge and evidence on breastfeeding when maternal infections occur and emphasized that there is no risk of hepatitis virus transmission during breastfeeding. After taking appropriate measures, mothers with transmittable diseases through breastfeeding can still breastfeed their babies. This review provides reasonable medical advice on whether to breastfeed when maternal infection occurs in order to increase breastfeeding rate.

Prevention of mother-to-infant transmission of hepatitis B: advances and challenges / 中华围产医学杂志

The prevention of mother-to-infant transmission (MTIT) of hepatitis B virus (HBV) plays a critical role in controlling chronic HBV infection.China has put tremendous efforts in preventing MTIT of HBV and now has achieved fruitful results.We briefly introduced the main measures and research advances in immunoprophylaxis against perinatal HBV infection,summarized the efficacy and safety of oral anti-HBV agents,which administered in the third trimester to the gravidas with high viral loads to prevent MTIT of HBV.We also proposed some challenging issues that require further investigation.

Long-term protection of infants against hepatitis B by neonatal immunoprophylaxis born from mothers infected with hepatitis B virus / 中华实用儿科临床杂志

Objective To evaluate the long-term efficacy of neonatal immunoprophylaxis in children born from mothers infected with hepatitis B virus (HBV),and to clarify whether a booster vaccination is required.Methods Totally 252 children of HBV infected mothers,who were negative for hepatitis B surface antigen (HBsAg) tested in Nanjing Drum Tower Hospital in 2012,were enrolled to participate in this study from July to September,2017.Revaccination of hepatitis B vaccine was recorded and other relevant informations were collected.HBV serologic markers were detected in each child.Results Totally 198 children (78.6％) were followed up.They were (8.4 ± 2.2) years old and 112 cases were boys.All 198 children were negative for both HBsAg and hepatitis B core antibody (anti-HBc).The overall positive rate of hepatitis B surface antibody (anti-HBs) (≥ 10 IU/L) was 65.7％.During period of 2012 to 2017,53 children were boosted with hepatitis B vaccine.Their median anti-HBs titer in 2017 was higher than that in 2012 (327.95 IU/L vs.158.01 IU/L),and the difference was significant (Z =-4.480,P ＜0.05).The other 145 children were not revaccinated,their median anti-HBs titer was decreased from 214.19 IU/L in 2012 to 70.49 IU/L in 2017,and the difference was significant (Z =-6.575,P ＜ 0.05).Of 145 children who were not revaccinated,25 cases had anti-HBs levels ＜ 10 IU/L and 120 cases ≥ 10 IU/L in 2012,and the other 47 cases also showed the antibody ＜ 10 IU/L in 2017,but none of them was infected with HBV.Conclusions Neonatal immunoprophylaxis in infants from HBV-infected can provide long-term protection against hepatitis B.The children with anti-HBs ＜ 10 IU/L are still immune to HBV and booster vaccination for them seems unnecessary.

Effect of different feeding patterns and delivery modes on cytomegalovirus infection in infants and their outcomes / 中华围产医学杂志

Objective To explore the influence of delivery mode and feeding pattern on cytomegalovirus (CMV) infection on infants born ≥ 32 gestational weeks,and to observe the outcomes after CMV infection.Methods In this retrospective study,378 pregnant women with positive CMV IgG and negative CMV IgM,and their offsprings (384 cases,including six pairs of twins),who got visited at five hospitals of our collaboration group during March 2013 and February 2016,were enrolled.Serum samples were retrieved from a previous study of these participants for CMV IgM and IgG detection with enzyme-linked immunosorbent assay.All participants were divided into exclusive artificial feeding (EAF) and breastfeeding groups (BF),and the latter included exclusive breastfeeding (EBF) and mixed feeding (MF).T or Chi-square or Fisher's exact tests were performed for statistical analysis.Results (1) Among the 378 pregnant women,there were 186 mothers and 190 infants (4 pairs of twins) in BF group,and the other 192 mothers and 194 infants (2 pairs of twins) in EAF group.The percentage of male infants were 54.7％(104/186) and 56.2％(109/194) in the BF and EAF group,respectively.The mean birth age was (38.9± 1.4) and (38.7± 1.7) weeks,and the age at followingup was (9.8± 2.2) and (10.5± 2.9) months,respectively.(2) The CMV IgG positive rate of infants in BF group was higher than in the EAF group [62.6％(119/190) vs 29.9％ (58/194),x2=41.403,P＜0.001].CMV IgG levels in infants were higher than the mothers [(537.1 ±249.5) vs (416.2±241.2) U/ml,t=4.609,P＜0.001].In infants with positive CMV IgG,the positive rates of CMV IgM were similar in the two groups [21.0％(25/119) vs 19.0％ (11/58),x2=0.101,P=0.751].(3) The positive rate of CMV IgG in vaginally born infants was higher than those born by caesarean section [55.2 (95/172) vs 38.7％ (82/212),x2=10.472,P=0.001].Further analysis in the EAF group showed that those infants born vaginally had a higher positive rate ofCMV IgG than those born by caesarean section [42.9％ (33/77) vs 21.4％ (25/117),~=10.231,P=0.001],while this figure did not show statistical difference in the BF group.(4) Infants with positive or negative CMV IgG were in similar age and gender proportion,as well as their height and weight.Among 36 infants with both positive CMV IgG and IgM,three failed in alanine aminotransferase (ALT) test due to hemolysis.However,among the other 33 cases,15.1％ (five cases) presented with lightly elevated ALT (42-107.2 U/L),which was similar to those infants with positive CMV IgG and negative CMV IgM (14/98,14.3％) and those with both negative CMV IgG and IgM (20/144,13.9％),(x2=0.036,P=0.982).Conclusions Although breastfeeding and vaginal birth may increase CMV infection rate in neonates and infants,but no obviously adverse prognosis was reported in those born over 32 gestational weeks.So we should encourage vaginal birth and breastfeeding in these population.

The study of correlation between serum homocysteine and platelet aggregation rate in type 2 diabetes patients with cerebral infarction / 国际检验医学杂志

Objective To explore the clinical values of the serum homocysteine (Hcy) and platelet aggregation rate in type 2 dia‐betes patient with cerebral infarction .Methods Totally 65 cases of type 2 diabetes patients with cerebral infarction ,55 simple type 2 diabetes patients and 50 cases who took health examination were enrolled in the study .The serum homocysteine and platelet ag‐gregation rate were detected ,the blood pressure ,weight and height of the patients were measured .The multi‐factor Logistic regres‐sion analysis was used to detecting the risk factors in type 2 diabetes patients with cerebral infarction .Results The serum homo‐cysteine level and platelet aggregation rate were significantly higher in diabetes patients with cerebral infarction than those simple diabetes patients or healthy group (P< 0 .05) .The levels of serum homocysteine and platelet aggregation rate were positively corre‐lated with the severity of diabetes patients with cerebral infarction .Conclusion Serum homocysteine and platelet aggregation rate are much higher in type 2 diabetes patients with cerebral infarction ,which indicated that we can predict the process of the cerebro‐vascular disease through detecting the serum homocysteine and platelet aggregation rate .

Effect of soluble vascular endothelial growth factor receptor-1 on atherosclerotic plaque / 中国组织工程研究

BACKGROUND: Angiogenesis in atherosclerotic plaque occurred on the basis of atherosclerotic lesions, and the new formed blood vessels promoted the development of angiogenesis. Soluble vascular endothelial growth factor receptor 1 (sFlt-1) gene transfection reduces neointimal formation after vascular injury in rabbits, also reduces early vascular inflammation and proliferation, and the formation of neointima lately. OBJECTIVE: To observe the effects of highly expressed sFlt-1 on atherosclerotic plaque. METHODS: A total of 48 male New Zealand rabbits were divided into four groups randomly: normal control group (n=8), sham operation group (n=8), bal oon injury+high lipid diet+pEGFP-N1 group (n=16) and bal oon injury+high lipid diet+pEGFP-N1-sFlt-1 group (n=16). Normal control group and sham operation group were supplied with normal diet. Bal oon injury+high lipid diet+pEGFP-N1 group and bal oon injury+high lipid diet+pEGFP-N1-sFlt-1 group were supplied with high lipid diet and injured by bal oon 2 weeks later. Bal oon injury+high lipid diet+pEGFP-N1 group was transfected with pEGFP-N1 and bal oon injury+high lipid diet+pEGFP-N1-sFlt-1 group was transfected with pEGFP-N1-sFlt-1. RESULTS AND CONCLUSION: In the bal oon injury+high lipid diet+pEGFP-N1 group and bal oon injury+high lipid diet+pEGFP-N1-sFlt-1 group, blood lipid levels apparently increased. At 3 days after model establishment, sFlt-1 expression levels noticeably increased, and atherosclerotic plaque formed to different degrees. Plaque area, plaque perimeter, plaque maximum thickness and the number of positive-cel s within the plaque were significantly less in the bal oon injury+high lipid diet+pEGFP-N1-sFlt-1 group than in the bal oon injury+high lipid diet+pEGFP-N1 group. These results confirm that sFlt-1 gene may express effectively in iliac artery wal of rabbit, inhibited the formation of atherosclerotic plaque and delayed the development of atherosclerotic plaque.

Relationship of cytokines levels andUreaplasma infection in midtrimester amniotic fluid with spontaneous preterm birth / 中华围产医学杂志

ObjectiveTo investigate the relationship between levels of inflammatory cytokines, Ureaplasma infection in midtrimester amniotic fluid and spontaneous preterm delivery.MethodsFrom April 2009 to March 2012, a total of 1 865 pregnant women who underwent amniocentesis in midtrimester with known pregnant outcomes in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, among whom 43 cases who delivered spontaneously before 37 weeks, were classified as preterm group, and the control group consisted of 373 normal term delivery women selected from the other 1 785 cases who term delivered during the same period. Cytokines, including interleukin (IL)-10, IL-1β, IL-6, monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in amniotic fluid, were measured by MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel and analysis system for liquid phase chips.Ureaplasma DNA was detected by polymerase chain reaction. Sum-rank test was used to compare the difference of cytokines between the two groups and receiver-operating characteristic curve and Logistic analysis were used to analyze the value of cytokines to predict spontaneous preterm delivery.ResultsThe median maternal age in preterm group was higher than in the control group [34(24-49) vs 29(20-47) years] (Z=-3.107,P=0.002), but there was no significant difference in levels of the five cytokines among women with different age in control group(20-24, 25-29, 30-34 and≥35 years old) (allP>0.05). The levels of IL-1β and IL-6 were not significantly different between two groups (allP>0.05), but levels of IL-10, MCP-1 and TNF-α in the preterm group were much higher than in the control group [11.22(4.79-468.73) vs 7.87(0.93-26.62), 1 358.86(553.16-7 635.81) vs 1 137.98 (311.80-5 196.33), 9.78(5.72-106.51) vs 8.37(2.56-30.20) pg/ml, respectively;Z were-4.333,-2.820 and-3.390, allP<0.01]. The areas under receiver-operating characteristic curve of IL-10, MCP-1 and TNF-αwere 0.70, 0.63 and 0.66. The appropriate cut-off level of IL-10 in amniotic fluid for prediction of preterm birth was 9.06 ng/ml, with a sensitivity of 74.4% and a specificity of 57.6%, and the latter increased to 100.0% when combined with IL-10, MCP-1 and TNF-α, but the sensitivity declined to 16.3%.Ureaplasma was identified in only two preterm cases and none in the controls. However, the levels of the five cytokines in the two infected cases in preterm group were 2.12–43.00 times of the rest cases in the same group, and 2.26–60.00 times of the controls.ConclusionsAlthough IL-10, MCP-1 and TNF-α levels in midtrimester amniotic fluid are increased, it is not able to predict spontaneous preterm birth neither independently nor combined together. Ureaplasma infection rate in amnion cavity is low, but may related to parts of spontaneous preterm delivery.

Characterization of binding capability of human breast milk to hepatitis B surface antigen / 中华围产医学杂志

Objective To investigate whether human breast milk may bind to hepatitis B surface antigen (HBsAg) and its characteristics.Methods Breast milk samples from five women with negative HBsAg and hepatitis B surface antibody (anti-HBs) at one to two months post delivery were fractioned into cream and skimmed milk by centrifugation.The human breast milk and each fraction as well as cow and goat milk samples,served as controls,were separately incubated with highly purified yeast recombinant HBsAg,followed by determination of their binding capability to HBsAg by enzyme linked immunosorbent assay (ELISA) and the inhibition rate for binding of HBsAg to anti-HBs by quantitative chemiluminescence microparticle immunoassay.After boiled for 1 min or pasteurized in 65 ℃ for 30 min,the thermal stability of the active components of milk was detected.One-way ANOVA and SNK tests were performed for statistical analysis.Results The operative concentration of HBsAg was 0.1 μg/ml.Breast milk from all five women showed significantly better binding capability to HBsAg than cow or goat milk (1.306±0.300 vs 2.157±0.150 and 2.232±0.093,F=34.303,P＜0.01).The quantitative experiments showed that the inhibition rate of human breast milk was higher than that of the control group [(74.26± 17.26)％ vs (0.00±5.50)％,F=57.806,P＜0.01].The binding ability to HBsAg of skimmed milk was comparable with that of whole milk,indicating milk protein(s) played critical roles in binding to HBsAg (0.877 ± 0.486 vs 0.513 ± 0.069 and 0.376 ± 0.146,F=44.475,P＜0.01).After boiled for 1 min or Pasteurization,the binding ability to HBsAg of whole breast milk remained,but that of skimmed milk went down (F=16.598,P＜0.01).Both whole breast milk and skimmed milk could inhibit the binding of HBsAg to anti-HBs (F=278.341 and 269.408,both P＜0.01).Conclusions The inhibition of binding to HBsAg by human breast milk indicates that human milk may interact with HBsAg.The active components mainly exist in milk proteins and are thermal stable.

Influence of amniocentesis on risk of mother-to-child transmission of hepatitis B virus / 中华围产医学杂志

Objective To investigate whether amniocentesis may increase the risk for mother-tochild transmission of hepatitis B virus (HBV).Methods Totally 40 children born to HBV-infected mothers who had amniocentesis performed in Nanjing Drum Tower Hospital, Nanjing University Medical School from January 2010 to December 2013, were followed up and screened for HBV markers.Amniotic fluid samples were collected and stored at-80 ℃ were tested for HBV markers.Among the 40 carrier mothers, three (7.5％) were hepatitis B e antigen (HBeAg)-positive.Relevant data such as antiviral history, administration of hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) in infants were collected.Chi-square test or Fisher's exact test was used for statistical analysis.Results The mothers were 21-41 years old, with a mean age of (31.5±5.5) years at the time of amniocentesis and mean gestational age of (21.2± 1.6) weeks (18.4-24.9 weeks).Indications for amniocentesis were mainly abnormal maternal serum alpha-fetoprotein levels (65.0％, 26/40)and maternal age over 35 years (10.0％, 4/40).None of the mothers received antiviral therapy and 14 (35.0％)underwent transplacental amniocentesis.Among 28 cases who had a store of amniotic fluid sample and were followed-up, one (7.1％) was positive for both hepatitis B surface antigen (HBsAg) and HBV DNA, and another was positive for HBsAg only.The average age of 40 children at follow-up was (2.0± 1.0) years (seven months to four years old), among which 23 were boys and 17 were girls.All of them received hepatitis B vaccine and HBIG.Positive rate of HBsAg and HBV DNA in HBeAg(+) mothers are higher than those in HBeAg(-) mothers [4.7％(2/43) vs 3/5, x2=14.705;0/43 vs 2/5, x2=17.948;both P ＜ 0.05].Thirty-seven children born to HBsAg(+)/HBeAg(-) mothers were negative for both HBsAg and hepatitis B core antibody (anti-HBc), and the other three born to HBsAg(+)/HBeAg(+) mothers were also negative for HBsAg and anti-HBc.Additionally, the positive rate of hepatitis B surface antibody in children was 90.0％ (36/40).Conclusions For those HBsAg(+)/HBeAg(-) mothers, amniocentesis does not elevate the risk for mother-to-child transmission of HBV, even performed transplacentally.However, further studies are needed for HBeAg-positive mothers.HBsAg or HBV DNA positive in amniotic fluid should be diagnosed as intrauterine infection of HBV.