Chlamydia trachomatis infection in the genital tract is associated with inflammation and hypospermia in the infertile male of China / 亚洲男科学杂志(英文版)

Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted bacterial disease worldwide. However, unlike that in female infertility, the role of CT infection in male infertility remains controversial. The objective of this retrospective study was to explore the impacts of CT infection in the genital tract on sperm quality, sperm acrosin activity, antisperm antibody levels, and inflammation in a large cohort of infertile males in China. A total of 7154 semen samples were collected from infertile male subjects, 416 of whom were CT positive (CT+ group) and 6738 of whom were CT negative (CT- group), in our hospital between January 2016 and December 2018. Routine semen parameters (semen volume, pH, sperm concentration, viability, motility, morphology, etc.), granulocyte elastase levels, antisperm antibody levels, and sperm acrosin activity were compared between the CT+ and CT- groups. Our results showed that CT infection was significantly correlated with an abnormally low semen volume, as well as an increased white blood cell count and granulocyte elastase level (all P < 0.05) in the semen of infertile males; other routine semen parameters were not negatively impacted. The antisperm antibody level and sperm acrosin activity were not affected by CT infection. These findings suggested that CT infection might contribute to inflammation and hypospermia but does not impair sperm viability, motility morphology, and acrosin activity or generate antisperm antibodies in the infertile males of China.

Analysis of clinical characteristics of extremely low birth weight premature infants during 2008-2017 / 中国新生儿科杂志

Objective To study the survival rate,complications and risk factors affecting clinical outcomes in extremely low birth weight (ELBW) premature infants.Method From January 2008 to December 2017,clinical data of ELBW infants admitted to the department of neonatology of our hospital were collected.The survival rates and the incidences of complications were compared between different subgroups of different birth weight (BW) and discharging date.The risk factors affecting the survival rate of ELBW infants were analysed using multivariate unconditional Logistic regression analysis.Result (1) A total of 438 ELBW infants were enrolled,representing 4.9％ (438/8 910) of all discharged preterm infants,and 2.6％ (438/16 948) of all discharged neonates during the study period.Among them,3 were excluded because of incomplete data and lost of follow-up.The BW was 900 (750,950) g and the gestational age was (28.0±2.1) weeks.The overall survival rate was 81.6％ (209/256) with 179 cases excluded for giving up treatment.(2) From 2008 to 2017,the percentages of ELBW infants among all discharged newborns and all discharged premature infants increased annually (x2 trend=6.818,27.850,P=0.009,＜0.001).(3) No significant differences existed in the survival rates of ELBW infants between 2013-2017 and 2008-2012(P＞0.05).The survival rates of different BW groups (＜700 g,700～799 g,800～899 g,and 900～999 g)increased from 40.0％ (6/15) to 88.5％ (139/157) (x2 trend=32.648,P＜0.001).(4) The main complications in ELBW infants were respiratory distress syndrome 87.5％ (224/256),retinopathy of prematurity 63.1％ (123/195),and bronchopulmonary dysplasia 63.0％ (126/200).(5) Multivariate unconditional logistic regression analysis showed that BW＜900 g (＜700 g∶ OR=10.147,95％CI 2.684～38.360;700～799 g∶ OR=6.978,95％CI 1.647～29.555;800～899 g∶ 0R=4.727,95％CI 1.060～21.082,P＜0.05),and gestational age＜28 weeks (OR=3.529,95％CI 1.601～7.778,P=0.002) were the risk factors for survival rate and antenatal steroids was the protective factor(OR=0.155,95％CI 0.069～0.353,P＜0.001).Conclusion The number of ELBW infants discharged from neonatology department increased annually.The survival rate of ELBW infants was positively correlated with BW.Antenatal steroids may improve the survival rate of ELBW infants.

Targeted elimination of mutant mitochondrial DNA in MELAS-iPSCs by mitoTALENs

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.