Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.
Animals ; Brain/growth & development* ; 5-Methylcytosine/metabolism* ; Mice ; Synapses/genetics* ; Proto-Oncogene Proteins/metabolism* ; DNA-Binding Proteins/metabolism* ; Dioxygenases/metabolism* ; Cognition/physiology* ; Gene Expression ; Mixed Function Oxygenases/metabolism* ; Epigenesis, Genetic ; Mice, Knockout ; Mice, Inbred C57BL

Objective: To quantitatively evaluate the clinical effect of platelet-rich plasma(PRP) intra-articular injection for early and middle stage knee osteoarthritis(KOA) treatment by 3.0T MRI T2 mapping sequence. Methods: Clinical data of 26 patients with early or middle stage KOA who received treatment from April to December 2021 at Department of Orthopaedic Surgery,the Second Affiliated Hospital,Zhengzhou University were retrospectively analyzed. In total, 8 patients were male and 18 were female,with age of (66.4±12.0)years(range:51 to 94 years). Four patients were bilateral KOA and 22 patients were unilateral KOA.All patients received PRP intra-articular injection. Patients underwent 3.0T MRI T2 mapping sequence scanning pre-treatment,3-month-after and 6-month-after treatment respectively. Those were used to measure and compare T2 values of medial and lateral femoral articular surface and patellofemoral articular surface. Visual analogue scale(VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded and evaluated. The results were analyzed using repeated measure ANOVA followed by Bonferroni multiple comparison test.The correlation between WOMAC scores and T2 values at pre-treatment and 6 months post-treatment was analyzed using Pearson correlation test. Results: After treatment, the patients' International Cartilage Regeneration＆Joint Preservation Society(ICRS) classification were partly improved(one case improved from grade Ⅲ to grade Ⅱ, one case improved from grade Ⅱ to grade Ⅰ),and all patients generally improved after treatment in clinical symptoms. Compared with pre-treatment,VAS and WOMAC scores of grade Ⅰ,Ⅱ,and Ⅲ of 6-month after treatment were declined significantly(all P<0.05).The T2 values of articular cartilage declined to varying degrees(the decrease in T2 values was about 2.06 ms in grade Ⅰ, 2.66 ms in grade Ⅱ, and 3.72 ms in grade Ⅲ).Three-month (VAS:4.8±1.3,WOMAC:21.5±4.0) and 6-month (VAS:4.2±1.4,WOMAC:17.2±2.9) after treatment, the VAS and WOMAC score were significantly higher than those before treatment (VAS:6.0±1.2, WOMAC:29.0±2.3) (F=48.846, F=346.746;both P<0.01). Multiple comparisons showed a statistically significant difference between pre-treatment and post-treatment VAS (P<0.01) and it also was significantly different between 3-month and 6-month post-treatment (P<0.01).At 3- and 6-month after treatment,WOMAC scores were significantly different from before treatment.And it also was significantly different between 3-month and 6-month post-treatment (P<0.01).There was a statistically significant improvement in T2 values of patellofemoral articular surface, medial and lateral femoral articular surface at pre-treatment((44.64±4.02)ms,(44.17±3.64)ms and(43.53±3.91)ms) and 3-month ((43.19±3.91)ms,(43.24±3.34)ms and (42.47±3.80)ms), 6-month ((41.49±3.64)ms,(41.83±3.15)ms and (41.10±3.42)ms) after treatment(F=148.845,F=73.657,F=86.268;all P<0.01).The results of the multiple comparisons showed a statistically significant difference in the T2 values of medial and lateral femoral articular surface and patellofemoral articular surface at each time point(all P<0.01).The Pearson correlation analysis suggested that the WOMAC score at pre-treatment was positively correlated with the medial condyle (r=0.856,P<0.01) and the patellofemoral joint surface T2 values (r=0.840,P<0.01);The WOMAC score at 6-month post-treatment was positively correlated with the medial condyle (r=0.731,P<0.01) and the patellofemoral joint surface T2 values (r=0.691,P<0.01). Conclusions: In the treatment of early and mid-stage KOA,MRI T2 mapping sequences are able to indicate the integrity of cartilage morphology and quantitatively evaluate cartilage repair. PRP has a good therapeutic effect on cartilage repair and reconstruction.
Humans ; Female ; Male ; Osteoarthritis, Knee/therapy* ; Retrospective Studies ; Orthopedic Procedures ; Platelet-Rich Plasma ; Magnetic Resonance Imaging

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To analyze the risk factors for refracture of adjacent vertebrae after percutaneous vertebroplasty (PVP) in super-old patients with osteoporotic vertebral compression fractures(OVCFs). METHODS: A retrospective analysis was performed on 40 patients(age≥90 years) with OVCFs who underwent PVP between June 2012 and June 2019. There were 7 males and 33 females, age from 90 to 101 years old with an average of (94.6±1.6) years. Patients were divided into two groups according to whether adjacent vertebral refracture occurred after PVP. Among them, 20 patients occurred refracture after PVP (refracture group) and 20 patients did not occur it(control group). The general information, radiological data and pelvic parameters of the two groups were collected. The items included age, gender, body mass index (BMI), fracture site and bone mineral density(BMD) T-value, fracture to operation time, compression degree of injured vertebra, recovery degree of anterior edge of injured vertebra, bone cement injection amount, bone cement leakage, pelvic index(PI), pelvic tilt angle (PT), sacral angle(SS), et al. Factors that may be related to refracture were included in the single-factor study, and multivariate Logistic regression analysis was performed on the risk factors with statistical significance in the single-factor analysis to further clarify the independent risk factors for refracture of adjacent vertebral bodies after PVP. RESULTS: There were no significant differences in age, gender, fracture site, fracture to operation time, compression degree of injured vertebra and recovery degree of anterior edge of injured vertebra between two groups (P>0.05). There were significant differences in BMI, BMD T-value, bone cement injection amount and bone cement leakage rate between two groups(P<0.05). The PI and PT values of the refracture group were higher than those of the control group(P<0.05). There was no significant difference in SS between two groups (P>0.05). Multivariate Logistic regression analysis showed that decreased BMD T-value, bone cement leakage, increased PT and PI values increased the risk of recurrence of adjacent vertebral fractures in OVCFs (P<0.05). CONCLUSION There are many risk factors for the recurrence of adjacent vertebral fractures in super-old patients with OVCFs. Patients with high PI and PT values may be one of the risk factors.
Aged, 80 and over ; Bone Cements ; Female ; Fractures, Compression/surgery* ; Humans ; Male ; Osteoporotic Fractures/surgery* ; Retrospective Studies ; Risk Factors ; Spinal Fractures/surgery* ; Spine ; Treatment Outcome ; Vertebroplasty/adverse effects*

In the 1960s, sperm cryopreservation was developed as a method to preserve fertility. Currently, techniques for the cryopreservation of human spermatozoa have been widely used in assisted reproduction. However, although sperm cryobiology has made notable achievements, the optimal method for the recovery of viable spermatozoa after cryopreservation remains elusive. Postthawing sperm quality can be affected by cryoprotectants, ice formation, storage conditions, and osmotic stress during the freezing process. This review discusses recent advances in different cryopreservation techniques, cryoprotectants, and freezing and thawing methods during cryopreservation and new indications for the use of cryopreserved spermatozoa.
Humans ; Male ; Semen Preservation/methods* ; Sperm Motility ; Semen ; Cryopreservation/methods* ; Spermatozoa ; Cryoprotective Agents/pharmacology*

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

Cellular Senescence ; Heart ; Humans ; Ventricular Remodeling