Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

This article reports the clinical features and gene mutation types of a large family with Nascimento form of syndromic X-linked intellectual developmental disorder (MRXSN), involving 9 individuals across 3 generations, and a literature review was conducted. In this family, 9 individuals had similar manifestations including mental retardation and unusual facies, and 4 of them had passed away. Genetic testing showed that the proband had the deletion of exons 2-3 of the UBE2A gene, which was inherited from the mother. Fluorescent quantitative polymerase chain reaction showed that the proband and his uncle had the deletion of exons 2-3 of the UBE2A gene; the proband's mother, grandmother, and great-aunt had a heterozygous deletion of exons 2-3 of the UBE2A gene; the proband's father, sister, and aunt had a normal copy number of exons 2-3 of the UBE2A gene. The 34 patients reported in the literature had diverse clinical phenotypes, and UBE2A gene mutations (22/34, 65%) and large fragment deletions (12/34, 35%) were the main mutation types. Moderate to severe mental retardation (34/34, 100%), speech and language impairment (33/34, 97%), and unusual facies (32/34, 94%) were the main clinical manifestations of MRXSN patients. The disease has obvious phenotypic heterogeneity, and early diagnosis facilitates optimal prenatal and postnatal management to improve reproductive outcomes.
Humans ; Male ; Ubiquitin-Conjugating Enzymes/genetics* ; Female ; X-Linked Intellectual Disability/genetics* ; Gene Deletion ; Child ; Pedigree ; Child, Preschool ; Adult

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective To explore the effect of hyperbaric oxygen combined with synchronous brain bionic electrical stimulation on patients with stroke-related sleep disorders.Methods From November,2023 to November,2024,a total of 68 stroke patients with stroke-related sleep disorders ad-mitted to Huashan Hospital,Fudan University were selected.They were randomly divided into control group(n=34)and experimental group(n=34).The control group received routine hyperbaric oxygen therapy,while the ex-perimental group received routine hyperbaric oxygen therapy combined with synchronous brain bionic electrical stimulation inside the chamber,for four weeks.Pittsburgh Sleep Quality Index(PSQI),sleep-monitoring wrist-bands,Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS)were used to assess the outcomes before and after treatment..Results Four patients in the control group and one in the experimental group dropped out.After treatment,the scores of each factors of PSQI decreased in both groups(t>2.693,P<0.05),and were lower in the experimental group than in the control group(t>2.699,P<0.01),expect hypnotic drug use(P>0.05);the total sleep time,deep sleep time and rapid eye movement sleep time became longer in both groups(|t|>7.270,P<0.001),and they were longer in the experimental group than in the control group(|t|>5.712,P<0.001);the scores of SAS and SDS decreased in both groups(t>9.530,P<0.001),and they were less in the experimental group than in the control group(t>4.740,P<0.001).Conclusion Synchronous brain bionic electrical stimulation in hyperbaric oxygen chamber could effectively prolong the total sleep time,deep sleep time and rapid eye movement time of patients with stroke-related sleep disorders,re-lieve anxiety and depression after stroke,and improve sleep quality.

Objective:To investigate the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage in Chinese population from childhood to middle age.Methods:This study is a population-based, long-term follow-up cohort study. Participants who had their blood pressure measured at least 5 times in the Hanzhong Adolescent hypertension cohort from 1987 to 2023 were included in this study. Group-based trajectory modeling was used to identify different systolic and diastolic blood pressure trajectories, and the subjects were divided into low-increasing group, moderate-increasing group and high-increasing group according to blood pressure trajectories. Blood pressure variability was assessed using standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Target organ damage was evaluated during the final follow-up in 2023 (middle age). Logistic regression models were used to analyze the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage.Results:A total of 2 447 subjects were included, with a median age of 48 years, of whom 1 373 were male (56.1%). Based on systolic blood pressure, 868 were in the low-increasing group, 1 238 in the moderate-increasing group, and 341 in the high-increasing group. For diastolic blood pressure, the distribution was 894, 1 263 and 290, respectively. Compared with the low-increasing group of systolic blood pressure, the moderate-increasing group (arteriosclerosis: OR=4.14, 95% CI 2.96-5.79; proteinuria: OR=2.06, 95% CI 1.38-3.07; left ventricular hypertrophy: OR=1.68, 95% CI 1.00-2.82) and high-increasing group (arterial stiffness: OR=15.44, 95% CI 10.14-23.50; proteinuria: OR=5.80, 95% CI 3.63-9.29; left ventricular hypertrophy: OR=2.93, 95% CI 1.55-5.53) had a higher risk of target organ damage (all P<0.005). The moderate-increasing group of diastolic blood pressure had a higher incidence of arterial stiffness ( OR=3.72, 95% CI 2.69-5.12) and proteinuria ( OR=1.67, 95% CI 1.15-2.42) than the low-increasing group (all P<0.005), while the high-increasing group had a significantly higher risk of all type of target organ damage compared to the low-increasing group (arterial stiffness: OR=10.84, 95% CI 7.08-16.61; proteinuria: OR=3.72, 95% CI 2.31-5.99; left ventricular hypertrophy: OR=2.38, 95% CI 1.23-4.59; all P<0.005). Additionally, higher systolic blood pressure variability was associated with an increased incidence of arterial stiffness (SD: OR=2.25, 95% CI 1.96-2.57; VIM: OR=1.64, 95% CI 1.45-1.86; ARV: OR=1.70, 95% CI 1.50-1.93) and proteinuria (SD: OR=1.65, 95% CI 1.44-1.89; VIM: OR=1.41, 95% CI 1.22-1.63; ARV: OR=1.45, 95% CI 1.26-1.67; all P<0.005). The results for diastolic blood pressure variability indicators were similar to those for systolic blood pressure. Conclusion:Early-life blood pressure trajectories are predictive of target organ damage risk in middle age. Higher blood pressure variability is related to an increased risk of arterial stiffness and proteinuria, but was less associated with left ventricular hypertrophy. Focusing on the risk of high blood pressure early in life can help prevent the occurrence of target organ damage in middle age.

OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.