Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective: To investigate the risk factors affecting the early diagnosis of ABO-hemolytic disease of the fetus and newborn (ABO-HDFN) in neonates with maternal-fetal blood group incompatibility, and to develop a risk prediction model and validate its predictive performance, so as to provide a reference for the early diagnosis of neonates with ABO-HDFN in primary hospitals. Methods: A total of 1 229 neonates with maternal-fetal blood group incompatibility suspected of ABO-HDFN, admitted to our hospital between between June 2021 and September 2024, were enrolled. The sample size was calculated by using the events per variable (EPV) method. The cohort was divided into a modeling group (n=860) and a validation group (n=369), and the results and clinical information of laboratory examination indicators were collected. Univariate and multivariate logistic regression analysis were used to explore the risk factors affecting the early diagnosis of ABO-HDFN in neonates with maternal-fetal blood group incompatibility. The risk prediction model was developed and internally validated by the Bootstrap method. The goodness-of-fit of the model was evaluated by the Hosmer-Lemeshow (H-L) test, and the receiver operating characteristic (ROC) curve was used to analyze the predictive performance of the model. The prediction model was validated by using the validation group data, and the predictive performance of the model was evaluated. Results: Among the 860 neonates with maternal-fetal incompatibility in the modeling group, 346 (346/860, 40.23%) were diagnosed with ABO-HDFN. Univariate and multivariate logistic regression analyses identified the following as significant risk factors for early diagnosis: the number of postnatal days at specimen collection, maternal type O blood group, parity >1, time of onset for pathologic jaundice, maternal-fetal blood group incompatibility due to A antigen, the level of total bilirubin, and the immature reticulocyte fraction (IRF). A risk prediction model was established, and the calibration degree of the model was validated by the Bootstrap internal validation method, Brier=0.143. The results of H-L test showed that χ =3.464, P=0.902. The area under the ROC curve (AUC) was 0.885. The maximum value of the Youden index was 0.611, the sensitivity was 0.832, and the specificity was 0.778. The results of the validation group showed that the area under the ROC curve was 0.863, with a sensitivity of 0.875 and specificity of 0.735. Conclusion: The risk prediction model developed based on these risk factors has good predictive performance for ABO-HDFN, facilitating early diagnosis of suspected ABO-HDFN cases by clinicians in primary hospitals.

Objective: To investigate the risk factors affecting the early diagnosis of ABO-hemolytic disease of the fetus and newborn (ABO-HDFN) in neonates with maternal-fetal blood group incompatibility, and to develop a risk prediction model and validate its predictive performance, so as to provide a reference for the early diagnosis of neonates with ABO-HDFN in primary hospitals. Methods: A total of 1 229 neonates with maternal-fetal blood group incompatibility suspected of ABO-HDFN, admitted to our hospital between between June 2021 and September 2024, were enrolled. The sample size was calculated by using the events per variable (EPV) method. The cohort was divided into a modeling group (n=860) and a validation group (n=369), and the results and clinical information of laboratory examination indicators were collected. Univariate and multivariate logistic regression analysis were used to explore the risk factors affecting the early diagnosis of ABO-HDFN in neonates with maternal-fetal blood group incompatibility. The risk prediction model was developed and internally validated by the Bootstrap method. The goodness-of-fit of the model was evaluated by the Hosmer-Lemeshow (H-L) test, and the receiver operating characteristic (ROC) curve was used to analyze the predictive performance of the model. The prediction model was validated by using the validation group data, and the predictive performance of the model was evaluated. Results: Among the 860 neonates with maternal-fetal incompatibility in the modeling group, 346 (346/860, 40.23%) were diagnosed with ABO-HDFN. Univariate and multivariate logistic regression analyses identified the following as significant risk factors for early diagnosis: the number of postnatal days at specimen collection, maternal type O blood group, parity >1, time of onset for pathologic jaundice, maternal-fetal blood group incompatibility due to A antigen, the level of total bilirubin, and the immature reticulocyte fraction (IRF). A risk prediction model was established, and the calibration degree of the model was validated by the Bootstrap internal validation method, Brier=0.143. The results of H-L test showed that χ =3.464, P=0.902. The area under the ROC curve (AUC) was 0.885. The maximum value of the Youden index was 0.611, the sensitivity was 0.832, and the specificity was 0.778. The results of the validation group showed that the area under the ROC curve was 0.863, with a sensitivity of 0.875 and specificity of 0.735. Conclusion: The risk prediction model developed based on these risk factors has good predictive performance for ABO-HDFN, facilitating early diagnosis of suspected ABO-HDFN cases by clinicians in primary hospitals.

Objective To analyze the causes of HIV-2 specific bands in the Western blot (WB) tests and to understand previous HIV-2 infection status in this city. Methods A total of 68 samples with HIV-2 specific bands in WB were analyzed using two confirmatory reagents. The test results were further analyzed in combination with epidemiological data, nucleic acid testing and gene sequencing. Results When tested with MP reagent, 66 samples (97.06%) were found to be positive for HIV-2 antibody, while the other two were negative or undetermined for HIV-2 antibody. When tested with MIKROGEN reagent, 67 samples (98.53%) were found to be positive for HIV-1 antibody, and one sample was negative for HIV-1 antibody. Further HIV-1 nucleic acid testing was conducted on these samples, and all 68 samples tested positive for HIV-1 RNA, with the results all exceeding 5,000 copies/ml. After BLAST comparison, it was found that the homology similarity of 68 samples to the HIV-1 reference strain sequence was >90%, but there was no similarity with the HIV-2 reference strain sequence. Conclusion The results of the serological test, nucleic acid test and gene sequencing of the 68 samples all have indicated HIV-1 infection. Combined with the epidemiological data, it can be concluded that the double reaction of HIV-1 and HIV-2 antibodies in WB tests of these 68 samples is very likely to be a non-specific cross-reaction rather than HIV-2 infection. This study indicates that no HIV-2 infection cases have been found in Chengdu so far.

Persistent infection with high-risk human papillomavirus(HR-HPV) is the primary etiological factor in cervical lesions and cervical cancer. Toll-like receptors(TLRs), as important pattern recognition receptors of the innate immune system, play a key role in the persistence of cervical HR-HPV infection. The "latent pathogen theory" in traditional Chinese medicine(TCM) holds that latent pathogens have both "latent" and "triggered" characteristics, which closely resemble the persistent infection and latent pathogenic potential of cervical HR-HPV. Guided by the "latent pathogen theory" and using contemporary immunological techniques, this paper explores the bidirectional immunomodulatory effects of TLRs in the persistence of cervical HR-HPV infection and their relationship with latent pathogens. The results indicate that TLRs play a crucial role in immune recognition and modulation. Dysregulation and overactivation of TLRs can induce chronic inflammation, allowing cervical HR-HPV to persist and evade immune detection. TLR dysfunction, coupled with a deficiency in healthy Qi that prevents the expulsion of pathogens, is a critical factor in the pathogenicity of latent pathogens. Restoring healthy Qi to modulate the immune functions of TLRs emerges as an important strategy for clearing cervical HR-HPV infection. By harmonizing the spleen and kidney and regulating immune balance, it is possible to reverse cervical HR-HPV infection, providing a scientific basis for clinical research.
Humans ; Toll-Like Receptors/genetics* ; Female ; Papillomavirus Infections/genetics* ; Papillomaviridae/immunology* ; Persistent Infection/genetics* ; Uterine Cervical Neoplasms/immunology* ; Animals ; Medicine, Chinese Traditional ; Cervix Uteri/immunology* ; Human Papillomavirus Viruses

The AP2/ERF transcription factor family is a class of transcription factors widely present in plants, playing a crucial role in regulating flowering, flower development, flower opening, and flower senescence. Based on transcriptome data from flower, leaf, and stem samples of two Lonicera macranthoides varieties, 117 L. macranthoides AP2/ERF family members were identified, including 14 AP2 subfamily members, 61 ERF subfamily members, 40 DREB subfamily members, and 2 RAV subfamily members. Bioinformatics and differential gene expression analyses were performed using NCBI, ExPASy, SOMPA, and other platforms, and the expression patterns of L. macranthoides AP2/ERF transcription factors were validated via qRT-PCR. The results indicated that the 117 LmAP2/ERF members exhibited both similarities and variations in protein physicochemical properties, AP2 domains, family evolution, and protein functions. Differential gene expression analysis revealed that AP2/ERF transcription factors were primarily differentially expressed in the flowers of the two L. macranthoides varieties, with the differentially expressed genes mainly belonging to the ERF and DREB subfamilies. Further analysis identified three AP2 subfamily genes and two ERF subfamily genes as potential regulators of flower development, two ERF subfamily genes involved in flower opening, and two ERF subfamily genes along with one DREB subfamily gene involved in flower senescence. Based on family evolution and expression analyses, it is speculated that AP2/ERF transcription factors can regulate flower development, opening, and senescence in L. macranthoides, with ERF subfamily genes potentially serving as key regulators of flowering duration. These findings provide a theoretical foundation for further research into the specific functions of the AP2/ERF transcription factor family in L. macranthoides and offer important theoretical insights into the molecular mechanisms underlying floral phenotypic differences among its varieties.
Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Transcription Factors/chemistry* ; Lonicera/classification* ; Flowers/metabolism* ; Phylogeny ; Gene Expression Profiling ; Multigene Family

PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*

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