Objective To evaluate the impact of an integrated management mode of prenatal diagnosis-postnatal treatment for congenital heart disease (CHD) on perioperative and long-term outcomes of the arterial switch operation (ASO), and to analyze the efficacy of ASO in a single center. Methods This retrospective study analyzed the clinical data of 183 children who underwent ASO at Guangdong Provincial People’s Hospital from 2018 to 2024. The cohort included 106 (57.9%) patients of transposition of the great arteries with intact ventricular septum (TGA/IVS), 61 (33.3%) patients of transposition of the great arteries with ventricular septal defect (TGA/VSD), and 16 (8.7%) patients of Taussig-bing anomaly (TBA). Perioperative indicators were compared between 91 patients in the prenatal-postnatal integrated management group (an integrated group) and 92 patients in the traditional management group (a non-integrated group). Long-term survival and reoperation rates were analyzed using Kaplan-Meier curves. Results The overall perioperative mortality rate was 4.9% (9/183), showing a downward trend year by year. The primary cause of perioperative mortality was low cardiac output syndrome (LCOS), which occurred in 12 patients (6.6% incidence) with a mortality rate of 75.0%. The integrated group had a higher proportion of males (89.0% vs. 72.8%, P<0.05) and lower body weight [3.1 (2.7, 3.3) kg vs. 3.3 (3.0, 3.7) kg, P<0.05] compared to the non-integrated group. The age at surgery was significantly earlier in the integrated group [7 (3, 10) d vs. 14 (9, 48) d, P<0.05], and all children in the integrated group underwent ASO within the optimal surgical window (100.0% vs. 82.6%, P<0.05). Intraoperatively, cardiopulmonary bypass time [173 (150, 207) min vs. 186 (159, 237) min, P<0.05] and aortic cross-clamp time [100 (90, 117) min vs. 116 (97, 142) min, P<0.05] were significantly shorter in the integrated group. Although the integrated group had longer postoperative mechanical ventilation time [145 (98, 214) h vs. 116 (77, 147) h, P<0.05] and higher 48-hour maximum vasoactive inotropic score [15 (10, 21) points vs. 12 (8, 16) points, P<0.05], there was no statistically significant difference in the incidence of severe complications (LCOS, necrotizing enterocolitis, extracorporeal membrane oxygenation) or mortality rate (3.3% vs. 6.5%, P=0.51) between the two groups, despite earlier surgical intervention and a higher proportion of critically ill cases in the integrated group. The length of hospital stay in the emergency surgery group was significantly shorter than that in the elective surgery group [20 (15, 28) d vs. 25 (21, 30) d, P<0.05], suggesting that early surgery may be of potential benefit. A total of 163 patients were successfully followed up for a median of 4.7 years, with a 5-year survival rate of 95.1% and a freedom from reintervention survival rate of 95.1%. There were no late deaths, and the most common postoperative complication was pulmonary artery stenosis. Conclusion The integrated management model allowed critically ill children with lower body weights to safely undergo surgery, significantly optimizing the timing of surgery and shortening intraoperative times. The long-term risk of reoperation after ASO is primarily concentrated on pulmonary artery stenosis, necessitating long-term follow-up and monitoring.

OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Methods: Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results: Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.

Methods: Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results: Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.

Methods: Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results: Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.

Gegen Qinlian Decoction(GQD) is a classic prescription for the clinical treatment of ulcerative colitis(UC). This study, based on the differences in efficacy observed in UC mice under different level of bile acids treated with GQD, aims to clarify the impact of bile acids on UC and its therapeutic effects. It further investigates the expression of bile acid receptors in the liver of UC mice, and preliminarily reveals the mechanism through which GQD affects bile acid synthesis in the treatment of UC. A UC mouse model was established using dextran sulfate sodium(DSS) induction. The efficacy of GQD was evaluated by assessing the general condition, disease activity index(DAI) score, colon length, and histopathological changes in colon tissue via hematoxylin and eosin(HE) staining. ELISA and Western blot were used to evaluate the inflammatory response in colon tissue. The total bile acid(TBA) level and liver damage were quantified using an automatic biochemistry analyzer. The expression levels of bile acid receptors and bile acid synthetases in liver tissue were detected by Western blot and RT-qPCR. The results showed that compared with the model group, GQD treatment significantly improved the DAI score, colon shortening, and histopathological damage in UC mice. The levels of pro-inflammatory factors TNF-α and IL-6 in the colon were significantly reduced. Serum TBA levels were significantly decreased, while alkaline phosphatase(ALP) levels significantly increased. After administration of cholic acid(CA), UC symptoms in the CA + GQD group were significantly aggravated compared with the GQD group. The DAI score, degree of weight loss, colon injury, serum TBA, and liver injury markers all increased significantly. However, compared with the CA group, the CA + GQD group showed a marked reduction in TBA levels and a significant improvement in UC-related symptoms, indicating that GQD can alleviate UC damage exacerbated by CA. Further investigation into the expression of bile acid receptors and synthetases in the liver showed that under GQD treatment, the expression of farnesoid X receptor(FXR) and small heterodimer partner(SHP) significantly increased, while the expression of G protein-coupled receptor 5(TGR5) and cholesterol 7α-hydroxylase(Cyp7A1) significantly decreased. These findings suggest that GQD may affect bile acid receptors and synthetases, inhibiting bile acid synthesis through the FXR/SHP pathway to treat UC.
Animals ; Colitis, Ulcerative/genetics* ; Bile Acids and Salts/biosynthesis* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Male ; Humans ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Colon/metabolism* ; Disease Models, Animal ; Liver/metabolism* ; Mice, Inbred C57BL

This study explores whether the current external quality assessment (EQA) level and acceptable bias for basic semen analysis in China are clinically useful. We collected data of semen EQA from Andrology laboratories in the Hunan Province (China) in 2022 and searched for data in the published literature from January 2000 to December 2023 in China. On the basis of these data, we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics. We compared these findings with quality specifications based on biological variation from optimal, desirable, and minimum levels of bias to seek a unified and more suitable semen EQA bias evaluation standard for China's national conditions. Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories, ranging from 8.2% to 56.9%. A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility (PR), whereas 100.0% and 75.0% of laboratories met only the minimum quality specifications for sperm concentration and total motility (nonprogressive [NP] + PR), respectively. The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification, whereas the Z value for PR was equivalent only to the minimum performance specification. This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation. These specifications should be unified among external quality control (EQC) centers based on biological variation.
Semen Analysis/standards* ; Humans ; China ; Male ; Quality Control ; Sperm Motility ; Sperm Count/standards*