Objective To clarify the risk factors of diaphragmatic dysfunction (DD) after cardiac surgery with extracorporeal circulation. Methods A retrospective analysis was conducted on the data of patients who underwent cardiac surgery with extracorporeal circulation in the Department of Cardiovascular Surgery of Peking University People's Hospital from January 2023 to March 2024. Patients were divided into two groups according to the results of bedside diaphragm ultrasound: a DD group and a control group. The preoperative, intraoperative, and postoperative indicators of the patients were compared and analyzed, and independent risk factors for DD were screened using multivariate logistic regression analysis. Results A total of 281 patients were included, with 32 patients in the DD group, including 23 males and 9 females, with an average age of (64.0±13.5) years. There were 249 patients in the control group, including 189 males and 60 females, with an average age of (58.0±11.2) years. The body mass index of the DD group was lower than that of the control group [(18.4±1.5) kg/m2 vs. (21.9±1.8) kg/m2, P=0.004], and the prevalence of hypertension, chronic obstructive pulmonary disease, heart failure, and renal insufficiency was higher in the DD group (P<0.05). There was no statistical difference in intraoperative indicators (operation method, extracorporeal circulation time, aortic clamping time, and intraoperative nasopharyngeal temperature) between the two groups (P>0.05). In terms of postoperative aspects, the peak postoperative blood glucose in the DD group was significantly higher than that in the control group (P=0.001), and the proportion of patients requiring continuous renal replacement therapy was significantly higher than that in the control group (P=0.001). The postoperative reintubation rate, tracheotomy rate, mechanical ventilation time, and intensive care unit stay time in the DD group were higher or longer than those in the control group (P<0.05). Multivariate logistic regression analysis showed that low body mass index [OR=0.72, 95%CI (0.41, 0.88), P=0.011], preoperative dialysis [OR=2.51, 95%CI (1.89, 4.14), P=0.027], low left ventricular ejection fraction [OR=0.88, 95%CI (0.71, 0.93), P=0.046], and postoperative hyperglycemia [OR=3.27, 95%CI (2.58, 5.32), P=0.009] were independent risk factors for DD. Conclusion The incidence of DD is relatively high after cardiac surgery, and low body mass index, preoperative renal insufficiency requiring dialysis, low left ventricular ejection fraction, and postoperative hyperglycemia are risk factors for DD.

OBJECTIVE To investigate the mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture based on the AMP-activated protein kinase （AMPK）/silencing information regulatory factor 1 （SIRT1）/ peroxisome proliferator activated-receptor-γ coactivator-1α （PGC-1α） signaling pathway. METHODS Rats with hip fracture surgery were assigned into model group， esketamine group （10 mg/kg）， inhibitor group （250 μg/mL AMPK inhibitor Compound C）， and esketamine+inhibitor group （10 mg/kg esketamine + 250 μg/mL Compound C）， and rats undergoing sham surgery were used as the control group， with 12 rats in each group. New object recognition and Barnes maze experiments were used to E-mail：448231@163.com evaluate cognitive function in rats. The levels of serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β），superoxide dismutase （SOD）， malondialdehyde （MDA）， gamma-aminobutyric acid （GABA）， dopamine （DA） and glutamate （Glu）， and the apoptosis of hippocampal neurons were detected. The pathological morphology of the hippocampal tissue and the ultrastructure of mitochondria were observed. The mRNA expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax），the mRNA and protein expression of AMPK， SIRT1 and PGC-1α， as well as the expression of phosphorylated （p）-AMPK in hippocampal tissue， were detected. RESULTS Compared with the control group， the hippocampal neurons in the model group of rats were disordered， with more neurons necrotic and swollen mitochondria；the new object recognition index， the SOD， GABA， DA levels， Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly reduced， while the latency and number of errors for locating unknown holes， the TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly increased/prolonged （P＜0.05）. Compared with the model group， the esketamine group showed reduced pathological damage to the hippocampal tissue of rats， and the new object recognition index， the SOD， GABA and DA levels， the Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly increased，while the latency and error frequency for locating unknown holes， TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly decreased （P＜0.05）；the inhibitor group showed the opposite trend of changes in these indicators compared to the esketamine group （P＜0.05）.AMPK inhibitor could reverse the improvement effect of esketamine on the above indicators after hip fracture surgery in rats （P＜0.05）. CONCLUSIONS Esketamine may improve postoperative inflammatory response and oxidative stress levels in rats with hip fracture by activating the AMPK/SIRT1/PGC-1α signaling pathway， inhibiting neuronal cell apoptosis， improving mitochondrial structure， and promoting postoperative cognitive function recovery.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

Objective:To explore the genetic basis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency (OTCD) and MECP2 duplication syndrome.Methods:A proband who was admitted to the Neonatal Intensive Care Unit of Gansu Provincial Maternal and Child Health Care Hospital on December 19, 2017 was selected as the study subject. High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were carried out for her pedigree, and short tandem repeat-based linkage analysis and chromosome copy number variation sequencing (CNV-seq) were used for the prenatal diagnosis.Results:The proband, a 3-day-old female, was found to harbor heterozygous deletion of exons 7-9 of the OTC gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4). The proband was diagnosed with OTCD, which was in keeping with her acute encephalopathy and metabolic abnormalities (manifesting as hyperammonemia, decreased blood citrulline, and increased urine orotic acid). Prenatal diagnosis was carried out for the subsequent pregnancy. The fetus did not harbor the exons 7-9 deletion of the OTC gene, but was found to carry a duplication in Xq28 region (which encompassed the whole region of MECP2 duplication syndrome) and was positive for the SRY sequence. The same duplication was also found in the proband and her mother. Considering the possible existence of X-chromosome inactivation, the proband was diagnosed with two X-linked recessive disorders including OTCD and MECP2 duplication syndrome, and the fetus was determined as a male affected with the MECP2 duplication syndrome. Conclusion:Discoveries of the pathogenic variants underlying the OTCD and MECP2 duplication syndrome have enabled clinical intervention, treatment, genetic counseling and prenatal diagnosis for this pedigree.

Objective:To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD).Methods:Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.Results:Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c. 49G>C (p.Gly17Arg) and c. 106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c. 199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c. 106-2A>G and c. 49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 49G>C (p.Gly17Arg), c. 106-2A>G, and c. 199-10T>G variants were classified as likely pathogenic (PM2_supporting+ PP3+ PM3_strong+ PP4), pathogenic (PVS1+ PM2_supporting+ PM5+ PP3), and pathogenic (PVS1+ PM2_supporting+ PP3+ PP5), respectively. Conclusion:Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.

Objective:To explore the genetic characteristics of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome (RTT).Methods:A male infant who was admitted to Gansu Provincial Maternity and Child Health Care Hospital in May 2020 was selected as the study subject. Clinical data of the infant was collected. Genomic DNA was extracted from peripheral blood samples from the infant and his parents, and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Result:The patient, a 4-day-old male infant, had presented with poor response, poor intake, feeding difficulties, and deceased at 8 months after birth. WES revealed that he has harbored a 0.643 Mb deletion in the 16p11.2 region, which encompassed key genes of the 16p11.2 microdeletion syndrome such as ALDOA, CORO1A, KIFF22, PRRT2 and TBX6. His father has carried the same deletion, but was phenotypically normal. The deletion was predicted to be pathogenic. The child was also found to harbor a maternally derived c. 763C>T (p.R255X) hemizygous variant of the MECP2 gene, which was also predicted to be pathogenic (PVS1+ PS4+ PM2_Supporting). Conclusion:The 16p11.2 deletion and the MECP2: c.763C>T (p.R255X) variant probably underlay the pathogenesis in this infant.

Objective To screen the key characteristic genes of metastatic nasopharyngeal carcinoma(mNPC)and analyze the immune cell infiltration in tumor microenvironment using machine learning algorithm.Methods Firstly,the training set GSE103611 was downloaded from the GEO database,and the data were subjected to differential expression gene(DEGs)screening,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genome(KEGG)and immune cell infiltration analysis.Second,the predicted genes in DEGs were screened by least absolute shrinkage and selector operation(LASSO)regression,and the characteristic genes were screened by using the expression level of the predicted genes and receiver operating characteristic(ROC).Third,the correlation between characteristic genes and immune cells was further analyzed to determine the key characteristic genes.Finally,the expression levels of key characteristic genes and ROC were verified using the reverse validation set GSE1245 data.Results A total of 136 DEGs were obtained,and their KEGG were mainly enriched in cytochrome P450,tumor necrosis factor(TNF)signaling pathway,prion disease,EB virus infection,and other pathways.GO was mainly enriched in the negative regulatory processes of peptide-based tyrosine phosphorylation modification,viral gene expression,and B cell and leukocyte activation.The difference in the degree of infiltration of the 22 immune cells in nasopharyngeal carcinoma(NPC)and mNPC was not significant.Two key characteristic genes(DAZ1 and SCCPDH)of mNPC were finally obtained by LASSO regression,and they were significantly correlated with immune cells in the mNPC microenvironment(P＜0.05).In the reverse validation data set,the differential expressions of DAZ1 and SCCPDH between non-NPC(nNPC)and NPC groups were not significant(P＞0.05),and the AUC values of ROC of both were less than 0.6.Conclusion DAZ1 and SCCPDH are the key characteristic genes of mNPC and can be used as important markers for mNPC and immunotherapy.