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.

As a traditional nutritional and healthy cash crop in China, tea has certain significance in promoting human health and preventing and controlling chronic diseases. Studies have shown that the nutritional health effect of tea is due to its rich functional components, mainly including tea polyphenols, tea pigments, tea polysaccharides, theanine, alkaloids and other bioactive substances. At present, researchers from the academic circles have continuously carried out animal and human experiments on the health effects of various functional components of tea, which has accumulated abundant research data and materials. Based on this, this article reviews the literature on the nutritional and health effects of the main functional components of tea, and adopts the method of evidence-based research to screen and extract relevant data for qualitative and quantitative meta-analysis. Subsequently, the nutritional health effects of the five functional components of tea, namely tea polyphenols, tea pigments, tea polysaccharides, theanine, and alkaloids, are summarized and outlined. Studies have shown that tea polyphenols, tea pigments, tea polysaccharides, theanine and alkaloids have different health effects and are expected to play their unique roles in promoting human health and preventing and controlling diseases.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Copper death is a newly discovered copper-dependent cell death mode that causes protein-toxic stress and triggers cell death by affecting mitochondrial tricarboxylic acid cycling and iron-sulfur tuftin loss. In recent years, with the in-depth study of the mechanism of copper death, it has been found that the genes related to copper death may be related to the clinical characteristics and prognosis of tumors, which can be used as potential biological targets for the diagnosis or treatment of tumors. At the same time, drugs targeting copper ions such as copper ionophores, copper chelators and copper containing complexes are widely studied. Further study on the mechanism of copper death in the development of tumor can provide new ideas for tumor diagnosis and treatment.

Objective:To explore the clinical and genetic characteristics of a child with autosomal recessive primary microcephaly (MCPH).Methods:A case study has been carried out on a boy who had presented at the Inner Mongolia Maternity and Child Health Care Hospital for microcephaly and mental deficiency in September 2022. Prenatal ultrasound images were retrospectively analyzed, and whole exome sequencing and Sanger sequencing were carried out for his family. A literature review was also carried out using keywords such as " ASPM gene", "microcephaly", "prenatal diagnosis", "primary microcephaly", " ASPM", "MCPH5", "MCPH", "autosomal recessive microcephaly", and "prenatal diagnosis on ultrasonography" on the PubMed database, Wanfang Data and China National Knowledge until September 2023. This study was approved by Medical Ethics Committee of the Inner Mongolia Maternity and Child Health Care Hospital (Ethics No. 2021-093-1). Results:The proband had shown progressive reduction in biparietal diameter (BPD) and head circumference (HC) during the fetal period. He was found to harbor compound heterozygous variants of the ASPM gene, which included a paternally derived c. 8044C>T (p.R2682X) and a maternally derived c.8652dup (p.A2885Sfs*35). Both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4; PVS1+ PM2_Supporting+ PM3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). For other fetuses in his family, prenatal ultrasound and genetic testing were all normal. Literature research has identified 11 relevant articles, which included 14 MCPH cases. All of the MCPH5 cases had shown various degrees of reduced BPD/HC on fetal imaging (100%, 15/15). Developmental delay, intellectual disability, and attention deficits were noted in all survived cases, with one case having seizures (12.5%, 1/8). Their genotypes had included homozygotes (46.2%, 6/13) and compound heterozygotes (53.8%, 7/13) for nonsense variants (45%, 9/20) and frameshifting variants (55%, 11/20). Conclusion:The compound heterozygous variants c. 8044C>T (p.R2682X) and c. 8652dup (p.A2885Sfs*35) of the ASPM gene probably underlay the reduced BPD and HC in this proband with MCPH.

Objective To investigate the correlations microRNA-203a-3p(miR-203a-3p)and paired allographic box protein 2B(PHOX2B)expression levels in glioma tissues with clinical features and prognosis.Methods Ninety-six glioma patients admitted to our hospital from June 2017 to April 2020 were included in the study.The resected glioma tissues and corresponding paracancerous tissues from the patients were collected intraop-eratively.qRT-PCR and immunohistochemistry were conducted to detect the expression of miR-203a-3p and PHOX2B mRNA in glioma tissues and paracancerous groups.Pearson's method was used to analyze the correlation between miR-203a-3p and PHOX2B mRNA.Kaplan-Meier survival curves were used to analyze the correlations of miR-203a-3p and PHOX2B mRNA with the prognosis of glioma patients.COX regression was used to analyze the risk factors affecting the prognosis of glioma patients.Results The miR-203a-3p level and positive expression rate of glioma tissues were significantly lower than that of paracancerous tissues(P<0.05),and the PHOX2B mRNA level and positive expression rate were significantly higher than that of paracancerous tissues(P<0.05).By Pearson correlation analysis,the miR-203a-3p and PHOX2B mRNA levels of glioma patients were negatively correlated(P<0.05).miR-203a-3p and PHOX2B were associated with KPS score,tumor tissue necrosis,and WHO grading(P<0.05).Kaplan-Meier curve analysis yielded the results that the survival rate of the miR-203a-3p highly expressed group was significantly higher than that of the lowly expressed group(P<0.05),and the survival rate of the PHOX2B mRNA highly expressed group was significantly lower than that of the lowly expressed group(P<0.05).COX regression analysis showed that miR-203a-3p,PHOX2B mRNA,tumor tissue necrosis,and WHO grading were the risk factors affecting the prognosis of glioma patients(P<0.05).Conclusion The expression level of miR-203a-3p is obviously reduced and the expression level of PHOX2B mRNA is obviously increased in glioma,both showing close correlation with clinical characteristics and prognosis.

Objective:To summarize the current research status, assessment tools, and influencing factors of fatigue in patients receiving maintenance hemodialysis (MHD) and provide a reference for the management of fatigue in this patient population.Methods:A literature search was conducted in databases including PubMed, Web of Science, ProQuest, Cochrane Library, Science Direct, Embase, CINAHL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for studies related to fatigue in patients receiving MHD. The search timeframe was from establishing the databases to January 23, 2024.Results:A total of 46 studies were included. Various assessment tools for fatigue in patients receiving MHD were identified, though specific tools were limited. The Short Form 36 Vitality Subscale (SF-36 VS) was the most commonly used assessment tool. The main factors influencing fatigue in these patients included sociodemographic, dialysis-related, disease-related, physical, nutritional, and psychological factors.Conclusions:Fatigue is a significant symptom in patients receiving MHD. Healthcare professionals must develop specific tools for accurately assessing fatigue in this population and explore standardized management plans.

Objective To investigate the correlation between the Controlling Nutritional Status (CONUT) score and wound repair of diabetic foot ulcer (DFU). Methods A total of 80 DFU patients treated in the Hospital from November 20, 2019 to November 20, 2022 were randomly selected as the study objects and divided into non-wound repair group (n=47) and wound repair group (n=33) based on wound repair status. Wound repair and hospital stay were recorded; clinical characteristics and the CONUT score were compared between the wound repair group and the non-wound repair group; the influencing factors of DFU wound repair were analyzed by the multivariate Logistic regression model. Results The hospital stay of patients in the non-wound repair group was 16.00 (10.50 to 24.00) days, which was significantly shorter than 44.00 (31.00 to 61.80) days of patients in the wound repair group (P < 0.05). The total cholesterol (TC), ankle-brachial index (ABI), the CONUT score, and malnutrition rate of patients in the non-wound repair group were significantly higher than those in the wound repair group (P < 0.05). The results of multivariate Logistic regression analysis showed that the CONUT score, malnutrition, TC and ABI were the independent risk factors for wound repair of DFU (P < 0.05). Conclusion Malnutrition, ABI, TC and CONUT score in DFU patients can adversely affect wound repair, and the CONUT score can accurately predict the risk of wound repair in patients, serving as a reliable reference for clinicians in early assessment of DFU.

Objective To investigate the roles of histone H3K27me3 methylation and its regulatory enzymes JMJD3 and EZH2 in the differentiation of Th17 cells in ankylosing spondylitis(AS),to unveil their potential involvement in the pathogenesis of AS,and to provide new strategies and targets for the clinical treatment of AS by analyzing the methylation state of H3K27me3 and its interactions with Th17-related factors.Methods A total of 84 AS patients(42 active AS patiens and 42 patients in the stable phase of AS)were enrolled for the study,while 84 healthy volunteers were enrolled as the controls.Blood samples were collected.Peripheral blood mononuclear cells were isolated.ELISA assay was performed to examine Th17 cells and the relevant cytokines IL-21,IL-22,and IL-17.The mRNA expressions of RORc,JAK2,and STAT3 were analyzed by RT-PCR,the protein expressions of RORc,JAK2/STAT3 pathway protein,H3K27me3 and the relevant protease(EZH2 and JMJD3)were determined by Western blot.Correlation between H3K27me3,EZH2 and JMJD3 and the key signaling pathway molecules of Th cell differentiation was analyzed by Pearson correlation analysis.Results The mRNA expressions of RORc,JAK2,and STAT3 were significantly higher in the active phase group than those in the stable phase group(P<0.05).The relative grayscale values of H3K27me3 and EZH2 in the active phase group were lower than those of the stable phase group,which were lower than those of the control group,with the differences being statistically significant(P<0.05).The relative grayscale values of JMJD3,RORc,JAK2,pJAK2,STAT3,and pSTAT3 proteins were significantly higher in the active phase group than those in the stable phase group,which were higher than those in the control group(all P<0.05).The proportion of Th17 and the expression level of inflammatory factors in the active period group were higher than those in the other two groups(P<0.05).H3K27me3 was negatively correlated with RORc,JAK2,STAT3,and IL-17,JMJD3 was positvely correlated with JAK2,STAT3,and IL-17,and EZH2 was negatively correlated with JAK2,STAT3,and IL-17(all P<0.05).Conclusion The low expression of H3K27me3 in AS is influenced by the gene loci JMJD3 and EZH2,which can regulate the differentiation of Th17 cells and thus play a role in the pathogenesis and progression of AS.

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.
Animals ; Brain Ischemia ; Carotid Stenosis/drug therapy* ; Cognitive Dysfunction/etiology* ; Digoxin ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; White Matter