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.

Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans ; Ribosomes/physiology* ; Ribosomal Proteins/metabolism* ; Mutation ; Animals ; Cell Nucleolus/metabolism* ; Protein Biosynthesis ; Phase Separation

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.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Objective:To investigate the effect of "four-staff co-management" follow-up mode on risk factor control and medium-term prognosis improvement in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:This was a intervention study. Patients with coronary heart disease who were admitted to the Xiamen Cardiovascular Hospital of Xiamen University from June 2021 to January 2022 and successfully discharged after PCI were included. According to the different types of follow-up after discharge, patients were divided into the traditional follow-up group and the "four-staff co-management" follow-up group. The "four-staff co-management" follow-up mode means that specialists, specialist managers in third-level A hospitals and general practitioners and health managers in basic hospitals were jointly responsible for post-discharge follow-up of PCI patients. Baseline clinical data were collected. The primary endpoints were the rate of compliance of coronary heart disease risk factor control at 12 months after surgery, the rate of secondary surgery, and the incidence of mid-term major adverse cardiovascular and cerebrovascular events (MACCE). Unplanned secondary PCI included symptom-driven secondary PCI and asymptomatic secondary PCI. MACCE includes myocardial infarction, hospitalization for heart failure, stroke, major bleeding, all-cause death, and composite endpoints including these events.Results:A total of 2 181 patients were enrolled, including 1 097 patients in the traditional follow-up group and 1 084 patients in the "four-staff co-management" follow-up group. At baseline, there were no statistically significant differences in gender, age, discharge diagnosis, co-existing diseases, echocardiographic indexes, and coronary artery lesions between the two groups (all P>0.05). There were no significant differences between the two groups in total PCI stent length, maximum internal diameter of stent, proportion of patients using drug balloon, proportion of patients with a planned second surgery during hospitalization, and discharge with drugs (all P>0.05). Twelve months after PCI, the reduction in HbA1c and low-density lipoprotein cholesterol was greater in the "four-staff co-management " follow-up group than that in the traditional follow-up group (all P<0.05), and the rate of reaching the standard for low-density lipoprotein cholesterol was higher than that in the traditional follow-up group ( P=0.001), but there was no statistical significance between the two groups for blood pressure and blood glucose (all P>0.05). During the follow-up period, the proportion of symptom-driven second operation patients was lower in the "four-staff co-management" follow-up group than that in the traditional follow-up group ( P<0.001), and there was no significant difference in the proportion of asymptomatic second operation patients between the two groups ( P=0.191). The proportion of hospitalized patients with heart failure in the "four-staff co-management" follow-up group was lower than that in the traditional follow-up group ( P=0.029), and there was no significant difference in the proportion of myocardial infarction, cerebral infarction, cerebral hemorrhage, massive hemorrhage, death and complex endpoint events between the two groups (all P>0.05). Conclusion:The "four-staff co-management" follow-up mode can effectively improve the control of risk factors and medium-term prognosis in patients with coronary heart disease after PCI.

Meckel′s cartilage (MC) was first delineated in 1820 by the German anatomist Johann Friedrich Meckel the Younger through his examination of human embryos. During early development, MC functions as a supportive structure for the mandible and serves as a template for the subsequent formation of the jaw bones. Ultimately, MC transforms into either skeletal tissue, ligaments, or completely resorbs, integrating with the continuously developing osseous structures. This review elucidates the influence of MC development and degeneration on mandibular morphogenesis, delineating cellular processes and key factors that govern chondrogenic fate determination. The analysis reveals how the alterations of MC affect mandibular and craniofacial development. As a transient cartilaginous structure, investigation into MC may yield valuable insights for understanding oral and craniomaxillofacial pathologies.

Objective:Exploring the association between Life's Crucial 9 (LC9) and the risk of thyroid dysfunction (TD), as well as its potential predictive capacity.Methods:A total of 247 600 TD-free participants from the UK Biobank were enrolled in the study. The LC9 score was divided into three CVH groups: low (0-), medium (50-), and high (80-100). Cox proportional hazards regression models were used to calculate the HRs and 95% CIs of the risk of TD with LC9 CVH status. Calculate Harrell's concordance index ( C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to evaluate the predictive ability of the LC9 score and Life's Essential 8 (LE8) score. Results:During a median follow-up of 12.3 years, 5 515, 911, and 4 869 new cases of TD, hyperthyroidism, and hypothyroidism were documented, respectively. Participants with a high LE8 CVH group had 57.00% ( HR=0.43, 95% CI: 0.38-0.49), 55.00% ( HR=0.45, 95% CI: 0.34-0.60), and 58.00% ( HR=0.42, 95% CI: 0.37-0.47) lower risk of TD, hyperthyroidism, and hypothyroidism, respectively, than those with low CVH group. Compared with the LE8 score, the improvement in C-index for the LC9 score predicted TD risk was 0.004 (95% CI: 0.001-0.007), the NRI was 0.101 (95% CI: 0.021-0.103), and the IDI was 0.001 (95% CI: 0.000-0.001). Conclusions:The better CVH status, defined by LC9, was associated with a lower risk of TD. Compared to the LE8 score, the LC9 score demonstrated a significant enhancement in both risk discrimination and reclassification capability for TD risk.

Objective:To explore the advantages of robotic-arm assisted total hip arthroplasty (rTHA) in acetabular component positioning and lower limb length assessment in patients with severe pelvic coronal tilt.Methods:A retrospective analysis was conducted on the data of 122 patients with unilateral end-stage hip disease and coronal pelvic tilt angle >3° who underwent total hip arthroplasty (THA) at the First Medical Center of PLA General Hospital from June 2022 to December 2023. Among them, 44 patients underwent rTHA, and 78 underwent manual THA (mTHA). The rTHA group included 18 males and 26 females, with an average age of 60.5±9.3 years; the mTHA group included 41 males and 37 females, with an average age of 58.5±8.4 years. Compare the differences in the anteversion angle, abduction angle, pelvic tilt angle, leg length discrepancy (LLD) of the acetabular prosthesis, and the proportions of patients with LLD>0.5 cm and >1 cm between the two groups of patients after surgery. Calculate the proportion of outlier rates of acetabular abduction angle (<30° or >45°), and proportions within Callanan's safe zone. The early efficacy of the hip joint was evaluated by using the modified Harris score and joint range of motion.Results:All patients were followed up for 6 to 12 months, with an average of 8 months. All the surgical incisions of the patients achieved primary healing. Postoperative comparisons showed no statistically significant differences in acetabular abduction angle (39.5°±3.3° vs. 38.4°±7.3°) or anteversion angle (20.7°±1.6° vs. 19.7°±1.6°) between rTHA and mTHA groups ( P>0.05). However, pelvic tilt angle [2.5° (1.1°, 3.6°) vs. 3.5° (2.3°, 5.9°)] showed a statistically significant difference ( U=4.371, P=0.008). The rTHA group exhibited smaller absolute LLD [0.2 (0.1, 0.4) cm vs. 0.5 (0.2, 0.5) cm] and lower proportions of LLD >0.5 cm [14% (6/44) vs. 49% (38/78)] and >1 cm [2% (1/44) vs. 18% (14/78)], with statistical significance ( P<0.05). The rTHA group had a lower outlier rate for acetabular abduction angle (<30°or >45°) compared to the mTHA group [2% (1/44) vs. 33% (26/78)], with statistical significance (χ 2=10.388, P<0.001). Taking the Callanan safety zone as the standard, the proportion of acetabular cups within the safe zone was significantly higher in the rTHA group (98%, 43/44) compared to the mTHA group (67%, 52/78), with a statistically significant difference (χ 2=13.998, P<0.001). The modified Harris score and hip joint range of motion in the mTHA group increased from 47.6±6.6 points and 83° (73°, 88°) before the operation to 83.5±11.2 points and 118° (110°, 122°) at the last follow-up, respectively. The rTHA group increased from 46.5±9.2 points and 79° (71°, 90°) before the operation to 85.0±12.5 points and 124° (116°, 130°) at the last follow-up. The differences in the modified Harris score and hip joint range of motion between the two groups before the operation and at the last follow-up were statistically significant ( P<0.05). However, there was no statistically significant difference between the groups at the last follow-up ( P>0.05). No THA-related complications occurred during follow-up period. Conclusion:For patients with end-stage hip joint diseases with coronal tilt exceeding 3°, robotic-assisted technology significantly improves the accuracy of acetabular component placement during THA and offers better control of postoperative LLD.

Objective:To explore the influence of different scanning positions based on chest phantom of computed tomography(CT)scan on chest on image quality and radiation dose.Methods:A thermoluminescent dosimeter(TLD)was placed at the breast area of simulating anthropoid chest phantom.GE Revolution evo CT was used to conduct scan on the conventional supine position(supine group)and prone position(prone group)for chest phantom.Different noise indexes(NI=10-23)were adjusted to control ration doses,and other parameters were fixed,and each group collected 12 sequence images.The average value(AV),standard deviation(SD)of the CT scan at region of interest(ROI)under different scanning positions were recorded to calculate the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the image.The radiation dose at the breast area was measured by TLD,and the volume CT dose index(CTDIvol)and dose-length product(DLP)were recorded.Results:Under different scanning positions,the radiation dose of breast organs in the prone group was lower than that in the supine group,there was a statistically significant difference between the two groups(t=6.57,P<0.05),while there were not statistically significant differences in CTDIvol and DLP between the two groups(P>0.05).There were not statistically significant differences in the CT values,SD,SNR,CNR of lung tissue,and the CT values of breast tissue between the two groups of images(P>0.05).The SD,SNR and CNR of breast tissue in the prone group were lower than those in the supine group,and the differences were statistically significant(t=-13.33,-10.59,6.70,P<0.05).There were no statistically significant differences in the subjective scores of the clarity of the edge of the tissue within lung,the layers of soft tissue of the breast,noise,and artifacts in the bone tissue between the two groups of images(P>0.05).Conclusion:When low-dose CT physical examination on chest is conducted in clinical practice,the scanning of prone position during undergoing CT scan on chest can obtain image quality that can meet the requirements in diagnosing lung,and reduce the radiation dose on the breast,and conform to the technical principle of optimal radiation protection.