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 establish and validate a whole blood (WB) supply model, thereby providing practical experience for the clinical application of WB in domestic trauma emergency care and informing the development of a wartime blood supply system for the military. Methods: A “10×24” WB supply model was established by formulating blood collection protocols, storage standards, and transfusion criteria. Multiple WB samples were tested under specific storage conditions to assess key indicators at different time points, including red blood cell (RBC), white blood cell (WBC), and platelet counts, hemoglobin concentration, coagulation parameters (PT, APTT, TT, FIB), coagulation factor activity, thromboelastography (TEG) parameters, and electrolyte levels. Additionally, clinical data from hemorrhagic patients who met the criteria for WB transfusion and were admitted between March and July 2024 were analyzed to evaluate WB transfusion volume. Results: RBC counts and hemoglobin levels remained stable in WB stored at 4℃ for up to 10 days. However, platelet counts and coagulation function (PT, APTT) significantly declined with prolonged storage, while potassium levels increased. From March to July 2024, the model was successfully applied to 23 patients with acute hemorrhage, with a median WB transfusion volume of 543 mL. A detailed case study of a severe traumatic hemorrhagic shock patient was reported, who was successfully treated with 5.5 units of refrigerated WB combined with component blood. Conclusion: The “10×24” WB supply model demonstrated acceptable changes in critical quality parameters under strict management and a 10-day rotation cycle. This model effectively supports the treatment of acute hemorrhage and holds promise for integration into the future wartime blood supply system of the military.

OBJECTIVE: To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back. METHODS: Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage. RESULTS: All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site. CONCLUSION The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Plastic Surgery Procedures ; Myocutaneous Flap/surgery* ; Shoulder/surgery* ; Skin Transplantation ; Superficial Back Muscles/transplantation* ; Soft Tissue Injuries/surgery* ; Wound Healing ; Treatment Outcome ; Perforator Flap

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

Objective:To explore the impact of baseline remnant cholesterol levels at a single time point and cumulative remnant cholesterol exposure on the progression trajectories of arterial stiffness.Methods:This prospective cohort study included 2 401 eligible participants from the Beijing Health Management Cohort who consecutively attended health examinations in 2010-2011, 2012-2013, and 2014-2015. The remnant cholesterol value measured in 2014-2015 served as the baseline remnant cholesterol level at a single time point. The cumulative exposure indices were calculated based on remnant cholesterol values from three health examinations from 2010 to 2015, including cumulative exposure, cumulative exposure burden, and duration of high remnant cholesterol exposure. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). The follow-up continued until December 31, 2019, with annual check-ups. During the follow-up period, a group-based trajectory model was employed to construct the progression trajectories of baPWV. The associations between the baseline remnant cholesterol level, cumulative exposure indices of remnant cholesterol and baPWV trajectories were examined using ordinal logistic regression models, adjusting for traditional cardiovascular risk factors and low-density lipoprotein cholesterol (LDL-C) levels.Results:The age of the 2 401 participants was 61 (54, 69) years, with 1 801 (75.01%) being male. The group-based trajectory model indicated that the best-fit model categorized the participants into three subgroups: low-rising group (1 036 individuals, 43.15%), moderate-rising group (1 137 individuals, 47.36%), and high-rising group (228 individuals, 9.50%). After adjusting for traditional cardiovascular risk factors, baseline remnant cholesterol levels at a single point ( OR=1.170, 95% CI: 1.074-1.274), cumulative remnant cholesterol exposure ( OR=1.194, 95% CI: 1.096-1.303), cumulative remnant cholesterol exposure burden ( OR=1.270, 95% CI: 1.071-1.507), and high-remnant cholesterol exposure duration (6 years: OR=1.351, 95% CI: 1.077-1.695) were significantly associated with the risk of developing a poor baPWV progression trajectory. These results remained significant after adjusting for cumulative average LDL-C levels. The association between baseline remnant cholesterol levels and baPWV progression became insignificant after adjusting for cumulative remnant cholesterol levels ( OR=1.053, 95% CI: 0.923-1.197), while the association between cumulative remnant cholesterol exposure and baPWV progression remained significant after adjusting for baseline remnant cholesterol levels ( OR=1.145, 95% CI: 1.008-1.305). Conclusions:Higher levels of baseline remnant cholesterol and cumulative remnant cholesterol are independent risk factors for the progression of arterial stiffness. These associations remain significant even after adjusting for traditional cardiovascular risk factors and LDL-C levels. Furthermore, the effect of cumulative remnant cholesterol levels on the progression of arterial stiffness was stronger than the effect of baseline remnant cholesterol levels.

Although a great deal of research has been done on sepsis in children，its pathogenesis remains controversial and unresolved，one of which is immune dysfunction.Immunosuppression is the core part of immune dysfunction，and it is related to the disease progression，treatment options，and prognosis changes in patients with sepsis.Since T lymphocytes play a crucial role in immune function，they have been regarded as an important indicator for judging changes in immune function in clinical practice.This review explained the mechanism of immunosuppression caused by some T lymphocyte subsets and its clinical application value in the evaluation，prognosis and immune intervention of sepsis.

Objective To investigate the frequency of therapy-oriented oral radiation in Nanping, China and its distribution, and to provide a basis for the rational application of therapy-oriented oral radiation and the effective allocation of resources in Nanping. Methods A questionnaire was designed to investigate the frequency of therapy-oriented oral radiation in all oral radiation diagnosis and treatment institutions in Nanping. Results In 2021, there were 54 oral radiation diagnosis and treatment institutions and 79 oral radiation machines in Nanping. The total frequency of therapy-oriented oral radiation was 61593 visits and the radiation frequency was 19.54 visits per thousand patients. The average annual frequency of medical institutions at all levels was 721.87 to 3713.25 visits per institution; the male-to-female composition ratio of frequency of therapy-oriented oral radiation in December 2021 was 50.5%:49.5%. The proportion of radiation frequency of different devices was as follows: 38.7% (intraoral dental film), 46.5% (oral panorama), 10.3% (oral computed tomography [CT]), and 4.5% (cranial photography). The proportion of radiation frequency in patients of different ages was as follows: 17.1% (0−15 years), 48.2% (15−40 years), and 34.7% (over 40 years). The frequency of therapy-oriented oral radiation grew by 77.43%, 35.18%, and 8.16% every two years from 2015 to 2021, respectively. Conclusion The frequency level of therapy-oriented oral radiation in Nanping is at the level of Class II health care. The distribution of therapy-oriented oral radiation is highly unbalanced and is related to the level of economic development. Private healthcare institutions are growing rapidly, and public healthcare institutions of grade two and above occupy the main healthcare resources. The oral panorama accounts for the most, cranial photography accounts for the least, and oral CT is the fastest-growing portion. Therapy-oriented oral radiation is predominantly performed in the young and middle-aged populations, regardless of sex. Except for intraoral dental films, the general trend is upward.