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.

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.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

ObjectiveTo assess the level of internal exposure to PCP in a community population in Shanghai， to investigate the factors affecting the level of PCP， and to analyze the correlation between the exposure and thyroid hormone levels. MethodsA total of 464 residents of a community in Shanghai were selected as the study subjects. A questionnaire survey was conducted to obtain the demographic information， dietary situation， lifestyle and behavioral habits， and disease history of the individuals， and blood samples were collected. Gas chromatography-electron trap was applied to determine the PCP levels in serum. Multicategorical logistic regression analysis was used to analyze the possible influencing factors of PCP exposure in humans. Thyroid hormone levels were used as the dependent variable and serum PCP as the independent variable. Multiple linear regression analysis was used to assess the association between PCP and thyroid hormones in the community population after controlling the confounding factors such as age， gender， literacy， annual personal income， and chronic diseases. ResultsThe detection rate of serum PCP in 464 subjects was 90.3%， and the median serum PCP level was 0.43 μg·L^-1. The differences in PCP levels among different age groups were statistically significant. There were no significant differences in PCP levels among different gender and BMI groups. The study of PCP exposure factors showed that age， frequency of using plastic products， consumption of freshwater fish， type of occupation， annual income， and consumption of tea or coffee were the potential influencing factors for PCP exposure. Among them， age， frequency of using plastic products， consumption of tea or coffee， and consumption of freshwater fish were positively associated with PCP levels， and annual personal income was negatively associated with it. The results of multiple linear regression analysis showed that among men， PCP levels were positively correlated with TSH （b=0.105， 95%CI：0.017‒0.313） and negatively correlated with FT4 （b=-0.026， 95%CI：-0.057‒0.004）， and among women， PCP levels were positively correlated with TSH （b=0.092， 95%CI：-0.211‒0.904） and FT3 （b=0.017， 95%CI：-0.058‒0.230） and negatively correlated with FT4 （b=-0.013， 95%CI：-0.011‒0.037）. ConclusionSerum PCP detection is common among community residents in Shanghai. Different demographic characteristics or behavioral habits may increase or decrease PCP exposure. PCP exposure then affects human thyroid hormone levels.

Objective:To explore the strategies and technical points for breast reconstruction using free lower abdominal skin flap transplantation through lateral chest incision.Methods:The data of patients who underwent unilateral breast reconstruction with free lower abdominal flap transplantation using lateral thoracic incision in Hunan Cancer Hospital from October 2022 to March 2023 were retrospectively analyzed. Lateral thoracic incision was used in the recipient area. Firstly suitable radical mastectomy was performed for patients with early onset of breast cancer or recurrence after breast-conserving surgery, and prosthetic dilator removal or breast capsule release was performed for patients with dilator removed or capsular contracture after breast cancer prosthesis reconstruction. After that, the free lower abdominal skin flap breast reconstruction was completed under the same incision. During the operation, blood vessel preparation in the recipient area, skin flap preparation in the donor area, blood vessel anastomosis and breast shaping were completed successively according to the actual situation of the patient. Postoperative observation of complications, follow-up evaluation of reconstructed breast appearance and donor site healing were carred out.Results:A total of 15 female patients were included, aged range from 24 to 57 years old, with an average of 42.3 years old. There were 9 cases of early breast cancer, 2 cases of breast cancer recurrence after breast conserving surgery, 2 cases of breast cancer with dilator removed after breast reconstruction, and 2 cases of capsule contracture after breast cancer prosthesis reconstruction. The length of the lateral chest incision was 7.5-11.2 cm, with an average of 8.7 cm. Six cases were performed with 3/4 of the lower abdominal skin flaps, using a unilateral inferior abdominal vascular pedicle. The volume of the flaps ranged from 19.0 cm × 10.0 cm × 4.5 cm to 23.0 cm × 13.0 cm × 6.0 cm. The weight ranged from 280 to 510 g, with an average of 370 g. Nine cases were performed by cutting the entire lower abdominal skin flap and using bilateral inferior abdominal vascular pedicle. The volume of the skin flaps ranged from 27.0 cm × 11.0 cm × 5.0 cm to 30.0 cm × 14.0 cm × 6.5 cm. The weight ranged from 420 to 730 g, with an average of 530 g. Nine cases were selected as the main trunk of the thoracic and dorsal blood vessels, 4 cases were selected as the anterior serratus branch of the thoracic and dorsal blood vessels, and 2 cases were selected as the main trunk of the thoracic and dorsal blood vessels combined with the anterior serratus branch. One flap experienced venous crisis and the surgery failed, while the remaining 14 flaps survived smoothly. Follow-up period was 6-17 months, with an average of 10.4 months. The reconstructed breast had a satisfactory appearance and texture, without skin flap contraction or deformation. The skin flap donor area and breast recipient area only had linear scars, and there was no significant impact on abdominal wall and shoulder joint function. There was no tumor recurrence or metastasis during follow-up.Conclusion:When the side chest incision is used to perform the related operations of breast cancer radical resection, the free lower abdominal skin flap can be transplanted into the same incision for breast reconstruction. The effect is satisfactory, and the damage of the affected area is further reduced.

Objective:To explore the clinical value and therapeutic effects of endoscopic nipple-sparing mastectomy combined with immediate breast reconstruction using an oblique pedicled rectus abdominis myocutaneous flap(ORAMF).Methods:The data of patients admitted to Hunan Cancer Hospital from May to September 2023 who underwent breast cancer resection followed by immediate breast reconstruction with ORAMF were analyzed retrospectively. Surgical methods: firstly, axillary anterior sentinel lymph node biopsy and subcutaneous glandular excision for breast cancer were performed through a lateral chest incision using an endoscopic technique. Subsequently, a unilateral ORAMF was prepared by removing the epidermis and creating subcutaneous tunnels on the surface of the rectus abdominis myocutaneous flap under direct visualization. The subcutaneous tunnel of the flap was then extended to the deep surface of the breast with the assistance of an endoscope, allowing for the transfer of the ORAMF to reconstruct the breast. Post surgery, the flap survival was monitored, and after discharge, patients received enhanced anti-scar treatment and functional rehabilitation exercises. Follow-up assessments included the evaluation of the reconstructed breast shape, incision scarring in both the donor and recipient areas, abdominal wall function, tumor recurrence and metastasis.Results:A total of 8 female patients with unilateral breast cancer were included in this study, aged between 27 and 52 years, with a mean age of 41.7 years old. The body mass index of the patients ranged from 19.1 to 22.5 kg/m 2. All patients had early-stage breast cancer. During the operation the average mass of the resected breast was 245 g(ranging from 220 to 285 g). The length of the lateral thoracotomy incision varied from 6.9 to 9.5 cm, with a mean length of 7.7 cm. In 3 cases, the ipsilateral ORAMF was used for breast reconstruction, while in 5 cases, the contralateral ORAMF was utilized. The dimensions of the flap were as follows: length (20.4±0.7) cm, width (10.8±1.5) cm, thickness (5.4±0.9) cm, with the volume of the flap cutting ranging from 19.7 cm×9.2 cm×4.4 cm to 21.2 cm×11.8 cm×5.9 cm. All of the flaps exhibited good blood supply and survived successfully without the need for additional anastomotic vessels. The patients were followed up for a period of 8 to 10 months post-operation, with an average follow-up of 8.7 months. The reconstructed breasts maintained a good shape and texture, showing no contracture or deformation of the flap, and were generally symmetrical with the healthy breast. The incisions in both the flap donor area and the recipient area had healed well, leaving only linear scars, and the function of the abdominal wall was not significantly compromised. No recurrence or metastasis was observed during the follow-up period. Conclusion:The endoscopic technique helps to preserve the integrity of the breast skin tissue to the greatest extent possible, reducing scarring and assisting in the creation of subcutaneous tunnels to facilitate the transposition of the ORAMF for breast reconstruction. For carefully selected patients with moderately small breasts and ample subcutaneous tissue in the lower abdomen, the preparation of a unilateral ORAMF for breast reconstruction can yield superior results. This approach minimizes additional damage to the donor area, enhancing the safety of the surgery while significantly reducing the complexity of the operation.