OBJECTIVES: Pyroptosis plays a critical role in tubulointerstitial lesions of diabetic kidney disease (DKD). Annexin A2 (ANXA2) is involved in cell proliferation, apoptosis, and adhesion and may be closely related to DKD, but its specific mechanism remains unclear. This study aims to investigate the role and molecular mechanism of ANXA2 in high glucose-induced pyroptosis of renal tubular epithelial cells, providing new targets for DKD prevention and treatment. METHODS: Human renal tubular epithelial HK-2 cells were divided into a normal glucose group (5.5 mmol/L), a high glucose group (30.0 mmol/L), and a osmotic control group (24.5 mmol/L mannitol+5.5 mmol/L glucose). ANXA2 expression was modulated by overexpression of plasmids and small interfering RNA (siRNA). Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) assay, apoptosis by flow cytometry, and ANXA2, p50, and p65 subcellular localization by immunofluorescence. Western blotting was employed to detect α-smooth muscle actin (α-SMA), fibronectin (FN), and collagen type IV (Col-IV). Real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting were used to analyze nuclear factor-κB (NF-κB) subunits p50/p65 and the pyroptosis pathway factors NLR family Pyrin domain containing 3 (NLRP3), caspase-1, inferleukin (IL)-1β, and IL-18. Protein interactions between ANXA2 and p50/p65 were examined by co-immunoprecipitation, while chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to examine NF-κB binding to the ANXA2 promoter. RESULTS: High glucose upregulated ANXA2 expression and promoted its nuclear translocation (P<0.01). High glucose reduced cell proliferation, increased apoptosis, and elevated α-SMA, FN, and Col-IV expression (all P<0.05); ANXA2 overexpression aggravated these effects (all P<0.05), while ANXA2 knockdown reversed them (all P<0.05). High glucose activated NF-κB and increased NLRP3, caspase-1, L-1β, and IL-18 mRNA and protein expression (all P<0.05); ANXA2 overexpression further enhanced this, whereas knockdown suppressed NF-κB activation and downstream factors (all P<0.05). Co-immunoprecipitation confirmed ANXA2 directly binds the NF-κB subunit p65. ChIP assays revealed p65 binds specifically to ANXA2 promoter regions (ChIP-2, ChIP-4, and ChIP-6), and luciferase activity in corresponding mutant constructs (M2, M4, and M6) was significantly increased versus controls (all P<0.05), confirming positive transcriptional regulation of ANXA2 by p65. CONCLUSIONS ANXA2 and NF-κB form a positive feedback loop that sustains NLRP3 inflammasome activation, promotes pyroptosis pathway activation, and aggravates high glucose-induced renal tubular epithelial cell injury. Targeting ANXA2 or blocking its interaction with p65 may be a novel strategy to slow DKD progression.
Humans ; Pyroptosis/drug effects* ; Annexin A2/physiology* ; Epithelial Cells/cytology* ; Kidney Tubules/cytology* ; Glucose/pharmacology* ; Diabetic Nephropathies/metabolism* ; NF-kappa B/metabolism* ; Cell Line ; Cell Proliferation ; Transcription Factor RelA/metabolism* ; Feedback, Physiological

The unique characteristics of the deep space environment, microgravity, cosmic radiation, and extreme temperature fluctuations, are emerging as major driving forces for pharmaceutical innovation. These factors provide new avenues for optimizing drug formulations, improving crystal structure quality, and accelerating the discovery of therapeutic targets. Advances in deep space research not only help overcome critical bottlenecks in terrestrial drug development but also promote progress in structure-based drug design and deepen understanding of cellular stress-response mechanisms. Current progress in space-based pharmaceutical research primarily includes the study of disease mechanisms under microgravity, protein crystallization in microgravity, and drug development utilizing deep space radiation and resources. However, the operational complexity, high costs, and limited data reproducibility of space experiments remain key challenges hindering widespread application. Looking ahead, with the integration of automation, artificial intelligence analysis, and on-orbit manufacturing, deep space drug development is expected to achieve greater scalability and precision, opening a new frontier in biopharmaceutical science.
Drug Design ; Drug Development/methods* ; Humans ; Weightlessness ; Space Flight ; Artificial Intelligence ; Extraterrestrial Environment

Objective:To analyze the efficacy of unilateral arytenoid chondroplasty combined with minimally invasive mucosal flap plasty in the management bilateral vocal cord paralysis.Methods:A total of 66 patients with bilateral vocal cord paralysis hospitalized in the First Hospital of Sun Yat-sen University from January 2018 to December 2023 were retrospectively analyzed, among whom there were 8 males and 58 females, with ages ranging from 35 to 86 years old(mean age (57.8±11.6) years). All patients underwent suspension laryngoscopic CO 2 laser unilateral arytenoid chondroplasty and mucosal flap under general anesthesia. Postoperative follow-up period extended from 6 months to 6 years, with a median duration of 28 months. The study compared the degree of dyspnea and voice quality (subjective and objective evaluation) of the patients pre- and post-operatively, and analyzed the clinical differences between patients with and without preoperative or intraoperative tracheotomy, the extubation rate of tracheotomized patients, the recurrence rate, and the complication rate. Continuous variables conforming to normal distribution were tested by t-test and categorical variables by χ2 test,the Wilcoxon rank-sum test was used to analyze the improvement in dyspnea before and after surgery. Results:Compared with the preoperative period, 59 patients showed improvement in postoperative dyspnea ( U=161.5, P<0.01); there was no significant difference in voice disorder index 10, subjective auditory-perceptual assessment, and maximal vocalization time ( P>0.05), all of which remained within the relative normal range. Tracheotomy was performed in 32 out of 66 patients, with predominantly degree Ⅲ- dyspnea (46.9%, 15/32), including 26 patients with preoperative tracheotomy and 6 patients with intraoperative tracheotomy. Among the 34 patients who did not undergo tracheotomy, the majority presented with degree Ⅱ-dyspnea (82.4%, 28/34). All patients achieved successful extubation following surgery, with a mean median time to extubation of 1 month. Conclusions:The combination of unilateral arytenoid chondroplasty and minimally invasive mucosal flap plasty represents a refined and effective therapeutic approach for bilateral vocal cord paralysis. This minimally invasive technique has the potential to reduce the rate of tracheotomy.

Objective To investigate the value of combining preoperative magnetic resonance imaging(MRI)and postoperative pathological assessment of lymph node metastasis in predicting overall survival in rectal cancer patients.Methods This retrospective study collected clinical,pathological and image information of 2610 patients histopathologically confirmed with rectal adenocarcinoma at the Sixth Affiliated Hospital of Sun Yat-sen University between January 2016 and December 2021.All patients underwent MRI scans and were divided into three groups according to lymph node status assessed by preoperative MRI(MRIN)and postoperative pathology(PN):MRIN+but PN-(MRIN+group),PN+but MRIN-(PN+group),MRIN+and PN+(MRI-PN+group).Inverse probability weighting(IPW)was used to adjust for confounding factors.Kaplan-Meier curves were used to estimate overall survival and log-rank tests were used to compare the difference.Univariate Cox regression models were used to analyze the correlation between tumor characteristics and overall survival,and bidirectional stepwise Cox regression models were used to identify independent risk factors for overall survival.Results The MRI-PN+group showed higher tumor staging,more frequent perineural invasion,more distant metastases,and a higher risk of death compared to the P N+group and MRIN+group(all P＜0.05).Kaplan-Meier curves showed that the 3-year survival rates for the MRIN+group,PN+group,and MRI-PN+group were 90.5%,79.1%,and 76.4%,respectively;the 5-year survival rates were 85.7%,71.5%,and 59.2%,respectively.Stepwise Cox regression showed that age,tumor location,carcino-embryonic antigen,carbohydrate antigen 19-9,lymph nodes number,pathological tumor stage,lymphovascular invasion,perineural invasion,distant metastasis,neoadjuvant therapy and adjuvant therapy,and MRI-pathology lymph node status were independent risk factors for overall survival in rectal cancer(all P＜0.05).Conclusion Evaluating the lymph node status by combining preoperative MRI and postoperative pathology helps predict overall survival in rectal cancer patients more accurately.

We report the first in man experience of robotic assisted transcatheter edge-to-edge repair(TEER)with pure Trans-esophageal echocardiography-guidance.A 55y female was diagnosed with heart failure with 4+functional MR despite optimal medical treatment.TEER procedure was planned with robotic assistance.After guiding catheter,the robotic system was incorporated into the TEER device to replace manual operation.Under pure echo-guidance one clip was successfully placed in A2/P2 region with marked reduction of MR to 1+.Patient was discharged without complication.

We report the successful treatment of mitral regurgitation by remote robotic transcatheter edge-to-edge repair(TEER)under pure transesophageal echocardiographic guidance in a 70-year-old male patient with severe mitral regurgitation due to ischemic cardiomyopathy.The patient showed no significant improvement after coronary interventional treatment and guideline-directed medical therapy before TEER.Following a multidisciplinary discussion,a TEER procedure was indicated and performed.The procedure utilized robotic assistance guided by echocardiography,combined with 5G communication technology,to remotely operate the surgical robot in Shenzhen from Beijing.Postoperatively,the patient's mitral regurgitation was reduced to trace,symptoms were markedly improved,there were no severe complications,and the patient was discharged five days after the operation.The integration of pure echo-guided interventional technology with remote robotic operation holds significant importance for enhancing the capabilities in treating cardiovascular diseases at the primary hospitals.

Objective:To use pan-genomics and subtractive proteomics techniques to screen the new antibacterial targets from the Staphylococcus aureus genome,and to lay the foundation for the development of anti-Staphylococcus aureus drugs.Methods:The genome sequencing data of 50 strains with sequencing level Complete were collected by searching the whole genome sequencing data in the National Center for Biotechnology Information(NCBI)Database with Staphylococcus aureus as the keyword;BPGA tool was used to conduct the pan-genomics analysis on the genomic data to obtain the core genes of Staphylococcus aureus;subtractive proteomics technique was used to screen the potential antibacterial targets from the core genes.These potential antibacterial targets were used as the receptors;LibDock software was used to screen the potential anti-Staphylococcus aureus drugs from the US Food and Drug Administration(FDA)-approved drug library;molecular docking technology was used to analyze the binding abilities of the drugs and targets.Results:There were 14 379 gene families in the 50 Staphylococcus aureus genomes,of which 1 620 were the core genes.The subtractive proteomics analysis results showed that tyrosine autokinase 1335 was the potential anti-Staphylococcus aureus target.LibDock software screened out nine compounds,including balofloxacin,tenofovir disoproxil fumarate,and adefovir,that may exert anti-Staphylococcus aureus effects on this target protein.The molecular docking results showed there was good binding abilities between the targets and the compounds.Conclusion:Tyrosine autokinase may be the potential target for antii-Staphylococcus aureus.

Objective:To conduct a systematic evaluation of prognostic factors for retreatment of esophageal cancer patients with locoregional recurrence after radical chemoradiotherapy, and provide a clinical reference for selecting individualized retreatment schemes and improving their survival.Methods:A retrospective analysis was performed on the clinical data of 85 patients with esophageal cancer who experienced locoregional recurrence at least 1 year after radical radiotherapy or chemotherapy at the Department of Radiation Oncology in the Fourth Hospital of Hebei Medical University from January 2008 to December 2017. The effects of different nutritional and immune status and retreatment schemes on survival were compared, and the prognostic factors for retreatment were subjected to comprehensive subgroup analysis.Results:As of December 2021, the follow-up rate for all patients was 93%. The 1-, 2-, 3-, and 5-year overall survival rates of all patients after retreatment were 31.5%, 18.6%, 10.6%, and 6.6%, respectively. For patients who received radiotherapy or chemoradiotherapy, the 1-, 2-, 3-, and 5-year overall survival rates were 36.8%, 22.3%, 13.0% and 9.3%, respectively. Multivariable analysis showed that the time interval between the first treatment and recurrence, the retreatment schemes after recurrence, the level of serum albumin before retreatment, and the prognostic nutritional index before retreatment were independent prognostic factors for survival after retreatment ( P<0.05). Subgroup analysis was performed on the combinations of peripheral blood hemoglobin level, albumin level, and prognostic nutritional index before retreatment, as well as systemic immune inflammation index and short-term curative effect after retreatment. The results showed that the comprehensive analysis of blood routine and serum albumin indicators could accurately predict the survival after retreatment. Conclusions:The nutritional and immune status of patients with locoregional recurrence of esophageal cancer after chemoradiotherapy can be used to predict the prognosis of retreatment. The time interval between the first treatment and recurrence and the retreatment scheme significantly affect the survival after retreatment. The retreatment scheme should be rigorously evaluated and appropriately selected to improve the benefit-risk ratio.

Immunotherapy has made breakthrough in the field of tumor treatment. How to accurately predict the response of tumor patients to immunotherapy in the early stage is currently a clinical challenge. Nuclear medicine molecular imaging provides a new technological means for early accurate diagnosis, treatment monitoring, early warning of recurrence and metastasis, and guidance for personalized treatment of diseases. Therefore, it plays an irreplaceable role in precise diagnosis and treatment of tumors and patient stratification. This article reviews the progress of molecular imaging research on immune cells and related targets within the tumor microenvironment.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.