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.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Cervical chylous leakage is rare after central lymph node dissection for thyroid cancer, and the coexistence of chylothorax is even more uncommon. This article reports a case of a 39-year-old female patient who underwent total thyroidectomy and left central lymph node dissection for papillary thyroid carcinoma complicated by follicular adenoma. On the second postoperative day, the patient developed white, milky drainage from the neck, suggesting chylous leakage, and experienced mild chest tightness, cough, and low-grade fever. Chest CT revealed bilateral pleural effusion, with the left side being more severe. On the third day, ultrasound-guided left-sided pleural puncture and drainage were performed and hydrothorax triglycerides and total cholesterol levels were measured, chylothorax were diagnosed as a result.After conservative treatment including a low-fat diet, fasting, nutritional support, neck pressure dressing and negative pressure suctionand closed chest drainage, the patient's condition improved rapidly. The patient was discharged on the 8th postoperative day with full recovery. No recurrence has been observed during follow-up to date.

Objective:To explore the clinical characteristics and genetic etiology of a patient with De-differentiated liposarcoma (DDLPS).Methods:A 38-year-old female patient with DDLPS who had visited Hunan Provincial People′s Hospital in January 2025 was selected as the study subject. A retrospective study method was adopted to collect the patient′s clinical data, including current and past medical history, auxiliary examinations, pathological diagnosis, and results of genetic testing. This study was approved by the Ethics Committee of Hunan Provincial People′s Hospital (Ethics No.: KY2025-150).Results:The patient had presented with abdominal pain and abdominal mass. Imaging studies revealed ascites and space-occupying abdominal lesions. Postoperative pathological examination showed that the tumor was composed of spindle cells, and its morphology and immunohistochemistry had made it difficult to distinguish between DDLPS and leiomyosarcoma. High-throughput sequencing revealed characteristic molecular alterations of DDLPS, and fluorescence in situ hybridization confirmed MDM2 gene amplification, leading to a diagnosis of DDLPS. Conclusion:The patient was diagnosed with DDLPS. Her clinical manifestations and pathological features were consistent with the characteristics of DDLPS. Molecular pathological testing played a crucial role in the diagnosis and provided a crucial reference for subsequent treatment.

Objective:To investigate the association between serum klotho level and risk of all-cause mortality in the population with diabetic kidney disease (DKD).Methods:It was a retrospective cohort study. DKD patients from the National Health and Nutrition Examination Survey (NHANES) database in the United States, which covered five survey cycles from 2007 to 2016 were selected. Relevant demographic and laboratory examination data were collected, and all-cause mortality was regarded as the endpoint event. Patients were divided into high serum klotho group and low serum klotho group according to the optimal klotho threshold of predicting survival outcomes, and the differences of baseline characteristics between the two groups were compared. The weighted Kaplan-Meier method was used to draw the survival curves of the high and low serum klotho groups during the follow-up period. Log-rank test was used to compare the survival rates between the two groups. Weighted Cox proportional hazards regression analysis and further stratified analysis were used to estimate the correlation between serum klotho level and the risk of all-cause mortality.Results:A total of 633 DKD patients were included in this study, with age of 65 (56, 72) years, and 323 (51.03%) males. Among them, there were 510 patients in the high klotho level (>556.6 ng/L) group, and 123 patients in the low klotho level (≤556.6 ng/L) group. The serum creatinine level in the high klotho level group was significantly lower than that in the low klotho level group ( Z=-2.650, P=0.010), while the estimated glomerular filtration rate (eGFR, Z=2.489, P=0.015) and fasting blood glucose ( Z=2.275, P=0.026) were significantly higher than those in the low klotho level group. There was no statistically significant difference between the two groups in terms of age, gender distribution, racial distribution, proportion of smoking, body mass index, proportion of hypertension, total cholesterol, triglyceride, and urine albumin/creatinine ratio (all P>0.05). The follow-up time was 81 (49, 116) months, and a total of 204 (32.23%) all-cause death events occurred. Kaplan-Meier survival analysis showed that the survival rate of the high klotho level group was significantly higher than that of the low klotho level group (Log-rank test, χ2=4.21, P=0.040). Cox proportional hazards regression analysis showed that, after adjusting for gender, age, race, smoking, body mass index, hypertension, blood glucose, triglyceride, total cholesterol and eGFR, the risk of all-cause death in the low klotho level group was 1.63 times than that in the high klotho level group ( HR=1.63, 95% CI 1.03-2.63). Further stratified analysis showed that there was no interaction effect of age, gender, race and eGFR on the impact between low serum klotho level and the risk of all-cause death (all P>0.05), indicating that the correlation between low serum klotho level and the risk of all-cause death was consistent when DKD individuals were divided into different subgroups. Conclusions:Low serum klotho level are significantly associated with increased risk of all-cause mortality in the DKD population. Maintaining an adequate serum klotho level may reduce the risk of death in DKD patients.

Chronic obstructive pulmonary disease(COPD)is a common disease with a high global incidence and mortality rate.It is charac-terized by chronic inflammation and structural airway obstruction that is not fully reversible,leading to shortness of breath caused by air trapping and increased physical exertion.Over the past few decades,the incidence of COPD has continued to rise.Although commonly used therapeutic agents,such as glucocorticoids and bronchodilators,have demonstrated significant symptomatic relief,they primarily target symptoms rather than halting disease progression.Therefore,further research is needed to better understand the underlying mechanisms of COPD and to develop novel therapeutic strategies for its prevention and management.Early studies on the pathogenesis of COPD primarily focused on airway epithelial cell injury,while relatively less attention was given to pulmonary vascular endothelial cells(PVECs).However,recent evidence indicates that COPD is not only an airway and systemic inflammatory disorder but also a vascular disease,with PVECs playing a critical role in its pathogenesis.PVECs are among the main cellular targets damaged in COPD and are involved in mediating its initiation and progression.In this review,we summarize emerging evidence that highlights the close association between PVEC injury and COPD pathogenesis.We also explore the roles and mechanisms of various therapeutic interventions targeting PVECs,including chemical agents and traditional Chinese medicine,in the treatment of COPD.

Objective : To explore the relationship between single nucleotide polymorphisms ( SNPs) in D-loop region of mitochondrial DNA ( mtDNA) and mtDNA copy number and the risk of dermatomyositis ( DM) ，and its in- fluencing factors． Methods : 74 patients with DM and 92 healthy controls were included in the study． Genomic DNA was extracted from peripheral blood and the target fragment of mtDNA D-loop region was amplified by PCR technique，and the products were subsequently sequenced．Serum levels of ROS were assessed using a high-sensi- tivity reactive oxygen species detection kit．The expression levels of cytokines，interleukin ( IL) -5，IL-13，inter- feron-γ ( IFN-γ) ，IL-2，IL-6，IL-10，tumor necrosis factor-α ( TNF-α) and IL-4 were measured using Flow Fluo- rescence Immunmicrobeads Assay．Wilcoxon rank-sum test was used to assess the potential correlation between cy- tokines and SNPs associated with DM risk．The relative copy number of mtDNA was measured using quantitative re- al-time polymerase chain reaction ( qPCR) analysis． Results : Two SNPs ( 16304T / C，16519T / C) were found to be associated with the risk of developing DM，and alleles 16304C ( χ2 = 4. 937，P = 0. 026) and 16519C ( χ2 = 4. 405，P = 0. 036) in the mitochondrial D-loop region were confirmed to be associated with DM development risk． The DM risk-associated allele 16304C was significantly associated with lower IL-4 expression ( P = 0. 016) ．The mtDNA copy number was significantly higher in DM patients than in controls ( P ＜0. 001) ． Conclusion Mitochondrial D-loop SNPs can be potential biomarkers for DM risk，and SNPs may be involved in DM by influencing cytokines．DM shows high expression of mtDNA copy number，and the increase in mtDNA copy number may lead to mitochondrial dysfunction，which triggers the pathogenesis of DM．

Objective:To investigate the clinical characteristics and prognosis of T-lymphoblastic lymphoma (T-LBL).Methods:A retrospective case series study was conducted. Clinical data of patients diagnosed with T-LBL at the Affiliated Hospital of Jining Medical University from January 2013 to March 2023 were retrospectively analyzed, and their clinical characteristics and prognosis were statistically analyzed.Results:A total of 22 T-LBL patients were included. Among them, there were 19 males (86.4%) and 3 females (13.6%), and the median age at onset was 19.5 (15, 28) years old. Based on Ann Arbor staging, 3 cases (13.6%) were classified as stage Ⅰ-Ⅱ, while 19 cases (86.4%) were stage Ⅲ-Ⅳ; 10 cases (45.5%) presented with B symptoms, 12 cases (54.5%) without B symptoms; 16 cases (72.7%) showed elevated lactic dehydrogenase (LDH) level. At onset, 7 patients (31.8%) had mediastinal masses, 3 patients (13.6%) had central nervous system involvement, and 17 patients (77.3%) had bone marrow involvement. The overall response rate (ORR) and complete remission rate among the 22 patients were 81.82% (18/22) and 31.82% (7/22), respectively. The ORR was 84.21% (16/19) in 19 patients treated with ALL-like regimens. Among 3 patients treated with NHL-like regimens, 1 case achieved complete remission and 1 case achieved partial remission. Seven patients received allogeneic hematopoietic stem cell transplantation, with a median overall survival (OS) time of 22 months; the median OS time of patients without allogeneic hematopoietic stem cell transplantation was 14 months. The 3-year OS rates in the allogeneic hematopoietic stem cell transplantation group and group without allogeneic hematopoietic stem cell transplantation were 64.30% and 16.00%, and the difference in OS between the two groups was statistically significant ( P = 0.043). Two patients with disease progression prior to transplantation died of multidrug-resistant bacterial infections after transplantation. Conclusions:T-LBL is rare, and it is a highly aggressive tumor that predominantly occurs in adolescent males. Allogeneic hematopoietic stem cell transplantation can prolong OS, reduce relapse and improve the prognosis of patients.

Objective To investigate the correlation between total oxidation state(TOS),superoxide dis-mutase(SOD),glutathione reductase(GR)and androgen receptor(AR)expression,as well as their predictive value for castration-resistant prostate cancer(CRPC).Methods A retrospective analysis was conducted on the clinical data of 382 patients with prostate cancer who received endocrine therapy in our hospital from Janu-ary 2021 to March 2023.These patients were divided into a CRPC group(91 cases)and a non-CRPC group(291 cases)based on whether they progressed to CRPC within one year.The clinical data of the two groups were compared,and the levels of TOS,SOD,GR,and AR expression before and after treatment were com-pared between the two groups.The correlation between TOS,SOD,GR,and AR expression was analyzed using the Spearman method.The relationship between TOS,SOD,GR,and AR expression in the CRPC group was analyzed using partial correlation analysis.Logistic regression analysis was used to investigate the impact of TOS,SOD,and GR on the occurrence of CRPC after 1 month of treatment,and receiver operating charac-teristic(ROC)curve analysis was used to evaluate the predictive efficacy of TOS,SOD,and GR on CRPC af-ter 1 month of treatment.Results Gleason score ≥8 and T4 in clinical stage in CRPC group were higher than those in non-CRPC group,and the difference was statistically significant(P＜0.05).After 1 month and 1 year of treatment,the positive expression rates of TOS and AR in both groups were higher than before treatment,while the levels of SOD and GR were lower than before treatment,with a statistically significant difference(P＜0.05).After 1 month and 1 year of treatment,the TOS level and AR positive expression rate in the CRPC group were higher than those in the non-CRPC group,while the SOD and GR levels were lower than those in the non-CRPC group,with statistical significance(P＜0.05).Spearman correlation analysis showed that TOS was positively correlated with AR expression in the CRPC group after 1 month and 1 year of treat-ment(P＜0.05),while SOD and GR were negatively correlated with AR expression(P＜0.05).Logistic re-gression analysis showed that,Gleason score ≥8,T4 in clinical stage,and TOS,SOD,and GR after 1 month of treatment were all associated with the occurrence of CRPC(P＜0.05).It was found that after adjusting for Gleason score and clinical stage,TOS,SOD,and GR were still independent factors for CRPC after 1 month of treatment(P＜0.05).The ROC curve analysis results showed that the area under the curve of TOS,SOD,and GR combined to predict CRPC after 1 month of treatment was 0.938(95％CI:0.908-0.960),which was higher than that of each indicator alone.Conclusion The expression of TOS,SOD,GR,and AR is correlated to some extent,and combined detection has certain predictive value for CRPC.It can be used as an auxiliary indicator for clinical prediction of CRPC and has certain guiding value for subsequent clinical decisions for patients.

WD repeat domain 1(WDR1)is a highly conserved cytoskeleton-associated protein that plays a crucial role in physiological processes such as actin cytoskeleton remodeling,dynamic regulation of intercellular junctions,cell division,and migration.WDR1 exhibits abnormal high ex-pression in various malignant tumors,including breast cancer,ovarian cancer,and thyroid cancer,and has been demonstrated to significantly promote the invasive and migratory capabilities of tumor cells,suggesting its important role in the malignant progression of tumors.Moreover,the expression level of WDR1 is closely related to the clinical prognosis of patients with multiple malignant tumors.Especially in patients with esophageal cancer and osteosarcoma,its high expression often indicates a poor overall survival rate.WDR1 can promote tumor initiation and progression by regulating the Wnt/β-Catenin signaling pathway and the Hippo-YAP signaling pathway.Meanwhile,its expression is also subject to multi-level regulation by transcription activation factors and long non-coding RNAs(lncR-NAs),thereby influencing the proliferation,migration,and other biological behaviors of tumor cells.Additionally,WDR1 can further drive the invasive growth and metastatic potential of tumors by regu-lating the epithelial-mesenchymal transition(EMT)process.This article aimed to systematically re-view the research progress in recent years regarding the biological functions and molecular mechanisms of WDR1 in tumor initiation and development,with a view to providing new theoretical foundations and research directions for the early diagnosis,prognosis assessment,and individualized treatment of clinical tumors.