Objective: To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1). Methods: The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential. Results: Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05). Conclusion YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.

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.

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.

Objective:To explore the effect of NOD-like receptor thermal protein 3 ( NLRP3) knockout in γ-aminobutyric acid (GABA)-ergic neurons in the hippocampal CA1 area on improving cognitive dysfunction in mice after traumatic brain injury (TBI). Methods:Forty-eight healthy male NLRP3 flox/flox mice weighing 25-28 g were randomly divided into 4 groups ( n=12): sham-operated+control virus group (SV group), sham-operated+ NLRP3 specific knockout group (SG group), TBI+control virus group (TV group), TBI+ NLRP3 specific knockout group (TG group). TBI in the TV and TG groups was established by free-fall method, while surgical procedures such as scalp incision and cranial window opening without impact were given to the SV and SG groups. Adenovirus was injected into the hippocampal CA1 area of SG and TG groups 21 d before TBI to induce NLRP3 specific knockout in GABA-ergic neurons in the hippocampal CA1 area; empty virus was injected into the CA1 area of SV and TV groups. Cognitive function was evaluated using novel object recognition test 30 and 31 d after TBI, and learning and memory functions were assessed using Morris water maze test 32-36 d after TBI. Field potentials in the hippocampal CA1 area were recorded during novel object recognition 31 d after TBI. After behavioral tests, these mice were sacrificed. Immunofluorescent staining was used to detect the fluorescent intensity of microtubule-associated protein2 (MAP2), glutamic acid decarboxylase 67 (GAD67), and postsynaptic density protein 95 (PSD95) in the hippocampal CA1 area, as well as percentage of pyroptosis-associated inflammatory factor interleukin-18 (IL-18)/GAD67 double-positive neurons in total GAD67 positive neurons. Results:Compared with the SV and SG groups, the TV and TG groups had decreased novel object recognition index, decreased number of platform crossings during the experimental period, increased escape latency on day 3 and day 4 of the training period in Morris water maze test, decreased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, decreased fluorescent intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, increased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Compared with the TV group, the TG group had increased novel object recognition index, increased number of platform crossings in Morris water maze test, decreased escape latency during the training period, increased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, increased fluorescence intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, decreased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Conclusion:Specific inhibition of NLRP3 expression in GABA-ergic neurons in the hippocampal CA1 area can improve cognitive dysfunction in mice after TBI, whose mechanism may be related to inhibited GABA-ergic neuronal pyroptosis in the hippocampal CA1 area.

BackgroundPatients with depressive disorder commonly experience sleep disturbances. Previous studies have indicated that group exercise therapy is beneficial in alleviating depressive symptom among patients with depressive disorder. However， there is a lack of research on the impact of group exercise therapy on improving sleep quality in patients with depressive disorder. ObjectiveTo explore the impact of group exercise therapy on sleep quality in patients with acute mild-to-moderate depression during the acute phase， so as to provide references for clinically improving the sleep quality of patients with mild to moderate depressive disorder during the acute phase. MethodsFrom December 2018 to July 2021， patients with mild-to-moderate depressive disorder during the acute phase （n=40）， who met the diagnostic criteria for depressive disorder according to International Classification of Diseases， tenth edition （ICD-10） ，were recruited from the outpatient clinic of Beijing Anding Hospital， Capital Medical University. All participants underwent an 8-week moderate-intensity group exercise therapy program comprising three sessions per week， each lasting 60 minutes. Assessments were conducted at baseline and after 2， 4， 6 and 8 weeks of intervention using Visual Analogue Scale （VAS）， Hamilton Depression Scale-17 item （HAMD-17） and Pittsburgh Sleep Quality Index （PSQI）. The reduction scores at each time point relative to baseline treated as the dependent variables， time as the independent variable， baseline scores as covariates， with time as a fixed effect and baseline values as random effects. Data were analyzed using a linear mixed-effects model. ResultsThe PSQI scores of patients at baseline， 2， 4 ， 6 and 8 weeks after the intervention were （10.62±5.12）， （9.07±3.58）， （7.39±3.66）， （6.54±3.84） and （5.50±3.41）， respectively. The results of linear mixed effect model analysis showed that after 2， 4， 6 and 8 weeks of intervention， patients scored lower than baseline， with statistically significant differences observed in all cases （P<0.01）. The HAMD-17 sleep fcctor scores at baseline， 2， 4， 6 and 8 weeks were （2.25±1.56）， （2.06±1.49）， （1.36±1.27）， （1.22±1.46） and （0.97±1.34）， respectively. The results of linear mixed effects model analysis showed that the HAMD-17 sleep factor scores of 4， 6 and 8 weeks of intervention were lower than that of baseline， and the difference was statistically significant （P<0.05 or 0.01）. The VAS scores at baseline， 2， 4， 6 and 8 weeks after the intervention were （3.18±2.17）， （4.74±2.22）， （6.01±2.31）， （6.54±2.16） and （7.90±1.64）， respectively. The results of linear mixed effect model analysis showed that VAS scores of 2， 4， 6 and 8 weeks of intervention were higher than baseline，and the difference was statistically significant （P<0.01）. ConclusionGroup exercise therapy may improve sleep quality and alleviate depressive symptoms in patients with mild-to-moderate depressive disorder during the acute phase. ［Funded by National Key Research and Development Plan Project （number， 2016YFC1307200）； Beijing Municipal Hospital Scientific Research and Cultivation Plan Project （number， PX2024070）］

Objective:To construct a rapid admission evaluation model for medical consumables of same category,and to achieve a balance between scientificity,efficiency and practicality in the management of medical consumables.Methods:Based on the mini health technology assessment(Mini-HTA)model,combined with expert heuristics,a rapid qualitative analysis of the intended use and technical characteristics of the same category of medical consumables were conducted.Expert opinions were solicited through the Delphi method,and a rapid admission evaluation model of same category of medical consumables was constructed.A total of 80 high-value medical consumables of 10 categories in clinical use in Sichuan Provincial People's Hospital from June 2023 to March 2024 were selected,and the traditional admission process method and expert heuristics optimization method were used to make admission decisions for medical consumables,with 40 high-value medical consumables for each method.The differences in the decision-making process and approval time between the two different admission methods were compared and analyzed.Results:The admission decision-making system indicators of the rapid admission evaluation model of medical consumables of same category included 6 primary indicators of clinical efficacy,reliability,economics,values and aspirations,hospital management and corporate services,and 25 secondary indicators.The approval process for medical consumables admission decision-making using the rapid admission evaluation model of medical consumables of same category had been reduced from 10 in the traditional admission process to 2,and the approval time had been shortened from an average of 7.03 days to 2.43 days.Conclusion:The rapid admission evaluation model for the approval of medical consumables of same category based on expert heuristics can significantly optimize the admission approval process of medical consumables,improve the comprehensiveness and transparency of medical consumables admission decisions,and improve the management efficiency of medical consumables.