AIM:To investigate the biological functions and molecular mechanisms of long noncoding RNA LINC01615 in head and neck squamous cell carcinoma(HNSCC)cells.METHODS:Transcriptome sequencing data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to analyze the expres-sion level of LINC01615 in HNSCC cells and its correlation with patient survival.RT-qPCR was used to detect the expres-sion levels of LINC01615 in HNSCC and normal control cells.An siRNA-mediated LINC01615 knockdown HNSCC cell model was established,and high-content screening cell counting,ATP and CCK8 assays were performed to analyze cell proliferation.Transwell assays were conducted to assess cell migration and invasion.Bioinformatics analysis was em-ployed to predict potential target genes of LINC01615 and the biological processes and signaling pathways involved.RT-qPCR and Western blot were used to validate the regulatory effect of LINC01615 on the candidate target gene TEAD2.Transcriptome data from TCGA and GEO databases were analyzed to determine the expression pattern of TEAD2 in HN-SCC.Functional cell experiments were performed to investigate the impact of TEAD2 knockdown on HNSCC proliferation,migration,and invasion.Rescue experiments were conducted to examine whether LINC01615 influenced the malignant phenotypes(proliferation,migration,and invasion)of HNSCC cells by regulating TEAD2 expression.RESULTS:The expression levels of LINC01615 were significantly higher in HNSCC tissues and cells than those in normal control tissues and cells,respectively(P<0.01).Knockdown of LINC01615 significantly inhibited HNSCC proliferation,migration,and invasion(P<0.01).Bioinformatics analysis identified 134 candidate target genes of LINC01615,which were primarily en-riched in tumor-related biological processes and signaling pathways,including angiogenesis,regulation of endothelial cell proliferation,regulation of cell migration,HPV infection,Hippo signaling pathway,and PI3K-Akt signaling pathway.Knockdown of LINC01615 led to a significant decrease in TEAD2 expression in HNSCC cells(P<0.01).Functional cell studies demonstrated that TEAD2 knockdown suppressed HNSCC proliferation,migration,and invasion,whereas TEAD2 overexpression reversed the inhibitory effects of LINC01615 knockdown on these malignant phenotypes.CONCLUSION:LINC01615 is upregulated in HNSCC tissues and cells,functioning as an oncogene.Mechanistic studies reveal that LINC01615 promotes HNSCC proliferation,migration,and invasion by upregulating TEAD2,a key transcription factor in the Hippo signaling pathway.These findings may provide a novel potential biomarker for the clinical diagnosis and treat-ment of HNSCC.

AIM:To investigate the biological functions and molecular mechanisms of long noncoding RNA LINC01615 in head and neck squamous cell carcinoma(HNSCC)cells.METHODS:Transcriptome sequencing data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to analyze the expres-sion level of LINC01615 in HNSCC cells and its correlation with patient survival.RT-qPCR was used to detect the expres-sion levels of LINC01615 in HNSCC and normal control cells.An siRNA-mediated LINC01615 knockdown HNSCC cell model was established,and high-content screening cell counting,ATP and CCK8 assays were performed to analyze cell proliferation.Transwell assays were conducted to assess cell migration and invasion.Bioinformatics analysis was em-ployed to predict potential target genes of LINC01615 and the biological processes and signaling pathways involved.RT-qPCR and Western blot were used to validate the regulatory effect of LINC01615 on the candidate target gene TEAD2.Transcriptome data from TCGA and GEO databases were analyzed to determine the expression pattern of TEAD2 in HN-SCC.Functional cell experiments were performed to investigate the impact of TEAD2 knockdown on HNSCC proliferation,migration,and invasion.Rescue experiments were conducted to examine whether LINC01615 influenced the malignant phenotypes(proliferation,migration,and invasion)of HNSCC cells by regulating TEAD2 expression.RESULTS:The expression levels of LINC01615 were significantly higher in HNSCC tissues and cells than those in normal control tissues and cells,respectively(P<0.01).Knockdown of LINC01615 significantly inhibited HNSCC proliferation,migration,and invasion(P<0.01).Bioinformatics analysis identified 134 candidate target genes of LINC01615,which were primarily en-riched in tumor-related biological processes and signaling pathways,including angiogenesis,regulation of endothelial cell proliferation,regulation of cell migration,HPV infection,Hippo signaling pathway,and PI3K-Akt signaling pathway.Knockdown of LINC01615 led to a significant decrease in TEAD2 expression in HNSCC cells(P<0.01).Functional cell studies demonstrated that TEAD2 knockdown suppressed HNSCC proliferation,migration,and invasion,whereas TEAD2 overexpression reversed the inhibitory effects of LINC01615 knockdown on these malignant phenotypes.CONCLUSION:LINC01615 is upregulated in HNSCC tissues and cells,functioning as an oncogene.Mechanistic studies reveal that LINC01615 promotes HNSCC proliferation,migration,and invasion by upregulating TEAD2,a key transcription factor in the Hippo signaling pathway.These findings may provide a novel potential biomarker for the clinical diagnosis and treat-ment of HNSCC.

Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Objective:To explore the assessment value of liver enzyme changes before and after hepatectomy on the prognosis of patients with primary hepatocellular carcinoma(HCC). Methods:A retrospective analysis was conducted on the clinical data of 421 patients with primary HCC who received at the First and Second Affiliated Hospitals of Xi'an Jiaotong University from January 2016 to December 2020.The univariate and multivariate COX regression analyses were used to screen the risk factors affecting the prognosis of patients with primary HCC,and the optimal cut-off value was selected to group the most valuable indicators among them,further analyzing the different factors among subgroups.The Kaplan-Meier method was used to assess the prognosis of the subgroups,and the survival curves were plotted and statistically tested. Results:Multivariate COX regression analysis revealed that Barcelona Clinic Liver Cancer(BCLC)stage,tumor number,alpha-fetoprotein(AFP),the quantitative change of γ-glutamyl transpeptidase(GGT)and total bilirubin(TBIL)before and after surgery were independent risk factors affecting the prognosis of patients with primary HCC(P＜0.01),and there were differences in hepatitis B virus surface antigen(HBsAg),TNM stage,BCLC stage,tumor size,tumor number,tumor differentiation degree,AFP,surgery type,intraoperative bleeding volume,postoperative albumin-bilirubin(ALBI)and white blood cell count between the high and low GGT variation groups(P＜0.05).Kaplan-Meier survival analysis showed that the prognosis of patients with primary HCC between the high and low GGT variation groups was significantly different,with a hazard ratio of 2.603 for mortality and 1.449 for recurrence(both P＜0.01). Conclusion:The quantitative change of GGT before and after hepatectomy has an evaluation value for the prognosis of patients with primary HCC,and the quantitative change of GGT greater than 29.5 is an independent risk factor for the prognosis of patients with primary HCC.

Objective:To analyze the distribution and drug resistance of pathogens of bacterial bloodstream infection in patients with hematological diseases in the Department of Hematology of Tianjin Medical University General Hospital, and to provide etiological data for clinical empirical anti-infection treatment.Methods:A retrospective analysis was conducted on the general clinical information, pathogenic bacteria and drug susceptibility test results of patients with hematological diseases diagnosed with bacterial bloodstream infection by menstrual blood culture in our center from January 2016 to December 2022.Results:Patients included 498 inpatients, with a total of 639 bacterial strains. Among the patients, 86.9% patients had malignancies, and 76.7% had agranulocytosis. Symptoms of concurrent infections, including those of the respiratory tract, oral mucosa, skin and soft tissues, and abdominal sources were observed in 68.3% patients. Gram-negative bacteria (G -) accounted for 79.0% of the isolated bacteria, and gram-positive bacteria (G +) accounted for 21.0%. The top five isolated pathogens were Klebsiella pneumoniae (22.5%), Escherichia coli (20.8%), Pseudomonas aeruginosa (15.0%), Enterococcus faecium (5.5%), and Stenotrophomonas maltophilum (5.0%). Escherichia coli exhibited a decreasing trend of resistance to quinolones, cephalosporins, and carbapenems. Klebsiella pneumoniae exhibited increasing rates of resistance to quinolones and cephalosporins between 2016 and 2018, but the rated decreased after 2019. The resistance rate to carbapenems exhibited by Pseudomonas aeruginosa was approximately 20%. Carbapenem-resistant strains of Pseudomonas aeruginosa strains were first detected in 2017, with a peak resistance rate of 35.7%, detected in 2019. A 60.0% resistance rate to methicillin was observed in methicillin-resistant coagulase-negative staphylococci (MRCNS), and one case of linezolid-resistant MRCNS was detected. Conclusions:Pathogenic bacteria of bacterial bloodstream infections were widely distributed in our center, and precautions are warranted against carbapenem resistant P. aeruginosa and Klebsiella pneumoniae.

Arsenic compounds are widely used for the therapeutic intervention of multiple diseases.Ancient pharmacologists discovered the medicinal utility of these highly toxic substances,and modern phar-macologists have further recognized the specific active ingredients in human diseases.In particular,Arsenic trioxide(ATO),as a main component,has therapeutic effects on various tumors(including leukemia,hepatocellular carcinoma,lung cancer,etc.).However,its toxicity limits its efficacy,and con-trolling the toxicity has been an important issue.Interestingly,recent evidence has pointed out the pivotal roles of arsenic compounds in phase separation and membraneless organelles formation,which may determine their toxicity and therapeutic efficacy.Here,we summarize the arsenic compounds-regulating phase separation and membraneless organelles formation.We further hypothesize their potential involvement in the therapy and toxicity of arsenic compounds,highlighting potential mecha-nisms underlying the clinical application of arsenic compounds.

The rapid development of digital intelligence technologies is providing a powerful boost to the high-quality development of the healthcare system.Considering the current state of our healthcare services and guided by General Secretary Xi Jinping's insights on new quality productive forces and the directives from Third Plenary Session of Communist Party of China's 20th Central Committee,the high-quality development of the healthcare service system should focus on digital intelligence technologies such as cloud computing,big data,privacy computing,blockchain,Internet of Things(IoT),mobile computing,and AI.The key measures should include the optimization of production factors,services,and governance.Emphasis should be placed on enhancing the efficient and intensive development of the development model,ensuring the high-quality and continuous integration of the supply model,and transitioning to scientific and modern management methods.Herein,we analyzed the"factor optimization—service optimization—governance optimization"development mechanism driven by digital intelligence and proposed corresponding implementation pathways,intending to provide references for establishing a high-quality and efficient healthcare service system with Chinese characteristics.

Objective:This study aimed to investigate the role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria (PNH) patients.Methods:A retrospective analysis was conducted on the clinical data and gene sequencing results of 45 patients with classic PNH admitted to the Department of Hematology, Tianjin Medical University General Hospital, from June 2018 to February 2022. MUC4 gene mutations in patients with classic PNH were summarized, and the risk factors for thrombotic events in these patients were analyzed. Additionally, the effects of MUC4 gene mutations on the cumulative incidence and survival of thrombotic events in patients with classic PNH were determined.Results:The detection rate of MUC4 gene mutations in patients with classic PNH who experienced thrombotic events (thrombotic group) was 68.8% (11/16), which was significantly higher than that in the non-thrombotic group [10.3% (3/29) ] ( P<0.001). All mutations occurred in exon 2. MUC4 mutation ( OR=20.815, P=0.010) was identified as an independent risk factor for thrombotic events in patients with classic PNH. The cumulative incidence of thrombotic events was 78.6% (11/14) in the MUC4 gene mutation group (mutation group) and 16.1% (5/31) in the non-mutation group, showing a statistically significant difference between the two groups ( P<0.001). Survival analysis showed a lower overall survival (OS) rate in the thrombotic group compared with that in the non-thrombotic group [ (34.4±25.2) % vs. (62.7±19.3) % ] ( P=0.045). The OS rate of patients was (41.7±29.9) % in the mutation group and (59.1±18.3) % in the non-mutation group ( P=0.487) . Conclusion:MUC4 gene mutations are associated with an increased incidence of thrombotic events in classic PNH patients, highlighting their role as independent risk factors for thrombosis in this population. These mutations can be considered a novel predictive factor that aids in evaluating the risk of thrombosis in patients with classic PNH.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone