Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Objective:Investigate key genes influencing vascular calcification through bioinformatics analysis and experimental validation.Methods:Three vascular calcification datasets (GSE159832, GSE229679 and GSE37558) were obtained from the Gene Expression Omnibus database. Subsequently, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and conventional gene set enrichment analysis (GSEA) were performed on the common differential expressed genes(DEGs). For in vitro validation, a vascular smooth muscle cell calcification model was established by stimulating mouse primary vascular smooth muscle cells with high phosphate and calcium chloride (Pi+CaCl 2). Cells were divided into a control group and a Pi+CaCl 2 group. To investigate the role of TK1, cells were transfected with TK1-targeting siRNA (siTK1) or control siRNA (siControl) prior to Pi+CaCl 2 stimulation, creating siControl+Pi+CaCl 2 and siTK1+Pi+CaCl 2 groups. The association between key DEGs and vascular calcification was assessed at the protein and mRNA levels using Western blot and quantitative real-time PCR, respectively. Changes in the phosphorylation of the downstream effector, AKT (p-AKT/AKT), were also measured. Results:A total of 2275, 449, and 381 DEGs were identified from the three vascular calcification datasets (GSE159832, GSE229679, and GSE37558), respectively. Two common DEGs-phosphoserine aminotransferase 1 and thymidine kinase 1 (TK1)-were identified across all datasets. GO enrichment analysis revealed that TK1 was significantly enriched in pathways related to ribosome biogenesis, assembly, and rRNA processing and maturation. GSEA-KEGG analysis indicated significant enrichment in the PI3K-AKT signaling pathway, pathways in cancer, neurodegenerative diseases, cytoskeleton, and smooth muscle contraction. Conventional GSEA of TK1 further confirmed significant enrichment in pathways including dynein, epithelial tight junctions, axon guidance, and vascular smooth muscle contraction pathways. At the experimental level, both protein and mRNA expression of TK1, along with the p-AKT/AKT ratio, were significantly lower in the Pi+CaCl 2 group compared to the control group (all P<0.05). Furthermore, compared to the siControl+Pi+CaCl 2 group, the siTK1+Pi+CaCl 2 group exhibited decreased expression of differentiation markers, increased expression of calcification markers, and a further reduced p-AKT/AKT ratio (all P<0.05). Conclusion:Integrated bioinformatics and cellular validation demonstrate a correlation between TK1 expression and vascular calcification, suggesting a potential protective role for TK1 in this pathological process.

Objective To investigate the impact of sintilimab combined with TP chemotherapy regimen on immune function and prognostic survival in patients with advanced esophageal cancer.Methods A total of 82 patients with advanced esophageal cancer who received treatment in the hospital from January 2022 to October 2023 were enrolled.They were divided into two groups with 41 cases in each group using the random number table method.The control group was given the TP chemotherapy regimen,while the observation group was treated with sintilimab in addition to the TP chemotherapy regimen used in the control group.The treatment cycle was 21 days,and both groups received 4 cycles of treatment.After that,the observation group received sintilimab monotherapy for maintenance treatment for at least 1 year.The disease control rate(DCR)and objective response rate(ORR)of the patients were recorded.The immune function,levels of inflammatory factors and tumor markers before and after treatment were compared between the two groups.The swallowing function and quality of life of the patients before and after treatment were evaluated using the Swallowing Safety Assessment(SSA)and the Quality of Life Instruments for Cancer Patients-Esophageal Cancer(QLICP-ES).The occurrence of adverse reactions was also recorded.After the start of treatment,the patients were followed up for 18 months,and the overall survival(OS)and survival rate were recorded.Results In the observation group,the partial remission rate and disease control rate were 53.66%and 87.80%respectively,both higher than those in the control group.After treatment,the levels of CD3+and CD4+in the observation group were(50.48±5.61)%and(37.96±4.69)%respectively,which were higher than(44.73±5.12)%and(33.15±4.21)%in the control group.The immune function of the observation group was improved compared with the control group,while the levels of inflammatory factors and tumor markers were lower than those in the control group.The swallowing function and quality of life were significantly improved compared with the control group(P<0.05).The 18-month follow-up results showed that the median overall survival(OS)in the observation group was 16(9,17)months,and that in the control group was 9(7,14)months.The OS in the observation group was longer than that in the control group(χ2=13.394,P<0.001).The 18months survival rates in the observation group and the control group were 60.98%(25/41)and 36.59%(15/41)respec-tively,with the observation group being higher than the control group(χ2=4.881,P=0.027).Conclusion The sintilimab combined with TP chemotherapy regimen is beneficial for improving immune function and enhancing the survival status of patients with advanced esophageal cancer.

Objective:To investigate the effects of enolase 1(ENO1)on the proliferation,migration,and invasion of gastric cancer cells and its underlying molecular mechanisms.Methods:The expression levels of ENO1 in human gastric cancer cell lines(HGC27,MKN-45,N-87,MGC803,BGC-823)and human gastric mucosal epithelial cells(GES-1)were detected using WB assay.Gene editing tools such as CRISPR and overexpression system were used to construct ENO1 knockdown and knockdown-rescue cell lines.Both MKN-45 and BGC-823 cells were grouped into control(Ctrl)group,ENO1 knockdown(ENO1 KD)group,and ENO1 knockdown-rescue(ENO1 KD-OE)group.The effects of ENO1 knockdown or ENO1 knockdown-rescue on the proliferation,migration,invasion,and apoptosis of gastric cancer cells were evaluated using colony formation assay,EdU staining,scratch wound healing assay,Transwell chamber assay and flow cytometry.Additionally,a xenograft model was established in nude mice,and the effects of ENO1 on tumor growth were monitored using small animal in vivo imaging and tumor tissue block measurement.ENO1 was silenced in MKN-45 cells employing RNA interference technology,and the downstream target genes of ENO1 were identified using RNA co-immunoprecipitation sequencing(RIP-seq)and bioinformatics analysis.The molecular mechanisms by which ENO1 regulates the proliferation,migration and invasion of gastric cancer cells was also analyzed.Results:ENO1 was significantly upregulated in gastric cancer cell lines(P<0.01 or P<0.001).ENO1 knockdown significantly inhibited proliferation,migration,and invasion while promoting apoptosis in MKN-45 and BGC-823 cells(P<0.001,P<0.000 1).Rescue experiments showed that restoring ENO1 expression significantly enhanced cell proliferation,migration,invasion,and inhibited apoptosis(P<0.05,P<0.01,P<0.001,P<0.000 1).In vivo experiments demonstrated that ENO1 knockdown significantly inhibited tumor growth in nude mice(P<0.000 1).The differentially expressed genes interacting with ENO1 protein were primarily enriched in pathways related to RNA splicing.Additionally,ENO1 protein was found to interact with the PKM gene,and their expressions showed a positive correlation in gastric cancer tissues(r=0.886).Conclusion:ENO1 is highly expressed in gastric cancer cells.ENO1 interacts with precursor mRNA of PKM to influence its RNA splicing process,thereby regulating PKM2 expression and promoting gastric cancer progression.

Objective To investigate the impact of sintilimab combined with TP chemotherapy regimen on immune function and prognostic survival in patients with advanced esophageal cancer.Methods A total of 82 patients with advanced esophageal cancer who received treatment in the hospital from January 2022 to October 2023 were enrolled.They were divided into two groups with 41 cases in each group using the random number table method.The control group was given the TP chemotherapy regimen,while the observation group was treated with sintilimab in addition to the TP chemotherapy regimen used in the control group.The treatment cycle was 21 days,and both groups received 4 cycles of treatment.After that,the observation group received sintilimab monotherapy for maintenance treatment for at least 1 year.The disease control rate(DCR)and objective response rate(ORR)of the patients were recorded.The immune function,levels of inflammatory factors and tumor markers before and after treatment were compared between the two groups.The swallowing function and quality of life of the patients before and after treatment were evaluated using the Swallowing Safety Assessment(SSA)and the Quality of Life Instruments for Cancer Patients-Esophageal Cancer(QLICP-ES).The occurrence of adverse reactions was also recorded.After the start of treatment,the patients were followed up for 18 months,and the overall survival(OS)and survival rate were recorded.Results In the observation group,the partial remission rate and disease control rate were 53.66%and 87.80%respectively,both higher than those in the control group.After treatment,the levels of CD3+and CD4+in the observation group were(50.48±5.61)%and(37.96±4.69)%respectively,which were higher than(44.73±5.12)%and(33.15±4.21)%in the control group.The immune function of the observation group was improved compared with the control group,while the levels of inflammatory factors and tumor markers were lower than those in the control group.The swallowing function and quality of life were significantly improved compared with the control group(P<0.05).The 18-month follow-up results showed that the median overall survival(OS)in the observation group was 16(9,17)months,and that in the control group was 9(7,14)months.The OS in the observation group was longer than that in the control group(χ2=13.394,P<0.001).The 18months survival rates in the observation group and the control group were 60.98%(25/41)and 36.59%(15/41)respec-tively,with the observation group being higher than the control group(χ2=4.881,P=0.027).Conclusion The sintilimab combined with TP chemotherapy regimen is beneficial for improving immune function and enhancing the survival status of patients with advanced esophageal cancer.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Objective:Investigate key genes influencing vascular calcification through bioinformatics analysis and experimental validation.Methods:Three vascular calcification datasets (GSE159832, GSE229679 and GSE37558) were obtained from the Gene Expression Omnibus database. Subsequently, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and conventional gene set enrichment analysis (GSEA) were performed on the common differential expressed genes(DEGs). For in vitro validation, a vascular smooth muscle cell calcification model was established by stimulating mouse primary vascular smooth muscle cells with high phosphate and calcium chloride (Pi+CaCl 2). Cells were divided into a control group and a Pi+CaCl 2 group. To investigate the role of TK1, cells were transfected with TK1-targeting siRNA (siTK1) or control siRNA (siControl) prior to Pi+CaCl 2 stimulation, creating siControl+Pi+CaCl 2 and siTK1+Pi+CaCl 2 groups. The association between key DEGs and vascular calcification was assessed at the protein and mRNA levels using Western blot and quantitative real-time PCR, respectively. Changes in the phosphorylation of the downstream effector, AKT (p-AKT/AKT), were also measured. Results:A total of 2275, 449, and 381 DEGs were identified from the three vascular calcification datasets (GSE159832, GSE229679, and GSE37558), respectively. Two common DEGs-phosphoserine aminotransferase 1 and thymidine kinase 1 (TK1)-were identified across all datasets. GO enrichment analysis revealed that TK1 was significantly enriched in pathways related to ribosome biogenesis, assembly, and rRNA processing and maturation. GSEA-KEGG analysis indicated significant enrichment in the PI3K-AKT signaling pathway, pathways in cancer, neurodegenerative diseases, cytoskeleton, and smooth muscle contraction. Conventional GSEA of TK1 further confirmed significant enrichment in pathways including dynein, epithelial tight junctions, axon guidance, and vascular smooth muscle contraction pathways. At the experimental level, both protein and mRNA expression of TK1, along with the p-AKT/AKT ratio, were significantly lower in the Pi+CaCl 2 group compared to the control group (all P<0.05). Furthermore, compared to the siControl+Pi+CaCl 2 group, the siTK1+Pi+CaCl 2 group exhibited decreased expression of differentiation markers, increased expression of calcification markers, and a further reduced p-AKT/AKT ratio (all P<0.05). Conclusion:Integrated bioinformatics and cellular validation demonstrate a correlation between TK1 expression and vascular calcification, suggesting a potential protective role for TK1 in this pathological process.

Objective To study the inner ear appearance on three-dimensional real inversion recovery(3D re-al IR)imaging in patients with sudden sensorineural hearing loss,and to investigate the relationship between blood-labyrinth barrier permeability and pathogenesis and prognosis of sudden hearing loss.Methods A total of 41 pa-tients with sudden sensorineural hearing loss received 3D real IR at 3.0 T MRI,and the signal intensity of inner ear were recorded.We respectively measured cochlear signal intensity in affected and healthy ears,and medullary signal intensity,and calculated the cochlear/medulla ratio(CM ratio)separately.On the basis of CM ratio,we evaluated hearing levels at initial and after treatment,and the relationship between CM ratio and hearing prognosis.Results Among the 41 patients,33 cases(occupying 80.48％)individually had a higher CM ratio in the affected ear than in the healthy one.The CM ratio of the affected side was not higher than that of the healthy side in 8 cases,and the ef-fective rate was 100％,eighteen cases had below 1.5 times the CM ratio in affected ears as in healthy ears,with 77.78％effective rate of treatment;seven cases had 1.5 to 1.75 times,with 100％effective rate;two cases had 1.75 to 2 times,with 50％effective rate;and the rest 14 cases had over 2 times,with 14.28％effective rate(P＜0.05).Conclusion The variation of blood-labyrinth barrier permeability in patients with sudden hearing loss can be read on the 3D Real IR,and it indicates that 80.48％patients have higher-intensity signals in lateral cochlea.The CM ratio can be adopted to evaluate the extent of inner ear damage of patients more accurately.As the CM ratio ri-ses,patients'prognosis become worse,and patients with over 1.75 times the CM ratio in the affected ear as in the healthy one,mostly suffer poor prognosis.

Objectives:To evaluate the clinical outcome of acute respiratory distress syndrome (ARDS) in patients with Stanford Type A aortic dissection (AAD).Methods:A total of 212 patients diagnosed with AAD and receiving surgical treatment in the Affiliated Hospital of Jining Medical University from January 2016 to December 2021 were included. The patients were divided into ARDS group and non-ARDS group based on the definition of ARDS Berlin after surgery. The preoperative general clinical data of the two groups were compared by univariate analysis, and the preference-matching variables were screened. The patients were divided into ARDS group ( n=63) and non-ARDS group ( n=63) by using propensity matching score, and the clinical outcome indexes of ARDS group and non-ARDS group were compared after matching. Results:A total of 63 patients (29.7%) were diagnosed with ARDS after AAD. A total of 63 pairs of patients were successfully matched using propensity score to adjust preoperative confounding factors. After matching, the proportion of total arch surgery, operation time, perioperative blood loss, red blood cell transfusion and plasma transfusion in the ARDS group were significantly higher than those in the non-ARDS group, with statistical significance (all P<0.05). After the match, In the ARDS group, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score [18(14-24)points vs 13(12-15)points], mechanical ventilation time [86.0(57.3-158.0)h vs 41.5(23.8-60.4)h], intensive care unit (ICU) stay time [7.0(6.0-11.5)d vs 4.0(3.0-6.0)d] and hospital stay [18.0(14.0-24.5)d vs 13.5(10.8-18.0)d] were significantly higher than those in the non-ARDS group, with statistical significance (all P<0.05). There was no significant difference in in-hospital mortality (3.2% vs 1.6%) or within 30 days after discharge (6.3% vs 3.2%) between the two groups (all P>0.05). Conclusions:The incidence of ARDS is higher in patients diagnosed with AAD based on the Berlin definition, but there is no increase in the mortality rate within 30 days of hospital and discharge in ARDS group. The Berlin definition of ARDS may have some limitations in the application of ARDS in patients with AAD after surgery.

High-altitude regions,characterized by their elevated altitude,are subject to a complex set of environmental conditions including intense ultraviolet radiation,low oxygen levels,low temperatures,and low humidity.These distinctive environmental features lead to unique dietary patterns,lifestyles,and physiological adaptations.Notably,individuals who have just moved into high-altitude areas and those who live there on a long-term basis undergo specific adaptive adjustments in glucose metabolism.Typically,newcomers experience transient elevations in blood glucose levels,which gradually decline after prolonged residence at high altitudes to levels even lower than those found at low altitudes.In general,current findings of observational studies generally suggest a decreased risk of diabetes mellitus among populations inhabiting high-altitude regions.However,the glucose metabolism varies among populations from different high-altitude regions across the world,which indicates that the reshaping of glucose metabolism induced by high altitudes is a complicated phenomenon.This article provides an overview of the impact of various components of high-altitude environment,characteristic lifestyle factors,and socioeconomic development levels on glucose metabolism and the related diseases and the potential mechanisms involved.The aim is to offer valuable insights for researchers investigating glucose metabolism in high-altitude settings.