OBJECTIVE To explore the effects of dexmedetomidine （DEX） increasing serpin peptidase inhibitor clade E member 1 （SERPINE1） protein on the malignant biological behavior of thyroid carcinoma （THCA） cells. METHODS THCA cells （KTC-1， TPC-1） were treated with 1， 10 and 100 nmol/L DEX， and their viabilities， clone formation rates， migration rates and invasion number were examined. Potential biological functions of DEX in THCA cells were analyzed through whole genome sequencing and gene ontology enrichment analysis. The core targets of DEX were mined through a protein-protein interaction network. The expression characteristics of DEX core targets and their relationship with patient prognosis were evaluated. The effects of DEX on mRNA and protein expressions of core targets and protein secretion in 2 types of THCA cells were detected， and the effects of this target on DEX-related effects were validated preliminarily by knocking down the core target. RESULTS Compared with the control group （0 nmol/L DEX）， DEX at 1， 10 and 100 nmol/L significantly increased the viabilities of 2 types of THCA cells （except for the KTC-1 cells in the 1 nmol/L DEX group at 24 h）， concentration-dependently elevated the rates of clone formation， migration rates （except for 2 types of THCA cells in 1 nmol/L DEX group）， and the number of invasion （P＜0.05）. A total of 287 differently expressed genes （75 up- tongxueyan180@163.com regulated and 212 down-regulated） were enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B， Wnt， and senescence-associated secretory phenotypes in the 2 kinds of DEX-treated or non-treated THCA cells. SERPINE1 was a core target of DEX for THCA， and its mRNA and protein expression in THCA tissues/cells were significantly elevated and associated with poor prognosis of the patients （P＜0.05）. Compared with the control group， mRNA and protein expression of SERPINE1 was significantly up-regulated in 2 types of cells in the 1， 10 and 100 nmol/L DEX groups， while the secretion of this protein in conditioned medium was also significantly increased， all of which showed concentration-dependence （P＜0.05）. After knocking down SERPINE1， the promoting effects of DEX on the proliferation， colony formation， migration and invasion abilities of two types of THCA cells were significantly inhibited （P＜0.05）. CONCLUSIONS DEX can promote the proliferation， migration and invasion of THCA cell， and the above effects may be associated with the expression of increased secretory SERPINE1 protein.

Objective:To discuss the expression of programmed cell death-ligand 1(PD-L1)in the oral squamous cell carcinoma(OSCC)cells and its effect on biological behavior of the OSCC CAL27 cells,and to clarify the possible mechanism.Methods:Western blotting method was used to detect the expression levels of PD-L1 protein in the oral epithelial HOK cells and OSCC CAL27,TCA8113,and SCC15 cells;immunofluorescence staining method was used to detect the expression and localization of PD-L1 protein in the CAL27 cells.The CAL27 cells were divided into control group(transfected with si-NC)and si-PD-L1 group(transfected with si-PD-L1).Western blotting method was used to detect the interference efficiency of the cells in two groups;CCK-8 assay was used to detect the proliferative activities of the cells in two groups at different time points;plate clone formation assay was used to detect the numbers of clone formation of the cells in two groups;cell scratch healing assay was used to detect the scratch healing rates of the cells in two groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in two groups.Results:The expression level of PD-L1 protein in the OSCC cells was higher than that in the HOK cells(P<0.05 or P<0.01);PD-L1 expressed in the cytoplasm and nucleus of the CAL27 cells.The CCK-8 assay and plate clone formation assay results showed that compared with control group,the proliferative activities of the CAL27 cells in si-PD-L1 group at different time points were significantly decreased(P<0.05 or P<0.01),and the numbers of clone formation were significantly decreased(P<0.01).The cell scratch healing assay results showed that compared with control group,the scratch healing rates of the cells in si-PD-L1 group were significantly decreased(P<0.05 or P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in si-PD-L1 group were significantly decreased(P<0.01).Conclusion:The expression of PD-L1 in the OSCC cells is higher than that in normal oral epithelial cells,and knocking down PD-L1 expression can inhibit the proliferation,clone formation,migration and invasion capabilities of the OSCC cells.

Objective:To compare the real-world efficacy and safety profile of tenofovir amibufenamid (TMF) and tenofovir alafenamide (TAF) tablets in the treatment of patients with chronic hepatitis B (CHB).Methods:This retrospective study included patients with chronic hepatitis B who received TMF and TAF antiviral treatment at the Infectious Disease Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. The primary and secondary outcome was to study the patient HBV DNA conversion rate (<20 IU/ml), alanine aminotransferase (ALT) normalization rate, renal function, and lipid levels of patients at 48 weeks of treatment. The comparison of data between measurement data groups was differentiated using a t-test and Mann-Whitney U test. The inter-group comparison rate in count data was performed using the χ2 test or Fisher's exact probability. Results:A total of 440 cases were enrolled, including 220 in the TMF group (63 treatment-na?ve and 157 treatment-experienced) and 220 cases in the TAF group (61 treatment-na?ve and 159 treatment-experienced). In terms of efficacy, the HBV DNA seroconversion rates in the TMF group and TAF group were 90.5% and 85.2% ( P=0.372), respectively, while the ALT normalization rates were 92.1% and 88.5% ( P=0.505), respectively, at 48 weeks of treatment. The HBV DNA-negative conversion rate for the newly treated patients was 99.4% and 98.7%, respectively ( P=1.000), while the rates of ALT normalization were 94.9% and 92.3%, respectively ( P=0.863). In terms of safety profile, the serum creatinine level was lower in the TMF group than that in the TAF group at 48 weeks of treatment [TMF group 66.5 (56.3, 78.3) μmol/L, TAF group 70.6 (60.7, 77.8) μmol/L, Z=-2.282, P=0.022]. However, there was no statistically significant difference in other renal function and tubular function related indicators between the two groups of patients ( P>0.05). The serum high-density lipoprotein levels were higher in the TMF group than those in the TAF group [TMF 1.4 (1.1, 1.6) mmol/L vs. TAF group 1.3 (1.1, 1.6) mmol/L, Z=-2.204, P=0.027] at 48 weeks of treatment. However, there was no statistically significant difference in other blood lipid indicators between the two groups of patients ( P>0.05). Conclusion:There is no statistically significant difference in efficacy and safety profiles between TMF and TAF at 48 weeks in the treatment of patients with chronic hepatitis B, and the overall safety profile is favorable.

Bamboo leaf flavonoids(BLF)are compounds extracted from bamboo leaves,possessing properties including antioxidant,antimicrobial and anti-inflammatory properties.This study aimed to investigate the effects of BLF on liver damage,antioxidant function,and related gene expression in rats induced by diquat(DQ).Thirty-two 5-week-old male Sprague-Dawley(SD)rats were randomly divided into four experimental groups:the control group(Con),1 000 mg/kg BLF group(BLF),DQ stress group(DQ),and 1 000 mg/kg BLF+DQ stress group(BLF-DQ).The results showed that compared to the Con,the DQ group exhibited significantly decreased serum AST lev-els(P＜0.05),as well as decreased levels of T-AOC,GPX,SOD,and CAT in the liver(P＜0.05),and increased MDA levels in rats(P＜0.05).Additionally,the gene expression levels of HO-1,GPX,CAT,SOD1,and Nrf2 in the liver were significantly reduced(P＜0.05).In contrast,1 000 mg/kg BLF significantly decreased serum AST and ALT levels(P＜0.05),increased levels of T-AOC,GPX,CAT,and SOD in liver(P＜0.05),and significantly increased gene expression of HO-1,GPX,CAT,SOD1,Nrf2,and NQO1(P＜0.05).Compared to the DQ group,BLF-DQ significant-ly decreased liver index(P＜0.05),reduced serum AST and ALT levels(P＜0.05),increased lev-els of CAT,GPX,and T-AOC in liver(P＜0.05),decreased MDA levels(P＜0.05),and signifi-cantly upregulated gene expression levels of HO-1,GPX,CAT,SOD1,and Nrf2(P＜0.05).These findings indicated that BLF alleviate liver damage caused by DQ stress in rats,improve liver an-tioxidant function inhibition,activate the Nrf2 signaling pathway and PINK/Parkin mitophagy-re-lated gene expression.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Humans ; Cohort Studies ; Body Mass Index ; Percutaneous Coronary Intervention ; Coronary Artery Disease ; Inflammation ; Treatment Outcome ; Risk Factors

Objective : To explore differential expression of insulin like growth factor 1( IGF1) in oral squamous cell carcinoma (OSCC) tissues and cells , and to analyze its clinical significance of IGF1 . Methods : The protein expression of IGF1 was detected in 115 OSCC tissues (OSCC group) and 74 normal tissues (normal group) using immunohistochemical technique , and the relationship with the clinicopathological factors and prognosis of OSCC was analyzed. The IGF1 protein and mRNA levels in HOK and OSCC cell lines ( CAL⁃27 , TCA⁃8113 , SCC⁃15 and SCC⁃25) were detected by Western blot and qRT⁃PCR. Results : The high expression rate of IGF1 in OSCC group was 72. 17% , which was significantly higher than that in normal group (2. 70% ) ( P < 0. 001) . The proportion under ROC curve (AUC) of OSCC diagnosed by IGF1 was 0. 81 , the sensitivity was 0. 73 , and the specificity was 0. 82. The expression of IGF1 was related to the degree of differentiation , T stage and depth of invasion (P = 0. 03 , P = 0. 02 , P = 0. 02) , but not to gender, age , N stage , TNM stage , smoking , alcohol consumption , or HPV infection (P > 0. 05) . Kaplan⁃Meier and COX regression analysis showed that the high expression of IGF1 , the degree of differentiation , the T stage and the depth of infiltration were the related factors affecting the prognosis of patients (P < 0. 01 , P = 0. 04 , P = 0. 03 , P = 0. 04) . COX multivariate indicated that high expression of IGF1 was an independent factor affecting the prognosis of patients ( P = 0. 01) . Western blot and qRT⁃PCR results indicated that the expression of IGF1 in OSCC cell lines was higher than that in HOK (P < 0. 05) . Conclusion IGF1 can be a potential diagnostic and poor prognostic marker in oral squamous cell carcinoma.

Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.