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 analyze the prenatal diagnosis results and pregnancy outcomes of fetal growth re-striction(FGR)with varying severity and provide guidance for clinical counseling and management of FGR.Meth-ods:A total of 141 pregnant women with FGR treated at Sichuan Maternal and Child Health Hospital from January 2020 to June 2021 were selected for the retrospective study.They were divided into the mild FGR group(3th≤EFW＜10th,84 cases)and the severe FGR group(EFW＜3th,57 cases)based on different estimated fetal weight(EFW).All pregnant women underwent amniocentesis for prenatal diagnosis.The chromosome results and preg-nancy outcomes of the two groups were statistically analyzed.Results:19 cases(13.5%)of 141 fetuses with FGR were found with chromosome abnormalities.The rate of chromosomal abnormalities was 19.3%(11/57)in the severe FGR group,which was higher than the 9.5%(8/84)in the mild FGR group,but the difference was not statistically significant(P=0.095).110 cases underwent both karyotype analysis and chromosome microarray a-nalysis(CMA).The detection rate of chromosomal abnormalities in CMA was 13.6%,which was significantly higher than 4.5%in karyotype analysis(P=0.006).Among chromosomal abnormalities,chromosomal aneu-ploidy accounted for 21.05%(4/19),including 1 case of trisomy 18 and 2 cases of 47,XXY.Two cases with dele-tion in the 4p16.3 regions were found in the severe FGR group,and these deletions are associated with Wolf-Hir-schhorn syndrome.The termination rate of pregnancy and admission to the neonatal intensive care unit in the se-vere FGR group were higher than those in the mild FGR group.In contrast,the full-term delivery rate and newborn birth weight were lower in the severe FGR group compared to the mild FGR group,showing statistically significant differences(P＜0.05).There was no statistically significant difference in the rates of stillbirth and preterm birth be-tween the two groups(P＞0.05).Conclusions:The detection rate of chromosomal abnormalities using CMA in fetuses with FGR was higher than traditional karyotyping.Therefore,it is recommended to combine karyotyping with CMA for invasive prenatal diagnosis of FGR fetuses.The risk of adverse pregnancy outcomes increases with severe FGR,and monitoring should be intensified during pregnancy and the perinatal period to reduce adverse pregnancy outcomes.

Signal transducer and activator of transcription 3(STAT3)is an intracellular signaling factor that plays a critical role in various cellular processes,including the growth,differentiation,apoptosis,and immune response of cells.Aberrant activation of T helper cell 17(Th17)is closely associated with the morbidity and progress of various autoimmune diseases.STAT3 participates in the pathogenesis of Sj?gren syndrome by inducing excessive proliferation and abnormal differentiation of Th17 cells and affecting lymphocyte infiltration into exocrine glands.Therefore,targeting the STAT3 signaling pathway represents a potential novel therapeutic approach for the treatment of Sj?gren syndrome.This review summarizes the research of STAT3 in the pathogenesis and progression of Sj?gren syndrome through regulating Th17 cells,focusing on current inhibitors targeting the STAT3 signaling pathway as potential therapeutic targets for Sj?gren syndrome.

Objective To analyze the clinical characteristics of stiff left atrial syndrome (SLAS) after Mei mini maze procedure for atrial fibrillation (AF), and to explore its risk factors and treatments. Methods We retrospectively analyzed the clinical data of the patients who underwent Mei mini maze procedure in Xinhua Hospital between 2010 and 2020. According to whether SLAS occurred in the early postoperative period, patients were divided into a SLAS group and a non-SLAS group. The basic data, perioperative echocardiogram and laboratory test indexes of the two groups were compared. Results A total of 1 056 patients were collected. There were 672 (63.6%) males with an average age of 63.6±9.3 years, including 489 patients with persistent AF and 567 patients with paroxysmal AF. Fourteen (14/1 056, 1.3%) patients developed SLAS, with an average occurrence time of 2.1±1.1 days after the surgery. The average follow-up time of the whole group was 21.4±7.8 months. Two patients in the SLAS group developed SLAS again after discharge, and the occurrence time was 3 weeks and 4 weeks after the operation, respectively; while no SLAS occurred after discharge in the non-SLAS group. Diabetes and small preoperative left atrial diameter were risk factors for SLAS after surgery. Patients with SLAS had a good prognosis after adequate diuretic therapy. Conclusion The incidence of SLAS after Mei mini maze procedure for AF is low, and it mostly occurs in the early postoperative period. After adequate diuretic treatment, the prognosis is good.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Abstract: KRAS protein, a small GTPase encoded by the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene, is involved in cell proliferation, differentiation, migration and cell survival, and is known as a regulatory switch for the cell life cycle. However, KRAS gene is prone to mutation, leading to hyperactivation of its downstream signaling pathways, and has a vital role in driving tumorigenesis. KRAS mutations predominantly take place at residue G12, G13 or Q61, and different mutants have varying effects on protein physiological functions and tumor types. Due to its smooth surface and high affinity for nucleotides, KRAS had been considered to be “undruggable” until the launch of selective KRAS G12C inhibitors sotorasib and adagrasib, which broke the dogma. This review introduces the structure and functions of KRAS, as well as the status and progress of inhibitors directly targeting KRAS mutants (G12C, G12D, G12R, G12S) and pan-KRAS inhibitors, aiming to provide some insightful reference for the development of KRAS inhibitors.

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.

Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Objective:To analyze the prenatal diagnosis results and pregnancy outcomes of fetal growth re-striction(FGR)with varying severity and provide guidance for clinical counseling and management of FGR.Meth-ods:A total of 141 pregnant women with FGR treated at Sichuan Maternal and Child Health Hospital from January 2020 to June 2021 were selected for the retrospective study.They were divided into the mild FGR group(3th≤EFW＜10th,84 cases)and the severe FGR group(EFW＜3th,57 cases)based on different estimated fetal weight(EFW).All pregnant women underwent amniocentesis for prenatal diagnosis.The chromosome results and preg-nancy outcomes of the two groups were statistically analyzed.Results:19 cases(13.5%)of 141 fetuses with FGR were found with chromosome abnormalities.The rate of chromosomal abnormalities was 19.3%(11/57)in the severe FGR group,which was higher than the 9.5%(8/84)in the mild FGR group,but the difference was not statistically significant(P=0.095).110 cases underwent both karyotype analysis and chromosome microarray a-nalysis(CMA).The detection rate of chromosomal abnormalities in CMA was 13.6%,which was significantly higher than 4.5%in karyotype analysis(P=0.006).Among chromosomal abnormalities,chromosomal aneu-ploidy accounted for 21.05%(4/19),including 1 case of trisomy 18 and 2 cases of 47,XXY.Two cases with dele-tion in the 4p16.3 regions were found in the severe FGR group,and these deletions are associated with Wolf-Hir-schhorn syndrome.The termination rate of pregnancy and admission to the neonatal intensive care unit in the se-vere FGR group were higher than those in the mild FGR group.In contrast,the full-term delivery rate and newborn birth weight were lower in the severe FGR group compared to the mild FGR group,showing statistically significant differences(P＜0.05).There was no statistically significant difference in the rates of stillbirth and preterm birth be-tween the two groups(P＞0.05).Conclusions:The detection rate of chromosomal abnormalities using CMA in fetuses with FGR was higher than traditional karyotyping.Therefore,it is recommended to combine karyotyping with CMA for invasive prenatal diagnosis of FGR fetuses.The risk of adverse pregnancy outcomes increases with severe FGR,and monitoring should be intensified during pregnancy and the perinatal period to reduce adverse pregnancy outcomes.