Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective:To investigate the clinicopathological characteristics of acidophil stem cell pituitary neuroendocrine tumors (PitNET)/adenoma.Methods:Five cases of acidophil stem cell PitNET/adenoma were diagnosed between May 2022 and July 2023 at the Second Hospital of Hebei Medical University, Shijiazhuang, China. The clinicopathological features of the tumor were analyzed by using histology, immunohistochemistry, and electron microscopy. The relevant literature was reviewed.Results:There were 1 male and 4 females, aged from 23 to 69 years. Patient 3 was 55 years old at the time of diagnosis and first surgery, and relapsed 5 years later. The patients′ median age was 32 years. Patients 1 and 5 showed elevated blood prolactin, with various degrees of hormonal symptoms except Patient 3, who showed only tumor compression symptoms. Imaging studies showed that all cases involved the sellar floor. The tumors of Patients 1, 2 and 5 were closely related to the cavernous sinus segment of the internal carotid artery. The tumors exhibited a diffuse growth pattern with chromophobic to slightly acidophilic cytoplasm. A few of tumor cells showed chromophobic cytoplasm. The nucleoli were conspicuous. Intranuclear inclusion bodies and variably-sized clear vacuoles were observed occasionally. Under electron microscope, marked mitochondrial abnormalities were observed, including increased mitochondria number, expanded hypertrophy, and absence of mitochondrial ridge fracture. Some mitochondrial matrices were dense, while some were vacuolated.Conclusions:Acidophil stem cell PitNET/adenoma is a rare type of pituitary adenomas/PitNETs. It often has a more clinically aggressive manner with immature cells, diffuse expression of PIT1, prolactin, and varying degrees of growth hormone expression. Because of the obvious diversity of their clinical hormone status and hormone immune expression, the diagnosis of this type tumor is still a challenge.

Humans ; Uric Acid ; Cross-Sectional Studies ; Spondylarthritis/diagnostic imaging* ; C-Reactive Protein ; Spondylitis, Ankylosing

Objective:To analyze the consistency and correlation of indirect calorimetry (IC) and Harris-Benedict estimation method (H-B) in measuring energy consumption in patients with severe acute pancreatitis (SAP), as well as the characteristics of energy metabolism at resting state of SAP patients with different etiologies, and so as to guide the formulation of clinical energy nutrition support program.Methods:From February 1 to December 31, 2019, 61 SAP patients admitted into the intensive care unit of the First Affiliated Hospital of Nanchang University were enrolled. Collected relevant data of patients, such as the etiology of SAP, whether mechanical ventilation was needed, as well as the metabolic status. All SAP patients accepted IC test on the first day after admission to intensive care unit. According to the energy consumption measured by IC (hereinafter referred to as IC value) and the energy consumption measured by H-B (hereinafter referred to as H-B value), SAP patients were determined to be in high, normal or low metabolic state. Bland-Altman method and Pearson linear regression were used to analyze the consistency and correlation of the two methods in measuring energy consumption, and the linear equation was fitted. Paired t test was used for statistical analysis. Results:Among the 61 SAP patients, 13 cases were biliary SAP, 30 cases were hyperlipidemic SAP, 6 cases were alcoholic SAP, and 12 cases were SAP of other causes or unknown causes. Nineteen cases needed mechanical ventilation and 42 cases did not need mechanical ventilation. There were 70.5% (43/61) of SAP patients in high metabolic state, 13.1%(8/61) of SAP patients in normal metabolic state, and 16.4% (10/61) of SAP patients in low metabolic state. The IC value in 61 SAP patients was higher than H-B value((8 604.7±367.8) kJ/d vs. (6 491.2±133.7) kJ/d), and the difference was statistically significant ( t=5.95, P<0.001). The IC value in patients with hyperlipidemic, alcoholic and biliary SAP was (8 815.2±537.9), (7 631.2±890.5), and (8 108.0±933.1) kJ/d, respectively, and the H-B value was (6 869.6±204.5), (5 916.8±153.7), and (5 974.2±200.9) kJ/d, respectively. The IC value in patients with biliary or hyperlipidemic SAP were higher than H-B value, and the differences were statistically significant( t=2.29 and 3.38, both P<0.05). The IC value and H-B value in SAP patients with mechanical ventilation and without mechanical ventilation were (10 485.0±741.1) and (6 462.6±222.8) kJ/d, (6 595.1±364.7) and (6 503.2±166.7) kJ/d, respectively. The IC value in SAP patients with mechanical ventilation was higher than H-B value and the IC value in SAP patients without mechanical ventilation, and the differences were statistically significant ( t=4.71 and 5.20, both P<0.001). The consistency analyzed by Bland-Altman method showed that the two methods had obvious biases, and the average bias value was 92.2 kJ/d. The result of Pearson linear regression analysis indicated that there was a linear relationship between two methods ( r=0.44, P<0.001). The linear equation fitted by the univariate regression was Y=1.240 6 X+ 154.42, in which X was the H-B value and Y was the IC value. Conclusions:SAP patients are mostly in a hypermetabolic state in the early stages of the disease. The IC value is higher than H-B value, and it is recommended to use IC to measure energy consumption in SAP patients.

Objective:To investigate the effects of bromodomain and extraterminal domain (BET) inhibitor JQ1 combined with siPD-L1 on the proliferation and apoptosis of oral squamous cell carcinoma (OSCC) Scc-25 cells and its mechanism.Methods:Scc-25 cells were cultured in vitro and treated with different concentrations of JQ1 (0, 0.2, 1, 5 μmol/L). Cell proliferation was detected by cell count kit-8 (CCK-8) assay; the expression levels of programmed cell death ligand 1(PD-L1) and forkhead box M1(FoxM1) protein were detected by Western blot. Appropriate concentration of JQ1 was selected for subsequent experiments. Scc-25 cells were divided into four groups: control group (without any treatment), siPD-L1 group (transfected with siPD-L1), JQ1 group (added JQ1 after transfected with non-specific siRNA), and combined treatment group (added JQ1 after transfected with siPD-L1). CCK-8 assay was used to detect the proliferation ability of Scc-25 cells in each group. Western blot was used to detect the expression levels of cleaved caspase-3, PD-L1 and FoxM1, and flow cytometry was used to detect the apoptosis rate of cells in each group. Results:With the increase of JQ1 concentration, the proliferation ability of SCC-25 cells and the expression levels of PD-L1 and FoxM1 decreased gradually (all P<0.01). JQ1 concentration of 1 μmol/L had obvious inhibitory effect on cell proliferation and the expression levels of PD-L1 and FoxM1, so JQ1 concentration of 1 μmol/L was selected for subsequent experiments. The proliferation ability of Scc-25 cells, the expression of PD-L1 and FoxM1 proteins in JQ1 group, siPD-L1 group and combination treatment group were significantly lower than those in the control group (all P<0.01), and the expression of cleaved caspase-3 protein and the rate of apoptosis were significantly higher than those in the control group (all P<0.01); Moreover, the effect of the combination treatment group was more significant than that of siPD-L1 group, JQ1 group (all P<0.01). Conclusions:The combination of JQ1 and siPD-L1 could effectively inhibit the proliferation and promotes the apoptosis of OSCC Scc-25 cells, and its mechanism may be related to the suppression of PD-L1 and FoxM1 signaling pathways.

Hyperpyrexia usually refers to body temperature>41 ℃.Hyperpyrexia crisis is a kind of critical and severe condition, which is accompanied by convulsion, coma, shock and multiple organ failure, endangering the life of children and requiring immediate treatment.Pediatric emergency physicians should attach great importance to the clinical evaluation of children with hyperpyrexia, timely reduce the temperature, and prevent the occurrence of hyperpyrexia crisis.This review mainly focused on the definition, common causes, main pathogenesis, clinical manifestations, clinical evaluation and treatments of hyperpyrexia crisis.

OBJECTIVES: To explore the relevant protective and risk factors that affect spontaneous supratentorial large volume intracerebral hemorrhage. METHODS: Clinical data of hospitalized patients with spontaneous supratentorial intracerebral hemorrhage in Xiangya Hospital of Central South University from January 2014 to December 2018 were retrospectively analyzed. According to the amount of intracerebral hemorrhage (≥30 mL), the patients were divided into a large volume intracerebral hemorrhage group (255 cases) and a non-large volume intracerebral hemorrhage group (397 cases). Univariate and multivariate logistic regression analysis for the clinical data from the two groups of patients were performed. RESULTS: Systolic blood pressure, diastolic blood pressure, white blood cell count, neutrophil count, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, calcium ion concentration, and international standard ratio between the large volume intracerebral hemorrhage group and the non-large volume intracerebral hemorrhage group were significantly different (all CONCLUSIONS The occurrence of spontaneous supratentorial large volume intracerebral hemorrhage is the result of combination of multiple factors. The increased white blood cell count, the increased systolic blood pressure, the increased high-density lipoprotein cholesterol, and the increased international standard ratio may increase its risk, while the increased LDL cholesterol and calcium concentration may reduce its risk.
Blood Pressure ; Cerebral Hemorrhage ; Cholesterol, HDL ; Humans ; Retrospective Studies ; Risk Factors

Objective To investigate the relationship between multi‐dimensional myocardial strain and global cardiac function in different stages of cardiac dysfunction in spontaneously hypertensive rats ( SHR ) by two‐dimensional strain echocardiography . MethodsAccording to cardiac function measurements ,SHR of 28 to 102 weeks were divided into 3 groups :Normal group[ Group A , normal left ventricular ejection fraction( LVEF) and left ventricular end‐diastolic pressure( LVEDP) , n ＝13] ,diastolic dysfunction group ( Group B , normal LVEF but increased LVEDP , n ＝24) ,and systolic dysfunction group ( Group C ,decreased LVEF and increased LVEDP , n ＝ 17 ) ,with WKY rats at similar weeks of age as controls ( group a , n ＝ 7 ;group b , n ＝ 12 ; and group c , n ＝ 16 ) . Morphological parameters of left ventricular were measured by echocardiography . Using EchoPac workstation ,systolic peak longitudinal strain ,circumferential and radial strain were calculated at the left ventricular middle levels . Extracellular collagen content was observed histologically . Results Left atrial dimension increased in group B and larger in group C ,and dilated left ventricular and thickened wall were only found in group C .Systolic peak longitudinal strain of group B was significantly lower than group A and group a ( all P ＜ 0 .05 ) ,and deteriorated in group C( P ＜ 0 .05 ) ,while systolic peak circumferential and radial strain and LVEF were only significantly decreased in group C ( all P＜ 0 .05 ) ,w hile there was no significant difference between Group A and Group B( all P ＞0 .05) . Collagen content in endocardial and mid‐layer myocardium increased in group B and C , and increased epicardial collagen occurred in group C . Systolic peak longitudinal strain , circumferential and radial strain were correlated positively with LVEF( r ＝0 .65 ,0 .80 ,0 .80 ,all P ＜0 .01) . Conclusions In SHR ,systolic peak longitudinal strain obtained by echocardiography is decreased in the period of diastolic dysfunction ,w hile the damage of systolic peak circumferential and radial strain leads to the systolic dysfunction .

Objective: To investigate the relationship between multi-dimensional myocardial strain and global cardiac function in different stages of cardiac dysfunction in spontaneously hypertensive rats (SHR) by two-dimensional strain echocardiography. Methods: According to cardiac function measurements, SHR of 28 to 102 weeks were divided into 3 groups: Normal group[Group A, normal left ventricular ejection fraction(LVEF) and left ventricular end-diastolic pressure(LVEDP), n=13], diastolic dysfunction group (Group B, normal LVEF but increased LVEDP, n=24), and systolic dysfunction group (Group C, decreased LVEF and increased LVEDP, n=17), with WKY rats at similar weeks of age as controls (group a, n=7; group b, n=12; and group c, n=16). Morphological parameters of left ventricular were measured by echocardiography. Using EchoPac workstation, systolic peak longitudinal strain, circumferential and radial strain were calculated at the left ventricular middle levels. Extracellular collagen content was observed histologically. Results: Left atrial dimension increased in group B and larger in group C, and dilated left ventricular and thickened wall were only found in group C. Systolic peak longitudinal strain of group B was significantly lower than group A and group a(all P<0.05), and deteriorated in group C(P<0.05), while systolic peak circumferential and radial strain and LVEF were only significantly decreased in group C (all P<0.05), while there was no significant difference between Group A and Group B(all P>0.05). Collagen content in endocardial and mid-layer myocardium increased in group B and C, and increased epicardial collagen occurred in group C. Systolic peak longitudinal strain, circumferential and radial strain were correlated positively with LVEF(r=0.65, 0.80, 0.80, all P<0.01). Conclusions In SHR, systolic peak longitudinal strain obtained by echocardiography is decreased in the period of diastolic dysfunction, while the damage of systolic peak circumferential and radial strain leads to the systolic dysfunction.

Objective To observe the value of three-dimensional constructive interference in steady state (3D-CISS) sequence for displaying anterolateral ligament (ALL) of knee joint.Methods MR scans of right knee joint were performed on 30 healthy volunteers,and the protocol included axial and coronal fat saturation proton density weighted imaging (FS-PDWI) and 3D-CISS sequence.MRP and CPR (reconstructive angles including 0°,30°,60°,90°,120°,150° and 180°) images were generated from of 3D-CISS sequence.The visibility rates of the femoral part,meniscal part,tibial part,meniscal insertion,femoral footprint and tibial footprint of ALL were compared among different protocols.Results The visibility rates of tibial footprint and femoral footprint of ALL on 3D-CISS CPR images were both 96.67％ (29/30),and on 3D-CISS MPR images were both 93.33％ (28/30),all of them were higher than those on FS-PDWI images (all P＜0.017).The visibility rates of tibial part,meniscal part and meniscal insertion of ALL on 3D-CISS CPR images were 96.67％ (29/30),83.33％ (25/30) and 83.33％ (25/30),respectively,and all of them were higher than those on FS-PDWI images (all P＜0.05).There was no statistical difference of visibility rate of femoral part between 3D-CISS CPR images and FS-PDWI images (P=0.095).Conclusion 3D-CISS sequence with CPR can significantly enhance the ability to identify ALL.