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Objective To investigate the effect of glucagon-like peptide 1(GLP-1)receptor agonists exendin-4 on the secretion of cyclophilin A(CyPA)to inhibit atherosclerosis(AS)and vascular calcification in mice role of the process.Methods Twenty ApoE-/-mice were randomly divided into model group and exendin-4 group,10 mice in each group,and were fed with high-fat diet to establish AS model,another 10 wild-type C57BL/6J mice were taken as the control group,and the exendin-4 group was intraperitoneally injected with the GLP-1R agonist exendin-4,1/d,for 8 weeks.After 8 weeks,the ELISA method was used to determine the level of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and CyPA,serum calcium level was detected by methylthymol blue colorimetric method,oil red O staining to detect the development of atherosclerotic plaques in the aorta,HE staining was used to observe the pathological changes of the aorta,Von Kossa staining was used to observe the calcium deposition in the aorta,immunohistochemical staining,Real-time PCR and Western blotting were used to detect the expression levels of aortic RUNX2 and bone morphogenetic protein 2(BMP-2),immunofluorescent staining was used to detect the positive expression of CyPA in aortic tissue.Results Compared with the control group,the serum levels of TG,TC,LDL-C,Ca and CyPA in the model group increased(P<0.05),the atherosclerotic plaque areas of the aorta increased(P<0.05),the aortic wall was thickened significantly and a large number of inflammatory cells were infiltrated,a large amount of calcium deposits were deposited in the aortic parietal membrane,the positive expression area ratio of RUNX2 and BMP-2,the relative mRNA expression of RUNX2 and BMP-2,the relative protein expression of RUNX2 and BMP-2 in aortic tissue all increased(P<0.05),and the red fluorescence of CyPA expression in aortic tissue was enhanced significantly.Compared with the model group,the serum levels of TG,TC,LDL-C,Ca and CyPA in the exendin-4 group decreased(P<0.05),the atherosclerotic plaque areas of the aorta decreased(P<0.05),the thickening of the aortic wall and the infiltration of inflammatory cells were alleviated significantly,the calcium deposition in the aortic wall was reduced,the positive expression area ratio of RUNX2 and BMP-2,the relative mRNA expression of RUNX2 and BMP-2,the relative protein expression of RUNX2 and BMP-2 in aortic tissue all decreased(P<0.05),and at the same time,the red fluorescence of CyPA expression in aortic tissue was weakened significantly.Conclusion GLP-1 receptor agonists exendin-4 can inhibit atherosclerosis and vascular calcification in mice,and the mechanism may be related to the reduction of CyPA secretion.
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ObjectiveTo understand the mortality trends among residents of Fuling District, Chongqing, before and after theCOVID-19 outbreak, and to provide references for the government to formulate disease prevention and control policies and measures. MethodsData on mortality and population in Fuling District from 2017 to 2022 were collected to analyze population mortality and standardized mortality rates, and to compare the changes in the causes of death by year and before and after the pandemic. ResultsFrom 2017 to 2022, the crude mortality rate in Fuling District showed an upward trend (APC=3.04%, P<0.05), while the standardized mortality rate showed a downward trend (APC=-6.47%, P<0.01). The mortality rate of males was higher than that of females (P<0.05), with different age groups having different causes of death composition. The highest proportion of deaths in 0-year-old group was from infectious diseases, maternal and neonatal diseases, and nutritional deficiencies, the highest proportion of deaths in the 1‒24 age group, with the exception of those aged 5‒9, was from injuries, and the main cause of death for residents aged 25 and above was chronic diseases. The mortality rate of mental and behavioral disorders rose from the 13th to the 9th place. According to the epidemic situation of COVID-19, there were no changes in the top five causes of death among the entire population. The motility rate of endocrine, nutritional and metabolic diseases rose from the sixth to the fifth place in male population, and the motility rate of malignant tumor rose from the 3rd to the 2nd place in female population. ConclusionThere are no changes in the top five causes of death among the entire population of Fuling District before and after the COVID-19 outbreak. Chronic diseases remain the main cause of death. It is necessary to control the risk factors for cardiovascular and cerebrovascular diseases such as hypertension, diabetes, and dyslipidemia, and to curb the rising trend of mortality rates from strokes and acute myocardial infarction. For deaths caused by accidental injuries, targeted health education should be conducted for different populations.
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AIM:To clarify the effect of miR-519d-3p on high glucose-induced human retinal microvascular endothelial cells(HRMEC)dysfunction and angiogenesis, and to elucidate the regulatory mechanism of miR-519d-3p on hypoxia inducible factor 1 subunit alpha(HIF-1α).METHODS: The normal glucose(NG)and high glucose(HG)cell models were established by inducing HRMEC with 5 and 30 mmol/L glucose, respectively. Control group: HG cell model was transfected with negative control mimics; mannitol group: the control group was added with 25 mmol/L mannitol; miR-519d-3p overexpression group: HG cell model was transfected with miR-519d-3p mimics; miR-519d-3p combined with HIF-1α overexpression group: HG cell model was co-transfected with miR-519d-3p mimics and HIF-1α overexpression vector. The expression of miR-519d-3p in each group was tested by real-time fluorescence quantitative PCR. The expression of HIF-1α protein in each group was tested by Western blotting. The binding sites between miR-519d-3p and HIF-1α were detected by luciferase reporter gene assay. The cell proliferation of each group was detected by CCK-8. The cell apoptosis of each group was tested by Hoechst 33342 staining. The protein expression of extracellular fluid inflammatory factors tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in each group was tested by ELISA. The formation of new capillary lumen-like structures was detected by tubule formation assay.RESULTS: Compared with the NG, miR-519d-3p expression was significantly reduced in the HG cell model, while HIF-1α protein expression was significantly increased in the HG(all P<0.01). Compared with the control group, HIF-1α protein expression was significantly reduced in the miR-519d-3p overexpression group(P<0.01). The “CGUGAAA” sequence of miR-519d-3p could specifically bind to the “GCACUUU” sequence of HIF-1α 3'-untranslated region(3'-UTR). Compared with the control group, the miR-519d-3p overexpression group showed a significant increase in 24, 48 and 72h absorbance values, a significant decrease in cell apoptotic rate, a significant decrease in the concentrations of TNF-α, IL-1β and IL-6, and a significant decrease in the number of new capillary lumen-like structures(all P<0.01). Compared with the miR-519d-3p overexpression group, the miR-519d-3p combined with HIF-1α overexpression group showed a significant decrease in 24, 48 and 72h absorbance values, a significant increase in cell apoptotic rate, a significant increase in the concentrations of TNF-α, IL-1β and IL-6, and a significant increase in the number of new capillary lumen-like structures(all P<0.01). There was no difference between the control group and mannitol group in the comparison of the above indicators(all P>0.05).CONCLUSION: miR-519d-3p expression is down-regulated while HIF-1α protein expression is up-regulated in high glucose induced HRMEC model. HIF-1α is a target gene of miR-519d-3p. The miR-519d-3p targets HIF-1α to increase cell proliferation and reduce cell apoptosis and inflammation, thereby alleviating high glucose-induced HRMEC dysfunction and inhibiting angiogenesis.
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This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.
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Animales , Masculino , Ratas , Apoptosis , Isquemia Encefálica/metabolismo , Caspasa 3 , Interleucina-1 , Interleucina-6 , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Factor de Necrosis Tumoral alfa/genética , Flavonoides/farmacología , Rhododendron/químicaRESUMEN
OBJECTIVE@#To assess the safety and efficacy of Neuroform Atlas stent used in treatment of unruptured wide-neck intracranial aneurysms.@*METHODS@#Clinical data of 62 patients with unruptured wide-neck intracranial aneurysms undergoing Neuroform Atlas stent-assisted coiling from August 2020 to September 2021 were retrospectively analyzed. There were 64 aneurysms in those 62 patients. Among them, 25 aneurysms were located at the bifurcation of M1 segment on middle cerebral artery, 16 at the anterior communicating artery, 10 at the C7 segment of internal carotid artery, 5 at the C6 segment of internal carotid artery, 4 at the apex of basilar artery, 3 at the A3 segment of anterior cerebral artery, and 1 at the M2 segment of middle cerebral artery. All the patients underwent Neuroform Atlas stent-assisted coiling, including 49 patients with single stent assisted coiling and 15 patients with dual stents assisted coiling (14"Y"style and 1"X"style). After the procedure, the immediate DSA was performed to evaluate the status of aneurysm occlusion and the parent artery patency. The clinical follow-up was performed 3 months after the operation and evaluated based on the modified Rankin Scale(mRS).DSA image was reviewed at 6 months after operation and Raymond grading scale was used to assess the status of aneurysm occlusion and the parent artery patency.@*RESULTS@#A total of 62 patients with 64 aneurysms were all achieved technical success(100%).The immediate post-procedural Raymond scale was assessed, including Raymond Ⅰ in 57 aneurysms(89.1%, 57/64), Raymond Ⅱ in 6 aneurysms(9.3%, 6/64) and Raymond Ⅲ in 1 aneurysm(1.6%, 1/64). The peri-procedural complications rate was 4.8%(3/62), 2 patients developed intraoperative thrombosis and 1 patient suffered from local subarachnoid hemorrhage. Among them, 55 patients obtained 3 months clinical follow-up after operation and all the patients had good outcomes (mRS≤2), 50 patients with 52 aneurysms were followed up with DSA 6 months after operation, including Raymond Ⅰ in 45 aneurysms(86.5%, 45/52), Raymond Ⅱ in 4 aneurysms(7.7%, 4/52) and Raymond Ⅲ in 3 aneurysms(5.8%, 3/52).@*CONCLUSION@#Neuroform Atlas stent for the treatment of unruptured wide-neck intracranial aneurysms has high safety and good efficacy, and has its advantages over other traditional stents.
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Humanos , Aneurisma Intracraneal/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Embolización Terapéutica/métodos , Stents/efectos adversos , Angiografía CerebralRESUMEN
OBJECTIVES@#Serum cystatin C (Cys C) and blood lipid levels are related to the occurrence and development of chronic heart failure (CHF). However, there are few reports on the correlation between blood lipid level and serum Cys C level in patients with CHF. The aim of this study is to explore the correlation between serum Cys C level and blood lipid level in patients with CHF, and to provide valuable reference for clinical diagnosis and treatment of CHF.@*METHODS@#A total of 336 CHF patients who were hospitalized in the Department of Cardiovascular Medicine of Shaanxi Provincial People's Hospital from October 2017 to July 2018 were included and they were divided into a Cys C normal group (n=180) and a Cys C abnormal group (n=156) according to serum Cys C level of the patients. The general data, laboratory indicators, and cardiac ultrasound results were compared between the 2 groups. Pearson correlation analysis was used to detect the correlation between serum Cys C level and blood lipid level and other factors, and the data related to Cys C were further analyzed by multivariate logistic regression.@*RESULTS@#Compared with the Cys C normal group, patients in the Cys C abnormal group had lower left ventricular ejection fraction (LVEF) (P<0.001), older age (P=0.030), higher incidence rate of diabetes and smoking index (P=0.002 and P=0.003, respectively). The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and total bilirubin (TBIL) were higher (all P<0.001), while the levels of high density lipoprotein (HDL), apolipoprotein (Apo) A, and albumin (ALB) were lower (P<0.001, P=0.001, and P=0.003, respectively) in the Cys C abnormal group. Pearson correlation analysis showed that serum Cys C level was negatively correlated with platelet count, HDL, Apo A, ALB, and LVEF. It was positively correlated with smoking index, mean platelet volume, neutrophil ratio, BUN, and TBIL (all P<0.05). The results of multivariate logistic regression analysis showed that the decreased HDL level was a risk factor for the abnormality of serum Cys C in patients with CHF (OR=0.119, P=0.003), while Apo A was not a risk factor for its abnormality (P=0.337).@*CONCLUSIONS@#HDL might be the only blood lipid index associated with abnormal serum Cys C in patients with CHF.
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Humanos , Volumen Sistólico , Cistatina C , Función Ventricular Izquierda , Insuficiencia Cardíaca , Lípidos , Enfermedad CrónicaRESUMEN
Objective: To investigate the clinicopathologic and molecular characteristics of fumarate hydratase (FH) deficient uterine leiomyoma. Methods: Eighty cases of FH deficient uterine leiomyoma were diagnosed from April 2018 to September 2022 in Department of Pathology, Peking University Third Hospital. Sanger sequencing of FH gene exons (exon 1-10) were performed on tumor tissues and matched non-tumor tissues/peripheral blood for all cases. FH immunohistochemistry were performed in 74 cases; S-(2-succino)-cysteine (2SC) were also detected by immunohistochemistry in five cases. Results: Patients' age ranged from 18 to 54 (36.0±7.5) years, with more than 60% exhibiting clinical symptoms of multiple and large leiomyomas (the median diameter was 70 mm). More than four histologic features, including staghorn vasculature, alveolar-pattern edema, bizarre nuclei, oval nuclei arranged in chains, prominent eosinophilic nucleoli with perinucleolar haloes and eosinophilic intracytoplasmic globules were observed in 98.5% (67/68) patients. The immunohistochemical sensitivity of FH and 2SC were 97.3% and 100%, respectively. Based on the Sanger sequencing results, the cases were divided into germline variant group (31 cases), somatic variant group (29 cases) and no variant group (20 cases). Sixty-nine percent (20/29) of the patients with FH germline variation had clear family history. Conclusions: Clinical features, histological morphology, FH and 2SC immunohistochemistry and Sanger sequencing have their own significance and limitations in differential diagnosis of FH deficient uterine leiomyoma. In clinical practice, the above information should be fully integrated and studied for accurate pathologic diagnosis and selection of patients with FH germline variation.
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Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Fumarato Hidratasa/genética , Neoplasias Uterinas/patología , Leiomioma/patología , Mutación de Línea Germinal , Diagnóstico Diferencial , Leiomiomatosis/patología , Carcinoma de Células Renales/diagnósticoRESUMEN
Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
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Humanos , Alérgenos , Pueblo Asiatico , Desensibilización Inmunológica/efectos adversos , Hipersensibilidad/epidemiología , Estudios RetrospectivosRESUMEN
Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
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Humanos , Alérgenos , Pueblo Asiatico , Desensibilización Inmunológica/efectos adversos , Hipersensibilidad/epidemiología , Estudios RetrospectivosRESUMEN
Objective: To explore the effects of pregnancy complicated with moyamoya disease on maternal and fetal outcomes. Methods: The general clinical data and maternal and fetal outcomes of 20 pregnancies of 15 patients with moyamoya disease admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2022 were retrospectively analyzed. Results: (1) General information: among the 20 pregnancies of 15 clearly diagnosed pregnant women complicated with moyamoya disease, 12 were diagnosed before pregnancy (60%, 12/20), 3 were diagnosed during pregnancy (15%, 3/20), and 5 were diagnosed during puerperal period (25%, 5/20). There were 7 cases of primipara (35%, 7/20) and 13 cases of multipara (65%, 13/20). (2) Pregnancy complications and maternal and infant outcomes: among the 20 pregnancies of 15 pregnant women with moyamoya disease, there were 9 pregnancy complications (45%, 9/20), including 5 gestational hypertension (25%, 5/20), 2 severe pre-eclampsia (10%, 2/20), 1 hyperlipidemia and 1 gestational diabetes mellitus (5%, 1/20). There were 2 case of drug abortion in the first trimester, 3 cases of labor induction in the second trimester, and 15 cases of delivery during the third trimester. All the 15 deliveries were cesarean section, of which 11 (11/15) were cesarean sections with medical indications, and 4 (4/15) were cesarean sections caused by personal factors. General anesthesia was used in 5 cases (5/15), epidural block anesthesia in 7 cases (7/15), and combined spinal and epidural anesthesia in 3 cases (3/15). The median gestational age of 15 neonates was 37.2 weeks (34.0 to 40.8 weeks), with 10 cases (10/15) were full-term infants, and 5 (5/15) were preterm infants (3 of which were associated with hypertensive disorder complicating pregnancy). The birth weight of 15 neonates was (2 853±454) g. Four neonates were admitted to neonatal intensive care unit (NICU), of which 3 cases were admitted to NICU due to premature delivery and 1 case was admitted to NICU due to neonatal jaundice. There was no neonatal asphyxia or death. All neonates were followed up from 4 months to 6 years after birth, and all grew well. (3) Neurological symptoms during pregnancy: 8 cases (40%, 8/20) had neurological symptoms during pregnancy, and 6 cases (30%, 6/20) had hemorrhagic symptoms, of which 3 cases occurred during the puerperal period (3/6). There were 2 cases of ischemic symptoms (10%, 2/20), all of which occurred during the puerperal period (2/2). (4) Analysis of factors related to the occurrence of cerebral hemorrhage: the incidence of cerebral hemorrhage in patients with moyamoya disease diagnosed before pregnancy was significantly lower than that in those without a clear diagnosis, and the incidence of cerebral hemorrhage in women with moyamoya disease was lower than that in primipara (all P<0.01). The incidence of cerebral hemorrhage in moyamoya patients without hypertensive disorder complicating pregrancy was lower than that in patients with hypertensive disorder complicating pregrancy, but the difference was not statistically significant (P>0.05). Conclusions: Pregnancy combined with moyamoya disease has adverse effects on maternal and infant outcomes, and the incidence of pregnancy complications increases. Cerebral hemorrhage occurres in prenatal and puperium, while cerebral ischemia occurres mainly in puperium.
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Lactante , Embarazo , Recién Nacido , Femenino , Humanos , Resultado del Embarazo , Cesárea , Mujeres Embarazadas , Recien Nacido Prematuro , Enfermedad de Moyamoya/complicaciones , Estudios Retrospectivos , Complicaciones del Embarazo/epidemiología , Hemorragia CerebralRESUMEN
OBJECTIVE@#The activation of Janus kinase (JAK) and signal transducers and activators of transcription (STAT) plays an important role in the prognosis and targeted therapy of ovarian high-grade serous carcinoma (HGSC). Utilizing simple and practicable technique, this study aimed to evaluate the activation of JAK/STAT signaling pathway in ovarian HGSC patients, and investigated the correlation between the activation of JAK/STAT signaling pathway and the prognosis of the HGSC patients.@*METHODS@#We performed immunohistochemistry of phosphorylated STAT3 (pSTAT3) and phosphorylated STAT5 (pSTAT5) on paraffin imbedded slides of 73 ovarian HGSC patients, and evaluated the expression level and range of both markers. According to the grading score of the immunostaining of pSTAT3 and pSTAT5, we divided the 73 ovarian HGSC cases into STAT3 low/high expression and STAT5 low/high expression groups, and analyzed the prognosis of the patients in different groups, in order to explore the relationship between the expression of pSTAT3 and pSTAT5 proteins and the prognosis of the HGSC patients.@*RESULTS@#Some of the ovarian HGSC cases showed high expression of pSTAT3 and pSTAT5 protein level, which was related to the poorer prognosis of the HGSC patients. There was a significant difference in the expression level of pSTAT3 and pSTAT5 between the patients with better prognosis (survival time ≥3 years) and poorer prognosis (survival time < 3 years). The patients with higher protein expression of pSTAT3, pSTAT5 or both markers might have poorer prognosis, with significant shorter progression-free survival time and overall survival time (P < 0.001).@*CONCLUSION@#Immunostaining of pSTAT3 and pSTAT5 proteins might be helpful to evaluate and predict the prognosis of the ovarian HGSC patients, and to identify the patients who might have higher chances to respond to the STAT inhibitors and anti-angiogenesis therapy.
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Humanos , Pronóstico , Factor de Transcripción STAT5/metabolismo , Neoplasias , Transducción de Señal , InmunohistoquímicaRESUMEN
Objective:Based on the academic papers published by Peking University First Hospital in the past 11 years, this paper analyzes the international cooperation in scientific research and aims to provide reference for the formulation of future scientific research programs.Methods:Bibliometric analysis was used to analyze the current status and trend of international cooperation, the journal distribution and preferences, as well as the subject distribution and participation.Results:It is found that the international cooperation has made some progress in recent years, however, the international cooperation rate is basically the same, while the level of cooperation should be improved. The level of international cooperation varies among different disciplines, the more strong disciplines are higher than others. Most research are concentrated in clinical medicine, basic research and other interdisciplinary research need to be strengthened.Conclusions:For the next step, we should improve the top-level design of international cooperation, strengthen the international cooperation in basic research and interdisciplinary research, and promote the development of discipline construction.
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Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.
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Femenino , Humanos , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Reparación de la Incompatibilidad de ADN/genética , Neoplasias Endometriales/patología , Inestabilidad de Microsatélites , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Tipificación MolecularRESUMEN
Aim To investigate the inhibition effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-l, 4-dione ( DMDD) on renal tubular epithelial cell HK-2 endo¬plasmic reticulum stress and inflammatory responses induced by high glucose. Methods HK-2 cells were cultured in vitro and divided into normal group, high glucose group, endoplasmic reticulum stress inhibitor 4-PBA group (5 mmoL • L ) , DMDD high, medium and low dose groups (8,4,2 μmol • L
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Objective To investigate the effect of cholesterol on the proliferation and differentiation of neural stem cells (NSCs) in ob/ob obese mice, and to explore the possible mechanism of central nervous systym dysfunction caused by obesity. Methods Selected 64-month-old ob/ob and wild type (WT) mice, and cell proliferation antigen (Ki67) and doublecortin (DCX) immunofluorescenct staining were used to detect ob/ob mice lateral ventricle subventricular zone (SVZ) neurogenesis level. Cultured SVZ NSCs isolated from 184-month-old ob/ob and WT mice, and BrdU incorporation experiment and β-III-tubulin (Tuj1) immunofluorescent staining were employed to detect the self-renewal and differentiation ability of NSCs. Matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI- MS)was used to detect the lipid distribution in 4-month-old ob/ob and WT mice brain tissues, and measure the changes of cholesterol(ST) content and the expression genes related to cholesterol synthesis. Cultured 15 WT postnatal day 0(P0) mouse SVZ NSCs in vitro and electrotransfected with the small interfering RNA(siRNA) sequence of cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (Hmgcr) verified the knockdown efficiency, to detecte the effect of Hmgcr gene knockdown on NSCs by BrdU incorporation experiment and Tuj1 immunofluorescent staining. Results Compared with the WT mice, the number of Ki67
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There is a commonality between jingjin (muscle region of meridian) and the fascial network for coordinating the balance in the body. The occurrence and the progression of tumor may disrupt the overall coordination between the fascial network and jingjin directly or indirectly, thereby, the impairment of this coordination may result in cancer pain. Rooted on the theory of overall balance of the fascial network, and combined with understanding of pain in jingjin theory, professor HUANG Jin-chang emphasizes the importance of "relaxing the knot" in treatment of cancer pain. It is recommended to select the fascia reaction point as the target point, in accordance with the principle of balance adjustment and apply various acupuncture and moxibustion therapies, such as Fu's subcutaneous needling, small-needle scalpel therapy, fire needling, and moxibustion.
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Humanos , Moxibustión , Dolor en Cáncer , Puntos de Acupuntura , Terapia por Acupuntura , Fascia , Neoplasias/terapiaRESUMEN
The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.
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Development of extramural health care for chronic wounds is still in its infancy in China, and thus it is urgent and vital to establish a correct concept and practicable principles. The authors reviewed recent domestic and international literature and summarized the following treatment procedures and principles for extramural health care of chronic wounds. (1) The patient needs to do self-assessment of the wound by using available simple methods; (2) The patient consults with professional physicians or nurses on wound care to define the severity and etiology of the non-healing wound; (3) Professionals evaluate the existing treatment strategies; (4) Etiological treatments are given by professionals; (5) Patients buy needed dressings via the more convenient ways from pharmacies, e-commerce platform or others; (6) Professionals provide a standardized and reasonable therapeutic plan based on the patient's wound conditions; (7) Both professionals and the patient pay attention to complications to prevent adverse outcomes; (8) Professionals strengthen the public education on wound care and integrated rehabilitation. This review expected to provide new perspectives on the therapeutic strategies for chronic wounds in an extramural setting.
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Humanos , Cicatrización de Heridas , Instituciones de Salud , Atención a la Salud , China , Heridas y Lesiones/terapiaRESUMEN
To date, there is little information about the demography of vasectomy reversal (VR) patients or the factors currently influencing VR effectiveness in China, especially after the universal two-child policy was released in 2015. In this research, demographic data and perioperative medical records of VR patients were extracted from seven major hospitals in different provinces or municipalities of China. Meanwhile, a telephone survey of the patients was conducted to collect follow-up information. Eventually, 448 VR cases from the past 13 years were included. The results were analyzed by stratified comparison to investigate factors that can influence postoperative vas deferens patency and pregnancy rate. Appropriately statistical methods were used, and all of the protocols were approved by the Ethics Committees of the institutes in this research. The results showed that the annual operation volume of VR quadrupled after the two-child policy was implemented. Nonmicrosurgery and a long duration of vasectomy were significantly associated with a lower patency rate. A follow-up survey showed that the general postoperative pregnancy rate was 27.2%. For female partners over the age of 35 years, the postoperative pregnancy rate showed a more severe decline, but only 35.5% of them had been given a fertility examination before their husbands' VR surgery. Our work revealed that more patients in China have been demanding VR in recent years. High-quality microsurgery and a short duration of vasectomy are crucial for restoring patency by VR. Clinical andrologists should perform a preoperative fertility evaluation of the patients' female partners.
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Masculino , Embarazo , Humanos , Femenino , Adulto , Vasovasostomía , Estudios Retrospectivos , Conducto Deferente/cirugía , Vasectomía , China/epidemiologíaRESUMEN
OBJECTIVE@#To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD).@*METHODS@#Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.@*RESULTS@#The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05).@*CONCLUSIONS@#YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.