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Objective To investigate the distributions of vitamin K1 and K2 in infants of different age groups by comparing the serum levels of vitamin K1 and K2 in them.Methods 1177 infants from 0 to 3 months were divided into 6 age groups.Those born/treated in the subject units(pediatrics,neonatology,child health care,obstetrics)were selected as the study subjects and grouped by age:0~3 days(591 cases),4~7 days(255 cases),8~5 days(104 cases),1 month(118 cases),2 months(40 cases),and 3 months(69 cases).General data of the infants were collected,and the serum vitamin K1 and K2 levels were determined by HPLC-mass spectrometry(LC-MS)on a unified platform,and analyzed from the distribution of vitamin K1 and K2 at different ages.Results The distributions of vitamin K1 and K2 levels were statistically significant(P<0.001);newborns were highly vulnerable to vitamin K1 deficiency,and vitamin K2 deficiency was higher than vitamin K1 with age.Conclusion Maintaining the normal growth of vitamin K1 and K2 is crucial for the normal growth and development of infants of all ages,so we should pay close attention to the monitoring and supplement of vitamin K1 and K2.
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Objective:To investigate the efficacy and safety of atorvastatin combined with indobufen in the treatment of elderly patients with diabetic kidney disease (DKD) complicated with large atheromatous ischemic stroke (LAA-IS) during convalescence.Methods:The clinical data of 102 elderly patients with DKD complicated with LAA-IS during convalescence from September 2018 to April 2022 in Baoding Second Central Hospital were retrospectively analyzed. Among them, 51 patients were treated with atorvastatin combined with indobufen (observation group), 51 patients were treated with atorvastatin combined with aspirin (control group), and both groups were treated continuously for 6 months. The prethrombotic state indexes, neurological function and quality of daily life, carotid artery ultrasound indexes, renal fibrosis indexes before treatment and after treatment were compared between two group. The prethrombotic state indexes included arachidonic acid (AA) and adenosine diphosphate (ADP) induction platelet aggregation rate, fibrinogen (FIB), protein C; the National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function, and the modified Barthel index (MBI) was used to evaluate the quality of daily life; carotid artery ultrasound indexes included carotid artery intima-media thickness (IMT) and maximum plaque area; the renal fibrosis indexes included transforming growth factor-β 1 (TGF-β 1), matrix metalloproteinase-9 (MMP-9), hyaluronic acid and platelet derived growth factor-BB (PDGF-BB). The adverse reactions were recorded. Results:There were no statistical differences in the all indexes before treatment between two groups ( P>0.05). In two groups, compared before treatment, the AA induction platelet aggregation rate, ADP induction platelet aggregation rate, FIB, NIHSS score, IMT and maximum plaque area after treatment were significantly lower, the protein C and MBI score were significantly higher, and there were statistical differences ( P<0.01); but there were no statistical differences after treatment between two groups ( P>0.05). The TGF-β 1, MMP-9, hyaluronic acid and PDGF-BB after treatment in two groups were significantly lower than before treatment, and the indexes in observation group were significantly lower than those in control group: (39.46 ± 6.89) μg/L vs. (45.04 ± 8.20) μg/L, (278.46 ± 49.39) μg/L vs. (327.30 ± 57.28) μg/L, (102.37 ± 20.62) μg/L vs. (116.84 ± 24.97) μg/L vs. (25.26 ± 4.45) μg/L vs. (28.13 ± 5.08) μg/L, with statistically significant differences( P<0.01). The incidence of adverse reactions in observation group was significantly lower than that in control group: 7.84% (4/51) vs. 23.53% (12/51), and there was statistical difference ( P<0.05). Conclusions:Compared with atorvastatin combined with aspirin, atorvastatin combined with indobufen in elderly patients with DKD complicated with LAA-IS during convalescence has the same effect in improving the related indicators of prethrombotic state, reducing neurological function deficit, improving the ability of daily living, and reversing carotid atherosclerosis. However, atorvastatin combined with indobufen can further protect renal function with higher safety.
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Background and Purpose:Primary Ewing sarcoma of the thoracic wall(PEST)is a rare extraosseous Ewing sarcoma that occurs in the chest wall or thoracic cavity with a short survival,poor prognosis and a high rate of recurrence.Early diagnosis and treatment are the best way to prolong survival time since the cause of PEST is not clear.This study aimed to explore the clinicopathologic characteristics,diagnosis and treatment of PEST to improve clinical understanding of this disease.Methods:A total of 21 cases with PEST were treated at The First Affiliated Hospital of Soochow University,and reviews were published from 2018 to 2023.Clinical data,pathological features,treatment and follow-up of the patients were analyzed respectively.The survival was from the start of treatment to the death of the patient or the end of the follow-up.Cumulative survival was estimated by Kaplan-Meier method.Results:A total of 21 cases with PEST(male/female ratio,13∶8;sites of left/right chest ratio,6∶15;median age,20 years;mean age,28 years;median diameter of the tumor,8.0 cm;mean diameter of the tumor,18.1 cm)met the inclusion criteria.65.2%of the patients presented with the pain in the ipsilateral thoracic and abdominal area.In 47.1%of cases,the ipsilateral ribs were invaded with pleural effusion.Pathological morphology microscopy showed most tumor cells were tightly packed or lobular distribution of small blue round cells.In immunohistochemistry,CD99 and vimentin were positive in 100%and 80%cases respectively while neurogenic markers were expressed to varying degrees.EWSR1 separated signal was found by fluorescence in situ hybridization(FISH),and the EWSR1-FLI1 fusion was detected by next-generation sequencing(NGS)in two cases at our hospital.Two cases received neoadjuvant chemotherapy,10 patients received chemotherapy and radiotherapy after operation,5 cases were treated with radiotherapy only,1 case received surgery only,and 3 cases had no surgical data.A total of 14 cases were followed up for 3-38 month while 7 cases were lost to visit.Cumulative survival correlates with age at disease.The mean survival time was 19.98 months,and the median survival time was 13.00 months.Conclusion:Young males,right chest and the mass larger than 8 cm are more often found.Most cases can be initially diagnosed using histopathology and immunohistochemical markers.FISH or NGS of the EWSR1 gene test are a highly accurate method for diagnosis.The prognosis of PEST is extremely poor,and the cumulative survival rate is negatively correlated with the age of onset.Surgery,radiotherapy and chemotherapy are the main treatments for this disease.
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Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4%),121 cases were middle-onset group(31.8%),and 60 cases were late-onset group(15.8%).There were 26.6%of patients in the early-onset group in-itially diagnosed as depression,23.1%in the middle-onset group,and 11.7%in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.
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Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.
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ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription (YHP) on the learning and memory of accelerated aging model mice, as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups, including the model group, low-dose YHP group, high-dose YHP group, and donepezil group. Additionally, 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group, each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg-1 and 12.48 g·kg-1, while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial (MG) polarization marker inducible nitric oxide synthase (iNOS) and M2 MG polarization marker arginase-1 (Arg-1) in the hippocampus region. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of pro-inflammatory factor interleukin 1β (IL-1β) and anti-inflammatory factor transforming growth factor-β1 (TGF-β1). Furthermore, Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 (Aβ1-42) along with triggering receptor expressed on myeloid cells 2 (TREM2)/nuclear factor kappa B (NF-κB) signaling pathway-related proteins TREM2, phospho (p)-NF-κB p65, and phospho-inhibitory kappa B kinase β (IKKβ) in the hippocampus. ResultCompared with the control group, the model group exhibited a significantly prolonged escape latency (P<0.01), a significant reduction in neuron-specific nuclear protein (NeuN) expression in the hippocampus, a significant increase in iNOS expression in MG, and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased, while the TGF-β1 content was significantly decreased. Additionally, there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions (P<0.05, P<0.01). However, no significant changes were observed in escape latency, times of crossing the platform, and hippocampal NeuN expression in the YHP treatment control group. Conversely, iNOS expression in MG as well as the hippocampal p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions were significantly decreased. Furthermore, TREM2 expression was significantly increased (P<0.05, P<0.01). In comparison to the model group, the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform (P<0.05, P<0.01). In the high-dose YHP group, the escape latency was significantly shortened (P<0.05). In the low-dose YHP group, high-dose YHP group, the expression of NeuN in the hippocampus was significantly increased, the expression of iNOS in MG was significantly decreased, and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased, while the TGF-β1 content was significantly increased. Furthermore, the expression of TREM2 in the hippocampus was significantly increased, and the expressions of p-NF-κB p65, p-IKKβ, and Aβ1-42 were significantly decreased (P<0.01). ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway, reduce the release of neuroinflammatory factors, protect hippocampal neurons, and reduce the deposition of Aβ1-42, and finally delay the occurrence of learning and memory decline in SAMP8 mice.
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OBJECTIVES@#To explore the relationship of triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), and triglyceride-glucose-waist circumference index (TyG-WC) with blood pressure abnormalities in adolescents, providing theoretical basis for the prevention and control of hypertension in adolescents.@*METHODS@#A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys, physical measurements, and laboratory tests. Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG, TyG-BMI, and TyG-WC with blood pressure abnormalities in adolescents.@*RESULTS@#Multivariable logistic regression analysis revealed that after adjusting for confounding factors, the groups with the highest quartile of TyG, TyG-BMI, and TyG-WC had 1.48 times (95%CI: 1.07-2.04), 3.71 times (95%CI: 2.67-5.15), and 4.07 times (95%CI: 2.89-5.73) higher risks of blood pressure abnormalities compared to the groups with the lowest quartile, respectively. Moreover, as the levels of TyG, TyG-BMI, and TyG-WC increased, the risk of blood pressure abnormalities gradually increased (P<0.05). A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.002). Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearit =0.232), and between TyG-WC and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.224).@*CONCLUSIONS@#Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents, with linear or non-linear dose-response relationships.
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Adolescente , Humanos , Presión Sanguínea , Índice de Masa Corporal , Hipertensión/etiología , Glucosa , TriglicéridosRESUMEN
Clinical data of 102 patients with premature ovarian failure admitted to Zhang Zhongjing Hospital from December 2018 to December 2021 were retrospectively analyzed. Fifty-one patients received (control group), and another 51 patients received Chinse medicine Kuntai capsule in addition to sequential estrogen progesterone therapy(study group); both groups were treated for 3 menstrual cycles. After treatment, the total effective rate of the study group was higher than that of the control group (94.1% (48/51) vs. 72.6% (37/51), χ2=4.07, P=0.044). After treatment, the proportion of patients with mild Kupperman score and serum estradiol level in both groups were increased, and the proportion in study group was higher than that in the control group. The proportion of patients with moderate and severe Kupperman score and the total score decreased after treatment in both groups, and the proportion of patients with moderate Kupperman score in the study group was lower than that in the control group. Serum luteinizing hormone and folliclestimulating hormone levels were significantly decreased, and the levels in study group were lower than those in the control group. The levels of resistance index and PI were significantly decreased after treatment in both group and the study group decrease more markedly (all P<0.05). The peak systolic flow velocity level was increased after treatment in both groups and the study group increased more markedly (all P<0.05). It is suggested that the application of Chinese medicine Kuntai capsule combined with sequential estrogen progesterone therapy can effectively improve the clinical therapeutic effect, stabilize sex hormones, uterine microcirculation and effectively alleviate the condition of patients with premature ovarian failure.
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Objective:To explore the influence of interpregnancy interval (IPI) on pregnancy complications in multiparas.Methods:This was a retrospective cohort study involving 7 669 singleton parturients who delivered at ≥28 gestational weeks in the Affiliated Hospital of Southwest Medical University between December 2015 and December 2020 and had given birth in the third trimester before. Clinical data were collected, including the baseline characteristics, pregnancy complications, gestational weeks at delivery, and neonatal birth weight. According to the IPI, these women were divided into five groups: <12 months ( n=350), 12-<24 months ( n=945), 24-<60 months ( n=2 544), 60-<120 months ( n=2 478), and ≥120 months ( n=1 352). Based on the recommendation of the World Health Organization, pregnant women with an IPI of 24-<60 months were the control group. A multivariate logistic model was used to adjust for confounders and calculate the risks of pregnancy complications, including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). The influences of maternal age and previous delivery mode on the associations between IPI and maternal complications were analyzed. Analysis of variance (ANOVA), Chi-square test, and Cochran-Mantel-Haenszel Chi-square test were used for statistical analysis. Results:Compared with the control group, the incidence of GDM and HDP increased in the 60-<120 months group ( OR=1.23, 95% CI: 1.01-1.48 and OR=1.47, 95% CI: 1.13-1.92) and ≥120 months group ( OR=1.37, 95% CI:1.07-1.78 and OR=1.92, 95% CI: 1.39-2.64); the risks of uterine rupture/postpartum hemorrhage and placental abruption increased in the <12 months group ( OR=1.54, 95% CI: 1.01-2.34) and 12-<24 months group ( OR=2.38 95% CI: 1.13-5.02), respectively. In the 60-<120 months group, the risk of GDM increased only in non-elderly women (adjusted OR=1.71, 95% CI: 1.36-2.14), so did the risks of GDM and HDP in the ≥120 months group (adjusted OR=3.11, 95% CI: 2.10-4.62 and adjusted OR=1.81, 95% CI: 1.12-2.91). Among women who had undergone a previous cesarean section, the risk of GDM increased in the ≥120 months group (adjusted OR=1.35, 95% CI: 1.00-1.81). In the 60-<120 months group and ≥120 months group, the risk of HDP increased in postpartum women (adjusted OR=1.79, 95% CI: 1.08-2.95 and adjusted OR=3.32, 95% CI: 1.91-5.77). Conclusion:IPI≥60 months is a risk factor for GDM and HDP, and the associations between IPI and maternal complications are influenced by maternal age.
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Objective:To investigate any effect of repeated transcranial magnetic stimulation (rTMS) on the expression of P2X7 receptor (P2X7R) and glial fibrillary acid protein (GFAP) in the prefrontal cortex and hippocampus of mice modeling depression.Methods:Thirty C57BL/6 mice were divided into a control group ( n=10) and a depression group ( n=20). The mice of the control group were raised in group (five mice per cage), while those of the depression group were kept alone for six weeks to induce depression. Among them, 16 were successfully modeled and randomly divided into a model group ( n=8) and an rTMS group ( n=8). The rTMS group received five sessions per week of 10Hz rTMS for 4 weeks. Any changes in depression-like behavior were observed and the expression of P2X7R and GFAP in the prefrontal cortex and hippocampus was measured. Results:Compared to the control group, a significant decrease was observed in the sucrose consumption rate in the sucrose preference test, in the distance moved in the open field test and in the expression of GFAP protein. But there was a significant increase in the immobile time in the tail suspension test and in the expression of P2X7R protein in the prefrontal cortex and hippocampus in the model group. At the conclusion of the experiment the differences in the sucrose consumption rate, the distance moved, GFAP protein expression, immobile time and P2X7R protein expression between the rTMS and the model group were all statistically significant.Conclusion:rTMS can reduce depression-like behavior, at least in mice. That may be related to inhibiting P2X7R expression and promoting GFAP expression in the prefrontal cortex and hippocampus.
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Objective:To explore any effect of upper limb swing training guided by rhythmic auditory stimulation (RAS) on the walking ability of stroke survivors.Methods:Eighty stroke survivors were randomly divided into an observation group and a control group. Both groups received conventional rehabilitation treatment, including neuromuscular facilitation, muscle strength training, balance training and gait training, but the observation group was additionally provided with RAS-guided upper limb swing training for 20min once a day, 5d per week for 6 weeks. Before and after the intervention, balance and lower limb function were quantified in both groups using Holden′s walking function classification, the Fugl-Meyer lower extremity motor function scale (FMA-LE), the Berg Balance Scale (BBS) and the 10m walk test (10MWT). Limits of stability were also quantified.Results:After the treatment, the average Holden, FMA-LE and BBS scores, as well as the average 10MWT time were significantly better in the observation group than in the control group. The average stability limits and their maintenance were also superior.Conclusion:RAS-guided upper limb swing training can improve the gait, walking ability, walking stability, walking speed and balance of stroke survivors.
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Objective:To document any effect of clinical rehabilitation pathway management on intubation time, dysfunction and medical expenditure associated with tracheotomy after a stroke.Methods:A total of 154 stroke survivors undergoing tracheotomy were randomly divided into an observation group and a control group, each of 77. Both groups were given routine rehabilitation, while the observation group was additionally provided with clinical rehabilitation pathway management during the rehabilitation intervention. Kaplan-Meier analysis was performed before the experiment and after 2, 4 and 6 weeks of treatment. Clinical pulmonary infection scores (CPISs), scores on the Chelsea Physical Function Assessment Scale (CPAx) and hospitalization cost were compared between the two groups.Results:The median extubation time of the observation group (2d) was significantly shorter than that of the control group (10d). After 2, 4 and 6 weeks of treatment, the average CPIS scores of the observation group were in each case significantly lower than those before treatment and the control group′s averages at the same time points, even though after 4 and 6 weeks of treatment the control group′s average CPIS scores had improved significantly. After 2, 4 and 6 weeks of treatment, the average CPAx scores of the observation group were significantly higher than those before treatment and better than the control group′s averages, even though the control group too had improved significantly compared with before the treatment. Hospitalization days, total hospitalization cost, antibiotic cost and laboratory examination cost of the observation group were, on average, significantly lower than those of the control group.Conclusion:Rehabilitation path management can shorten the period of intubation, prevent pulmonary infections, relieve dysfunction, and reduce medical expenses for stroke survivors after a tracheotomy. It is worthy of clinical promotion.
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AIM: To investigate the expression level of inflammatory factors of aqueous humor before trabeculectomy in binocular chronic primary angle-closure glaucoma(CPACG)and its correlation with postoperative filtration bleb and intraocular pressure.METHODS: A total of 15 cases(30 eyes)with binocular CPACG who admitted to the Affiliated Eye Hospital of Nanjing Medical University from September to December 2021 and received trabeculectomy were selected. The surgery interval between two eyes was 7d, and the preoperative expression levels of monocyte chemoattractant protein-1(MCP-1), interleukin-17(IL-17), transforming growth factor-β(TGF-β), and interferon-γ(IFN-γ)of the aqueous humor in both eyes were respectively detected by enzyme-linked immunosorbent assay(ELISA). Furthermore, the intraocular pressure(IOP)and the morphology of filtering blebs at 1mo after surgery were measured.RESULTS: The concentrations of MCP-1, IL-17, TGF-β, and IFN-γ in aqueous humor from the first eye before surgery were 330.4±46.2, 357.3±46.9, 2347.5±363.8 and 527.7±101.6pg/mL respectively, and those concentrations in aqueous humor from the fellow eye were 298.2±40.7, 309.1±53.5, 1938.3±426.0 and 628.2±104.9pg/mL respectively. The preoperative expression levels of inflammatory factors of aqueous humor in both eyes were statistically significant(P≤0.05). Furthermore, the expression levels of IL-17 and TGF-β in the aqueous humor of patients with CPACG correlated with IOP and the height of filtering blebs at 1mo after surgery(P&#x003C;0.05).CONCLUSION: There may be changes in the expression levels of inflammatory factors of aqueous humor in the fellow eye after surgery of the first eye. Moreover, the preoperative expression level of IL-17 and TGF-β in aqueous humor possibly related to postoperative IOP and the height of filtering bleb.
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Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.
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Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Células HeLa , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Mutación , Transducción de Señal , Luciferasas/uso terapéutico , Hipoxia/genética , ARN Mensajero , Lípidos/uso terapéutico , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
This study analyzed the changes in macrophage phagocytosis after Echinococcus multilocularis protoscoleces(PSC)infection.The distribution of macrophages in hepatic alveolar echinococcosis patients was analyzed by immunohisto-chemistry.PD-1 blockade,PSCs and macrophages were co-cultured to analyze macrophage phagocytosis and the expression lev-els of CD47 and PD-1.Macrophages labeled by CD68 aggregated in close live tissue from the lession of alveolar echinococcosis patients.PSC infection resulted in lower intensity of Escherichia coli and higher expression of CD47 and PD-1 than observed in the control group(P<0.001).The intensity of Escherichia coli increasedin the PD-1 blockade group after PSC infection(q=40.63,P<0.05).PD-1 blockade restored macrophage phagocytosis after PSC infection.
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The purpose of this study was to investigate the epidemiological characteristics and risk factors of influenza in Hainan province,to provide evidence to support influenza prevention and control efforts.Pathogen monitoring data of influenza-like illness(ILI)in six national sentinel hospitals in Hainan province from 2013 to 2021 were analyzed in SPSS 20.0 software.A total of 50 415 ILI cases were detected during the 2013-2021 season,of which 5 581 were positive for influenza viruses,with a positivity rate of 11.07%.The dominant strains were type B,type A(H1N1)pdm09 and type A(H3N2).The positivi-ty rate of influenza virus was highest in people 5-14 years of age(17.56%)and lowest in people 0-4 years of age(7.32%).Influenza activity showed both a summer peak and a winter-spring peak in the 2014-2016,2017-2018 and 2019-2020 sea-sons,and was concentrated in April to September,with a maximum peak of 53.64%,and in November to March of the next year,with a peak of 47.30%.The 2013-2014,2016-2017 and 2018-2019 seasons showed only a winter-spring peak concen-trated between October and March of the next year,with a maximum peak of 54.17%,but no obvious summer peak.The pre-dominant influenza viruses during the eight surveillance seasons varied among H1N1,H3N2 and type B.The positive detection rate of influenza virus steeply declined during the 2020-2021 season:the positive detection rate was only 0.25%,and no obvi-ous epidemic period was observed.The intensity of influenza epidemic varied among monitoring years,and the dominant strains changed rapidly in Hainan Province.People 5-14 years of age were the key population affected.Summer,winter and spring were the key periods for influenza prevention and control.Etiological surveillance of influenza should continue to be strength-ened,the roles of health education and publicity should be emphasized,and the dual measures of influenza vaccination and non-drug intervention should be actively promoted to decrease the occurrence of influenza.
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Objective:To analyze the clinical characteristics and management strategy of carotid web (CW)-related stroke and improve the understanding of CW.Methods:The clinical data of 6 patients with CW-related stroke treated at Xuanwu Hospital, Capital Medical University, from January 2018 to September 2022 were retrospectively analyzed. Relevant data included clinical manifestations, bronchial magnetic resonance imaging (MRI), CT angiography (CTA)/digital subtraction angiography (DSA), carotid ultrasonography, and transcranial color-coded Doppler sonography (TCCD). Treatments and follow-ups were also reported.Results:All 6 patients were middle-aged or young, without traditional risk factors for cerebrovascular disease. The male-to-female ratio was 2∶4. All patients had recurrent strokes, with a score of 2-4 on the National Institutes of Health Stroke Scale at the time of onset. Head MRI showed 5 patients with cerebral infarction in the middle cerebral artery supply area; 1 patient had no intracranial infarction. No significant stenosis of the vessels at the site of the CW was observed in any of the 6 patients. Four patients had ipsilateral stenosis or occlusion of the middle cerebral artery, 1 patient had microembolic signals in the middle cerebral artery, and 1 patient had no significant abnormalities in the intracranial artery. All 6 patients were initially diagnosed by ultrasound. Diagnoses were confirmed by CTA/DSA in 5 cases; the other patient did not show any significant abnormalities. All 6 patients underwent a carotid endarterectomy after a pathological examination to confirm the diagnosis. Postoperatively, regular antiplatelet aggregation and statin lipid-lowering therapies were administered. A follow-up of 0.5 to 5.2 years showed no stroke recurrence in any patient.Conclusions:CW-related stroke is a rare cause of cryptogenic stroke and has a high recurrence rate. For stroke patients who do not have traditional risk factors for cerebrovascular disease while repeatedly experiencing embolic events of the internal carotid artery system, attention should be paid to the combination of the carotid and cerebral arteries, and comprehensive hemodynamic characteristics should be checked for the presence of a CW. Carotid artery ultrasound and TCCD combined with other imaging methods can improve the detection rate of a CW. Simple antiplatelet aggregation therapy cannot effectively prevent stroke recurrence. For patients with confirmed CW-related cerebral infarction, surgical resection can be performed, and the treatment effect can be evaluated using ultrasonography.
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AIM: To investigate the correlation between 25-hydroxyvitamin D and metabolically associated fatty liver disease in type 2 diabetes mellitus. METHODS: A total of 2 406 subjects in Standardized Metabolic Disease Control were recruited from the National Center for Standardized Metabolic Disease Control in The First Hospital of Lanzhou University. The population was divided into Q1, Q2, Q3 and Q4 according to 25(OH)D quartile. The prevalence of MAFLD and related clinical indicators among the four groups were compared, and the influencing factors of MAFLD were analyzed by Logistic regression. Restricted cubic spline (RCS) was used to explore the relationship between 25(OH)D and MAFLD. RESULTS: The prevalence of MAFLD was different with different vitamin D levels. The prevalence of MAFLD was lower in the group with high 25(OH)D level. The level of 25(OH)D in patients with MAFLD was lower than that in patients with T2DM alone, and the number of vitamin D deficiency was relatively higher. Multivariate regression analysis showed that 25(OH)D was not associated with the risk of MAFLD. RCS analysis also suggested that 25(OH)D was not associated with the risk of MAFLD. CONCLUSION: The prevalence of MAFLD is high in people with low vitamin D level, and vitamin D is not associated with the risk of MAFLD after multivariate adjustment.
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OBJECTIVES@#To study the relationship between skeletal muscle mass index (SMI) and metabolic phenotypes of obesity in adolescents, and to provide a basis for the prevention and control of adolescent obesity and related metabolic diseases.@*METHODS@#A total of 1 352 adolescents aged 12 to 18 years were randomly selected by stratified cluster sampling in Yinchuan City from October 2017 to September 2020, and they were surveyed using questionnaires, physical measurements, body composition measurements, and laboratory tests. According to the diagnostic criteria for metabolic abnormalities and the definition of obesity based on the body mass index, the subjects were divided into four metabolic phenotypes: metabolically healthy normal weight, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity. The association between SMI and the metabolic phenotypes was analyzed using multivariate logistic regression.@*RESULTS@#The SMI level in the metabolically unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity groups was lower than that in the metabolically healthy normal weight group (P<0.001). Multivariate logistic regression analysis showed that after adjusting for gender and age, a higher SMI level was a protective factors for adolescents to develop metabolic unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity phenotypes (OR=0.74, 0.60, and 0.54, respectively; P<0.001).@*CONCLUSIONS@#Increasing SMI can reduce the risk of the development of metabolic unhealthy/obesity.
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Adolescente , Humanos , Niño , Índice de Masa Corporal , Síndrome Metabólico/metabolismo , Músculo Esquelético/metabolismo , Obesidad Metabólica Benigna/diagnóstico , Obesidad Infantil , Fenotipo , Factores de RiesgoRESUMEN
Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.