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Neonatal onset multisystem inflammatory disease(NOMID), also known as chronic infantile neurological cutaneous and articular syndrome(CINCA), originates from perinatal period and mainly manifests urticaria, joint lesions, and central nervous system lesions.It is an autoinflammatory disease associated with mutations of NLRP3 located on chromosome 1q44.The early atypical clinical symptoms are prone to misdiagnosis.NOMID/CINCA should be differentiated from infectious diseases, familial cold autoinflammatory syndrome, Muckle-Wells syndrome, systemic juvenile idiopathic arthritis, mevalonate-kinase deficiency, tumor necrosis factor receptor-associated periodic syndrome, and other diseases.NOMID/CINCA is mainly diagnosed based on clinical symptoms, while genetic testing provides an essential supplementary for patients with atypical clinical manifestations.IL-1 targeted therapies including anakinra, rilonacept, and canakinumab, have been proven with sustained efficacy in treating NOMID/CINCA.This article reviews the progress on diagnosis and treatment of NOMID/CINCA.
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Objective:To investigate the clinical significance of changes of serum Clara cell secretory protein(CC16) and pulmonary surfactant protein A(SP-A) in neonates with acute respiratory distress syndrome(ARDS).Methods:The data of 30 neonates with ARDS who needed mechanical ventilation in neonatal intensive care unit of Xi′an Children′s Hospital from January 2016 to November 2018 were collected as observation group, including 12 cases in mild group, 10 cases in moderate group and 8 cases in severe group.The data of healthy newborns during the same period were taken as control group.The serum levels of CC16 and SP-A were detected by ELISA.The serum levels of CC16 and SP-A among different groups were compared.Results:The levels of serum CC16 and SP-A in ARDS group were (59.35±3.67)mg/L and(75.38±6.27)mg/L respectively, (11.26±1.32)mg/L and(18.15±2.69)mg/L in healthy group.The difference was significant( P<0.05). And the differences of serum CC16 and SP-A levels among different degree ARDS groups were significant( P<0.05). The levels of serum CC16 in mild, moderate and severe subgroup were(38.27±16.01)mg/L, (51.25±15.63)mg/L, (84.76±13.12)mg/L and SP-A were(47.02±7.18)mg/L, (73.12±7.98)mg/L, (96.45±12.50)mg/L, which increased with disease severity. Conclusion:Serum CC16 and SP-A are increased and correlated with the severity of neonatal ARDS, which may be used as the index for evaluating the severity of neonatal ARDS in the future.
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Objective:To investigate the turnover intention and its influencing factors in rural general practitioners in southwest Shandong province.Methods:In May 2020, a survey with self-designed questionnaire was conducted among 2 805 rural general practitioners in southwest Shandong province selected by multi-stage sampling method. Pearson chi square test (χ2) and binary logistic regression were used to analyze the factors influencing the turnover intention of rural general practitioners.Results:A total of 2 805 questionnaires were sent out, 2 693 were collected and 2 272 were valid, with an effective rate of 84.4%. Among 2 272 participants, 1 076 (47.4%) had medium to high level turnover intention. Binary logistic regression showed that part-time job ( OR=1.443, 95% CI: 1.105-1.884, P<0.01), average monthly night shifts ≥20 times ( OR=1.340, 95% CI: 1.106-1.623, P<0.01), daily working time ≥13 hours ( OR=1.358, 95% CI: 1.107-1.666, P<0.01), insomnia ( OR=2.075, 95% CI: 1.755-2.454, P<0.01), feeling depressed at work ( OR=2.987, 95% CI: 2.516-3.546, P<0.01), degree of emotional exhaustion ( OR=3.801, 95% CI: 3.188-4.533, P<0.01) and degree of de-personalization tendencies ( OR=2.493, 95% CI: 2.086-2.981, P<0.01) were the significant factors influencing the turnover intention of rural general practitioners. Conclusions:Rural general practitioners in southwest Shandong have a high-level turnover intention, part-time jobs, average number of night shift per month, working time, insomnia, depression and job burnout are the main factors affecting the turnover intention. Necessary measures should be taken by relevant departments to enhance the stability of rural general practitioners.
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The goal of the present study was to determine the effectiveness and safety of hemoperfusion (HP) in beagle dogs with chronic kidney disease (CKD). The experimental protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Institute of Pharmaceutical Research New Drug Evaluation Research (IACUC2019071501). Twelve CKD model beagles were randomly divided into two groups: a low-frequency treatment group (n = 6) and a high-frequency treatment group (n = 6). The dogs in the high- and low-frequency groups received HP treatment every 3 days and once per week, respectively, for two treatments, with each session lasting 2 h. The test results showed that high-frequency HP treatment significantly decreased the accumulation of toxins in the CKD beagles. Hematology, coagulation function, electrolytes and liver function indicated that the HP treatment was safe. The body index effects were consistent between the low- and high-frequency treatment groups. Therefore, HP treatment once every 3 days was safe at the animal level. Multiple HP treatments every 3 days were more conducive than weekly treatments to the removal of uremic toxins with better prognosis and had no associated safety hazards.
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Phosphoglycerate mutase 1 (PGAM1) is upregulated in many cancer types and involved in cell proliferation, migration, invasion, and apoptosis. However, the relationship between PGAM1 and prostate cancer is poorly understood. The present study investigated the changes in PGAM1 expression in prostate cancer tissues compared with normal prostate tissues and examined the cellular function of PGAM1 and its relationship with clinicopathological variables. Immunohistochemistry and Western blotting revealed that PGAM1 expression was upregulated in prostate cancer tissues and cell lines. PGAM1 expression was associated with Gleason score (P = 0.01) and T-stage (P = 0.009). Knockdown of PGAM1 by siRNA in PC-3 and 22Rv1 prostate cancer cell lines inhibited cell proliferation, migration, and invasion and enhanced cancer cell apoptosis. In a nude mouse xenograft model, PGAM1 knockdown markedly suppressed tumor growth. Deletion of PGAM1 resulted in decreased expression of Bcl-2, enhanced expression of Bax, caspases-3 and inhibition of MMP-2 and MMP-9 expression. Our results indicate that PGAM1 may play an important role in prostate cancer progression and aggressiveness, and that it might be a valuable marker of poor prognosis and a potential therapeutic target for prostate cancer.
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Phosphoglycerate mutase 1 (PGAM1) is upregulated in many cancer types and involved in cell proliferation, migration, invasion, and apoptosis. However, the relationship between PGAM1 and prostate cancer is poorly understood. The present study investigated the changes in PGAM1 expression in prostate cancer tissues compared with normal prostate tissues and examined the cellular function of PGAM1 and its relationship with clinicopathological variables. Immunohistochemistry and Western blotting revealed that PGAM1 expression was upregulated in prostate cancer tissues and cell lines. PGAM1 expression was associated with Gleason score (P = 0.01) and T-stage (P = 0.009). Knockdown of PGAM1 by siRNA in PC-3 and 22Rv1 prostate cancer cell lines inhibited cell proliferation, migration, and invasion and enhanced cancer cell apoptosis. In a nude mouse xenograft model, PGAM1 knockdown markedly suppressed tumor growth. Deletion of PGAM1 resulted in decreased expression of Bcl-2, enhanced expression of Bax, caspases-3 and inhibition of MMP-2 and MMP-9 expression. Our results indicate that PGAM1 may play an important role in prostate cancer progression and aggressiveness, and that it might be a valuable marker of poor prognosis and a potential therapeutic target for prostate cancer.
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Animals , Humans , Male , Mice , Apoptosis/genetics , Caspase 3/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Deletion , Gene Knockdown Techniques , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice, Nude , Neoplasm Invasiveness/genetics , Neoplasm Transplantation , PC-3 Cells , Phosphoglycerate Mutase/genetics , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Small Interfering , Transplantation, Heterologous , bcl-2-Associated X Protein/metabolismABSTRACT
Aim To investigate the effect of taurine-magnesium coordination compound (TMCC) on elec-trocardiogram of isolated guinea pig hearts, hoping to describe a primary research on its characteristic of anti-short QT syndrome. Methods The isolated guinea pig heart was retrograde perfused using Langendorff tech-nique. In order to determine the effects of TMCC on QT interval, transmural dispersion of repolarization, effective refractory period, instability of RR interval and instability of QT interval in the presence of potassi-um channel opener pinacidil, the electrocardiogram of isolated guinea pig hearts was recorded using Biopac physiological recorder. Results The shortened QT in-terval and the effective refractory period induced by pinacidil could be prolonged by TMCC; the increased transmural dispersion of repolarization induced by pinacidil could be decreased by TMCC; the increased instability of RR and QT interval induced by pinacidil could be decreased by TMCC. Conclusion TMCC has the effects of anti-SQT2 by prolonging the QT inter-val and the effective refractory period, reducing the transmural dispersion of repolarization and instability.
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OBJECTIVES@#To investigate the effect of taurine magnesium coordination compound (TMCC) on torsades de pointes (TdP) in isolated guinea pig hearts.@*METHODS@#Healthy male guinea pigs weighting 250~300 g were randomly divided into 4 groups:①TdP model group (=7):Isolated hearts were perfused by normal K-H solution 20 minutes, then perfused by slowly activated delayed rectifier potassium current(IKs) blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) to establish TdP model;②~④ TdP model + TMCC group (=6):Isolated hearts were perfused by normal K-H solution for 20 minutes, then perfused by IKs blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) for 60 minutes, at the same time TMCC which concentration was 1, 2, 4 mmol/L was administered respectively by Langendorff retrograde aortic perfusion method. Cardiac surface electrocardiogram of guinea pigs was collected and recorded by Biopac electrophysiological recorder. Incidence of TdP, transmural dispersion of repolarization (TDR), instability of QT interval were acquired from Lead Ⅱ electrocardiograph (ECG) wave forms to describe the effect of TMCC on TdP model. Datas were acquired at the time of 20 min and pre-TdP, in case there was no TdP observed, a value of 60 min was entered for calculation purpose.@*RESULTS@#Incidence of TdP in TdP model group was 6/7. TdP incidence could be decreased significantly by 1, 2, 4 mmol/L TMCC, and was 5/6, 1/6, 0/6 respectively. Compared with the pre-drug, Chromanol 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(0.05). Compared with the TdP model group, 2, 4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293B under hypokalemic solution(<0.05). During the establishment of TdP model, P waves in more than one cardiac cycle continuously were disappeared in ECG. However, P wave could always be seen independent in ECG acquired from TdP model + TMCC group.@*CONCLUSIONS@#TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).
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Animals , Male , Anti-Arrhythmia Agents , Pharmacology , Electrocardiography , Guinea Pigs , In Vitro Techniques , Long QT Syndrome , Magnesium , Pharmacology , Random Allocation , Taurine , Pharmacology , Torsades de Pointes , Drug TherapyABSTRACT
Objective To investigate the bystander effect injury to lung-heart-liver-spleen caused by 12C6+ beam radiation,and explore the prevention and treatment effect of Guiqiyiyuan ointment on the injury and its mechanism.Methods Ninety healthy male Wistar rats were randomly divided into 3 groups:NC group (normal control,normal saline 2ml/kg,n=30),SR group (simple radiation,8Gy,2ml/kg,n=30),GO group (Guiqiyiyuan ointment 11.83g/kg,radiation,8Gy,n=30).All the rats received intragastric administration for 7 days.The right side of the lung was modeled by 12C6+ beam radiation.After modeling,the rats were killed at 48h.The heart,liver and spleen were taken.The malonaldehyde (MDA),glutathione (GSH),glutathione peroxidase (GSH-Px),superoxide dismutase (SOD) contents were measured by colorimetry,DNA methylation rate was assayed by ELISA,and the expressions of Dnmt1,Dnmt3a and Dnmt3b were detected by immunohistochemistry.Results Compared with NC group,the contents of SOD,GSH and GSH-Px decreased (P<0.01),MDA increased (P<0.01),the level of DNA methylation decreased (P<0.01),and the expressions of Dnmt1,Dnmt3a and Dnmt3b increased in SR group (P<0.01).Compared with SR group,the contents of SOD,GSH and GSH-Px increased (P<0.01),MDA decreased (P<0.01),the level of DNA methylation increased (P<0.01),and the expressions of Dnmt1,Dnmt3a and Dnmt3b decreased in GO group (P<0.01).Dnmtl,Dnmt3a and Dnmt3b proteins were expressed in the cytoplasm of myocardial cells,hepatocytes and peripheral B cells of the white pulp in spleen,in all the groups.The color of NC group was light brown-brown,showing a weak positive expression.The color of SR group was brown-brown,showing a strong positive expression.The color of GO group was light brown-tan,showing a moderate positive expression.Conclusion The Guiqiyiyuan ointment can reduce the bystander effect caused by the 12C6+ beam radiation,and its mechanism is related to improving the oxidative stress reaction and the level of DNA methylation.
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<p><b>OBJECTIVE</b>To investigate the risk factors for concurrent sepsis in neonates with necrotizing enterocolitis (NEC).</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of 273 neonates with NEC. The risk factors for concurrent sepsis were analyzed from the aspects of perinatal factors and treatment regimen before the diagnosis of NEC.</p><p><b>RESULTS</b>The incidence rate of concurrent sepsis in NEC was 32.2% (88/273). The neonates with stage III NEC had a significantly higher incidence rate of concurrent sepsis than those with stage II NEC (69.0% vs 15.9%; P<0.05). Of all neonates with sepsis, 62.5% experienced sepsis within 3 days after the diagnosis of NEC, and 37.5% experienced sepsis more than 3 days after the diagnosis. Compared with those without concurrent sepsis, the neonates with concurrent sepsis had significantly lower gestational age and birth weight (P<0.05). The neonates who had scleredema, had stage III NEC, needed gastrointestinal decompression after the diagnosis of NEC, and experienced a long time of gastrointestinal decompression tended to develop sepsis more easily (P<0.05). Scleredema (OR=9.75, 95%CI: 2.84-33.52, P<0.001), stage III NEC (OR=12.94, 95%CI : 6.82-24.55, P<0.001), and gastrointestinal decompression (OR=2.27, 95%CI: 1.14-4.5, P=0.02) were independent risk factors for concurrent sepsis in NEC.</p><p><b>CONCLUSIONS</b>Scleredema, stage III NEC, and gastrointestinal decompression are independent risk factors for concurrent sepsis in neonates with NEC.</p>
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Humans , Infant, Newborn , Enterocolitis, Necrotizing , Retrospective Studies , Risk Factors , SepsisABSTRACT
Some physiological and ethical problems make it difficult to obtain semen samples from adolescents with varicocele (VC) and to directly evaluate their fertility. Therefore we can only rely on indirect methods to assess the influence of VC on the future fertility of the adolescent patients. Most of the VC adolescents may have normal semen parameters in the adulthood. Thus whether and when to intervene in adolescent VC remain a controversy in andrology. Physical examination is the most common method for screening adolescent VC and ultrasonography is very effective for its diagnosis and evaluation. Other important diagnostic indicators include the widely accepted testicular atrophy index, recently proposed peak retrograde venous flow, total testis volume, and scrotal temperature. Based on the latest literature, this review offers some proposals for the evaluation and intervention of adolescent VC.
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Adolescent , Humans , Male , Infertility, Male , Diagnosis , Semen , Semen Analysis , Testis , Pathology , Varicocele , DiagnosisABSTRACT
<p><b>OBJECTIVE</b>To observe effects of Tanshinone- II A sulfonate on expression of Nuclear factor-kappaB (NF-kappaB), Vascular Cell Adhesion Molecule-1 (VCAM-1) and hemorrheology during spinal cord ischemia reperfusion injury,and explore the function and mechnism.</p><p><b>METHODS</b>Fifty-four New Zealand rabbits (aged 3 months,weighted 2.0 +/- 0.2 kg) were randomly divided into 6 in sham group (lumbar artery were separated in operation,0.8 ml/kg saline were injected at 0.5 h before and after operation), 24 in ischemia group ( lumbar artery were clipped after seperation, and the same dose of saline), 24 in Tanshinone group (lumbar artery were clipped after seperation, and the same dose of Tanshinone- II A sulfonate) . Abdomincal aorta blood were drawed after treatment respectively at 0.5 h, 1 h, 4 h and 8 h, and tesetd whole blood viscosity [high cut (mpa.s)/150(l/s), middle cut (mpa.s)/60(l/s) and low cut (mpa.s)/10(l/s)], capillary plasma viscosity, red cell aggregation index, rigid index, deformation index and electrophoresis index. Spinal cord tissues were divided into two sections,one fixed in 4% paraformaldehyde, another stored in liquid nitrogen. Immunohistochemical method and ELISA were used to test change of content of NF-kappaB and VCAM-1.</p><p><b>RESULTS</b>1) The expression of NF-kappaB in Tanshinone group were lowest, and in ischemia group were highest. 2) Compared with sham group, VCAM-1 in ischemia group at different time were obviously increased,especially at 0.5, 1 and 4 h (P<0.01), and had meaning at 8 h (P<0.05). Compare between Tanshinone group and ischemia group, VCAM-1 at 0.5 h were obviously decreased (P<0.01), and had meaning at 1 h, 4 h and 8 h (P<0.05). 3) There were no postive vasvular expression in sham group, and at 0.5 h in Tanshinone group and ischemia group. The highest postive vasvular expression in ischemia group were at 1 h, 4 h and 8 h, and had significant meaning at 1 h and 4 h between ischemia group and Tanshinone group (P<0.05), and 8 h were obviously most. 4) The whole blood viscosity in ischemia group at 10 s(-1), 60 s(-1), 150 s(-1) were highest, and capillary viscosity increased (P<0.05 or P<0.01). While capillary viscosity, red cell aggregation index, figid index, deformation index in Tanshinone group decreased obviously (P<0.01).</p><p><b>CONCLUSION</b>Tanshinone-II A sulfonate can relieve spinal cord ischemia reperfusion injury by regulating expression of NF-kappaB, VCAM-1, decreasing whole blood viscosity, capillary plasma viscosity, red cell aggregation index, rigid index, and improve hemorhelogy.</p>