The diagnostic value of serum levels of pro calcitonin, β2 defensins, C-reactive protein and the positive rate of group B streptococci in preterm premature rupture of membranes with amniotic infection / 中国医师杂志

Objective:To explore the diagnostic value of serum levels of pro calcitonin (PCT), β2 defensins (HBD-2), C-reactive protein (CRP) and the positive rate of group B streptococci (GBS) in preterm premature rupture of membranes (PROM) with amniotic infection.Methods:This study was a retrospective study. 156 pregnant women with preterm PROM who were diagnosed by the Obstetrics Department of the Hospital of Southern University of Science and Technology from January 2017 to January 2022 were selected as the study subjects. According to whether there was amniotic infection, they were divided into 57 infected women and 99 non infected women. The levels of serum PCT, HBD-2 and CRP before delivery were compared between the two groups, and the positive rate of GBS in vaginal discharge was detected, and the receiver operating curve (ROC) was used to analyze the value of various indicators in diagnosing amniotic cavity infection in preterm PROM mothers.Results:The serum levels of PCT, HBD-2, CRP, and GBS positivity in the infected group were significantly higher than those in the non infected group, with statistically significant differences (all P<0.01); The area under the curve (AUC) value, sensitivity, and specificity of serum PCT for diagnosing preterm PROM with amniotic cavity infection were 0.894, 82.56%, and 80.74%, respectively; The AUC value of HBD-2 for diagnosing preterm PROM with amniotic cavity infection was 0.792, the sensitivity was 70.78%, and the specificity was 77.59%; The AUC value, sensitivity, and specificity of CRP in diagnosing preterm PROM with amniotic cavity infection were 0.756, 68.94%, and 72.78%, respectively; The positive rate of GBS in vaginal discharge was 0.733, the sensitivity was 64.91%, and the specificity was 81.82%. Conclusions:The serum levels of PCT, HBD-2, CRP and the positive rate of GBS in vaginal discharge of pregnant women with preterm PROM complicated with amniotic infection will increase significantly. All indicators have high practical value for the diagnosis of preterm PROM complicated with amniotic infection.

Effects of ADRB2 gene regulatory region polymorphism on the efficacy of SABA in the treatment of acute asthma attack in children / 中国药房

OBJECTIVE To explore the effects of ADRB2 gene regulatory region polymorphism on the efficacy of short-acting beta 2 receptor agonists （SABA） in the treatment of acute asthma attack in children. METHODS A total of 127 children with acute mild to moderate bronchial asthma who received SABA treatment for 7 days in the General Hospital of Northern Theater Command from October 2016 to October 2020 were selected to detect their genotype distribution and compare the improvement of pulmonary functional indicators and curative effect among different genotypes. The effect of the high-order interaction of gene polymorphism on therapeutic effect was investigated. RESULTS Among 127 children， there were 80， 44 and 3 cases of TT， TA and AA types at locus rs2895795， 93， 32 and 2 cases of CC， CG and GG types at locus rs11168070， and 41， 64 and 22 cases of GG， GA and AA types at locus rs12654778， respectively， in accordance with Hardy-Weinberg equilibrium （P＞0.05）. After treatment， the improvement rate of the peak expiratory flow in percent predicted value （PEF%pred） and the improvement rate of the forced expiratory flow at 75% vital capacity in percent predicted value （FEF75%pred） in children with TA type were significantly lower than that of TT type at locus rs2895795 （P＜0.05）； the improvement rates of PEF%pred and FEF75%pred in children with CG type were significantly lower than that of CC type at locus rs11168070 （P＜0.05）； the improvement rates of PEF%pred in children with GA and AA type were significantly lower than that of GG type at locus rs12654778 （P＜0.05）. The differences in fractional exhaled nitric oxide before and after treatment were not statistically significant among different genotypes at each locus （P＞0.05）. The proportion of remarkable improvement of children with TT type at locus rs2895795 was 2.358 times that of children with TA+ AA type （P＜0.05）， and there was no significant effect of higher-order interaction of ADRB2 polymorphism on the efficacy in children with asthma （P＞0.05）. CONCLUSIONS Polymorphisms in the regulatory region of the ADRB2 gene in children with bronchial asthma are associated with the efficacy of SABA in the treatment of acute asthma attack in children. At locus rs2895795， rs11168070 and rs12654778， the improvement of lung function of children with wild-type is more obvious， and the efficacy of SABA treatment on children with TT type is better at locus rs2895795.

Value of Model for End-Stage Liver Disease score and albumin-bilirubin score combined with β2-microglobulin in predicting liver cirrhosis with acute kidney injury / 临床肝胆病杂志

ObjectiveTo investigate the value of combined determination of Model for End-Stage Liver Disease （MELD） score， albumin-bilirubin （ALBI） score， and β2-microglobulin in the diagnosis of liver cirrhosis with acute kidney injury （AKI）. MethodsClinical data were collected from 258 patients with liver cirrhosis who attended The First Affiliated Hospital of Zhengzhou University from October 2019 to October 2022， and according to the presence or absence of AKI， they were divided into AKI group with 117 patients and non-AKI group with 141 patients. The changes in each index were compared between the two groups and between the patients with different stages of kidney injury. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the efficacy of each index in the diagnosis of liver cirrhosis with AKI. ResultsCompared with the non-AKI group， the AKI group had significantly higher age （t=2.307， P=0.022）， proportion of patients with hepatic encephalopathy （χ2=18.064， P<0.001） or with spontaneous peritonitis （χ2=16.397， P<0.001）， mortality rate （χ2=45.251， P<0.001）， levels of creatinine （Z=-8.737， P<0.001） and β2-microglobulin （Z=-8.829， P<0.001）， and scores of CTP （Z=-4.058， P<0.001）， ALBI （t=2.563， P=0.011）， and MELD （Z=-5.628， P<0.001）， as well as a significantly shorter length of hospital stay （Z=-3.391， P=0.001）. There were significant differences in creatinine， β2-microglobulin， MELD score， and ALBI score between the patients with stage 1， 2 or 3 AKI （P<0.05）， while there was no significant difference in CTP score between these three groups （P>0.05）. The combined determination of ALBI score， MELD score， and β2-microglobulin had an area under the ROC curve （AUC） of 0.837 （95% confidence interval ［CI］： 0.782 — 0.892）， with a sensitivity of 75.2% and a specificity of 90.8%； ALBI score combined with MELD score had an AUC of 0.700 （95%CI： 0.636 — 0.764）， ALBI score combined with β2 microglobulin had an AUC of 0.823 （95%CI： 0.765 — 0.881）， and MELD combined with and β2 microglobulin had an AUC of 0.835 （95%CI： 0.779 — 0.890）， suggesting that combined determination of ALBI score， MELD score， and β2-microglobulin had a better diagnostic efficacy than ALBI score， MELD score， or β2-microglobulin used alone or in pairs， as well as a better diagnostic efficacy than creatinine. ConclusionCombined determination of ALBI score， MELD score， and β2-microglobulin has a relatively high value in the diagnosis of liver cirrhosis with AKI.

Inhibition of pyrrolidine dithiocarbamate on transforming growth factor-beta 2 induced epithelial-mesenchymal transition in human lens epithelial cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the mechanism of pyrrolidine dithiocarbamate(PDTC)on transforming growth factor-beta 2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(LECs).METHODS: LECs were treated with various doses of PDTC chemicals following TGF-β2 caused EMT on these cells. Cell proliferation and lateral migration were discovered using the CCK-8 and cell scratch test. The markers of EMT, including E-cadherin, α-SMA and nuclear factor-κB(NF-κB)signaling pathway-related expression, were tested by Western Blot as well as the changes in the expression of the apoptosis-related proteins BAX, BCL-2, Caspase-3, and Cyclin D1.RESULTS: The proliferation and migration viability of cells in the TGF-β2 treated group was increased compared to the group without TGF-β2, and the expression of α-SMA increased whereas the E-cadherin expression decreased. With the effect of TGF-β2, NF-κB p65 and phosphorylated NF-κB p65 expression increased, the concentration of TGF-β2 that had the greatest capacity for proliferation and migration was 10 ng/mL(P&#x003C;0.05). Mechanism study of PDTC-induced EMT reversal and apoptosis showed that cell viability and migratory capability were both significantly reduced after PDTC intervention; PDTC prevents IκB phosphorylation, thus inhibiting NF-κB nuclear translocation. Protein associated to the NF-κB signaling pathway, and protein expression of NF-κB/IκBα/p-IκBα/Iκκ-α/p-Iκκ-α was decreased(P&#x003C;0.05), PDTC increased the expression of the pro-apoptotic protein BAX/Caspase-3, expression of the inhibitor of apoptosis protein BCL-2 and the cell cycle protein Cyclin D1 was reduced. The expression of NF-κB/IκB mRNA was reduced, expression of the apoptosis-related mRNA BAX increased, while BCL-2 reduced.CONCLUSION: The EMT in LECs cells induced by TGF-β2 can be significantly reversed by PDTC, which may be related to the decreased expression of NF-κB p65/IκB/Iκκ-α and activation of apoptosis-related protein. PDTC can reverse EMT by inhibiting NF-κB signaling pathway and induce apoptosis of abnormally proliferated cells, which will provide new potential therapeutic agents for posterior capsular opacification(PCO)treatment.

COVID-19 coagulopathy and antiphospholipid syndrome

The presence of thrombotic events in COVID-19 patients has been described since the beginning of the pandemic. This association has been confirmed in most of the reported studies. Autopsy reports have shown that most thromboses are located in the lung, although they have also been observed in other organs such as the skin and kidneys. SARS-CoV2 infection induces a generalized prothrombotic state, which is attributed to a combination of factors such as hypoxia, excess cellular apoptosis, and mainly to overactivation of the immune system. Among immune-mediated prothrombotic situations, antiphospholipid syndrome (APS) stands out. Recurrent thrombotic events are observed in APS in the presence of antiphospholipid antibodies (aPL). There are numerous studies that report high prevalence of aPL in patients with COVID-19 infection. However, the results show discrepancies in the data on the prevalence of aPL, and its role in the pathogenesis of thrombosis in these patients. This could be due to the heterogeneity of the detection procedures for aPL or to transient elevations of non-pathogenic aPL levels in the context of infection. In this review we try to clarify the role of aPL in COVID-19 infection, and attempt to answer the question of whether it is a coagulopathy of its own, or secondary to APS.

La presencia de eventos trombóticos en los pacientes con COVID-19 se describió desde el inicio de la pandemia, asociación que ha sido confirmada en la mayoría de los estudios reportados. Los informes de necropsias han puesto de manifiesto que la mayoría de las trombosis se localiza en el pulmón, aunque también se han observado en otros órganos, como la piel y los riñones. La infección por SARS-CoV-2 induce un estado protrombótico generalizado que se atribuye a una conjunción de factores como la hipoxia, el exceso de apoptosis celular y, sobre todo, una hiperactivación del sistema inmune. Entre las situaciones protrombóticas inmunomediadas destaca el síndrome antifosfolipídico, en el cual se observan eventos trombóticos de repetición en presencia de anticuerpos antifosfolipídicos (AAF). Existen numerosos estudios que reportan una elevada prevalencia de AAF en los pacientes con infección por la COVID-19; sin embargo, los resultados muestran discordancias en los datos de prevalencia de AAF y su rol en la patogenia sobre la trombosis en estos pacientes, lo que que podría deberse a la heterogeneidad de los procedimientos de detección de los AAF o a elevaciones transitorias de los niveles de AAF no patogénicos en el contexto de la infección. En esta revisión se busca aclarar el papel de los AAF en la infección por COVID-19, intentando responder a la pregunta de si se trata de una coagulopatía propia o es secundaria a un síndrome antifosfolipídico.

Association between beta-2 adrenergic receptor variants and clinical outcomes in children and adolescents with acute asthma

ABSTRACT Objective To investigate whether different genotypes of p.Arg16Gly, p.Gln27Glu, p.Arg19Cys and p.Thr164Ile variants interfere in response to treatment in children and adolescents with moderate to severe acute asthma. Methods This sample comprised patients aged 2 to 17 years with a history of at least two wheezing episodes and current moderate to severe asthma exacerbation. All patients received multiple doses of albuterol and ipratropium bromide delivered via pressurized metered-dose inhaler with holding chamber and systemic corticosteroids. Hospital admission was defined as the primary outcome. Secondary outcomes were changes in forced expiratory volume in the first second after 1 hour of treatment, and for outpatients, length of stay in the emergency room. Variants were genotyped by sequencing. Results A total of 60 patients were evaluated. Hospital admission rates were significantly higher in carriers of the genotype AA relative to those with genotype AG or GG, within the p.Arg16Gly variant (p=0.03, test χ2, alpha=0.05). Secondary outcomes did not differ between genotypes. Conclusion Hospital admission rates were significantly higher among carriers of the genotype AA within the p.Arg16Gly variant. Trial registration: ClinicalTrials.gov: NCT01323010

Emerging role of natural products in cancer immunotherapy

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

Correlation of plasma beta-2 microglobulin levels with total magnetic resonance imaging burden of cerebral small-vessel disease in elderly patients with lacunar stroke / 中华老年医学杂志

Objective:To investigate the relationship between plasma beta-2 microglobulin(β2M)levels and the total magnetic resonance imaging(MRI)burden of cerebral small-vessel disease(CSVD)in elderly patients with lacunar stroke.Methods:A total of 93 elderly patients with lacunar stroke admitted to the Department of Neurology, Changzhou Second People's Hospital form August 2018 to August 2019 were enrolled retrospectively, all with complete records of cranial magnetic resonance imaging and plasma β2M measurement.According to the total MRI CSVD burden, which ranges from an ordinal score of 0 to 4, patients were divided into 5 groups.Single-factor analysis was used to compare clinical data between the 5 groups.The association between the plasma β2M level and total MRI CSVD burden was analyzed by ordered multiple Logistic regression models.Results:Among elderly patients with lacunar infarction, 19 had a CSVD score of 0, 19 had a score of 1, 23 had a score of 2, 21 had a score of 3, and 11 had a score of 4, with statistically significant differences in age, percentage with diabetes, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, plasma β2M, and eGFR between the 5 groups( P<0.05). Spearman correlation analysis showed that plasma β2M level was significantly positively correlated with total MRI CSVD burden( r=0.687, P<0.001). In ordered multivariate logistic regression models, after adjustment for possible confounding factors such as age, sex and hypertension, the results demonstrated that plasma β2M level( OR=5.253, 95% CI: 2.350-11.740, P<0.001)was an independent risk factor for total MRI CSVD burden. Conclusions:In elderly lacunar stroke patients, the plasma β2M level is closely related to the total MRI CSVD burden and can be used as a marker for predicting the severity of lesions.

Efficacy of inhalation therapy with montelukast sodium, budesonide and formoterol in combination in the treatment of bronchial asthma in adult patients and its effects on cytokines / 中国基层医药

Objective:To investigate the efficacy of combination treatment with montelukast sodium, budesonide and formoterol in the treatment of bronchial asthma in adults and its effects on cytokines.Methods:A total of 100 adult patients with bronchial asthma who received treatment in The First People's Hospital of Yongkang from January 2019 to December 2020 were included in this study. They were randomly assigned to receive either budesonide inhalation alone (control group, n = 50) or combination inhalation of montelukast sodium, budesonide and formoterol (observation group, n = 50) for 12 weeks. Efficacy was compared between the two groups. Lung function [forced expiratory volume in one second (FEV 1), peak expiratory flow (PEF) and FEV 1/forced vital capacity (FVC) ratio], cytokines [interleukin (IL)-2, IL-4, IL-6], Asthma Quality of Life Questionnaire (AQLQ) score, and Asthma Control Test (ACT) score measured before and 12 weeks after treatment were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [92.00% (46/50) vs. 72.00% (36/50), χ2 = 6.77, P < 0.05). After 12 weeks of treatment, FEV 1, PEF and FEV1/FVC in the observation group were (2.17 ± 0.23) L, (246.56 ± 17.86) L/s, and (83.86 ± 3.98)%, respectively, which were significantly higher than (1.86 ± 0.17) L, (203.12 ± 20.10) L/s, (74.82 ± 5.67)% in the control group ( t = 7.66, 11.42, 9.22, P < 0.05). Serum IL-2 level in the observation group was significantly higher than that in the control group [(10.85 ± 0.86) ng/L vs. (8.94 ± 1.03) ng/L, t = 10.06, t < 0.05]. Serum IL-4 and IL-6 in the observation group were (24.98 ± 3.08) ng/L and (98.46 ± 9.76) μg/L, respectively, which were significantly lower than (36.75 ± 4.34) ng/L and (125.84 ± 13.19) μg/L in the control group ( t =15.63, 11.79, both P < 0.05). AQLQ score and ACT score in the observation group were (121.03 ± 8.69) points and (22.08 ± 1.35) points, respectively, which were significantly higher than (110.93 ± 7.86) points and (19.74 ± 1.76) points in the control group ( t = 6.095, 7.460, both P < 0.05). Conclusion:Inhalation therapy with montelukast sodium, budesonide and formoterol produces obvious therapeutic effects on bronchial asthma in adult patients and the combined therapy can reduce inflammatory reactions.

Correlations of anti-cardiolipin antibody and anti-β2 glycoprotein I antibody with ischemic stroke in patients with systemic autoimmune diseases / 中国基层医药

Objective:To correlate anti-cardiolipin antibody (aCL) and anti-β2 glycoprotein I antibody (aβ2GPI) with ischemic stroke (IS) in patients with systemic autoimmune diseases (SADs).Methods:A total of 104 patients with SADs who received treatment in the Affiliated Hospital of North Sichuan Medical College during January to December 2019 were included in this study. They were divided into two groups whether they had IS (IS group, n = 42) or not (non-IS group, n = 62). aPL positive rate was qualitatively compared between the IS and non-IS groups. aCL and aβ2GPI expression levels were quantitatively compared between the IS and non-IS groups. Logistic regression analysis was performed to evaluate the risk factors for IS in patients with SADs. Results:aPL positive rate in the IS group was significantly higher than that in the non-IS group [61.9% (26/42) vs. 40.3% (25 /62), χ2 = 4.66, P = 0.031]. The aCL-IgM and aβ2GPI-IgM levels in the IS group were (22.82 ± 27.27) RU/mL and (18.70 ± 23.95) RU/mL, respectively, which were significantly higher than those in the non-IS group [(13.34 ± 8.43) RU/mL, (7.61± 5.80) RU/mL, t = -2.18, -2.76, P = 0.034, 0.009]. Logistic regression analysis showed that aPL is an independent risk factor for IS ( P = 0.037). Conclusion:aCL and aβ2GPI are closely related to the occurrence of IS and are the independent risk factors for IS in patients with SADs.

Clinical and laboratory characteristics of Brazilian versus non-Brazilian primary antiphospholipid syndrome patients in AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) clinical database and repository

Abstract Background: Antiphospholipid syndrome (APS) is characterized by episodes of thrombosis, obstetric morbidity or both, associated with persistently positive antiphospholipid antibodies (aPL). Studying the profile of a rare disease in an admixed population is important as it can provide new insights for understanding an autoimmune disease. In this sense of miscegenation, Brazil is characterized by one of the most heterogeneous populations in the world, which is the result of five centuries of interethnic crosses of people from three continents. The objective of this study was to compare the clinical and laboratory characteristics of Brazilian vs. non-Brazilian primary antiphospholipid syndrome (PAPS) patients. Methods: We classified PAPS patients into 2 groups: Brazilian PAPS patients (BPAPS) and PAPS patients from other countries (non-BPAPS). They were compared regarding demographic characteristics, criteria and non-criteria APS manifestations, antiphospholipid antibody (aPL) profile, and the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). Results: We included 415 PAPS patients (88 [21%] BPAPS and 327 [79%] non-BPAPS). Brazilian patients were significantly younger, more frequently female, sedentary, obese, non-white, and had a higher frequency of livedo (25% vs. 10%, p < 0.001), cognitive dysfunction (21% vs. 8%, p = 0.001) and seizures (16% vs. 7%, p = 0.007), and a lower frequency of thrombocytopenia (9% vs. 18%, p = 0.037). Additionally, they were more frequently positive for lupus anticoagulant (87.5% vs. 74.6%, p = 0.01), and less frequently positive to anticardiolipin (46.6% vs. 73.7%, p < 0.001) and anti-ß2-glycoprotein-I (13.6% vs. 62.7%, p < 0.001) antibodies. Triple aPL positivity was also less frequent (8% vs. 41.6%, p < 0.001) in Brazilian patients. Median aGAPSS was lower in the Brazilian group (8 vs. 10, p < 0.0001). In the multivariate analysis, BPAPS patients still presented more frequently with livedo, cognitive dysfunction and sedentary lifestyle, and less frequently with thrombocytopenia and triple positivity to aPL. They were also less often white. Conclusions: Our study suggests a specific profile of PAPS in Brazil with higher frequency of selected non-criteria manifestations and lupus anticoagulant positivity. Lupus anticoagulant (not triple positivity) was the major aPL predictor of a classification criteria event.

Roles of sodium channel-voltage-gated-beta 2B in learning and memory improvements of transgenic mice with Alzheimer's disease / 中华行为医学与脑科学杂志

Objective:To explore the potential role of amyloid precursor protein (APP) in the sodium-channel-voltage-beta 2B (SCN2B)-mediated improvement of memory and cognitive function in Alzheimer's Disease (AD).Methods:The SCN2B gene knockout mice (SCN2B -/-) were hybridized with APP gene knockout mice (APP -/-), APP gene heterozygous mice (APP +/-) and APP gene transgenic mice (APP +/+), and the tail tissue of the same mouse was genotyped by PCR gene detection.The mice were divided into SCN2B -/-APP -/- group, SCN2B -/-APP +/- group and SCN2B -/-APP +/+ group.The C57BL/6 wild-type mice were Wild type (WT) group, with 9 mice in each group.SCN2B -/-APP -/-, SCN2B -/-APP +/-, SCN2B -/-APP +/+ transgenic mice and the wild-type mice at the age of 6 months, 12 months, and 18 months were tested by Morris water Maze and Y maze test to detect the cognitive function between each group.Meanwhile, SCN2B -/-APP -/-, SCN2B -/-APP +/-, SCN2B -/-APP +/+ transgenic mice aged 6, 12, 18 months and age-match wild-type were selected to detect neuronal processes in hippocampal CA1 region, and the number of neuronal processes in basal and distal regions of hippocampal CA1 region was quantitatively analyzed.SPSS 21.0 statistical software was used for data statistics and analysis.The differences between the two groups were compared and analyzed by independent-sample t test, the comparison between multiple groups was analyzed by one way analysis of variance (ANOVA), and repeated measurement ANOVA was used to analyze behavioral deta. Results:Repeated measurement ANOVA was used to analyze the data of water maze test. The data showed that the interaction effect of escape latency group and time was significant in 18 month old mice ( Ftime×group=3.63, P<0.01). Simple effect analysis showed that compared with SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the escape latency of mice in SCN2B -/-APP +/+ group was significantly prolonged from day 4 to 6 (4th day: (47.00±2.00)s, (43.11±1.96) s, (41.89±3.06)s, t=-4.16, 1.00, both P<0.05; 5th day: (45.22±2.54) s, (36.33±2.78) s, (37.00±2.45)s, t=-7.08, -0.54, both P<0.05; 6th day: (38.11±2.03)s, (34.11±2.32)s, (33.00±2.91)s, t=-3.90, 0.90, both P<0.05). The residence time in the target quadrant was shortened((18.00±1.73)s, (25.56±1.33)s, (24.33 ±1.94)s; t=10.37, 1.56, both P<0.05). (2) Y-maze results showed that compared with SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the number of novel arm entry in 18 month old mice in SCN2B -/-APP +/+ group was decreased((50.22±3.68), (57.22±3.74), (58. 44±5.14) ; t=3.40, -0.48, both P<0.05), and the residence time of stay in the new arm was reduced((10.89±0.62)min, (14.33±0.59)min, (13.89±0.74)min; t= 8.16, 0.44, both P<0.05), and the distance of movement in the new arm was significantly reduced ((37.26±2.01)m , (45.67±2.45)m , (46.11±3.27)m ; t=7.81, 0.91, both P<0.05). (3) Golgi staining showed that SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the number of apical dendrites in hippocampal neurons of 18 month old mice in SCN2b -/-App +/+ group(number of apical dendrites: (1.78±0.37), (3.67±0.81), (3.00±1.21); t=3.36, 1.41, both P<0.05) and the number of basal dendrites (the number of basal dendrites: (1.11±0.50), (3.11±0.50), (2.56±0.69); t=4.06, 1.21, both P<0.05). Conclusion:SCN2B knockdown can improve the ability of spatial learning and memory in aged mice.Overexpression of APP can partially offset the improvement of cognitive function caused by SCN2B knockdown, and may be affected by the number of basal and distal processes of neurons in the hippocampal CA1 region of the mice.

In vivo evidence of angiogenesis inhibition by ß2-glycoprotein I subfractions in the chorioallantoic membrane of chicken embryos

The vascular network expansion and functioning are important factors affecting normal intra-uterine fetal development. This study addressed the previously reported antiangiogenic potential of beta-2-glycoprotein I (β2GPI) in vivo in the chick embryo model of angiogenesis. The effects of two naturally occurring β2GPI forms on the development of the chorioallantoic membrane (CAM) vessels and the chicken embryo were investigated. β2GPI monomers and dimers were obtained by fractioned purification and characterized using SDS-PAGE, immunoblot, and ELISA. The egg exposure was performed by injection of small volumes of 2.5 µg/mL solutions of the β2GPI subfractions. Angiogenesis was evaluated through quantitative measurements of vascular architecture parameters in the captured CAM images, using computational analysis of texture contrasts and computer vision techniques. Quantitative information was assigned to the CAM vasculature modifications. In vivo, the β2GPI dimer completely halted the formation of CAM vessels and led to embryo death after 48 h of exposure. The β2GPI monomer allowed the embryo to develop up to the 10th day, despite early changes of CAM vessels. The impaired normal vessel growth proceeded as a self-limited effect. The β2GPI monomer-exposed eggs showed reduced vascularization on the 6th day of incubation, but embryos were viable on the 10th day of incubation, with ingurgitated CAM vessels implying sequelae of the angiogenesis inhibition. Both subfractions impaired CAM vasculature development. The β2GPI dimer proved to be largely more harmful than the β2GPI monomer. β2GPI modification by cleavage or dimerization may play a role in angiogenesis control in vivo.

Beta-adrenergic pathway activation in head and neck cancer: a comprehensive analysis of the clinical and genomic features using integrated bioinformatics / Ativação da via beta-adrenérgica no câncer de cabeça e pescoço: uma análise abrangente das características clínicas e gênomicas utilizando a bioinformática

O estresse crônico leva à ativação da via de sinalização beta-adrenérgica. Sua ativação tem sido implicada na progressão de diferentes tipos de câncer, mas seu papel nos carcinomas espinocelulares de cabeça e pescoço (CECPs) permanece indefinido. O objetivo deste estudo foi investigar o papel da ativação da via betaadrenérgica na progressão dos CECPs, avaliar seu impacto na sobrevida dos pacientes e buscar possíveis terapias para pacientes que encontravam-se com a via beta-adrenérgica ativa. Quinhentos e vinte pacientes do The Cancer Genome Atlas com CECPs primários foram divididos em dois grupos: ADRB2baixa / SLC6A2baixa e ADRB2alta / SLC6A2alta. A associação de características clinicopatológicas e genômicas entre os grupos foram analisadas utilizando bioinformática. Os genes diferencialmente expressos (DEGs) foram identificados através da análise da expressão diferencial. A análise de sobrevida também foi realizada com base nas expressões ADRB2 e SLC6A2. Foram identificados medicamentos em potencial para tratamento de CECPs com base nos DEGs. Houve associação entre as expressões ADRB2 e SLC6A2 com idade, raça, localização do tumor, grau histológico, invasão perineural e status do HPV p16. Foram identificados 898 DEGs entre os grupos. Foi demonstrado que a expressão ADRB2alta / SLC6A2alta influenciou a proliferação, adesão e invasão de células CECPs além da angiogênese. Pacientes com carcinomas espinocelular de laringe e faringe apresentando expressão ADRB2alta / SLC6A2alta tiveram menor sobrevida. Por fim, 56 drogas antineoplásicas e imunoterápicas aprovadas pelo Food Drugs Administration foram identificadas como potenciais alvos para o tratamento personalizado. Significância: Estes achados sugerem fortemente um papel proeminente da sinalização beta-adrenérgica no CECPs ao estimular um fenótipo tumoral mais agressivo. Estas alterações tiveram um impacto negativo no prognóstico dos pacientes com CECP em região de faringe e laringe(AU)

Chronic stress leads to the activation of the beta-adrenergic pathway. Its activation has been implicated in the progression of different types of cancer but its role on head and neck squamous cell carcinomas (HNSCCs) remains undefined. The aim of this study was to investigate the influence of the beta-adrenergic pathway activation in the progression of HNSCCs, assess its impact in the survival of the patients, and explore the potential targets. Five hundred and twenty The Cancer Genome Altas patients with primary HNSCCs were divided in two groups: ADRB2low / SLC6A2low and ADRB2high / SLC6A2high. The association of clinicopathological and genomic features between the groups was analyzed using a bioinformatic approach. Differentially expressed genes (DEGs) were identified through differential expression analysis. Survival analysis was also performed based on ADRB2 and SLC6A2 expressions. Potential drugs for treatment of HNSCC were identified based on the DEGs. There was association between ADRB2 and SLC6A2 expressions with age, race, tumor site, histologic grade, perineural invasion, and HPV p16 status. It was identified 898 DEGs between the groups. It was demonstrated that ADRB2high / SLC6A2high expression influenced HNSCC cells proliferation, adhesion, invasion, and angiogenesis. Patients with larynx and pharynx squamous cell carcinomas presenting ADRB2high / SLC6A2high expression showed had lower survival rates. Finally, 56 Food Drugs Administration-approved antineoplastic and immunotherapeutic drugs were identified as potential targets for the personalized treatment. Significance: These findings strongly suggest a prominent role of beta-adrenergic pathway in HNSCC by stimulating a more aggressive tumoral phenotype. These alterations were shown to negatively impact the prognosis of patients with larynx and pharynx squamous cell carcinomas(AU)

Changes of serum LDH, CEA and β2-MG levels in non-Hodgkin's lymphoma patients in different situations and their clinical significance / 中国医师杂志

Objective To investigate the changes of serum carcinoembryonic antigen (CEA),lactate dehydrogenase (LDH),β2-microglobulin (β2-MG) levels in non-Hodgkin's lymphoma (NHL) patients and their clinical significance.Methods From February 2015 to February 2018,54 patients with NHL who were hospitalized in Shiyan People's Hospital were selected as the observation group.All patients underwent two cycles of chemotherapy combined with radiation therapy.Another 54 healthy subjects were selected as the control group.To observe the changes of serum LDH,β2-MG,CEA levels in the control group,and compare the changes of serum LDH,β2-MG,CEA levels before and after treatment with different clinical stages,different conditions,and different effects in NHL.Results The levels of serum LDH,β2-MG,and CEA in the observation group were higher than those in the control group (P ＜ 0.05);the levels of serum LDH,β2-MG,and CEA in patients with NHL in stage Ⅲ to Ⅳ were higher than those in stage Ⅰ to Ⅱ (P ＜0.05);the levels of serum LDH,β2-MG,and CEA in patients with NHL in the middle-high-risk and high-risk groups were higher than those in the middle-risk and low-risk groups (P ＜ 0.05);after treatment,the levels of serum LDH,β2-MG,and CEA in stable disease (SD) and progression disease (PD) patients were not significantly different from those before treatment (P ＞ 0.05).While after treatment,the levels of serum LDH,β2-MG and CEA in complete relief (CR) and partial remission (PR) patients were lower than those before treatment (P ＜ 0.05),and were lower than those in SD and PD patients.Conclusions The level of serum LDH,β2-MG and CEA in patients with NHL increased,and the combined detection of the level changes is of great clinical value in the determination of clinical stage,malignant degree,clinical efficacy and prognosis of NHL patients.

Changes of serum LDH, CEA and β2-MG levels in non-Hodgkin's lymphoma patients in different situations and their clinical significance / 中国医师杂志

Objective@#To investigate the changes of serum carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), β2-microglobulin (β2-MG) levels in non-Hodgkin's lymphoma (NHL) patients and their clinical significance.@*Methods@#From February 2015 to February 2018, 54 patients with NHL who were hospitalized in Shiyan People's Hospital were selected as the observation group. All patients underwent two cycles of chemotherapy combined with radiation therapy. Another 54 healthy subjects were selected as the control group. To observe the changes of serum LDH, β2-MG, CEA levels in the control group, and compare the changes of serum LDH, β2-MG, CEA levels before and after treatment with different clinical stages, different conditions, and different effects in NHL.@*Results@#The levels of serum LDH, β2-MG, and CEA in the observation group were higher than those in the control group (P<0.05); the levels of serum LDH, β2-MG, and CEA in patients with NHL in stage Ⅲ to Ⅳ were higher than those in stage Ⅰ to Ⅱ (P<0.05); the levels of serum LDH, β2-MG, and CEA in patients with NHL in the middle-high-risk and high-risk groups were higher than those in the middle-risk and low-risk groups (P<0.05); after treatment, the levels of serum LDH, β2-MG, and CEA in stable disease (SD) and progression disease (PD) patients were not significantly different from those before treatment (P>0.05). While after treatment, the levels of serum LDH, β2-MG and CEA in complete relief (CR) and partial remission (PR) patients were lower than those before treatment (P<0.05), and were lower than those in SD and PD patients.@*Conclusions@#The level of serum LDH, β2-MG and CEA in patients with NHL increased, and the combined detection of the level changes is of great clinical value in the determination of clinical stage, malignant degree, clinical efficacy and prognosis of NHL patients.

Antiphospholipid and Antinuclear Antibodies in Children with Idiopathic Epilepsy: A 2-Year Prospective Study

Beta-2 agonistas para el tratamiento de bronquiolitis / Beta-2 agonists for the treatment of bronchiolitis

INTRODUCCIÓN La bronquiolitis es la inflamación aguda de las vías aéreas de pequeño calibre, teniendo como causa principal las infecciones virales. Es altamente frecuente en menores de dos años, sobretodo en menores de 12 meses. Existe gran controversia sobre el manejo de esta patología, siendo especialmente cuestionable el uso de beta-2 agonistas de corta acción tanto en el ámbito ambulatorio como hospitalario. MÉTODOS Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos siete revisiones sistemáticas que en conjunto incluyen 47 estudios primarios, de los cuales 44 corresponden a ensayos aleatorizados. Concluimos que el uso de beta-2 agonistas podría no tener ningún beneficio en el manejo de la bronquiolitis, en términos de necesidad de hospitalización y/o duración de la misma. Por otra parte, podría aumentar efectos adversos como arritmias, sin embargo, la certeza de esta evidencia es baja

Comparative study of adverse drug reaction pattern of two anti-asthma groups of drugs in a tertiary care hospital

Background: Bronchial Asthma is one of the worldwide health problems associated with increased morbidity and also mortality. Bronchial Asthma is a disease of airways that is characterized by increased responsiveness of the trachea-bronchial tree. Anti asthmatic drugs are associated with adverse effects which can affect the compliance and course of treatment. Monitoring adverse drug reactions in asthma will play a vital role in alerting physicians about the possibility and circumstances of such events, thereby protecting the user population from avoidable harm.Methods: The study was conducted in 500 bronchial asthma patients (250 patients in Beta 2 agonist group (Salbutamol) and 250 patients in Methylxanthine group (Deriphyllin) who fulfilled the study criteria and were observed for three months at Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai. Their prescriptions were collected and analysed. Adverse drug reactions(ADRs) in each group were collected and evaluated. The causality assessment was done by WHO-UMC assessment scale and severity by using Modified Hartwig-Seigel severity assessment scale.Results: Total 38% of patients taking anti-asthma drugs were encountered adverse drug reactions and were more common in elderly females (61 to 70 years). Adverse Drug Reactions were more common in Methylxanthine group (48%) compared to Beta 2 agonist group (28%). Headache (38%) was the commonest ADR in Methylxanthine group and Tremors (31%) in Beta 2 agonist group. Most of ADRs were mild (95 %), manageable and comes under possible (60 %) category of WHO causality assessment scale.Conclusions: Treatment of Bronchial Asthma is mainly based on Beta 2 agonist and Methylxanthine group. So, occurrence of ADR is much common. Our study offers a representative idea of the ADR profile of anti asthmatic drugs. Constant vigil in detecting ADRs and subsequent dose adjustments can make therapy with anti asthmatic drugs safer and more effective. This, in turn, will improve compliance.