Vascular Endothelial Growth Factor Expression in Breast Carcinoma and its Association with Expression of Estrogen Receptors, Progesterone Receptors and HER-2/neu and Molecular Subtypes

Background: The management of breast carcinoma depends on several molecular markers and tumor stages. In the last decades, estrogen receptors (ER), progesterone receptors (PR), and HER-2/neu have shown good therapeutic responses. Among other molecular markers, vascular endothelial growth factor (VEGF) is becoming more widely used as a prognostic indicator in patients with breast carcinoma. Anti-VEGF therapy already has been proven as an effective chemotherapeutic agent in some other carcinomas. The study aimed to find out the immunohistochemical expression of Vascular Endothelial Growth Factor (VEGF) in breast carcinoma and its possible correlation with the expression of ER, PR, and HER-2/neu and molecular subtypes to evaluate its prognostic value. Material & Methods: This study was conducted in the Department of Pathology, BIRDEM General Hospital, Dhaka, from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Slides of all cases were stained with ER, PR, HER-2/neu, and VEGF antibodies following the avidin-biotin-peroxidase staining method. Results: Among 45 cases, 60% showed positive immunohistochemical expression of VEGF. Most of these cases (71.1%) were ER/PR positive. VEGF did not show a significant association with other molecular markers or molecular subtypes. Conclusion: Although, the potential prognostic value of VEGF has not been confirmed. Based on the findings of the current study, it can be assumed that VEGF plays an important role in the pathogenesis of breast cancer. So, it may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Chinese medicine Jiangzhuo mixture regulates glucose and lipid metabolism in obese rats through TLR4/I κB α/NF- κB signaling pathway / 浙江大学学报·医学版

OBJECTIVES@#To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats.@*METHODS@#Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues.@*RESULTS@#Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05).@*CONCLUSIONS@#Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.

Platycladi Semen oil ameliorates Aβ_(25-35)-induced brain injury in mice based on network pharmacology and gut microbiota / 中国中药杂志

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aβ_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aβ_(25-35), 200 μmol·L~(-1), 0.15 μL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aβ_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aβ_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

Effect of hemopurification on acute chlorfenapyr poisoning / 中华急诊医学杂志

Objective:To evaluate the therapeutic effect of hemopurification on acute chlorfenapyr poisoning according to the blood concentration of chlorfenapyr and to provide experience for clinical treatment.Methods:Two patients who presented to our Emergency Department following an ingestion of chlorfenapyr and then were treated with hemopurification in 2022 were included. The concentrations of chlorfenapyr and its highly toxic metabolite tralopyril were dynamically monitored, and the clinical data of the patients were collected.Results:Case 1 was given hemoperfusion for the first time 13 hours after ingestion. During l hour hemoperfusion, the tralopyril decreased by 28.82%. The concentration increased and exceeded the pre-perfusion level after 2 hours of hemoperfusion. After three times of hemoperfusion, the concentrations of chlorfenapyr and tralopyril were still higher than those before the first time, reaching 248 ng/mL and 1 307 ng/mL respectively. The concentration of chlorfenapyr showed a downward trend after 130 h, and the tralopyril in blood reached the peak 3 164 ng/mL at 130 h and decreased to 2 707 ng/mL at 178 h. In case 2, the blood chlorfenapyr and tralopyril concentration was 392 ng/mL and 7 598 ng/mL respectively 150 hours after ingestion. The blood chlorfenapyr concentration decreased by 37.75% respectively after first hemoperfusion, and the tralopyril concentration decreased by 38.02% respectively. During 85 hours of continuous veno-venous hemodiafiltration (CVVHDF), the concentration of tralopyril was maintained at 4 234~6 410 ng/mL. Case 1 was followed up to 12 days and lost follow-up. Case 2 died and the survival time was 247 hours.Conclusions:Hemoperfusion can scavenge tralopyril, but CVVHDF has poor scavenging ability for tralopyril. And the apparent volume of distribution (Vd) of chlorfenapyr and tralopyril are large. After ingestion, chlorfenapyr spreads to various tissues quickly, and it is easy to accumulate in the adipose tissue. The chlorfenapyr in the tissue slowly is released back to the blood and stays in the blood for a long time. The peak concentration of chlorfenapyr appeared earlier than that of tralopyril. Clinicians should pay attention to the early removal of toxins from the digestive tract.

Effects of S1P/S1PR1 pathway on high glucose induced epithelial-mesenchymal transition of rat renal tubular epithelial cells by regulating ROS/NLRP3 / 中国药理学通报

Aim To explore the effect of S1P/S1PR1 signaling pathway on high glucose(HG)-induced epithelial-mesenchymal transition of rat renal tubular epithelial cells and its possible mechanism. Methods Cells were treated with different concentrations of glucose, and intracellular S1P expression was detected by ELISA and S1PR1 protein expression was detected by Western blot. The cells were divided into normal control group, HG group and HG + siS1PR1 group. The expression of E-cadherin, Vimentin, Fibronectin and Twist mRNA were detected by RT-qPCR and E-cadherin, α-SMA, Vimentin, NLRP3, ASC and NF-κB protein expression were detected by Western blot, and the levels of reactive oxygen species(ROS) were detected by flow cytometry. The cells were divided into normal control group, S1P group and S1P + siS1PR1 group. Vimentin, Snail, α-SMA, NLRP3, ASC and NF-κB protein expressions were detected by Western blot, and ROS levels were measured by fluorescence microscopy. Results ELISA results showed that the content of S1P in cells increased significantly under high glucose stimulation. Western blot results showed that S1PR1 protein expression was significantly higher at 30 mmol · L

Improvement of indirect immunofluorescence technique to detect antineutrophil cytoplasmic antibodies and its impact on test positivity rate

The indirect immunofluorescence (IIF) technique for antineutrophil cytoplasmic antibodies (ANCA) detection is subject to substantial differences across laboratories. This study aimed to assess the impact of improvements in the IIF-ANCA technique on the positivity rate of ANCA tests. A cross-sectional study was performed with serum samples from patients with ANCA-associated vasculitis (AAV), autoimmune hepatitis (AIH), and ulcerative colitis (UC). A paired analysis was performed for IIF-ANCA results using the traditional method and a modified protocol after a series of specific adjustments in the technique based on the protocol of IIF-ANCA test performed at a nation-wide private laboratory in Brazil. ANCA specificity was assessed by ELISA for anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) antibodies. Sixty-one patients were evaluated. The positivity rate of IIF-ANCA tests at disease presentation performed at the University reference laboratory was 32.3% in AAV, AIH, and UC patients, whereas the positivity rates of IIF-ANCA and ELISA tests in other laboratories were 75.0 and 72.7%, respectively. After modifications in the IIF-ANCA technique, there was a significant increase in the positivity rate (14.8 vs 34.3%; P=0.0002) and in median titers [1/40 (1/30-1/160) vs 1/80 (1/40-1/80); P=0.0003] in AAV, AIH, and UC patients. UC had the highest increment in positive results from 5.3 to 36.8%. There was poor agreement between MPO- or PR3-ANCA and both IIF-ANCA techniques. In conclusion, modifications in the IIF-ANCA protocol led to a significant improvement in its positivity rate and titers.

Wolff-Parkinson-White Apresentado como QRS Alternante e Outros Diagnósticos Diferenciais em uma Grande Coorte de Triagem de ECG Pré-Participação / Wolff-Parkinson-White Presenting as QRS Alternans and Other Differential Diagnoses in a Large Pre-Participation ECG Screening Cohort

Resumo Fundamento A síndrome de Wolff-Parkinson-White (WPW) é uma condição pró-arrítmica que pode exigir restrição de atividades extenuantes e é caracterizada por sinais de ECG, incluindo ondas delta. Observamos casos de padrões intermitentes de WPW apresentando-se como QRS alternante ('WPW alternante') em uma grande coorte de triagem de ECG pré-participação de homens jovens que se candidataram ao recrutamento militar. Objetivos Nosso objetivo foi determinar o padrão de WPW alternante, as características do caso e a prevalência de outros diagnósticos diferenciais relevantes apresentando-se como alternância de QRS em um ambiente de pré-participação. Métodos Cento e vinte e cinco mil cento e cinquenta e oito recrutas militares do sexo masculino prospectivos foram revisados de janeiro de 2016 a dezembro de 2019. Uma revisão de prontuários médicos eletrônicos identificou casos de WPW alternante e padrões ou síndrome de WPW. A revisão de prontuários médicos eletrônicos identificou casos de diagnósticos diferenciais relevantes que podem causar alternância de QRS. Resultados Quatro indivíduos (2,2%) apresentaram WPW alternante em 184 indivíduos com diagnóstico final de padrão ou síndrome de WPW. Dois desses indivíduos manifestaram sintomas ou achados eletrocardiográficos compatíveis com taquicardia supraventricular. A prevalência geral de WPW alternante foi de 0,003%, e a prevalência de WPW foi de 0,147%. As WPW alternantes representaram 8,7% dos indivíduos com QRS alternantes, e QRS alternantes tiveram prevalência de 0,037% em toda a população. Conclusões A WPW alternante é uma variante da WPW intermitente, que compreendeu 2,2% dos casos de WPW em nossa coorte de triagem pré-participação. Não indica necessariamente um baixo risco de taquicardia supraventricular. Deve ser reconhecido na triagem de ECG e distinguido de outras patologias que também apresentam QRS alternantes.

Abstract Background Wolff-Parkinson-White (WPW) syndrome is a proarrhythmic condition that may require restriction from strenuous activities and is characterized by ECG signs, including delta waves. We observed cases of intermittent WPW patterns presenting as QRS alternans ('WPW alternans') in a large pre-participation ECG screening cohort of young men reporting for military conscription. Objectives We aimed to determine the WPW alternans pattern, case characteristics, and the prevalence of other relevant differential diagnoses presenting as QRS alternans in a pre-participation setting. Methods One hundred twenty-five thousand one hundred fifty-eight prospective male military recruits were reviewed from January 2016 to December 2019. A review of electronic medical records identified cases of WPW alternans and WPW patterns or syndrome. Reviewing electronic medical records identified cases of relevant differential diagnoses that might cause QRS alternans. Results Four individuals (2.2%) had WPW alternans out of 184 individuals with a final diagnosis of WPW pattern or syndrome. Two of these individuals manifested symptoms or ECG findings consistent with supraventricular tachycardia. The overall prevalence of WPW alternans was 0.003%, and the prevalence of WPW was 0.147%. WPW alternans represented 8.7% of individuals presenting with QRS alternans, and QRS alternans had a prevalence of 0.037% in the entire population. Conclusions WPW alternans is a variant of intermittent WPW, which comprised 2.2% of WPW cases in our pre-participation screening cohort. It does not necessarily indicate a low risk for supraventricular tachycardia. It must be recognized at ECG screening and distinguished from other pathologies that also present with QRS alternans.

A cross-sectional study of immunohistochemical evaluation of surface epithelial ovarian tumors

Background: Ovarian cancer is one of the most common malignancies in female patients. In recent years, immunohistochemistry (IHC) has emerged as an important tool in the diagnosis of ovarian tumors. The study aimed to assess estrogen receptors (ERs), progesterone receptors (PRs), Her-2-neu, and Ki-67 by IHC in surface epithelial ovarian tumors and to correlate the findings with different variables. Materials and Methods: It was a cross-sectional study. Oophorectomy/salpingo-oophorectomy/cystectomy specimens were included in this study. IHC was done on 10% neutral buffer formalin-fixed paraffin-embedded tissue sections by using Dako FLEX Ready to use mouse monoclonal antibodies and DakoEnvisionTM FLEX/ HRP detection reagent. Results: The study includes 81 cases of surface epithelial ovarian tumors (a benign serous tumor [20], a benign mucinous tumor [18], a borderline mucinous tumor [5], low-grade serous carcinoma [8], high-grade serous carcinoma [19], mucinous carcinoma [7], endometrioid carcinoma [2], borderline Brenner tumor [1], and malignant Brenner tumor [1]. ER had higher expression in malignant cases (51.33%) than in benign cases (15.8%). PR had higher expression in malignant tumors (54.05%) incomparable to benign (18.42%) and borderline tumors (16.66%). PR had higher expression in high grade. Expression of Her-2-neu positivity was found to be 29.7% out of the total 81 cases. Her-2-neu was found in 11 high-grade tumors among 31 malignant cases. CA-125 levels were significantly higher in malignant ovarian tumors (P = 0.0143). Proliferation activity was considered low if proliferation index (PI) <10% and high if PI >10%. The study showed high PI in malignant tumors. Conclusion: Expression of these marks in adjunct to H&E diagnosis may prove beneficial in differentiating benign, borderline, and malignant cases, in which a diagnosis of borderline cases based on sole H & E is doubtful.

Dynamic evaluation of left ventricular systolic function in patients with pregnancy-induced hypertension by three-dimensional speckle tracking imaging / 中国基层医药

Objective:To investigate the clinical efficacy of three-dimensional speckle tracking imaging in the dynamic evaluation of left ventricular systolic function in patients with pregnancy-induced hypertension.Methods:50 patients with pregnancy-induced hypertension, who received prenatal examination in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from July 2019 to June 2020 and finally gave birth, were included in the observation group. An additional 50 healthy pregnant women who concurrently received prenatal examination were included as controls. All participants underwent routine echocardiography and three-dimensional speckle tracking imaging examinations. Parameters related to left ventricular systolic function were recorded. Routine echocardiography parameters and three-dimensional speckle tracking imaging parameters were compared between the observation and control groups.Results:There were no significant differences in routine echocardiography parameters (including heart rate, left ventricular end-diastolic diameter, interventricular septum thickness in end-diastole, left ventricular posterior wall thickness in diastole, and left ventricular ejection fraction) between before treatment, after treatment, and 3 months after delivery in the observation group, and between observation and control groups before treatment (all P > 0.05). The absolute values of left ventricular global longitudinal strain (LVGLS) [(-18.41 ± 2.23)% vs. (-26.03 ± 2.79)%], left ventricular global circumferential strain (LVGCS) [(31.29 ± 3.09)% vs. (37.45 ± 3.68)%], left ventricular global radial strain (LVGRS) [(-19.37 ± 2.19)% vs. (-24.59 ± 2.74)%], and left ventricular global area peak systolic strain (LVGAS) [(-26.61 ± 3.18)% vs. (-39.23 ± 3.96)%] measured before treatment were significantly lower in the observation group than in the control group ( t = 6.31 -14.87, all P < 0.05). The absolute values of LVGLS, LVGCS, LVGRS, and LVGAS in the observation group were significantly higher after treatment [(-24.79 ± 2.68)%, (35.94 ± 3.25)%, (-22.48 ± 2.41)%, (-37.54 ± 3.38)%] and 3 months after delivery [(-25.64 ± 2.72)%, (36.63 ± 3.47)%, (-23.91 ± 2.69)%, (-38.49 ± 3.64)%] than before treatment ( t = 4.08 - 10.59, P < 0.05). There were no significant differences in LVGLS, LVGCS, LVGRS, and LVGAS between observation group and control groups at each time point studied ( t = 0.47 - 1.19, P = 0.182 - 0.652 > 0.05). The absolute svalues of LVGLS, LVGCS, LVGRS and LVGAS in patients with pregnancy-induced hypertension were positively correlated with left ventricular ejection fraction values ( r = 0.638 - 0.775, P = 0.009 - 0.041 < 0.05). Conclusion:Three-dimensional speckle tracking imaging can be used to dynamically evaluate the impairment of left ventricular systolic function in patients with pregnancy-induced hypertension. This technique helps guide early intervention and prognosis evaluation and has a high clinical application value.

Correlation of prolongation of PR interval with carotid atherosclerosis in middle-aged and elderly patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective:To investigate the relationship between prolonged PR interval and carotid atherosclerosis(CAS)in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 537 middle-aged and elderly inpatients with T2DM in the Southern Branch of the Sixth People′s Hospital of Shanghai Jiaotong University from January 2019 to January 2021 were selected as the research objects. Color Doppler ultrasound was used to detect bilateral carotid artery intima-media thickness(CIMT). The subjects were divided into carotid atherosclerosis group(CAS group, n=352)and non-carotid atherosclerosis group(NCAS group, n=185). The difference in the PR interval of ECG between the two groups was compared. Pearson or Spearman rank correlation analysis was used for evaluating the correlation of PR interval and CAS lesions with various clinical index. The relationship between PR interval and CAS lesions was adopted by multivariate logistic regression analysis. Results:The average PR interval of middle-aged and elderly patients with T2DM was(164.57±23.02)ms. The average PR interval in CAS group was significantly higher than that in NCAS group [(169.76±24.28) vs (154.70±16.42)ms, P<0.01]. The results of multifactorial logistic regression analysis showed that age, low density lipoprotein-cholesterol, serum osteocalcin, and PR interval were independent factors influencing the development of CAS lesions in middle-aged and elderly patients with T2DM( OR=1.079, 1.936, 0.879, 1.039, respectively, P<0.05 or P<0.01)where each 1 ms increase in PR interval was associated with a 3.9% increase in the risk of CAS in middle-aged and elderly patients with T2DM( OR=1.039, 95% CI 1.006-1.073, P=0.020). Multivariate logistic regression analysis showed that middle-aged and elderly type 2 diabetic patients with PR interval≥158 ms were 4.072 times more likely to have CAS lesions than those with PR interval<158 ms( OR=4.072, 95% CI 1.417-11.702, P<0.01). Conclusion:The PR interval of electrocardiogram is correlated with CAS lesions in middle-aged and elderly patients with T2DM. Middle-aged and elderly type 2 diabetic patients with significantly prolonged PR interval should be reminded to screen for CAS lesions early.

Effects of the S1PR3 specific agonist peptide GPS-725.017 on acute lung injury in mice / 中华急诊医学杂志

Objective:To design a modified S1PR3 specific agonist, GPS-725.017, and investigate its protective effect on acute lung injury by promoting macrophage clearance of bacteria.Methods:A short peptide derived from the intracellular region of S1PR3 receptor was named GPS725.017, which was modified with norleucine (Nle) and myristicacid (myr) at its N terminus. Mice were divided into the sham operation group, solvent group and GPS-725.017 treatment group. The acute lung injury model was induced by endotracheal injection of E. coli (5×10 6 CFU), and the experimental group was treated with GPS-725.017 (10 mg/kg). The 48-h survival rate of mice was recorded. After 5 h of modeling, the bacterial load and inflammatory cytokines in peripheral blood and lung were detected, and Vps34 protein content in alveolar macrophages was determined by Western blot. After 12-h of modeling, lung tissues were collected for H&E staining and pathological scores. Results:Compared with the solvent group, the survival rate of mice in the GPS-725.017 treatment group was significantly improved ( P<0.01), the bacterial CFU in blood and alveolar lavage fluid was significantly lower than that in the solvent group ( P<0.001), and the levels of TNF-α and IL-1β in blood and alveolar lavage fluid were significantly lower than those in the solvent group ( P<0.001). Western blot showed that the expression level of Vps34 protein in alveolar macrophages was significantly higher than that in the solvent group ( P<0.01). Histopathology result showed that the pathological damage of lung in the treatment group was significantly less than that in the solvent group ( P<0.001). Conclusions:The modified synthetic S1PR3 specific agonist GPS-725.017 could specifically activate the S1PR3 receptor on the membrane of alveolar macrophages and up-regulate the expression level of intracellular Vps34 protein, which can promote the removal of bacteria in alveolar macrophages, significantly reduce the degree of lung injury and improve the survival rate in ALI mice.

p53R72P polymorphisms in Mongolian patients with hepatocellular carcinoma / Монголын Анагаах Ухаан

Introduction@#Hepatocellular carcinoma incidence and mortality per 100,000 population in Mongolia is the highest in the world. The individual’s genetic factors and new genetic changes are considered an important effect on the origin and development cancer. We aimed to investigate whether p53R72P polymorphisms were associated with the risk of hepatocellular carcinoma in Mongolian patients.@*Material and Method@#p53R72P polymorphisms were evaluated in 80 controls and 38 HCC cases using a PCRrestriction fragment length polymorphism assay.@*Results@#The mean age was 58.5±13.6 years in the case group and 63.2±8.1 years in the control group. Hepatocellular carcinoma is most common in 50-59 (n=14, 36.8%) and 60-69 (n=14, 36.8%) ages. Of the HCC group, 4 (10.8%) were diagnosed with tumor at stage II, 23 (62.2%) at stage III, and 11 (27%) at stage IV. </br>The results revealed that the heterozygous (Arg/Pro (PR)) genotype of p53R72P increased statistically significant the risk of hepatocellular carcinoma (OR=4.222, 95% CI 1.669-10.684) compared to the wildtype (R/R) genotype. (p=0.002). Moreover, the homozygous (Pro/Pro (P/P)) genotype of p53R72P increased the risk of carcinoma (OR=1.333, 95% CI 0.414-4.299) but not statistically significant. (p=0.63). Heterozygous (Arg/Pro (PR)) genotype of p53R72P in the tumor tissue was associated with a statistically significant (OR=3.3, 95% CI 1.274-8.57) increase in the risk of HCC (p=0.014). Pro/Pro (PP) genotype increased the risk of the carcinoma by 2.4 times (OR=2.44, 95% CI 0.865-6.908), but it was not significant. (p=0.092). Pro/Pro (PP) genotype of p53R72P in the tumor tissue compared to normal tissue of a case group increased the risk of cancer by 1.8 times (OR=1.833, 95% CI 0.472- 7.126), which was not statistically significant (p=0.382).@*Conclusion@#Taken together, Heterozygous (Arg/Pro (PR)) genotype of p53R72P increases the risk of hepatocellular carcinoma in Mongolians. Further studies with larger populations are needed to confirm these results.

Impacto del uso de PCR múltiple en diagnóstico etiológico y tratamiento de infecciones respiratorias agudas en un hospital privado del norte del país / Impact of the use of multiplex PCR on etiological diagnosis and treatment of acute respiratory infections in a private hospital of the north of the country

Resumen Antecedentes y objetivo: Las enfermedades del sistema respiratorio son causa frecuente de prescripción de antibióticos. Actualmente se emplean nuevas tecnologías para su diagnóstico como el FilmArray Respiratory Panel. El objetivo de este estudio es identificar la correlación entre el diagnóstico y tratamiento de infecciones de vías respiratorias con el resultado de PCR para virus respiratorios. Material y métodos: Estudio descriptivo, transversal, retrospectivo, se incluyeron 134 pacientes atendidos en el Hospital Christus Muguerza en Saltillo, Coahuila. Para todos los casos se analizaron los resultados del panel y el tratamiento que recibieron los pacientes. Resultados: El 58 % recibió tratamiento antibiótico a su ingreso, el 13 % tratamiento combinado (antibiótico + antiviral), 27 % recibió tratamiento sintomático y el 2 % fue tratado con antiviral de primera instancia. Posterior al resultado el 38 % continuó con antibiótico, el 30 % con antibiótico y antiviral, 13.8 % se manejó con antiviral y el 18.2 % con tratamiento sintomático. Conclusión: A pesar de la alerta mundial por la resistencia a los antimicrobianos se sigue tratando a los pacientes con antibióticos, por una situación que se cree está influenciada por varios factores.

Abstract Background and objective: Respiratory system diseases represent one of the leading cause of prescription of antibiotics. At present, new technologies for the diagnosis are being used, including the FilmArray Respiratory Panel. The objective was to identify the correlation between the diagnosis and treatment of respiratory tract infections with the result of PCR for respiratory viruses. Material and methods: Descriptive, cross-sectional, restrospective study. 134 patients were included treated at the Christus Muguerza Hospital in Saltillo, Coahuila. For all cases, the positive results of this test and the treatment patients received were analyzed. Results: 58 % received antibiotic treatment at admission, 13 % received combined treatment (antibiotic + antiviral), 27 % received symptomatic treatment since their admission and 2 % whit antiviral. After receiving a positive result for respiratory viruses, 38 % continued with antibiotics, 30 % with antibiotics and antivirals, 13.8 % only managed with antivirals and 18.2% with symptomatic treatment. Conclusion: Although we are currently on global alert for resistance to antibiotics, there is a lack of awareness about the prescription of antibiotics, due to a situation which is believed to be influenced by several factors.

Qualitative and quantitative analysis of Paris polyphylla var. chinensis by UPLC-Q-TOF-MS/MS and HPLC / 中国中药杂志

Paridis Rhizoma(PR) is prepared from the dried rhizome of Paris polyphylla var. yunnanensis(PPY) or P. polyphylla var. chinensis(PPC) in Liliaceae family. The rapid development of PPY or PPC planting industry resulted from resource shortage has caused the waste of a large number of non-medicinal resources. To clarify the chemical compositions in rhizomes, fibrous roots, stems, leaves, seeds and pericarps of PPC, and explore the comprehensive application value and development prospect of these parts, the qualitative and quantitative analyses on the different parts of PPC were carried out by ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) and high performance liquid chromatography(HPLC). A total of 136 compounds were identified, including 112 steroidal saponins, 6 flavonoids, 11 nitrogen-containing compounds and 7 phytosterols. Rhizomes, fibrous roots, and seeds mainly contained protopennogenyl glycosides and pennogenyl glycosides; leaves and stems mainly contained protodiosgenyl glycosides and diosgenyl glycosides; pericarps mainly contained pennogenyl glycosides, followed by diosgenyl glycosides. The total level of four saponins was the highest in fibrous roots and rhizomes, followed by those in the pericarps and arillate seeds, and the lowest in the stems and exarillate seeds. This study can provide data support for the comprehensive development and rational application of non-medicinal parts of PPC.

TGF-β1-regulated miR-3691-3p targets / 亚洲男科学杂志(英文版)

Transforming growth factor-β1 (TGF-β1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-β1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA. miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue, and its expression level correlated inversely with aggressive clinical pathological features. Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation, migration, and invasion, and promoted apoptosis. The miR-3691-3p target genes E2F transcription factor 3 (E2F3) and PR domain containing 1, with ZNF domain (PRDM1) were upregulated in miR-3691-3p-overexpressing PCa cells, and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation, migration, and invasion. Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis. Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p, both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue. Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1. These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.

The Role of SPHK￣S1P Axis in Angiogenesis￣related Diseases / 中国生物化学与分子生物学报

Angiogenesis refers to the process of forming new blood vessels based on original blood vessels. Pathological angiogenesis is a sign of a series of diseases such as cancer, cardiovascular diseases, and retinopathy. Sphingosine 1-phosphate (S1P) is a signaling lipid synthesized by sphingosine kinase (SPHK) that exerts its diverse biological and pathophysiological roles through five G protein-coupled receptors (S1PR1-5) and initiates various signaling cascades by activating receptors that affect cell fate, vascular tension, endothelial function and integrity, and lymphocyte transport. The imbalance ofproduction and signal is closely related to pathological processes such as endothelial dysfunction and abnormal angiogenesis. Accumulating evidence suggests that the SPHK-S1P axis plays an important role in angiogenesis, especially in the development of tumors, diabetes retinopathy, atherosclerosis, myocardial infarction and other cardiovascular diseases. Studies on its roles and functions can provide new insights and drug therapeutic targets for the treatment of angiogenesis-related diseases. This review describes the molecular mechanisms by which the SPHK-S1P axis affects endothelial cell and smooth muscle cellproliferation, endothelial cell migration and the formation of lumen by endothelial cells, pericytes and smooth muscle cells through SPHK and S1PR1-5. The review also elaborates how the SPHK-S1P axis affects angiogenesis in tumors, cardiovascular diseases, diabetes and retinopathy through SPHK and S1PR1-5, and aims to provide new therapeutic strategy for related diseases by understanding the molecular mechanism of the SPHK-S1P axis in angiogenesis.

Role of TIPE2 in endogenous protective mechanism of acute lung injury in septic mice: the relationship with TAK1/p38 MAPK/NF-κB signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of tumor necrosis factor-alpha-induced protein-8 like-2 (TIPE2) in endogenous protective mechanism of acute lung injury (ALI) in septic mice and the relationship with transforming growth factor-β-activated protein kinase (TAK1)/p38-mitogen-activated phosphokinase (p38 MAPK)/nuclear factor κB (NF-κB) signaling pathway.Methods:Sixteen male wild-type mice and 16 TIPE2-knockout mice, aged 6-8 weeks, weighing 20-25 g, were randomly divided into 4 groups: wild-type sham operation group (group WT-sham), wild-type ALI group (group WT-ALI), TIPE2-knockout sham operation group (group KO-sham) and TIPE2-knockout ALI group (group KO-ALI), with 8 mice in each group.The ALI model was established by cecal ligation and perforation (CLP) in septic mice.Mice were sacrificed at 24 h after CLP to acquire left carotid artery blood samples and lung tissue sections.Lung tissue sections were stained with hematoxylin & eosin (H&E) to examine the pathological changes and lung injury scores were assessed.Arterial blood samples were collected from the left carotid artery for blood gas analysis, and oxygenation index (OI) was calculated.Bronchoalveolar lavage fluid was collected to measure polymorphonuclear neutrophil (PMN) count.The expression of TIPE2, phosphorylated TAK1 (p-TAK1), phosphorylated p38 MAPK (p-p38) MAPK and phosphorylated NF-κB p65 (p-NF-κB p65) was detected using Western blot analysis.The levels of interleukin-1beta (IL-1β) and IL-6 in serum were determined by enzyme-linked immunosorbent assay.Results:Compared with group WT-sham, the lung injury score, PMN counts and concentrations of IL-1β and IL-6 in serum were significantly increased, the expression of p-TAK1, p-p38 MAPK and p-NF-κB p65 was up-regulated, the PaO 2 and OI were decreased, and the expression of TIPE2 was down-regulated in WT-ALI and KO-ALI groups ( P<0.05). Compared with group WT-ALI, the lung injury score, PMN counts and concentrations of IL-1β and IL-6 in serum were significantly increased, the expression of p-TAK1, p-p38 MAPK and p-NF-κB p65 was up-regulated, the PaO 2 and OI were decreased, and the expression of TIPE2 was down-regulated in group KO-ALI ( P<0.05). Conclusion:TIPE2 is involved in the endogenous protective mechanism underlying ALI in septic mice, which is related to inhibiting activation of TAK1/p38 MAPK/NF-κB signaling pathway.

Endocarditis por bartonella asociada a glomerulonefritis y neurorretinitis / Bartonella endocarditis associated with glomerulonephritis and neuroretinitis

La endocarditis bacteriana con hemocultivo negativo constituye un dilema diagnóstico. Tanto Bartonella como Coxiella pueden causarla, con presentaciones clínicas similares que pueden simular una vasculitis sistémica no infecciosa. Sin embargo, difieren en el tipo y la duración del tratamiento, por lo que es fundamental identificar el agente etiológico. Presentamos un caso de endocarditis por Bartonella henselae asociada a glomerulonefritis y neurorretinitis, con hemocultivo negativo, anticuerpos anticitoplasma de neutrófilos y antiproteinasa 3 positivos, y serología positiva para Bartonella con reacción cruzada para Coxiella burnetti. El diagnóstico etiológico fue confirmado a posteriori mediante amplificación y secuenciación parcial del gen ribC a partir de tejido de la válvula cardíaca. El paciente recibió tratamiento antibiótico e inmunosupresor seguido de recambio valvular aórtico y presentó evolución favorable.

Blood-culture negative endocarditis is a diagnostic challenge. Both Bartonella and Coxiella can cause it with similar clinical presentations mimicking a systemic vasculitis. The identification of the etiologic agent is essential because they differ in treatment type and duration. We present a case of blood-culture negative endocarditis caused by Bartonella henselae, associated with glomerulonephritis and neuroretinitis, with negative blood culture, positive anti-neutrophil cytoplasmic and antiproteinase 3 antibodies. The serology was positive for Bartonella with cross-reactivity to Coxiella burnetti. The etiological diagnosis was achieved by polymerase chain reaction amplification and sequencing of a ribC gene fragment. The patient received antibiotic and immunosuppressive treatment followed by replacement of the aortic valve with favorable medium-term evolution.

Internal Consistency Study of EORTC QLQ-C30 and QLQ-PR25 Questionnaires for Quality of Life Assessment among Prostate Cancer Patients in a University Hospital, Kuala Lumpur, Malaysia

@#Prostate cancer is forth most common diagnosed tumors in Malaysian male. The use of a self-reported, quality of life assessment is important for clinical practice, care taker and researcher to evaluate the level of quality of life. The aim of this study was to measure the internal consistency of the translated Malay Language EORTC QLQ-C30 and EORTC PR-25 questionnaires among prostate cancer patient at National University of Malaysia hospital in Kuala Lumpur, Malaysia. Methods This was a cross sectional study conducted between July 2017 and Dec 2017. The respondent comprised of 110 Malaysian prostate cancer patients who were under follow up at Urology and Oncology Clinic. Sets of translated Malay language EORTC QLQ C30 and EORTC PR-25 consisted of functional, symptom and global health status domains were administered to assess their quality of life. Results The translated questionnaires were acceptable by 110 respondents. Cronbach`s α coefficient result were 0.913 (EORTC QLQ-C30) and 0.829 (EORTC PR25) respectively suggested that this instrument had good internal consistency. Conclusions Our study confirmed that translated Malay language EORTC QLQ-C30 and QLQ-PR25 questionnaires are acceptable, reliable and valid instrument to be used among Malaysian prostate cancer patients.

Study on the change of PR interval shortening in ECG examination in different periods of pregnancy / 中国基层医药

Objective To research the change of PR interval shortening in ECG examination in different periods of pregnancy.Methods From March 2016 to August 2016,616 pregnant women who underwent maternity examinations in the Women and Children's Hospital of Ningbo were selected in this study.According to the different gestational periods, they were divided into the early pregnancy group ( 198 cases ), the mid -pregnancy group (232 cases) and the late pregnancy group (186 cases).And another 241 non -pregnant women who underwent health examination in our hospital during the same period were selected as controls .All pregnant and non -pregnant women were examined by electrocardiogram ,and the results of electrocardiogram were analyzed.The average heart rate,the average PR interval and the shortened ratio of PR interval were compared between the two groups of women and women with different pregnancy periods ,and the short PR interval distribution of women in different pregnancy periods was observed.Results The average heart rate level ,PR interval and PR interval shortening ratio of pregnant women and non -pregnant women were (76.55 ±7.81) times／min,(0.096 ±0.008) s,12.66% and (72.56 ± 6.49)times／min,(0.138 ±0.014) s,4.98%,respectively.The average heart rate and the shortening ratio of PR interval in pregnant women were significantly higher than those in non -pregnant women, while the average PR interval in pregnant women was significantly lower than that in non -pregnant women,the differences were statistically significant (t＝7.565,χ2 ＝10.879,t＝52.672,all P＜0.05).With the increase of pregnancy cycle ,the shorter the average heart rate and PR interval of pregnant women ,the shorter the average PR interval.The average heart rate,PR interval and PR interval shortening ratio in the early pregnancy group , the mid -pregnancy group and the late pregnancy group were (75.41 ±6.65) times／min,(0.103 ±0.010) s,8.59% and (77.03 ±7.12) times／min, (0.095 ±0.009)s,11.21%and (79.74 ±8.43) times／min,(0.088 ±0.008) s,18.82%,respectively.There were statistically significant differences among the three groups ( t ＝16.720, 116.440, χ2 ＝9.791, all P ＜0.05 ). Conclusion Pregnancy women are prone to have shorten PR interval ,and its incidence increases with the increase of pregnancy cycle,but in most cases belongs to benign electrophysiological changes ,and the prognosis is good without special treatment.It is of great significance for clinical diagnosis and treatment to reduce the outcome of bad pregnancy by observing the shortening of the PR interval of electrocardiogram during the pregnancy .