The role of roxadustat in chronic kidney disease patients complicated with anemia

The incidence of chronic kidney disease (CKD) is increasing worldwide and the current prevalence rate is 13.4%. There are > 120 million CKD patients in China and this number is expected to increase. One of the main abnormalities in patients with CKD and kidney impairment is decreased synthesis of erythropoietin (EPO), which causes anemia and affects iron metabolism. The probability of developing is higher in anemia patients with CKD than in the general population, and the incidence increases as kidney function decreases. Deficient EPO production by the kidney is the most important cause of renal anemia. Notably, anemia in patients with CKD has multiple causes, such as bleeding caused by platelet dysfunction, iron deficiency due to digestive and absorption disorders of the gastrointestinal tract, and shorter red blood cell life. Anemia is also a leading cause of hospitalization in patients with CKD. A new oral medication to treat renal anemia, the hypoxia-inducible factor prolyl hydroxylase inhibitor called roxadustat (FG-4592), regulates iron metabolism and promotes erythropoiesis. This drug has a therapeutic effect on patients with CKD. Roxadustat showed advantages over EPO in clinical experiments. This review summarizes the mechanisms of action, clinical applications, effectiveness, and safety of roxadustat.

Effect of astragaloside IV on PI3K/Akt signaling pathway in substantia nigra of mice with Parkinson′s disease / 中华麻醉学杂志

Objective:To evaluate the effect of astragaloside IV on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in substantia nigra of mice with Parkinson′s disease.Methods:Forty-five SPF healthy male C57BL/6 mice, aged 8 weeks, weighing 19-25 g, were divided into 3 groups ( n=15 each) using a random number table method: control group (group C), Parkinson′s disease group (group PD) and astragaloside IV group (group A). The mouse model of Parkinson′s disease was developed by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) 30 mg/kg everyday for 7 consecutive days.Astragaloside 20 mg/kg was intraperitoneally injected everyday at 30 min before MPTP injection for 7 consecutive days before the model was prepared in group A, and the equal volume of normal saline was given instead in group C. Behavior was measured at 1 day interval after completion of administration.The mice were then sacrificed, and the substantia nigra of the brain tissue were obtained for determination of the expression of tyrosine hydroxylase(TH), phosphorylated PI3K(p-PI3K), phosphorylated Akt(p-Akt), glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) (by Western blot). Results:Compared with C group, the total distance of movement and latency of falling were significantly shortened, the hanging score was decreased, the step width was increased, the expression of TH, p-PI3K, p-Akt and BDNF in substantia nigra was down-regulated, and the expression of GFAP was up-regulated in PD group and A group ( P<0.05). Compared with PD group, the total distance of movement and the latency to fall were significantly prolonged, the hanging score was increased, the step width was reduced, and the expression of TH, p-PI3K, p-Akt and BDNF in the substantia nigra was up-regulated, and the expression of GFAP was down-regulated in group A ( P<0.05). Conclusions:The mechanism by which astragaloside IV improves motor dysfunction is related to the activation of PI3K/Akt signaling pathway, up-regulation of BDNF expression and inhibition of astrocyte activation in mice with Parkinson′s disease.

Relationship between glutathione peroxidases family and survival prognosis in patients with colorectal cancer / 国际肿瘤学杂志

Objective:To investigate the relationship between glutathione peroxidases (GPXs) gene expression in colorectal cancer tissues and survival prognosis, and to construct and evaluate a nomogram prediction model of GPXs for survival prognosis of colorectal cancer patients.Methods:The GPXs gene expresion data and other clinical data of 620 patients with colorectal cancer (455 cases of colon cancer and 165 cases of rectal cancer) were downloaded from The Cancer Genome Atlas (TCGA) database, and the GPXs gene expression data of 820 normal people were downloaded as controls, preprocessed by R language, and the gene expression data were analyzed for differential expression. Spearman rank correlation was used to analyze the correlation between GPXs gene expression and tumor mutation burden (TMB) in colorectal cancer tissues. Cox risk regression model was used to analyze the influencing factors of survival and prognosis of colorectal cancer patients. Nomogram models were constructed to predict overall survival (OS) of colon cancer and rectal cancer patients, and its predictive performance was evaluated by calibration curve.Results:In the GPXs family, there were statistically significant differences in the mRNA expressions of GPX1, GPX2, GPX3, GPX4, GPX5, GPX7 and GPX8 between colon cancer patients and normal population, and the mRNA expressions of GPX1, GPX2, GPX4 and GPX8 in colon cancer patients were higher than those in normal population (all P<0.05) . There were statistically significant differences in the mRNA expressions of GPX1, GPX2, GPX3, GPX4, GPX7 and GPX8 between rectal cancer patients and normal population, and the mRNA expressions of GPX1, GPX2, GPX4, GPX7 and GPX8 in rectal cancer patients were higher than those in normal population (all P<0.05) . Spearman rank correlation analysis showed that GPX2 ( r s=-0.27, P<0.001) and GPX7 ( r s=-0.11, P=0.043) expressions were negatively correlated with TMB in colon cancer. There were no significant correlations between GPXs genes expressions and TMB in rectal cancer tissues (all P>0.05) . In colon cancer, univariate analysis showed that GPX3 ( HR=1.22, 95% CI: 1.05-1.43, P=0.012) , GPX4 ( HR=1.39, 95% CI: 1.01-1.92, P=0.045) , age ( HR=1.02, 95% CI: 1.01-1.04, P=0.010) and pTNM-stage ( HR=1.78, 95% CI: 1.43-2.21, P<0.001) were the influencing factors of OS. Multivariate analysis showed that GPX4 ( HR=1.96, 95% CI: 1.09-3.51, P=0.024) , age ( HR=1.02, 95% CI: 1.00-1.04, P=0.042) and pTNM-stage ( HR=1.61, 95% CI: 1.21-2.15, P=0.001) were the independent risk factors of OS. In rectal cancer, univariate analysis showed that age ( HR=1.08, 95% CI: 1.04-1.13, P<0.001) was the influencing factor of OS. Multivariate analysis showed that GPX7 ( HR=0.44, 95% CI: 0.22-0.88, P=0.020) , GPX8 ( HR=3.17, 95% CI: 1.63-6.17, P=0.001) and age ( HR=1.10, 95% CI: 1.04-1.16, P=0.001) were the independent influencing factors of OS. The consistency index (C-index) of the nomogram model for predicting OS in patients with colon cancer and rectal cancer were 0.71 (95% CI: 0.63-0.79) and 0.88 (95% CI: 0.82-0.94) respectively. The calibration curve showed that the prediction curve of the two models had a good fit with the real curve. Conclusion:GPX4 is an independent risk factor affecting the prognosis of colon cancer patients. Patients with high GPX4 expression have a poor prognosis. GPX7 and GPX8 are independent prognostic factors for rectal cancer patients, and the rectal cancer patients with low GPX7 expression and high GPX8 expression have poor prognosis. The nomogram constructed based on the above factors can better predict the prognosis of patients with colon cancer and rectal cancer.

Prevalence and prediction of pre-hospital medical trauma in Urumqi / 中华急诊医学杂志

Objective To investigate the current situation of pre-hospital trauma emergency medical care of Urumqi in 2011-2018 and predict the situation in the next five years,so as to provide a basis for rational allocation of pre-hospital emergency resources and improvement of health service system.Methods A total of 427 754 pre-hospital emergency patients were collected from January 1,2011 to December 31,2008 in Urumqi.Epidemiological methods were performed for statistical description and analysis.The single-factor gray model [GM (1,1)],multi-factor grey model and moving average model (MA1) was established for predicting the number of pre-hospital trauma patients each year.The single-factor gray model [GM (1,1)] and SARIMA model were used for the seasonal prediction.Results The male-female ratio of pre-hospital trauma patients was 1.98:1 and the incidence rate of male patients (534.91/100 000) was significantly higher than that of female patients (274.88/100 000) (x2=7 659.707,P＜0.01),and the incidence rate of male patients was 1.95 times higher than that of female patients.The trauma patients aged 35-59 years accounted for the largest proportion (42％),and the incidence of the disease was the highest among those aged ≥ 60 years old (644.23/100 000).The incidence ofpre-hospital trauma increased year by year (from 408.86/100 000 in 2011 to 550.02/100 000 in 2017),with a high incidence in summer (27 123,31.03％),especially in August (9 535,10.91％),most of which occurred in the new urban area (high-tech zone) (23 157,26.50％).The single-factor gray model [GM (1,1)],multi-factor gray model,and moving average model (MA1) predicted that the total number of pre-hospital trauma patients in 2023 was 13 118,11 715 and 13 305,respectively,and the MAE were 451.125 0,607.428 6,and 205.125 0,respectively.The single-factor gray model [GM (1,1)] and SARIMA model predicted the value in the summer of 2023 would be 3 638 and 4 999,respectively,and the MAE were 47.129 0 and 110.370 4,respectively.Conclusions The pre-hospital trauma in Urumqi is mainly male and young work-age adults,the incidence of the elderly is the highest,summer is the season of high incidence,and the new urban area (high-tech zone) is the primary district.The moving average model (MA1) model has a more accurate annual prediction,and the single-factor gray model [GM (1,1)] is the best model for seasonal prediction.The pre-hospital trauma emergency medical care demand will continue to increase in the next five years.The health administrative department should enlarge the allocation of pre-hospital emergency resources and improve the emergency service capabilities and efficiencies.

Prevalence and prediction of pre-hospital medical trauma in Urumqi / 中华急诊医学杂志

Objective@#To investigate the current situation of pre-hospital trauma emergency medical care of Urumqi in 2011-2018 and predict the situation in the next five years, so as to provide a basis for rational allocation of pre-hospital emergency resources and improvement of health service system.@*Methods@#A total of 427 754 pre-hospital emergency patients were collected from January 1, 2011 to December 31, 2008 in Urumqi. Epidemiological methods were performed for statistical description and analysis. The single-factor gray model [GM (1,1)], multi-factor grey model and moving average model (MA1) was established for predicting the number of pre-hospital trauma patients each year. The single-factor gray model [GM (1,1)] and SARIMA model were used for the seasonal prediction.@*Results@#The male-female ratio of pre-hospital trauma patients was 1.98:1 and the incidence rate of male patients (534.91/100 000) was significantly higher than that of female patients (274.88/100 000) (χ2=7 659.707, P<0.01), and the incidence rate of male patients was 1.95 times higher than that of female patients. The trauma patients aged 35-59 years accounted for the largest proportion (42%), and the incidence of the disease was the highest among those aged≥ 60 years old (644.23/100 000). The incidence of pre-hospital trauma increased year by year (from 408.86/100 000 in 2011 to 550.02/100 000 in 2017), with a high incidence in summer (27 123, 31.03%), especially in August (9 535, 10.91%), most of which occurred in the new urban area (high-tech zone) (23 157, 26.50%). The single-factor gray model [GM (1,1)] , multi-factor gray model, and moving average model (MA1) predicted that the total number of pre-hospital trauma patients in 2023 was 13 118, 11 715 and 13 305, respectively, and the MAE were 451.125 0, 607.428 6, and 205.125 0, respectively. The single-factor gray model [GM (1,1)] and SARIMA model predicted the value in the summer of 2023 would be 3 638 and 4 999, respectively, and the MAE were 47.129 0 and 110.370 4, respectively.@*Conclusions@#The pre-hospital trauma in Urumqi is mainly male and young work-age adults, the incidence of the elderly is the highest, summer is the season of high incidence, and the new urban area (high-tech zone) is the primary district. The moving average model (MA1) model has a more accurate annual prediction, and the single-factor gray model [GM (1,1)] is the best model for seasonal prediction. The pre-hospital trauma emergency medical care demand will continue to increase in the next five years. The health administrative department should enlarge the allocation of pre-hospital emergency resources and improve the emergency service capabilities and efficiencies.

Effect of Acupuncture at Point Neiguan on Myocardial Ultramicrostructure in Myocardial Hypertrophy Mice / 上海针灸杂志

Objective To investigate the effect of acupuncture at point Neiguan on mouse myocardial hypertrophy.Methods Thirty-sixty healthy C57BL6 mice were randomized into blank, model and treatment groups, 12 rats each. In the treatment group, an acupuncture needle was inserted into point Neiguan and retained for 15 min, once daily. After nine days of treatment, the ratios of cardiac weight/tibial length were compared between the groups. Left ventricular myocardial tissues were processed by Masson trichrome staining in every group of mice. The differences in myocardial fiber arrangement and collagen fiber distribution between the groups were observed under the ordinary optical microscope in 100 times of field of vision. Sarcomere structure, myofibril arrangement, collagen fibers and mitochondria in injured myocardial tissues were observed by transmission electron microscopy. Results Heart rate increased significantly in the model group and decreased significantly in the acupuncture group compared with the blank group. Cardiac weight and the ratios of cardiac weight/tibial length increased significantly in the model and acupuncture groups compared with the blank group (P<0.01) and decreased significantly in the acupuncture group compared with the model group (P<0.01). In the model group, myocardial tissues had compensatory hypertrophy with incontinuous status, and myocardial transverse striations had severe disorder/disruption, karyopyknosis appeared and cytoplasmic eosinophilic change became obvious in few of the rats. The results were better in the acupuncture group than in the model group. In the model group, part of myofibrils had focal fusion, interstitial collagen fibers proliferated and mitochondria had swelling and compensatory increase. The results were also better in the acupuncture group than in the model group.Conclusions Acupuncture at point Neiguan can reduce the production of collagen fibers and mitochondria, improve the arrangement of sarcomere structure and delay the progression of myocardial hypertrophy.

Discovery of a Residual Focus of Bancroftian Filariasis after Declaration of its Transmission Interruption in Guangxi / 中国寄生虫学与寄生虫病杂志

Objective To describe the discovery of a residual foci of bancroftian filariasis in Fuchuan County where the disease was announced to have been eliminated, and reveal its epidemiologic feature.Methods The investigation was carried out from August 2007 to March 2008 among residents in Changtang village where the first caseof filariasiswas found and the neighboring villages.They were screened with two thick blood smears.Immunochromatographic technology(ICT) was conducted for those going out but returned and those in surrounding areas.Vector mosquitoes were collected and dissected to find filaria larvae.Historical documents were reviewed and relevant people were interviewed.Results In Changtang administrative village, 1 052 residents were screened and 19 cases with microfilaremia were found in 2 natural villages, with a Mf-positive rate of 1.8%(5.1% in Gangshang and 1.4% in Yinshan respectively).No Mf-positive case was found in 4 119 residents screened in other 3 villages.The average microfilaria density in the 19 cases was 17.37/60 ?l blood.All the 19 cases belonged to 12 families, and 13 cases were relatives to each other, which showed a feature of spatial clustering and family clustering.More patients were identified in the age groups of 20-29 and 50-59, and 57.9% of them were older than 50 years.No larvae were found in 54 Culex pipiens fatigans dissected.Conclusion The Changtang village is identified as a residual focus of bancroftian filariasis with a low, limited endemicity.More cases have been among the elderly with a low average microfilaremia.

Study on the mechanism of SS-GH axis responses in experimental intracerebral hemorrhage / 临床神经病学杂志

Objective To observe the changes of SS activity and regulation of GH surrounding cerebral hemorrhage and the hypothalamus,and explore the disorder of SS GH to the affect of local neuronal internal circumstances in stress.Methods With intracerebral hemorrhage model in rats, SS GH content in the hypothalamus and cerebral hemorrhage periphery was determined using the radioimmunoassay.Results The SS content in the hypothalamus far from hematoma and the area surrounding cerebral hematoma elevated obviously, and reached its peak along with the hematoma content,meanwhile the GH content of relevant area trended to upregulate remarkably too.Conclusion While the SS content in the hypothalamus and the area surrounding cerebral hematoma elevated, the GH content of relevant area trended to rise remarkably too, the phenomenon indicated the stress disorder of SS GH axis during the highest peak of hematoma.