Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

Effect of Wenweiyang decoction on mast cell activation and SCF/c-Kit signaling pathway in rats with functional dyspepsia / 中国病理生理杂志

AIM:To investigate the mechanism of action of Wenweiyang decoction(WWYD)in treating func-tional dyspepsia in rats based on mast cell activation and stem cell factor(SCF)/receptor tyrosine kinase c-Kit signaling pathway.METHODS:Sixty SD rats were randomly divided into control group,model group,ranitidine hydrochloride capsule group,and low-,medium-and high-dose WWYD groups,with 10 rats in each group.The rat model of functional dyspepsia was established by tail clamping and irregular feeding compound senna method.After modeling,the rats in con-trol group and model group were given normal saline,while those in low-,medium-and high-dose(0.743 g/mL,1.485 g/mL and 2.970 g/mL)WWYD groups and ranitidine hydrochloride capsule(3 g/L)group were treated with corresponding drugs by intragastric administration.After treatment,the propulsion rate of the small intestine was measured by the carbon ink propulsion method.Rat duodenal mast cells were observed and counted by toluidine blue staining.ELISA was used for determination of mast cell tryptase(MCT)and histamine(HA)content in rat duodenum.The mRNA levels of SCF and c-Kit in duodenum were detected by RT-qPCR.Western blot and immunohistochemistry were employed to determine the ex-pression levels of SCF and c-Kit in the duodenum.RESULTS:Compared with model group,WWYD treatment signifi-cantly increased the propulsion rate of the small intestine in rats(P<0.05).ELISA results showed that WWYD reduced the number of mast cells and the content of MCT and HA in the duodenal mucosa tissue of rats(P<0.05).Western blot and immunohistochemistry results suggested that WWYD up-regulated the protein expression levels of c-Kit and SCF in the duodenal tissue of rats(P<0.05),and increased the numbers of SCF and c-Kit positive cells.RT-qPCR results indicated that WWYD up-regulated the mRNA expression of c-Kit and SCF in the duodenum of rats(P<0.05).Moreover,the small intestinal propulsion rate was negatively correlated with MCT and HA content,and positively correlated with the expres-sion of SCF and c-Kit.CONCLUSION:Wenweiyang decoction promotes rat duodenal motility,and its mechanism may be related to the inhibition of rat duodenal MCT and HA production and activation of SCF/c-Kit signaling pathway.

Application of OCTA in screening microvascular changes in non-proliferative diabetic retinopathy / 西安交通大学学报(医学版)

【Objective】 To investigate the clinical effect of optical coherence tomography angiograph (OCTA) applied in retinal microvascular screening in patients with non-proliferative diabetic retinopathy (NPDR). 【Methods】 Thirty patients with NPDR (NPDR group) diagnosed at The Third Affiliated Hospital of Soochow University and 30 healthy volunteers (control group) were selected to receive OCTA examination. The area, perimeter, and circularity of the fovea avascular zone (FAZ) were measured and blood flow density in the superior, inferior, nasal, temporal quadrants of the macular superficial retinal capillary layer (SCP) and the peripapillary radial capillary layer (RPC) of the optic disc were quantified. 【Results】 In NPDR group, blood flow density in the four quadrants of macular SCP and RPC were decreased significantly compared with that in control group (43.68±3.03 vs. 46.98±3.04, 42.79±3.17 vs. 50.45±2.25, 43.21±2.67 vs. 47.44±2.42, 44.21±3.22 vs. 51.72±5.32, 46.43±3.54 vs. 53.02±2.62, 45.97±3.67 vs. 52.53±2.82, 44.63±2.73 vs. 48.19±3.67, 41.73±3.15 vs. 45.12±3.31) (all P<0.01). The area and perimeter of FAZ in NPDR group were significantly higher than those in control group [(0.50±0.06 vs. 0.43±0.47) mm2, (3.10±0.21 vs. 2.87±0.22) mm]. The circularity of FAZ was significantly lower in NPDR group than in control group [(0.63±0.05 vs. 0.67±0.05)%, P<0.01]. 【Conclusion】 OCTA can detect early retinal microstructure changes in NPDR, and thus can be used as an auxiliary screening of NPDR to provide information for early diagnosis and treatment.

Fgf8P2A-3×GFP/+: A New Genetic Mouse Model for Specifically Labeling and Sorting Cochlear Inner Hair Cells / 神经科学通报·英文版

The cochlear auditory epithelium contains two types of sound receptors, inner hair cells (IHCs) and outer hair cells (OHCs). Mouse models for labelling juvenile and adult IHCs or OHCs exist; however, labelling for embryonic and perinatal IHCs or OHCs are lacking. Here, we generated a new knock-in Fgf8P2A-3×GFP/+ (Fgf8GFP/+) strain, in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements. After confirming that GFP expression accurately reflects the expression of Fgf8, we successfully obtained both embryonic and neonatal IHCs with high purity, highlighting the power of Fgf8GFP/+. Furthermore, our fate-mapping analysis revealed, unexpectedly, that IHCs are also derived from inner ear progenitors expressing Insm1, which is currently regarded as an OHC marker. Thus, besides serving as a highly favorable tool for sorting early IHCs, Fgf8GFP/+ will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool.

A novel method for detecting circulating tumor cells immunity based on micro-nano technique / 生物工程学报

This study was to develop a new method for detecting circulating tumor cells (CTCs) with high sensitivity and specificity, therefore to detect the colorectal cancer as early as possible for improving the detection rate of the disease. To this end, we prepared some micro-column structure microchips modified with graphite oxide-streptavidin (GO-SA) on the surface of microchips, further coupled with a broad-spectrum primary antibody (antibody1, Ab1), anti-epithelial cell adhesion molecule (anti-EpCAM) monoclonal antibody to capture CTCs. Besides, carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) were coupled with colorectal cancer related antibody as specific antibody 2 (Ab2) to prepare complex. The sandwich structure consisting of Ab1-CTCs-Ab2 was constructed by the microchip for capturing CTCs. And the electrochemical workstation was used to detect and verify its high sensitivity and specificity. Results showed that the combination of immunosensor and micro-nano technology has greatly improved the detection sensitivity and specificity of the immunosensor. And we also verified the feasibility of the immunosensor for clinical blood sample detection, and successfully recognitized detection and quantization of CTCs in peripheral blood of colorectal cancer patients by this immunosensor. In conclusion, the super sandwich immunosensor based on micro-nano technology provides a new way for the detection of CTCs, which has potential application value in clinical diagnosis and real-time monitoring of disease.

Observation on the therapeutic efficacy and survival rate of oral Etoposide in children with disseminated medulloblastoma after the standard treatment plan / 中华实用儿科临床杂志

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.

Clinical feature analysis of medulloblastoma with extraneural metastasis in children / 中华实用儿科临床杂志

Objective:Summarizing the clinical characteristics of extraneural metastasis in childhood medulloblastoma.Methods:A total of 616 cases with medulloblastoma treated in Beijing Shijitan Hospital from April 2010 to April 2019 were analyzed retrospectively, among which 11 cases developed extraneural metastasis.The age of onset, location and time of extraneural metastasis, pathological and molecular typing, treatment and prognosis were descriptively analyzed.The differences of blood biochemical indexes between medulloblastoma cases with and without extraneural metastasis were statistically analyzed by t test. Results:As of February 2020, the median follow-up period was 16 months (ranging from 3 to 69 months). Eleven cases, including 8 males and 3 females, were diagnosed with extraneural metastasis, with the incidence being about 1.8%.The median age of medulloblastoma was 6 years (2-10 years), and the median age at presentation of extraneural metastasis was 7 years (2-12 years). Extraneural metastasis occurred from 0.5 months to 38.0 months after the operation, and the affected location includes bone (6 cases), bone marrow (3 cases), lung (3 cases), pelvis (2 cases) and abdominal cavity (1 case). In these patients, the range of lactic dehydrogenase (LDH) was (2 298.00±1 570.70) U/L and neuron-specific enolase (NSE) was (201.00±68.34) μg/L, which were significantly higher than those in patients without extraneural metastasis [(249.50±46.28) U/L and (22.80±7.12) μg/L, all P<0.05]. Partial patients were treated with chemotherapy, while the majority of them were treated with palliative treatment in the terminal stage, with the survival period mostly less than 10 months. Conclusions:Although there is a low incidence of extraneural metastasis in medulloblastoma pediatric patients, the prognosis of these patients with extraneural metastasis is poor and most of them would die within one year.The most common sites include bone, followed by bone marrow and lungs, which may be related to the spread of cerebrospinal fluid and the increased levels of LDH and NSE.

Effect of neutrophil-lymphocyte ratio at the initial visit on the survival of children with newly diagnosed medulloblastoma / 中华实用儿科临床杂志

Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.

Peripheral insulin resistance aggravated cognitive impairment and phosphorylated Tau protein in MAPT transgenic mice / 中华行为医学与脑科学杂志

Objective:To investigate the effects of insulin resistance induced by long-term high-fat diet on cognitive function and brain phosphorylated Tau protein in pR5 MAPT Tau transgenic mice.Methods:Eight-week-old female pR5 MAPT transgenic mice were divided into standard diet(STD) group (pR5 STD, n=8) and high-fat diet(HFD) group (pR5 HFD, n=8). Female wild-type C57BL/6 mice fed with STD were used as control group (WT STD, n=8). The experiment was carried out for 30 weeks until the mice were old.During the experiment, the weight of mice was measured once a week and fasting blood glucose was measured once every two weeks.Thirty weeks later, glucose tolerance test and insulin tolerance test were carried out.Forced swimming test and tail suspension test were used to evaluate the depressive behavior of mice, and elevated plus maze test was used to evaluate the anxiety behavior, Morris water maze test was used to evaluate spatial memory behavior.The levels of total Tau protein and phosphorylated Tau proteins H7-tau, p-tau-Ser396 and p-tau-Thr231 were detected by Western blot.SPSS 17.0 software was used for statistical analysis, repeated measurement ANOVA was used for the data of glucose tolerance test and insulin tolerance test, one-way ANOVA was used for multi group comparison, and LSD test was used for further pairwise comparison. Results:After 30 weeks of high-fat diet, there were significant differences in body weight and fasting blood glucose among the three groups ( F=808.31, 1 117.18, both P<0.01). The body weight of mice in pR5 HFD group ((54.35±2.52)g) was higher than those in pR5 STD group ((24.95±1.15) g) and WT STD group ((23.86±1.10) g) (both P<0.01), and the fasting blood glucose of mice in pR5 HFD group ((8.12±0.24) mmol/L) was significantly higher than those in pR5 STD group ((4.64±0.13) mmol/L) and WT STD group ((4.45±0.22) mmol/L) (both P<0.01). Glucose tolerance test showed that within 120 minutes after injection of glucose, there was a significant time and group interaction in the blood glucose value among the three groups ( F=113.30, P<0.01). After glucose injection, the peak value of blood glucose in pR5 HFD group was delayed, suggesting that glucose tolerance in pR5 HFD group was impaired.The insulin tolerance test showed that there was a significant interaction between time and group in the insulin tolerance among the three groups ( F=209.92, P<0.01). After injection of insulin, the blood glucose in pR5 HFD group decreased slowly, reaching the valley value at 60 min, and then the blood glucose increased significantly, suggesting that the sensitivity of pR5 HFD group mice to insulin decreased significantly.There were significant differences in the percentage of forced swimming immobility time and tail suspension immobility time among the three groups ( F=37.05, 59.29, both P<0.01). The two indexes of pR5 STD group and pR5 HFD group were both higher than those of WT STD group (all P<0.01), and those of pR5 HFD group were both higher than those of pR5 STD group (both P<0.01). The results of elevated plus maze showed that there were significant differences in the activity distance and time in open arm among the three groups ( F=7.82, 10.37, both P<0.05) .The activity distance ((0.40±0.21) m) and activity time ((27.38±8.80) s) of pR5 HFD group were significantly lower than those of pR5 STD group ((2.31±1.74) m, (63.56±27.52)s) (both P<0.05). The space exploration test showed that the residence time in the target quadrant of pR5 HFD group ((15.56±1.16)s) was less than that of pR5 STD group((19.18±0.64)s)( P<0.01), and the time of entering the platform area of pR5 HFD group((1.43±0.06)s) was less than that of pR5 STD group((1.66±0.12)s)( P<0.01). Western blot showed that there were significant differences in the levels of total Tau protein, H7-tau, p-tau-Ser396 and p-tau-Thr231 protein among the three groups ( F=101.50, 80.60, 55.47, 30.89, all P<0.05). Further pairwise comparison showed that the levels of the four Tau proteins showed: the levels of the proteins in pR5 STD group and pR5 HFD group were all higher than those of WT STD group (all P<0.01), and those in pR5 HFD group were all higher than those in pR5 STD group (all P<0.05). Conclusion:Long-term high fat diet causes obesity, hyperglycemia and peripheral insulin resistance, and promotes the cognitive impairment of MAPT mice, which is related to the increase of Tau protein phosphorylation in the brains of MAPT mice.

Influencing factors for drug-induced liver injury among patients with pulmonary tuberculosis in Ningbo City / 预防医学

Objective@#To investigate the factors affecting drug-induced liver injury among patients with pulmonary tuberculosis in Ningbo City from 2015 to 2019, so as to provide insights into the prevention of drug-induced liver injury.@*Methods@#Demographic features, presence of drug-induced liver injury, and disease history prior to anti-tuberculosis therapy were captured from patients with pulmonary tuberculosis in Ningbo City from 2015 to 2019 through the Tuberculosis Management Information System of the Chinese Disease Control and Prevention Information System and Ningbo Regional Diagnosis and Treatment Information Platform. Factors affecting drug-induced liver injury was identified using the multivariable logistic regression analysis.@*Results@#A total of 9 397 patients with pulmonary tuberculosis were enrolled, among whom 66.43% ( 6 242 case ) were male, 65.89% ( 6 192 cases ) were at ages of <60 years, and 92.35% ( 8 678 cases ) were treatment-naïve. There were 1 425 patients with drug-induced liver injury (15.16% incidence), including 729 cases with grade 1 (51.16%), 24 cases with grade 2 (1.68%), 7 cases with grade 3 (0.49%), 7 cases with grade 4 ( 0.49% ), and 658 cases with ungraded drug-induced liver injury ( 46.18% ). The median duration between drug administration and development of drug-induced liver injury was 24 ( interquartile range, 44 ) days. Multivariable logistic regression analysis identified treatment-naïve ( OR=1.464, 95%CI: 1.153-1.859 ) and history of liver disease ( OR=2.001, 95%CI: 1.709-2.342) as risk factors for drug-induced liver injury in patients with pulmonary tuberculosis.@*Conclusion@#The incidence of drug-induced liver injury was 15.16% among pulmonary tuberculosis patients in Ningbo City from 2015 to 2019. Treatment-naïve and a history of liver disease are associated with drug-induced liver injury among patients with pulmonary tuberculosis.

Effects of long-term high fat diet on depressive-like behavior in mice and mechanism of metabolic imbalance of BDNF / 中华行为医学与脑科学杂志

Objective:To study the effects of long-term high fat diet on glucose metabolism, depressive-like behavior and the expression of proBDNF/mature BDNF and p75NTR in brain of mice.Methods:Totally 16 8-week-old C57BL/6 mice were randomly divided into two groups with 8 in each group.The mice in STD group were given standard diet (STD) and the mice in HFD group were given high fat diet (HFD). The body weight and food intake were measured every week, and the fasting blood glucose was measured every 4 weeks.After 30 weeks, glucose tolerance test and insulin tolerance test were used to measure islet function, while forced swimming test and tail suspension test were used to detect depression behavior.The brain tissues of mice were collected and the concentrations of proBDNF, mature BDNF and p75NTR were measured by Elisa.The correlation between the above factors and body weight, blood glucose and depression behavior of mice was analyzed.Results:Obesity, hyperglycemia, insulin resistance and depression were observed in HFD group.The concentration of proBDNF in HFD group((4.95±1.12) pg/μg) was significantly higher than that in STD group ((2.19±0.19) pg/μg)) ( t=2.68, P<0.05), the concentration of mature BDNF((1.39±0.18)pg/μg) was significantly lower than that in STD group ((2.26±0.23) pg/μg)) ( t=-2.90, P<0.05), and the concentration of p75NTR ((3.56±1.23)pg/μg)) was significantly higher than that in STD group ((1.42±0.16)pg/μg)) ( t=5.78, P<0.05). Spearman correlation analysis showed that proBDNF and p75NTR were positively correlated with body weight, blood glucose and immobile time, while mature BDNF was negatively correlated with body weight, blood glucose and immobile time. Conclusion:Imbalance of proBDNF and mature BDNF, the upregulation of proBDNF-p75NTR pathway caused by long-term HFD may be the mechanism of the interaction between metabolic abnormality and depression.Regulating the balance of proBDNF and material BDNF signal pathway may play a positive role in the emotional disorders associated with metabolic disorders.

Analysis of prognostic factors and survival status of children with medulloblastoma / 中华实用儿科临床杂志

Objective@#To investigate the prognostic factors and survival status of children with medulloblastoma (MB) by using retrospective analysis.@*Methods@#From February 2011 to December 2017, 224 children with newly-diagnosed MB were enrolled in this study, which was carried out at Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University.The overall survival (OS) rate and progression-free survival (PFS) rate were calcula-ted by using Kaplan-Meier method, the difference between 2 groups was tested by Log-rank method, and prognostic factors were analyzed by COX regression.@*Results@#Until December 30, 2018, the median survival time of all these 224 children was 4.1 years, the survival rate was 74.6%, complete response (CR) rate was 60.3%, and the relapse rate was 1.7%. The 5-year PFS rate and 5- year OS rate of all patients were (58.2±3.6)% and (72.5±3.3)%, respectively. Survival rates of children in the high-risk group, with metastatic disease, aged <3 years, and with positive tumor cells in the cerebrospinal fluid(CSF) were very low. The 5-year OS rates were (54.8±5.3)%, (57.7±5.9)%, (41.6±8.7)%, and (53.0±7.3)%, respectively.Compared to others, the children with MB large-cell/anaplastic histology [5-year OS rate was (35.3±13.6)%] and MB group 3 subtype [3-year OS rate was (25.0±13.0)%] lived a miserable life.Meanwhile, the children in the stand-risk group, without metastatic disease, no large-cell/anaplastic histology, age older than 3 years, and with tumor cell negative in CSF, lived a better life. The 5-year OS rates were (87.5±3.5)%, (80.3±3.7)%, (70.6±5.5)%, (78.3±3.3)%, and (78.4±3.5)%, respectively, and all of them were over 70.0%. No WNT tumors progressed or relapsed, and 5- year OS rate was 100.0%. The survival status of SHH subgroup was inferior to that of group 4 subtype[(64.8±5.8)% vs.(83.5±3.8)%, χ2=5.417, P=0.015]. With COX analysis, age and tumor cells in CSF at the time of diagnosis were independent risk factors for OS and PFS of MB (PFS: Wald=8.485, P=0.004; Wald=11.702, P=0.001; OS: Wald=16.274, P=0.000; Wald=7.191, P=0.007).@*Conclusions@#Survival of children with MB more than 3 years old has been reached a perfectly high level.Age and tumor cells in CSF are independent risk factors for the OS and PFS. However, the prognosis of large-cell/anaplastic histology, malignancy cell positive in CSF, group 3 and children under 3 years old, is still poor, and intensive treatment is needed urgently for those patients.

A review of guidelines for diabetic retinopathy screening / 中华眼底病杂志

Diabetic retinopathy (DR) is the most common cause of preventable blindness in the working-age population.In addition to optimizing the hyperglycemia,hypertension,hyperlipidemia and other risk factors,regular fundus examination is essential for early diagnosis asymptomatic DR and timely treat the sight-threatening DR,so as to reduce blindness and severe visual impairment caused by DR.Clinical practice guidelines for the screening and management of DR have been implemented throughout the world,but there are reasonable differences between existing guidelines in the recommended timing of first retinal examination,screening intervals,methods for examination and criteria for referral to an ophthalmologist.It is of great clinical significance to have a detailed understanding of the current guidelines for DR screening and their clinical basis.

Early diagnosis and treatment of secondary lung damage in children with malignant brain tumors after radiation therapy / 中华实用儿科临床杂志

Objective To investigate the early diagnosis and treatment of craniospinal irradiation(CSI)in-duced lung injury (RILI)in children with malignant brain tumors.Methods From January 2014 to January 2016,a total of 145 children with malignant brain tumors from Beijing Shijitan Hospital,Capital Medical University were enrolled in this study.All children received postoperative CSI.Ten children were diagnosed as RILI by high－resolution computed tomography (HRCT)scanning before the start of subsequent chemotherapy and 42 days after CSI.Oral Pred-nisone acetate tablets 0.5－1.0 mg/(kg·d)were given to treat RILI and compound Sulfamethoxazole to prevent sec-ondary lung inflammation.Antibiotic treatment and symptomatic support were given to 2 patients because of the com-bined infection.Then every 4 weeks HRCT was performed and the dosage of Prednisone was adjusted.Clinical charac-teristics and treatment effects were observed synthetically.Results Up to January 2018,the median follow－up time was 28 months (ranged from 26 to 48 months),only 10 patients suffered from RILI,and the morbidity was 6.9%.Eight of 10 patients had medulloblastoma,1 case with pineoblastoma,and 1 case with atypical teratoma/rhabdomyoid tumor. They were 6 boys and 4 girls,and the median age was 8 years old (ranged from 5 to 13 years old).The time points of diagnosis of lung damage were 39－52 days after the end of radiotherapy,and lesions were located in the dorsal or basal segments of lower lobe of unilateral or bilateral lung in HRCT scanning.No obvious respiratory symptoms or other dis-comfort was found except for frequent cough in 2 patients.Lung lesions were gradually reduced and disappeared within 2 to 8 months after treatment with Prednisone and compound Sulfamethoxazole.Two cases suffered severe infection be-fore or during the subsequent chemotherapy,and the condition was gradually improved after anti－infection treatment based on drug sensitivity test.Then subsequent chemotherapy underwent successfully.Conclusions RILI presents mild symptoms or asymptomatic.Routine lung imaging after radiotherapy is beneficial to the early diagnosis of lung damage, and early treatment with Prednisone and prophylaxis with compound Sulfamethoxazole has a good prognosis.

Customer satisfaction survey of health management centers at Hangzhou public hospitals / 中华医院管理杂志

Objective To learn customer satisfaction for health management centers at public hospitals in Hangzhou. Methods From July to September 2015, 660 customers from the health management centers of 6 public hospitals in Hangzhou were randomly selected for questionnaire survey. The survey included their satisfaction for the technical attitude, service content design, waiting time, environment facilities, management regulations, and service charges. Univariate analysis was carried out on the satisfaction scores of customer demographics. Two-class logistic regression was used to analyze the factors affecting customer satisfaction. Results The average customer satisfaction score was 3. 62 ± 0. 55. Their satisfaction with technical attitude, service content design, environmental facilities and management regulations was higher. They were less satisfied with waiting time(3. 20 ± 0. 85) and service charge(3. 36 ± 0. 71). Conclusions Overall satisfaction of customers for such centers is high. In the future, we should further strengthen the information management and procedures of these centers, and link health management services with commercial insurance, for less economic burden on the people.

The consistency and reproducibility of macular perfusion parameters in early diabetic retinopathy using optical coherence tomography angiography / 中华眼底病杂志

Obejctive To investigate the consistency and reproducibility ofmacular perfusion parameters in early diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA).Methods A prospective cross-sectional observational study.Forty-six patients (46 eyes) diagnosed with mild nonproliferative DR were included in this study.There were 24 males and 22 females,with the mean age of 59.16± 10.32 years.Two macular scan sizes of 3 mm× 3 mm and 6 mm× 6 mm were performed by the same operator,and the same test was performed by another operator.The superficial retinal layer (SRL) and deep retinal layer (DRL) in the foveal avascular zone (FAZ) and vessel density (VD) were quantified.The consistency of the two scan sizes and the reproducibility of the same scan size were also evaluated.The consistency was determined by the intraclass correlation coefficient (ICC).If the intraclass correlation coefficient (ICC)＞0.80,consistency was good;if 0.4≤ICC＜0.8,consistency was general;if ICC＜0.40,consistency was poor.Results In the 3 mm × 3 mm and 6 mm × 6 mm scanning sizes,the mean results of the two examiners were calculated.The FAZ of SRL were 0.39±0.13 mm2 and 0.42±0.15 mm2,FAZ of DRL were 0.74±0.22 mm2 and 0.89±0.23 mm2.The VD of SRL were (32.23±2.86)％ and (31.91 ±3.01)％,VD of DRL were (43.73 ±4.64)％ and (45.12± 5.49)％.The consistency analysis showed that the ICC of SRL-FAZ and DRL-FAZ were 0.920 and 0.812,respectively;the ICC of VD were 0.833 and 0.830,respectively.The consistency was good.The reproducibility analysis of different examiners in the same scan size was better in the consistency of SRL FAZ and VD.Conclusion OCTA in two scanning sizes to measure FAZ and VD of early DR has good consistency and reproducibility.

Comparison of confocal laser scanning colorful fundus imaging and color fundus photography for detection of diabetic retinopathy / 中华眼底病杂志

Objective To compare the imaging characteristics and detection of various types of lesions in diabetic retinopathy (DR) with colorful laser scanning fundus imaging (MSLI) and traditional color fundus photography (CFP).Methods Prospective case series observational study.A total of 38 eyes of 38 patients with DR diagnosed by clinical examination were included in the study.Among them,21 were male and 17 were female;the mean age was 62.6± 11.2 years;the average duration of diabetes was 14.3±7.5 years.All the patients were performed CFP,MSLI,frequency domain optical coherence tomography (SD-OCT),fluorescein angiography (FFA) examination.Using the Helielberg Spectralis HRA+OCT MSLI inspection,one scan simultaneously obtained 488 nm blue reflection (BR),515 nm green light reflection (GR),820 nm infrared light reflection (IR),and multicolor image (MC).The detection of traditional CFP and MC on microaneurysm (MA),hard exudation (HEX),cotton plaque (CWS),intraretinal hemorrhage (IRH),intraretinal microvascular abnormality (IRMA),venous bead (VB),venous ring (VL),macular edema (DME),macular anterior membrane (MEM) and laser photocoagulation (LB) were comparatively observed.The results of FFA examination were used as the diagnostic criteria for lesions.SD-OCT was used to determine the location and depth of lesions and the diagnostic reference for DME and MEM.Results The numbers of eyes with MA (x2=10.460),DME (x2=4.006),MEM (x2=4.444) was significantly higher in MC than that of traditional CFP.But the number of eyes with IRH (Z2=0.103),CWS (x2=1.515),HEX (x2=0.227),IRMA (x2=0.051),VB (x2=0.001),VL (x2=0.149),VH (x2=0.693) and LB (x2=0.720) were not statistically significant between two methods (P＞0.05).The imaging quality of MSLI mode is obviously better than that of traditional CFP.Among them,GR imaging shows the best structural changes of superficial retina in MA,CWS,HEX,MEM,etc.IR imaging shows clear depth in deep retina such as LB.DME was green on MC and the weak low-reflection dark area was visible on the IR image,which were consistent with the DME range indicated by the SD-OCT examination.Conclusions Compared with the traditional CFP,the MSLI can clearly show the DR lesion.The number of checkouts is high on MA,DME and MEM by MC image.

Survival of children with relapsed medulloblastoma treating with high-dose chemotherapy and intrathecal Methotrexate:a retrospective study in a single institution / 中华实用儿科临床杂志

Objective To investigate the treatment value of intensified chemotherapy combined with intrathe-cal Methotrexate(ITMTX)in the treatment of children with relapsed medulloblastoma.Methods From February 2011 to February 2014,40 relapsed patients in Beijing Shijitan Hospital,Capital Medical University,aged 10.6 years(2.7 to 17.7 years),were received 4 cycles of carboplatin and Etoposide continuously infusion for 96 h,and sequentially fo-llowed with Ifosfamide,Etoposide and Nedaplatin for 3 cycles,then administrated oral Temozolomide(TMZ)and Etopo-side for 12 cycles.All patients were divided into ITMTX group,which were performed ITMTX during every chemothera-py or every 3 weeks,and no intrathecal Methotrexate(no-ITMTX)group,which were not performed with ITMTX.Re-sponses were evaluated,and the objective response time,time to tumor progress(TTP),time to treatment failure (TTF),and recurrence-free interval(RFI)of the two groups were contrasted.The side-effects of chemotherapy and ITMTX were analyzed,overall survival was calculated using Kaplan-Meier method,and chi-square test or t test was used to compare the difference between two groups.Results Until 30thDecember 2016,the follow-up time was 29.4 months(ranging from 2 to 57 months). The 3-year overall survival(OS)rate was(53.5 ± 8.1)%,and 45.0% pa-tients were objective response,and the mean objective response time was 2 months,and the RFI was 18 months.For IT-MTX patients,the 3-year OS rate was(66.6 ± 11.5)%,the objective response ratio was 70.0%,and mean objective response time was 1.5 months,24 months free-event of TTP and TTF was 70.0% and 90.0%,respectively,and the RFI was 22.5 months.For no-ITMTX patients,the 3-year OS rate was(40.0 ± 11.0)%,objective response ratio was 20.0%,and mean objective response time was 2.5 months(1.5-4.0 months),24 months free-event of TTP and TTF was 35.0% and 50.0%,respectively,and the RFI was 5 months(0-40 months).Compared with those of no-ITMTX patients,the RFI,24 months TTP and TTF of ITMTX patients were much better,there were statistical signi-ficances(all P<0.05).The main side-effects of chemotherapy was gastrointestinal hematologic side-effects,and re-covered quickly with supportive treatment.No obvious Methotrexate induced neurotoxicity was found.Conclusion Based on high-dose chemotherapy,ITMTX can further improve the long-term survival of patients with relapsed medulloblas-toma,and it is more feasible and suitable for relapsed MB children in China.

Clinical characteristic and survival analysis of childhood supratentorial primitive neuroectoderma:a center re-trospective study / 中华实用儿科临床杂志

Objective To analyze the survival rate and adverse effect of therapy of childhood supratentorial primitive neuroectoderma (sPNET)patients in order to investigate a suitable therapy. Methods Between December 2012 and December 2014,18 children,aged from 0. 6 to 13. 6 years old,were treated with pediatric himtumor(HIT)-2000 protocol in Beijing Shijitan Hospital,Capital Medical University. All patients were performed tumor gross total re-section,and someone accepted irradiation therapy firstly. The adverse effect of radiotherapy and chemotherapy was ana-lyzed,and the 3 - year progression - free survival (PFS)rate and overall survival (OS)rate were calculated by using Kaplan - Meier method. Results Till September 2017,the mean follow - up time was 3. 0 years (0. 2 - 4. 8 years), and the survival rate was 72. 2％ (13 / 18 cases). Eleven cases(11 / 18 cases,61. 1％)were complete remission,but 7 cases (7 / 18 cases,38. 9％)relapsed during or after therapy. The 3 - year PFS and OS rates were (66. 7 ± 11. 1)％and (71. 8 ± 10. 7)％,respectively. Moreover,14 patients received craniospinal irradiation,and their 3 - year PFS and OS rates were (68. 8 ± 13. 3)％ and (85. 7 ± 9. 4)％,respectively,there was no significant difference between the overall rates(all P >0. 05). During the follow - up period,all patients were not involved radiation - reduced brain necro-sis,myelitis,and pancreatic injury. During the whole central radiotherapy,14 children had different degree of blood rou-tine abnormalities,mainly manifested in leukocytes and thrombocytopenia,and the blood routine was restored to normal after subcutaneous injection of granulocyte stimulating factor. The adverse reactions of the gastrointestinal tract were re-latively mild,mainly nausea and vomiting,and the improvement of the gastric mucosa and the protection of the gastric mucosa were all improved. The gastrointestinal tract adverse reactions caused by HIT - 2000 were mainly nausea,vomi-ting,abdominal pain,diarrhea,constipation,and so on. The incidence of hematological adverse reactions was high,up to 100％,of which 2 cases were cured by active anti infection and symptomatic treatment due to the lack of granulocytic and fever. Conclusion HIT - 2000 protocol is a feasible and efficient therapy method for sPNET of Chinese children patients,and the adverse effects are tolerable.

The visual acuity changes in patients with different patterns of optical coherence tomography of diabetic macular edema after intravitreal ranibizumab injection and/or laser photocoagulation / 中华眼底病杂志

Objective To observe the visual acuity change in patients with different patterns of optical coherence tomography (OCT) of diabetic macular edema (DME) after intravitreal ranibizumab injection and/or laser photocoagulation.Methods A retrospective observational case series.Seventy patients (99 eyes) with DME were enrolled.Best-corrected visual acuity (BCVA) was evaluated using the international vision test chart,and then convert the result to the logarithm of the minimum angle of resolution (logMAR).According to the morphological characteristics of OCT,the DME was divided into 3 patterns,including diffuse macular edema (DRT),cystoid macular edema (CME) and serous neuroepithelial layer detachment.The average follow-up was (80.43 ± 74.89) days.The patients were divided into 3 groups according to the different treatments,including intravitreal ranibizumab injection group (group A,21 patients,25 eyes),intravitreal ranibizumab injection and laser photocoagulation group (group B,23 patients,26 eyes),laser photocoagulation group (group C,26 patients,48 eyes).The changes of absolute BCVA (ABCVA) and improved visual acuity were compared between different treatment groups and different OCT patterns.ABCVA =logMAR BCVA before treatment-logMAR BCVA after treatment.Improvement more than 0.3 of logMAR value was considered as improved visual acuity.Results There was no significant difference in ABCVA between different treatment groups (F=0.050,P＞0.05).The improved visual acuity in group A and B were great than group C (x2=5.645,6.301;P＜0.05).In group A,B and C,there was no significant difference in ABCVA and improved visual acuity between different OCT patterns (P＞0.05).Improved visual acuity of DRT and CME eyes were higher in group A&B (70.59％ and 50.00％) than in group C (26.47％ and 14.29％),the difference was statistically significant (x2=5.075,4.453;P＜0.05).Conclusions There is no obvious change of visual acuity in patients with different OCT patterns of DME after the same treatment by intravitreal ranibizumab injection and/or laser photocoagulation.The improved visual acuity is not consistent in same OCT patterns after different treatment.