Virtual Screening and Testing of GSK-3 Inhibitors Using Human SH-SY5Y Cells Expressing Tau Folding Reporter and Mouse Hippocampal Primary Culture under Tau Cytotoxicity

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

Risk Factors Analysis of Thromboembolism in Patients with Lymphoma Chemotherapy / 中国实验血液学杂志

OBJECTIVE@#To evaluate the risk factors affecting thromboembolism in lymphoma patients with chemotherapy.@*METHODS@#Three hundred and four consecutive lymphoma patients treated by chemotherapy between January 2012 and July 2019 were enrolled and retrospectively analyzed, consisting of 111 patients with thromboembolism and 193 without thromboembolism. Univariate analysis was used to compare the clinical characteristics and related laboratory examination between the patients, while multivariate Logistic regression analysis were used to identify the risk factors affecting thromboembolism in lymphoma patients with chemotherapy.@*RESULTS@#Univariate analysis showed that the female, BMI <18.5 or >24, ≥60 years old, with abnormal platelets before chemotherapy, prolonged single hospitalization days and patients at Ann Arbor stage III and IV could increase the incidence of thromboembolism in lymphoma patients treated by chemotherapy. Multivariate Logistic regression analysis showed that abnormal platelet count before chemotherapy, patients at Ann Arbor stage III and IV, and female were all the independent risk factors affecting thromboembolism in lymphoma patients thromboembolism after chemotherapy (P<0.05).@*CONCLUSION@#For lymphoma chemotherapy patients, female, abnormal platelet count before chemotherapy and Ann Arbor stages III and IV show a significantly higher risk for thromboembolism. Thus, preventive anticoagulation therapy is recommended.

Trajectories of mental health symptoms predict long-term quality of life among Wenchuan adolescent survivors: A 10-year follow-up study / 中华创伤杂志(英文版)

PURPOSE@#Previous studies usually examine the associations between psychological distresses and quality of life (QOL) with a variable-centred approach, while little is known about the effect of the individual variance in time-varying changes of psychological distresses on QOL. Therefore, this study aimed to examine whether individual variance in psychological distresses during the early phases post-earthquake would develop different QOL's levels among adolescent survivors 10-year after the Wenchuan earthquake.@*METHODS@#Data were extracted from the Wenchuan Earthquake Adolescent Health Cohort Study. The current study included 744 adolescent survivors who effectively completed surveys at 6 months, 24 months, and 10 years after the earthquake. Self-report questionnaires were administered to collect information on socio-demographic characteristics, earthquake exposure, life events, anxiety symptoms, depressive symptoms, posttraumatic stress symptoms (PTSS), and QOL. Data were analysed using hierarchical multiple regression.@*RESULTS@#Trajectories of psychological distresses were classified as follow: resistance (anxiety 40.73%; depression 54.70%; PTSS 74.46%), recovery (anxiety 17.20%; depression 9.27%; PTSS 10.35%), delayed dysfunction (anxiety 10.35%; depression 18.15%; PTSS 6.18%), and chronicity (anxiety 31.72%; depression 17.88%; PTSS 9.01%). After controlling covariates, hierarchical multiple regression only revealed that the anxiety trajectory with delayed dysfunction remained significantly predictive for four domains of QOL (physical health, psychological health, social relationships, and environment).@*CONCLUSION@#The current study highlights the importance of focusing on the variations in trajectories of anxiety symptoms among disaster survivors and providing individualized mental health services to improve survivors' QOL.

Antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism and its common pharmacodynamic substances / 中国中药杂志

This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.

Treatment of senile lumbar spinal stenosis by unilateral approach and bilateral decompression with large channel endoscopy / 中国骨伤

OBJECTIVE@#To evaluate clinical effect of unilateral approach and bilateral decompression via large channel endoscopic system for the treatment of lumbar spinal stenosis.@*METHODS@#The clinical data of 32 patients with lumbar spinal tenosis treated by unilateral approach and bilateral decompression via large channel endoscopy from February 2018 to February 2019 were retrospectively analyzed. There were 18 males and 14 females, aged 65 to 84 years old with an average of (70.6± 8.4) years. The course of disease was from 1 to 12 years. All 32 cases were accompanied by numbness or pain in the lower limbs, of which 28 cases were accompanied by intermittent claudication. Narrow segments were L@*RESULTS@#All the patients were followed up for 12-24 (17.68±2.43) months and all operations were successfully completed with the operation time of 70-160(85.64±11.94) min. Spinal dural tear occurred in 1 case during the operation, and sensory disturbance in the other side of lower limb in a short period of time occurred in 2 cases, all improved after corresponding treatment. Postoperative imaging showed that the spinal canal was significantly enlarged and the nerve root was fully released. Before operation and 3 days, 3 months, 1 year after operation, VAS scores of low back pain were 4.62 ±1.41, 2.73 ±1.35, 1.21 ±1.17, 1.11 ±0.34, respectively;VAS scores of leg pain were 6.83 ± 1.71, 3.10±1.50, 1.08±0.19, 0.89±0.24, respectively. VAS scores of low back pain and leg pain each time point after operation were obvious improved (@*CONCLUSION@#It is a safe and effective way to treat lumbar spinal stenosis with unilateral approach and bilateral decompression via large channel endoscopic system. It has the advantages of sufficient decompression, less trauma, fast recovery, high safety and low incidence of postoperative complications. It can minimize the damage to the stable structure of the lumbar spine and is an ideal minimally invasive operation for the treatment of lumbar spinal stenosis.

Psychosocial impact of the COVID-19 pandemic on paediatric healthcare workers

INTRODUCTION@#Frontline healthcare workers (HCWs) exposed to coronavirus disease 2019 (COVID-19) are at risk of psychological distress. This study evaluates the psychological impact of COVID-19 pandemic on HCWs in a national paediatric referral centre.@*METHODS@#This was a survey-based study that collected demographic, work environment and mental health data from paediatric HCWs in the emergency, intensive care and infectious disease units. Psychological impact was measured using the Depression, Anxiety, Stress Scale-21. Multivariate regression analysis was performed to identify risk factors associated with psychological distress.@*RESULTS@#The survey achieved a response rate of 93.9% (430 of 458). Of the 430 respondents, symptoms of depression, anxiety and stress were reported in 168 (39.1%), 205 (47.7%) and 106 (24.7%), respectively. Depression was reported in the mild (47, 10.9%), moderate (76, 17.7%), severe (23, 5.3%) and extremely severe (22, 5.1%) categories. Anxiety (205, 47.7%) and stress (106, 24.7%) were reported in the mild category only. Collectively, regression analysis identified female sex, a perceived lack of choice in work scope/environment, lack of protection from COVID-19, lack of access to physical activities and rest, the need to perform additional tasks, and the experience of stigma from the community as risk factors for poor psychological outcome.@*CONCLUSION@#A high prevalence of depression, anxiety and stress was reported among frontline paediatric HCWs during the COVID-19 pandemic. Personal psychoneuroimmunity and organisational prevention measures can be implemented to lessen psychiatric symptoms. At the national level, involving mental health professionals to plan and coordinate psychological intervention for the country should be considered.

Paediatric emergency department attendances during COVID-19 and SARS in Singapore

INTRODUCTION@#We evaluated the impact of public health measures on paediatric emergency department attendances during the COVID-19 and severe acute respiratory syndrome (SARS) outbreaks in Singapore.@*METHODS@#Between 1 January 2020 and 31 July 2020, we retrospectively reviewed paediatric emergency department attendances and admissions in a tertiary paediatric hospital in Singapore before and after a national lockdown to combat the spread of COVID-19 in Singapore. Hospital attendances and admissions were compared with data from a corresponding period in 2019 (1 January 2019 to 31 July 2019), as well as during and after the SARS outbreak (1 January 2003 to 31 December 2004).@*RESULTS@#Compared with a corresponding non-outbreak period, emergency department attendances decreased in line with nationwide public health measures during the COVID-19 and SARS outbreaks (2020 and 2003 respectively), before increasing gradually following lifting of restrictions, albeit not to recorded levels before these outbreaks. During the COVID-19 outbreak, mean daily attendances decreased by 40%, from 458 per day in January-July 2019, to 274 per day in January-July 2020. The absolute number of hospital inpatient admissions decreased by 37% from January-July 2019 (19,629) to January-July 2020 (12,304). The proportion of emergency department attendances requiring admission remained similar: 20% in January-July 2019 and 21% in January-July 2020.@*CONCLUSION@#Nationwide public health measures in Singapore have had an impact on paediatric emergency department attendances and hospital inpatient admissions. Data from this study could inform planning and resource allocation for emergency departments in Singapore and internationally.

Epidemiology and risk stratification of minor head injuries in school-going children

INTRODUCTION@#Head injuries occur commonly in children and can lead to concussion injuries. We aim to describe the epidemiology of head injuries among school-going children and identify predictors of brain concussions in Singapore.@*METHODS@#This is a retrospective study of children 7-16 years old who presented to the Emergency Department (ED) of KK Women's and Children's Hospital in Singapore with minor head injury between June 2017 and August 2018. Data including demographics, clinical presentation, ED and hospital management were collected using a standardised electronic template. Multivariable logistic regression analysis was performed to identify early predictors for brain concussion. Concussion symptoms were defined as persistent symptoms after admission, need for inpatient intervention, or physician concerns necessitating neuroimaging.@*RESULTS@#Among 1,233 children (mean age, 6.6 years; 72.6% boys) analysed, the commonest mechanism was falls (64.6%). Headache and vomiting were the most common presenting symptoms. A total of 395 (32.0%) patients required admission, and 277 (22.5%) had symptoms of concussion. Older age (13-16 years old) (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.12-2.08), children involved in road traffic accidents (aOR 2.12, CI 1.17-3.85) and a presenting complaint of headache (aOR 2.64, CI 1.99-3.50) were significantly associated with symptoms of concussion.@*CONCLUSION@#This study provides a detailed description of the pattern of head injuries among school-going children in Singapore. High risk patients may require closer monitoring to detect post-concussion syndrome early.

Cost of inpatient rehabilitation for children with moderate to severe traumatic brain injury

AIM@#To evaluate the cost of inpatient rehabilitation for children with moderate to severe traumatic brain injury (TBI). Secondary aim was to identify factors associated with high inpatient rehabilitation cost.@*METHOD@#Retrospective review of a tertiary hospital's trauma registry was performed from 2011-2017. All patients aged 16 years or younger who sustained TBI with Glasgow Coma Scale ≤13 were included. Data on patient demographics, mechanism and severity of injury, hospital duration and inpatient rehabilitation cost were collected. We performed a regression analysis to identify factors associated with high rehabilitation cost.@*RESULTS@#There were a total of 51 patients. The median duration of inpatient rehabilitation was 13.5 days (interquartile range [IQR] 4-35), amounting to a median cost of SGD8,361 (IQR 3,543-25,232). Daily ward costs contributed the most to total inpatient rehabilitation cost. Those with severe TBI had longer duration of inpatient rehabilitation that resulted in higher cost of inpatient rehabilitation. Presence of polytrauma, medical complications, post-traumatic amnesia and TBI post-non-accidental injury (NAI) were associated with higher cost of inpatient rehabilitation.@*CONCLUSION@#The cost of inpatient rehabilitation for paediatric patients post-TBI is significant in Singapore. Patients with TBI secondary to NAI had significantly higher cost of inpatient rehabilitation. Ways to reduce duration of hospitalisation post-TBI and early step-down care or outpatient rehabilitation should be explored to reduce cost.

A review of child sexual abuse cases presenting to a paediatric emergency department

INTRODUCTION@#Child sexual abuse (CSA) adversely affects a child's growth and well-being. This study aimed to describe the profile of children presenting to a tertiary paediatric emergency department(ED) with CSA.@*METHODS@#Children 0-16 years old presenting to KK Women's and Children's Hospital ED from June 2016 to August 2020 with sexual abuse were retrospectively reviewed. We performed a secondary analysis on girls and stratified them by age <13 and ≥13 years old.@*RESULTS@#There were 790 patients who made 833 visits for CSA. Victims were predominantly girls (747, 94.8%) and perpetrators were predominantly men (763, 96.6%). The abuse first occurred before the age of 13 years in 315 victims (39.9%). For 468 (59.2%), more than one incident occurred before presentation. Compared to girls ≥13 years old, girls <13 years old were more frequently abused by a family member (47.7% versus 8.0%, @*CONCLUSION@#The findings highlight common characteristics of CSA cases, and can aid the future identification and protection of vulnerable children. The fact that most children presented after more than one incident suggests the need to more closely monitor and protect potentially at-risk children.

Systemic Inflammatory Biomarkers, Especially Fibrinogen to Albumin Ratio, Predict Prognosis in Patients with Pancreatic Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. @*Materials and Methods@#Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. @*Results@#Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. @*Conclusion@#The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

A comparison between endoscopic CO2 laser cauterization and open neck surgery in the treatment of congenital piriform fistula / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the efficacy, advantages and disadvantages of endoscopic CO2 laser cauterization (ECLC) and open neck surgery in the treatment of congenital pyriform sinus fistula (CPSF). Methods: From September 2014 to March 2017, 80 cases with confirmed diagnosis of CPSF received initial treatment at Guangdong Provincial People's Hospital were prospectively analyzed, including 34 males and 46 females, aged 18 to 672 (194.17±141.18) months. They were consecutively divided into endoscopic group and open-surgery group, with 40 cases in each group. Both groups of patients received surgical treatment under general anesthesia. The endoscopic group was treated by endoscopic CO2 laser cauterization, and the open-surgery group underwent the following surgery: first, we performed suspension laryngoscopy examination to confirm the presence of fistula in the bottom of the piriform fossa, then open-neck resection of congenital piriform sinus fistula with recurrent laryngeal nerve and/or lateral branch of superior laryngeal nerve anatomy plus partial thyroidectomy were performed. The data between the two groups were compared, including the operative time, intraoperative blood loss, postoperative pain, average length of stay, neck cosmetic scores, complications and cure rates. All patients were followed up in outpatient clinics. Statistical analysis was performed using SPSS 20.0 software. P<0.05 indicates that the difference is statistically significant. Results: All patients were successfully completed the operation. The operative time, intraoperative blood loss, postoperative pain and average length of hospital stay in the endoscopic group were significantly less than those in the open group [(27.4±5.5) min to (105.8±52.5) min, (0.6±0.5) ml to (33.6±41.5) ml, (1.7±0.9) points to (4.6±0.7) points, (5.9±2.9)d to(8.9±3.3)d, t values were-9.400, -5.031, -16.199, -4.293, P values were all<0.01]; The neck cosmetic score in the endoscopy group was significantly greater than that of the open group [(9.9±0.4) against (5.8±0.9) points, t=25.847, P<0.01]. Compared with the open group (15.0%, 6/40), the complication rate of the endoscopic group (7.5%, 3/40) was not statistically significant (χ²=0.50, P>0.05). Three months after the first treatment, the cure rate in the endoscopic group (82.5%, 33/40) was significantly lower than that in the open-neck group (100.0%, 40/40), χ²=5.64, P<0.05. The follow-up time was 12 months after the last treatment. Eighty cases were followed up and none was lost to follow-up. During the follow-up period, the cure rate of the endoscopy group (97.5%, 39/40) was compared with that of the open group (100.0%, 40/40), and the difference was not statistically significant. Conclusions: In the treatment of CPSF, the two-surgical method each has their advantages. Compared with open-neck surgery, ECLC is simpler, repeatable. ECLC has shorter time in operation and hospital stay, less complications, and less postoperative pain and more precise cosmetic results. It could be preferred for the initial treatment of CPSF and relapsed cases after cauterization. But subject to relatively low cure rate of one-time cauterization and uncertain long-term efficacy, it cannot completely replace the open-neck surgery at present.

Clinical Value of Serum Amyloid A and Misfolded Transthyretin for Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To evaluate the clinical value of serum amyloid A (SAA1/2) and misfolded transthyretin (TTR) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients.@*METHODS@#30 R/R DLBCL patients were enrolled as observation group, 20 remission/stabilization DLBCL and 10 chronic lymphadenitis patients were enrolled as control group. SELDI technique, Tris-Tricine sodium dodecyl sulfate-polyacrylamide gel electro-phoresis, the shotgun-LTQ-MS method, and bioinformatics technique were used to detected and analyzed SAA and TTR in R/R DLBCL patients. SPSS 21.0 software was used to analyze the relationship between the high expression of SAA, misfolded TTR in serum and the clinicopathological features, survival time of R/R DLBCL. patients Chi-square test was used to analyze clinical count data, Kaplan-Meier curve was used for survival analysis, and Log-Rank test was used to compare single-factor survival differences.@*RESULTS@#The high expression of SAA and TTR (SAA@*CONCLUSION@#Both SAA and misfolded TTR are poor prognosis factors of R/R DLBCL patients.

Risk Stratification of Paediatric Sports Injuries Seen at a Tertiary Hospital

INTRODUCTION@#In this study, we described paediatric sports injuries seen in the paediatric emergency department of a large, tertiary paediatric hospital in Singapore and evaluated risk factors for severe sports injuries.@*METHODS@#This is a retrospective review of a paediatric trauma surveillance registry from February 2012 to October 2017, including patient demographics, type of sports, circumstances, type of injuries, and clinical management in the hospital. Patients 5 to 17 years old with a sports-related injury were included. We performed logistic regression to identify predictors of severe sports injuries (defined by Injury Severity Score of ≥9), injuries requiring hospitalisation, trauma team activation, resuscitation, or those that resulted in death.@*RESULTS@#Among 10,951 patients analysed, the most common injuries sustained were fractures (4,819, 44.0%), sprains and contusions (3,334, 30.4%). For patients with severe injuries, the median length of hospital stay was 2 days (IQR 1-3 days), and time away from sports was 162 days (IQR 104-182 days). Predictors for severe injuries include transportation by emergency medical service (aOR 6.346, 95% CI 5.147-7.823), involvement in rugby (aOR 2.067, 95% CI 1.446-2.957), neurological injuries (aOR 4.585, 95% CI 2.393-4.365), dislocations (aOR 2.779, 95% CI 1.744-4.427), fractures (aOR 1.438, 95% CI 1.039-1.990), injuries to the head and neck (aOR 2.274, 95% CI 1.184-4.365), and injuries to the abdomen and pelvis (aOR 5.273, 95% CI 3.225-8.623).@*CONCLUSION@#Predictors for severe sports injuries identified may aid in risk stratification and resource allocation.

Differences in Utilisation of the General and Paediatric Emergency Departments by Paediatric Patients

INTRODUCTION@#Paediatric patients presenting to the general emergency departments (EDs) differ from those presenting to paediatric EDs. General EDs vary in preparedness to manage paediatric patients, which may affect delivery of emergency care with varying clinical outcomes. We aimed to elucidate the differences in utilisation patterns of paediatric and general EDs by paediatric patients.@*METHODS@#This study was conducted in a public healthcare cluster in Singapore consisting of 4 hospitals. A retrospective review of the medical records of paediatric patients, defined as age younger than 16 years old, who attended the EDs from 1 January 2015 to 31 December 2018, was performed. Data were collected using a standardised form and analysed.@*RESULTS@#Of the 704,582 attendances, 686,546 (97.4%) were seen at the paediatric ED. General EDs saw greater number of paediatric patients in the emergent (P1) category (921 [5.1%] versus 14,829 [2.2%]; @*CONCLUSION@#General EDs need to build their capabilities and enhance their preparedness according to the paediatric population they serve so that optimal paediatric emergency care can be delivered, especially for critically ill patients who are most in need of life-saving and timely treatment.

Screening for bioactive components of Desmodium styracifolium and its mechanisms study based on calcium oxalate monohydrate -induced HK-2 damage model / 药学学报

To screen active components of Desmodium styracifolium in protecting calcium oxalate monohydrate (COM) -induced human proximaltubular epithelial cell (HK-2) damage model, and furtherly explore its mechanism of action, total flavonoids of Desmodium styracifolium (TFDS) and eight flavonoids (schaftoside, isoschaftoside, vicenin-2, isovitexin, isoorientin, apigenin, luteolin and genistein) were tested by COM-induced HK-2 damage model. MTT assay was used to detect the effects of different components on the cell viability of COM-induced HK-2 damage model. The lactate dehydrogenase (LDH) release in the cell supernatant and the activity level of superoxide dismutase (SOD) and reactive oxygen species (ROS) of cell were detected by the kit. Western blot was used to detect the expression levels of NLRP3, caspase-1, HMGB1 in HK-2 of different groups. Compared with the model group, the cell activity was significantly increased after 24 h co-culture with TFDS and four flavonoids (isoorientin, apigenin, genistein and luteolin). These active components can reduce the LDH leakage and ROS in cell supernatant and increase the activity of SOD, with regulating the expression of NLRP3, caspase-1, HMGB1. TFDS, apigenin, isoorientin, luteolin and genistein can protect COM-induced HK-2 cell damage, including enhancing cell viability, protecting cell membrane integrity and enhancing oxidative stress, and regulate the expression of proteins related to NLRP3 inflammasome.

Clinical Efficacy of Modified Weijingtang and Maxing Shigan Tang Combined with Half-dose Hormones on Refractory Mycoplcasma Pneumoniae Pneumonia in Children Caused by Toxic Heat Closing Lung / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of modified Weijingtang and Maxing Shigan Tang combined with half-dose hormones in the treatment of mycoplcasma pneumoniae pneumonia in children caused by toxic heat closing lung. Method::Totally 120 cases were randomly divided into control group and observation group, with 60 cases in each group. In addition to the basic therapy, control group was given Lianhua Qingwen granules + methanilone (10 mg·kg-1, 2 times/day), while observation group was given modified Weijingtang and Maxing Shigan Tang + methanilone (10 mg·kg-1, 1 time/day) for 14 days. Lung function indicators [maximal voluntary ventilation (MVV), time of peak tidal expiratory flow (TPTEF), forced expiratory volume in one second (FEV1), volume peak time expiratory flow (VPTEF)], plasma myocardial enzyme profile [creatine kinase (CK), creatine kinase isoenzyme (CKMB), lactate dehydrogenase (LDH), hydroxybutyric acid dehydrogenase (HBDH)], immune function [immunoglobulin G (IgG), immunoglobulin M (IgM), erythrocyte immune complex (RBC-ICR), erythrocyte C3b receptor (RBC-C3bR)], inflammatory factors [tumor necrosis factor-alpha (TNF-α), gamma-interferon (IFN-γ), interleukin-13 (IL-13), interleukin-17A (IL-17A)], clinical efficacy and adverse reactions were observed before and after treatment. Result::Four cases fell off during the study period. The total effective rate in observation group was 96.6%(57/59), which was higher than that in control group 84.2%(48/57, P<0.05). Compared with control group after treatment, lung function, RBC-C3bR and IL-13 were increased in observation group (P<0.05), while myocardial enzyme spectrum, IgG, IgM, RBC-ICR, TNF-α, IFN-γ and IL-17A were decreased in observation group (P<0.05). The incidence of adverse reactions in observation group was, lower than that in control group(P<0.05). Conclusion::Modified Weijingtang and Maxing Shigan Tang combined with half-dose hormones can improve lung function, myocardial enzyme profile, immune function and inflammatory factor levels of refractory mycoplasma pneumoniae in children caused by toxic heat closing lung, with a incidence of adverse reactions.

Effect of Tianwang Buxin Pills on Behavior, HPA Axis, BDNF Expression and Phosphorylation of GSK3β in Mice with Chronic Unpredictable Stress / 中国实验方剂学杂志

Objective:To investigate the effect of Tianwang Buxin pills on behavior， hypothalamus pituitary adrenal axis （HPA axis）， hippocampal glycogen synthase kinase 3β （GSK3β） phosphorylation and brain-derived neurotrophic factor （BDNF） expression in mice with chronic unpredictable stress， and explore its mechanisms for antidepressant-like action. Method:Totally 60 male ICR mice were randomly divided into normal group， chronic stress model group， fluoxetine hydrochloride group （10 mg·kg-1） and Tianwang Buxin pills high， middle and low dose groups （3.6， 1.8， 0.9 g·kg-1）. The mice were subjected to the chronic unpredictable stress （CUS） protocol for a period of 28 d to induce depressive-like behavior. Then， a sucrose preference test， open-field test and novelty-suppressed feeding test were performed to detect the behavior changes. The blood， adrenal gland and hippocampus of mice were collected. The contents of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The changes of GSK3β phosphorylation and BDNF expression in hippocampus were detected by Western blot， and the adrenal index was then calculated. Result:As compared with the normal group， the sucrose water preference was significantly decreased （P<0.01）， the number of opening activities was significantly reduced （P<0.05）， the feeding latency of novelty inhibition was prolonged （P<0.01）， the serum ACTH and CORT contents were significantly increased （P<0.05，P<0.01）， GSK3β phosphorylation and BDNF expression levels in hippocampus were significantly decreased （P<0.01）， and adrenal index was significantly increased in model group （P<0.01）. As compared with the model group， Tianwang Buxin pills treatment significantly reversed the CUS-induced behavioral abnormalities in depression model mice （P<0.05， P<0.01）， significantly decreased the levels of plasma ACTH and CORT （P<0.01） and adrenal and adrenal gland index （P<0.01）， while increased GSK3β phosphorylation and BDNF expression in hippocampus （P<0.05， P<0.01）， with its effect similar to that of fluoxetine hydrochloride. Conclusion:Tianwang Buxin pills produced antidepressant-like effects in chronic unpredictable stress mice， and its mechanism may be associated with inhibiting HPA axis activity and up-regulating GSK3β phosphorylation and BDNF protein expression in hippocampus.

Effect of P53 Expression on Prognosis of Patients with Double Expressor Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of P53 expression on prognosis of patients with double expressor lymphoma(DEL) and the interaction between the expression of MYC, BCL2 and P53 in diffuse large B-cell lymphoma(DLBCL).@*METHODS@#Eighty-eight patients with newly diagnosed DLBCL from 1st September 2012 to 31th May 2018 in Shanxi Dayi Hospital affiliated to Shanxi Medical University were selected. The expressions of MYC、BCL2、P53、CD10、BCL6、MUM and Ki-67 were tested by immunohistochemistry method. The overall survival of patients was analyzed by the Kaplan-Meier method and compared by the log-rank test. The prognostic effect of MYC, BCL2 and P53 expression was analyzed by univariate and multivariate analysis.@*RESULTS@#Compared with patients without P53 expression, the patients with P53 expression had higher LDH level, higher NCCN-IPI scores, lower response to chemotherapy，poorer overall survival(OS) and a higher rate of death(P0.05). Among lymphoma patients with MYC/P53, MYC/BCL2 and BCL2/P53 co-expression, the patients with MYC/P53 co-expression had the worse OS (3 year OS rate：31.6%), followed by the subgroup of patients with MYC/BCL2/P53(3 year OS rate：46.2%), patients with MYC/BCL2/P53 expression(3 year OS rate： 636%) showed a longer OS compared with the other two subgroups（P<0.05）. Multivariate analysis demonstrated that P53 expression and NCCN-IPI were independent prognostic factors in this patient cohort.@*CONCLUSION@#P53 and MYC expressions have a synergistically negative prognostic effect in DLBCL patients. P53 expression augments the negative prognostic effect of MYC/BCL2 double expression. Patients with MYC/P53 co-expression have a worse prognosis in comparison with the patients with MYC/BCL2 double expression.

Effect of Traditional Chinese Medicine on Hepatic Disease by Inhibiting TLR4 Signaling Pathway / 中国实验方剂学杂志

Liver disease is the general term for all diseases that occur in the liver. In recent years, traditional Chinese medicine has certain advantages in the treatment of liver diseases. With a high experimental study value, good clinical efficacy and less adverse reactions, it has broad prospects. Toll-like receptor 4 (TLR4) signaling pathway is closely related to liver diseases. Its mechanism is to activate nuclear factor-κB (NF-κB) through tlr4-mediated signaling pathway, inhibit the secretion of such inflammatory factors as interleukin-1(IL-1), interleukin-6(IL-6) and tumor necrosis factor-alpha (TNF-α), and the inflammatory damage of liver cells, so as to further inhibit the effect of IL-1,IL-6, TNF-α in activating Hepatic Stellate Cell(HSC). The ways of blocking TRL4 pathway are as follows:Inhibiting the expression of TLR4,Inhibiting the dimerization of TLR4. Blocking intracellular signal transduction:①acting on the binding protein; ②acting on the kinase IRAKs; ③acting on TLRAFst. In these ways, the TRL4 pathway is blocked, the inflammation is inhibited, and the anti-liver disease effect is achieved. Therefore, inhibiting or enhancing TLR4 signaling pathway or intervening in some links of TLR4 signaling pathway has become a new strategy for the treatment of liver diseases. Toll-like receptor 4 signaling pathway has become one of the targets of traditional Chinese medicine (TCM) against liver diseases. In this paper, the recent literatures on the effect of TCM in resisting activation of TLR4 signaling pathway and the effect of anti-liver diseases through monomers and effective parts of TCM, extracts of TCM and compound prescriptions of TCM were collected and summarized to provide important guiding significance and direction for the treatment of liver diseases by TCM and WM in the next step.