Assessment of the Benefits of Targeted Interventions for Pandemic Control in China Based on Machine Learning Method and Web Service for COVID-19 Policy Simulation

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019(COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web inter...     

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

Effect of different modeling time on intestinal bacteria in letrozole induced PCOS rats

Objective: The differences of ovarian morphology, reproductive hormones, glucose and lipid metabolism and intestinal bacteria in rats with polycystic ovary syndrome (PCOS) induced by triazole were compared. Method: Eighteen 21 SPF female SD rats were randomly divided into group A (3-week group), group B (5-week group) and group D (control group) by random number table.Group A received letrozole + CMC-Na mixture by gavage in the first 3 weeks and CMC-Na solution by gavage in the last 2 weeks, group B received letrozole + CMC-Na mixture by gavage for 5 weeks, and group D received CMC-Na solution by gavage for 5 weeks, and all three groups of rats were fed with normal diet.At the end of gavage, the body weight of rats in each group was observed, the histological changes of ovaries were observed by hematoxylin-eosin (HE) staining, the serum levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), total cholesterol (TC), triglyceride (TG), fasting blood glucose (Glu), fasting insulin (FINS) and lipopolysaccharide (LPS) were measured by enzyme-linked immunosorbent assay (ELISA), and the LH/FSH ratio and insulin resistance index (HOMA IR) were calculated; the intestinal bacteria of rats were detected by 16S rRNA technique. Result: 1. Comparison of ovary histomorphology: Under light microscope, multiple luteum and oocytes were observed in mature follicles in group D, and granulosa cells were orderly arranged and multilayered, without cystic dilated follicles. There were no mature follicles in the ovarian tissues of group A and GROUP B. The follicles were irregular in structure and more cystic dilated follicles were visible. The number of granular cells in some follicles decreased or even disappeared. 2. Comparison of sex hormone levels: compared with group D, T level in group B was significantly increased (P < 0.001), and T level in group A had an upward trend (P > 0.05); The LH/FSH levels in group A and B were significantly increased (P < 0.001; P < 0.001). Compared with group A, E2 in group B was significantly decreased (P < 0.05) and T was significantly increased (P < 0.01). 3. Comparison of glucose and lipid metabolism levels: Compared with group D, TC levels in groups A and B were significantly increased (P < 0.01; P < 0.01). Compared with group A, TG in group B was significantly increased (P < 0.05). There were no significant differences in Glu, FINS and HOMA-IR levels among all groups. 4. Comparison of LPS levels: Compared with group D, the serum LPS levels of rats in groups A and B were significantly increased (P < 0.001; P < 0.01). 5. Intestinal flora analysis and comparison: At the phylum level, compared with group D, the abundance of Firmicutes in group B increased (P < 0.01), Firmicutes in group A showed an upward trend (P > 0.05), and the abundance of Bacteroidetes in groups A and B decreased (P < 0.05). At the genus level, compared with group D, Lactobacillus in group B increased (P < 0.01). The results of LEfSe analysis showed that there were differences in the composition of various intestinal bacteria among the three groups (LDA > 3).Conclusion: The phenotype of PCOS rats was related to the length of modeling, and the phenotypic characteristics of PCOS in rats at 5 weeks of modeling were more typical than those in rats at 3 weeks of modeling; PCOS can cause changes in intestinal flora, and the changes in the structure of intestinal flora between groups are related to different modeling duration.     

Spatial-temporal Analysis of Tuberculosis at the Community Level in the Baoshan District,Shanghai 2014–2019

<正>Mycobacterium tuberculosis is the primary bacteria that leads to human tuberculosis(TB),which usually affects the pulmonary organs. TB is one of the top 10 causes of death worldwide;however, China is one of eight countries that together account for two-thirds of the total number of cases globally.     

Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma

Objective:O6 methylguanine-DNA methyltransferase(MGMT)promoter methylation is a biomarker widely used to predict the sensitivity of IDH-wildtype glioblastoma to temozolomide therapy.Given that the IDH status has critical effects on the survival and epigenetic features of glioblastoma,we aimed to assess the role of MGMT promoter methylation in IDH-mutant glioblastoma.Methods:This study included 187 IDH-mutant glioblastomas and used 173 IDH-wildtype glioblastomas for comparison.KaplanMeier curves and multivariate Cox regression were used to study the predictive effects.Results:Compared with IDH-wildtype glioblastomas,IDH-mutant glioblastomas showed significantly higher(P<0.0001)MGMT promoter methylation.We demonstrated that MGMT promoter methylation status,as determined by a high cutoff value(≥30%)in pyrosequencing,could be used to significantly stratify the survival of 50 IDH-mutant glioblastomas receiving temozolomide therapy(cohort A);this result was validated in another cohort of 25 IDH-mutant glioblastomas(cohort B).The median progression-free survival and median overall survival in cohort A were 9.33 and 13.76 months for unmethylated cases,and 18.37 and 41.61 months for methylated cases,and in cohort B were 6.97 and 9.10 months for unmethylated cases,and 23.40 and 26.40 months for methylated cases.In addition,we confirmed that the MGMT promoter methylation was significantly(P=0.0001)correlated with longer OS in IDH-mutant patients with GBM,independently of age,gender distribution,tumor type(primary or recurrent/secondary),and the extent of resection.Conclusions:MGMT promoter methylation has predictive value in IDH-mutant glioblastoma,but its cutoff value should be higher than that for IDH-wildtype glioblastoma.     

The Mechanisms of Pei‑yuan‑Tong‑nao Capsule as a Therapeutic Agent against Cerebrovascular Disease

Objective: Pei?Yuan?Tong?Nao (PYTN) capsule has been widely used for the treatment of cerebrovascular disease (CVD), including cerebral ischemia. However, due to the complexity of traditional Chinese Medicine (TCM) and the lack of proper inspection methods, the pharmacological mechanisms of the actions of PYTN capsule on CVD remain ambiguous. In this investigation, a network pharmacology method was used to investigate the mechanism of action of PYTN capsule in the treatment of CVD. Methods: In this method, a chemical similarity ensemble approach was employed to predict putative targets for chemicals derived from PYTN capsule. Results: Thus, a total of 351 compounds and 650 proteins were identified as potential active ingredients and putative CVD?related targets. In addition, two interaction networks were constructed, including a network between putative targets of PYTN capsule and known CVD?related targets, and a network between candidate active compounds and putative CVD?related targets. Conclusion: The mechanism of PYTN capsule in the treatment of CVD was found to be based on three functional modules, namely, antioxidation, anti?inflammation, and antiapoptosis modules through multiple signaling pathways, such as PI3K?Akt, mitogen?activated protein kinase, and TNF signaling pathways. We hope that this work can provide insight into the pharmacological mechanisms of TCMs in the treatment of CVD and provide a basis for further development and the discovery of more effective clinical strategies for the treatment of complicated diseases.     

Ultra-early amplitude decrement after repetitive nerve stimulation supports early neuromuscular junction injury in amyotrophic lateral sclerosis:a prospective cross-sectional study

The dying-back hypothesis holds that the damage to neuromuscular junctions and distal axons in amyotrophic lateral sclerosis occurs at the earliest stage of the disease.Previous basic studies have confirmed early damage to neuromuscular junctions,but it is difficult to obtain such evidence directly in clinical practice.In this prospective cross-sectional study,we recruited 22 patients with early amyotrophic lateral sclerosis with disease duration < 12 months and with clinical symptoms limited to the upper limbs.We also recruited 32 healthy controls.Repetitive nerve stimulation was performed,and patients were followed for 12 months.We found a significant change in the response to repetitive nerve stimulation in amyotrophic lateral sclerosis patients without spontaneous electromyographic activity.Patients that were prone to denervation had an increased decrement response of target muscles after repetitive nerve stimulation.These results suggest that changes in response to repetitive nerve stimulation may occur before denervation in amyotrophic lateral sclerosis patients.The damage to lower motor neurons is more obvious in patients with a higher percentage of repetitive never stimulation-related amplitude decrements.This study was approved by the Institutional Ethics Committee of Peking University Third Hospital(approval No.M2017198) on August 24,2017.     

Biomechanical behavior of brain injury caused by sticks using finite element model and Hybrid-III testing

Objective: To study the biomechanical mechanism of head injuries beaten with sticks, which is common in the battery or assaultive cases. Methods: In this study, the Hybrid-III anthropomorphic test device and finite element model (FEM) of the total human model for safety (THUMS) head were used to determine the biomechanical response of head while being beaten with different sticks. Total eight Hybrid-III tests and four finite element simulations were conducted. The contact force, resultant acceleration of head center of gravity, intracranial pressure and von Mises stress were calculated to determine the different biomechanical behavior of head with beaten by different sticks. Results: In Hybrid-III tests, the stick in each group demonstrated the similar kinematic behavior under the same loading condition. The peak values of the resultant acceleration for thick iron stick group, thin iron stick group, thick wooden stick group and thin wooden stick group were 203.4 g, 221.1 g, 170.5 g and 122.2 g respectively. In finite element simulations, positive intracranial pressure was initially observed in the frontal comparing with negative intracranial pressure in the contra-coup site. Subsequently the intracranial pressure in the coup site was decreasing toward negative value while the contra-coup intracranial pressure increasing toward positive values. Conclusions: The results illustrated that the stiffer and larger the stick was, the higher the von Mises stress, contact force and intracranial pressure were. We believed that the results in the Hybrid-III tests and THUMS head simulations for brain injury beaten with sticks could be reliable and useful for better understanding the injury mechanism.     

Root canal systems in mandibular first premolars with C-shaped root configurations. Part I: Microcomputed tomography mapping of the radicular groove and associated root canal cross-sections

The purpose of this study was to investigate the morphology of the radicular grooves and root canal cross-sections in mandibular first premolars that exhibit a C-shaped root. Eighty-six mandibular first premolars with C-shaped roots were scanned from the coronal to anatomical apex using microCT80. The location, length, and depth of the radicular grooves were measured. The cross-sectional morphology of root canal systems was evaluated at 11 levels. Results were subject to the Kruskal-Wallis test. Of the 86 C-shaped roots, a total of 93 radicular grooves were noted. Most of the grooves (78.5%) were located on the mesiolingual surface of the root. The C-shaped canal could vary considerably in shape at different levels, and the incidence of two canals at the middle and apical was 21% and 80%, respectively. This study shows that radicular grooves may present relevant morphologic variations in the root canal system when the C-shaped root is present.