Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

IgG4-related disease (IgG4-RD) involving the ureter manifested as a ureteral tumor is rare. This paper reports a case of a female patient who was found with a mass at the left ureteropelvic junction for one week during physical examination. Urinary ultrasound and MRI showed a 3 cm mass at the left ureteropelvic junction with hydronephrosis, and the serum level of IgG4 was elevated. B-ultrasonic guided biopsy of the mass was performed. Histopathological findings showed lymphoplasmic infiltration and the ratio of IgG4/IgG positive cells>0.5. We finally diagnosed IgG4-RD and started using glucocorticoid for her treatment. One month later, CT-scan revealed that the tumor became smaller and the serum IgG4 decreased to the normal range.

Ectopic prostate is rare.This paper reports a case of a male patient who was found a mass in the pelvis for 20 days during physical examination.Urinary ultrasound, CT scan and MRI showed a pelvic mass that was about 4 cm×5 cm in size.Serum total prostate specific antigen (tPSA) was 6.09 ng/ml, and free PSA (fPSA) was 1.97 ng/ml. B-ultrasonic guided biopsy of the prostate and the mass was performed. Pathological findings suggest benign prostatic hyperplasia, weakly positive P504S and positive 34βE12. Pelvic mass is the prostate tissue with negative P504S and positive 34βE12. Finally, the ectopic prostate was diagnosed. Although it is rare, ectopic prostate should also be considered as a differential diagnosis of the pelvic tumor.

ObjectiveTo study the effect of modified Erchentang on the expression of key molecules in the high mobility group Box 1 protein （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway in bronchioles of rats with chronic obstructive pulmonary disease （COPD）， to explore the mechanism of modified Erchentang against bronchiolar inflammation of COPD rats via HMGB1/RAGE/NF-κB signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， modified Erchentang low-， medium- and high-dose groups （5， 10， 20 g·kg^-1·d^-1） and ethyl pyruvate （HMGB1 inhibitor） group， with 10 in each group. The COPD rat model was prepared by cigarette smoke combined with tracheal injection of lipopolysaccharide （LPS）. After modeling， the modified Erchentang groups were given corresponding drugs （ig） and Ringer's solution （4 mL， ip）， while the EP group was treated with equal volume of normal saline （ig） and EP （0.04 g·kg^-1·d^-1， ip）. The normal group and the model group received equal volume of normal saline （ig） and Ringer's solution （ip） for 21 consecutive days. The contents of HMGB1， chemokine （C-X-C motif） ligand 1 （CXCL1）， CXCL2 and monocyte chemotactic protein-1 （MCP-1） in bronchoalveolar lavage fluid （BALF） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of HMGB1， RAGE and NF-κB p65 were determined by Real-time polymerase chain reaction （Real-time PCR）， and the protein expressions of HMGB1， RAGE， p-NF-κB p65， and alpha-smooth muscle actin （α-SMA） in bronchioles tissue of rats were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the forced vital capacity （FVC）， forced expiratory volume in the first second （FEV1） and FEV1/FVC in the model group were decreased （P<0.01） while the contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF were increased （P<0.01）. And the model group presented higher mRNA expressions of HMGB1， RAGE and NF-κB p65 （P<0.01） and protein expressions of HMGB1， RAGE， p-NF-κB p65 and α-SMA （P<0.05， P<0.01） than the normal group. Compared with the model group， the modified Erchentang medium- and high-dose groups had increased FEV1/FVC （P<0.05， P<0.01）， lowered contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF （P<0.05， P<0.05）， and reduced mRNA expressions of HMGB1， RAGE and NF-κB p65 （P<0.05， P<0.01） and protein expressions of HMGB1， RAGE， p-NF-κB p65 and α-SMA （P<0.05， P<0.01）. ConclusionModified Erchentang can resist bronchiolar inflammation of COPD rats. The mechanism may be related to down-regulating the mRNA expressiona of HMGB1 and RAGE， inhibiting the activity of NF-κB， and reducing the release of HMGB1， CXCL1， CXCL2 and MCP-1， thus suppressing the inflammatory injury and abnormal repair of bronchioles.

Objective:Explore the main measures and operation mechanism to improve the scientific and technological innovation capacity of district and county hospitals by taking advantage of medical consortium, to achieve the goal of targeted poverty alleviation.Methods:Combine the practical exploration and empirical study on the main measures and operating mechanism to improve the scientific and technological innovation capacity of district and county hospitals, pre-and post comparison were conducted to analyze the effectiveness.Results:During the construction of medical consortium, a district-level general hospital has seen obvious increase in the comparison of many achievement indicators of scientific and technological innovation, with the growth rate ranging from 66.67% to 700%.Conclusions:Based on medical consortium, the operation mechanism that takes discipline construction as the starting point and key discipline establishment as the target, Scientific and technological innovation incubation platform, incentive mechanism and regular summary and evaluation can encourage district and county hospitals to improve scientific and technological innovation ability.

Objective: To examine the Quality of life among school-aged children with dyslexia in target city and to provide scientific evidence for improving the quality of life of children with dyslexia. Methods: By using cluster sampling,students from grade 3 to grade 6 from 6 primary schools in a middle-sized were selected and administered with questionnaire survey. According to the criteria of dyslexia, dyslexic children and non-dyslexic children were identified and the difference of the Quality of Life was compared. Results: Totally 3 673 children were collected, and 119 of them were identified as dyslexia(3.24%).The prevalence of dyslexia differed by gender,grades,educational level of parents(χ2=24.77,11.75,18.50,9.79,P<0.05). The Quality of Life which below the average proportion accounted for 30.3% of dyslexic children and 16.7% of normal children. Quality of life scored signiticantly different between dyslexic children and non-dyslexia children, including psychosocial functioning domain(134.54±30.88)(143.49±32.53), physical and mental health domain(2.71±0.84)(2.92±0.81) vs (2.83±0.90)(3.06±0.87), the living satisfaction domain(2.95±0.87)(3.14±0.87)(t=-6.09，-5.48，-5.44，-4.50，P<0.01),with dyslexic group significantly lower than that of non-dyslexic group. Conclusion The Quality of Life of Dyslexic children was in a poor condition.

To investigate the high-risk factors for newborn hearing loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn hearing screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. Our results revealed that 721 transferred newborns who didn't pass the hearing screening received audiological and medical evaluation and 367 were confirmed to have hearing loss. Of them, 177 neonates with hearing loss who met the matching requirements were included in the study as subjects. Univariate analysis showed that high-risk factors related to hearing loss incuded age of father, education backgrounds of parents, parity, birth weight, gestational weeks, craniofacial deformity, history of receiving treatment in neonatal intensive care unit (NICU), neonatal disease, family history of otopathy and family history of congenital hearing loss. Multivariate Logistic regression analysis revealed that 4 independent risk factors were related to bilateral hearing loss, including parity (OR=16.285, 95% CI 3.379-78.481), neonatal disease (OR=34.968, 95% CI 2.720-449.534), family history of congenital hearing loss (OR=69.488, 95% CI 4.417-1093.300) and birth weight (OR=0.241, 95% CI 0.090-0.648). It is concluded that parity, neonatal disease and family history of hearing loss are the promoting factors of bilateral hearing loss in neonates and appropriate intervention measures should be taken to deal with the risk factors.

To investigate the high-risk factors for newborn heating loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn heating screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. Our results revealed that 721 transferred newborns who didn't pass the heating screening received audiological and medical evaluation and 367 were confirmed to have heating loss. Of them,177 neonates with heating loss who met the matching requirements were included in the study as subjects. Univariate analysis showed that high-risk factors related to hearing loss incuded age of father, education backgrounds of parents, parity, birth weight, gestational weeks, craniofacial deformity,history of receiving treatment in neonatal intensive care unit (NICU), neonatal disease, family history of otopathy and family history of congenital hearing loss. Multivariate Logistic regression analysis revealed that 4 independent risk factors were related to bilateral hearing loss, including parity (OR=16.285, 95% CI 3.379-78.481), neonatal disease (OR=34.968, 95% CI 2.720-449.534),family history of congenital hearing loss (OR=69.488, 95% CI 4.417-1093.300) and birth weight (OR=0.241, 95% CI 0.090-0.648). It is concluded that parity, neonatal disease and family history of hearing loss are the promoting factors of bilateral hearing loss in neonates and appropriate intervention measures should be taken to deal with the risk factors.

OBJECTIVETo study the relationship between HLA-DRB1 alleles and idiopathic thrombocytopenic purpura (ITP) in children.

METHODSPCR-SSO was used to identify DRB1 alleles of 42 children with ITP. Among them, anti-GPIIb/IIIa and anti-GPIb/IX autoantibody were detected in 36 cases by modified monoclonal antibody specific immobilization of platelet antigens (MAIPA).

RESULTS(1) Compared with healthy controls, HLA-DRB1 * 17 was significantly increased (relative risk = 2.76, P < 0.05, etiologic factor = 0.106 4) and HLA-DRB1 * 1202 decreased (relative risk = 0.20, P < 0.025, prophylactic factor = 0.761 6) in children with ITP. (2) In comparison with patients with good response to steroids and IgG therapy, HLA-DRB1 * 11 was significantly increased (P < 0.025) in patients with a poor response, furthermore, most (5/6) of HLA-DRB1 * 11-positive patients were female teen-ager. (3) Twenty-seven patients (75%) had anti-GPIIb/IIIa and seventeen (47.22%) had anti-GPIb/IX autoantibodies, the positivity rates of both anti-GPIIb/IIIa (P = 0.02) and anti-GPIb/IX (P = 0.01) were associated with HLA-DRB1 * 02. However, the pos./itivity rates of autoantibodies between refractory and non-refractory patients showed no significant difference.

CONCLUSION(1) The DRB1 * 17 seems to predict susceptibility to ITP in children, while DRB1 * 1202 appears to be protective to against ITP. (2) The DRB1 * 11 plays an important role in resistance to steroid and IgG therapy in children with ITP. (3) It seems that the response to the antigenic epitope of GPIIb/IIIa and GPIb/IX is restricted by DRB1 * 02, while the presence of the autoantibodies couldn't predict prognosis. Our preliminary findings indicate that genetic factors influence the clinical course of ITP, but its exact mechanism needs to be further investigated.

Alleles ; Child ; Female ; Gene Frequency ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Humans ; Male ; Purpura, Thrombocytopenic, Idiopathic ; genetics ; immunology ; therapy