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 se-rotonin 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.

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.

Emergence agitation(EA)is a common complication after general anesthesia,especially in children and adolescents.Remifentanil,as a short-acting μ-receptor agonist,has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression.This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA.Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network,including regulation of microglial inflammatory pathways,and the modulation of cytokines and chemokines,etc.Clinical studies have shown that remifentanil can significantly shorten the recovery time,reduce the incidence of EA,and further optimize the analgesic effect and recovery quality by combining with other drugs(such as local anesthetics,sedatives,and opioid drugs).Future research should further explore the mechanism of action of remifentanil,optimize clinical treatment strategies,and conduct large-scale clinical trials to standardize the drug use plan,while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

As we all known,lipid metabolism participate in various diseases extensively.Abnormal lipid metabolism may contribute to hepatic adipose infiltration,diabetes,atherosclerosis and so forth.Accordingly,it is urgent to find chemicals that regulate lipid metabolism.A large number of experimental studies have shown that flavonoids in fructus aurantia are the active components of lowering blood lipids.This article will describe the concept,structure and classification of flavonoids.It will also introduce the mechanism of action of flavonoids in lipid metabolism from various diseases such as atherosclerosis,hypertension and type 2 diabetes.

OBJECTIVE: To evaluate the relationship between 24 h urinary ion content and kidney stones, and to explore the diagnostic values of kidney stone in primary gout patients. METHODS: Patients diagnosed with primary gout had ultrasound scanning of both feet and kidneys in Peking University First Hospital from Jan. 2020 to May 2021. Their clinical characteristics were compared between the positive and negative kidney stone groups, and the relationship between kidney stone and urinary ion composition were analyzed. Risk factors of kidney stone were analyzed. The explored diagnostic values were evaluated for urinary oxalate and citrate according with uric acid kidney stones by dual-energy computed tomography (DECT). RESULTS: Among the 100 gouty patients, 80 patients had uric acid crystal deposition in lower joints of extremity by ultrasonography, 61 patients had kidney stone, and 34 had kidney uric acid stones by DECT. All the multiple kidney stones were proved as uric acid kidney stones by DECT. Compared with patients without kidney stone group proved by ultrasonography, patients with kidney stone had longer gouty duration [(48.7±26.6) months vs. (84.0±30.6) months, P=0.01], higher 24 h urinary oxalate [(20.1±9.6) mg vs. (28.6±20.7) mg, P=0.001] and lower 24 h urinary citrate [(506.3±315.4) mg vs. (355.7±219.6) mg, P=0.001]. Compared with the patients without kidney stone by DECT, the patients with uric acid kidney stone also had longer disease duration [(49.1±28.4) months vs. (108.3±72.2) months, P=0.001], higher 24 h urinary oxalate [(23.6±16.9) mg vs. (28.5±18.8) mg, P < 0.05], lower 24 h urinary citrate [(556.0±316.3) mg vs. (391.7±261.2) mg, P < 0.05], higher serum uric acid [(466.2±134.5) μmol/L vs. (517.2±18.1) μmol/L, P < 0.05] and higher 24 h urinary uric acid [(1 518.1±893.4) mg vs. (1 684.2±812.1) mg, P < 0.05]. Logistic regression analysis showed long gout disease duration (OR=1.229, 95%CI: 1.062-1.522, P < 0.05), high serum uric acid level (OR=1.137, 95%CI: 1.001-1.213, P=0.01), low 24 h urinary citrate (OR=0.821, 95%CI: 0.659-0.952, P=0.01) were all risk factors of kidney stones by ultrasonography. Also, long gout disease duration (OR=1.201, 95%CI: 1.101-1.437, P=0.005), high serum creatine uric level (OR=1.145, 95%CI: 1.001-1.182, P=0.04), low 24 h urinary citrate (OR=0.837, 95%CI: 0.739-0.931, P=0.02) were all risk factors of kidney uric acid stones by DECT. CONCLUSION Long disease duration and low 24 h urinary citrate were risk factors for kidney stones.
Humans ; Urinary Calculi ; Uric Acid/analysis* ; Citric Acid ; Kidney Calculi/diagnostic imaging* ; Gout/diagnostic imaging* ; Citrates ; Oxalates

Objective:To explore the spatio-temporal patterns and epidemic characteristics of imported dengue fever cases in six provinces (Yunnan, Guangxi, Guangdong, Hainan, Fujian and Zhejiang) of China from 2016 to 2018.Methods:In this study, we collected the surveillance data of imported dengue fever cases from 2016 to 2018 in six southern provinces of China. The risk intensity, spatio-temporal distribution and epidemiological characteristics of imported dengue fever cases in the six provinces were analyzed from the perspective of space, time and population.Results:Among the imported cases of dengue fever in China from other countries in the world, most of them were from Southeast Asia. In Zhejiang, Fujian and Guangdong provinces, there were greater number of imported cases with wide range of sources. While in Yunnan, Guangxi and Hainan provinces, the imported cases were almost from Southeast Asia. The incidence of imported dengue fever increased during the past three years, and the annual incidence peak was during August-November, but slight differences were observed among provinces. The age of the imported cases in Hainan[(37.0±19.6) years] was higher than that in southeastern coastal provinces[(36.0±11.7) years] and in southwestern provinces[(32.0±16.3) years]. The male-female ratio of the cases in southeastern coastal provinces (2.18∶1) were higher than those in southwestern provinces (1.04∶1) and Hainan (1.38∶1). The occupations of the cases were mainly workers and unemployed people in southeastern coastal provinces and farmers in southwestern provinces, but commercial personnel was the population with high incidence in both southeastern and southwestern provinces. Less imported dengue fever cases were reported in Hainan, the population distribution varied.Conclusions:There were differences in incidence pattern of imported dengue fever between southeastern coastal provinces and southwestern provinces as well as Hainan in China. Different prevention and control measures should be carried out in different areas to implement more precise prevention strategies.

Objective To investigate the effects of low GI cereals on metabolomics and pregnancy outcomes in women with gestational diabetes mellitus (GDM),in order to explore the preventive and therapeutic mechanisms and provide the basis for nutritional interventions.Metbods Pregnant women with gestational diabetes were assigned to the treatment group (n=31),using low GI grains 12 weeks for nutrition intervention and the control group (n =31) according to the random digital table method;30 healthy pregnant women were enrolled as normal control group.At 36th gestational week serum was analyzed by 1H-NMR metabolomics approach.Pregnancy outcomes were gathered for statistics after delivery.Comparison among groups and related influencing factors analysis were conducted.Results After nutritional intervention for 12 weeks,there were statistically significant differences in 15 potential biomarkers associated with gestational diabetes between the treatment group and the control group (P＜0.05),and no statistically significant difference between the treatment group and the normal control group (P＞0.05),that was the pregnant women in the treatment group were close to normal pregnant women.Cesarean rate,gestational weight gain,glycosylated hemoglobin during delivery,fasting insulin and newborn birth weight were significantly lower in the treatment group than in the control group.Multiple linear regression analysis showed that the GI of diet,fasting insulin and blood glucose were influencing factors for metabolomics in women with GDM.Conclusions Using low GI cereals intervention treatments,the pregnancy outcomes of GDM are improved distinctly with the possible mechanisms as adjusting the related biomarkers.Our study provides evidences for further exploring etiology and the therapeutic mechanisms of GDM,and individualized medical nutrition treatment strategy.

Objective To explore the value of water -based material decomposition images for detection of bone marrow edema (BME)in sacroiliitis with energy spectral CT.Methods The sacroiliac (SI)joints of nine spondyloarthropathy patients with sacroiliitis (the research group)and eight healthy volunteers (the control group) were underwent MRI and energy spectral CT.The mixed energy image of energy spectral CT was reconstructed to be mono energy image.Then,the mono image was divided into water -based image and calcium image by material divid-ed and analyzed software.The SI para -articular marrow region water -calcium relative concentration of research group was compared with that of control group.The BME diagnosis efficiency and optimal water -based concentration of energy spectral CT was analyzed by receiver operating characteristic (ROC)curve.Then,the sensitivity,specificity, positive likelihood ratio and negative likelihood ration were calculated.Results The water -based concentration of BME in research group (1 067.43 ±10.84)g/L was higher than that of control group (1 039.43 ±8.01)g/L(t =-3.14,P =0.003).Meanwhile,the calcium -based concentration of research group (68.98 ±20.53)g/L was not different from control group (78.03 ±26.39)g/L(t =1.88,P =0.066).ROC curve showed that the diagnosis efficiency was medium as the area of under curve was 0.75.When the optimal concentration of water -based was 1 052.00g/L,the diagnosis efficiency was the best.The sensitivity and specificity was 84.00%,62.50% respectively. Conclusion There are reference value and potential clinical value with energy spectral CT water -based concentra-tion detection for diagnosis BME in patients with sacroiliitis.

Objective To investigate the epidemiological characteristics of Plasmodium ovale in 2011-2014 for malaria control policy making during the phase of malaria elimination in China. Methods The data of individual Plasmodium ovale case (probable and confirmed) and population during 20011-2014 were collated from China National Notifiable Infectious Disease Reporting Information System, and the data of epidemiological investigation for individual Plasmodium ovale case (imported and indigenous) during 2011-2014 were collected from China Parasite Disease Prevention and Control Information System. All of the data didn't include China's Hongkong, Macao, Taiwan and foreign cases. The epidemiological characteristics, diagnosis and reporting were compared and analyzed. Results During study period of 2011-2014, a total of 373 Plasmodium ovale imported cases were reported, with male being 98.4% and median age being 40 years old. Jiangsu(100 cases), Guangxi(76 cases), Henan(55 cases), Anhui(28 cases)and Shandong(18 cases)reported Plasmodium ovale imported cases ranked the top 5 place in the list. Totally 182 counties from 21 provinces were reported Plasmodium ovale imported cases. 94.6% of ovale malaria imported cases (353/373) got infected from African countries and comprehensive hospitals, CDCs and hospital of infectious disease reported 40.0%, 37.8%, and 16.6%of Plasmodium ovale imported cases, respectively. 4 days of median time lag of Plasmodium ovale imported cases from date of onset to diagnosis was longer than 3 days. Conclusion From 2011 to 2014, the rising number of Plasmodium ovale imported cases reported from wilder scope of China. Diagnosis time lag of Plasmodium ovale was longer than that of other Plasmodium. Diagnosis and prompt treatment of Plasmodium ovale imported cases and relapse case should be highlighted.

Objective To explore pathogen spectrum constitution of acute diarrhea in outpatient and emergency of Zhejiang Province, and provide basis for treatment, prevention and control of the disease. Methods During January 2009 to December 2014, we selected seven sentinel hospitals in different regions of Zhejiang, monitored and researched on pathogen spectrum in patients with acute diarrhea from outpatient and emergency. We recorded patients' personal basic information, the main symptoms and signs, and collected stool samples (5 g). Eight kinds of bacteria (Vibrio cholerae, Shigella spp., Salmonella spp., Diarrheagenic E. coli, Vibrio parahaemolyticus, Aeromonas hydrophila, Yersinia enterocolitica and Plesiomonas shigelloides) and five kinds of viruses (Rotavirus, Norovirus, Sappovirus, Astrovirus and Adenovirus) were detected. Chi-square test and Fisher's exact probability method were used to compare different characteristics of patients with single bacterial infection, single virus infection and multiple infection (bacteria-bacteria, bacteria-viruses, virus-virus). Results During 2009 to 2014, 9 364 fecal
samples from acute diarrhea patients were collected and tested, among which 3 500 cases were tested positive, with total positive rate of 37.38%. Positive rates of bacteria and viruses were 13.14%(1 230 cases) and 20.75%(1 943 cases), respectively. Mixed infection positive rate of multiple pathogens was 3.49%(327 cases). Positive rate of Vibrio parahaemolyticus (5.96%, 558 cases) was the highest among bacterial pathogens, followed by pathogenic Escherichia coli (3.86%, 361 cases). Viruses were mainly Norovirus (10.73%, 1 005 cases) and rotavirus (8.35%, 782 cases). A big difference existed in diarrheogenic pathogen spectrum between patients less than 15 years old and patients equal or older than 15 years old. Pathogens for patients less than 15 years old were mainly virus, with the positive rate of 32.69%(1 014 cases). However, the positive rate of bacteria was 16.86% (1 056 cases) in patients equal or older than 15 years old. Single bacterial infection was highest in age group of 25-34 years old (18.62%, 302 cases) , single virus infection was highest in age group of 1-4 years old (41.12%, 435 cases) , and mixed infections of multiple pathogens were mainly existed in age group of 1-4 years old (7.37%, 78 cases) . Pathogen positive rate were increasing year by year. Pathogen positive rate of patients with acute diarrhea has obvious seasonality, with single bacterial infection being highest during July to September and single virus infection being highest during December to March. Pathogen spectrum of outpatient and emergency patients with acute diarrhea in Zhejiang Province changed a little from 2009 to 2014, mainly rotavirus (22.34% (782/3 500)), norovirus (28.71%(1 005/3 500)), vibrio parahaemolyticus (15.92%(558/3 500)) and Escherichia coli (10.31%(361/3 500)). However, pathogen spectrums in different years owned different features. Conclusion Common pathogens in outpatient and emergency patients with acute diarrhea in Zhejiang Province were tested with significant seasonal epidemic law. The composition of pathogenic spectrum was variant in different age group. Constitutes of major pathogen spectrum in different years differed a little.