Artificial intelligence technology is being widely applied in drug screening. This paper introduces the characteristics of artificial intelligence, and summarizes the application and progress of artificial intelligence technology especially deep learning in drug screening, from ligand-based and receptor structure-based aspects. This paper also introduces how to apply artificial intelligence to drug design from these two aspects. Finally, we discuss the main limitations, challenges, and prospects of artificial intelligence technology in the field of drug screening.

[ ABSTRACT] AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue ( GnRHa) and growth hormone ( GH) on the linear growth in mid-and late pubertal girls at great bone ages with central precocious puberty ( CPP) or early and fast puberty ( EFP) , and to determine the relation between C-type natriuretic pep-tide ( CNP) signaling pathway and the accelerative effect of GH on long bone growth in these girls.METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height ( PAH) , and divided into GnRHa treatment group ( treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group ( treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc) .The height, weight and pubertal stage were determined every 3 months.At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide ( NT-proCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity ( HV) , height SD score for bone age ( HtSDSBA ) , PAH and the serum indexes mentioned above were com-pared at the beginning and the end of the treatment.RESULTS: After 6 months of the treatment, HV, ΔHtSDSBA andΔPAH of the girls treated with GnRHa +GH were statistically higher than those of the girls given GnRHa alone ( P <0.01).Serum concentrations of NTproCNP, P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment.The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION:In the CPP or EFP girls who are in mid-and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height.This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.

Objective To study the effect on body mass index ( BMI ) caused by treatment with Gonadotropin-releasing hormone analogs ( GnRHa) in girls with central precocious puberty ( CPP) or early and fast puberty ( EFP ) . Methods The BMI in 318 girls ( 227 CPP and 91 EFP ) treated with GnRHa alone was analyzed. Among them 89 were followed up to their final adult height. Results Before GnRHa treatment was started, thegirlswithCPPandEFPhadameanBMIstandarddeviationscore(SDS)forchronologicalage(BMISDSCA)of0.39 ±0.84andforboneage(BMISDSBA)of-0.11±0.69. Attheendoftreatment,themeanBMISDSCAwas0.59±1.01 and BMISDSBA was 0. 24 ± 0. 89, both were significantly higher than those at initiation. The increment in BMISDSBA (0.38±0.50)wasgreaterthanthatinBMISDSCA(0.21±0.56). Moreover,theratioofoverweight(BMI>85%)was significantly elevated. BMISDSCA of 89 girls who were visited at their final adult height was 0. 17 ± 1. 15, which was similar with BMISDS at initiation and in normal population. Conclusion The mean BMISDSCA of CPP and EFP was significantly higher than the general population, while BMISDSBA was significantly lower. During GnRHa treatment, BMISDS tended to be elevated. But it was reversible, for the mean BMISDS was back to normal at final adult height.

Objective: To analyze and investigate the effects of implant location and axial direction on the stress distribution of implants, abutments, central screws, and crowns during immediate loading of maxillary mesial incisors with different alveolar fossa morphology based on three-dimensional finite element method. Methods: Referring to the oral CBCT images of a healthy adult, a three-dimensional finite element model was established for immediate implant loading of maxillary central incisors with three alveolar fossa morphs: labial, intermediate, and palatal; different implant sites(apical site, palatal/labial site) and axes(tooth long axis, alveolar bone long axis) were simulated; the established model was loaded with a force of 100 N. ANSYS software was applied to analyze the stress values of the implants, abutments, central screwss, and crownss. Results: The 3D finite element models of 12 maxillary central incisors with different alveolar sockets were successfully established;the implants and their superstructures were least stressed when the maxillary central incisors with partial labial and partial palatal shape were placed along the long axis of the alveolar bone in the palatal/labial position for immediate implant loading;the implants and their superstructures were least stressed when the maxillary central incisors with central shape were placed along the long axis of the tooth in the palatal position for immediate implant loading. The implant and its superstructure were subjected to the least stress when the implant was placed along the long axis of the tooth in the immediate loading position. Conclusion The bio-mechanical characteristics of the implant and its superstructure are influenced by the different socket morphology, implantation sites and axes. Therefore, in clinical practice, different implantation axes and implantation sites should be developed for different socket morphs.

Abnormalities, Multiple ; surgery ; Adolescent ; Humans ; Male ; Spleen ; abnormalities ; Testis ; abnormalities

Objective To investigate the influence of implant location and axial direction on stress distributions at the implant bone interface of maxillary central incisors with different alveolar fossa morphology by immediate implantation under immediate weight-bearing. Methods With reference to dental cone beam computed tomography (CBCT) image data from a healthy adult, the three-dimensional ( 3D) finite element models of maxillary central incisors with three types of alveolar fossa ( buccal, mediate, and palatal type) by immediate implatation under immediate weight-bearing were established. Different implant sites ( apical site, palatal / labial site) and axial directions (long axis of the tooth, long axis of the alveolar bone) were simulated. The established models were subjected to 100 N force at different angles (0°, 30°, 45°, 60°, 90°). The stresses in the alveolar bone around the implant were analyzed by the ANSYS software. Results Twelve 3D finite element models of maxillary central incisors with different alveolar fossa morphology by immediate implantation under immediate weight-bearing were successfully established. When alveolar fossa with buccal and mediate shape was applied with immediate implantation under immediate weight-bearing, it was easier to obtain good biomechanical properties of the implant-bone interface when implants were placed at palatal site along long axis of the alveolar bone. When alveolar fossa with palatal shape was applied with immediate implantation under immediate weight bearing, the equivalent stresses on peri-implant alveolar bone were much smaller than those on apical site, regardless of whether the implant was placed along long axis of the tooth or the long axis of the alveolar bone. Conclusions Different alveolar fossa morphology, implant location and axial direction will affect characteristics of implant-bone interface of maxillary central incisors with immediate implantation under immediateweight-bearing. In clinical practice, surgical planning on different axial direction and location of implantation should be developed for alveolar fossa with different morphology.

Objective To summarize the characterization of ovarian adrenal rest tumors (OART) in children and adolescent females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD).Method We have diagnosed 4 cases of CAH 21-OHD with OART in the recent 5 years in pediatric endocrinology unit of the first affiliated hospital of Sun Yat-Sen University.Clinical characterizations were summarized,including symptoms,growth patterns and bone age advancements,serum steroid concentrations,imaging results and the follow-up data.Result The 4 cases of OART accounted for 2.5 ％ of the CAH 21-OHD girls,which was much lower than the detection rate,29.5％,of testicular ART in our patient group during the same period.The 4 cases included 3 salt wasters and 1 with simple virilizm.OART were diagnosed at the age of 8.9 years,15.8 years,21.4 years and 9.3 years,respectively.Before the diagnosis of OART,their daily hydrocortisone doses reached 16 mg/(m2 · d)to 24 mg/(m2 · d).The patients presented with deteriorated acne,deepened voice,amenorrhea (2 cases),accelerated growth and advanced bone age,△BA/△CA reached 1.2 (during GnRHa treatment) and 2.0.Their serum adrenal steroids increased significantly and hyperplasia of adrenal glands were found in all patients.The diagnosis could be confirmed before the operation in only 1 case.The diagnosis could not be made until the planned sub-total adrenalectomy in the other 3 cases.The follow-up periods of OART were 4.8,4.7,3.8and 2.7years,respectively.Removal of OART resulted in symptoms relief at least partialy and lowered daily hydrocortisone doses,14 to 19 mg/(m2 · d).Conclusion The detection rate of OART was much lower than testicular ART.Before the diagnosis of OART,the patients presented with deteriorated virilescence,accelerated growth and advanced bone age,elevated serum adrenal steroids and hyperplasia of adrenal glands.Removal of the OART resulted in symptoms relief at least partialy.

BACKGROUNDUncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However, whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells.

METHODSThe alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed.

RESULTSPalmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion.

CONCLUSIONUCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway.

Animals ; Cells, Cultured ; Glucagon ; secretion ; Glucagon-Secreting Cells ; drug effects ; physiology ; Insulin ; pharmacology ; Insulin Receptor Substrate Proteins ; metabolism ; Ion Channels ; genetics ; physiology ; Iridoid Glycosides ; pharmacology ; Iridoids ; Mice ; Mitochondrial Proteins ; genetics ; physiology ; Oxidative Stress ; Palmitic Acid ; toxicity ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Phosphorylation ; RNA, Messenger ; analysis ; Signal Transduction ; Trans-Activators ; genetics ; physiology ; Transcription Factors ; Tyrosine ; analogs & derivatives ; metabolism ; Uncoupling Protein 2

OBJECTIVE: To examine the difference of manganese exposure level in different types of welding jobs and its effects on electric welding workers' health. METHODS: Eight-seven electric welding workers recruited in 2009 were selected by cluster sampling method as exposure group. The exposure group was divided into low,middle and high sub-exposure groups based on the different manganese exposure levels in workplace air. Thirty administrative and technical personnel were selected as control group. Manganese exposure levels of exposure group in workplace air were continuously measured from 2009 to 2013 for 5 years. The urine manganese levels of control and exposure groups were detected. Occupational health examination was conducted in these two groups in 2013. RESULTS: The trend of manganese exposure level in workplace air of exposure group from low to high was submerged arc welding post < gas tungsten arc welding post < hand welding post( P < 0. 01). The urine manganese levels in exposure group in 2010-2013 were higher than those of control group in the same corresponding year( P < 0. 01). With the increase of manganese exposure time,urine manganese levels increased in exposure group and the 3 sub-exposure groups( P < 0. 01); in 2012 and 2013,the urine manganese levels of exposure group showed an increasing trend with the increase of manganese exposure level( P < 0. 01). The positive rates of dizziness,body ache and memory lost in exposure group had an increasing trend with the increase of manganese exposure level( P < 0. 05). CONCLUSION: The difference of manganese exposure level in different types of welding jobs affects the urine manganese levels and health status of electric welding workers.

Objective:To evaluate the relationship between the relative variability of the platelet count in peripheral blood and the severity and prognosis of sepsis patients.Methods:Clinical data of 102 sepsis patients admitted to the Department of Critical Care Medicine (ICU), Zhongshan Hospital, Fudan University from March 2015 to June 2016 were collected.The clinical characteristics of patients with high and low platelet relative variability were compared.The relationship between the relative variability of blood platelet count and the severity of disease and mortality were analyzed.Results:The relative variability of the platelet count was negatively associated with the SOFA (Spearman r=-0.317, P=0.001) and APACHE Ⅱ (Spearman r=-0.397, P<0.001) scores upon admission into ICU.Multivariate regression analysis showed that the relative variability of platelet count was an independent predictor of ICU mortality in sepsis patients (OR=0.174, 95% CI 0.040-0.758, P=0.02).Conclusions:The relative variability of platelet count in sepsis patients can reflect the severity of the disease and predict the ICU mortality of these patients.