BACKGROUND:Network medical research contains various widely applicable networks with different structures, and construction methods. These networks are not organized in architecture yet, and there is a lack of overview about its application and research progress. OBJECTIVE:To organize various medical networks to a hierarchical architecture, and summarize their research progress. METHODS:A computer-based search of CNKI and PubMed databases was performed for articles about the network medicine published between 1999 and 2016 using the keywords ofdisease network, protein interaction network, metabolic network, gene regulatoryin English and Chinese, respectively. Then the main research contents, module property, construction methods, maturity and application progress of network medicine were discussed to predict the research direction. RESULTS AND CONCLUSION:The architecture of network medicine consists of molecular interaction network layer (interactome), disease network layer (diseasome) and drug network layer (drugome). In the interactome, protein-protein interaction network, metabolic network and gene regulatory network are in the order of organisms → mammals →human, and respective networks of human have been mapped but not mature;and new networks are being built. In diseasome, many disease networks have been constructed using a single element to cluster;and cluster by new element or combined elements can be considered in the future. Given this the current pharmacology is based on protein, there are few networks in the drugome the elements that constitute the drugome are only drug and protein.

Objective To study the distribution ,specimen types and characteristics of antibiotic resistance of Escherichia coli producing extended‐spectrum βlactamases(ESBLs) of the hospital in 2013 and to guide clinical drug use .Methods Analyzed the distribution and antibiotic resistance for the 375 strains of ESBLs‐producing E .coli ,and ESBLs was detected by disk diffusion phe‐notypic confirmatory test .Results The major distribution department was gynecology department which accounted for 42 .67% , followed by uropoiesis surgical department which accounted for 14 .67% ;the major specimen type was urine(55 .2% ) ,followed by puncture fluid(15 .47% )and excretion(14 .67% ) .For the 375 isolates of ESBLs‐producing E .coli ,the resistance rates to cefazolin , cefuroxime ,cefoperazone and cefotaxime were 100 .00% ,to SMZco was 78 .10% ,while the resistance rate to imipenem was 0 .00% , and to amikacin and fosfomycin were 4 .30% and 10 .10% respectvely ,the resistance rates to piperacillin/tazobactam and aztreonam were 17 .10% and 66 .70% respectvely .Conclusion ESBLs producing Escherichia coli have severe multidrug resistance .Antibiotics should be chosen and used rationally in accordance with results of drug susceptibility testing ,meanwhile the monitoring of ESBLs′infection rate and drug resistance should be strengthened .

Objective To investigate the roles of a epoprostenol(PGI2) analog (Iloprost) in regulating the differentiation of CD4+ T cells to Treg cells and the possible mechanism.Methods Naǐve CD4+ T cells were isolated from human peripheral blood samples by using the magnetic-activated cell sorting (MACS) and then cultured under Treg-polarizing condition.The percentages of Treg cells and the expression of Foxp3 at mRNA level were respectively measured by using flow cytometry and RT-PCR for evaluation the effects of Iloprost on the differentiation of CD4+ T cells to Treg cells.The cAMP accumulation assay was used to detect the level of intracellular cAMP.Flow cytometry analysis was performed to detect the phosphorylation of signal transducer and activator of transcription 5 (STAT5).Results lloprost decreased the percentage of Treg cells and inhibited the expression of Foxp3 at mRNA level in a dose dependent manner (P＜0.05).However,the inhibitory effects of Iloprost were weakened when IP receptors were blocked by IP antagonist (CAY10449).A six-fold increase in the levels of intracellular cAMP in Treg cells was induced by Iloprost (P＜0.05) and a similar effect could be achieved by using a cAMP agonist,db-cAMP (P＞0.05).H-89,a protein kinase A inhibitor,inhibited the Iloprost-induced expression of cAMP in Treg cells.Moreover,Iloprost inhibited the IL-2 mediated phosphorylation of STAT5 (P＜0.05) and a similar effect could be achieved by using db-cAMP (P＞0.05).The Iloprost-mediated down-regulation of pSTAT5 was blocked by using H-89.Conclusion PGI2 could activate the cAMP-PKA signaling pathway by binding to the IP receptor,resulting in inhibited phosphorylation of STAT5 and suppressed differentiation of naǐve CD4+ T cells to Treg cells.

Objective To investigate the improvement of postpartum pelvic floor by rehabilitation training assessed with three-dimensional transperineal ultrasound . Methods One hundred cases of healthy postpartum women were randomly divided into two groups :control group and training group .The control group received the customary education ,and the training group received pelvic floor rehabilitation training . At 6 and 12 weeks postpartum ,levator hiatus area ,thickness of the levator ani muscle ,bladder neck mobility ,and bladder posterior horn were measured with three-dimensional transperineal ultrasound in all the subjects . Meanwhile ,the muscle strength situations were tested . Results At 12 weeks postpartum ,the anal levator hiatal area ,bladder neck mobility and bladder posterior horn in the training group were lower than those of the control group[ ( 21 .6 ± 3 .2) cm 2 vs ( 25 .6 ± 2 .4 ) cm 2 ,( 27 .9 ± 5 .3) mm vs ( 31 .5 ± 5 .9) mm ,( 126 .3 ± 21 .2)° vs (135 .3 ± 11 .6)°] ( P < 0 .05) . Compared with control group ,the thickness of the levator ani muscle increased in training group [ ( 13 .6 ± 2 .3) mm vs ( 15 .3 ± 2 .5) mm ] ( P < 0 .05) . The incidence of stress urinary incontinence in the training group ( 5% ) was significantly lower than the control group ( 12 .5% ) at 12 weeks postpartum ( χ2 = 5 .487 , P = 0 .025) . The muscle strength had no significant difference at 6 weeks postpartum . At 12 weeks postpartum ,the pass rate of class Ⅰ muscle fiber was 78 .5% ,and that of class Ⅱ muscle fiber was 83 .3% in the training group ;the pass rate of class Ⅰ muscle fiber was 28 .5% ,and class Ⅱ muscle fiber was 37 .3% in the control group , the improvement was significant at 12 weeks postpartum . Conclusions The result of the transperineal real-time ultrasonographic evaluation of post-natal pelvic floor rehabilitation training has high consistency with the measurement of muscle strength . The ultrasound examination is simple and accurate ,and has highly applicable value in evaluating the effect of post-pelvic rehabilitation training .

Objective:To study the anti-inflammatory effect of the ethanol extract of Coptis chinensis Franch.in vitro.Methods: An inflammatory cell model was established by stimulating the mouse peritoneal macrophages in vitro with lipopolysaccharide(LPS).LPS stimulated of RAW264.7 cells for a long time after administration of intervention.Effect of ethanol extract of Coptis chinensis Franch.on RAW264.7 cell growth activity was analyzed by MTT assay.The production of tumor necrosis factor-α(TNF-α),IL-1β,IL-6,NO,prostaglandin E2(PGE2) was determined by ELISA.The expression of mRNA of TNF-α,induced nitric oxide synthase(iNos) and HO-1 was detected by real-time fluorescent quantitative PCR(RT-PCR).Results: The ethanol extract of Coptis chinensis had no inhibition effect on the scope of RAW 264.7 cells the scope of 5-80 mg/L.Each treatment group concentration of interleukin-6 (IL-6),interleukin-1β (IL-1β),TNF-α,NO,prostaglandin E2 (PGE2) content of LPS stimulation model group were significantly (P<0.01),and content was not related to concentration.Real-time quantitative (RT-PCR) showed,the concentration of each treatment group were significantly lower iNos,HO-1 and TNF-α mRNA expression (P<0.05,P<0.05,P<0.01),and content was not related to concentration.Conclusion: Coptis chinensis Franch.ethanol extract has anti-inflammatory effects in vitro,the mechanism may be related to inhibition of TNF-α,NO and other inflammatory factors and the impact of the activation of arachidonic acid (AA) metabolism.

BACKGROUND: The proliferation of peripheral blood stem cells among peripheral blood mononuclear cells (PBMCs) invitro remains unclear. There is no optimal marker for tracing PBMCs transplanted in vivo.OBJECTIVE: To observe the degree of PBMC proliferation in stem cell medium by EdU labeling and to explore thefeasibility of EdU-labeled peripheral blood stem cells.METHODS: New Zealand rabbit PBMCs were isolated and cultured for 1 to 5 days in stem cell medium supplementedwith EdU. The cells were observed and counted at 0, 1, 2, 3, 4 and 5 days in culture. The cells were harvested at eachtime point and stained with EdU fluorescent reagents. Then, confocal microscopy and flow cytometry were used to detectEdU-labeled cells.RESULTS AND CONCLUSION: (1) Freshly isolated rabbit PBMCs were rounded and showed clear outline. After 1 dayculture, most of the cells were suspended in the medium, spherical or round. There were also a few cell clusters andadherent cells scattered in a triangle or polygon shape; after 2 days culture, more cell debris were observed, and mostcells were round; when cultured for 3-5 days, increased cell debris, smaller cell mass and decreased cell densitysignificantly were observed. (2) With the prolongation of culture time, the cell count decreased gradually. (3) Whencultured for 1 day, EdU labeled cells in red were scattered. The number of cells marked with EdU red label increasedsignificantly at day 2 and remained unchanged after 3 days of culture. At 5 days of culture, the number of red cellsmarkedly decreased; the highest positive rate of EdU-labeled cells was (2.38±0.10)% at 2 days after culture. To conclude,these results showed that the proportion of proliferating cells in rabbit PBMCs was very low. EdU is capable of labelingproliferative cells among PBMCs.

Objective: To observe the effect of whole-body vibration therapy on the lower extremity the motor function of children with spastic diplegia. Methods: Fifty-six children with spastic diplegia were randomly divided into a treatment group and a control group, each of 28. Both groups were given routine rehabilitation exercise training, while the treatment group was additionally provided with 15 minutes of whole-body vibration therapy every day, 5 days a week for 12 weeks. Their GMFM-88 D (standing) and E (walking and jumping) scores were recorded before and after the treatment along with the active and passive range of motion of the ankle in dorsiflexion, and the root mean square surface electromyogram signals from the tibialis anterior and gastrocnemius muscles. Berg balance scale scores were also assigned before and after the treatment for both groups. Results: There were no significant differences between the two groups before the treatment. Afterward all of the evaluations except the signals from the tibialis anterior muscle in active ankle dorsiflexion had improved significantly. The improvements were all significantly better in the treatment group. Conclusion Whole-body vibration therapy can effectively improve the lower extremity motor function of children with spastic diplegia.

Gallbladder cancer is a high malignancy which is predisposed to invade adjacent organs and have lymph node metastasis. Gallbladder cancer is not sensitive to radiotherapy or chemotherapy with the worst prognosis among biliary tract cancers. At present, radical resection is the only possible method to cure gallbladder cancer. However, there are still many controversies about the surgical strategies, the extent of liver resection and lymph node dissection, and the treatment of incidental gallbladder cancer. In addition, under the background of the great success of immunotherapy and targeted therapy in a variety of solid tumors, it is also a question worthy of further considerations that whether the status of surgery in the treatment of advanced gallbladder cancer will be changed in the near future.

Objective:To explore the effect of miRNA-511-3p (miR-511-3p) on the proliferation and apoptosis of lung cancer cells, and the possible role of ATP2A2 and endoplasmic reticulum stress therein.Methods:Lung cancer tissues and paracancerous normal tissues (>2 cm from the tumor) were retrospectively collected from 69 lung cancer patients who were admitted to Huizhou Central People's Hospital from January 2020 to March 2022. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the transcript-level relative expression of miR-511-3p in cancer and paracancerous tissues, as well as immortalized lung epithelial cell line BEAS-2B, human lung cell line CCD-19Lu, and human lung carcinoma cell lines A549, H1975 and H1299. The lung cancer cell line A549 with the lowest relative expression level of miR-511-3p was selected for subsequent experiments. The cells were divided into miR control group (transfected with miR-511-3p irrelevant sequence), miR-511-3p overexpression group (transfected with miR-511-3p mimic), and miR-511-3p knockdown group (transfected with miR-511-3p repressor); and the additional A549 cells were taken and divided into ATP2A2 overexpression control group (transfected with its empty plasmid), ATP2A2 overexpression group (transfected with ATP2A2 overexpression plasmid), and ATP2A2 knockdown control group (transfected with irrelevant small interfering RNA plasmid) and ATP2A2 knockdown group (transfected with ATP2A2 small interfering RNA plasmid). The transcript-level relative expression of miR-511-3p and ATP2A2 in A549 cells in each group was detected by qRT-PCR; the relative expressions of ATP2A2 protein and endoplasmic reticulum stress marker proteins in each group were detected by Western blotting; the targeting relationship between miR-511-3p and ATP2A2 mRNA was verified by dual-luciferase reporter gene assay; CCK-8 assay was used to detect the proliferation ability of A549 cells in each group (expressed as absorbance value); flow cytometry was used to detect the percentage of apoptotic cells in A549 cells in each group; inorganic phosphorus colorimetry was used to detect the activity of Ca 2+-ATPase in A549 cells in each group; fluorescent probe assay was used to detect the Ca 2+ concentration in A549 cells in each group. Results:The transcript-level relative expression of miR-511-3p in lung cancer tissues and paracancerous tissues of 69 patients were 0.08±0.03 and 0.17±0.12, respectively, and the difference was statistically significant ( t= 6.04, P<0.05). The percentage of apoptotic cells in A549 cells in the miR-511-3p overexpression group, miR-511-3p knockdown group and miR control group was (58.1±6.1)%, (11.0±1.3)% and (22.0±2.1)%, respectively. The percentage of apoptotic cells in the miR-511-3p overexpression group was higher than that in the miR control group, and the percentage of apoptotic cells in the miR-511-3p knockdown group was lower than that in the control group, and the differences were statistically significant ( t values were 9.70 and 7.64, respectively, both P<0.05). After 24, 48 and 72 h of culture, the proliferation ability of A549 cells in the miR-511-3p overexpression group was lower than that in the miR control group, the proliferation ability of A549 cells in the miR-511-3p knockdown group was higher than that in the miR control group, and the differences were statistically significant (all P < 0.05). The percentage of apoptotic cells in A549 cells of ATP2A2 knockdown group and ATP2A2 knockdown control group were (58.2±1.5)% and (23.8±1.0)%, respectively, and the difference was statistically significant ( t= 33.94, P < 0.05); the percentage of apoptotic cells in A549 cells of ATP2A2 overexpression group and ATP2A2 overexpression control group were (13.8±2.0)% and (23.8±1.0)%, respectively, and the difference was statistically significant ( t= 7.96, P < 0.05). The transcript-level relative expression of ATP2A2 in A549 cells of miR-511-3p overexpression group was lower than that of miR control group, the transcript-level relative expression of ATP2A2 in A549 cells of miR-511-3p knockdown group was higher than that of control group, and the differences were statistically significant ( t values were 5.76 and 6.40, respectively, both P < 0.05); the relative expression of ATP2A2 protein in A549 cells of miR-511-3p overexpression group was lower than that of its control group, and the relative expression of ATP2A2 protein in A549 cells of miR-511-3p knockdown group was higher than that of its control group, and the differences were statistically significant (both P < 0.05). Dual-luciferase reporter gene assay verified the targeting relationship between miR-511-3p and ATP2A2 mRNA. The percentage of apoptotic cells in A549 cells in the control group, miR-511-3p overexpression group, ATP2A2 overexpression group, and miR - 511 - 3p overexpression+ ATP2A2 overexpression group were (21.5±3.0)%, (58.1±5.0)%, (13.3±1.2)%, and (20.5±4.0)%, respectively, and the difference was statistically significant (F= 73.28, P < 0.001); the percentage of apoptotic cells in A549 cells in the control group, miR-511-3p knockdown group, ATP2A2 knockdown group, and miR-511-3p knockdown+ ATP2A2 knockdown group were (23.5±3.0)%, (11.3±1.2)%, (60.1±7.0)%, and (25.6±5.0)%, respectively, and the difference was statistically significant ( F= 78.45, P < 0.001). The Ca 2+-ATPase activity in A549 cells of ATP2A2 overexpression group was higher than that of its control group, the Ca 2+-ATPase activity in A549 cells of ATP2A2 knockdown group was lower than that of its control group, and the differences were statistically significant ( t values were 4.61 and 6.07, respectively, both P < 0.05); the intracellular Ca 2+ concentration in A549 cells of ATP2A2 overexpression group was lower than that of its control group, the intracellular Ca 2+ concentration in A549 cells of ATP2A2 knockdown group was higher than that of its control group, and the differences were statistically significant ( t values were 3.30 and 3.95, respectively, both P < 0.05). The Ca 2+-ATPase activity in the miR-511-3p overexpression group was lower than that in the miR control group, the Ca 2+-ATPase activity in the miR- 511-3p knockdown group was higher than that in the miR control group, and the differences were statistically significant ( t values were 6.54 and 4.16, respectively, both P < 0.05); the intracellular Ca 2+ concentration in A549 cells of miR-511-3p overexpression group was higher than that of miR control group, the intracellular Ca 2+ concentration in A549 cells of miR - 511 - 3p knockdown group was lower than that of miR control group, and the differences were statistically significant ( t values were 3.60 and 6.23, respectively, both P < 0.05). The relative expressions of endoplasmic reticulum stress markers GRP78, PERK, p - eIF2a, ATF4, and CHOP proteins in A549 cells with knockdown of ATP2A2 or overexpression of miR-511-3p were higher than those in the corresponding control groups, and the differences were statistically significant (all P < 0.05); the relative expressions of all proteins in A549 cells with overexpression of ATP2A2 or knockdown of miR-511-3p were lower than those in the corresponding control groups (all P < 0.05). Conclusions:Changes in miR-511-3p level may affect the proliferation and apoptosis of lung cancer cells, and the mechanism may be that it affects the apoptosis of lung cancer cells by targeting ATP2A2 to regulate the endoplasmic reticulum stress.