Purpose Cortex is one of the frequently involved sites of multiple sclerosis (MS),and the cortex and corpus callosum lesions of MS are gradually concerned.The study aims to observe the changes of cerebral cortex and corpus callosum of MS in experimental autoimmune encephalomyelitis (EAE) model by using 7.0T MRI diffusion tensor imaging (DTI).Materials and Methods Twenty female C57BL/6 mice of 6-8 week old were enrolled in the study,10 of which were induced by MOG35-55 to make EAE models and the rest 10 of which were taken as control group.On the 20 days after model establishment,the head T2WI and DTI were performed on both control and EAE mice.DTI quantitative indicators such as fractional anisotropy (FA),mean diffusivity (MD),axial dispersion coefficient λ//,and radial dispersion coefficient λ ⊥ in region of interest including bilateral prefrontal cortex,bilateral cingulate cortex and corpus callosum were compared between the two groups.Results No obvious lesions were observed on the T2WI in both control and EAE groups.In the experimental group,the FA mapping suggested the integrity of the left side of the corpus callosum was destroyed.The FA,MD,λ// λ ⊥ of bilateral prefrontal cortex and corpus callosum showed significant difference between experimental group and control group (P＜0.05);the increase of λ ⊥ in bilateral cingulate was significantly different from that in the control group.Meanwhile,HE staining in the experimental group showed that inflammatory cells gathered around the cortical and subcortical vessels.The LFB staining in experimental group showed a bit paler than that in the control group,and the corpus callosum showed patchy demyelination.Conclusion The technique of 7.0T MRI DTI sequence can detect cortex and corpus callosum lesions which cannot be found by conventional MRI,so that it provides radiological evidence for the study of MS with cortex and corpus callosum lesions.

Objective To evaluate dynamic contrast-enhanced MRI (DCE-MRI) with Patlak model for depicting the perfusion and permeability characteristics of lesions and normal-appearing white matter (NAWM) regions in patients with relapsing-remitting multiple sclerosis (RRMS). Methods Twenty-three patients with clinical confirmed RRMS were retrospectively analyzed, who had underwent conventional MRI and DCE-MRI using a 3.0 T MR scanner . The clinical characteristics and imaging data were collected. Post-processing was performed using the Patlak model. Volume transfer constant (Ktrans), fractional plasma volume (Vp) and perfusion parameters including cerebral blood flow (CBF) and cerebral blood volume (CBV) were represented as median and interquartile range(IQR). The four parameters of non-enhanced(NE) lesions, NAWM regions located close to NE lesions(NAWM close) and NAWM regions located far from NE lesions (NAWM far) were compared using the Kruskal-Wallis H rank sum test. Artificial color mappings were also proceeded. Results MR imaging biomarkers Ktrans was 0.132(0.064, 0.233) min-1 for NE lesions, 0.111 (0.060, 0.233) min-1 for NAWM close and 0.077(0.044, 0.185) min-1 for NAWM far, respectively. CBV was 10.660(5.555, 22.193) ml · 100 g-1 for NE lesions, 9.359(4.883, 16.290) ml · 100 g-1 for NAWM close, 6.814 (4.699, 13.623) ml·100 g-1 for NAWM far, respectively. Ktrans and CBV of NE lesions was significantly higher than that of NAWM far(χ2=7.582,P<0.05;χ2=6.394,P<0.05, respectively). Ktrans and CBV of NAWM close showed no significant differences compared with NE lesions and NAWM far. Vp and CBF had no significant differences between NE lesions, NAWM close and NAWM far regions(P>0.05). Conclusion DCE-MRI with Patlak model can measure perfusion and permeability characteristics and hemodynamic abnormalities of NE lesions and NAWM regions in patients with multiple sclerosis.

Purpose Intravoxel incoherent motion (IVIM) MR is a method developed in recent years which can quantitatively evaluate the diffusion and perfusion characteristics of microenvironment.The aim of this study was to investigate the application value of IVIM in assessing relapsing-remitting multiple sclerosis (RRMS).Materials and Methods A retrospective analysis of the clinical data of 27 patients with RRMS confirmed clinically at the First Affiliated Hospital of Chongqing Medical University from Jun.2015 to Jan.2016 was carried out in the study.All the patients underwent the conventional MRI and IVIM MRI based on multi-b-factor (b values of 10,20,30,40,50,100,150,200,350,500,650,800,1000 s/mm2) with 3.0T MR scanner.The apparent diffusion coefficient (ADC),ADCslow,ADCfast and f values were evaluated since they could reflect the diffusion and perfusion status of RRMS lesions and normal-appearing white matter (NAWM) regions.Results The ADC,ADCslow,ADCfast and f values of the non-enhancing (NE) lesions were significantly higher than those in the NAWM regions both near and far from NE lesions (P＜0.05).However,the ADC,ADCslow,ADCfast and f values in the NAWM regions close to the NE lesions had no significant differences with those in the NAWM regions far from the lesions (P＞0.05).Conclusion The IVIM MRI can measure the diffusion and perfusion status of the lesions and NAWM in RRMS patients,which,therefore,is helpful in speculation of the pathological changes of RRMS lesions and in its injury classification and identification.

PurposeMultiple sclerosis (MS) is characterized by time and spatial multiple, and it is the main reason for disabled young people. This paper aims to investigate the application of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with dual-compartment Tofts model in relapsing-remitting multiple sclerosis (RRMS) and its correlation with clinical scoring.Materials and MethodsThe clinical data of 25 patients with RRMS were retrospectively studied. The patients underwent the conventional MRI and the DCE-MRI examination. The result was processed by dual-compartment Tofts model and quantitative measurement was carried out in terms of volume transfer constant (Ktrans), rate constant between EES and blood plasma (Kep) and the volume of EES per unit volume of tissue (Ve), cerebral blood flow (CBF) and cerebral blood volume (CBV) of the lesions and normal-appearing white matter (NAWM) regions. The correlation between imaging biomarkers, expanded disability states scale (EDSS) and disease duration were also analyzed.Results ① The differences of MR imaging biomarkers Ktrans and Kep were significant between the regions of nonenhancing (NE) lesions, the NAWM regions near NE lesions and the NAWM regions far from NE lesions (χ2=6.777 and 22.343,P<0.05); however, Ve in the NE lesions had no significant differences compared with that in the NAWM regions near and far from NE lesions (P>0.05).②The CBF and CBV among these three groups had no signiifcant differences (P>0.05).③The CBF of NE lesions was signiifcantly correlated with disease duration (r=0.518,P<0.05);however, the other markers like Ktrans, Kep, Ve, CBF and CBV were neither signiifcantly correlated with EDSS nor with disease duration (r=-0.371-0.052,P>0.05).Conclusion DCE-MRI with Tofts model can quantitatively measure microvascular permeability and perfusion characteristics of lesions and NAWM regions, which thus reflects hemodynamic changes in patients with multiple sclerosis.

The function of drugs is based on the interaction between drug molecules and their targets.Qualitative analysis and quantitative detection of drug-target interactions run through the whole process from drug discovery to clinical practice.After decades of development, the study methods on the interaction between drug molecules and target proteins have been transformed from traditional biochemical experiments to a diversity of efficient and accurate technology systems supported by advanced molecular biology and biophysics theory.In this review, representative methods and techniques were introduced from aspects of target discovery and validation, affinity determination, interaction sites and structural analysis, which might provide some references for drug discovery and mechanism exploration.

Objective:To prepare the hydrogel scaffolds with different concentrations of laponite and compare their osteogenic properties.Methods:The scaffolds of gelatin/sodium alginate hydrogel into which laponite was added according to the mass ratios of 0%, 1%, 2%, and 3% were assigned into groups T0, T1, T2, and T3. In each group, the compressive modulus was measured and the leaching solution for 24 h extracted to measure the ion release. Bone marrow mesenchymal stem cells (BMSCs) were cultured in the extract medium from each group and common medium (blank group) ( n=3) in the in vitro experiments to determine the expression of osteogenic genes Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and type I collagen after 7 days of culture. In the in vivo experiments, the scaffolds were implanted into the femoral condyle defects in rats, and a blank group with no scaffolds was set. The bone repair in each group was evaluated by hematoxylin-eosin(HE) staining and immunohistochemical staining. Results:The compressive modulus in group T2 [(139.05±6.43) kPa] was significantly higher than that in groups T0, T1 and T3 [(68.83±3.76) kPa, (101.18±3.68) kPa and (125.40±3.28) kPa] ( P<0.05). The ion contents of lithium, magnesium and silicon released from the 24 h leaching solution in group T2 were (0.031±0.005) μg/mL, (3.047±0.551) μg/mL and (5.243±0.785) μg/mL, insignificantly different from those in group T3 ( P> 0.05) but significantly larger than those in group T1 ( P>0.05). The in vitro experiments showed that the expression levels of Runx2, ALP and type I collagen in group T2 were 1.59±0.11, 2.02±0.08 and 1.06±0.17, significantly higher than those in the other groups ( P<0.05). HE staining showed that the implanted hydrogel was tightly bound to the bone tissue. Immunohistochemical staining showed that the numbers of Runx2 and osteocalcin positive cells in group T2 were significantly higher than those in the other groups. Conclusions:With ideal biocompatibility, hydrogel scaffolds with different concentrations of laponite can slowly release the decomposed ions of lithium, magnesium and silicon to promote the osteogenic differentiation of BMSCs and the repair of bone defects in vivo. A 2% concentration of laponite in the hydrogel scaffolds may result in the best results.

Objective:To prepare biomimetic tissue engineering scaffolds of gelatin/sodium alginate/laponite composite hydrogel loaded with BMSCs by 3D biological printing technique，and explore the osteogenic effect of 3D printing on hydrogel scaffolds containing bone marrow mesenchymal stem cells（BMSCs）.Methods:BMSCs were routinely extracted and identified by flow cytometry. Gelatin，sodium alginate and laponite were mixed and then BMSCs were added to prepare cell-containing composite hydrogel scaffolds using 3D bioprinting. Non-printed scaffolds containing cells were prepared by injection molding method. In vitro，the prepared scaffolds were divided into the printing group with cells and non-printing group with cells according to whether they were printed，with 12 samples per group. Another simple cell culture group was set as control. Then，the internal structure of the composite hydrogel was observed by scanning electron microscope，and the expansion rate and water content of the scaffolds were measured by freeze-drying method. At day 3 after culture，the growth status of BMSCs was observed by phalloidine staining. cell counting kit（CCK）-8 assay was used to detect cell activity in scaffolds at days 1，3，and 7 after culture and RT-PCR to detect the expression of osteogenesis related genes Osterix，osteocalcin（OCN）and collagen I at days 7 and 14 ofter culture. In vivo，four groups were set according to printing or not and whether containing cells or not：printing implant group with cells，non-printing implant group with cells，printing implant group without cells and non-printing implant group without cells，with 9 samples per group. Scaffolds in four groups were implanted to the posterior gluteal muscle pouches（random on left or right）of 36 8-week-old SD rats，respectively. The samples were taken X-ray images at 2，4 and 8 weeks after operation，respectively. The osteogenic differentiation of tissues at 8 weeks was observed by HE and Masson staining. Results:The flow cytometry showed that the cells were BMSCs. Internal pores of hydrogels were obvious，and cells stretched freely in the pores. Differences of the swelling rate and water content were not statistically significant between printing group with cells［（1，039.37±30.66）%，（91.21±0.26）%］and non-printing group with cells［（1，032.38±35.05）%，（91.16±0.28）%］（ P>0.05）. At day 3 after culture in vitro，the cells grew well in the hydrogel. After culturing for 1 day in vitro，there was no significant difference in absorbance between printing group with cells and non-printing group with cells（ P>0.05）. At day 3 after culture，there was no significant difference in absorbance between printing group with cells and non-printing group with cells，but both groups showed a higher level than simple cell culture group（ P<0.05）. At day 7 after culture，the absorbance in printing group with cells（2.72±0.17）was higher than that in non-printing group with cells（2.35±0.11），and both of which were higher than that in simple cell culture group（1.95±0.12）（ P<0.05）. At day 7 after culture in vitro，there was no statistically significant difference in the expression of osteogenic differentiation-related genes between printing group with cells and the non-printing group with cells（ P>0.05），but they were all higher than those in simple cell culture group（ P<0.05）. At day 14 after culture in vitro，the expression of osteogenesis-related genes Osterix（1.650±0.095），OCN（2.725±0.091），collagen I（2.024±0.091）in printing group with cells were higher than those in non-printing group with cells（1.369±0.114，2.174±0.198，1.617±0.082，respectively）and those in simple cell culture group（1.031±0.094，1.116±0.092，0.736±0.140，respectively）（ P<0.05）. After implantation for 2 weeks in vivo，with no statistically significant difference in the gray values of X-ray films in each group（ P>0.05）. At weeks 4 and 8 after implantation，the gray values of X-ray films in printing implant group with cells and non-printing implant group with cells were higher than those in printing implant group without cells and non-printing implant group without cells（ P<0.01）. At 8 weeks after implantation，HE staining showed that the scaffolds were degraded in different degrees and immersed with cells，with collagen production seen in Masson staining as well. Conclusions:Composite hydrogel scaffolds can provide a good three-dimensional environment for BMSCs growth. 3D bioprinting can promote the proliferation and osteogenic differentiation of BMSCs in hydrogel scaffolds. In addition，BMSCs-loaded scaffolds can be degraded slowly in vivo with good ectopic osteogenic ability.

Objective:To understand and explore the incidence and influencing factors of malnutrition in patients with inflammatory bowel disease.Methods:This study was a cross-sectional study. Patients with inflammatory bowel disease hospitalized in the Department of Gastroenterology of a tertiary hospital in Shenzhen from March 1 to August 31, 2021 were enrolled. Indicators related to nutrition and clinical outcome were collected, including height, weight, body mass index (BMI), nutritional risk screening (NRS 2002) results, malnutrition diagnosis as per Global Leadership Initiative on Malnutrition (GLIM) criteria and Pittsburgh Sleep Quality Index (PSQI). Chi-square test, t-test and Wilcoxon rank sum test were used as appropriate for univariate analysis, and binary logistic regression analysis was used for multivariate analysis.Results:A total of 188 patients were included in this survey. There were 145 (77.1%) patients with no malnutrition, 38 (20.2%) with moderate malnutrition, and 5 (2.7%) with severe malnutrition according to GLIM criteria. In the subgroup of 47 ulcerative colitis patients, 12 (25.5%) were with moderate malnutrition and 3 (3.4%) were with severe malnutrition. In the subgroup of 141 Crohn's disease patients, 26 (18.4%) were with moderate malnutrition and 2 (1.4%) were with severe malnutrition. When divided by the presence or absence of malnutrition, there were statistically significant differences in age ( t = -2.237, P = 0.026), disease stage ( χ 2 = 22.299, P < 0.001), history of digestive tract resection ( χ 2 = 6.890, P = 0.009), intestinal infection ( χ 2 = 4.010, P = 0.045), gastrointestinal symptoms ( χ 2 =11.884, P = 0.001), hemoglobin ( t = 5.160, P < 0.001), serum albumin ( t = 3.96, P < 0.001), prealbumin ( t = 5.061, P < 0.001) and PSQI scores ( t = -4.744, P < 0.001). Multivariate analysis showed that the stage of disease, history of partial resection of digestive tract, gastrointestinal symptoms, hemoglobin, prealbumin and PSQI scores were the main influencing factors of malnutrition. Conclusions:IBD patients at older age, at active stage, and with history of partial digestive tract resection, intestinal infection, gastrointestinal symptoms, low hemoglobin, low serum albumin, low prealbumin and poor sleep quality are more likely to develop malnutrition. Timely intervention should be carried out to improve the nutritional status of these patients.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.