Objective To investigate the localization,zone and activation intensity of olfactory center in young versus elderly healthy volunteers by functional magnetic resonance imaging (BOLD-fMRI),so as to elucidate the effect of age on olfactory center in healthy population.Methods Thirteen right-handed healthy adult volunteers were recruited and divided into two groups:young group (5 males and 3 females,mean aged 23 years) and elderly group (2 males and 3 females,mean aged 69.2 years).The olfactory stimulus was r-undecalactone,and it was given according to a block design.The fMRI detection was performed on Philips Achieva 3.0 T MR scanner,and data of BOLE-fMRI was processed and analyzed to get cerebration image by using SPM2.Results In groupaveraged maps,both young and elderly group showed significant olfactory activation in right parahippocampal gyrus,left hippocampal sulcus,right and left superior temporal gyrus,etc,subcortical activation in right thalamus,dorsal pons,and cerebellum activation in cerebellar vermis.Activations in right inferior frontal gyrus,right middle frontal gyrus,right medial occipito-temporal gyrus and right fimbria of hippocampus were observed only in young group,while activation in bilateral middle temporal gyrus was observed only in elderly group.Activation area was apparently smaller and activation degree was lower in elderly group than in young group.Activation intensity in right superior parietal lobule and bilateral superior temporal gyri was higher in male group than in female group (t=13.7,6.08,5.36,respectively,all P＜0.001).Conclusions The intensity of activation in olfactory center is lower in the elderly than in the young,and absence of part of the active regions is found in the elderly,which demonstrates the regression of olfactory center in the elderly.The olfactory center shows right-predominant activation,and olfactory activation intensity in some cortical regions is higher in males than in females.

Objective To explore the effect of inferior hypothermy treatment on serum TNF and IL-6 in patients with severe cerebral trauma.Methods 46 patients were randomly divided into two groups:inferior hypothermy group(24 C88e8)and normal group(22 cases).There are the same basic treatments within the two groups,in the inferior hypothermy group we also sive them hypothermy treatment rectal temperature:32～34℃ which need to last for nearly 4～5 days,at the same time we give patients the lyric cocktail.the TNF,IL-6 and GCS grades on the lst and 14th day were tested.Results TNF and IL-6 as compared with normal group are higher than the inferior hypothermy group,the differences between the two groups are of statistical significance(P＜0.01).The difference of GCS grades between the two groups are of stafictical significance(P＜0.05).Conclusion The inferior hypothermy tbempy which inhibits TNF and IL-6 releasing after severe cerebral trauma and the following damages plays a very important role in the cerebral trauma therapy.

OBJECTIVE To provide references for clinical diagnosis of catheter-related bloodstream infections(CRBSIs) and focus on studying the spectras of pathogenic bacteria and the drug sensitiveness. METHODS A total of 137 patients enrolled from Jan 2005 to Dec 2007 in our hospital with positive catheter cultures were admitted to our retrospective analysis.Pathogenic bacteria,contaminant bacteria and the drug sensitiveness of main pathogenic bacteria were analyzed. RESULTS From them 80 patients were diagnosed CRBSIs.Among 92 strains of pathogenic bacteria,43(46.7%) strains were Gram-positives,31(33.7%) coagulase negative staphylococci(CNS) strains,31(33.7%) Gram-negative bacilli strains and 18(19.6%) were Candida strains. CONCLUSIONS CNS are the most common bacteria of CRBSIs,and the second are Candida.The common pathogen show multi-drug resistance.

Objective To seek differentially expressed proteins for human epithelial growth factorreceptor-2 (HER-2)negative and positive breast carcinoma through establishing proteins profiles,and to providenew prognostic markers and therapeutic targets for patients with breast cancer.Methods HER-2 positiveand negative breast cancer protein expression profiles were established using proteomic isobaric tags for relativeand absolute quantitation (iTRAQ)technology.Differences of protein expression were identified and parts ofdifferential expression proteins were analyzed by bio-informatics,including protein function annotation and GOclassification analysis and Kyoto Encyclopedia of Gene and Genome (KEGG)pathway analysis.Results Proteomicanalysis of breast cancer tissue with identified HER-2 positive and negative groups showed 4 999 differentiallyexpressed proteins by iTRAQ.Based on the criteria of the ratio of HER-2(+)/HER-2(-)≥3,119up-regulated proteins were identified in HER-2 positive group.Based on the criteria of the ratio of HER-2(+)/HER-2(-)≤0.5,47 down-regulated proteins were identified in HER-2 positive group.The results ofGO analysis showed that the molecular function,biological process and cellular composition of differentiallyexpressed proteins were complex between HER-2 positive and negative breast cancer.There were differences inthe distribution of up-regulated proteins and down-regulation of proteins.KEGG pathway analysis showed thatdifferentially expressed proteins involved in 168 signal pathways.Conclusion There are differentiallyexpressed proteins between HER-2 positive and negative breast cancer,which involve complex molecular func-tion,biological process and signaling pathway.

Objective To investigate the distribution and drug resistance of pathogens in intensive care unit (ICU) so as to provide scientific basis for antibiotic adoption and the prevention and control of nosocomial infections. Methods The various specimens collected from the patients admitted into ICU in the First People's Hospital of Shunde Affiliated to the South Medical University from January 2007 to December 2014 were used to isolate the pathogens that might cause nosocomial infections and retrospectively analyze their clinical distribution and drug resistance. Kirby-Bauer paper diffusion and minimal inhibitory concentration (MIC) methods were applied to test the drug sensitivity, and according to National Committee for Clinical Laboratory Standards/Clinical and Laboratory Standards Institute (NCCLS/CLSI) standard, the results were identified.Results The sputum was the major specimen source in ICU, accounting for 68.8%, followed by urine (12.4%) and blood (6.8%). All together 557 pathogens in ICU causing nosocomial infections were isolated of which there were 377 gram-negative (G-) bacilli (67.7%), 103 gram-positive (G+) cocci (18.5%), and 77 fungi (13.8%). Among G- bacilli, the top three wereAcinetobacter baumannii (34.5%), Klebsiella pneumonia (17.8%), andPseudomonas aeruginosa (13.0%). Beside carbapenem, the drug resistance rates of Acinetobacterbaumannii to other antibiotics were more than 40%. The main G+ coccus causing nosocomial infection wasSaphylococcus aureus (36.9%) in ICU. The drug resistance rates ofSaphylococcus aureus to penicillin, gentamicin and erythromycin were higher than 50%. In 77 fungus strains,Candida albicans was ranked the first, accounting for 41.6%.Conclusion The main infection site in ICU is primarily respiratory tract, the G- bacilli are the predominate pathogens, and the drug resistance to antibiotics found in this report is serious, so clinically, the antibiotics should be properly used to avoid the occurrence of pathogenic strain with drug tolerance.

Objective:To explore whether the introduction of the O-PIRTAS (objective, preparation, instructive vedio, review, test, activity, summary) teaching model can help in curriculum learning and improve students' medical humanities literacy.Methods:Taking 118 sophomores of clinical medicine and nursing majors from Xiamen Medical College as control group, and 122 students as experimental group and as control group, the research lasting 8 weeks was carried out around five modules. The control group adopted the traditional teaching mode, while the experimental group used the O-PIRTAS model. After teaching, by comparing the exam results and issuing questionnaires, the teaching effects of the two methods on students' caring ability, empathy, emotional intelligence and supportive communication ability were compared. SPSS 22.0 was used for t test and chi-square test. Results:The average score of the experimental group [(83.61±2.13) points] was higher than that of the control group [(78.03±2.02) points], with significant differences ( t=3.60, P<0.001). As for the statistical analysis of the questionnaire, the students in experimental group scored higher in empathy, emotional intelligence and supportive communication skills than those in control group ( t=-3.20, P=0.002; t=-3.93, P<0.001; t=-4.00, P<0.001). Conclusion:Applying O-PIRTAS flipped classroom teaching model to medical humanities English courses helps to improve students' curriculum learning and medical humanities literacy, improve the effectiveness of the classroom and better play the educational role of the curriculum.

Objective:To understand the identification value of pointing gestures in children with autism spectrum disorder(ASD) and its relationship with functional development.Methods:From December 2020 to November 2021, 1 099 children from Children’s Health Care Center of Beijing Children’s Hospital were tested by pointing gestures test, including 942 ASD children and 157 typical developed children.And the data of children's neuropsychological development scale from 800 children aged 1.0-5.9 were collected.SPSS 20.0 was used for statistical analysis. Trend test was used to analyze the distribution of pointing gestures test sensitivity in autistic children, and ANOVA was used to analyze the relationship between pointing gestures test scores and functional development fields.Results:The sensitivity of pointing gestures was 83.5% in children aged 1.0-10.0 years, 76.3%-93.1% in children aged 1.0-4.9 years, and 93.1%-95.1% in children aged 1.0-2.9.With the increase of age, the sensitivity of pointing gestures in autistic children (linear-by-linear association =164.889, P<0.001) and the Yoden index had a decreasing trend. The positive predictive value (91.53%-100.00%) and negative predictive value (75.36%-91.84%) were found in the children aged 1.0-10.0 years.The sensitivity of pointing gestures test was 44.9% in children with mild autism aged 1.0-10.0 years and 46.5%-65.9% in children with mild autism aged from 1.0-3.9 years. The sensitivity of pointing gestures test was 81.5% in children with moderate autism aged from 1.0-10.0 years and 87.3%-97.8% in children with moderate autism aged 1.0-3.9 years. The sensitivity of the pointing gestures test was 97.2% in children with severe autism aged 1.0-10.0 years, and 100.0% in children with severe autism aged 1.0-3.9 years. The sensitivity of the pointing gestures in mild, moderate and severe autism children decreased with age (linear-by-linear association values were 16.725, 64.232, 66.732 respectively, all P<0.001). The children with severe autism mainly scored 2 points (80.3%, 419/522) on the pointing gestures test , and children with moderate autism mainly scored 1 point(64.2%, 170/265) on the pointing gestures test. There were significant differences in functional development among different pointing gestures test groups.Functional development score in the autism children with 0 score of pointing gestures test was significantly higher than those with 1 score and 2 scores of pointing gestures test (all P<0.05). Conclusion:Pointing gestures has good sensitivity in children with autism (especially 1.0-4.9 years of age), and may serve as an objectively observable screening method. The better children with autism score on the pointing gestures, the better their functional development.

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia