BACKGROUND:A previous study by our group found that protein phosphatase 2Cm(PP2Cm)null mice developed significantly fewer symptoms of renal failure relative to wild-type mice,and thus it was speculated that PP2Cm may play an important protective role in the development of renal fibrosis,however,the molecular mechanisms remain undefined. OBJECTIVE:To investigate the effect of the PP2Cm gene on the transcriptome of human renal tubular epithelial cells. METHODS:Cultured human renal tubular epithelial cells were transfected with the PP2Cm gene into human renal tubular epithelial cells using plasmids.The expression of PP2Cm in the cells was detected by fluorescence quantitative PCR assay and western blot assay,and subsequently,cell RNA was separately extracted for transcriptome sequencing to look for differentially expressed genes between transfected and control groups.The resulting differential genes were further subjected to GO analysis and KEGG analysis using bioinformatics methods. RESULTS AND CONCLUSION:There were 796 differentially expressed genes,553 of which were downregulated genes and 243 upregulated genes,in human renal tubular epithelial cells transfected with the PP2Cm gene compared with untransfected blank cells by sequencing analysis.GO analysis results showed that the upregulated genes were significantly enriched in cellular biosynthetic processes,protein translation,intrinsic apoptotic signaling pathways,and so on.The downregulated expressed genes were significantly enriched in endothelial cell proliferation,cell adhesion and other signaling pathways.KEGG analysis results showed that the significantly up-regulated genes were enriched in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.The downregulated expressed genes were significantly enriched in signaling pathways such as pantothenate and coenzyme A biosynthesis.Our results show that PP2Cm overexpression can affect a number of signaling pathways related to a range of biological processes in renal tubular epithelial cells,which may be important in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.

Objective To observe the changes of plasma gastrointestinal hormones in motion sickness sensitive and insensitive individuals before and after vertical oscillation stimulation,and to construct a susceptibility prediction model for motion sickness.Methods A total of 60 healthy male volunteers were enrolled to receive sinusoidal vertical oscillation stimulation for 45 min.The motion sickness susceptibility questionnaire(MSSQ)was filled out before the experiment.Immediately after motion,the severity of motion sickness was evaluated by Graybiel scale.The motion sickness sensitive(Graybiel score≥8 and MSSQ susceptibility index＞21,n=15)and insensitive(Graybiel score≤2 and MSSQ susceptibility index＜5,n=15)participants were screened.Plasma levels of glucagon-like peptide-1(GLP-1),cholecystokinin(CCK),leptin,ghrelin,neuropeptide Y(NPY)and orexin A(OXA)were detected by enzyme-linked immunosorbent assay before and after vertical oscillation stimulation.Logistic regression model was used to analyze the predictive effect of plasma gastrointestinal hormone levels on susceptibility to motion sickness,and a combined predictive model was established.Receiver operating characteristic(ROC)curve was used to analyze predictive value of the model.Results Ghrelin and CCK levels were significantly increased in the sensitive group after stimulation compared with those before stimulation(both P＜0.01),while NPY and leptin levels were significantly decreased(both P＜0.01).Similar results were also observed when compared with the insensitive group after stimulation.Multivariate logistic regression analysis showed that plasma ghrelin,CCK and NPY were independent predictors of susceptibility to motion sickness.The established susceptibility prediction model for motion sickness was logit(P)=-0.051 ×ghrelin+0.060× NPY-0.169 ×CCK+33.397.ROC curve analysis showed that area under curve(AUC)value of the prediction model was 0.988,the sensitivity and specificity were 100.0％and 93.3％,respectively,and the prediction effect was better than ghrelin,CCK and NPY alone(AUC=0.792,0.880,0.838).Conclusion The changes of peripheral gastrointestinal appetite regulating hormone levels may be related to the susceptibility to motion sickness.The combined use of these indicators can predict the susceptibility to motion sickness.

Teaching clinics represent a unique form of outpatient training of resident physicians and serve as a crucial instrument and core component of standardized training of general practice residents. This article reviews the common model and innovations of teaching clinics of general practice in China, and analyzes their reported effectiveness in enhancing the capabilities of consultation of resident physicians, the teaching capabilities of general practice trainers, as well as satisfaction levels of involved participants. It outlines the challenges encountered in implementing teaching clinics, including inadequate teaching facilities and equipment, incomplete incentive system for teaching, difficulties in patient recruitment, and weaknesses in the teaching capabilities of trainers. To address these challenges, this article proposes corresponding strategies based on realistic needs, including the improvement of facilities and equipment in teaching clinics, the establishment of incentive systems for teaching clinics, the expansion of patient recruitment channels for teaching clinics, and the enhancement of training for trainers' teaching capabilities. This is envisaged to provide both theoretical bases and practical guidance for the effective execution and standardized development of teaching clinics in general practice residency training bases.

Objective:To report the clinical features of KCNQ2-associated epilepsy and the novel mutations and unreported clinical phenotype of KCNQ2 gene, so as to provide help for treatment selection and prognosis evaluation.Methods:Among 979 patients with epilepsy and developmental delay who were admitted to the Department of Neurology,Children′s Hospital Affiliated to Capital Institute of Pediatrics from July 2015 to October 2019, a total of 13 patients were selected from 12 families with KCNQ2 gene mutation by whole exome sequencing technology. Suspected mutations were verified by Sanger sequencing on the probands and their parents to identify the source. The clinical phenotype and genotype were analyzed according to these results.Results:Among the 13 patients with epilepsy, the onset age of four cases were older than six months [two cases in infancy (epilepsy encephalopathy), one case in early childhood (epilepsy encephalopathy) and one case in adolescence (benign epilepsy)]. Eight cases were treated with oxcarbazepine, of whom five cases were seizure free, and two cases showed partial response (>50%). Two cases treated with topiramate were seizure free. Five novel mutations were found in this research, including c.379T>G(p.Y127D), c.1A>C(initial codon mutation), c.708G>C(p.W236C), c.1027G>T(p.A343S) and c.1649T>G(p.V550G).Conclusions:Although it was rare in clinical work, the variation of KCNQ2 gene existed in patients with childhood-onset epilepsy and adolescent-onset epilepsy. Meanwhile, five novel mutations of KCNQ2 gene were reported, which further expanded its gene spectrum. This research supported that oxcarbazepine was the efficient medicine for the KCNQ2-associated epilepsy. Genetic testing showed great help to the treatment of epilepsy.

Objective:To investigate the correlation between tooth movement and profile change in patients with class Ⅱ division 1 malocclusion.Methods:Pre- and post-treatment lateral cephalograms of 42 patients [10 males and 32 females, (23.8±6.3) years old, mean treatment time: 1.9 years] with class Ⅱ division 1 malocclusion were collected in Department of Oral & Cranio-Maxillofacial Surgery, Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2012 to November 2017. The patients were treated with extraction of four first premolars or two maxillary first premolars. Cephalometric analysis was carried out before and after treatment. Thirty parameters were measured. The changes of soft and hard tissue after orthodontic treatment and their correlations were analyzed using bivariate linear regression. Related factors affecting the upper and lower lip, nasolabial angle (NLA) and mentolabial angle (MLA) were analyzed according to the standardized regression coefficient ( Beta). Results:Among all the 30 parameters, 18 parameters were statistically different before and after treatment. After treatment, upper central incisor sagittal distance [(63.87±7.14) mm] and upper lip sagittal distance [(77.73±7.60) mm] were significantly decreased ( P<0.05). The changes in 14 parameters after treatment showed linear relationship including strong positive correlation between upper lip sagittal retraction and upper central incisor sagittal retraction ( r=0.649, P<0.01). There were moderate positive correlations between upper lip and upper central incisor vertical movement ( r=0.544, P<0.01). While the sagittal change of gnathion and the Y-axis angle showed moderate negative correlations ( r=0.537, P<0.01). The stepwise multiple linear regression showed that the retraction of upper lip process was correlated with the retraction of upper central incisor, the increase of occlusal plane angle and the increase of upper central incisor angle, which was most correlated with the retraction of upper central incisor ( Beta=0.79). The downward displacement of upper lip process was correlated with the downward displacement of upper incisor, the decrease of upper central incisor angle, the decrease of the distance between maxillary first molar and palatal plane, and the increase of occlusal plane angle, which was more correlated with the downward displacement of upper incisor and the increase of occlusal plane angle ( Beta=0.59). The downward displacement of lower lip process was correlated with the downward displacement of upper incisor and lower incisor, which was more correlated with the upper incisor ( Beta=0.36). Conclusions:The relationship among nose, lips and chin was more coordinated. Incisor retraction had significant influence on lip prominence, and the lower lip position was highly related to the movement of upper incisor in sagittal and vertical dimension after orthodontic treatment in patients with class Ⅱ division 1 malocclusion. However, tooth movement had limited impact on the chin position.

COVID-19 is an emerging infectious disease caused by SARS-CoV-2. After the infection of the virus, the host immune system is stimulated to produce multifarious specific antibodies to decrease or eliminate effects of the pathogen. Study of the specific antibodies dynamic characteristics in patients with COVID-19 is very important for the understanding and diagnosis of the disease, research and development of vaccine, and planning of prevention and control strategy. This paper reviews and summarizes the domestic and oversea research on dynamic characteristics of specific antibodies of COVID-19 patients, including the antibody producing, duration and level, and its possible influencing factors in order to improve the understanding of the immunological characteristics of COVID-19.

OBJECTIVE: To explore the genetic basis for a pedigree affected with X-linked recessive mental retardation Claes-Jensen type. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient, his parents (phenotypically normal) and two elder brothers with similar clinical manifestations. Whole exome sequencing was carried out for the proband, and the result was verified by Sanger sequencing. RESULTS: The proband was found to harbor a hemizygous c.1565C>T missense variant in exon 11 of the KDM5C gene. The transition has resulted in replacement of serine by phenylalanine at position 522 (p.Ser522Phe). Sanger sequencing showed that the patient's two elder brothers and mother carried the same variant, which was predicted to be probably damaging by SIFT, PolyPhen2 and Mutation_Taster. The three affected brothers presented with similar clinical phenotypes characterized by mental retardation, speech delay, behavioral problem, self-limited epilepsy responsible to medication, short stature and microcephaly. The mother only had mild cognitive impairment and learning disability. The same variant was not found in their father and was unreported previously. CONCLUSION The c.1565C>T (p.Ser522Phe) of the KDM5C gene probably underlay the X-linked recessive mental retardation Claes-Jensen type in this pedigree.
Aged ; Female ; Histone Demethylases/genetics* ; Humans ; Male ; Mental Retardation, X-Linked/pathology* ; Mutation, Missense/genetics* ; Pedigree ; Phenotype ; Whole Exome Sequencing

Objective:To investigate the value of serum C -reactive protein/prealbumin ratio (CRP/PA) in predicting the disease progression of adult patients with traumatic brain injury. Methods:A prospective study was conducted. Patients with traumatic brain injury who were over 18 years old and were followed up for more than 72 hours admitted to the department of emergency of Huashan North Hospital Affiliated to Fudan University from May 2018 to December 2019 were enrolled. The levels of serum CRP, PA were measured immediately after injury and at 6, 24, 48 and 72 hours after injury, and the CRP/PA ratio was calculated. Glasgow coma score (GCS) was dynamically measured and head CT was reviewed regularly. If the GCS decreased by more than 3 and/or the intracranial injury was aggravated by CT scan within 72 hours after injury, the patients were included in the aggravating group. If there were no above changes, they were included in the stable group. The differences of each index between the two groups were compared, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of each index at different time points on the patient's disease progress.Results:A total of 106 patients were selected, including 89 patients in the stable group and 17 patients in the aggravating group, and the baseline data of the two groups were balanced. CRP, CRP/PA increased and PA decreased in brain trauma patients 6 hours after injury, and reached the peak value or valley value at 48 hours. Compared with the stable group, CRP/PA significantly increased at 24, 48 and 72 hours in the aggravating group [24 hours: 34.18 (20.19, 67.10) vs. 13.98 (4.36, 38.30), 48 hours: 71.10 (45.55, 96.97) vs. 16.02 (5.05, 41.76), 72 hours: 23.25 (4.46, 38.61) vs. 4.72 (2.38, 12.95), all P < 0.05]. ROC curve analysis showed that CRP/PA ratio at 24 hours and 48 hours after injury could be used as a predictor of disease progression. The area under the ROC curve (AUC) of 24 hours CRP/PA was 0.71, 95% confidence interval (95% CI) was 0.58-0.84, the cut -off value was 28.29, the sensitivity was 76.5%, and the specificity was 73.0%. The AUC of 48 hours CRP/PA was 0.76, 95% CI was 0.62-0.90, and the cut -off value was 37.18, the sensitivity was 88.2%, and the specificity was 70.8%. Conclusion:The dynamic monitoring of CRP/PA ratio in adult after traumatic brain injury can evaluate the disease condition, and the CRP/PA ratio of 24 hours and 48 hours can predict the progress of the disease.

Objective To establish a "patient-centered" integrated information platform for emergency interconnection. Methods Based on the existing software, hardware and network systems of the hospital, design ideas of the modularization, process and standardized were used to reshape the process of emergency diagnosis and treatment in department of emergency-critical care medicine of Huashan North Hospital,Fudan University, and develop integrated information platform for emergency interconnection, including triage, emergency physician workstation, electronic medical records, clinical pathways of key diseases, medical integration, electronic handover classes, imaging, testing, ultrasound, drug counseling and medication safety, performance appraisal and management systems of scientific research, etc. Results The information platform for emergency interconnection was successfully developed. The functional logic of each system was clear and concise. It had strong compatibility, stable performance and powerful processing capability. It could quickly query the target content and support free and fast switching of each window. At present, daily diagnosis and treatment of emergency patients were realized by informationization, which completely liberated the manual labor of medical staff, shortened the processing time of unit patient, and significantly improved efficiency of the work. At the peak of the patients' visit, the overall operation of the emergency department was stable, and all the work was carried out in an orderly manner. There was no delay of the diagnosis and treatment for critically ill patients in the emergency department. Emergency access to patients with key diseases was smooth, and waiting time was significantly shortened. Clinical decision-making of medical staff had been effectively regulated. The success rates of the patients with acute trauma or acute respiratory failure were significantly improved, the time of the critical treatment were significantly shortened in patients with emergency respiratory cardiac arrest or acute ST-segment elevation myocardial, and compliance rate of the door-to-balloon time met the requirements of the Emergency Room to Balloon Expansion Time (DTB) Alliance. Conclusion The integrated information platform for emergency interconnection ran through the whole process of emergency diagnosis and treatment, based on emergency clinical practice, which could meet the needs of daily work in emergency department and help improve the quality of emergency medical and department management.

Objective To investigate the distribution and drug resistance of pathogen caused community-onset bloodstream infection (COBSI) in patients of affiliated hospital of university,and to provide evidence for the clinical therapy.Methods The clinical data of patients with COBSI in emergency department admitted to Huashan North Hospital Affiliated to Fudan University from January 2014 to December 2017 were collected,and the distribution and drug resistance of pathogen were retrospectively analyzed.The patients were divided into community-acquired bloodstream infection (CABSI) group and health care-associated bloodstream infection (HCABSI) group according to clinical diagnosis.The source of patients,past health status,blood culture isolation of pathogens,drug sensitivity test results were recorded,and the trend of drug resistance of main pathogens to common antibiotics from 2014 to 2017 were analyzed.Results A total of 258 pathogens were isolated from patients,including 186 Gram-negative pathogens (G-pathogens,72.09％) and 72 Gram-positive pathogens (G+ pathogens,27.91％),while the fungal strain was not isolated.The two most frequently isolated G-pathogens causing CABSI were Escherichia coli (80 isolates,65.57％) and Klebsiella pneumonia (24 isolates,19.67％),including extended-spectrum beta-lactamases (ESBLs)-producing Escherichia coli (37 isolates) and Klebsiella pneumonia (3 isolates),the average detection rates were 46.25％ and 12.50％ respectively.The two most frequently isolated G+ pathogens were Streptococcus (32 isolates,57.14％) and Staphylococcus (15 isolates,26.79％),but methicillin-resistant Staphylococcus aureus (MRSA) had not been isolated.The two most frequently isolated G-pathogens causing HCABSI were Escherichia coli (45 isolates,70.32％) and Klebsiella pneumonia (7 isolates,10.94％),including ESBLs-producing Escherichia coli (20 isolates) and Klebsiella pneumonia (1 isolate),the average detection rate was 44.44％ and 14.29％,respectively.The most frequently isolated G+ pathogens were Staphylococcus (10 isolates,62.50％),Streptococcus (3 isolates,18.75％) and Enterococcus faecium (3 isolates,18.75％),including MRSA (3 isolates).ESBLs-positive Escherichia coli and Klebsiella pneumoniae were almost completely resistant to cefazolin and highly resistant to ampicillin,ampicillin sodium and sulbactam sodium,ceftriaxone and furadantin,with the drug resistance rates of higher than 50％,and the drug resistance rate was significantly higher than that of corresponding ESBLs-producing negative pathogens.Escherichia coli were completely sensitive to piperacillin tazobactam,imipenem,and ertapenem,but Klebsiella pneumoniae had some resistance to piperacillin tazobactam and imipenem.Methicillinresistant coagulase-negative Staphylococci (MRCNS) were highly resistant to common antibiotics,while Streptococcus strains and MRSA had low resistance rates,and all pathogens were completely sensitive to linezolid and vancomycin.The average annual resistance rate of Escherichia coli to common antibiotics in CABSI group was increased,but the difference was significant only for ciprofloxacin (from 2014 to 2017,they were 37.5％,28.6％,52.6％,65.2％,respectively,Z =5.076,P =0.024).The average annual resistance rate of Klebsiella pneumonia to cefazolin and ciprofloxacin in CABSI group and that of Escherichia coli to ceftriaxone in HCABSI group showed an increasing trend without significant differences.Conclusions Escherichia coli and Klebsiella pneumoniae were the main pathogens of emergency COBSI,ESBLs-producing Escherichia coli were more common,and the average annual drug resistance rate to common clinical antibiotics was increasing.The drug resistance of ESBLs-producing Escherichia coli and Klebsiella pneumoniae was more serious than that of ESBLs-producing negative pathogens,so antibiotics should be used rationally.