Cell Nucleus ; Cellular Senescence/genetics* ; CRISPR-Cas Systems/genetics*

OBJECTIVE: To explore clinical rules based on the big data of the emergency department of the Second Affiliated Hospital of Guangzhou Medical University, and to establish an integrated platform for clinical research in emergency, which was finally applied to clinical practice. METHODS: Based on the hospital information system (HIS), laboratory information system (LIS), emergency specialty system, picture archiving and communication systems (PACS) and electronic medical record system of the Second Affiliated Hospital of Guangzhou Medical University, the structural and unstructured information of patients in the emergency department from March 2019 to April 2022 was extracted. By means of extraction and fusion, normalization and desensitization quality control, the database was established. In addition, data were extracted from the database for adult patients with pre screening triage level III and below who underwent emergency visits from March 2019 to April 2022, such as demographic characteristics, vital signs during pre screening triage, diagnosis and treatment characteristics, diagnosis and grading, time indicators, and outcome indicators, independent risk factors for poor prognosis in patients were analyzed. RESULTS: (1) The data of 338 681 patients in the emergency department of the Second Affiliated Hospital of Guangzhou Medical University from March 2019 to April 2022 were extracted, including 15 modules, such as demographic information, triage information, visit information, green pass and rescue information, diagnosis information, medical record information, laboratory examination overview, laboratory information, examination information, microbiological information, medication information, treatment information, hospitalization information, chest pain management and stroke management. The database ensured data visualization and operability. (2) Total 140 868 patients with pre-examination and triage level III and below were recruited from the emergency department database. The gender, age, type of admission to the hospital, pulse, blood pressure, Glasgow coma scale (GCS) and other indicators of the patients were included. Taking emergency admission to operating room, emergency admission to intervention room, emergency admission to intensive care unit (ICU) or emergency death as poor prognosis, the poor prognosis prediction model for patients with pre-examination and triage level III and below was constructed. The receiver operator characteristic curve and forest map results showed that the model had good predictive efficiency and could be used in clinical practice to reduce the risk of insufficient emergency pre-examination and triage. CONCLUSIONS The establishment of high-quality clinical database based on big data in emergency department is conducive to mining the clinical value of big data, assisting clinical decision-making, and improving the quality of clinical diagnosis and treatment.
Adult ; Humans ; Big Data ; Emergency Service, Hospital ; Triage/methods* ; Intensive Care Units ; Hospitalization ; Retrospective Studies

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Animals ; Disease Models, Animal ; Female ; Gene Editing ; Humans ; Lamin Type A/metabolism* ; Macaca fascicularis ; Progeria/pathology*

Objective: To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation. Methods: Twenty-two patients were collected in the Department of Pediatrics, Peking University First Hospital from April 2007 to July 2016.The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing. Results: Twenty-two de novo KCNQ2 missense mutations from 22 patients with neonatal/infantile epileptic disorders were found.These patients had an onset of epilepsy in early infancy (median age: 2 days). The seizure type of the first onset was mainly focal seizure.Atypical absence epilepsy, a novel phenotype of KCNQ2 mutation-induced epilepsies was found.The mortality of these patients was high, as 5 patients of the 22 patients died in the follow-up period, 4 of which might result from sudden unexpected death in epilepsy.In the 22 patients, 8 patients with anti-epileptic monotherapy became seizure-free.Of the 8 patients with a monotherapy, 3 patients were treated with valproic acid and no clinical onset was observed. Conclusions This study expands the phenotype of KCNQ2-related epileptic disorders.These patients have high mortality.Valproate acid is the potentially effective monotherapy for these patients.

Objective To investigate the effect of alprostadil in the treatment of interventional angiography in elderly patients with coronary heart disease after contrast nephropathy prevention.Methods From February 1,2014 to January 31,2017,60 elderly patients with coronary heart disease with interventional therapy in Yuncheng Central Hospital of Shanxi Province were divided into two groups,with 30 cases in each group.The control group received hydration therapy,the observation group was given alprostadil combined with hydration therapy.The biochemical index changes before surgery and three days after surgery and incidence of contrast nephropathy were compared between the two groups.Results Before surgery and three days after surgery,the tumor necrosis factor alpha,beta 2 microglobulin, urea and creatinine in the two groups were not changed significantly.Three days after surgery,24h urine protein, superoxide dismutase,glutathione peroxidase,interleukin －6 and C reactive protein levels in the two groups were increased,the increase amplitude of the observation group was smaller.Three days after surgery,the five indicators of the observation group were (185.54 ±86.47)mg,(2.01±1.32)mg/L,(6.18 ±2.13)g/L,(135.56 ±41.58)ng/L, (1.21±1.05 )mg/L,respectively,the differences were ststistically significant between the two groups (t ＝1.21, 1.24,1.50,1.26,1.22;P＝0.03,0.03,0.04,0.03,0.04).Three days after surgery,the creatinine clearance rate of the observation group was (98.67 ±21.56)mL/min,which was higher than that of the control group(t＝2.71,P＝0.01).The incidence rate of contrast induced nephropathy in the observation group (3.33%)was lower than that in the control group(χ2＝5.19,P＝0.02).Conclusion Alprostadil can effectively prevent contrast nephropathy in elderly patients with coronary heart disease after interventional therapy.

Objective:To construct the "3+2" counterpart cut-through sectional training nursing major un-dergraduate curriculum system, which is oriented by vocational competence. Methods: The preliminary draft of"3+2" nursing undergraduate curriculum setting was established base on the literature review and expert group in-terview, and the 25 experts was conducted two rounds of expert questionnaire consultation using Delphi method. Results:Experts' opinions tended to be consistent after two rounds of consultation, the expert authority coefficient was 0 . 92 , the coordination coefficient of Kendall was 0 . 44 in the second round of expert consultation and finally established 5 curriculum groups, including total 28 courses of public elementary courses, professional basic cour-ses, professional core courses, professional oriented courses and centralized practice courses. Conclusion: It should construct the"3+2" counterpart cut-through nursing major undergraduate curriculum system, which is o-riented by vocational competence, and achieve effective connection between the knowledge structure and the quality of the nursing students, in order to provide the reference for perfecting the curriculum system of vocational educa-tion in our country.

Objective To evaluate the ability of texture analysis in early phase of enhanced MRI in predicting pathological complete response(pCR) after neoadjuvant chemotherapy(NAC) for breast cancer. Methods This retrospective study enrolled 64 breast cancers samples from 64 patients that were diagnosed by core-needle biopsy and received NAC before operation in Peking University Cancer Hospital between July and Dec 2015. MRI were conducted after NAC. Regions of interest were drawn to cover the whole enhanced areas on subtraction images of early phase to pre-enhanced phase on MRI, and were sent to an in-house developed texture-analyzing software to achieve parameters including average signal intensity (SIav), mean signal intensity (SIm), signal intensity range(SIr), skewness, kurtosis, energy and entropy. Groups of pCR (no invasive tumor) and non-pCR were separated based on pathology results. Differences of MRI parameters were compared by independent-sample t test (normal distribution) or Mann-Whitney U test (abnormal distribution) and ROC curve were drawn to evaluate the diagnostic abilities. Results Post-operation pathology found 28 pCR and 36 non-pCR. ROIs of 13 samples were not drawn because no residual enhanced areas could be found on subtraction images of post-NAC MRI. For 51 lesions (17 pCR and 34 non-pCR) that still had residual enhancement, tumor volume, SIav, SIr, energy and entropy of pCR group were all significantly lower than that of non-pCR group (P＜0.05). ROC curves were drawn, yielding AUC=0.669 for non-enhancement criterion, and the accuracy, sensitivity and specificity were 70.3%, 39.3% and 94.4%. AUCs for volume, SIav, SIr, Energy and Entropy were 0.870, 0.772, 0.810, 0.883 and 0.881 respectively. Conclusion Texture analysis on early-enhanced phase of breast MRI is able to help to improve the diagnostic ability in predicting complete response on in breast cancer after NAC.

Objective To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF) β1 in hyperuricemic rats.Methods Forty male SD rats were divided into 4 groups:normal control group (NC group),oteracil potassium group (OP group),oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group).Each group had 10 rats and balanced in body weights.To induce hyperuricemia,rats were given oteracil potassium by gastric garage once a day for eight weeks.Rats in OF group and OB group were given either febuxostat or benbromarone starting with oteracil potassium,and rats in NC group was given saline only.Blood samples were taken before,and at the end of 4 and 8 weeks of the treatments and serum uric acid,creatinine,blood usea nitrogen (BUN),IL-6 and TGFβ1 contents were measured at each time point.Renal pathological changes were observed via HE and Masson staining,and the expression of α-SMA and E-cadherin were detected by immunohistochemistry.Results Compared with those in NC group,the levels of serum uric acid,creatinine,BUN,IL-6 and TGFβ1 in the another three groups were increased significantly (all P ＜ 0.01).However,the IL-6 and TGFβ1 contents in OF group were much lower than those in OP group (P ＜0.01).HE and Masson staining showed that OF group had less damage and tubulointerstitial fibrosis than OP group and OB group (P ＜0.01).Moreover,the expression of α-SMA was significantly down-regulated (P ＜ 0.01) and that of E-cadherin was significantly up-regulated in OF group compared with those in OP group.Conclusion Febuxostat treatment significantly inhibited EMT and reduced the levels of IL-6 and TGFβ1 in hyperuricemia rats.

Objective To Analyze the clinical outcomes of pediatric liver transplantation (LT) for liver-based metabolic disorders.Methods We conducted a retrospective analysis on 42 pediatric patients with liver-based metabolic disorders from June 2013 to March 2017,and analyzed the pediatric end stage liver disease model (PELD),growth and development,type of transplant,postoperative complications and prognosis of patients.Results There were 42 children with liver-based metabolic disorders (15.56%) out of all the 270 children who underwent LT.The median age was 51.0 months (range,3.4-160.9 months).Of the 42 children,19 received living donor liver transplantation (LDLT),18 cases received deceased donor liver transplantation (DDLT) and 5 cases received domino liver transplantation.1-,2-and 3-year cumulative survival rate of 42 recipients was 97.7%,93.6% and 93.6%,and that of the grafts was 95.3%,91.4% and 91.4%,respectively.As compared with the 194 children with biliary atresia who underwent LT,significant difference was found in PELD and weight Z-score between the two groups.Conclusion Liver transplantation is a valuable option for children with metabolic disorders,and it has gained a better prognosis.