Objective To investigate the effect of dapagliflozin on myocardial work and energy metabolism in patients with heart failure with reduced ejection fraction(HFrEF)without type 2 diabetes mellitus(T2DM).Methods Patients with HFrEF without T2DM who visited Wuzhou People's Hospital from January 2021 to January 2022 were randomly divided into conventional group and dapagliflozin group(conventional treatment+dapagliflozin).After treatment(12 months),myocardial work[global work index(GWI),global constructed work(GCW),global wasted work(GW),and global work efficiency(GWE)],energy metabolism[(free fatty acids(FFA)and β-hydroxybutyric acid(β-HB)],traditional cardiac function[left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular ejection fraction(LVEF)],clinical efficacy,prognosis[mortality,rehospitalization,and incidence of major adverse cardiovascular events(MACE)]and adverse reactions were compared between the two groups.Results A total of 128 patients with HFrEF without T2DM were enrolled,including 63 patients in the dapagliflozin group and 65 patients in the conventional group.After treatment,the LVEDD,LVESD,GWW,NT-pro BNP in the dapagliflozin group was significantly lower than that in the conventional group(P＜0.05),while the LVEF,GWI,GCW,GWE,β-HB acid and FFA were significantly higher than those in the conventional group(P＜0.05).The total effective rate and hypoglycemia rates in the dapagliflozin group were significantly higher than those in the conventional group(P＜0.05),and the rehospitalization rate and MACE rate were significantly lower than those in the conventional group(P＜0.05).There were no significant differences in mortality,renal adverse events,urinary tract infections and gastrointestinal symptoms between the two groups(P＞0.05).Conclusion Dapagliflozin has significant clinical efficacy in patients with HFrEF without T2DM,which can increase the serum levels of FFA and ketones,improve effective work,and reduce ineffective work,but it is necessary to be vigilant against hypoglycemia.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Preimplantation genetic testing is an important part in assisted reproductive technology,which can block the intergenerational inheritance of a single gene or chromosomal diseases.Preimplantation genetic testing for polygenic disease risk(PGT-P)is one of the latest developments in the field.With the development of artificial intelligence and genetic detection technology,PGT-P can be used to analyze genetic material,calculate polygenic risk scores and convert these into incidence probability.Embryos with relatively low incidence probability can be screened for transfer,in order to reduce the possibility that the offspring suffers from the disease in the future.This has significant clinical and social significance.At present,PGT-P has been applied clinically and made phased progress at home and abroad.But as a developing technology,PGT-P still has some technical limitations as unstable results,environmental influences and racial differences cannot be ruled out.From the ethical perspective,if the screening indications are not strictly regulated,it is likely to cause new social problems.In this paper,we review the technical details and recent progress in PGT-P,and discuss the prospects of its future development,especially how to establish a complete and suitable screening model for Chinese population.

Objective To search and integrate relevant evidence of Traditional Chinese Medicine rehabilitation care during recovery of stroke patients with limb dysfunction,and to provide the evidence for clinical practice.Methods We systematically search domestic and foreign guideline websites,professional association websites,and databases such as Cochrane Library,PubMed,Embase,CNKI,CBM for evidence on Chinese medicine rehabilitation care for limb dysfunction following stroke.The search included guidelines,clinical decisions,evidence summaries,systematic reviews,expert consensuses,and randomized controlled trials,with the search timeframe spanning from the inception of the respective databases to May 2023.The literature was evaluated and rated for quality by 2 researchers independently.Results A total of 17 articles,including 7 guidelines,4 systematic reviews,1 evidence summary and 5 randomized controlled trials were included to summarize 28 pieces of evidence on Traditional Chinese Medicine rehabilitation care for stroke patients with limb dysfunction.The evidence can be categorized into 4 areas,including evaluation,Traditional Chinese Medicine nursing technology,health education and precautions.Conclusion Traditional Chinese Medicine nursing technology for stroke patients with limb dysfunction have various forms and rich contents.Appropriate Traditional Chinese Medicine nursing techniques should be selected according to the actual situation and the willingness of patients to promote the rehabilitation of their limb functions.

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of prurigo nodularis (PN) in the real world.Methods:PN patients who were subcutaneously injected with dupilumab for over 12 weeks were collected from the China Type Ⅱ Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project Database from June 2021 to October 2022. Their clinical data were retrospectively analyzed, which included demographic data, and changes in pruritus numeric rating scale (NRS), investigator global assessment for PN-Stage (IGA PN-S), dermatology life quality index (DLQI) and hospital anxiety and depression scale (HADS) scores before and after treatment. Differences in scores before and after treatment, as well as in efficacy between patients with and without a history of atopic diseases, were analyzed using Wilcoxon signed-rank test, paired t-test or chi-square test. Results:A total of 66 PN patients were collected, including 42 males and 24 females, and they were aged 8 to 89 (44.12 ± 24.17) years. Thirty-six patients had a history of atopic diseases, and 27 had a family history of atopic diseases. After 12-week treatment with dupilumab, the pruritus NRS, IGA PN-S and DLQI scores in the 66 patients significantly decreased from the baseline scores (7.00 [5.00, 8.00], 3.00 [3.00, 4.00], 12.00 [7.75, 20.25], respectively) to 3.00 [2.00, 4.25], 2.00 [2.00, 3.00], 5.00 [1.75, 8.25], respectively (all P < 0.001). Among the 66 patients, 39 continued the regular treatment with dupilumab after 12 weeks and were followed up to 16 weeks; their pruritus NRS and IGA PN-S scores at week 16 further decreased compared with those at week 12 (both P < 0.05). There were no significant differences in the proportion of patients showing an improvement of ≥ 4 points in the NRS score or the proportion of patients achieving IGA 0/1 at week 12 between the patients with history of atopic diseases and those without (both P > 0.05). Before treatment, 32 PN patients were accompanied by mild to severe anxiety and/or depression; after 12-week treatment, the HADS-A scores in the 28 patients with anxiety (HADS-A scores > 7 points) and the HADS-D scores in the 20 patients with depression (HADS-D scores > 7 points) significantly decreased compared with their baseline scores (both P < 0.001) ; 18 (56.52%) patients achieved remission in anxiety and depression (both HADS-A and HADS-D scores < 7 points). Among the 66 PN patients, there were 13 minor patients, including 7 males and 6 females, and they were aged 8 to 17 (13.77 ± 3.09) years; after 12-week treatment, their pruritus NRS, IGA PN-S, and DLQI scores significantly decreased compared with the corresponding baseline scores (all P < 0.05) ; 8 minor patients continued dupilumab treatment for 16 weeks, with a further decrease in the IGA PN-S score compared with that at week 12 ( P < 0.05), but without significant differences between the pruritus NRS and DLQI scores at week 16 and those at week 12 (both P > 0.05). Adverse reactions were observed in 7 adult patients, including eye pruritus, local injection reactions, and systemic erythema accompanied by pruritus on the day of injection. No adverse reactions were reported in minor patients. Conclusion:In the real world, dupilumab could markedly alleviate pruritus, skin lesions, anxiety and depression symptoms in PN, improve the quality of life, and exhibited a good safety profile.

Chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) are diseases that occur after acute pulmonary embolism resulting from residual and organized intra-pulmonary thrombus, with or without pulmonary hypertension(PH). The prognosis of these diseases has been dramatically improved with the continuous progress of treatment and the updated concept of the comprehensive treatment strategy. However, there is a lack of awareness of these diseases among medical practitioners, and a lack of epidemiological data in China, with unknown pathogenesis and non-specific clinical manifestations. Therefore, it is easy to misdiagnosis, underdiagnosis and delay diagnosis in clinical practice. To enhance the understanding of medical personnel, this paper summarizes the definition, epidemiology, pathology, pathogenesis, diagnosis and treatment of CTEPH and CTEPD.

Objective:To summarize the clinical features, diagnosis, treatment, and outcomes of necrotizing pneumonia(NP)in children, so as to improve the understanding of NP.Methods:Children with NP admitted to the Children′s Medical Center of Hunan Provincial People′s Hospital from December 2012 to June 2020 were selected and divided into respiratory support group(nine cases) and non-respiratory support group(27 cases) according to whether they received respiratory support; and they were also divided into pleural effusion group(28 cases) and non-pleural effusion group(eight cases) according to whether combined with pleural effusion.The clinical data of all children were collected, and the differences between different groups were compared.Results:There were thirty-six children with NP, included 14 boys and 22 girls, with a median age of 30(12, 49) months, and the disease duration was 34(25, 42)days.All children had cough, 34 cases had fever, and the fever peak was 39.5(39.1, 40.0) ℃.Laboratory tests(all peaks) showed that blood white blood cell count was 20.77(15.65, 28.35)×10 9/L, neutrophil count was 15.11(8.52, 20.65)×10 9/L, C-reactive protein(CRP) was 104.00(23.45, 146.50)mg/L, D-dimer was 5.12(1.88, 8.04)mg/L, and lactate dehydrogenase(LDH) was 347.95(284.68, 447.81)U/L.The detection rate of pathogens was 58.33%(21/36), and the most common was Staphylococcus aureus(28.57%, 6/21). Eight cases underwent surgical treatment, including five cases of thoracoscopic surgery and three cases of thoracotomy.All patients improved and were discharged from hospital.The differences in hospital stay, white blood cell count, CRP, procalcitonin and LDH levels between respiratory support group and non-respiratory support group were statistically significant, and the median age, white blood cell count, CRP, D-dimer and LDH between pleural effusion group and non-pleural effusion group were statistically significant(all P<0.05). Further multivariate Logistic regression analysis showed that LDH was a risk factor for NP children receiving respiratory support( P<0.05), the area under the ROC curve of LDH was 0.802, whose the cut-off value was 471.21 U/L.There were no statistically significant differences in the indexes between effusion group and non-pleural effusion group. Conclusion:Children with NP are prone to repeated high fever, high inflammatory markers, and a long course of disease.Staphylococcus aureus is the most common pathogen.Serum LDH≥471.21 U/L is an early independent predictor of respiratory support for NP.

This article introduces a high-throughput molecular screening chip： peptide arrays. As a kind of biochip， the peptide arrays are easy to synthesis， stable in probe chemistry， high-throughput in screening and highly specific compared with other biochips. To analyze the new high-throughput data， researchers have recently proposed a series of deep learning and bioinformatics methods to study the binding characteristics of peptide probes and target molecules. Those algorithms could be used to predict the binding affinity of protein targets against peptides. Moreover， peptide arrays could also play important roles in analyzing protein-protein interactions，screening novel drug peptides， disease diagnosis and general health assessment based on recent reports. The application of this new technology could provide novel insights into public health research.

Objective:To evaluate the expression level of hsa-miR-422a in hypertrophic scars and to identify the target genes of hsa-miR-422a along with their biological functions using bioinformatics approaches.Methods:From June 2020 to December 2020, tissue samples of 3 hypertrophic scar and 3 normal skin were collected from patients (3 males, 3 females, aged 20-42 years) in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine. Primary fibroblasts were isolated and cultured. Real-time quantitative PCR was performed to quantify the expression of hsa-miR-422a. To construct a ceRNA network, starbase and Target Scandata bases were utilized to predict genes as well as long noncoding RNAs (lncRNAs) that may sponge hsa-miR-422a. GO and KEGG pathway enrichment analyses were conducted on the target genes of hsa-miR-422a; protein-protein interaction (PPI) networks were constructed to identify the hub genes whose functions were predicted by functional enrichment analyses. The expression of hub genes was validated through real-time quantitative PCR in hypertrophic scars.Results:The expression of hsa-miR-422a was significantly lower in the hypertrophic scar tissue samples and fibroblasts compared to that in the normal skin ( P<0.05). 133 target genes as well as 1033 lncRNAs were predicted by starBase and TargetScandata bases and used to construct an hsa-miR-422a-centered ceRNA network. PPI networks of the target genes revealed 10 hub genes, including MAPK1, GRB2, and IGF1R, which were discovered to be related to protein serine/threonine/tyrosine kinase activity, ubiquitin protein ligase binding, fibroblast growth factor receptor signaling pathway, muscle cell proliferation, and many others; besides, they may be involved in FoxO, mTOR, Toll-like receptor, Ras, MAPK, PI3K-Akt signaling pathways and signaling pathways regulating pluripotency of stem cells. Three hub genes (MAPK1, GRB2, and IGF1R) were significantly upregulated in hypertrophic scars ( P<0.05). Conclusions:hsa-miR-422a is significantly downregulated in the hypertrophic scars and may target hub genes such as MAPK1 in ceRNA networks, ultimately modulating hypertrophic scar formation.

At present, most of the research on hip exoskeleton robots adopts the method of decoupling analysis of hip joint motion, decoupling the ball pair motion of hip joint into rotational motion on sagittal plane, coronal plane and cross section, and designing it into series mechanism. Aiming at the problems of error accumulation and man-machine coupling in series mechanism, a parallel hip rehabilitation exoskeleton structure is proposed based on the bionic analysis of human hip joint. The structure model is established and the kinematics analysis is carried out. Through the OpenSim software, the curve of hip flexion and extension, adduction and abduction angle in a gait cycle is obtained. The inverse solution of the structure is obtained by the D-H coordinate system method. The gait data points are selected and compared with the inverse solution obtained by ADAMS software simulation. The results show that the inverse solution expression is correct. The parallel hip exoskeleton structure can meet the requirements of the rotation angle of the hip joint of the human body, and can basically achieve the movement of the hip joint, which is helpful to improve the human-computer interaction performance of the exoskeleton.
Humans ; Exoskeleton Device ; Hip Joint ; Gait ; Biomechanical Phenomena ; Computer Simulation