OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective:To develop an original-mirror alignment associated deep learning algorithm for intelligent registration of three-dimensional maxillofacial point cloud data,by utilizing a dynamic graph-based registration network model(maxillofacial dynamic graph registration network,MDGR-Net),and to provide a valuable reference for digital design and analysis in clinical dental applications.Methods:Four hundred clinical patients without significant deformities were recruited from Peking University School of Stomatology from October 2018 to October 2022.Through data augmentation,a total of 2 000 three-dimensional maxillofacial datasets were generated for training and testing the MDGR-Net algorithm.These were divided into a training set(1 400 cases),a validation set(200 cases),and an internal test set(200 cases).The MDGR-Net model constructed feature vectors for key points in both original and mirror point clouds(X,Y),established correspondences between key points in the X and Y point clouds based on these feature vectors,and calculated rotation and translation matrices using singular value decomposi-tion(SVD).Utilizing the MDGR-Net model,intelligent registration of the original and mirror point clouds were achieved,resulting in a combined point cloud.The principal component analysis(PCA)algorithm was applied to this combined point cloud to obtain the symmetry reference plane associated with the MDGR-Net methodology.Model evaluation for the translation and rotation matrices on the test set was performed using the coefficient of determination(R2).Angle error evaluations for the three-dimensional maxillofacial symmetry reference planes were constructed using the MDGR-Net-associated method and the"ground truth"iterative closest point(ICP)-associated method were conducted on 200 cases in the inter-nal test set and 40 cases in an external test set.Results:Based on testing with the three-dimensional maxillofacial data from the 200-case internal test set,the MDGR-Net model achieved an R2 value of 0.91 for the rotation matrix and 0.98 for the translation matrix.The average angle error on the internal and external test sets were 0.84°±0.55° and 0.58°±0.43°,respectively.The construction of the three-dimensional maxillofacial symmetry reference plane for 40 clinical cases took only 3 seconds,with the model performing optimally in the patients with skeletal Class Ⅲ malocclusion,high angle cases,and Angle Class Ⅲ orthodontic patients.Conclusion:This study proposed the MDGR-Net association method based on intelligent point cloud registration as a novel solution for constructing three-dimensional maxillo-facial symmetry reference planes in clinical dental applications,which can significantly enhance diagnos-tic and therapeutic efficiency and outcomes,while reduce expert dependence.

Objective To standardize nursing management on postoperative patients with a left ventricular assist-ant device(LVAD).Methods The first draft of the Consensus was formed on the basis of literature review.2 rounds of expert consultations and a round of online meeting discussion were held for adjustments and modifications the draft of the Consensus.Results The recovery rate of the inquiry questionnaire was 93.75%.The authority coefficients of the 2 rounds of inquiry experts were 0.927 and 0.920.The concentration degree of expert opinions for each indicator was greater than 3.5 score,and the coefficient of variation was less than 0.25.The Kendall harmony coefficients for 2 rounds of correspondence were 0.402 and 0.407(P<0.01).The final Consensus formed through expert consultations and meetings includes 7 themes:hemodynamic monitoring,LVAD function monitoring,coagulation function monitoring,percutaneous cable and wound care,exercise rehabilitation care,health education and guidance,and pre-discharge assessment.Conclusion The Consensus is scientific,rigorous,and authoritative.The Consensus covers all aspects of postoperative care for patients with LVAD,and it will benefit to clinical practice.

OBJECTIVES: To develop a Chinese version of the Stress Adaption Scale (SAS) and to assess its reliability and validity among Chinese patients with multimorbidity. METHODS: The Brislin model was used to translate, synthesize, back-translate, and cross culturally adapt the SAS. A total of 323 multimorbidity patients selected by convenience sampling method from four hospitals in Zhejiang province. The critical ratio method, total question correlation method, and graded response model (item characteristic curve and item discrimination) were used for item analysis. Cronbach's alpha coefficient and split-half reliability were used for the reliability analysis. Content validity analysis, structural validity analysis, and criterion association validity analysis were performed by expert scoring method, confirmatory factor analysis, and Pearson correlation coefficient method, respectively. RESULTS: The Chinese version of the SAS contained 2 dimensions of resilience and thriving, with a total of 10 items. In the item analysis, the critical ratio method showed that the critical ratio of all items was greater than 3.0 (P<0.001); the correlation coefficient method showed that the Pearson correlation coefficients for all items exceeded 0.4 (P<0.01). The graded response model showed that items of the revised scale exhibited distinct item characteristic curves and all items had discrimination parameters exceeding 1.0. In the reliability analysis, Cronbach's alpha coefficient of the revised Chinese version of the SAS scale was 0.849, and the split-half reliability was 0.873. In the validity analysis, the item-level content validity index and scale-level content validity index both exceeded 0.80. In the confirmatory factor analysis, the revised two-factor model showed satisfactory fit indices (χ²/df=3.115, RMSEA=0.081, RMR=0.046, GFI=0.937, AGFI=0.898, CFI=0.936, TLI=0.915). In the criterion-related validity analysis, the Chinese version of the SAS score was negatively correlated with the Perceived Stress Scale and the Treatment Burden Questionnaire, with correlation coefficients of －0.592 and －0.482, respectively (both P<0.01). CONCLUSIONS The Chinese version of the SAS has good reliability and validity, which can be used to evaluate the stress adaption capacity among multimorbidity patients in China, and provides a reference for developing individualized health management measures.
Humans ; Adaptation, Psychological ; Asian People ; China ; Multimorbidity ; Reproducibility of Results ; Stress, Psychological/psychology* ; Surveys and Questionnaires ; Translating ; Cross-Cultural Comparison

OBJECTIVES: To develop a Chinese version of the Long-Term Conditions Questionnaire (LTCQ) and to test its reliability and validity in Chinese patients with chronic diseases. METHODS: With the consent of the original authors, a Chinese version of LTCQ was developed according to the cultural adjustment guidelines. A questionnaire survey was conducted on 319 patients with chronic diseases in Sir Run Run Shaw Hospital, Wuyi County First People's Hospital and Hangzhou Gongchen Bridge Street Health Service Center. The questionnaire was evaluated by item analysis (including frequency analysis, total question correlation method and critical ratio method), reliability analysis (Cronbach's alpha coefficient) and validity analysis [including content validity (expert scoring method) and structural validity (exploratory factor analysis)]. RESULTS The Chinese version of the LTCQ included 20 entries, with a Cronbach's alpha coefficient of 0.926, a retest reliability of 0.829, a split-half reliability of 0.878, an entry content validity index of 1, and a content validity index at the questionnaire level of 1. Four common factors were extracted by exploratory factor analysis, namely physical state and daily life, psychological state, support and coping, and safe environment, with a cumulative variance contribution rate of 67.244%. Discussion: The Chinese version of the LTCQ developed in this study has good reliability and validity and it may be used to assess the long-term conditions of patients with chronic diseases in China.
Humans ; Asian People ; China ; Chronic Disease ; Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires

Objective:To establish an intelligent registration algorithm under the framework of original-mirror alignment algorithm to construct three-dimensional (3D) facial midsagittal plane automatically. Dynamic Graph Registration Network (DGRNet) was established to realize the intelligent registration, in order to provide a reference for clinical digital design and analysis.Methods:Two hundred clinical patients without significant facial deformities were collected from October 2020 to October 2022 at Peking University School and Hospital of Stomatology. The DGRNet consists of constructing the feature vectors of key points in point original and mirror point clouds (X, Y), obtaining the correspondence of key points, and calculating the rotation and translation by singular value decomposition. Original and mirror point clouds were registrated and united. The principal component analysis (PCA) algorithm was used to obtain the DGRNet alignment midsagittal plane. The model was evaluated based on the coefficient of determination (R 2) index for the translation and rotation matrix of test set. The angle error was evaluated on the 3D facial midsagittal plane constructed by the DGRNet alignment midsagittal plane and the iterative closet point (ICP) alignment midsagittal plane for 50 cases of clinical facial data. Results:The average angle error of the DGRNet alignment midsagittal plane and ICP alignment midsagittal plane was 1.05°±0.56°, and the minimum angle error was only 0.13°. The successful detection rate was 78% (39/50) within 1.50° and 90% (45/50) within 2.00°.Conclusions:This study proposes a new solution for the construction of 3D facial midsagittal plane based on the DGRNet alignment method with intelligent registration, which can improve the efficiency and effectiveness of treatment to some extent.

OBJECTIVE: To analyze the clinical features of severe or critical ill adult patients with coronavirus disease (COVID-19). METHODS: The clinical data of 75 patients with severe or critical COVID-19 in Honghu People's Hospital from January to March in 2020 were collected. RESULTS: Of the 75 patients with COVID-19 pneumonia, 41 were male (54.67%) and 34 were female (45.33%) with a mean age of 67.53 ±12.37 years; 43 patients had severe and 32 had critical COVID-19, and 49.3% of the patients had underlying diseases. The main clinical manifestations included fever (78.67%) and coughing (70.67%). Compared with the severe patients, the critically ill patients had higher proportions of patients over 60 years old with elevated white blood cell count, increased prothrombin time, and higher levels of hsCRP, PCT, D-dimer, ALT, LDH, cTnI and NT-proBNP. Univariate logistic regression analysis showed that an age over 60 years, leukocytosis, hs-CRP elevation, prolonged prothrombin time, and increased levels of D-dimer, NT-proBNP and cTnI were associated with severe COVID-19. Multivariate logistic regression showed that an age over 60 years (OR=8.165, 95% : 1.483-45.576, =0.017), prolonged prothrombin time (OR=7.516, 95% : 2.568-21.998, =0.006) and elevated NT-proBNP (OR=6.194, 95% : 1.305-29.404, =0.022) were independent risk factors for critical type of COVID-19. CONCLUSIONS An age over 60 years, a prolonged prothrombin time and elevated NT-proBNP level are important clinical features of critically ill patients with COVID-19, and can be deemed as early warning signals for critical conditions of the disease.
Aged ; Betacoronavirus ; Coronavirus Infections ; Critical Illness ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; Retrospective Studies

Once pulp necrosis or apical periodontitis occurs on immature teeth, the weak root and open root apex are challenging to clinicians. Berberine (BBR) is a potential medicine for bone disorders, therefore, we proposed to apply BBR in root canals to enhance root repair in immature teeth. An in vivo model of immature teeth with apical periodontitis was established in rats, and root canals were filled with BBR, calcium hydroxide or sterilized saline for 3 weeks. The shape of the roots was analyzed by micro-computed tomography and histological staining. In vitro, BBR was introduced into stem cells from apical papilla (SCAPs). Osteogenic differentiation of stem cells from apical papilla was investigated by alkaline phosphatase activity, mineralization ability, and gene expression of osteogenic makers. The signaling pathway, which regulated the osteogenesis of SCAPs was evaluated by quantitative real time PCR, Western blot analysis, and immunofluorescence. In rats treated with BBR, more tissue was formed, with longer roots, thicker root walls, and smaller apex diameters. In addition, we found that BBR promoted SCAPs osteogenesis in a time-dependent and concentration-dependent manner. BBR induced the expression of β-catenin and enhanced β-catenin entering into the nucleus, to up-regulate more runt-related nuclear factor 2 downstream. BBR enhanced root repair in immature teeth with apical periodontitis by activating the canonical Wnt/β-catenin pathway in SCAPs.
Animals ; Berberine ; pharmacology ; Cell Differentiation ; drug effects ; Dental Papilla ; Male ; Osteogenesis ; drug effects ; Periapical Periodontitis ; therapy ; Rats ; Stem Cells ; cytology ; drug effects ; metabolism ; Wnt Signaling Pathway ; drug effects ; Wnt3A Protein ; genetics ; metabolism ; X-Ray Microtomography