BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Young Adult ; Cyanosis ; Deglutition Disorders ; EGF Family of Proteins ; Muscle Hypotonia ; Muscle Weakness ; Muscular Diseases/genetics* ; Retrospective Studies

The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external environment. Disruption of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers, including prostate cancer (PCa). Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with PCa. This review begins with patterns of the circadian clock, highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels, and discusses possible new approaches to PCa therapy that target the circadian clock.
Humans ; Male ; Carcinogenesis ; Circadian Clocks/physiology* ; Circadian Rhythm/physiology* ; Prostatic Neoplasms/physiopathology*

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.
Male ; Humans ; Endothelial Cells ; Ligands ; Prostatic Neoplasms/pathology* ; Prostate/pathology* ; Prostatectomy ; Aldehyde Dehydrogenase, Mitochondrial ; DNA-Binding Proteins ; Transcription Factors

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.
Male ; Humans ; Prognosis ; Neoplasm Recurrence, Local/pathology* ; Prostatic Neoplasms/pathology* ; Prostatectomy ; Drug Resistance ; Aldehyde Dehydrogenase, Mitochondrial

Objective To investigate the current situation and risk factors of falls in the rural community elderly aged 65 years and above in Chongqing City, and to provide references for developing preventive measures. Methods The multistage cluster random sampling method was used to select several rural communities in Chongqing City from September to December, 2019, and then the elderly aged 65 years and above who lived in the communities for one year were chosen to serve as the surveyed subjects. A self designed questionnaire (sociodemographic factors, exercise status, illness and medication status and fall to related information) was used to collect the data regarding falls occurring in the last year. The chi-square test and multi factor multi-variant logistic regression analysis were utilized to analyze the data, the used software was SPSS 25.0. Results A total of 801 rural community elderly people in Chongqing City were surveyed．The average age was (71.64±5.85) years old. 7.12% of elderly need cane or walker. 6.87% of them self-reported their health was poor. 42.57% of elderly seldom have the habit of exercise. The prevalence of heart disease, diabetes, osteoporosis, arthritis, cataract, deafness self-reported was 8.99%、8.11%、17.48%、25.97%、13.73% and 6.24% respectively. Totally 104 elderly people experienced 128 falls in the past 12 months, and the incidence rates of falls and falling times were 12.84% and 15.98% respectively．The multi-variant logistic regression analysis showed that poor heath status self-reported（OR=4.04，95% , CI：1.71-9.52）, diabetes （OR=2.68，95% CI： 1.41-5.12）, osteoporosis （OR=1.91 , 95% CI：1.16-3.15）, arthritis （OR=2.60 , 95% CI：1.65-4.11） and non self-care（OR=2.44，95% CI：1.16-5.16） were the risk factors for falls in the rural community elderly. Conclusions The incidence rate of falls in the rural community elderly aged 65 years and above in Chongqing City was low．It is necessary to formulate comprehensive intervention measures for the risk factors of fall so as to reduce the incidence rate of falls in the elderly.

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.
Humans ; Fecal Microbiota Transplantation/methods* ; Treatment Outcome ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Steroids

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: To evaluate the pink and white esthetics of conventional and socket shield technique (SST) immediate implant restoration. Methods: Thirty volunteers were recruited according to preset criteria, and were assigned to 3 groups. Natural teeth group (ten undergraduates or postgraduates from Peking University School and Hospital of Stomatology in January 2020, n=10): all volunteers' maxillary anterior teeth were natural teeth with healthy gingiva, and none of the teeth were restored by crowns or composite. Conventional group and SST group (patients had a maxillary central incisor immediate implant placed in Department of Prosthodontics, Peking University School and Hospital of Stomatology during October 2016 to January 2021, n=10 for each group): the volunteer had an unrestored natural maxillary central incisor, and the contralateral maxillary central incisor was restored by conventional or SST immediate implant placement, temporization and all ceramic final restoration, photos were taken 12 months post-surgery. Three groups of evaluators namely layperson (staff from Second Clinical Division of Peking University School and Hospital of Stomatology and 2 family members, n=10), dental students (class 2015 undergraduates from Peking University School and Hospital of Stomatology, n=10) and prosthodontists (from Department of Prosthodontics, Peking University School and Hospital of Stomatology, n=10) were invited to assess the esthetics using pink esthetic score (PES) and white esthetic score (WES). The results were statistically analyzed. Results: PES and WES of natural teeth group [9(8, 10) and 8(7, 10)] were significantly higher than conventional group [7(6,8) and 7(6,9)] (H=287.08, 132.79,P<0.01) and SST group [7(6, 9) and 8(7, 9)] (H=216.01, 101.21, P<0.01). SST group yielded higher PES than the conventional group (H=-71.06, P<0.01), yet had similar WES (H=-31.57, P>0.05). Dental students had significant lower PES and WES than prosthodontists (H=-120.90, -218.86, P<0.01) and layperson (H=-109.55, 134.97, P<0.01). Prosthodontists and layperson got similar PES (H=-11.36, P>0.05), however yielded different WES (H=-83.89, P<0.01). Conclusions: SST immediate implant placement obtained better pink esthetics than conventional protocol 12-month after implant surgery, profession may have significant impact on evaluators during pink and white esthetic evaluation.
Crowns ; Dental Implants ; Dental Implants, Single-Tooth ; Esthetics, Dental ; Humans ; Immediate Dental Implant Loading ; Maxilla/surgery* ; Treatment Outcome

BACKGROUND: This study commenced to uncover the role of long non-coding RNA FBXL19 antisense RNA 1 (FBXL19-AS1) in the development of ulcerative colitis (UC) and its possible mechanism. METHODS: FBXL19-AS1 expression in the colonic sigmoid mucosa of UC patients was detected. A colitis model was induced in mice using 5% dextran sodium sulfate. Hematoxylin–eosin staining was performed for histopathological examination. Apoptosis was detected by Tunel staining and tissue fibrosis was detected by immunohistochemistry. Also, intestinal permeability was examined. The concentrations of inflammatory factors IL-1b and IL-18 were detected by enzyme-linked immunosorbent assay. The relationship between FBXL19-AS1, miR-339-3p and RHOB was verified by RNA immunoprecipitation assay and dual luciferase reporter assay. RESULTS: The expression of FBXL19-AS1 was increased in dextran sodium sulfate (DSS)-induced colitis mouse model. FBXL19-AS1 interference or miR-339-3p overexpression inhibited DSS-induced colonic epithelial cell apoptosis and inflammatory response, and improved intestinal epithelial barrier defects, thereby ameliorating DSS-induced colitis injury in mice. FBXL19-AS1 sponged miR-339-3p while miR-339-3p targeted RHOB. Overexpression of RHOB reversed the protective effect of inhibition of FBXL19-AS1 on DSS-induced colitis in mice. CONCLUSION FBXL19-AS1 reduces miR-339-3p-mediated targeting of RHOB and aggravates intestinal epithelial barrier defect in DSS-induced colitis in mice.