Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Pan-vascular medicine is an emerging discipline focusing on atherosclerotic diseases,with the concept of multidisciplinary integration,emphasizing on exploring the mechanism of disease development from the whole of the organism's structure and function.At present,the basic mechanism system of pan-vascular diseases has yet to be perfected.The pan-vascular concept is highly compatible with the idea of Chinese medicine that focuses on the overall view.Deficiency of all qi is the root cause of pan-vascular diseases,while phlegm,blood stasis,and water-dampness and other tangible evils stagnate in the veins and channels as the symptoms of the disease,therefore,the disease mechanism can be highly summarized as"stagnation due to qi deficiency".Deficiency leads to the stagnation,blocking the veins and channels,and the deficiency worsens due to the stagnation and then damages the veins and channels,thus,it develops into a disease.Based on the theory of"stagnation due to qi deficiency",this paper takes endothelial cell dysfunction as the entry point of pan-vascular diseases,and considers that low endothelial cell immunity is the initiating factor of pan-vascular diseases,and that the widespread persistence of microinflammatory state is the key pathology to pan-vascular diseases.

Single-cell transcriptome sequencing (scRNA-seq) can resolve the expression characteristics of cells in tissues with single-cell precision, enabling researchers to quantify cellular heterogeneity within populations with higher resolution, revealing potentially heterogeneous cell populations and the dynamics of complex tissues. However, the presence of a large number of technical zeros in scRNA-seq data will have an impact on downstream analysis of cell clustering, differential genes, cell annotation, and pseudotime, hindering the discovery of meaningful biological signals. The main idea to solve this problem is to make use of the potential correlation between cells and genes, and to impute the technical zeros through the observed data. Based on this, this paper reviewed the basic methods of imputing technical zeros in the scRNA-seq data and discussed the advantages and disadvantages of the existing methods. Finally, recommendations and perspectives on the use and development of the method were provided.
Cluster Analysis ; Transcriptome

Objective:To explore the early predictors of high flow oxygen treatment failure for post-operation patients with hypoxemia.Methods:The post-operation adult patients with hypoxemia (100 mmHg0.05). There were significant differences of HR/SpO 2 and ROX index at 8 to 12 h after extubation between the two groups (both P<0.05). Conclusions:HR/SpO 2 is more early and accurate in predicting HFNC failure than ROX index for post-operation patients with hypoxemia. However, both the predictors should be further evaluated.

Objective:To observe the effect of high-flow nasal cannula oxygen therapy (HFNC) in patients with chronic obstructive pulmonary disease (COPD) and mild hypercapnia, and to evaluate the early predictive ability of physiological parameters in these patients.Methods:A retrospective cohort study was conducted based on Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) updated in September 2020 and the data of adult patients with COPD and mild hypercapnia [45 mmHg (1 mmHg = 0.133 kPa) < arterial partial pressure of carbon dioxide (PaCO 2)≤ 60 mmHg] from 2008 to 2019 were collected. These patients were assigned to the HFNC group or non-invasive ventilation (NIV) group according to whether they received HFNC or NIV. Baseline data such as gender, age, body mass index (BMI), simplified acute physiology scoreⅡ (SAPSⅡ), Charlson comorbidity index (CCI) and physiological parameters were collected. A propensity score matching was conducted according to the baseline data of the HFNC group patients. The 48-hour and 28-day intubation rates, 28-day mortality, length of intensive care unit (ICU) stay, the length of hospital stay, and the changes in physiological parameters within 48 hours after treatment were compared between the two groups. The receiver operating characteristic curve (ROC curve) was drawn and the ratio of heart rate over pulse oxygen saturation (HR/SpO 2) and ROX index [SpO 2 / (inhaled oxygen concentration, FiO 2×respiratory rate, RR)] were analyzed to predict the 24-hour and 48-hour intubation rates. Results:A total of 524 520 inpatient records were screened and 153 patients were included, while 37 patients in the HFNC group and 116 patients in NIV group. There were 31 patients in the HFNC group and 84 patients in the NIV group remained after propensity score matching according to the baseline data. There were no significant differences in the baseline data of gender, age, BMI, SAPSⅡ, CCI score, physiological parameters and prognosis data except the length of ICU stay. The length of ICU stay in HFNC group was significant longer than that of the NIV group [days: 4.6 (3.1, 10.0) vs. 3.1 (1.6, 5.8), P < 0.05]. HR and RR at 40- 48 hours were significantly lower than those at 0-8 hours after treatment only in the HFNC group [HR (bpm): 84.1±12.2 vs. 91.1±16.4, RR (times/min): 19.8±4.9 vs. 21.6±4.1, both P < 0.05]. Both in the HFNC group and NIV group the pH increased (7.42±0.08 vs. 7.36±0.05 and 7.41±0.06 vs. 7.36±0.05, both P < 0.05) and PaCO 2 decreased significantly [mmHg: 46.3 (39.5, 51.0) vs. 49.8 (45.5, 54.0) and 46.0 (40.5, 51.5) vs. 49.5 (45.5, 55.3), both P < 0.05]. The HR, PaO 2 were higher in the HFNC group than those in the HFNC group at 40-48 hours after treatment [HR (bpm): 91.1±15.4 vs. 84.1±12.2, PaO 2 (mmHg): 99.5 (86.0, 132.3) vs. 85.8 (76.5, 118.0), both P < 0.05], PaO 2/FiO 2 were lower in the HFNC group than that in the HFNC group at 40-48 hours after treatment [mmHg: 223.8 (216.5, 285.0) vs. 278.0 (212.3, 306.0), P < 0.05]. Both HR/SpO 2 and ROX index at 4 hours after treatment had predictive value for 24-hour and 48-hour intubation in the HFNC group. The areas under ROC curve (AUC) of HR/SpO 2 at 4 hours after treatment in the HFNC group were larger than those of ROX index for predicting 24-hour and 48-hour intubation (24-hour: 0.649 vs. 0.574, 48-hour: 0.692 vs. 0.581, both P < 0.01); the 95% confidence interval (95% CI) of 4 hours HR/SpO 2 and for ROX index predicting 24 hours and 48 hours intubation were 0.497-0.780, 0.567-0.799, 0.450-0.694 and 0.454-0.716, respectively. The high sensitivity of HR/SpO 2 and ROX index in predicting 24-hour and 48-hour intubation were 84.6%, 92.9%, 88.2% and 94.4%, respectively, and the low specificity were 52.3%, 23.7%, 54.7% and 29.6%, respectively. Conclusions:HFNC can be used in COPD patients with mild hypercapnia, but it cannot replace NIV. The accuracy of ROX index at 4 hours after HFNC treatment in predicting intubation in COPD patients with mild hypercapnia is poor.

Background and Objectives: Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study. Methods: and Results: Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS＋hucMSC-ex, LPS＋negative control-siRNA-ex (NC-ex), or LPS＋ Galectin-3-siRNA-ex (si-ex) in vitro. The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex in vivo. Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. β-catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and β-catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities. Conclusions HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased β-catenin levels.

Background and Objectives: Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study. Methods: and Results: Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS＋hucMSC-ex, LPS＋negative control-siRNA-ex (NC-ex), or LPS＋ Galectin-3-siRNA-ex (si-ex) in vitro. The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex in vivo. Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. β-catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and β-catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities. Conclusions HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased β-catenin levels.