Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients, may mediate immune evasion.

BACKGROUND: For the first time, we investigated the oncological role of plexin domain-containing 1 (PLXDC1), also known as tumor endothelial marker 7 (TEM7), in hepatocellular carcinoma (HCC). AIM: To investigate the oncological profile of PLXDC1 in HCC. METHODS: Based on The Cancer Genome Atlas database, we analyzed the expression of PLXDC1 in HCC. Using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting, we validated our results. The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features, such as patient survival, methylation level, tumor immune microenvironment features, and immune cell surface checkpoint expression. Finally, to assess the immune evasion potential of PLXDC1 in HCC, we used the tumor immune dysfunction and exclusion (TIDE) website and immunohistochemical staining assays. RESULTS: Based on immunohistochemistry, qRT-PCR, and Western blot assays, overexpression of PLXDC1 in HCC was associated with poor prognosis. Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor. In HCC patients with high methylation levels, the prognosis was worse than in patients with low methylation levels. Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling, and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup. The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis, and PLXDC1-related risk scores were also associated with a poor prognosis. CONCLUSION: As a result of this study analyzing PLXDC1 from multiple biological perspectives, it was revealed that it is a biomarker of poor prognosis for HCC patients, and that it plays a role in determining immune evasion status.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Construction of Risk Prediction Model of Type 2 Diabetic Kidney Disease Based on Deep Learning.

Background: This study aimed to develop a diabetic kidney disease (DKD) prediction model using long short term memory (LSTM) neural network and evaluate its performance using accuracy, precision, recall, and area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Methods: The study identified DKD risk factors through literature review and physician focus group, and collected 7 years of data from 6,040 type 2 diabetes mellitus patients based on the risk factors. Pytorch was used to build the LSTM neural network, with 70% of the data used for training and the other 30% for testing. Three models were established to examine the impact of glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), and pulse pressure (PP) variabilities on the model's performance. Results: The developed model achieved an accuracy of 83% and an AUC of 0.83. When the risk factor of HbA1c variability, SBP variability, or PP variability was removed one by one, the accuracy of each model was significantly lower than that of the optimal model, with an accuracy of 78% (P<0.001), 79% (P<0.001), and 81% (P<0.001), respectively. The AUC of ROC was also significantly lower for each model, with values of 0.72 (P<0.001), 0.75 (P<0.001), and 0.77 (P<0.05). Conclusion: The developed DKD risk predictive model using LSTM neural networks demonstrated high accuracy and AUC value. When HbA1c, SBP, and PP variabilities were added to the model as featured characteristics, the model's performance was greatly improved.

GLI family zinc finger protein 2 promotes skin fibroblast proliferation and DNA damage repair by targeting the miR-200/ataxia telangiectasia mutated axis in diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR-200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF-1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein-diacetate assays. Enzyme-linked immunosorbent assay was used to evaluate 8-oxo-7,8-dihydro-2'deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real-time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR-200a/b/c-3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR-200a/b/c-3p expression, and suppressed ATM and GLI2. MiR-200a/b/c-3p inhibition ameliorated HG-induced cell proliferation and DNA damage repair repression. MiR-200a/b/c-3p targeted ATM. Then, the silenced ATM reversed the miR-200a/b/c-3p inhibition-mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG-induced cell proliferation and DNA damage repair inhibition via miR-200a/b/c-3p. MiR-200a/b/c-3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR-200/ATM axis to enhance diabetic wound healing in DFU.

Perioperative Insulin Pump Therapy Decreases Readmission Risk and Improves Outcomes in Patients with Diabetes.

OBJECTIVE: To evaluate the impact of temporary insulin pump use during hospitalization on glycemia, postoperative complications, and cost/utilization in perioperative patients with diabetes. METHODS: Patients (n=159) with type 2 diabetes and hospitalized for elective surgery were recruited from three hospitals. Subjects were categorized into the insulin pump group and the multiple daily subcutaneous insulin injection group according to their treatment therapy. Data were collected at admission, discharge, and 3 months post-discharge. RESULTS: Subjects in the CSII group who were still on insulin therapy transitioned from CSII to MDII; however, their daily insulin dosages were lower than those in the MDII group (15.31±10.98 U/d vs. 23.48±17.02 U/d, P=0.015) after discharge. In terms of medical costs, the CSII group had significantly higher hospitalization costs than the MDII group (112.36±103.43 thousand RMB vs. 82.65±77.98 thousand RMB, P=0.043). After 3 months, the CSII group had significantly lower outpatient costs than the MDII group (3.17±0.94 thousand RMB vs. 3.98±1.76 thousand RMB, P ˂ 0.001). In the MDII group, 10 patients reported severe postoperative complications requiring re-hospitalization; there were no similar reports in the CSII group. CONCLUSION: Temporary use of insulin pump therapy for perioperative patients with diabetes results in a reduction in blood glucose and blood glucose fluctuation during hospitalization, HbA1c, and the risk of postoperative complication and readmission, thus significantly decreasing costs in this complex patient cohort. Further work is needed to better understand indications for utilizing pump therapy based on diabetes phenotype and the complexity of planned surgical intervention.

Salvianolic acid B attenuates diabetic nephropathy through alleviating ADORA2B, NALP3 in flammasome, and NFκB activity.

Diabetic nephropathy is one of the microvascular complications of diabetes. This study is aimed at investigating the role and mechanisms of salvianolic acid B (Sal B) in diabetic nephropathy. High glucose (HG)-induced human renal tubular epithelial HK-2 cells were treated with Sal B, BAY-60-6583 (agonist of adenosine 2B receptor), or PSB-603 (antagonist of adenosine 2B receptor) for 24 h. Adenosine A2b receptor (ADORA2B), NACHT, leucine-rich repeat (LRR), and pyrin (PYD) domains-containing protein 3 (NALP3), and nuclear factor Kappa B (NFκB) expressions, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels were examined. Following 6 weeks of Sal B treatment, db/db mice blood and kidney tissue were harvested for biochemical detection with hematoxylin-eosin (H&E), Masson's, periodic acid schiff (PAS), and Sirius red staining and detection of ADORA2B, NALP3, NFκB, interleukin 1ß (IL-1ß), and toll-like receptor 4 (TLR4) activity. NFκB, NALP3, and ADORA2B were found to be downregulated in Sal B treated HK-2 cells exposed to high glucose (HG), accompanied by elevated levels of MMPs and reduced intracellular ROS production. Sal B-treated diabetic mice had the improvement in body weight, water intake, hyperglycemia, hyperlipidemia, and liver and kidney function. Altogether, Sal B attenuates HG-induced kidney tubule cell injury and diabetic nephropathy in diabetic mice, providing clues to other novel mechanisms by which Sal B is beneficial in diabetic nephropathy.

Gastrointestinal/genitourinary adverse event after intensity modulated versus three-dimensional primary radiation therapy in the treatment of prostate cancer: systematic review and meta-analysis.

Objective: Prostate cancer (PCa) is one of the most common cancers in the world. The potential benefits of intensity modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3D-CRT) for PCa primary radiation therapy treatment have not yet been clarified. Therefore, this meta-analysis was conducted to assess whether IMRT could improve clinical outcomes in comparison with 3D-CRT in patients diagnosed with PCa. Materials and methods: Relevant studies were identified through searching related databases till December, 2022. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. Results: The incidence of grade 2 or worse acute adverse gastrointestinal (GI) event was analyzed and the pooled data revealed a clear decreasing trend in the IMRT compared with 3D-CRT (RR=0.62, 95% CI: 0.45-0.84, p=0.002). IMRT slightly increased the grade ≥ 2 acute genitourinary (GU) adverse event in comparison with the 3D-CRT (RR=1.10, 95% CI: 1.02-1.19, p=0.015). The IMRT and the 3D-CRT of patients showed no substantial differences in grade ≥ 2 late GI adverse event (RR =0.62, 95% CI: 0.36-1.09, p=0.1). In those included studies, there was no significant difference between IMRT and 3D-CRT in grade 2-4 late GU adverse event (RR =1.08, 95% CI: 0.77-1.51, p=0.65). There was a significant difference in biochemical control favoring IMRT (RR =1.13, 95% CI: 1.05-1.22, p=0.002). IMRT showed modest increase in biochemical control in comparison with 3D-CRT. Conclusion: In general, based on the above results, IMRT should be considered as a better choice for the treatment of PCa. More randomized controlled trials are needed to determine the subset of patients diagnosed with PCa.

Correlation Between the Variability of Different Obesity Indices and Diabetic Kidney Disease: A Retrospective Cohort Study Based on Populations in Taiwan.

Purpose: To investigate the association of five obesity indices and the variability of these indices with diabetic kidney disease (DKD) in patients with type 2 diabetes and compare the predictive validity of these markers for the risk of DKD in this large longitudinal cohort study. Patients and Methods: A total of 2659 patients with type 2 diabetes who did not have DKD were enrolled between 2006 and 2019 at Lee's United Clinic in Taiwan. Data were collected for each subject, including demographic data, personal medical history, clinical parameters and calculated Body mass index (BMI), visceral adiposity index (VAI), lipid accumulation product (LAP), body roundness index (BRI) and variability of five obesity indices. Cox regression analysis was performed to determine the relationship between different obesity indicators and DKD risk. Cox's proportional hazards model was evaluated the predictive effect of obesity indices on DKD. Results: The risk of developing DKD increased with an increase in the BRI, LAP, VAI, WC and BMI (all P trend<0.05), and the variability of VAI was significantly associated with DKD [HR=1.132, 95% CI (1.001, 1.281)] after adjusting for corresponding variables. BRI had the strongest predictive effect on DKD. BRI had the best predictive performance, with AUC of 0.807, 0.663 and 0.673 at 1, 3 and 5 years, respectively. Cox regression analysis of risk factors for DKD in patients stratified by BRI quartiles showed that patients in the Q4 group had the highest risk of developing DKD [HR=1.356, 95% CI (1.131, 1.626)]. Conclusion: BMI, WC, VAI, LAP, BRI and VAI variability were associated with a significant increase in the risk of DKD events, and BRI was superior and alternative obesity index for predicting DKD.

Exosomal circHIPK3 derived from umbilical cord-derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR-20b-5p/ULK1/Atg13 axis.

BACKGROUND: Umbilical cord-derived mesenchymal stem cells (UCMSCs) could alleviate diabetes-induced injury. Hence, this investigation aimed to explore the role and mechanism of UCMSCs-derived exosomal circHIPK3 (exo-circHIPK3) in diabetes mellitus (DM). METHODS: HFF-1 cells were cultured in high glucose (HG) medium or normal medium, and treated with UCMSCs-derived exo-circHIPK3 or miR-20b-5p mimics or Unc-51-like autophagy activating kinase 1 (ULK1) overexpression vector. The surface markers of UCMSCs were analyzed using a flow cytometer. The differentiation potential of UCMSCs was evaluated using oil red O staining, alizarin red staining and alkaline phosphatase (ALP) staining. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The miRNA expressions were analyzed by reverse transcription-quantitative polymerase chain reaction (qRT-PCR). Protein levels were quantified by western blot. An immunofluorescence staining was used for observing LC3 expression. The interaction between miR-20b-5p and circHIPK3, and between miR-20b-5b and ULK1 were identified by a RNA immunoprecipitation (RIP) assay and a luciferase reporter assay. RESULTS: Up-regulation of circHIPK3 was found in UCMSCs-derived exosomes. Exo-circHIPK3 decreased the miR-20b-5p level while increasing the contents of ULK1 and autophagy-related gene 13 (Atg13) in HG-induced fibroblasts. In addition, exo-circHIPK3 activated HG-induced fibroblast autophagy and proliferation. Overexpressed miR-20b-5p promoted fibroblast injury by inhibiting cell autophagy via the ULK1/Atg13 axis in HG conditions of high glucose. Moreover, exo-circHIPK3 enhanced autophagy and cell viability in HG-induced fibroblasts through the miR-20b-5p/ULK1/Atg13 axis. CONCLUSION: UCMSCs-derived exosomal circHIPK3 promoted cell autophagy and proliferation and accelerated the fibroblast injury repair by the miR-20b-5p/ULK1/Atg13 axis.

The correlation between trajectories of serum C3 variability and clinical course in Pediatric-onset systemic lupus erythematosus.

OBJECTIVE: The aim of this study is to investigate the usefulness which 2-year trajectories of C3 variability have in predicting clinical remission and systemic corticosteroids (SCS) use in pediatric patients with systemic lupus erythematosus (pSLE). METHODS: We recruited 189 confirmed pSLE patients from the electronic database of our hospital, all had undergone SCS treatment. The follow up period was 4.17-14.83 years. We used Group-Based Trajectory modeling to divide the patients into four different trajectory groups by their initial 2-year C3 variability. We divided the patients into groups A, B or C by their clinical course and SCS use. Statistical methods included Kruskal-Wallis and Chi-square tests and logic regression test. RESULTS: There were 4 separate trajectories. The distribution of groups A, B and C in these 4 trajectories showed a significant difference (p = 0.005). Initial C3 and C4 levels in these 4 revealed significant differences (p â‰¦ 0.001, p â‰¦ 0.016). When compared to other trajectories, trajectory1 showed a higher risk for persistent SCS use (p < 0.05). The distributions of severe clinical manifestations, including proteinuria, hematuria, CNS involvement and thrombocytopenia were different in these 4 trajectories (p = 0.003). Nevertheless, none of the above manifestations contributed to the risk of persistent SCS use. CONCLUSIONS: We have found 4 distinct C3 trajectories in pSLE patients. Distributions of clinical outcome groups were different in these 4 trajectories. Patients with trajectory1 displayed a higher risk for persistent SCS use, thus an earlier institution of immunosuppressant(s) and biological agents can be considered for these children.

Pediatric restrictive cardiomyopathy: a case report.

Restrictive cardiomyopathy (RCM) is a rare childhood cardiomyopathy that is a challenging diagnostic problem for clinicians. We describe a case of an 8-year-old girl with a 2-year history of shortness of breath on exertion. Electrocardiogram and echocardiography showed biatrial enlargement, while cardiac magnetic resonance showed biatrial dilation and normal pericardial thickness. Left and right heart catheterization revealed a left ventricular (LV) end-diastolic pressure (EDP) of 20 mmHg, right ventricular (RV) EDP of 13 mmHg, and pulmonary arterial systolic pressure of 51 mmHg. LV and RV pressure traces showed that LV and RV pressures moved concordantly with respiration, and that the systolic area index was 0.98. Cardiac catheterization data were therefore supportive of RCM. Next-generation sequencing identified a heterozygous variant of the troponin I gene (TNNI3; c.574C>T). Combining these findings led to a diagnosis of RCM. The patient's parents chose conservative treatment, but at the 12-month follow-up she died of worsening heart failure and cerebral infarction. This case emphasizes the need for cardiac catheterization and genetic testing in RCM, and suggests that anticoagulants should be recommended to reduce the risk of thromboembolic events.

Study on the application of 3D printing head film fixation technology in cranial radiotherapy.

Objective: To investigate the use of 3D printing technology to customize individualized precise radiotherapy head masks for cranial radiotherapy patients. Through the comparison with thermoplastic head film, evaluate the effect of this material on deep dose attenuation and body surface dose, and evaluate its positioning accuracy and repeatability for clinical application. Methods: Thirty patients with head and neck radiotherapy were divided into the control group and the experimental group. The control group used the traditional thermoplastic head film fixation technique for body position fixation, and the experimental group used the 3D printing head film fixation technique. The patient setup was verified by kV-CBCT scanning to obtain the translational setup error and rotational setup error in the X, Y, and Z directions. Results: At a depth of 5 cm, both materials have a radiation attenuation rate of <1%. At the surface location, the body surface dose of control group increased by approximately 27%. With a 3D printing head film, the body surface dose increased by approximately 18%. The positioning of two groups of patients was verified by the kV-CBCT, and a total of 232 data sets were obtained. The average translation positioning errors in the X, Y, and Z direction of control group and experimental group were 1.29 mm, 1.42 mm, 1.38 mm and 1.16 mm, 1.24 mm, 1.16 mm, respectively. The average rotation positioning error in the X, Y, and Z direction of control group and experimental group were 1.29°, 1.02°, 1.01° and 1.08°, 0.96°, 1.00°, respectively. The translational setup errors in the Y and Z directions and rotational setup errors in the X direction significantly differed between the control and experimental groups (all p<0.05), but no statistical significance was found in the other directions (all p>0. 05). Conclusion: Compared to the traditional thermoplastic head membranes, 3D printing head membranes has shown a reliable and reproducible interactional positioning accuracy. Of course, further investigations are needed before the new technology can be used on a regular basis.

Study on the thermal release characteristics and the correlation transformation mechanism of microscopic active groups of oxidized coal combustion in a deep mined-out area.

With the normalization of deep mining, the risk of residual coal spontaneous combustion (CSC) in deeply mined areas has gradually increased. To investigate the thermal characteristics and microgroup transformation mechanisms during the secondary oxidation of deep-well oxidized coal, a deep-well oxidation process was simulated in a synchronous thermal analyzer, and the thermal parameters of the oxidized coal were tested. The correlated transformation pathways of microscopic active groups was studied by electron paramagnetic resonance (EPR) and in situ diffuse reflectance (in situ FTIR) experiments during the reoxidation of oxidized coal. The results showed that with increasing deep-well ambient temperature and oxidation temperature, the characteristic temperature of coal gradually decreased, exothermic heat release gradually increased, and active aliphatic structures and -OH, -CHO and other active functional groups gradually accumulated and became distributed more uniformly. When the thermal conditions and oxidation temperature were very high (> 160 °C), the active free radicals in the oxidized coal were rapidly consumed, resulting in a gradual decrease in the characteristic temperature and heat release during the secondary oxidation process, while the contents of peroxy and carboxyl groups continued to increase. In the slow oxidation stage of oxidized coal, methyl groups were mainly transformed with hydroxyl and peroxide groups (r > 0.96), and the associated oxidative consumption of -CHO and -COOH mainly occurred in the rapid oxidation stage (r > 0.99). Geminal diols and peroxy groups are important intermediates in the coal-oxygen composite reaction process. With an increase in the deep-well temperature and initial oxidation temperature, the reoxidation tendency and heat release capacity of residual coal in the goaf gradually increased, and the risk of CSC intensified. The research results provide a theoretical reference for the prevention and control of coal fires in deep mines and play an important role in guiding environmental management and gas emissions reduction measures in mining areas.

[Analysis of Influencing Factors of Chlorophyll-a in Lake Taihu Based on Bayesian Network].

Global warming has aggravated the problem of lake eutrophication. As a typical large, eutrophic, shallow lake in China, the issue of cyanobacterial harmful algal blooms (cyanoHABs) was particularly prominent in Lake Taihu. We took Lake Taihu as the study area, using the meteorological (temperature, wind speed, rainfall, and sunshine hours), water quality (total nitrogen, total phosphorus, conductivity, pH, and chemical oxygen demand), and biological (chlorophyll-a in phytoplankton) monitoring data from 1992 to 2020. We built a simulation model of chlorophyll-a based on the Bayesian network model with continuous variables to study the chlorophyll-a level of Lake Taihu under different meteorological and water quality conditions. The 75th percentile of chlorophyll-a concentration was used as the threshold to judge the risk of cyanobacterial bloom. When the probability of chlorophyll-a concentration below this threshold was greater than 75%, it was regarded as "low risk" of cyanobacterial bloom outbreak. The results showed that the average level of "temperature wind ratio" (ratio of air temperature to wind speed) in spring was 6.67℃·s·m-1, and the probability of high chlorophyll-a was less than 75% when the total phosphorus concentration was less than 0.130 mg·L-1. The average "temperature wind ratio" level in summer was 10.52℃·s·m-1, and the probability of high chlorophyll-a was less than 75% when the total phosphorus concentration was less than 0.257 mg·L-1. The average level of total phosphorus concentration in autumn was 0.154 mg·L-1, and the probability of high chlorophyll-a was less than 75% when the "temperature wind ratio" was less than 6.30℃·s·m-1. Based on the above research, the chlorophyll-a model constructed by the Bayesian network model with continuous variables was further used to simulate the nutrient control objectives under different climate change backgrounds. In order to control chlorophyll-a in Lake Taihu at the:"low risk" level of cyanoHABs, the target concentration thresholds of total phosphorus needed to be controlled under the climate level background from 1992 to 2000, 2001 to 2010, and 2011 to 2020 were given. From 1992 to 2000, the threshold value of total phosphorus concentration was 0.135 mg·L-1 in spring, 0.174 mg·L-1 in summer, and 0.171 mg·L-1 in autumn. From 2001 to 2010, the threshold value of total phosphorus concentration was 0.115 mg·L-1 in spring, 0.164 mg·L-1 in summer, and 0.162 mg·L-1 in autumn. From 2011 to 2020, the threshold value of total phosphorus concentration was 0.059 mg·L-1 in spring, 0.145 mg·L-1 in summer, and 0.145 mg·L-1 in autumn. The results showed that the control of cyanoHABs in eutrophic lakes required more stringent nutrient control strategies with global warming. It provided a reference for preventing and controlling cyanoHABs and eutrophication in Lake Taihu. Previous studies have used multiple regression models, hydrodynamic numerical models, and other methods to predict chlorophyll-a concentrations or cyanobacterial blooms in lakes. However, there has been no study on the prediction of cyanoHABs in lakes based on the Bayesian network model with continuous variables and the "dynamic" evaluation of nutrient thresholds. Therefore, based on the seasonal meteorological, water quality, and biological monitoring data of Lake Taihu from 1992 to 2020, the chlorophyll-a model of Lake Taihu was constructed for the first time based on the Bayesian network model with continuous variables to simulate the chlorophyll-a concentration of Lake Taihu under different climate indicators and total phosphorus concentrations. The weight of its influencing factors was also analyzed, and the nutrient control objectives under different climate scenarios were "dynamically" evaluated.

EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates.

BACKGROUNDS: It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD. METHODS: The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan-Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed. RESULTS: In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p < 0.05). Smoking was associated with elevated EZH2 expression (p < 0.001). EZH2 was highly expressed in lung cancers with positive KRAS expression, and the correlation was significant in lung adenocarcinoma (r = 0.3129, p < 0.001). CMap was applied to determine the top 15 positively correlated drugs/molecules and the top 15 negatively correlated drugs/molecules. MK-1775, MK-5108, fenbendazole, albendazole, BAY-K8644, evodiamine, purvalanol-a, mycophenolic-acid, PHA-793887, and cyclopamine are potential drugs for patients with lung adenocarcinoma and high EZH2 expression. CONCLUSIONS: Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes.

Experimental Investigation on Interface Performance of UHPC-Strengthened NC Structure through Push-Out Tests.

Strengthening concrete structures with ultra-high performance concrete (UHPC) can both improve the bearing capacity of the original normal concrete (NC) structure and prolong the service life of the structure due to the high strength and durability of UHPC. The key to the synergistic work of the UHPC-strengthened layer and the original NC structures lies in the reliable bonding of their interfaces. In this research study, the shear performance of the UHPC-NC interface was investigated by the direct shear (push-out test) test method. The effects of different interface preparation methods (smoothing, chiseling, and planting straight and hooked rebars) and different aspect ratios of planted rebars on the failure mode and shear performance of the pushed-out specimens were studied. Seven groups of push-out specimens were tested. The results show that the interface preparation method can significantly affect the failure mode of the UHPC-NC interface, which is specifically divided into interface failure, planted rebar pull-out, and NC shear failure. The critical aspect ratio for the pull-out or anchorage of planted rebars in UHPC is around 2. The interface shear strength of straight-planted rebar interface preparation is significantly improved compared with that of the chiseled and smoothened interfaces, and as the embedding length of the planted rebar becomes longer, it first increases greatly and then tends to be stable when the rebar planted in UHPC is fully anchored. The shear stiffness of UHPC-NC increases with the increase of the aspect ratio of planted rebars. A design recommendation based on the experimental results is proposed. This research study supplements the theoretical basis of the interface design of UHPC-strengthened NC structures.

UCMSCs-derived exosomal circHIPK3 promotes ulcer wound angiogenesis of diabetes mellitus via miR-20b-5p/Nrf2/VEGFA axis.

AIMS: Experiments confirmed that circular RNAs contributed to the pathogenesis of diabetic foot ulcers (DFUs). CircHIPK3 was upregulated in type 2 diabetes mellitus (T2DM), but its role in DFU remained unknown. Our study aimed to investigate the regulatory functions of exosomal circHIPK3 and its potential mechanisms in DFU. METHODS: Exosomal size and distribution, marker proteins, and circHIPK3 levels were evaluated by transmission electron microscope, ExoView R200, western blot, and qRT-PCR. Flow cytometry, MTT, Wound healing assays, and tube formation assays were used to assess the roles of exosomal circHIPK3 in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). The relationships between Nrf2/VEGFA/circHIPK3 and miR-20b-5p, and between Nrf2 and VEGFA were determined by luciferase reporter assay and RNA immunoprecipitation. We used cell and mice models to investigate the mechanisms of exosomal circHIPK3 under diabetic conditions. RESULTS: CircHIPK3 was significantly upregulated in exo-circHIPK3 rather than exo-vector. Exo-circHIPK3 remarkably inhibited cell apoptosis but promoted cell proliferation, migration, and tube formation in HG-treated HUVECs. Luciferase reporter and RIP assays showed that miR-20b-5p targeted and inhibited Nrf2 and VEGFA, and circHIPK3 acted as a ceRNA of miR-20b-5p to inhibit the binding to its downstream genes Nrf2 and VEGFA. Mechanistically, circHIPK3 promoted cell proliferation, migration, and angiogenesis via downregulating miR-20b-5p to upregulate Nrf2 and VEGFA. However, the overexpressed miR-20b-5p could abolish the promoting effects of circHIPK3 overexpression on cell proliferation, migration, and tube formation under HG conditions. CONCLUSION: UCMSCs-derived exosomal circHIPK3 protected HG-treated HUVECs via miR-20b-5p/Nrf2/VEGFA axis. The exosomal circHIPK3 might be a therapeutic candidate to treat DFU.

Effects of FasL inhibitors on corneal apoptosis and Treg after corneal transplantation in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of intravitreal injection FasL inhibitors on corneal apoptosis, Fas, FasL expression, Treg numbers in blood and lymph nodes and rejection index in rats after corneal transplantation.METHODS:A total of 24 SD rats(24 eyes)who received penetrating keratoplasty were randomly divided into two groups: PBS group received intravitreal injection of PBS(12 rats, 12 eyes)and FasL inhibitor group(12 rats, 12 eyes). Rejection index was recorded every week and blood samples and lymph node were collected at 1, 3 and 5wk after surgery to analyze the proportions of Treg. Corneal tissue was collected for detecting the expression of Fas and FasL and number of apoptosis.RESULTS: The expression of Fas, FasL in FasL inhibitor group decreased significantly compared with the PBS group(all P&#x003C;0.05); Corneal cell apoptosis significantly decreased in FasL inhibitor group, and it was the lowest at 5wk after surgery; Treg numbers in blood and lymph nodes significantly increased in FasL inhibitor group at 3wk after surgery(all P&#x003C;0.05); rejection index of corneal transplantation in the FasL inhibitor group was significantly lower than that of PBS group(all P&#x003C;0.05).CONCLUSION:Intravitreal injection of FasL inhibitors after corneal transplantation could reduce the apoptosis in all layers of cornea, increase the number of Tregs in blood and lymph nodes, and alleviate rejection.

Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration.

Mesothelioma lies one of the most malignant tumors, in which the identification of the corresponding biomarkers is extremely critical. This study aims to investigate the prognostic value of enhancer homolog 2 (EZH2) mRNA expression in mesothelioma patients accompanied with its immune infiltration analysis. Gene expression, clinical information and enrichment analysis were obtained based on the Cancer Genome Atlas (TCGA), the immune infiltration analysis and bioinformatics analysis were performed. Clinical information and gene expression were obtained from 86 patients with mesothelioma based on TCGA database. Survival analysis, GSEA enrichment analysis, and immune infiltration analysis of EZH2 expression were carried out using R (version 3.6.3) (statistical analysis and visualization). The correlation of EZH2 expression with immune cell infiltration in mesothelioma was analyzed according to the TIMER database (Fig. https://cistrome.shinyapps.io/timer/ ). A univariate and multivariate analysis of general data obtained from the TCGA database was performed, involving age, gender, stage, pathological type, and whether they had received radiotherapy, the results indicated the association of high expression of EZH2 with poor prognosis in mesothelioma patients, with the worse prognosis in the High group (HR = 2.75, 95% CI 1.68-4.52, P < 0.010). Moreover, ROC curves showed that EZH2 expression predicted 1-year survival with an AUC of 0.740, 2-year survival with an AUC of 0.756, and 3-year survival with an AUC of 0.692, suggesting a robust predictive effect of EZH2 expression on prognosis. KEGG pathway analysis indicated five pathways showing the strongest positive correlation with EZH2 expression: cell cycle, DNA replication, Cell adhesion molecules cams, Primary immuno deficiency, Tsate transduction, and five pathways showing the strongest negative correlation with EZH2 expression: Glycolysis gluconeogenesis, Drug metabolism, cytochrome P450, retinol metabolism, fatty acid metabolism ribosome. We investigated the correlation between EZH2 expression and the level of immune infiltration in mesothelioma tissues. The results indicated that EZH2 expression played a critical role in immune infiltration, of which the high expression was correlated with the reduced number of NK cells, Mast cells, and Th17 cells. Moreover, mesothelioma patients with high EZH2 expression differ from those with low EZH2 expression in their tumor immune microenvironment. EZH2, as a new prognostic biomarker for mesothelioma, contributes to elucidating how changes in the immune environment promote the development of mesothelioma. Further analysis, EZH2 may serve as a biological test to predict the prognosis of mesothelioma.

Clinical Effect of Abdominal Massage Therapy on Blood Glucose and Intestinal Microbiota in Patients with Type 2 Diabetes.

The aim of the study was to investigate the clinical effects of abdominal massage on patients with type 2 diabetes mellitus (T2DM) and its influence on the intestinal microflora. We conducted a randomized, controlled clinical trial. A total of 60 patients with T2DM, who met the inclusion criteria, were randomly allocated to the control group, the routine massage group, and the abdominal massage group. The control group received health education and maintained their hypoglycemic drug treatment plan. The routine massage group and the abdominal massage group received different massage interventions. In addition to glucose and lipid metabolism indicators, we quantitatively analyzed the gut microbiota to assess the effects of massage on the intestinal microflora of patients with T2DM. Compared with the control group, the abdominal massage improved levels of glycated hemoglobin, total cholesterol, Enterobacter, and Bifidobacteria with significant differences (P = 0.02, P = 0.03, P = 0.03, and P = 0.03). The comparison within group showed that the levels of the four bacterial genera in the abdominal massage group revealed significant differences before and after treatment (P = 0.006, P < 0.001, P < 0.001, and P = 0.002). The comparison between the routine massage group and the abdominal massage group was not significantly different in all levels of test indices. The abdominal massage group regulated levels of Enterobacter and Lactobacilli to a greater extent than the routine massage group. Additionally, abdominal massage decreased Enterococcus levels. The results of this study showed that abdominal massage has clinical advantages over routine massage. Specifically, this intervention may correct microflora disturbances to a certain extent.