Effect of oral health education on improving knowledge, attitude, practice, and oral health status of patients with liver cancer: A quasi-experimental study.

PURPOSE: To evaluate the effectiveness of the PRECEDE-PROCEED model (PPM) in helping patients with liver cancer be aware of their knowledge, skills, and abilities in self-oral health behaviors and improve their oral health status. METHODS: This is a quasi-experimental study of 90 patients with liver cancer assigned to an oral health education or a control group. The intervention group was educated with the PRECEDE-PROCEED model. A brief oral scale and the knowledge, attitude, and practice oral health questionnaire were employed to measure the oral health status and cognitive behavioral ability to seek oral health in patients. RESULTS: Among 102 eligible patients, 90 (88.23%) agreed to participate in the present study and were divided to intervention (n = 45) or control (n = 45) groups. After the intervention and one month after discharge, the oral health scores of patients in the Intervention group were lower than those of the control group (P < 0.05). In addition, after the intervention and one month after discharge, the patients in the test group had higher scores on knowledge, beliefs, and behaviors of oral health than the control group (P < 0.05). One month after discharge, the mean knowledge and skills scores were significantly higher in the intervention group than in the control group. CONCLUSIONS: Our findings suggest that oral health education may be a useful health intervention for patients with liver cancer. It may also improve the knowledge and beliefs of liver cancer patients seeking oral health. Larger long-term investigations are necessary to provide more support for these preliminary conclusions.

Using machine-learning models to predict extubation failure in neonates with bronchopulmonary dysplasia.

AIM: To develop a decision-support tool for predicting extubation failure (EF) in neonates with bronchopulmonary dysplasia (BPD) using a set of machine-learning algorithms. METHODS: A dataset of 284 BPD neonates on mechanical ventilation was used to develop predictive models via machine-learning algorithms, including extreme gradient boosting (XGBoost), random forest, support vector machine, naïve Bayes, logistic regression, and k-nearest neighbor. The top three models were assessed by the area under the receiver operating characteristic curve (AUC), and their performance was tested by decision curve analysis (DCA). Confusion matrix was used to show the high performance of the best model. The importance matrix plot and SHapley Additive exPlanations values were calculated to evaluate the feature importance and visualize the results. The nomogram and clinical impact curves were used to validate the final model. RESULTS: According to the AUC values and DCA results, the XGboost model performed best (AUC = 0.873, sensitivity = 0.896, specificity = 0.838). The nomogram and clinical impact curve verified that the XGBoost model possessed a significant predictive value. The following were predictive factors for EF: pO2, hemoglobin, mechanical ventilation (MV) rate, pH, Apgar score at 5 min, FiO2, C-reactive protein, Apgar score at 1 min, red blood cell count, PIP, gestational age, highest FiO2 at the first 24 h, heart rate, birth weight, pCO2. Further, pO2, hemoglobin, and MV rate were the three most important factors for predicting EF. CONCLUSIONS: The present study indicated that the XGBoost model was significant in predicting EF in BPD neonates with mechanical ventilation, which is helpful in determining the right extubation time among neonates with BPD to reduce the occurrence of complications.

Current advances on the therapeutic potential of scutellarin: an updated review.

Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.

Wireless Bioelectronics for In Vivo Pressure Monitoring with Mechanically-Compliant Hydrogel Biointerfaces.

Recent electronics-tissues biointefacing technology has offered unprecedented opportunities for long-term disease diagnosis and treatment. It remains a grand challenge to robustly anchor the pressure sensing bioelectronics onto specific organs, since the periodically-varying stress generated by normal biological processes may pose high risk of interfacial failures. Here, a general yet reliable approach is reported to achieve the robust hydrogel interface between wireless pressure sensor and biological tissues/organs, featuring highly desirable mechanical compliance and swelling resistance, despite the direct contact with biofluids and dynamic conditions. The sensor is operated wirelessly through inductive coupling, characterizing minimal hysteresis, fast response times, excellent stability, and robustness, thus allowing for easy handling and eliminating the necessity for surgical extraction after a functional period. The operation of the wireless sensor has been demonstrated with a custom-made pressure sensing model and in vivo intracranial pressure monitoring in rats. This technology may be advantageous in real-time post-operative monitoring of various biological inner pressures after the reconstructive surgery, thus guaranteeing the timely treatment of lethal diseases.

Diagnostic performance of a multiplexed gastrointestinal PCR panel for identifying diarrheal pathogens in children undergoing hematopoietic stem cell transplant.

BACKGROUND: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection. METHODS: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays. RESULTS: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%). CONCLUSIONS: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.

The emerging roles of ac4C acetylation "writer" NAT10 in tumorigenesis: A comprehensive review.

The quick progress of epigenetic study has kindled new hope for treating many cancers. When it comes to RNA epigenetics, the ac4C acetylation modification is showing promise, whereas N-acetyltransferase 10 plays a wide range of biological functions, has a significant impact on cellular life events, and is frequently highly expressed in many malignant tumors. N-acetyltransferase 10 is an acetyltransferase with important biological involvement in cellular processes and lifespan. Because it is highly expressed in many malignant tumors, it is considered a pro-carcinogenic gene. The review aims to introduce NAT10, summarize the effects of ac4C acetylation on tumor growth from multiple angles, and discuss the possible therapeutic targeting of NAT10 and the future directions of ac4C acetylation investigations.

Metagenomic next-generation sequencing in detecting pathogens in pediatric oncology patients with suspected bloodstream infections.

BACKGROUND: Studies on mNGS application in pediatric oncology patients, who are at high risk of infection, are quite limited. METHODS: From March 2020 to June 2022, a total of 224 blood samples from 195 pediatric oncology patients who were suspected as bloodstream infections were enrolled in this study. Their clinical and laboratory data were retrospectively reviewed, and the diagnostic performance of mNGS was assessed. RESULTS: Compared to the reference tests, mNGS showed significantly higher sensitivity (89.8% vs 32.5%, P < 0.001) and clinical agreement (76.3% vs 51.3%, P < 0.001) in detecting potential pathogens and distinguishing BSI from non-BSI. Especially, mNGS had an outstanding performance for virus detection, contributing to 100% clinical diagnosed virus. Samples from patients with neutropenia showed higher incidence of bacterial infections (P = 0.035). The most identified bacteria were Escherichia coli, and the overall infections by gram-negative bacteria were significantly more prevalent than those by gram-positive ones (90% vs 10%, P < 0.001). Overall, mNGS had an impact on the antimicrobial regimens' usage in 54.3% of the samples in this study. CONCLUSIONS: mNGS has the advantage of rapid and effective pathogen diagnosis in pediatric oncology patients with suspected BSI, especially for virus. IMPACT: Compared with reference tests, mNGS showed significantly higher sensitivity and clinical agreement in detecting potential pathogens and distinguishing bloodstream infections (BSI) from non-BSI. mNGS is particularly prominent in clinical diagnosed virus detection. The incidence of bacterial infection was higher in patients with neutropenia, and the overall infection rate of Gram-negative bacteria was significantly higher than that of Gram-positive bacteria. mNGS affects the antimicrobial regimens' usage in more than half of patients.

miR-33a-3p regulates METTL3-mediated AREG stability and alters EMT to inhibit pancreatic cancer invasion and metastasis.

Recent studies have shown that amphoteric regulatory protein (AREG), a member of the epidermal growth factor (EGF) family, is expressed in many cancers and is an independent prognostic indicator for patients with pancreatic cancer, but whether AREG is regulated at the epigenetic level to promote the development of pancreatic cancer (PC) has not been elucidated. Our results support the notion that AREG is overexpressed in pancreatic cancer tissues and cell lines. Functionally, the deletion of AREG impedes pancreatic cancer (PC) cell proliferation, migration, and invasion. In addition, we identified and validated that methyltransferase-like 3 (METTL3) induced the m6A modification on AREG and facilitated the stability of AREG mRNA after sequencing. Additionally, we obtained experimental evidence that miR-33a-3p targets and inhibits METTL3 from taking action, as predicted by using the miRDB and RNAinter. Remediation experiments showed that miR-33a-3p inhibits PC progression through METTL3. In summary, this research reveals that miR-33a-3p inhibits m6A-induced stabilization of AREG by targeting METTL3, which plays a key role in the aggressive progression of PC. AREG could be a potential target for PC treatment.

Phthalates (PAEs) and reproductive toxicity: Hypothalamic-pituitary-gonadal (HPG) axis aspects.

Phthalates (PAEs) are widely used for their excellent ability to improve plastic products. As an essential endocrine axis that regulates the reproductive system, whether dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis is involved in reproductive toxicity mediated by environmental endocrine disruptors PAEs has become a hot topic of widespread concern. This study systematically reviewed the adverse effects of multiple PAEs on the HPG axis in different models and objectively discussed the possible underlying mechanisms. The abnormal release of gonadotropin-releasing hormone and gonadotropin, dysfunction of sex hormone receptors and steroid hormone synthesis, and general damage, including cell proliferation, oxidative stress, apoptosis, and autophagy have been confirmed to be involved in this process. Although it is widely established that PAEs induce HPG axis dysfunction, the specific mechanisms involved remain unclear. From a systematic review of relevant publications, it appears that the abnormal expression of peroxisome proliferator-activated, aryl hydrocarbon, and insulin receptors mediated by PAEs is key upstream event that induces these adverse outcomes; however, this inference needs to be further verified. Overall, this study aimed to provide reliable potential biomarkers for future environmental risk assessment and epidemiological investigation of PAEs.

The DEAD-box RNA helicase, DDX60, Suppresses immunotherapy and promotes malignant progression of pancreatic cancer.

Excessive proliferation, invasion, metastasis, and immune resistance in pancreatic cancer (PC) makes it one of the most lethal malignant tumors. Recently, DDX60 was found to be involved in the development of various tumors and in immunotherapy. Therefore, we aimed to investigate whether DDX60 is a new factor involved in PC immunotherapy. The DDX60 mRNA was screened using transcriptome sequencing (RNA-seq). The Cox and survival analysis of DDX60 was performed using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, clinical and immune infiltration data in the databases were analyzed and plotted using the R language. Clinical samples and in vitro experiments were used to determine the molecular evolution of DDX60 during PC progression. We found that DDX60 was upregulated in PC tissues (P value = 0.0083) and was associated with poor prognosis and short survival time of patients with PC. Results of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set variation analyses showed that viral defense, tumor, and immune-related pathways were significantly enriched in samples with high DDX60 expression. The Pearson correlation test demonstrated that DDX60 expression correlated strongly with immune checkpoint and immune system-related metagene clusters. Our results indicated that DDX60 promoted cell proliferation, migration, and invasion and was related to poor prognosis and immune resistance. Therefore, DDX60 may be a promising novel target for PC immunotherapy.

Synthesis and evaluation of Piperine analogs as thioredoxin reductase inhibitors to cause oxidative stress-induced cancer cell apoptosis.

Inhibiting thioredoxin reductase (TrxR) to disrupt the redox equilibrium and induce tumor cell apoptosis is a significant tumor therapeutic strategy. Piperine, a natural product from black pepper, has been demonstrated to suppress tumor cell proliferation by enhancing reactive oxygen species (ROS), subsequently leading to cell death. However, the development of Piperine as an active molecule is hampered by its weak cytotoxicity. To develop a compound with higher activity, we synthesized 22 Piperine analogs and evaluated their pharmacological properties. Ultimately, B5 was screened by the results of cytotoxicity and inhibition of TrxR activity. In contrast to Piperine, B5 had significant cytotoxicity with a 4-fold increase. The structure-activity relationship demonstrated that the introduction of an electron-withdrawing group into the benzene ring adjacent to the amino group, particularly in the meta-position, was positive and that shortening the olefin double bond had no appreciable impact on cytotoxicity. Further investigating the physiological activity of B5 in HeLa cells, we found that B5 selectively inhibits the activity of TrxR by binding to Sec residues on TrxR. B5 then induces cellular oxidative stress and finally leads to apoptosis. As a result, the study of B5 paved the way for further investigation into the modification and function of Piperine analogs as TrxR inhibitors.

Linc00662 m6A promotes the progression and metastasis of pancreatic cancer by activating focal adhesion through the GTF2B-ITGA1-FAK pathway.

Recurrence and metastasis are major factors associated with the poor prognosis of pancreatic cancer (PC). Previous studies have indicated that METTL3-mediated N6-methyladenosine (m6A) modification is closely associated with PC progression and prognosis. However, its underlying regulatory mechanisms remain unclear. In this study, we found that METTL3 was upregulated in PC tissues and cells and was associated with malignant tumor progression and poor progression-free survival in PC. Linc00662 was screened as a m6A-enriched RNA that promoted tumor growth and metastasis in PC cells and mouse models and was associated with poor clinical prognosis. Four m6A motifs were identified in Linc00662, which maintained the stability of Linc00662 in an IGF2BP3-coupled manner and were closely associated with the pro-tumor properties of Linc00662 in vitro and in vivo. ITGA1 was identified as a downstream gene regulated by Linc00662. Linc00662 recruites GTF2B to activate the transcription of ITGA1 in a m6A-dependent manner and initiates the formation of focal adhesions through the ITGA1-FAK-Erk pathway, thereby promoting malignant behavior in PC cells. The FAK inhibitor-Y15 obviously repressed tumor progression in Linc00662-overexpressing PC cells in vitro and in vivo. This study proposes a novel regulatory mechanism of Linc00662 in oncogene activation in PC and indicates that Linc00662 and its downstream genes are potential targets for PC therapy.

HOXB13 facilitates hepatocellular carcinoma progression by activating AKT/mTOR signaling pathway.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the sixth most common malignancies worldwide and is accompanied by high mortality. Homeobox B13 (HOXB13) has been shown to be involved in the development of various cancers. This study aimed to investigate the role of HOXB13 in HCC progression. MATERIALS AND METHODS: The expression of HOXB13 in HCC tumor tissues was analyzed using qRT-PCR and immunohistochemical staining . After overexpression or downregulation of HOXB13 in HCC cell lines, cell proliferation was detected by CCK8 assay and Ki67 staining and cell invasion ability were tested by transwell assay. Western blot assay was applied to analyze the effect of HOXB13 on related signaling pathways. In addition, the role of HOXB13 on HCC in vivo was explored using a HCC mouse model. IF and WB were performed to detect cell proliferation, apoptosis and related protein expression in mice tumor tissues. RESULTS: The results showed that the expression of HOXB13 was significantly increased in HCC tissues compared with adjacent tissues and positively correlated with the tumor stage and survival of HCC patients. Overexpression of HOXB13 promoted the proliferation and invasion of HCC cells and up-regulated the protein expression of AKT, mTOR and MMP2. In contrast, the downregulation of HOXB13 resulted in the opposite results. In vivo experiments, HOXB13 significantly promoted tumor growth in mice bearing HCC by promoting cell proliferation and inhibiting cell apoptosis. CONCLUSIONS: This study suggested that HOXB13 can facilitate HCC progression by activation of the AKT/mTOR signaling pathway. HOXB13 may be a novel target for HCC therapy.

SVF-GEL Cryopreserved for Different Times Exhibits Varied Preservation and Regeneration Potential After Transplantation in a Mouse Model.

BACKGROUND: Matrix vascular component (SVF) gels derived from fat preserve tissue integrity and cell viability under cryopreserved conditions, making them easy to inject again for later use. Here, we compared the preservation power and regeneration potential of SVF-gel under different cryopreservation times. METHODS: The SVF-gel stored under - 20 °C, without cryoprotectant cryopreservation for 5, 15, and 45 days, with fresh SVF-gel as control. We evaluated the rate of volume retention after thawing the SVF-gel and the apoptosis rate of adipose-derived stem cells. Next, we analyzed retention rated, adipogenesis, angiogenesis, and connective tissue hyperplasia of the grafts, one month after subcutaneously transplanting the specimen into immunodeficient mice. RESULTS: SVF-gel cryopreserved for 5 and 15 days exhibited no significant different in apoptosis rates relative to the control group. Extending the cryopreservation time to 45 days resulted in significantly increased and decreased apoptosis and volume retention rates of SVF-gel, respectively. SVF-gel grafts cryopreserved for 5 and 15 days exhibited no significant differences from those in the control group, although their weights and volumes still fluctuated. Extending the cryopreservation time to 45 days resulted in significantly decreased retention rates of the grafts. Histologically, extending freezing time resulted in a gradual decline in the graft's health adipose tissue, as well as decreased angiogenesis, and connective tissue hyperplasia. CONCLUSION: Simple freezing of SVF-gel at - 20 °C conferred them with sufficient cell viability. Notably, short-term cryopreservation did not significantly increase the apoptosis rate, and it still had a certain regeneration after transplantation. However, prolonging freezing time to 45 days resulted in increased apoptosis rate and worsened transplantation effect. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Identification and Validation of a Novel Model: Predicting Short-Term Complications After Local Flap Surgery for Skin Tumor Removal.

BACKGROUND The aim was to analyze the risk factors for the occurrence of complications after local flap transfer and to construct a simple prediction model to help surgeons in the perioperative screening of high-risk patients. MATERIAL AND METHODS Short-term complications were defined as any postoperative infection, dehiscence, bleeding, subcutaneous effusion, fat liquefaction, arteriovenous crisis, and tissue necrosis that required medical consultation or intervention. To explore 16 factors influencing short-term complications after local flap transfer, least absolute shrinkage and selection operator (LASSO) logistic regression was used to reduce the dimensionality of the data and to screen for predictors. Independent risk factors affecting the development of complications after local flap transfer were analyzed using logistic multiple regression models. The consistency (C-)index, receiver operating characteristic (ROC) curves, and calibration curves were used to check the model's discrimination and calibration. Decision curve analysis (DCA) curves were used to evaluate the clinical applicability of this model, and internal validation was assessed using bootstrap validation. RESULTS The C-index of the nomogram model to predict short-term complications after local flap transfer was 0.763 (95% CI: 0.702-0.824), the area under the ROC curve was 0.763, and the internal validation C-index was 0.747. The calibration curve showed good agreement between observed and predicted values, and the DCA showed the model can benefit patients. CONCLUSIONS The model identified the relevant factors influencing short-term complications after local flap transfer, facilitating the identification and targeted intervention of patients at high risk of flap complications after surgery.

Green autofluorescence of the index fingernails is a novel biomarker for noninvasive determinations on the status of tobacco smoking.

It is critical to discover novel biomarkers for tobacco smoking. Our study has indicated the green autofluorescence (AF) of Index Fingernails as a novel biomarker for rapid and noninvasive determinations on the status of tobacco smoking: The green AF intensity of the Index Fingernails of the smokers was remarkably higher than that of the nonsmokers in the natural populations. When the AF intensity of the Fingernails was used as the variable, the area under curve (AUC) for differentiating the smokers from the nonsmokers was 0.91. Similar results were obtained by analyzing the green AF of the Index Fingernails of the healthy populations and the patients of acute ischemic stroke. Collectively, our study has indicated the green AF of the Index Fingernails as a novel biomarker for tobacco smoking, based on which the first method for noninvasive, rapid and economical determinations on the status of tobacco smoking may be established.

Staphylococcal superantigen-like protein 10 induces necroptosis through TNFR1 activation of RIPK3-dependent signal pathways.

Staphylococcal aureus (S. aureus) infection can lead to a wide range of diseases such as sepsis and pneumonia. Staphylococcal superantigen-like (SSL) proteins, expressed by all known S. aureus strains, are shown to be involved in immune evasion during S. aureus infection. Here, we show that SSL10, an SSL family protein, exhibits potent cytotoxicity against human cells (HEK293T and HUVEC) by inducing necroptosis upon binding to its receptor TNFR1 on the cell membrane. After binding, two distinct signaling pathways are activated downstream of TNFR1 in a RIPK3-dependent manner, i.e., the RIPK1-RIPK3-MLKL and RIPK3-CaMKII-mitochondrial permeability transition pore (mPTP) pathways. Knockout of ssl10 in S. aureus significantly reduces cytotoxicity of the culture supernatants of S. aureus, indicating that SSL10 is involved in extracellular cytotoxicity during infection. We determined the crystal structure of SSL10 at 1.9 Å resolution and identified a positively charged surface of SSL10 responsible for TNFR1 binding and cytotoxic activity. This study thus provides the description of cytotoxicity through induction of necroptosis by the SSL10 protein, and a potential target for clinical treatment of S. aureus-associated diseases.

An automated, rapid fluorescent immunoassay to quantify serum soluble programmed death-1 (PD-1) protein using testing-on-a-probe biosensors.

OBJECTIVES: Soluble programmed death-1 (sPD-1) plays an essential role in the pathogenesis and progression of various diseases, including chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). Currently, there is no Food and Drug Administration-approved sPD-1 immunoassay available for routine clinical testing. Most sPD-1 detections employed enzyme-linked immunosorbent assay (ELISA) method for research purpose, which is complicated by intensive manual operation and cannot achieve automatic detection. Therefore, we aimed to develop an automated, rapid immunoassay for sPD-1 measurement based on testing-on-a-probe (TOP) biosensors and evaluate its performance in patients with hepatic diseases. METHODS: We developed an automatic fluorescent immunoassay using TOP biosensors using a pair of mouse anti-PD-1 monoclonal antibodies (mAbs), which were evaluated by biolayer interferometry. The sensitivity, linearity, and repeatability of the novel immunoassay were analyzed, and its compatibility with an established ELISA kit was evaluated. Further, we quantified sPD-1 level in healthy individuals as well as patients with CHB, hepatic cirrhosis, and HCC. RESULTS: The TOP assay to quantify sPD-1 was developed and performed on an automatic fluorescent analyzer within 20 min, which showed good precision with coefficients of variation less than 10% and good linearity ranging from 2 to 3,000 pg/mL. The results tested by our TOP assay correlated well with the established ELISA assay (r=0.92, p<0.0001). Using our TOP assay, sPD-1 was significantly elevated in patients with chronic hepatitis, hepatic cirrhosis and hepatocarcinoma if compared to healthy control, respectively (p<0.0001). CONCLUSIONS: An automated, rapid fluorescent immunoassay to quantify serological sPD-1 protein using TOP biosensors was developed and showed acceptable analytical performance including precision, linearity, and good correlation with the established ELISA assay, with the great potential in clinical practice.

Inhibition of USP7 suppresses advanced glycation end-induced cell cycle arrest and senescence of human umbilical vein endothelial cells through ubiquitination of p53.

Diabetes mellitus is a n arising public health concern, and diabetic foot is one of the most common complications of diabetes. Current management for diabetic foot cannot reach optimal remission. In this study, we aim to explore the mechanism underlying the pathogenesis of diabetic foot and provide novel strategies for the treatment of diabetic foot. A total of 10 normal skin tissues and 20 diabetic foot ulcer specimens are collected. Cell proliferation is determined by CCK-8 assay. Cell cycle is determined by flow cytometry, and cell senescence is evaluated by ß-galactosidase staining. Co-immunoprecipitation assay is used to explore the interaction between USP7 and p53. Advanced glycation end products (AGEs) are used to establish diabetic cell model, and streptozotocin (STZ) is used to establish diabetic rat model. Our results showed that USP7 expression is increased in diabetic foot ulcer and in human umbilical vein endothelial cells (HUVECs) after treatment with AGEs. Inhibition of USP7 can reduce cell cycle arrest and cell senescence in HUVECs. Moreover, USP7 can interact with p53 and promote its expression through mediating its deubiquitination. Knockdown of p53 can reverse USP7-mediated cell cycle arrest and cell senescence in HUVECs. In diabetic rats, HBX 41108, the specific inhibitor of USP7, can significantly accelerate wound healing. Our study reveals that the inhibition of USP7 can suppress AGEs-induced cell cycle arrest and cell senescence of HUVECs through promoting p53 ubiquitination. USP7 is a potential target for the treatment of diabetic foot ulcers.

Predictors of Bronchopulmonary Dysplasia in 625 Neonates with Respiratory Distress Syndrome.

OBJECTIVE: This study was designed to investigate the predictors of bronchopulmonary dysplasia in neonates with respiratory distress syndrome. METHODS: This was a single-center retrospective cohort study conducted between 1 January 2015 and 31 December 2020. A total of 625 neonates with respiratory distress syndrome (RDS) were enrolled. Demographic data, clinical presentations, complications and related treatment information were collected and analyzed. We used bivariate and multivariate logistic-regression analyses to determine significant predictors of bronchopulmonary dysplasia (BPD) in RDS neonates. RESULTS: In these 625 neonates, 102 (16.3%) of them developed BPD. Bivariate analysis and multivariate logistic-regression analyses revealed that birthweight, gestational age under 32 weeks, duration of oxygen therapy over 10 days, asphyxia, patent ductus arteriosus, transfusion of red blood cells (packed red blood cells) and surfactant use were significantly associated with the development of BPD. CONCLUSION: Birthweight, gestational age <32 weeks, total duration of oxygen therapy >10 days, asphyxia, patent ductus arteriosus, need for red blood cell infusion, and the use of pulmonary surfactant were important predictors of BPD in neonates with RDS.