Analysis of Bulk Transcriptome Sequencing Data and in vitro Experiments Reveal SIN3A as a Potential Target for Diabetic Foot Ulcer.

Background: Diabetic foot ulcers (DFUs) represent a severe complication of diabetes associated with reduced quality of life, lower limb amputations, hospitalizations, increased incidence, and mortality. Importantly, a significant number of pathogenic genes remain unexplored in DFUs. Methods: A series of bioinformatics analyses were performed on publicly available bulk transcriptome sequencing datasets GSE134431 and GSE80178 to explore the transcriptomic changes in DFUs and select core genes for in vitro functional validation. In a focused examination, the differential expression analysis unveiled distinctions in gene expression patterns between DFUs and non-ulcerated diabetic skin tissues. Enriched functional annotations of differentially expressed genes were explored using the DAVID online tool. Protein-protein interaction analysis was conducted to investigate interactions among differentially expressed genes and select core genes. Knockdown or overexpression of core genes in HaCaT keratinocytes was performed to assess their impact on cell proliferation and migration. Results: Ten core genes were identified. Cell Counting Kit-8 (CCK-8) and scratch assays demonstrated that downregulation of the core gene SIN3A significantly inhibited the migration and proliferation of HaCaT keratinocytes, while overexpression of SIN3A reversed the high-glucose-induced suppression of HaCaT cell viability and migration. Conclusion: SIN3A expression is downregulated in DFUs. In vitro, SIN3A promotes the proliferation and migration of HaCaT keratinocytes, suggesting it may be a potential therapeutic target for DFUs.

Comparisons of Electrolyte Balance Efficacy of Two Gelatin-Balanced Crystalloid for Surgery Patients Under General Anesthesia: A Multi-Center, Prospective, Randomized, Single-Blind, Controlled Study.

Purpose: This study aimed to compare the electrolyte balance efficacies of two Gelatin-Balanced Crystalloid in clinical applications. Methods: A multi-center, prospective, randomized, single-blind, parallel controlled study was conducted among non-cardiac surgery patients, with clinical registration number ChiCTR2200062999. They were randomized into Succinylated Gelatin, Multiple Electrolytes and Sodium Acetate Injection (SG-MESAI) group (experimental group) and Succinylated Gelatin Injection (SGI) infusion group (control group). The same anesthetic induction technique, anesthetic method, and calculation method for the volume of colloid infusion were used in the two groups. Between-group differences in the changes in base excess (BE), Chloride ion (Cl-), bicarbonate radical (HCO3⁻) and other parameters were recorded at 15 min, 30 min after the infusion relative to the baseline. Hemodynamic indicators were determined at 30 min after colloid infusion. Safety follow-up was conducted by administering the following tests within 48 h±12 h after surgery. Results: A total of 225 subjects (full analysis set) were finally enrolled, with 110 subjects in the experimental group and 115 subjects in the control group. The baseline data were comparable between the two groups. At 15 min after infusion, the mean changes in BE, Cl- and HCO3⁻ concentration in the experimental group were smaller than those of the control group (P<0.001). At 30 min after surgery, the mean changes in BE, Cl-, HCO3⁻concentration and pH value were smaller in the experimental group than in the control group (P<0.05). The incidences of adverse events and adverse reactions in the experimental group was less than the control group, but the difference was not statistically significant (P≥0.05). Besides, no serious adverse events or adverse reactions were reported in any subjects. Conclusion: Succinylated Gelatin, Multiple Electrolytes and Sodium Acetate Injection maintained the balance of BE, Cl-, HCO3⁻ and pH value in a better way than Succinylated Gelatin Injection in non-cardiac surgery patients under general anesthesia.

Mechanisms of diabetic foot ulceration: A review.

Diabetic foot ulcers (DFUs) are associated with complex pathogenic factors and are considered a serious complication of diabetes. The potential mechanisms underlying DFUs have been increasingly investigated. Previous studies have focused on the three aspects of diabetic peripheral vascular disease, neuropathy, and wound infections. With advances in technology, researchers have been gradually conducting studies using immune cells, endothelial cells, keratinocytes, and fibroblasts, as they are involved in wound healing. It has been reported that the upregulation or downregulation of molecular signaling pathways is essential for the healing of DFUs. With a recent increase in the awareness of epigenetics, its regulatory role in wound healing has become a much sought-after trend in the treatment of DFUs. This review focuses on four aspects involved in the pathogenesis of DFUs: physiological and pathological mechanisms, cellular mechanisms, molecular signaling pathway mechanisms, and epigenetics. Given the challenge in the treatment of DFUs, we are hopeful that our review will provide new ideas for peers.

Human Keratinocyte-Derived Exosomal MALAT1 Promotes Diabetic Wound Healing by Upregulating MFGE8 via microRNA-1914-3p.

Purpose: Diabetic wound is a highly prevalent and refractory disease. Extensive studies have confirmed that keratinocytes and macrophages play an important role in the process of wound healing. Additionally, exosomes are regarded as a vital intercellular communication tool. This study aimed to investigate the role of human keratinocyte-derived exosomal MALAT1 in the treatment of diabetic wound by influencing the biological function of macrophages. Methods: We mainly assessed the function of MALAT1 on the biological changes of macrophages, and the expression of MALAT1 in the keratinocyte-exosomes analyzed by quantitative real-time polymerase chain reaction (RT-qPCR). The downstream interaction between RNAs or proteins was assessed by mechanistic experiments. Besides, we evaluated the effects of human keratinocyte-derived exosomal MALAT1 on diabetic wound healing in vivo to verify in vitro results. Results: We demonstrated that human keratinocyte-derived exosomal MALAT1 enhanced the biological functions of high glucose-injured macrophages, including phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. Mechanistically, MALAT1 accelerated the expression of MFGE8 by competitively binding to miR-1914-3p, thereby affecting the function of macrophages and the signal axis of TGFB1/SMAD3, and finally promoting the healing of diabetic wounds. Human keratinocyte-derived exosomal MALAT1 might promote collagen deposition, ECM remodeling, and expression of MFGE8, VEGF, and CD31 but reduce the expression of TGFB and SMAD3 in an in vivo model of diabetic mice wounds, which accelerated diabetic wound healing and restored its function. Conclusion: The current study revealed that human keratinocyte-derived exosomal MALAT1 would suppress miR-1914-3p to activate MFGE8 and eventually promote wound healing by enhancing macrophage phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. It proposed that keratinocyte-derived exosomes might have the capacity to serve as a new method for the clinical treatment of diabetic wound.

Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host.

Stem cell therapy emerges as an effective approach for treating various currently untreatable diseases. However, fatal and unknown risks caused by their systemic use remain to be a major obstacle to clinical application. We developed a functional single-cell RNA sequencing (scRNA-seq) procedure and identified that transcriptomic heterogeneity of adipose-derived stromal cells (ADSCs) in cultures is responsible for a fatal embolic risk of these cells in the host. The pro-embolic subpopulation of ADSCs in cultures was sorted by gene set enrichment analysis (GSEA) and verified by a supervised machine learning analysis. A mathematical model was developed and validated for the prediction of embolic risk of cultured ADSCs in animal models and further confirmed by its application to public data. Importantly, modification of culture conditions prevented the embolic risk. This novel procedure can be applied to other aspects of risk assessment and would help further the development of stem cell clinical applications.

Removal of both anionic and cationic dyes from wastewater using pH-responsive adsorbents of L-lysine molecular-grafted cellulose porous foams.

High adsorption efficiency, active to both anionic and cationic dyes and simple desorption are three main challenges of the existed adsorbents for decolorization of the dye-contained wastewaters. Porous foams based on L-lysine (Lys) molecular-grafted cellulose were firstly designed and fabricated to overcome those challenges. Cellulose were grafted with Lys in 1-butyl-3-methylimidazolium chloride (BMIMCl) via a chemical connection resulted from glycidyl methacrylate (GMA). The synthesized cellulose derivative (Cell-g-PGMA-Lys) was regenerated in the morphology of foam by non-solvent induced phase inversion from the BMIMCl-based solutions. The presence of Lys moieties and porous structure of Cell-g-PGMA-Lys were confirmed with a series of instrumental analysis. Both anionic reactive brilliant red X-3B (RBR X-3B) and cationic methylene blue (MB) were effectively adsorbed on and desorbed from Cell-g-PGMA-Lys by adjusting the solution pH value. Cell-g-PGMA-Lys had higher adsorption capacities than most of the reported adsorbents and was easy to separate from the decolorized water. It could be reused many times with little reduction of the adsorption capacity, which remained 86.9% and 92.5% for RBR X-3B and MB respectively after six adsorption-desorption cycles. The isothermal and kinetic adsorption proved that dyes were adsorbed single-layered on Cell-g-PGMA-Lys depending upon the electrostatic interaction between adsorbent and adsorbate.

The effects of circFBXL5 on the malignant biological behaviors of bladder cancer T24 cells by targeting miR-515-5p and its molecular mechanisms / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨circFBXL5通过靶向miR-515-5p影响膀胱癌T24细胞的增殖、迁移、侵袭及其分子机制。方法： 收集2020年4月至2020年6月间在苏州市中西医结合医院手术切除的41例膀胱癌组织及其癌旁组织，采用qPCR法检测circFBXL5、miR-515-5p的表达；双荧光素酶报告实验验证circFBXL5与miR-515-5p之间的靶向关系，体外培养人膀胱癌T24细胞，实验分为si-NC组、si-circFBXL5组、anti-miR-NC+si-circFBXL5组和si-circFBXL5+anti-miR-515-5p组；MTT法、细胞克隆形成实验、FCM、Transwell实验和WB法分别检测转染后T24细胞的增殖、细胞克隆形成、迁移、侵袭和凋亡及BAX、Bcl-2蛋白水平。结果：膀胱癌组织中circFBXL5呈高表达，miR-515-5p呈低表达（均P<0.05）；circFBXL5靶向且负向调控miR-515-5p的表达；敲减circFBXL5后T24细胞的增殖抑制率、凋亡率和BAX蛋白水平均显著增高（均P<0.05），细胞克隆形成数和迁移、侵袭细胞数均显著减少（均P<0.05），Bcl-2蛋白水平显著降低（P<0.05）；同时敲减circFBXL5和miR-515-5p可部分逆转敲减circFBXL5对T24细胞增殖的抑制作用。结论：circFBXL5通过调控miR-515-5p表达影响膀胱癌T24细胞的增殖、迁移、侵袭，circFBXL5和miR-515-5p可能膀胱癌治疗的潜在分子靶标。

Effects of Occupational Exposure to Waste Anesthetic Gas on Oxidative Stress and DNA Damage.

OBJECTIVE: The aim of the study was to investigate the potential effects of waste anesthetic gas (WAG) on oxidative stress, DNA damage, and vital organs. METHODS: A total of 150 members of the staff at a hospital were assigned to an exposure group or control group. The 68 operating room (OR) staff in the exposure group were exposed to WAG, and the 82 non-OR staff in the control group were not exposed to WAG. Air samples were collected in the OR, and the sevoflurane concentrations in the samples were determined. Superoxide dismutase (SOD), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) in plasma from the participants were determined to assess oxidative stress. Western blot analysis was used to detect γH2AX in peripheral blood to assess DNA damage. Hematopoietic parameters, liver function, kidney function, and changes in electrophysiology were assessed to identify the effects on the vital organs. RESULTS: The mean (±standard deviation) sevoflurane concentration in 172 air samples from 22 operating rooms was 1.11 ± 0.65 ppm. The superoxide dismutase activity and vital organ parameters (lymphocyte, hemoglobin, and total protein concentrations and heart rate) were significantly lower (P < 0.05) in the exposed group than the control group. The malondialdehyde, total bilirubin, and creatinine concentrations and QT and QTc intervals were significantly higher (P < 0.05) in the exposed group than the control group. There were no significant differences between the glutathione peroxidase activities and γH2AX concentrations for the exposed and control groups. CONCLUSIONS: Long-term occupational exposure to waste anesthetic gas may affect the antioxidant defense system and probably affects vital organ functions to some extent. No correlation between DNA damage and chronic exposure to WAG was observed.

Quality appraisal of clinical guidelines for venous thromboembolism prophylaxis in patients undergoing hip and knee arthroplasty: a systematic review.

INTRODUCTION: Venous thromboembolism (VTE) occurs in up to 40%-80% of patients after hip and knee arthroplasty. Clinical decision-making aided by guidelines is the most effective strategy to reduce the burden of VTE. However, the quality of guidelines is dependent on the strength of their evidence base. The objective of this article is to critically evaluate the quality of VTE prevention guidelines and the strength of their recommendations in VTE prophylaxis in patients undergoing hip and knee arthroplasty. METHODS: Relevant literature up to 16 March 2020 was systematically searched. We searched databases such as Web of Science, PubMed, EMBASE, Cumulative Index of Nursing and Allied Health Literature, China National Knowledge Infrastructure and WanFang and nine guidelines repositories. The identified guidelines were appraised by two reviewers using the Appraisal of Guidelines for Research and Evaluation II and appraised the strength of their recommendations independently. Following quality assessment, a predesigned data collection form was used to extract the characteristics of the included guideline. RESULTS: We finally included 15 guidelines. Ten of the included guidelines were rated as 'recommended' or 'recommended with modifications'. The standardised scores were relatively high in the domains of Clarity of Presentation, and Scope and Purpose. The lowest average standardised scores were observed in the domains of Applicability and Stakeholder Involvement. In reference to the domains of Rigour of Development and Editorial Independence, the standardised scores varied greatly between the guidelines. The agreement between the two appraisers is almost perfect (intraclass correlation coefficients higher than 0.80). A considerable proportion of the recommendations is based on low-quality or very-low-quality evidence or is even based on working group expert opinion. CONCLUSIONS: In summary, the majority of the recommendations are based on low-quality evidence, and further confirmation is needed. Furthermore, guideline developers should pay more attention to methodological quality, especially in the Stakeholder Involvement domain and the Applicability domain.

Association of insomnia disorder with sociodemographic factors and poor mental health in COVID-19 inpatients in China.

PURPOSE: To examine insomnia disorder and its association with sociodemographic factors and poor mental health in 2019 novel coronavirus (COVID-19) inpatients in Wuhan, China. DESIGN: and Methods: A total of 484 COVID-19 inpatients in Wuhan Tongji Hospital were selected and interviewed with standardized assessment tools. Insomnia disorder was measured by the Chinese version of the Insomnia Severity Index (ISI-7), a total score of 8 or more was accepted as the threshold for diagnosing insomnia disorder. RESULTS: The prevalence of insomnia disorder in the whole sample was 42.8%. Binary logistic regression analysis revealed that female gender, younger age, and higher fatigue and anxiety severity were more likely to experience insomnia disorder. CONCLUSION: Given the high rate of insomnia disorder status among COVID-19 inpatients in Wuhan, China, and its negative effects, follow-up assessments and appropriate psychological interventions for insomnia disorder are needed in this population.

Dialdehyde-ß-cyclodextrin-crosslinked carboxymethyl chitosan hydrogel for drug release.

A simple method was proposed for preparing the dialdehyde-ß-cyclodextrin (DA-ß-CD) cross-linked carboxymethyl chitosan (CMCS) hydrogels for drug delivery. DA-ß-CD was yielded from the sodium periodate oxidation of ß-CD. Phenolphthalein (PhP) was adopted as a model drug to study the drug loading and releasing properties of the obtained hydrogels. The results show that the ability of the hydrogel to load drug is affected by the aldehyde content of DA-ß-CD. The inclusion constant of DA-ß-CD toward PhP is lower than that of the original ß-CD and decreased with the rising of the aldehyde content. An increased cross-linking degree between DA-ß-CD and CMCS slows the PhP release to some extent. In comparison with glyoxal/CMCS, DA-ß-CD/CMCS presents better PhP release properties. Only 19.2 % of PhP loaded in glyoxal/CMCS was released within 24 h. Half of PhP loaded in DA-ß-CD/CMCS was released in 2 h and about 90 % was released within 12 h.

Nurses' objective knowledge regarding venous thromboembolism prophylaxis: A national survey study.

Venous thromboembolism (VTE) is a common vascular disorder with high mortality and morbidity. Clinical nurses are a pivotal group that can serve as first-line health care providers. Lack of knowledge about VTE is an important barrier to effective nursing performance. This study aimed to determine nurses' knowledge of VTE prophylaxis through a nationwide survey across China, to understand gaps between current knowledge, and guidelines, and to help improve clinical nursing.The survey included 5 topics with 68 items on VTE, including basic knowledge, risk assessment, basic prophylaxis, physical prophylaxis, and pharmacological prophylaxis.The survey was distributed to 106 AAA-grade hospitals throughout China; 5218 valid questionnaires were submitted for analysis. There were 5097 women and 121 men respondents, with average age 30.29 ±â€Š8.60 years. The average rate of correct responses regarding VTE knowledge was 59.90 ±â€Š15.63%; 77.81% of subjects answered more than half of the survey items correctly. Better knowledge about thromboprophylaxis was observed among nurses who were more highly educated, more experienced, had received continuing education, intensive care unit (ICU), and lead nurses. Correct response rates were 68.39 ±â€Š17.03%, 60.35 ±â€Š21.01%, 75.51 ±â€Š22.85%, 41.72 ±â€Š17.47%, and 46.01 ±â€Š21.22% for basic knowledge, risk assessment, basic prophylaxis, physical prophylaxis, and pharmacological prophylaxis, respectively.Respondents showed satisfactory results regarding basic prophylaxis, basic knowledge, and risk assessment for VTE; respondents had poorer knowledge regarding physical and pharmacological prophylaxis. Better mastery of knowledge about thromboprophylaxis was observed among nurses who were more highly educated, more experienced, had received continuous education, ICU, and lead nurses.This study suggested that nurse trainers should develop comprehensive educational programs that focus on low correct rate aspects. Higher-level continuous education could improve nurses' knowledge of thromboprophylaxis.

Waste anesthetic gas exposure and strategies for solution.

As inhaled anesthetics are widely used, medical staff have inevitably suffered from exposure to anesthetic waste gases (WAGs). Whether chronic exposure to WAGs has an impact on the health of medical staff has long been a common concern, but conclusions are not consistent. Many measures and equipment have been proposed to reduce the concentration of WAGs as far as possible. This review aims to dissect the current exposure to WAGs and its influence on medical staff in the workplace and the environment, and summarize strategies to reduce WAGs.

Surgical valve repair of isolated pulmonary valve endocarditis.

Isolated pulmonary valve endocarditis (IPE) is an uncommon clinical entity. We reported 4 cases of IPE without underlying heart diseases that required surgical interventions. Two of the present patients had predisposing factors that included a history of abdominal surgery in Case 1 and intravenous drug abuse in Case 3. All four patients presented with persistent fever together with pulmonary symptoms despite appropriate antibiotic management. Three of the patients underwent elective pulmonary valve repair, but Case 3 underwent an urgent surgical intervention due to uncontrolled septic shock. Pulmonary valve repair was performed using autologous pericardial patch in all 4 patients. All of them had immediate postoperative recovery and satisfactory outcomes in the follow-up.

Complete resection of a mediastinal solitary extramedullary plasmacytoma and reconstruction of right pulmonary artery and superior vena cava.

Solitary extramedullary plasmacytoma located in the thorax is a rare tumor. We present a 21-year-old patient who was diagnosed with a mediastinal solitary extramedullary plasmacytoma. Complete resection of the tumor with reconstruction of the right pulmonary artery and superior vena cava was performed. The patient is alive without evidence of recurrence 8 months after the operation. Extensive resection and reconstructive surgery with the addition of radiotherapy can prolong the patient's life.

Primary cardiac pheochromocytoma with multiple endocrine neoplasia.

PURPOSE: Cardiac pheochromocytoma with multiple endocrine neoplasia syndrome (MENS) is rare. We present a rare case of concurrent cardiac pheochromocytoma and pituitary adenoma, a rare variant of the MEN syndromes and a review of the literature with special emphasis on diagnosis and treatment. METHODS: Different from the single MENS type I or type II, Variant MENS' symptoms and signs are so nontypical that it is easy to make a misdiagnosis or missed diagnosis. One patient with variant MENS was treated surgically and relevant case data were collected. RESULTS: The perioperative course was uneventful. At 24-month follow-up, catecholamine levels returned to normal and no symptoms of pheochromocytoma was found. CONCLUSIONS: Cardiac pheochromocytoma with Multiple Endocrine Neoplasia can be treated by operation with good prognosis. Surgical removal to provide relief or effective control of symptoms is the treatment of choice.

Intravenous leiomyomatosis with intracardiac extension.

Intravenous leiomyomatosis with right intracardiac extension is rare. Surgical treatment of the tumor is still controversial because of the high postoperative risk of morbidity and mortality. We describe a series of 5 patients with these lesions who underwent elective operations with different strategies, including one-staged or two-staged resections and cardiopulmonary bypass with beating heart, cardioplegic arrest, or deep hypothermic circulatory arrest. We believe that this report represents one of the largest series of patients encountered in a single institution. In conclusion, radical resection is always possible and the outcomes are satisfactory with planned surgery.

Isolation and characterization of wheat straw lignin with a formic acid process.

There is a commercial need to increase the amount of industrial produced lignin. An 86.24 wt.% formic acid solution with 0.2M H(2)SO(4) as the catalyst was used to isolate the lignin of dewaxed wheat straw at different residence times and reaction temperatures. Lignin was extracted and purified separately from hydrolysates and residual solids after treatment. The lignin obtained has been characterized by FTIR (Fourier transform infrared), GPC (Gel permeation chromatography), and (1)H NMR (Nuclear magnetic resonance). Results from these analyses indicated that oxidative cleavage of bonds in the lignin macromolecule has occurred during the formic acid treatment, leading to formation of oligomers of lignin with lower molecular weight. Moreover, it was found that guaiacyl unit is the main structure, the content of syringyl unit is higher than that of the hydroxybenzyl unit and beta-O-4 together with beta-5 ether bonds is also identified in the molecular structure of lignin of wheat straw obtained from the formic acid process.