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Enhanced catalytic performance of penicillin G acylase by covalent immobilization onto functionally-modified magnetic Ni<sub>0.4</sub>Cu<sub>0.5</sub>Zn<sub>0.1</sub>Fe<sub>2</sub>O<sub>4</sub> n

by Zhixiang Lv, Zhou Wang, Shaobo Wu, Xiang Yu

With the emergence of penicillin resistance, the development of novel antibiotics has become an urgent necessity. Semi-synthetic penicillin has emerged as a promising alternative to traditional penicillin. The demand for the crucial intermediate, 6-aminopicillanic acid (6-APA), is on the rise. Enzyme catalysis is the primary method employed for its production. However, due to certain limitations, the strategy of enzyme immobilization has also gained prominence. The magnetic Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles were successfully prepared by a rapid-combustion method. Sodium silicate was used to modify the surface of the Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles to obtain silica-coated nanoparticles (Ni0.4Cu0.5Zn0.1Fe2O4-SiO2). Subsequently, in order to better crosslink PGA, the nanoparticles were modified again with glutaraldehyde to obtain glutaraldehyde crosslinked Ni0.4Cu0.5Zn0.1Fe2O4-SiO2-GA nanoparticles which could immobilize the PGA. The structure of the PGA protein was analyzed by the PyMol program and the immobilization strategy was determined. The conditions of PGA immobilization were investigated, including immobilization time and PGA concentration. Finally, the enzymological properties of the immobilized and free PGA were compared. The optimum catalytic pH of immobilized and free PGA was 8.0, and the optimum catalytic temperature of immobilized PGA was 50°C, 5°C higher than that of free PGA. Immobilized PGA in a certain pH and temperature range showed better catalytic stability. Vmax and Km of immobilized PGA were 0.3727 μmol·min-1 and 0.0436 mol·L-1, and the corresponding free PGA were 0.7325 μmol·min-1 and 0.0227 mol·L-1. After five cycles, the immobilized enzyme activity was still higher than 25%.

A Mendelian randomization study on the causal association of circulating cytokines with colorectal cancer

by Youqian Kong, Xiaoyu Wang, Hongyun Xu, Shaoxuan Liu, Rui Qie

Background

Circulating cytokines have been associated with colorectal cancer (CRC). However, their causal correlation remains undetermined. This investigation uses genetic data to evaluate the mechanism that links circulating cytokines and CRC via Mendelian Randomization (MR).

Methods

A two-sample MR evaluation was carried out to investigate the mechanism associating circulating cytokines and CRC in individuals of European ancestry. The Genome-wide association studies statistics, which are publically accessible, were used. Eligible instrumental SNPs that were significantly related to the circulating cytokines were selected. Multiple MR analysis approaches were carried out, including Simple Mode, inverse variance weighted (IVW), MR-Egger, Weighted Mode, Weighted Median, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.

Results

The evidence supporting the association of genetically predicted circulating levels with the increased risk of CRC was revealed; these included vascular endothelial growth factor (OR = 1.352, 95% CI: 1.019–1.315, P = 0.024), interleukin-12p70 (OR = 1.273, 95% CI: 1.133–1.430, P = 4.68×10−5), interleukin-13 (OR = 1.149, 95% CI: 1.012–1.299, P = 0.028), interleukin-10 (OR = 1.230, 95% CI: 1.013–1.493, P = 0.037), and interleukin-7 (OR = 1.191, 95% CI: 1.023–1.386 P = 0.024). Additionally, MR analysis negative causal association between macrophage colony stimulating factor and CRC (OR = 0.854, 95% CI: 0.764–0.955, P = 0.005). The data from Simple Mode, Weighted Median, MR-Egger, and Weighted Mode analyses were consistent with the IVW estimates. Furthermore, the sensitivity analysis indicated that the presence of no horizontal pleiotropy to bias the causal estimates.

Conclusion

This investigation identified a causal association between circulating cytokines levels risk of CRC and may provide a deeper understanding of the pathogenesis of CRC, as well as offer promising leads for the development of novel therapeutic targets for CRC.

Risk prediction and treatment assessment in glioma patients using SEER database: a prospective observational study

Por: Li · X. · Shao · Y. · Wang · Z. · Zhu · J.
Objectives

To use a nomogram to predict the risk of mortality and estimate the impact of current treatment on the prognosis of glioma patients.

Methods

A total of 3798 cases were obtained from the Surveillance Epidemiology and End Results database according to the selection criteria. A nomogram was built on the independent clinical factors screened by the variance inflation factor, univariate analyses and a multivariate Cox regression model. Then, categorising the overall population into high-risk, medium-risk and low-risk groups using nomogram-derived risk scores, to study the impact of treatment on different subgroups’ survival outcomes. Furthermore, based on the postmatch cohorts, the influences of treatment on survival outcomes were assessed by the log-rank test.

Result

Age, race, stage of disease, histological type, histological grade, surgery, radiotherapy and chemotherapy were identified as the independent prognostic factors. A nomogram with good discrimination and consistency was built. Generally, the patients who underwent surgery, radiotherapy and chemotherapy were more likely to achieve better prognosis than those who did not, except for those who received radiotherapy in the low-risk cohort and those who underwent surgery in the high-risk cohort. Furthermore, the isocitrate dehydrogenase 1/2 (IDH1/2) wild-type patients with surgery, radiotherapy or chemotherapy tended to have higher survival probabilities, while some inconsistent results were observed in the IDH mutant-type cohort.

Conclusion

Surgery, radiotherapy and chemotherapy improved the prognosis, while appropriate selection of topical treatment for the low-risk or high-risk patients deserves further consideration. IDH status gene might be a reliable indicator of therapeutic effectiveness.

Understanding the patterns and health impact of indoor air pollutant exposures in Bradford, UK: a study protocol

Por: Ikeda · E. · Hamilton · J. · Wood · C. · Chatzidiakou · L. · Warburton · T. · Ruangkanit · A. · Shao · Y. · Genes · D. · Waiblinger · D. · Yang · T. C. · Giorio · C. · McFiggans · G. · O'Meara · S. P. · Edwards · P. · Bates · E. · Shaw · D. R. · Jones · R. L. · Carslaw · N. · McEachan · R.
Introduction

Relative to outdoor air pollution, there is little evidence examining the composition and concentrations of indoor air pollution and its associated health impacts. The INGENIOUS project aims to provide the comprehensive understanding of indoor air pollution in UK homes.

Methods and analysis

‘Real Home Assessment’ is a cross-sectional, multimethod study within INGENIOUS. This study monitors indoor air pollutants over 2 weeks using low-cost sensors placed in three rooms in 300 Born in Bradford (BiB) households. Building audits are completed by researchers, and participants are asked to complete a home survey and a health and behaviour questionnaire, in addition to recording household activities and health symptoms on at least 1 weekday and 1 weekend day. A subsample of 150 households will receive more intensive measurements of volatile organic compound and particulate matter for 3 days. Qualitative interviews conducted with 30 participants will identify key barriers and enablers of effective ventilation practices. Outdoor air pollution is measured in 14 locations across Bradford to explore relationships between indoor and outdoor air quality. Data will be analysed to explore total concentrations of indoor air pollutants, how these vary with building characteristics, and whether they are related to health symptoms. Interviews will be analysed through content and thematic analysis.

Ethics and dissemination

Ethical approval has been obtained from the NHS Health Research Authority Yorkshire and the Humber (Bradford Leeds) Research Ethics Committee (22/YH/0288). We will disseminate findings using our websites, social media, publications and conferences. Data will be open access through the BiB, the Open Science Framework and the UK Data Service.

Influence of closed‐incision negative‐pressure wound therapy on the incidence of surgical site wound infection in patients undergoing spine surgery: A meta‐analysis

Abstract

The present meta-analysis was conducted to comprehensively assess the impact of closed-incision negative-pressure wound therapy (ciNPWT) on the incidence of surgical site infections (SSIs) in patients undergoing spinal fusion surgery, thereby aiming to provide evidence-based support for the prevention of postoperative wound infections during spinal surgery. Relevant studies pertaining to the application of ciNPWT in spinal surgery were retrieved through searches of the PubMed, Embase, MEDLINE and Cochrane Library databases, spanning from their inception to May 2023. The literature screening and data extraction were performed by two researchers based on predefined inclusion and exclusion criteria, followed by a quality assessment of the included studies. Meta-analyses were performed using the odds ratios (ORs) and standardised mean differences (SMDs) as effect variables. RevMan 14.0 and STATA 17.0 were employed for meta-analysis of the extracted data. In total, eight articles involving 1198 patients, including 391 in the experimental group and 807 in the control group, were included. The meta-analysis results revealed that ciNPWT significantly reduced the incidence of SSIs in patients undergoing spinal fusion surgery (OR, 0.39; 95% CI: 0.22–0.67, p = 0.0007); however, it did not lead to a reduction in hospital stay duration (SMD: −0.48, 95% CI: −0.98 to 0.01, p = 0.06). Existing evidence suggests that ciNPWT has a positive impact on patients undergoing spinal fusion surgery, as it significantly reduces the incidence of postoperative surgical site wound infections; however, it does not result in a shorter hospital stay for patients.

Effect of mitomycin C and 5‐fluorouracil on wound healing in patients undergoing glaucoma surgery: A meta‐analysis

Abstract

Increased intraocular pressure (IOP) is a risk factor for glaucoma. One treatment option is trabeculectomy. Antimetabolic agents are used in the operation to decrease the post-operative scarring of the wound. The two most common medicines are Mitomycin C (MMC) and 5-Fluorouracil (5-FU). The aim of this research is to assess the effect of MMC on post-operation wound healing in comparison with 5-FU in addition to trabeculectomy. Well, we went through four common databases. Our language was limited to English during the study. The last time we looked at the e-databases was August 2023. Case control studies were performed where MMC resulted in better wound healing than 5-FU. Researchers selected a total of 1023 trials and eventually selected six trials for data analysis. Four hundred and ninety one cases of glaucoma were treated with trabeculectomy. Among them, 246 were given MMC and 245 were given 5-FU during operation. Six trials showed that there was no statistical difference between MMC and 5-FU in the incidence of post-operative wound leak in glaucoma patients who received trabeculectomy (OR, 1.21; 95% CI, 0.63–2.30 p = 0.57); Five trials demonstrated that MMC was associated with a reduced risk of post-operative corneal damage compared to 5-FU injection (OR, 0.18; 95% CI, 0.06–0.56 p = 0.003); In both trials, the incidence of post-operative bleeding was not significantly different from that of 5-FU injected in the MMC group (OR, 0.33; 95% CI, 0.05–2.16 p = 0.25). Our results indicate that MMC is superior to 5-FU in the reduction of post-operative corneal injury. Additional comparisons between MMC and 5-FU are required in order to increase the reliability and effectiveness of these findings.

Long-term efficacy of transanal local excision versus total mesorectal excision after neoadjuvant treatment for rectal cancer: A meta-analysis

by Yihui Lei, Li Lin, Qiming Shao, Weiping Chen, Guoyan Liu

Aim

The purpose of this meta-analysis is to compare the long-term efficacy of transanal local excision (TLE) versus total mesorectal excision (TME) following neoadjuvant therapy for rectal cancer.

Method

The Web of Science, Pubmed, Medline, Embase, and the Cochrane Library were systematically searched for correlational research. The Newcastle-Ottawa Scale and the Cochrane risk of bias tool were used to assess the quality of cohort studies (CSs) and randomized controlled trials (RCTs), respectively. Statistically analyzed using RevMan5.4.

Result

A total of 13 studies, including 3 randomized controlled trials (RCTs) and 10 cohort studies (CSs), involving 1402 patients, were included in the analysis. Of these, 570 patients (40.66%) underwent TLE, while 832 patients (59.34%) underwent TME. In the meta-analysis of CSs, no significant difference was observed between the TLE group and TME group regarding 5-year overall survival (OS) and 5-year disease-free survival (DFS) (P > 0.05). However, the TLE group had a higher rates of local recurrence (LR) [risk ratio (RR) = 1.93, 95%CI (1.18, 3.14), P = 0.008] and a lower rates of 5-years local recurrence-free survival (LRFS) [hazard ratio (HR) = 2.79, 95%CI (1.04, 7.50), P = 0.04] compared to the TME group. In the meta-analysis of RCTs, there was no significant difference observed between the TLE group and TME group in terms of LR, 5-year OS, 5-year DFS, and 5-year disease-specific survival (P > 0.05).

Conclusion

After undergoing neoadjuvant therapy, TLE may provide comparable 5-year OS and DFS to TME for rectal cancer. However, neoadjuvant therapy followed by TLE may has a higher LR and lower 5-year LRFS compared to neoadjuvant therapy followed by TME, so patients should be carefully selected. Neoadjuvant therapy followed by TLE may be a suitable option for patients who prioritize postoperative quality of life. However, the effectiveness of this approach requires further research to draw a definitive conclusion.

Quercetin and its derivatives for wound healing in rats/mice: Evidence from animal studies and insight into molecular mechanisms

Abstract

Aimed to clarify the effect of quercetin and its derivatives on wound healing in animal experiments. PubMed, Embase, Science Direct, Web of Science, SinoMed, Vip Journal Integration Platform, China National Knowledge Infrastructure and WanFang databases were searched for animal experiments investigating the effect of quercetin and its derivatives on wound healing to April 2023. The Review Manager 5.4 software was used to conduct meta-analysis. Eighteen studies were enrolled in this article. According to the SYRCLE's RoB tool assessment, these studies exposed relatively low methodological quality. It was shown that animals with cutaneous wound receiving quercetin had faster wound healing in wound closure (%) than the control group. Moreover, the difference in efficacy gradually emerged after third day (WMD = 7.13 [5.52, 8.74]), with a peak reached on the tenth day after wounding (WMD = 19.78 [17.82, 21.74]). Subgroup analysis revealed that quercetin for wound closure (%) was independent of the types of rats and mice, wound area and with or without diabetes. Clear conclusion was also shown regarding the external application of quercetin for wound healing (WMD = 17.77 [11.11, 24.43]). A significant reduction in the distribution of inflammatory cells occurred in the quercetin group. Quercetin could increase blood vessel density (WMD = 1.85 [0.68, −3.02]), fibroblast distribution and collagen fraction. Biochemical indicators, including IL-1β, IL-10, TNF-α, TGF-β, vascular endothelial growth factor (VEGF), hydroxyproline and alpha-smooth muscle actin (α-SMA), had the consistent results. Quercetin and its derivatives could promote the recovery of cutaneous wound in animals, through inhibiting inflammatory response and accelerating angiogenesis, proliferation of fibroblast and collagen deposition.

Clinical application of posterior tibial artery or peroneal artery perforator flap in curing plate exposure after ankle fracture fixation

Abstract

The study aims to evaluate the clinical application of posterior tibial artery or peroneal artery perforator flap in the treatment of plate exposure after ankle fracture fixation. A posterior tibial artery or peroneal artery perforator flap was used on 16 patients with plate exposure after ankle fracture fixation in our hospital between July 2018 and July 2021. The time required to harvest the flap, the amount of intraoperative blood loss, the duration of postoperative drainage tube placement, the outcome of the flap and the healing observed at the donor site are reported. The sizes of the flaps were 2.5–7.0 cm × 5.0–18.0 cm and averaged 4.0 cm × 12.0 cm. The time required to harvest the posterior tibial artery or peroneal artery perforator flap ranged from 35 to 55 min and averaged 45 min. The amount of intraoperative blood loss ranged from 20 to 50 mL and averaged 35 mL. The duration of postoperative drainage tube placement ranged from 3 to 5 days and averaged 4 days. A total of 15 flaps survived and one flap had partial necrosis and survived after conservative treatment. All donor area defects were directly sewed and stitched without complications. There are multiple advantages of the posterior tibial artery or peroneal artery perforator flap, including simple preparation technique, reliable repair of the defects and without the need for performing microvascular anastomosis. It can be safely used in curing plate exposure after ankle fracture fixation and worth popularizing in grassroots hospitals.

Effect of open surgical and percutaneous dilatational tracheostomy on postoperative wound complications in patients: A meta‐analysis

Abstract

Tracheostomy is one of the most common operations. The two main methods of tracheostomy are open surgical tracheostomy (OST) and percutaneous dilatational tracheostomy (PDT). In critical cases, the combination of these two approaches is especially crucial, with the possibility of successful outcomes and low complications. Thus, the purpose of this system is to analyse the effects of both methods on the outcome of postoperative wound. In this research, we performed a systematic review of Cochrane Library, PubMed, Web of Science and Embase, to determine all randomized controlled trials (RCTs) that are comparable in terms of postoperative injury outcomes. Eleven RCTs were found after screening. This study will take the necessary data from the selected trials and evaluate the documentation for RCTs. PDT was associated with a lower incidence of infection at the wound site than OST (OR, 4.46; 95% CI: 2.84–7.02 p < 0.0001), and PDT decreased blood loss (OR, 2.88; 95% CI: 1.62–5.12 p = 0.0003). But the operation time did not differ significantly in both PDT to OST (MD, 4.65; 95% CI: −1.19–10.48 p = 0.12). The meta-analyses will assist physicians in selecting the best operative procedure for critical cases of tracheostomy. These data can serve as guidelines for clinical management and in the design of future randomized, controlled studies.

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