Publications by authors named "Weiguang Li"

114 Publications

Analysis of Continuous Prevalence Survey of Healthcare-Associated Infections Based on the Real-Time Monitoring System in 2018 in Shandong in China.

Biomed Res Int 2021 11;2021:6693889. Epub 2021 Jun 11.

Department of Infection Control, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.

Background: Healthcare-associated infection (HAI) is a serious threat to the safety of patients worldwide. The prevalence survey is widely used to explore and study the characteristics of HAI. However, the annual continuous prevalence survey of hospital-acquired infections has not been reported so far.

Aim: This study is aimed at examining the occurrence and development trend of HAIs dynamically and accurately.

Methods: An annual continuous HAI prevalence survey based on the real-time monitoring system was conducted in representative hospitals from different regions in Shandong in China. . A total of 64 hospitals participated in the survey, and 2,741,433 patients were monitored in 2018. The highest prevalence of HAIs in Shandong was 3.83% (February 15), the lowest was 1.85% (February 28), and the average was 2.45%. The percentile distribution of prevalence of HAIs in this study was as follows: P10, 2.23%; P25, 2.31%; P50, 2.41%; P75, 2.55%; and P90, 2.73%.

Conclusion: This study dynamically and accurately showed the occurrence and development trend of HAIs in Shandong in 2018. The results of this study can be used as a reference for the HAI prevalence survey in various medical institutions in Shandong and provide the basis for the regional HAI prevention and control strategy.
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http://dx.doi.org/10.1155/2021/6693889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213461PMC
June 2021

Investigation and Analysis of Sharp Injuries among Health Care Workers from 36 Hospitals in Shandong Province, China.

Biomed Res Int 2021 11;2021:5698483. Epub 2021 Jun 11.

Department of Infection Control, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.

Background: This study investigated and analyzed the current situation of sharp injuries among health care workers (HCWs) in China's Shandong Province.

Methods: By means of questionnaire survey, the incidence of sharp injuries among HCWs from 36 hospitals in China's Shandong Province in October 2019 was investigated, and the results of this survey were compared with those of October 2012.

Results: A total of 48165 HCWs were investigated. 549 cases of sharp injuries occurred. The incidence of sharp injuries was 1.14%, which was significantly lower than that in October 2012 (9.71%). In the occupational distribution of sharp injuries among HCWs, the proportion of nurses was 58.65%, doctors 23.32%, and interns 12.02%. Among the distribution of sharp injury departments, general wards, operating rooms, intensive care units, disinfection supply centers, and outpatient clinics were the high-incidence sites of occupational exposure among HCWs. The main instruments causing sharp injuries in HCWs were syringes, scalp steel needles, surgical suture needles, vacuum blood collection needles, and glass slides. Drug administration, double-handed loop needle cap, blood extraction, surgical suture needle, and arteriovenous needle extraction were high-risk operations causing sharp instrument injuries in HCWs.

Conclusion: The incidence of sharp injuries among HCWs from 36 hospitals in Shandong Province in October 2019 was significantly lower than that in October 2012. Sharp injuries were a common type of occupational exposure for HCWs. The occurrence of sharp injuries should be effectively reduced by changing wrong habitual behavior and implementing standard protective measures.
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http://dx.doi.org/10.1155/2021/5698483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214496PMC
June 2021

Inter and intra-observer errors for postoperative total hip radiographic assessment using computer aided design.

Acta Orthop Belg 2021 Mar;87(1):65-71

Plain radiographic assessment of primary total hip arthroplasty following surgery remains to be the commonest radiological assessment. The current paper, studies the accuracy and concordance between observers reviewing these radiographs. A prospective radiographic and medical note review of ten patients who underwent total hip replacement for primary osteoarthritis, with a mean age of 69 years. Early and 6 weeks postoperative x-rays were assessed for hip profile and version profile using computer aided design (CAD) by two observers on two different occasions. The observers were Orthopaedic surgeons who perform arthroplasty of the hip. The results were analyzed statistically. Dimensions, including Femoral offset, medial offset and ilioischial offset showed a high degree of inter- film and intra-film correlation, with inter-class cor- relation (ICC) over 0.8. Except of the intra-film correlation of ilioischial offset measured on the post- operative films (p=0.067) by the first rater, all the intra and inter film correlation were significantly over the benchmark of 0.6. In terms of stem alignment, cup inclination and cup version, the intra-film correlation by rater n°2 ranges from 0.574 to 0.975 and were significantly over the benchmark of 0.6, except in the case of cup inclination measured on the 6 th​ week follow-up ; meanwhile the intra-film correlation by rater n°1 ranges from 0.581 to 0.819 and none were significantly over the benchmark of 0.6. The inter-rater reliability and inter-film correlation showed a dichotomy of results among different dimensions of the measurement. Dimensions of femoral offset, medial offset and ilioischial offset showed a substantial degree of reliability in terms of inter-rater reliability, inter-film correlation, and intra-rater/film reliability.
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March 2021

Exogenous N-acyl-homoserine lactones accelerate resuscitation of starved anaerobic granular sludge after long-term stagnation.

Bioresour Technol 2021 Jun 3;337:125362. Epub 2021 Jun 3.

Tianjin Key Laboratory of Clean Energy and Pollution Control, School of Energy and Environmental Engineering, Hebei University of Technology, Tianjin 300401, PR China. Electronic address:

So as to accelerate the resuscitation of starved anaerobic granular sludge after long-term stagnation, an innovative method was tried derived from the regulation of N-acyl-homoserine lactones (AHLs)-mediated quorum sensing (QS). The mixture of four AHLs was added to the starved anaerobic granular sludge system in this research. The results confirmed that the exogenous AHLs shortened the recovery time of the granular sludge, and improved the treatment performance and methanogenic capacity of the recovered anaerobic sludge to the level before stagnation. At the same time, exogenous AHLs enhanced the synthesis of extracellular polymeric substances (EPS) during the resuscitation period of starved anaerobic granular sludge. The outcomes of microbial composition detection showed that the change of bacterial and methanogenic bacteria communities towards accelerated performance recovery was significantly correlated with exogenous AHLs. This exploration provided a new technical idea for speeding up the recovery of starved anaerobic granular sludge.
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http://dx.doi.org/10.1016/j.biortech.2021.125362DOI Listing
June 2021

Insights into influences of sucrose amendment on nitrification and denitrification in sewage sludge composting.

Chemosphere 2021 Aug 15;276:130245. Epub 2021 Mar 15.

Institute of Microbiology, Heilongjiang Academy of Sciences, 150010, Harbin, China.

Sucrose amendment could promote ammonia assimilation and reduce nitrogen loss in sewage sludge (SS) composting, but the effects of sucrose amendment on nitrification and denitrification are still unknown that were firstly researched in present paper. Result showed that sucrose amendment reduced 33.0% of NO emission by changing the physicochemical indexes, nitrogen forms, related bacteria and functional genes. In the sucrose treatment, the higher nitrifying bacteria community, amoA and nxrA genes abundance were, the lower hao, narG、nirS、nirK and norB genes abundance were. Based on the correlation analysis, the number of nitrifying bacteria was significantly positively correlated with NO and nxrA abundance, indicating that sucrose amendment promoted the growth of nitrifying bacteria, the contents of NO and the activity of nitrite oxidation. Moreover, contents of NO were positively correlated with NO emission, narG, nirS and norB abundance, indicating that denitrification was the main path of NO generated.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130245DOI Listing
August 2021

Ginsenoside Rh1 attenuates ovalbumin-induced asthma by regulating Th1/Th2 cytokines balance.

Biosci Biotechnol Biochem 2021 Jul;85(8):1809-1817

Department of Geriatrics, Hangzhou Red Cross Hospital, Xiacheng District, Hangzhou City, Zhejiang Province, China.

Ginsenoside Rh1 (Rh1) has anti-inflammatory effects in asthma mice, but the underlying mechanism remains unclear. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to construct asthma model. Mice received Rh1 or tiotropium bromide 0.5 h before OVA challenge. Airway morphology and airway remodeling were assessed by HE staining and Masson's trichrome staining, respectively. Th1/Th2 cytokines in serum or broncho alveolar lavage fluid (BALF) were measured by ELISA kits. Rh1 significantly alleviated the lung resistance and airway resistance, and reduced the number of total inflammation cells, eosinophils, neutrophils, and lymphocytes in BALF of the asthmatic mice. The morphological changes and collagen deposition of airway were also reduced by Rh1 in asthmatic mice. The increase of Eotaxin, IL-4, IL-5, IL-13, and IL-33 and the decrease of IL-12 and IFN-γ in both BALF and serum of OVA exposed mice were reversed by Rh1. Rh1 attenuates OVA-induced asthma in the mice model by regulating Th1/Th2 cytokines balance.
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http://dx.doi.org/10.1093/bbb/zbab099DOI Listing
July 2021

Application of glucose for improving NH-N removal in micro-polluted source water by immobilized heterotrophic nitrifiers at low temperature.

Chemosphere 2021 Sep 1;278:130459. Epub 2021 Apr 1.

School of Environment, Harbin Institute of Technology, Harbin, China. Electronic address:

Bio-enhanced activated carbon (BEAC) filters have shown potential in source water purification. The key drawback of this system is the difficulty of the set-up at low temperature. Here, glucose was applied to help immobilize more functional heterotrophic nitrifiers and further improve NH-N removal by BEAC. Results showed that pre-loading glucose on granular activated carbon could achieve better immobilization efficiency with 5.12 × 10 CFU/g-DW C biomass and 3.77 mg TF/L/g-DW C dehydrogenase activity after artificial immobilization, which were separately 12.5 and 4.2 times of the control. 95-d running data at different conditions showed the superiority of both immobilization and NH-N removal could last and defend environment changes during relatively long period. Even at the end of operating, the abundance of targeting genus (Acinetobacter) still occupied 9.59% of microbial communities on BEAC, while this value was only 1.24% without pre-loading glucose. Biolog-ECO plate analysis found pre-loading glucose improved organic nitrogen metabolism effectively, along with carbohydrate, amino, alcohol, amine and carboxylic acid metabolism on BEAC.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130459DOI Listing
September 2021

Integrin-dependent microgliosis mediates ketamine-induced neuronal apoptosis during postnatal rat retinal development.

Exp Neurol 2021 Jun 26;340:113659. Epub 2021 Feb 26.

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China; Center for Brain Science, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. Electronic address:

Purpose: Remodeling of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) plays a pivotal role for microglia in developing retina. We tested whether integrin-dependent microgliosis mediates ketamine-induced neuronal apoptosis in the developing rat retina.

Methods: We performed immunofluorescence assays to investigate the role of integrin receptors expressed in the microglia in ketamine-induced neuronal apoptosis. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to investigate the protein and mRNA levels of cytokines (TNF-α, IL-1β) and/or chemokines (CCL2, CXCL6, CXCL10, and CXCL12). Experiments were performed using whole-mount retinas dissected from P7 Sprague-Dawley rats.

Results: Integrin receptors expressed in microglia were upregulated in ketamine-induced neuronal apoptosis in the early developing rat retina. Downregulating integrin receptors with RGD peptide ameliorated ketamine-induced microgliosis through: 1) ameliorating the change in microglia morphology from immature ramified microglia to an amoeboid state; 2) decreasing the number of microglia and intensity of activated microglia in the retinal ganglion cell layer (GCL); and 3) decreasing cytokine (TNF-α and IL-1β) and chemokine (CCL2, CXCL10) levels in the retinal tissue. Inhibition of activated microglia with minocycline or the blockade of cytokines (TNF-α and IL-1β) with a receptor antagonist (RA) attenuated neuronal apoptosis after exposure to ketamine.

Conclusions: The upregulation of integrin β1 receptors in the microglia acts as a signaling molecule, triggering microgliosis to aggravate ketamine-induced neuronal apoptosis via the release of TNF-α and IL-1β in the early developing rat retina.
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http://dx.doi.org/10.1016/j.expneurol.2021.113659DOI Listing
June 2021

Nitrate removal from low C/N wastewater at low temperature by immobilized Pseudomonas sp. Y39-6 with versatile nitrate metabolism pathways.

Bioresour Technol 2021 Apr 2;326:124794. Epub 2021 Feb 2.

Key Laboratory of Functional Inorganic Material Chemistry, Heilongjiang University, Harbin 150080, China.

For solving the challenge in nitrate removal from low C/N wastewater at low temperature, Pseudomonas sp. Y39-6 was isolated and used in nitrate removal. It showed aerobic-heterotrophic denitrification with rate of 1.77 ± 0.31 mg/L·h and unusual aerobic-autotrophic nitrate removal (rate of 0.324 mg/L·h). The aerobic-autotrophic nitrate removal mechanisms were deep investigated by analyzing the nitrate removal process and genomic information. At aerobic-autotrophic condition, the strain Y39-6 could assimilate nitrate to amino acid (NO + PHA + CO → CHON) with the carbon source from Polyhydroxyalkanoic acid (PHA) degradation and CO fixation. Flagella motivation, swarming activity and extracellular polymeric substances (EPS) production regulated Pseudomonas sp. Y39-6 forming biofilm. Carriers immobilized with Pseudomonas sp. Y39-6 were used in moving bed biofilm reactor (MBBR) and achieved 24.83% nitrate removal at C/N < 1 and 4 °C. Results of this study provided a practical way for nitrogen removal from low C/N wastewater in cold region.
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http://dx.doi.org/10.1016/j.biortech.2021.124794DOI Listing
April 2021

Effect of voltage intensity on the nutrient removal performance and microbial community in the iron electrolysis-integrated aerobic granular sludge system.

Environ Pollut 2021 Apr 27;274:116604. Epub 2021 Jan 27.

UNESCO-IHE, Institute for Water Education, Westvest 7, 2601, DA Delft, the Netherlands.

The effects of voltage intensity on the nutrient removal performance and microbial community in the iron electrolysis-integrated aerobic granular sludge (AGS) system were investigated over a period of 15 weeks. Results revealed that the application outcomes of iron electrolysis for AGS systems relied on voltage intensity. When a constant voltage of 1.5 V was applied, the sludge granulation was most obviously accelerated with a specific growth rate of the sludge diameter of 0.078 day, and the removal efficiencies of total nitrogen (TN) and total phosphorus (TP) increased by 14.1% and 20.2%, respectively, compared to the control reactor (without the iron electrolysis-integration). Moreover, the AGS developed at different voltages included different microbial communities, whose shifts were driven by the Fe content and the average diameter of AGS. Both heterotrophic nitrifiers and mixotrophic denitrifiers were significantly enriched in the AGS developed at 1.5 V, which effectively enhanced TN removal. Together with the response of the functional genes involved in Fe, N, and P metabolism, the electrolytic iron-driven nutrient degradation pathway was further elaborated. Overall, this study clarified the optimum voltage condition when iron electrolysis was integrated into the AGS system, and revealed the enhancement mechanism of this coupling technology on nutrient removal during the treatment of low-strength municipal wastewater.
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http://dx.doi.org/10.1016/j.envpol.2021.116604DOI Listing
April 2021

Improving sewage sludge compost process and quality by carbon sources addition.

Sci Rep 2021 Jan 14;11(1):1319. Epub 2021 Jan 14.

School of Environmental Engineering, Harbin Institute of Technology, Box no. 2602, 73 Huanghe Road, Harbin, 150090, Heilongjiang, China.

In present study, the effects of carbon sources on compost process and quality were evaluated in the lab-scale sewage sludge (SS) composting. The composting experiments were performed for 32 days in 5 L reactors. The results showed that carbon sources could change the nitrogen conversion and improve the compost quality. Especially, the readily degradable carbon source could promote organic matter degradation, improve nitrogen conversion process and accelerate compost maturation. The addition of glucose and sucrose could increase dissolved organic carbon, CO emission, dehydrogenase activity, nitrification and germination index during the SS composting. That's because glucose and sucrose could be quickly used by microbes as energy and carbon source substance to increase activity of microbes and ammonia assimilation. What's more, the NH emission was reduced by 26.9% and 32.1% in glucose and sucrose treatments, respectively. Therefore, the addition of readily degradable carbon source could reduce NH emission and improve compost maturity in the SS composting.
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http://dx.doi.org/10.1038/s41598-020-79443-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809052PMC
January 2021

A highly efficient protein degradation system in Bacillus sp. CN2: a functional-degradomics study.

Appl Microbiol Biotechnol 2021 Jan 2;105(2):707-723. Epub 2021 Jan 2.

State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, 72 Binhai Rd, Qingdao, 266237, Shandong, China.

A novel protease-producing Bacillus sp. CN2 isolated from chicken manure composts exhibited a relatively high proteolytic specific activity. The strain CN2 degradome consisted of at least 149 proteases and homolog candidates, which were distributed into 4 aspartic, 30 cysteine, 55 metallo, 56 serine, and 4 threonine proteases. Extracellular proteolytic activity was almost completely inhibited by PMSF (phenylmethylsulfonyl fluoride) rather than o-P, E-64, or pepstatin A, suggesting that strain CN2 primarily secreted serine protease. More importantly, analysis of the extracellular proteome of strain CN2 revealed the presence of a highly efficient protein degradation system. Three serine proteases of the S8 family with different active site architectures firstly fragmented protein substrates which were then degraded to smaller peptides by a M4 metalloendopeptidase that prefers to degrade hydrophobic peptides and by a S13 carboxypeptidase. Those enzymes acted synergistically to degrade intact substrate proteins outside the cell. Furthermore, highly expressed sequence-specific intracellular aminopeptidases from multiple families (M20, M29, and M42) accurately degraded peptides into oligopeptides or amino acids, thus realizing the rapid acquisition and utilization of nitrogen sources. In this paper, a systematic study of the functional-degradome provided a new perspective for understanding the complexity of the protease hydrolysis system of Bacillus, and laid a solid foundation for further studying the precise degradation of proteins with the cooperative action of different family proteases. KEY POINTS: • Bacillus sp. CN2 has relatively high proteolytic specific activity. • Bacillus sp. CN2 harbors a highly efficient protein degradation system. • The site-specific endopeptidases were secreted extracellular, while the sequence-specific aminopeptidases played a role in the cell.
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http://dx.doi.org/10.1007/s00253-020-11083-zDOI Listing
January 2021

Neutrophil-to-Lymphocyte Ratio Is Independently Associated With Severe Psychopathology in Schizophrenia and Is Changed by Antipsychotic Administration: A Large-Scale Cross-Sectional Retrospective Study.

Front Psychiatry 2020 30;11:581061. Epub 2020 Oct 30.

Neuro-Psychiatric Institute, Nanjing Medical University Affiliated Brain Hospital, Nanjing, China.

Immunological and inflammatory mechanisms play an important role in schizophrenia. The neutrophil-to-lymphocyte ratio (NLR) is a value obtained by dividing the absolute number of neutrophils by the absolute lymphocyte count and represents a biomarker of systemic inflammatory response. There are studies investigating NLR association with psychopathology. However, the relationship has been only studied in small numbers of patients with schizophrenia, which leads to conflicting results and makes the meta-analytic data difficult to interpret. The aim of this study is to perform large-scale cross-sectional analysis on the potential correlation between NLR and disease severity in schizophrenic patients with or without medication. This cross-sectional retrospective study was conducted in Nanjing Medical University Affiliated Brain Hospital. We identified inpatients with schizophrenia between July 12, 2018 and March 27, 2019 and collected data of NLR, the Clinical Global Impression Severity scale (CGI-S) score and the Brief Psychiatric Rating Scale (BPRS) score. The records of 1,144 identified patients (10.8% drug-free patients) were analyzed. We found that NLR was significantly decreased in schizophrenic patients after antipsychotic administration and there was the discrepant correlation between NLR and psychiatric symptoms in patients with or without antipsychotic medication. The results of multivariate logistic regressions showed that NLR was positively associated with the severity of disease (i.e., the CGI-S score and the BPRS total score) in drug-free patients, and it was negatively associated with the BPRS negative symptoms (i.e., the BPRS negative symptoms score) in drug-therapy patients. The study is the first to confirm the hypothesis that NLR is independently associated with severe psychopathology in schizophrenia and is changed by antipsychotic administration.
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http://dx.doi.org/10.3389/fpsyt.2020.581061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661461PMC
October 2020

Exogenous N-acyl-homoserine lactones promote the degradation of refractory organics in oligotrophic anaerobic granular sludge.

Sci Total Environ 2021 Mar 2;761:143289. Epub 2020 Nov 2.

Tianjin Key Laboratory of Clean Energy and Pollution Control, School of Energy and Environmental Engineering, Hebei University of Technology, Tianjin 300401, PR China. Electronic address:

For refractory industrial wastewaters, anaerobic granular sludge technology cannot be widely used because of its limited treatment capacity, so strengthening the anaerobic degradation of refractory organics should be discussed. In this paper, the feasibility of adding exogenous N-acyl-homoserine lactones (AHLs) to promote the degradation of refractory organics in oligotrophic anaerobic granular sludge was addressed. The results showed that, after easily-degradable organics were completely metabolized, exogenous AHLs strengthened the further degradation of refractory organics and improved the methanogenic activity of anaerobic granular sludge. In addition, adding AHLs could promote the secretion of more extracellular polysaccharides and proteins by anaerobic microorganisms to resist the oligotrophic environment. Microbiological analysis showed that adding AHLs significantly optimized the microbial community in oligotrophic anaerobic granular sludge. With the regulation of AHLs, the abundance proportion of hydrolytic acidifying bacteria for refractory organics in bacterial community and the abundance proportion of acetotrophic methanogens in methanogens community increased obviously. Exogenous AHLs showed concentration-related effects on the optimization of bacteria and methanogens, and AHLs of higher concentration were beneficial to the succession of community structure in a better direction. Exogenous regulation of AHLs-mediated QS provided an attractive strategy for enhancing the anaerobic degradation of refractory organics, and proposed a technical idea for the application of anaerobic granular sludge technology in refractory industrial wastewaters.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143289DOI Listing
March 2021

Ligation-occluded endoscopic injection sclerotherapy: a novel retrograde strategy for gastroesophageal varices obliteration.

Endoscopy 2020 Oct 23. Epub 2020 Oct 23.

Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1055/a-1275-9674DOI Listing
October 2020

Influence of spent mushroom substrate and molasses amendment on nitrogen loss and humification in sewage sludge composting.

Heliyon 2020 Sep 22;6(9):e04988. Epub 2020 Sep 22.

Institute of Microbiology, Heilongjiang Academy of Sciences, 150010, Harbin, China.

The present study included lab-scale sewage sludge (SS) composting amended by molasses and spent mushroom substrate (SMS) in 5 L composting reactor system. The influence of molasses and SMS amendment on nitrogen loss and humification of SS composting was evaluated. The results showed that SMS amendment, especially combination with molasses raised composting temperature, increased CO volatilization, promoted organic matter degradation, improve germination index and humification process. The addition of SMS and molasses contain carbohydrates used as carbon source and energy substance by microorganisms could increase microbial activity and ammonia assimilation. In the SMS + molasses treatments, NH volatilization was reduced by 33.1%-37.3% and NO volatilization was only 17.8%-25.4% of that in the control treatment, furthermore, the nitrogen loss rate was reduced by 27.2%-32.2%. Consequently, the addition of SMS and molasses improved the compost maturity and reduced nitrogen loss in the SS composting process.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511750PMC
September 2020

Enhanced Safety and Antitumor Efficacy of Switchable Dual Chimeric Antigen Receptor-Engineered T Cells against Solid Tumors through a Synthetic Bifunctional PD-L1-Blocking Peptide.

J Am Chem Soc 2020 11 2;142(44):18874-18885. Epub 2020 Oct 2.

The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province and State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 210009, P. R. China.

Chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) therapy has an excellent efficacy in cancer treatment, especially its impressive results in hematological malignancies. Unfortunately, its application on solid tumors is challenged by the off-target effects caused by lacking of tumor specific antigens and the immunosuppression caused by the tumor microenvironment. We constructed a switchable dual receptor CAR-T cell (sdCAR-T) whose activity relied upon double antigens (mesothelin and fluorescein isothiocyanate) and was strictly controlled by a "switch" (FPBM) consisting of a PD-L1 blocking peptide conjugated to fluorescein isothiocyanate. SdCAR-T cells were activated only when FPBM and cognate tumor cells expressing both PD-L1 and mesothelin coexist. Importantly, long-term proliferation experiments and the pharmacodynamic study showed a stronger antitumor activity of this system compared to the second generation mesothelin CAR-T cells. In view of this novel treatment paradigm being safer and more effective than traditional CAR-T cells, it may become a new strategy for the treatment of solid tumors.
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http://dx.doi.org/10.1021/jacs.0c08538DOI Listing
November 2020

TRPV4 Overexpression Promotes Metastasis Through Epithelial-Mesenchymal Transition in Gastric Cancer and Correlates with Poor Prognosis.

Onco Targets Ther 2020 21;13:8383-8394. Epub 2020 Aug 21.

Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Purpose: Transient receptor potential vanilloid 4 (TRPV4) has been reported to be involved in the progression of several human tumors. Nevertheless, clinical significance and molecular mechanism of TRPV4 in gastric cancer (GC) remain poorly defined.

Patients And Methods: Immunohistochemistry assays were used to investigate the correlation between the expression of TRPV4 and epithelial-mesenchymal transition (EMT) markers in human GC tissues. The correlations between TRPV4 expression and clinicopathological features and between TRPV4 expression and survival rates were also examined. TRPV4 knockdown was performed by using small interfering RNAs. In vitro, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and transwell assay were employed to further explore the biological functions of TRPV4, and Western blotting was used to evaluate the changes in the expression of TRPV4 protein and EMT-related proteins in HGC-27 and MGC-803 human GC cell lines.

Results: TRPV4 expression was upregulated in GC tissues and cell lines. TRPV4 overexpression was associated with greater depth of tumor invasion, lymph node metastasis, higher TNM stage, poor overall survival, and worse disease-free survival. TRPV4 expression was inversely correlated with E-cadherin expression and positively correlated with vimentin expression. In vitro, knockdown of TRPV4 inhibited GC cell proliferation, colony formation, and invasion. Furthermore, the knockdown of TRPV4 modulated EMT by upregulating E-cadherin expression and downregulating the expression of N-cadherin and vimentin. In addition, the EMT-related transcription factor Snail was downregulated, whereas the expression levels of other transcription factors such as Slug and Twist did not change.

Conclusion: TRPV4 was upregulated in human GC and the overexpression of TRPV4 could promote GC progression, partially through Snail-mediated EMT.
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http://dx.doi.org/10.2147/OTT.S256918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468412PMC
August 2020

Long noncoding RNA TTN-AS1 facilitates tumorigenesis and metastasis by maintaining TTN expression in skin cutaneous melanoma.

Cell Death Dis 2020 08 20;11(8):664. Epub 2020 Aug 20.

The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China.

The antisense transcript, emanating from the opposite strand to a protein-coding or sense strand, has been reported to have critical roles in gene regulation. The perturbation of an antisense RNA can alter the expression of sense messenger RNAs. In this study, a long noncoding RNA TTN-AS1 (lncRNA-TTN-AS1), which is transcribed in the opposite direction of the human titin (TTN) gene, has been identified and explored in skin cutaneous melanoma (SKCM). We found that the expression of TTN and lncRNA-TTN-AS1 had a significantly positive correlation in SKCM cells. Functionally, ectopic expression of TTN and lncRNA-TTN-AS1 promoted SKCM tumorigenesis and metastasis both in vitro and in vivo. Moreover, knockdown of TTN partially abrogated lncRNA-TTN-AS1 induced SKCM tumorigenesis. Mechanistically, hypomethylation of transcription initiation site was responsible for lncRNA-TTN-AS1 high expression levels. LncRNA-TTN-AS1 facilitated SKCM progression by promoting TTN expression at both transcriptional and posttranscriptional levels. As detailed, lncRNA-TTN-AS1 had a significant effect on the increase of TTN promoter activity. Besides, lncRNA-TTN-AS1 also induced the accumulation of TTN in cytoplasm by increasing the stability of TTN mRNA. Clinically, we found that high TTN and lncRNA-TTN-AS1 expression were positively correlated with poor overall survival of SKCM patients, and may be considered as novel biomarkers and drug targets for SKCM patients.
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http://dx.doi.org/10.1038/s41419-020-02895-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441063PMC
August 2020

Insights into the cellulose degradation mechanism of the thermophilic fungus based on integrated functional omics.

Biotechnol Biofuels 2020 12;13:143. Epub 2020 Aug 12.

State Key Laboratory of Microbial Technology, Microbial Technology Institute, Shandong University, No. 72 Jimo Binhai Road, Qingdao, 266237 Shandong People's Republic of China.

Background: Lignocellulose is the most abundant and renewable biomass resource on the planet. Lignocellulose can be converted into biofuels and high-value compounds; however, its recalcitrance makes its breakdown a challenge. Lytic polysaccharide monooxygenases (LPMOs) offer tremendous promise for the degradation of recalcitrant polysaccharides. , having many LPMO-coding genes, is a dominant thermophilic fungus in cellulose-rich and self-heating habitats. This study explores the genome, secretomes and transcript levels of specific genes of .

Results: The genome of encoded a comprehensive set of cellulose- and xylan-degrading enzymes, especially 18 AA9 LPMOs that belonged to different subfamilies. Extracellular secretomes showed that arabinose and microcrystalline cellulose (MCC) could specifically induce the secretion of carbohydrate-active enzymes (CAZymes), especially AA9 LPMOs, by under different carbon sources. Temporal analyses of secretomes and transcripts revealed that arabinose induced the secretion of xylanases by , which was obviously different from other common filamentous fungi. MCC could efficiently induce the specific secretion of LPMO2s, possibly because the insert in loop3 on the substrate-binding surface of LPMO2s strengthened its binding capacity to cellulose. LPMO2s, cellobio hydrolases (CBHs) and cellobiose dehydrogenases (CDHs) were cosecreted, forming an efficient cellulose degradation system of oxidases and hydrolases under thermophilic conditions.

Conclusions: The specific expression of LPMO2s and cosecretion of hydrolases and oxidases by the thermophilic fungus play an important role in cellulose degradation. This insight increases our understanding of the cellulose degradation under thermophilic conditions and may inspire the design of the optimal enzyme cocktails for more efficient exploration of biomass resources in industrial applications.
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http://dx.doi.org/10.1186/s13068-020-01783-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425565PMC
August 2020

Enhanced oral bioavailability of magnolol via mixed micelles and nanosuspensions based on Soluplus-Poloxamer 188.

Drug Deliv 2020 Dec;27(1):1010-1017

State Key Laboratory of Natural Medicines, The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province, Department of Marine Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.

Magnolol, known to have extensive biological activities, is the major bioactive ingredient isolated from the root and stem bark of . However, the clinical application of magnolol is limited by poor aqueous solubility and absorption. The aim of this study is to develop novel mixed micelles and nanosuspensions composed of two biocompatible copolymers, Soluplus and Poloxamer 188, and to improve the solubility and oral bioavailability of magnolol. The magnolol-loaded mixed micelles (MMs) and magnolol nanosuspensions (MNs) were prepared to use film hydration and antisolvent methods, respectively. The optimal MMs and MNs formulations were prepared to use magnolol, Soluplus, and Poloxamer 188 in ratios of 1:12:5 and 2:1:1, respectively. The average particle size of MMs was 111.8 ± 14.6, and MNs was 78.53 ± 5.4 nm. The entrapment and drug loading efficiency for MMs were 89.58 ± 2.54% and 5.46 ± 0.65%, correspondingly. The drug loading efficiency of MNs was 42.50 ± 1.57%. In the release study, MMs showed a slow drug release while that of MNs was fast. The results of the Caco-2 transcellular transport study indicated that both MMs and MNs increased the permeation of magnolol. MMs and MNs markedly promoted gastrointestinal drug absorption by 2.85 and 2.27-fold, respectively, as shown in the pharmacokinetics study. These results indicated that both MMs and MNs formulations prepared with Soluplus and Poloxamer 188 are promising drug delivery systems for improving the oral absorption of insoluble drugs in the gastrointestinal tract.
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http://dx.doi.org/10.1080/10717544.2020.1785582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470061PMC
December 2020

Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort.

Andrology 2021 01 15;9(1):42-47. Epub 2020 Sep 15.

Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Background: Since SARS-CoV-2 infection was first identified in December 2019, the novel coronavirus-induced pneumonia COVID-19 spread rapidly and triggered a global pandemic. Recent bioinformatics evidence suggested that angiotensin-converting enzyme 2-the main cell entry target of SARS-CoV-2-was predominantly enriched in spermatogonia, Leydig and Sertoli cells, which suggests the potential vulnerability of the male reproductive system to SARS-CoV-2 infection.

Objectives: To identify SARS-CoV-2 RNA in seminal plasma and to determine semen characteristics from male patients in the acute and recovery phases of infection.

Methods: From February 26 to April 2, 2020, 23 male patients with COVID-19 were recruited. The clinical characteristics, laboratory findings and chest computed tomography scans of all patients were recorded in detail. We also investigated semen characteristics and the viral RNA load in semen from these patients in the acute and recovery phases of SARS-CoV-2 infection using approved methods.

Results: The age range of the 23 patients was 20-62 years. All patients tested negative for SARS-CoV-2 RNA in semen specimens. Among them, the virus had been cleared in 11 patients, as they tested negative. The remaining 12 patients tested negative for SARS-CoV-2 RNA in semen samples, but were positive in sputum and fecal specimens. The median interval from diagnosis to providing semen samples was 32 days, when total sperm counts, total motile sperm counts, and sperm morphology of the patients were within normal ranges.

Discussion And Conclusion: In this cohort of patients with a recent infection or recovering from COVID-19, there was no SARS-CoV-2 RNA detected in semen samples, which indicates the unlikely possibility of sexual transmission through semen at about 1 month after first detection.
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http://dx.doi.org/10.1111/andr.12848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362062PMC
January 2021

Evaluation of bladder shape using transabdominal ultrasound: Feasibility of a novel approach for the detection of involuntary detrusor contractions.

Ultrasound 2019 Aug 26;27(3):167-175. Epub 2019 Feb 26.

Department of Urogynaecology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

Conventional assessment of overactive bladder syndrome uses invasive pressure-measuring catheters to detect bladder contractions (urodynamics). We hypothesised that bladder shape changes detected and measured using transabdominal ultrasound scan could provide a non-invasive and clinically useful alternative investigation of bladder contractions. This feasibility study evaluated a novel transabdominal ultrasound scan bladder shape test during conventional urodynamics and physiological bladder filling. The aim was to initially evaluate and refine a non-invasive approach for detecting and quantifying bladder shape changes associated with involuntary bladder contractions. To develop measurement techniques and characterise bladder shape changes during bladder filling, healthy female volunteers (n=20) and women with overactive bladder symptoms who had previously undergone urodynamics (n=30) completed symptom questionnaires and bladder diaries. The bladder shape test protocol included consumption of 1 l water before undergoing serial transabdominal ultrasound scan imaging of the bladder during physiological bladder filling and during episodes of urgency. In a further group of women with overactive bladder (n=22), serial transabdominal ultrasound scan images were captured during urodynamics so that shape changes occurring with bladder contractions could be characterised. In both healthy volunteers and women with overactive bladder, the transverse view of the bladder provided the most reliable plane to characterise and measure bladder shape changes. A sphericity index derived from the ratio between maximum inscribed and minimum circumscribed ellipses (πac/πac) offered a reliable and reproducible measurement system. Of participants undergoing transabdominal ultrasound scan during urodynamics, there were significant measurable differences in sphericity index between patients with bladder contractions (n=12) and patients with acontractile bladders ( < 0.001). Bladder shape changes detected during physiological filling and urodynamics have provided preliminary evidence to support further research into bladder shape test as a non-invasive diagnostic tool to identify involuntary bladder contractions in patients with overactive bladder syndrome.
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http://dx.doi.org/10.1177/1742271X19834062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273879PMC
August 2019

Effect of enriched thermotolerant nitrifying bacteria inoculation on reducing nitrogen loss during sewage sludge composting.

Bioresour Technol 2020 Sep 29;311:123461. Epub 2020 Apr 29.

School of Environment, Harbin Institute of Technology, Harbin 150090, China.

In the study, enriched thermotolerant nitrifying bacteria (TNB) was acquired from compost samples by domesticated cultivation under high temperature, and was inoculated into sewage sludge composting. The effect of inoculation on physical-chemical parameters, nitrogen loss and bacterial population involved in nitrogen transformation were determined. The results revealed that inoculation with enriched TNB improved the compost quality in terms of temperature, pH, organic matter degradation, C/N ratio and germination index. Compared to the control treatment, inoculation also decreased 29.7% of ammonia emission and reduced nitrogen loss by converting more NH-N into NO-N in composting. In addition, inoculation increased the population of nitrifying bacteria and was not capable of inhibiting the growth of indigenous ammonifying bacteria as well. The results suggested that inoculation with enriched TNB was a feasible way to reduce nitrogen loss and promote maturity in sewage sludge composting.
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http://dx.doi.org/10.1016/j.biortech.2020.123461DOI Listing
September 2020

Analysis of Air Purification Methods in Operating Rooms of Chinese Hospitals.

Biomed Res Int 2020 1;2020:8278943. Epub 2020 Feb 1.

Peking University First Hospital, Beijing 100034, China.

This research demonstrates the current use of air purification methods in the operating rooms (ORs) in China. 154 hospitals from 6 provinces were included in this survey to reflect the air purification methods of ORs in 2017. Air cleaning technology (ACT) is used in 124 (80.52%) hospitals. We find that the rates of using grade I, III, or IV clean operating room (COR) in tertiary hospitals are all higher than in lower level hospitals; the rate of using ACT in the ORs is higher, too. In addition, general hospitals have higher rate in using ACT in the ORs than specialized hospitals. The highest rate of using ACT in the ORs is in the eastern region of China. The number of hospitals using ACT, ultraviolet light disinfection, and air sterilizers (such as circulating air UV sterilizer) increased yearly. All grades of CORs can be maintained as required by more than 90% hospitals except grade II COR. In this research, we found air purification methods, especially the ACT, are widely used in hospitals' ORs. However, finding the way to select and use different air purification methods correctly is an urgent problem to be solved next.
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http://dx.doi.org/10.1155/2020/8278943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016480PMC
November 2020

Association between Loss of Sleep-specific Waves and Age, Sleep Efficiency, Body Mass Index, and Apnea-Hypopnea Index in Human N3 Sleep.

Aging Dis 2020 Feb 1;11(1):73-81. Epub 2020 Feb 1.

1State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.

Sleep spindles (SS) and K-complexes (KC) play important roles in human sleep. It has been reported that age, body mass index (BMI), and apnea-hypopnea index (AHI) may influence the number of SS or KC in non-rapid-eye-movement (NREM) 2 (N2) sleep. In this study, we investigated whether the loss of SS or KC is associated with the above factors in NREM 3 (N3) sleep. A total of 152 cases were enrolled from 2013 to 2017. The correlations between the number of SS or KC in N3 sleep and participants' characteristics were analyzed using Spearman rank correlation. Chi-squared test was used to assess the effects of age, sleep efficiency, and BMI on the loss of N3 sleep, N3 spindle and N3 KC. Our results showed that there were negative correlations between the number of SS in N3 sleep with age, BMI, and AHI ( < 0.001), and similar trends were found for KC as well. The loss of SS and KC in N3 sleep was related with age, BMI, and AHI ( < 0.01), as was the loss of N3 sleep ( < 0.01). However, sleep efficiency was not related with the loss of N3 sleep, SS and KC in N3 sleep ( > 0.05). The present study supports that age, BMI, and AHI are all influencing factors of SS and KC loss in human N3 sleep, but sleep efficiency was not an influencing factor in the loss of N3 sleep and the loss of SS and KC in N3 sleep.
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http://dx.doi.org/10.14336/AD.2019.0420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961777PMC
February 2020

Stillbirth: Perceptions among hospital staff in the Middle East and the UK.

Eur J Obstet Gynecol Reprod Biol X 2019 Oct 16;4:100019. Epub 2019 Apr 16.

Sidra Medicine, Sidra Outpatient Building, Al Luqta Street, Education City North Campus, Qatar Foundation, PO BOX 26999, Doha, Qatar.

Objectives Stillbirth is an important and yet relatively unacknowledged public health concern in many parts of the world. Public awareness of stillbirth and its potentially modifiable risk factors is a prerequisite to planning prevention measures. Cultural and regional differences may play an important role in awareness and attitudes to stillbirth prevention. The objective of this study was to evaluate and compare the awareness of stillbirth among hospital staff in Qatar and the UK, representing two culturally different regions. Study design An online population survey for anonymous completion was sent to the hospital email accounts of all grades of staff (clinical and non-clinical) at two hospitals in Qatar and one tertiary hospital Trust in the UK. The survey was used to gather information on the participants' demographic background, the experience of stillbirth, knowledge of stillbirth, awareness of information and support sources, as well as attitude towards investigation and litigation. Data were analysed using descriptive and comparative statistics (Chi-Square test and Fisher's exact test). Results 1002 respondents completed the survey, including 349 in the Qatar group and 653 in the UK group. There were significant differences in group demographics in terms of language, religion, gender, nationality and experience of stillbirth. The groups also differed significantly in the knowledge of stillbirth, its incidence and risk factors. The two groups took different views on apportioning blame on healthcare services in cases of stillbirth. The Qatar group showed significantly less awareness of available support organisations and relied significantly more on online sources of information for stillbirths (p < 0.001). Conclusions This comparative study demonstrated significant differences between the two culturally distinct regions in the awareness, knowledge and attitudes towards stillbirths. The complex cultural and other factors that may be contributory should be further studied. The results highlight the need for increasing public awareness around stillbirth as part of effective prevention strategies.
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http://dx.doi.org/10.1016/j.eurox.2019.100019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817628PMC
October 2019

Control of the pore size of honeycomb polymer film from micrometers to nanometers via substrate-temperature regulation and its application to photovoltaic and heat-resistant polymer films.

Nanotechnology 2020 Jan 17;31(1):015301. Epub 2019 Sep 17.

Key Laboratory of Advanced Display and System Applications of Ministry of Education, Shanghai University, Shanghai 200072, People's Republic of China.

Honeycomb porous polystyrene (PS) films with an aspect ratio of pore depth to pore diameter at approximately 1.0 were fabricated using the breath figure (BF) method. Two modes of water droplet coalescence in the pore growth were observed in real-time by optical microscopy. Pore size significantly increases with the increase in humidity and the decrease in substrate temperature. The porous pattern could emerge even at room temperature under high humidity of 80%. Boiling point and solvent density significantly influence the pore distribution and pore depth. Chloroform and tetrahydrofuran achieve more uniform hexagonal patterns than benzene and dichloromethane. Subsequently, to obtain nanometer porous PS film, the fast-evaporation BF process was designed by regulating the gradient substrate temperature and evaporation time, and porous mesoscopic PS film was obtained. The minimum pore diameter and corresponding pore depth are about 120 nm and 27 nm, respectively. Finally, the fast-evaporation BF process was applied to the honeycomb film formation of photovoltaic polymer poly(3-hexylthiophene) (P3HT), and the heat-resistant polymers polysulfone (PSF) and polyimide (PI).
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http://dx.doi.org/10.1088/1361-6528/ab4521DOI Listing
January 2020

What Is the Effect of Body Mass Index on Subjective Outcome Following Vaginal Hysterectomy for Prolapse?

Int Neurourol J 2019 Jun 30;23(2):136-143. Epub 2019 Jun 30.

Department of Urogynaecology, Sheffield Teaching Hospitals, Sheffield, UK.

Purpose: Obesity is a significant risk factor for pelvic organ prolapse (POP), but the effects of obesity on outcomes of surgery for POP are poorly understood. The aim of this study was to assess the relationship between POP symptomatology, subjective outcomes of surgery and body mass index (BMI) in women undergoing vaginal hysterectomy for POP.

Methods: Pre- and postoperative data from a validated pelvic floor questionnaire (electronic Personal Assessment Questionnaire-Pelvic Floor) were collected prospectively from 60 women undergoing vaginal hysterectomy for POP. Of these, 20 were normal weight (BMI 18.5-24.9 kg/m2), 20 were overweight (BMI 25-29.9 kg/m2), and 20 were women with obesity (BMI 30-34.9 kg/m2). The relationship between BMI and symptom scores for prolapse, impact on vaginal symptoms on quality of life (VS-QoL) and 'overall change in condition' was assessed. Pre- and postoperative symptom scores were compared using repeated mixed analysis of variance test for BMI as a categorical variable (normal, overweight, and obese). Spearman rank order correlation test was carried out to evaluate BMI as a continuous variable. All women underwent vaginal hysterectomy using a standardized technique.

Results: Overall, 93% of women reported improvement in their condition. The main finding was that 'overall change in condition' was negatively correlated with increasing BMI (rs=-0.324, P=0.028). Irrespective of BMI, significant improvements were observed in symptoms of prolapse and VS-QoL at 3-month postoperation.

Conclusion: With increasing BMI, women are likely to report lower levels of satisfaction following prolapse surgery, despite reporting equivalent improvements in symptoms. BMI is known to affect how individuals perceive their general health and well-being with obese individuals reporting poorer levels of subjective health status. Women with obesity may perceive change in their condition after prolapse surgery differently to women of normal weight. Reduction of weight prior to prolapse surgery could be considered in obese women to improve subjective outcomes of surgery.
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http://dx.doi.org/10.5213/inj.1938016.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606935PMC
June 2019

SolutolHS15+pluronicF127 and SolutolHS15+pluronicL61 mixed micelle systems for oral delivery of genistein.

Drug Des Devel Ther 2019 7;13:1947-1956. Epub 2019 Jun 7.

Department of Marine Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.

We aimed to prepare two oral drug delivery systems consisting of polyoxyl 15 hydroxystearate (HS15) with pluronicF127 (F127) and HS15 with pluronicL61 (L61) to overcome the challenges of genistein's poor oral bioavailability. This provides a good strategy for enhancing the potential value of genistein. We designed two binary mixed micelle systems employing the organic solvent evaporation method using surfactants (HS15, L61, and F127). Formulations (GEN-F and GEN-L) were characterized by transmission electron microscopy. Drug content analysis, including entrapment efficiency (EE%), drug loading (DL%), and the cumulative amount of genistein released from the micelles, was performed using HPLC. The permeability of optimum formulation was measured in Caco-2 cell monolayers, and the oral bioavailability was evaluated in SD rats. The solutions of GEN-F and GEN-L were observed to be transparent and colorless. GEN-F had a lower EE% of 80.79±0.55% and a DL% of 1.69±0.24% compared to GEN-L, which had an EE% 83.40±1.36% and a DL% 2.26±0.18%. TEM results showed that the morphology of GEN-F and GEN-L was homogeneous and resembled a spherical shape. The dilution and storage conditions had no significant effect on particle size and EE%. Genistein demonstrated a sustained release behavior when encapsulated in micelles. Pharmacokinetics study showed that the relative oral bioavailability of GEN-F and GEN-L increased by 2.23 and 3.46 fold while also enhancing the permeability of genistein across a Caco-2 cell monolayer compared to that of raw genistein. GEN-F and GEN-L as a drug delivery system provide an effective strategy for enhancing and further realizing the potential value of GEN.
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http://dx.doi.org/10.2147/DDDT.S201453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559771PMC
January 2020