Influencing Factors for Social Acceptance of Noma (Cancrum Oris) Patients in Niger: A Hospital-Based Cross-Sectional Study

Background: Noma, mostly identified in malnourished young children in the world’s low-income countries, causes severe orofacial disfigurement and significant mortality and morbidity. The majority of noma patients surviving with aesthetical effects are exposed to stigmatization and social rejection. Studies focusing on the socio-psychological impact of noma survivors have rarely been done. Our study aimed to identify the differences in social acceptance/rejection and the influencing factors associated with social acceptance in noma patients. Methods: A cross-sectional study was conducted at the NGO-Sentinelles (Niger) reception center on patients with noma from Zinder, Maradi, and Tahoua regions between 9th May 2017 and 2nd June 2017. The survey was conducted through a face-to-face interview on patients admitted to the center and those discharged from the centre after the treatment. The interview questionnaire comprised 45 questions (Cronbach’s alpha coefficient = 0.812) with pathological information, sociodemographic characteristics, and socio-psychological qualitative information. Findings: We recorded 50 noma patients (43 from Zinder and 7 from Maradi and Tahoua). The younger patients (1 - 5 years old), noma patients who stayed in school during follow-up treatment, patients who were referred by a health structure, patients enrolled into the centre in a short time (<30 days), and patients in the acute phase of noma had a significantly high social acceptance rate with 60.0%, 82.9%, 60.0%, 57.1% and 94.3% respectively;whereas single adults and cheek lesion site had the highest social rejection rate when compared to their corresponding factors with 60.0% and 86.7% respectively. There were significant differences in victims’ perception of noma [χ2 = 45.536, (P < 0.001)] and acceptance of their new faces [P = 0.023], between the social acceptance and social rejection rate, therefore all patients who accepted their new faces felt social acceptance. Social acceptance was significantly highly correlated with pathological history (admission method, phase of noma, care, and treatment received at center) with rs ranging from 0.609 to 0.810, moderately correlated with patient’s sociodemographic characteristics (age, marital status, and region) with rs ranging from 0.381 to 0.474. Lowly correlated with clinical evolution after treatment (rs = 0.293). Logistic regression results showed that the likelihood of social acceptance increased when the patient’s age was young (≤15 years), their marital status was minor, they were enrolled at the school before noma appearance, they were referred to the centre after diagnosis, the admission time to the centre was short (≤30 days), acute phase of noma, and care received at the centre was non-surgery. The location of the lesion on the cheek was a risk factor for social acceptance, indicating cheek lesions from noma increased the likelihood of social rejection in our study. Conclusion: The sociodemographic characteristics, pathological history, and psychological aspects of noma patients were correlated and were found to be important factors influencing their social acceptance/rejection rate.

Long-term outcomes of a phase Ⅱ randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

Background:Salvage treatment for locally recurrent nasopharyngeal carcinoma(NPC) is complicated and relatively limited.Radiotherapy,combined with effective concomitant chemotherapy,may improve clinical treatment outcomes.We conducted a phase Ⅱ randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.Methods:Between April 2002 and January 2008,69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group(n = 34) or radiotherapy alone group(n = 35).All patients received intensity-modulated radiotherapy.The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days(range 23-53 days).The concomitant chemotherapy schedule was cisplatin 30 mg/m^2 by intravenous infusion weekly during radiotherapy.Results:The median follow-up period of all patients was 35 months(range 2-112 months).Between concomitant chemoradiotherapy and radiotherapy groups,there was only significant difference in the 3-year and 5-year overall survival(OS) rates(68.7%vs.42.2%,P = 0.016 and 41.8%vs.27.5%,P = 0.049,respectively).Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4(33.0%vs.13.2%,P = 0.009),stages Ⅲ-Ⅳ(34.3%vs.13.2%,P = 0.006),recurrence interval >30 months(49.0%vs.20.6%,P = 0.017),and tumor volume >26 cm^3(37.6%vs.0%,P = 0.006).Conclusion:Compared with radiotherapy alone,concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC,especially those with advanced T category(rT3-4) and stage(lll-IV) diseases,recurrence intervals >30 months,and tumor volume >26 cm^3.

慢性阻塞性肺疾病患者FeNO与外周血IL-8、TNF-α和VEGF水平的相关性研究

目的探讨慢性阻塞型肺疾病(COPD)急性加重期患者呼出气一氧化氮(FeNO)的变化,以及与外周血白细胞介素-8(IL-8)、肿瘤坏死因素-α(TNF-α)、血管内皮生长因子(VEGF)水平的相关性。方法选取2016年3月2018年5月西宁市第一人民医院收治的COPD急性加重期患者75例为急性观察组,同期门诊65例COPD稳定期患者为稳定对照组,另选取45例该院健康体检者为健康对照组。比较3组受试者FeNO、肺功能及外周血IL-8、TNF-α、VEGF水平,并且分析急性观察组FeNO与外周血IL-8、TNF-α、VEGF水平的相关性。结果①急性观察组第1秒用力呼气容积(FEV1)和第1秒用力呼气容积/用力肺活量(FEV1/FVC)低于稳定对照组(P<0.05),而稳定对照组FEV1和FEV1/FVC低于健康对照组(P<0.05);②急性观察组FeNO及外周血IL-8、TNF-α、VEGF水平高于稳定对照组和健康对照组(P<0.05);稳定对照组外周血IL-8、TNF-α、VEGF水平高于健康对照组(P<0.05);③急性观察组外周血IL-8(r=0.535,P=0.000)、TNF-α(r=0.313,P=0.006)及VEGF(r=0.226,P=0.049)与FeNO呈正相关。结论COPD急性加重期患者FeNO及外周血IL-8、TNF-α、VEGF水平高于健康人群和COPD稳定期患者,并且这些指标呈正相关,可能作为临床诊断的指标。

Cross-linking Copolymerization of Acrylic Acid and Multi-armed Cross-linkers

The overall cross-linking copolymerization of acrylic acid and multi-armed cross-linkers are investigated by in situ interferometry. The results show that the more arms the cross-linkers have, the higher the polymerization rate is. However, they also mean the existence of less cross-linking efficiency and some defects in gel network.

IN SITU INTERFEROMETRIC STUDY ON THE GELATION PROCESS OF POLYACRYLIC ACID GELS

In situ interferometry was used to investigate the gelation process of polyacrylic acid (PAA) gels. The basicprinciple of the in situ interferometry technique is illustrated. It can give sufficient information for non-destructive andsuccessful investigation of the whole gelation process. The effect of initiator concentration on the gelation process wasstudied. The polymerization rate of AA increases with increasing initiator concentration. The error arising from the thermaleffect in the gelation process can be neglected.

Effect of butyl phthalide on serum cytokines, soluble apoptosis factors and antioxidant molecules in patients with vascular dementia

Objective:To study the effect of butyl phthalide on serum cytokines, soluble apoptosis factors and antioxidant molecules in patients with vascular dementia. Methods:86 patients with vascular dementia admitted in our hospital between January 2014 and January 2016 were selected for retrospective study and divided into observation group and control group (n=43) according to double-blind randomized control. Observation group received butyl phthalide capsule (0.2 g/time, 3 times/d) treatment on the basis of conventional treatment, control group received conventional treatment alone, and both lasted for 24 weeks. After 24 weeks of treatment, ELISA was used to determine serum levels of vascular repair factors and soluble apoptosis factors of two groups of patients, and radioimmunoassay was used to determine serum levels of antioxidant molecules. Results:After 24 weeks of treatment, serum vascular repair factors heme oxygenase-1 (HO-1), angiogenin I (AngI) and vascular endothelial growth factor (VEGF) levels of observation group were higher than those of control group, matrix metalloproteinase-9 (MMP-9) level was lower than that of control group, and differences between groups were statistically significant (P<0.05);serum soluble factor-related apoptosis (sFas) and soluble factor-related apoptosis ligand (sFasL) levels were lower than those of control group (P<0.05);serum antioxidant molecules superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAC), catalase (CAT), glutathione S-transferase (GST) and glutathione reductase (GR) levels were higher than those of control group (P<0.05). Conclusions:Butyl phthalide can prompt vascular repair in patients with vascular dementia, and also inhibit apoptosis process and balance the body’s oxidation/antioxidation system function.

Treatment of Alzheimer's disease with small-molecule photosensitizers

Alzheimer's disease is a neurodegenerative disease that signals for excessβ-amyloid(Aβ)aggregation.Although people have made great attempts to control the aggregation of Aβ,no effective medications have been produced yet.Due to its excellent temporal and spatial selectivity,photodynamic treatment has been gradually employed and interfered in the aggregation process of Aβ,with some achievement.To enhance the research and application of photodynamic therapy in Alzheimer's disease,this paper reviews the progress of small-molecule photosensitizers in the treatment of Alzheimer's disease in recent years and outlines existing tactics and potential obstacles.

Corrigendum to“Improving cooperativity of transcription activators by oligomerization domains in mammalian cells”[Synth Syst Biotechnol 8(1)(2023)114-120]

The authors regret that following the publication of the original article,the authors noticed that Funds in Acknowledgements section was incorrect,in which a fund(No.2020YFA0906903)supporting most of experimental results of Dr.Xinmao Chen was missed by us.We sincerely apologize again for the oversight and appreciate your understanding in allowing us to correct this matter.

Improving cooperativity of transcription activators by oligomerization domains in mammalian cells

Cooperative activation is critical for the applications of synthetic biology in mammalian cells.In this study,we have developed cooperative transcription factor by fusing oligomerization domain in mammalian cells.Firstly,we demonstrated that two oligomerized domains(CI434 and CI)successfully improved transcription factor cooperativity in bacterial cells but failed to increase cooperativity in mammalian cells,possibly because the additional mammalian activation domain disrupted their oligomerization capability.Therefore,we chose a different type of oligomerized domain(CarHC),whose ability to oligomerize is not dependent on its C-terminal domains,to fuse with a transcription factor(RpaR)and activation domain(VTR3),forming a potential cooperative transcription activator RpaR-CarH-VTR3 for mammalian regulatory systems.Compared with RpaR-VTR3,the cooperativity of RpaR-CarH-VTR3 was significantly improved with higher Hill coefficient and a narrower input range in the inducible switch system in mammalian cells.Moreover,a mathematical model based on statistical mechanics model was developed and the simulation results supported the hypothesis that the tetramer of the CarH domain in mammalian cells was the reason for the cooperative capacity of RpaR-CarH-VTR3.

Peptide-Cross-Linked Protein-Imprinted Polymers: Easy Template Removal and Excellent Imprinting Effect

Molecular imprinting of proteins remains a huge chal-lenge because of two major obstacles:difficulty in template removal and low imprinting efficiency.Herein,we propose a new strategy to simultaneously overcome these two challenges by creating molecu-larly imprinted polymers(MIPs)with nanoscale shape-memorable imprint cavities.These novel MIPs were developed by simply cross-linking the polymers with a peptide cross-linker instead of commonly used cross-linkers.Due to the unique pH-induced helix–coil transition of the peptide cross-linker,adjusting the pH from 5.5 to 7.4 leads to an expansion of the imprint cavities,thus facilitating template removal.Returning the pH back to 5.5 restores the original size and shape of the imprint cavities due to the precise refolding of peptide.A template protein can there-fore be readily removed under mild conditions,while simultaneously achieving a significantly improved imprinting effect.

Mechanistic insights into the novel glucose-sensitive behavior of P(NIPAM-co-2-AAPBA)

A glucose-sensitive polymer,poly(N-isopropylacrylamide-co-2-acrylamidophenylboronic acid)(P(NIPAM-co-2-AAPBA)),was synthesized by reversible addition fragmentation chain transfer(RAFT)copolymerization.Addition of glucose results in reduced solubility and hence increased turbidity,rather than the normal increase in solubility(decreased turbidity)observed for other PBA-based glucose-sensitive polymers.The novel glucose-sensitive behavior is explained by a new mechanism,in which glucose acts as an additive and depresses the lower critical solution temperature(LCST)of the polymer,instead of increasing solubility by increasing the degree of ionization of the PBA groups.Experimental and theoretic analysis for the influence of glucose on the thermal behavior of P(NIPAM-co-2-AAPBA)reveals that glucose depresses the LCST of P(NIPAM-co-2-AAPBA)copolymers in a two-stage manner,a fast decrease at low glucose concentrations followed by a slow decrease at high glucose concentrations.For low glucose concentrations,the binding of glucose with PBA groups on the polymer chain increases the number of glucose molecules proximal to the polymer which influences the thermal behavior of the polymer,causing a rapid decrease in LCST.Importantly,the transition occurs at a glucose concentration equal to the reciprocal of the binding constant between PBA and glucose,thus providing a novel method to determine the binding constant.Other saccharides,including mannose,galactose and fructose,also depress the LCST of P(NIPAM-co-2-AAPBA)copolymer in the same way.

Engineered DNase-inactive Cpf1 variants to improve targeting scope for base editing in E.coli

The development of base editing(BE)technology has opened a new avenue for research studies in bacteriology,particularly for bacterial species in which the DNA double-strand breaks(DSBs)introduced by CRISPR/Cas system would lead to cell death.However,a major limitation of BE-mediated gene editing is the restricted editable sites in the target bacterial genome due to highly diverse genomic compositions,such as GC content.Herein,we developed a broad-spectrum DNase-inactive Cpf1(dCpf1)variant from Francisella novicida(bsdFnCpf1)through directed evolution.The resulting optimized mutant showed a substantially expanded targeting range,including previously non-canonical protospacer-adjacent motifs(PAMs),especially the GC-rich PAMs.Cytidine deaminase APOBEC1 and uracil DNA glycosylase inhibitor(UGI)were fused with bsdFnCpf1 to achieve specific C to T mutations at multiple target sites with canonical or non-canonical PAMs in the E.coli genome without compromising cell growth.We anticipate that bsdFnCpf1 could be applied for multiplex gene regulation and BE in species that have been reported to be suitable for Cpf1.

Aquaporin 1 overexpression may enhance glioma tumorigenesis by interacting with the transcriptional regulation networks of Foxo4,Maz,and E2F families

Background The glioblastoma has served as a valuable experimental model system for investigating the growth and invasive properties of glioblastoma.Aquaporin-1(AQP1)in facilitating cell migration and potentially contributing to tumor progression.In this study,we analyzed the role of AQP1 overexpression in glioblastoma and elucidated the main mechanisms involved.Methods AQP1 overexpression recombinant vector was introduced into C6 rat glioma cells to construct an AQP1 overexpression C6 cell line,and its effect on cell viability and migration ability was detected by MTT and Transwell.RNA was extracted by Trizol method for gene sequencing and transcriptomics analysis,and the differentially expressed genes(DEGs)were enriched for up-and downregulated genes by Principal component analysis(PCA),and the molecular mechanism of AQP1 overexpression was analyzed in comparison with the control group using the NCBI GEO database.Statistical analysis was performed using Mann-Whitney paired two tailed t test.Results The cell viability of AQP1-transfected cell lines increased by 23%and the mean distance traveled increased by 67%compared with the control group.Quantitative analysis of gene expression showed that there were 12,121 genes with an average transcripts per million(TPM)value greater than 1.DEGs accounted for 13%of the genes expressed,with the highest correlation with upregulated genes being FOXO4 and MAZ,and the highest with down-regulated genes being E2F TFs.Conclusions AQP1 may be implicated in glioma formation by interacting with the transcriptional regulation networks involving the FOXO4,MAZ,and E2F1/2.These findings shed light on the potential significance of AQP1 in glioma pathogenesis and warrant further investigations to unravel the underlying molecular mechanisms.