The influence of Chinese culture and customs on the beliefs and health-related behaviours of Chinese women with gestational diabetes mellitus: A qualitative study.

OBJECTIVE: The study aimed to explore the influence of Chinese culture and customs on the beliefs and health-related behaviours of Chinese women with gestational diabetes mellitus (GDM). METHODS: This descriptive qualitative study conducted semi-structured interviews with 15 Chinese women between November 2022 and January 2023. The interview data were analysed using thematic analysis. RESULTS: Three major themes are found: (1) beliefs in health, (2) beliefs in illness and GDM and (3) beliefs in health-related behaviours. They worried about the negative effects of GDM on the infant and family, so they actively sought medical advice to maintain health. However, it is challenging for them to balance adhering to healthcare professionals' advice and avoiding practical difficulties in the impact of the Chinese sociocultural context. CONCLUSION: This study emphasizes the influence of Chinese culture and customs on the beliefs and health-related behaviours of women with GDM. Healthcare providers should recognize the influence of Chinese culture, customs and beliefs on women with GDM and their families, in order to provide individualized education to help them maintain health-related behaviours.

SPRi/SERS dual-mode biosensor based on ployA-DNA/ miRNA/AuNPs-enhanced probe sandwich structure for the detection of multiple miRNA biomarkers.

MicroRNA (miRNA) has broad application prospects in the early detection of various cancers. In this work, a SPRi/SERS dual-mode biosensor was developed on the same gold chip by AuNPs as the reinforcing medium. High throughput and sensitivity detection of three typical cervical cancer markers miRNA21, miRNA124 and miRNA143 were achieved based on the sandwich structure of polyA blocks-DNA capture probe/target miRNA/AuNPs-assistant probe or SERS nanoprobes. AuNPs greatly improved the SPR response due to mass increase and more sensitive refractive index changes. Meanwhile, due to the LSPR effect of AuNPs, the signal of SERS nanoprobe can be amplified. The miRNAs were detected in serum to verify its practicality. SPRi achieved detection of three miRNAs simultaneously. LODs were 6.3 fM, 5.3 fM and 4.6 fM, respectively, and wide dynamic response range of 500 pM-10 nM. While SERS assay ensured high sensitivity with LODs as low as 1 fM, 0.8 fM and 1.2 fM, respectively, and with the recoveries in the range of 90.0 %-100.2 %. The redundant detection signals of the two modes can provide more reliable data to prevent false positive or false negative detection, and have great application prospects in detection of cancer-related nucleic acids in early stage of disease.

Efficient interfacial self-assembled MXene/Ag NPs film nanocarriers for SERS-traceable drug delivery.

Combining the unique advantages of two-dimensional transition metal carbon/nitrogen compounds (MXene) and the excellent surface-enhanced Raman scattering (SERS) performance of noble metal materials, MXene/Ag NPs films were proposed as nanocarriers for SERS-traceable drug delivery. The films were prepared by two-step self-assembly on positively charged silicon wafers using virtue of the high evaporation of ethyl acetate, the Marangoni effect, and an oil/water/oil three-phase system. With 4-mercaptobenzoic acid (4-MBA) as the probe molecule, the SERS detection limit was 10-8 M and had shown a good linear relationship in the range of 10-8-10-3 M. Simultaneously, the film had good uniformity, repeatability, and stability. When Ti3C2Tx/Ag NPs films were used as nanocarriers, the anticancer drug doxorubicin (DOX) was loaded onto the surface through 4-MBA, and the tracking and monitoring were realized by SERS. The addition of glutathione (GSH) triggered the thiol exchange reaction, resulting in the shedding of 4-MBA from the surface of the film, which indirectly achieved the efficient release of DOX. Furthermore, the loading of DOX and the drug release effect triggered by GSH maintained a certain stability in serum, which provided a potential possibility for the subsequent loading and release of drugs by films with three-dimensional structures as scaffolds in biological therapy. Self-assembled MXene/Ag NPs film nanocarriers for SERS-traceable drug delivery and GSH-triggered high-efficiency drug release.

The phenotype and genotype of PAX9 mutations causing tooth agenesis.

OBJECTIVES: The purpose of this study was to identify associations between PAX9 mutations and clinical features of non-syndromic tooth agenesis patients. MATERIALS AND METHODS: Non-syndromic tooth agenesis patients were found to have mutations by whole exome sequencing (WES). Additionally, conservation analysis and three-dimensional structure prediction were also applied to identify mutated proteins. RESULTS: Eight non-syndromic tooth agenesis probands were identified with PAX9 mutations (c.C112T; C.131_134del; c.G151A; c.189delG; c.305delT; c.C365A; c.394delG; c.A679C). All of the probands were missing more than six teeth (oligodontia). The mutations (c.131_134del,p.R44fs; c.189delG,p.T63fs; c.305delT,p.I102fs and c.394delG,p.G123fs) caused premature termination of the PAX9 protein. The c.C112T(p.R38X) mutation created a truncated protein. Bioinformatic prediction demonstrated that the three missense mutations change the PAX9 structure suggesting the corresponding functional impairments. CONCLUSIONS: We reported that eight mutations of PAX9 caused non-syndromic tooth agenesis and analyzed the relationship between PAX9 mutations and non-syndromic tooth agenesis. CLINICAL RELEVANCE: Our study revealed that PAX9 mutations might be the mutations most associated with non-syndromic tooth agenesis in humans, which greatly broadened the mutation spectrum of PAX9-related non-syndromic tooth agenesis.

Aging in Place or Institutionalization? A Multiscale Analysis of Independent-Living Older Adults From Four Large Cities in China's Yangtze River Delta.

Background and Objectives: Aging in place (AIP) has been adopted as a key strategy to cope with the global public health challenge posed by population aging. The current study aimed to understand the association between older adult's AIP preference and various social and physical environmental factors at different scales. Research Design and Methods: Following the ecological model of aging, this paper conducted a questionnaire survey of 827 independent-living older adults (60 years old and above) from four big cities in China's Yangtze River Delta region and employed a structural equation modeling method for analysis. Results: Older adults from more developed cities exhibited a stronger preference for AIP than those from less developed cities. Individual characteristics, mental health, and physical health had a direct impact on AIP preference, whereas the effect of the community social environment was not significant. The perceived and objectively measured community-built environment indirectly affected AIP preference via mediation and chain effects. Discussion and Implications: Complex paths affecting AIP preference were identified. At the city level, the social environment had a stronger influence than the physical environment on AIP, and the opposite pattern was observed at the community level. Mental health and physical health had opposite effects on AIP preference. Although physical health was negatively associated with AIP, age-friendly communities with compact, diverse, and accessible built environments have a positive impact on older adults' physical health and therefore should be promoted.

Structural insights into pathogenic mechanism of hypohidrotic ectodermal dysplasia caused by ectodysplasin A variants.

EDA is a tumor necrosis factor (TNF) family member, which functions together with its cognate receptor EDAR during ectodermal organ development. Mutations of EDA have long been known to cause X-linked hypohidrotic dysplasia in humans characterized by primary defects in teeth, hair and sweat glands. However, the structural information of EDA interaction with EDAR is lacking and the pathogenic mechanism of EDA variants is poorly understood. Here, we report the crystal structure of EDA C-terminal TNF homology domain bound to the N-terminal cysteine-rich domains of EDAR. Together with biochemical, cellular and mouse genetic studies, we show that different EDA mutations lead to varying degrees of ectodermal developmental defects in mice, which is consistent with the clinical observations on human patients. Our work extends the understanding of the EDA signaling mechanism, and provides important insights into the molecular pathogenesis of disease-causing EDA variants.

Research progress on selective tooth agenesis caused by LRP6 gene mutation / 口腔疾病防治

@#Selective tooth agenesis (STA) is an abnormal number of teeth due to genetic factors or the environment and is most commonly observed for permanent teeth. LRP6 is one of the common causative genes of STA and is inherited by an autosomal dominant mechanism, leading to non-syndrome tooth agenesis (NSTA) or syndrome tooth agenesis (STA). NSTA is only involved in tooth number and appearance abnormalities, whereas STA caused by LRP6 gene mutation results abnormal ear development, oral-facial clefting, sparse hair and hypohidrosis. In this paper, we review the phenotype and gene mutation traits of selective STA caused by LRP6 gene mutation identified in recent years and describe 38 patients with tooth agenesis from 24 mutation sites of LRP6 gene. We analyzed the percentage of missing teeth and found that the lateral incisor in the maxilla and the second premolar in the maxilla and mandible were most commonly lost, whereas all central incisors in the maxilla remained. LRP6 gene plays a major role in tooth development via the WNT/β-catenin signaling pathway, and LRP6 gene mutation can lead to a series of abnormal manifestations due to the disruption of the signaling pathway. The literature showed that LRP6 gene mutations occurred mostly at the E1 or E2 subdomain, meaning that STA due to the mutants extracellularly disturbed the WNT/β-catenin signaling pathway. However, mature treatments for selective congenital tooth loss are lacking.

Case report: Novel junctional sarcoplasmic reticulum protein 1 intergenic region-anaplastic lymphoma kinase fusion in a patient with lung adenocarcinoma responds to alectinib.

Novel anaplastic lymphoma kinase (ALK) fusions are still being discovered in non-small cell lung cancer (NSCLC). Most patients with ALK+ NSCLC respond favorably to ALK tyrosine kinase inhibitors. In this case report, we identified a novel nonreciprocal ALK fusion, namely, junctional sarcoplasmic reticulum protein 1 (JSRP1) intergenic region-ALK fusion (Jintergenic: A20) via next-generation sequencing in a female patient initially diagnosed with stage IV B lung adenocarcinoma. Further examination of biopsy specimen and analysis of clinical samples by a multidisciplinary team confirmed the diagnosis of ALK+ NSCLC. At the 2- and 4-months follow-up after receiving alectinib, the patient responded rapidly, implying that alectinib had a remarkable therapeutic effect. We identified a novel JSRP1 intergenic region-ALK fusion as a carcinogenic mutation that responds to alectinib, thereby expanding the spectrum of ALK fusion partners in ALK + NSCLC. This study may help clinicians detect oncogenic mutations and provide timely treatment to patients with ALK+ NSCLC.

Two novel ectodysplasin A gene mutations and prenatal diagnosis of X-linked hypohidrotic ectodermal dysplasia.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is mainly caused by ectodysplasin A (EDA) gene mutation. Fetus with genetic deficiency of EDA can be prenatally corrected. This study aimed at revealing the pathogenesis of two HED families and making a prenatal diagnosis for one pregnant female carrier. DESIGNS: Genomic DNA was extracted from two HED patients and sequenced using whole exome sequencing (WES). The detected mutations were confirmed in patients and family members using Sanger sequencing. The expression of soluble ectodysplasin A1 (EDA1) protein was studied by western blot. The transcriptional activity of NF-κB pathway was tested by dual luciferase assay. The genomic DNA of fetus was extracted from shed chorion cells and EDA gene was screened through Sanger sequencing. RESULTS: We identified two novel EDA mutations: c.1136T>C (p.Phe379Ser) and c.[866G>C;868A>T] (p.[Arg289Pro;Ser290Cys]). Further examinations revealed that these two mutated EDA1 proteins showed completely impaired solubility, and the transcriptional NF-κB activation induced by these missense mutant-type EDA1 proteins was significantly reduced compared with wild-type EDA1. Furthermore, the analysis of amniotic fluid samples from a pregnant heterozygote indicated that the fetus was a c.1136T>C mutation female carrier. CONCLUSIONS: This study extended the mutation spectrum of X-linked hypohidrotic ectodermal dysplasia (XLHED) and applied prenatal diagnosis for the pregnant carrier, which can be helpful in genetic counseling, prenatal diagnosis, and intervention for the XLHED family.

Highly uniform self-assembled monolayers of silver nanospheres for the sensitive and quantitative detection of glutathione by SERS.

The homeostasis and imbalance of glutathione (GSH), an important antioxidant in organisms, are one of the key signals that reflect the health of organisms. In this paper, a novel SERS sensing platform based on Ag film@Si that self-assembled using silver nanospheres was proposed, which was used for the highly sensitive and selective detection of GSH. With the aid of an oil/water/oil three-phase system, the nano-silver film was self-assembled and finally deposited on silicon wafers. The heterobifunctional crosslinking agent N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), which contains pyridine rings and disulfide bonds, was involved in the exchange reaction between the sulfhydryl groups and disulfide bonds. With the addition of GSH, the breakage of disulfide bonds was promoted, thereby enhancing the SERS signal of SPDP. GSH can be detected sensitively by detecting the changes in the SPDP signal. The detection limit of GSH is 10 nM, and the method is still highly stable when the external environment is serum or other more complex environments.

Dihydroartemisinin Increases the Sensitivity of Photodynamic Therapy Via NF-κB/HIF-1α/VEGF Pathway in Esophageal Cancer Cell in vitro and in vivo.

BACKGROUND/AIMS: Although photodynamic therapy (PDT) can relieve esophageal obstruction and prolong survival time of patients with esophageal cancer, it can induce nuclear factor-kappa B (NF-κB) activation in many cancers, which plays a negative role in PDT. Dihydroartemisinin (DHA), the most potent artemisinin derivative, can enhance the effect of PDT on esophageal cancer cells. However, the mechanism is still unclear. METHODS: We generated stable cell lines expressing the super-repressor form of the NF-κB inhibitor IκBα and cell lines with lentivirus vector-mediated silencing of the HIF-1α gene. Esophageal xenograft tumors were created by subcutaneous injection of Eca109 cells into BALB/c nude mice. Four treatment groups were analyzed: a control group, photosensitizer alone group, light alone group, and PDT group. NF-κB expression was detected by an electrophoretic mobility shift assay, hypoxia-inducible factor α (HIF-1α) and vascular endothelial growth factor (VEGF) by real-time PCR, NF-κB, HIF-1α, and VEGF protein by western blot, and Ki-67, HIF-1α, VEGF, and NF-κB protein by immunohistochemistry. RESULTS: PDT increased NF-κB activity and the gene expression of HIF-1α and VEGF in vitro and in vivo. In contrast, the DHA groups, particularly the combined DHA and PDT treatment group, abolished the effect. The combined treatment significantly inhibited tumor growth in vitro and in vivo. NF-κB activity and HIF-1α expression were also reduced in the stable IκBα expression group, whereas the former showed no change in HIF-1α-silenced cells. CONCLUSION: DHA might increase the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway.

Anticancer Effects of Dihydroartemisinin on Human Esophageal Cancer Cells In Vivo.

Despite recent advances in chemotherapy and surgical resection, the 5-year survival rate of esophageal cancer still remains at the low level. Therefore, it is very important to discover a new agent to improve the life expectancy of patients with esophageal cancer. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently exhibited promising anticancer activity against various cancer cells. But so far, the specific mechanism remains unclear. We have previously demonstrated that DHA reduced viability of esophageal cancer cells in a dose-dependent manner in vitro and induced cell cycle arrest and apoptosis. Here, we extended our study to further observe the efficacy of DHA on esophageal cancer cells in vivo. In the present study, for the first time, we found that DHA significantly inhibits cell proliferation in xenografted tumor compared with the control. The mechanism was that DHA induced cell apoptosis in both human esophageal cancer cell lines Eca109 and Ec9706 in vivo in a dose-dependent manner. The results suggested that DHA was a promising agent against esophageal cancer in the clinical treatment.