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Aim This study was to explore role of immune landscape and the immune cells in acute lymphoblastic leukemia (ALL) progression. Background The most prevalent genetic alteration in childhood ALL is the ETV6-RUNX1 fusion. The increased proliferation of B progenitor cells could expedite the disease’s progression due to irregularities in the cell cycle. Nevertheless, the mechanisms by which particular cell clusters influence the cell cycle and promote the advancement of ALL are still not well understood. Objective This study was to explore role of immune landscape and the immune cells in ALL progression. Methods Single-cell RNA sequencing (scRNA-seq) data of ETV6-RUNX1 and healthy pediatric samples obtained from GSE132509 were clustered and annotated using the Seurat package, and differentially highly expressed genes identified in each cluster were analyzed using DAVID for pathway annotation. Chromosome amplification and deletion were analyzed using the inferCNV package. SCENIC evaluated the regulation of transcription factors and target gene formation in cells. cellphoneDB and CellChat were served to infer ligand-receptor pairs that mediate interactions between subpopulations. The role of the target gene in regulating ALL progression was assessed using RT-qPCR, Transwell and scratch healing assays. Results The bone marrow mononuclear cells (BMMCs) from ETV6-RUNX1 and healthy pediatric samples in GSE132509 were divided into 11 clusters, and B cell cluster 1 was identified as B progenitor cell, which was amplified on chromosome 6p. B progenitor cells were divided into seven clusters. Expression levels of amplified genes in chromosome 6p of B progenitor cell cluster 5 were the highest, and its specific highly expressed genes were annotated to pathways promoting cell cycle progression. Regulons formed in B progenitor cell cluster 5 were all involved in promoting cell cycle progression, so it was regarded as the B progenitor cell cluster that drives cell cycle progression. The key regulator of the B progenitor cell is E2F1, which promotes the migration and invasion ability of the cell line HAP1. The major ligand-receptor pairs that mediate the communication of B progenitor cell cluster 5 with cytotoxic NK/T cells or naive T cells included FAM3C−CLEC2D, CD47−SIRPG, HLAE−KLRC2, and CD47−KLRC2. HLAE−KLRC1 and TGFB1−(TGFBR1+TGFBR2). Conclusion This study outlined the immune cell landscape of ETV6-RUNX1 ALL and identified chromosome 6p amplification in B progenitor cells, described the major B progenitor cell cluster driving cell cycle progression and its potential regulatory mechanisms on NK cells and T cells, providing cellular and molecular insights into ETV6-RUNX1 ALL.

Parkinson's disease (PD) is characterized by the accumulation of misfolded α-synuclein protein and the loss of dopaminergic neurons in the substantia nigra. Abnormal α-synuclein aggregates form toxic Lewy bodies, ultimately inducing neuronal injury. Mitochondrial dysfunction was reported to be involved in the neurotoxicity of α-synuclein aggregates in PD. However, the specific mechanism by which abnormal α-synuclein aggregates cause mitochondrial disorders remains poorly defined. Previously, we found that cofilin-1, a member of the actin-binding protein, regulates α-synuclein pathogenicity by promoting its aggregation and spreading in vitro and in vivo. In this study, we further investigated the effect of cofilin-1 on α-synuclein induced mitochondrial damage. We discovered that α-synuclein aggregates accelerate the translocation of cofilin-1 to mitochondria, promote its combination with the mitochondrial outer membrane receptor Tom 20, and ultimately activate the oxidative damage and apoptosis pathway in mitochondria. All these results demonstrate the important regulatory role of cofilin-1 in the mitochondrial neurotoxicity of pathological α-synuclein during the progression of PD.

Abstract Aims To establish a comprehensive understanding of the roles of midwives and the challenges they encounter in the prevention, diagnosis and management of postpartum haemorrhage (PPH) following normal vaginal delivery. Design We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis for Scoping Reviews (PRISMA‐ScR) recommendations. Methods We considered studies related to the roles of midwives and the challenges they encounter in the prevention, diagnosis and management of PPH during vaginal delivery. We excluded guidelines, consensuses, abstracts of meetings and non‐English language studies. Databases, including the Cochrane Library, PubMed, Web of Science, Ovid, Medline, Embase, JBI EBP and BIOSIS Previews, were searched on January 1, 2023, with no time limitations. Results We included 28 publications. Midwives play important roles in the prevention, diagnosis and management of postpartum haemorrhage during vaginal delivery. In the prevention of PPH, midwives' roles include identifying and managing high‐risk factors, managing labour and implementing skin‐to‐skin contact. In the diagnosis of PPH, midwives' roles include early recognition and blood loss estimation. In the management of PPH, midwives are involved in mobilizing other professional team members, emergency management, investigating causes, enhancing uterine contractions, the repair of perineal tears, arranging transfers and preparation for surgical intervention. However, midwives face substantial challenges, including insufficient knowledge and skills, poor teamwork skills, insufficient resources and the need to deal with their negative emotions. Midwives must improve their knowledge, skills and teamwork abilities. Health care system managers and the government should give full support to midwives. Future research should focus on developing clinical practice guidelines for midwives for preventing, diagnosing and managing postpartum haemorrhage.

Abstract Abundant cellular transcripts occupy most of the sequencing reads in the transcriptome, making it challenging to assay for low-abundant transcripts. Here, we utilize the adaptive sampling function of Oxford Nanopore sequencing to selectively deplete and enrich RNAs of interest without biochemical manipulation before sequencing. Adaptive sampling performed on a pool of in vitro transcribed RNAs resulted in a net increase of 22-30% in the proportion of transcripts of interest in the population. Enriching and depleting different proportions of the Candida albicans transcriptome also resulted in a 11-13.5% increase in the number of reads on target transcripts, with longer and more abundant transcripts being more efficiently depleted. Depleting all currently annotated Candida albicans transcripts did not result in an absolute enrichment of remaining transcripts, although we identified 26 previously unknown transcripts and isoforms, 17 of which are antisense to existing transcripts. Further improvements in the adaptive sampling of RNAs will allow the technology to be widely applied to study RNAs of interest in diverse transcriptomes.

Abstract Spindle cell sarcoma (SCS) is rare in clinical practice. The objective of this study was to establish nomograms to predict the OS and CSS prognosis of patients with SCS based on the Surveillance, Epidemiology, and End Results (SEER) database. The data of patients with SCS between 2004 and 2020 were extracted from the SEER database and randomly allocated to a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to screen for independent risk factors for both overall survival (OS) and cancer-specific survival (CSS). Nomograms for OS and CSS were established for patients with SCS based on the results of multivariate Cox analysis. Then, we validated the nomograms by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Finally, Kaplan‒Meier curves and log-rank tests were applied to compare patients with SCS at three different levels and in different treatment groups. A total of 1369 patients with SCS were included and randomly allocated to a training cohort (n = 1008, 70%) and a validation cohort (n = 430, 30%). Age, stage, grade, tumour location, surgery, radiation and diagnosis year were found to be independent prognostic factors for OS by Cox regression analysis, while age, stage, grade, tumour location and surgery were found to be independent prognostic factors for CSS. The nomogram models were established based on the results of multivariate Cox analysis for both OS and CSS. The C-indices of the OS model were 0.76 and 0.77 in the training and validation groups, respectively, while they were 0.76 and 0.78 for CSS, respectively. For OS, the 3- and 5-year AUCs were 0.801 and 0.798, respectively, in the training cohort and 0.827 and 0.799, respectively, in the validation cohort; for CSS, they were 0.809 and 0.786, respectively, in the training cohort and 0.831 and 0.801, respectively, in the validation cohort. Calibration curves revealed high consistency in both OS and CSS between the observed survival and the predicted survival. In addition, DCA was used to analyse the clinical practicality of the OS and CSS nomogram models and revealed that they had good net benefits. Surgery remains the main treatment method for SCS patients. The two nomograms we established are expected to accurately predict the personalized prognosis of SCS patients and may be useful for clinical decision-making.

Abstract The mid-eastern segment of the Qilianshan fault zone (QLF) on the northeastern margin of the Qinghai–Tibet Plateau is considered one of the key seismic hazard areas. The Zhangye Ms5.0 earthquake and Menyuan Ms6.9 earthquake are the two Ms ≥ 5.0 earthquakes in recent years. The spatio-temporal evolution of Rn across the fault before the two Ms ≥ 5.0 earthquakes were explored by combining a solid seismogenic model and numerical simulation results in this study. The results demonstrates the spatial distribution of Rn concentration intensity varies over time, indicating the evolving characteristics of fracture zone activity. The time-series variation characteristics are closely related the Zhangye Ms5.0 earthquake and Menyuan Ms6.9 earthquake. Overall, in the seismic source area and surrounding medium area of Zhangye Ms5.0 earthquake, the soil gas Rn anomaly across faults characterized by a turning upward trend after continuous decline. The closer to the source area, the more obvious the upward trend. For Menyuan Ms6.9 earthquake, the survey line (HT1) located in the main fracture zone of the earthquake and the survey line (HT7,30km from the epicenter) closer to the epicenter also showed a similar trend, while the other measurement lines in far-field exhibit declining trend before the Menyuan Ms6.9 earthquake. Therefore, the continuous decline trend of soil gas may be crucial information for medium-term earthquake preparation in the seismogenic zone, and the trend of turning upward after continuous decline is a significant signal of short-term seismogenic event in far-field. This research could improve the understanding of the anomalous features of soil gas precursors and tracking the active sections of the fault. According to the model, the earthquake area canseismic source area, the surrounding medium area be divided into three sections: the seismic source area, the surrounding medium area, and the fracture fragmentation area.

Abstract Background Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. Results Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3′UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3′UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection. Conclusions This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis.

Abstract Aims The aims are to describe the key components of family integrated care intervention for preterm infants in the neonatal intensive care unit (NICU) and assess the impact on breastfeeding outcomes for those infants. Design A scoping review. Methods We conducted a systematic study search based on the databases, including PubMed, Scopus, Cochrane, Web of Science, MEDLINE, CINAHL, CNKI and Wanfang Database in December 2022. The search time ranged from database establishment to 31 December 2022. Papers by manual searching were also listed on the references. We adopted Joanna Briggs Institute Reviewer's Manual methodology and followed the PRISMA guidelines for Scoping Reviews (PRISMA‐ScR) to conduct the review. Two independent reviewers filtered the papers, extracted data and synthesized the findings. A table was used to extract data and synthesize results. Results After systematic searching, 11 articles that implemented family integrated care (FIcare) were finally included in this scoping review. By analysing the implementation of this nursing model, we identified seven main components: NICU staff training, parent education, parent participation in infants' care, parent involvement in medical plans, peer support, NICU environmental support and mobile app for parents. Based on the extracted breastfeeding data, this scoping review concludes that family integrated care shows a positive effect on increasing breastfeeding rates at discharge. Through this scoping review, we find that family integrated care is feasible and it can support breastfeeding of preterm infants. Further studies will be needed to provide more evidence that family integrated care could facilitate breastfeeding of preterm infants. Impact This scoping review provides evidence for the positive role of family integrated care on breastfeeding outcomes. The analysis may contribute to the implementation of family integrated care. No patient or public contribution No further public or patient contribution was made in view of the review‐based nature of the research.

Background The quality of life of patients with nephrotic syndrome requires a lot of focus, and improvements. A relevant scale can be used to measure it, but there is no nephrotic syndrome-specific quality of scale. Objective To develop a Quality of Life Instruments for Chronic Diseases-Nephrotic Syndrome〔QLICD-NS (V2.0) 〕 combined with QLICD-GM (V2.0), then verify it using the classical test theory. Methods From 2017 to 2021, an item pool was established according to literature review and the results of a semi-structured questionnaire, then the items were screened in accordance with a pre-test and importance score rated by physicians and patients, after that, the draft of the QLICD-NS (V2.0) was developed. The draft version was tested using onsite interview and questionnaire survey in nephrotic syndrome patients treated in Department of Nephrology, the Affiliated Hospital of Guangdong Medical University from March to November 2021. The first measurement was conducted on the day of admission, the second measurement was conducted with some of the patients, and the third measurement was conducted on the day of discharge. The coefficient of variation, correlation coefficient and Cronbach's α, factor analysis and classical test theory were used to evaluate QLICD-NS (V2.0) . Results The QLICD-NS (V2.0) contains 15 items, belonging to three domains of clinical symptoms, adverse drug reactions and psychological effects. The Cronbach's α measuring the split-half reliability was greater than 0.7 for the scale and each of the three domains. With the Chinese version of SF-36 as the calibration standard, the domains of the QLICD-NS (V2.0) were highly correlated with their counterpart domains of the Chinese version of SF-36. The standardized response mean was greater than 0.80 for all domains and items (except for the cognition and social support items), indicating that the responsiveness of the QLICD-NS (V2.0) was good. Scanning the QR code in the text can obtain the detailed evaluation of the scale. Conclusion The QLICD-NS (V2.0) compiled by us includes 15 items, and has proven with good reliability, validity and responsiveness.

Acid-base dissociation constant (pKa) is a key physicochemical parameter in chemical science, especially in organic synthesis and drug discovery. Current methodologies for pKa prediction still suffer from limited applicability domain and lack of chemical insight. Here we present MF-SuP-pKa (multi-fidelity modeling with subgraph pooling for pKa prediction), a novel pKa prediction model that utilizes subgraph pooling, multi-fidelity learning and data augmentation. In our model, a knowledge-aware subgraph pooling strategy was designed to capture the local and global environments around the ionization sites for micro-pKa prediction. To overcome the scarcity of accurate pKa data, low-fidelity data (computational pKa) was used to fit the high-fidelity data (experimental pKa) through transfer learning. The final MF-SuP-pKa model was constructed by pre-training on the augmented ChEMBL data set and fine-tuning on the DataWarrior data set. Extensive evaluation on the DataWarrior data set and three benchmark data sets shows that MF-SuP-pKa achieves superior performances to the state-of-the-art pKa prediction models while requires much less high-fidelity training data. Compared with Attentive FP, MF-SuP-pKa achieves 23.83% and 20.12% improvement in terms of mean absolute error (MAE) on the acidic and basic sets, respectively.

BackgroundDue to cosmetic disfigurement, melasma can negatively affect the quality of life and emotional and mental health, further leading to depression.ObjectivePrevalence rates of depression in patients with melasma vary widely across studies. The aim of this systematic review and meta-analysis was to estimate the prevalence of depression among melasma patients.MethodsThe PubMed, Embase, Web of Science, and Scopus databases were searched to identify articles evaluating the prevalence of depression in melasma patients from their inception to 12 July 2023. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and a meta-analysis was performed using the Stata 14.0 software.ResultsSixteen studies met the eligibility criteria out of the 859 studies, containing a total of 2,963 melasma patients for this systematic review and meta-analysis. Meta-analyses revealed that the pooled prevalence of depression among patients with melasma was 43.4% (95% CI 30.5–56.2%, Q-value = 808.859, d.f. = 15, p

Objective To investigate factors that differentiate elderly adults in rural China who accept free vision screening and cataract surgery from those who could benefit from vision care but refuse it when offered.Design We conducted a population-based, cross-sectional study between October and December 2016. Logistic regression models were used to examine the predictors of accepting free vision screening and cataract surgery.Setting Rural communities in Handan, China.Participants Adults aged 50 years or older, with presenting visual acuity ≤6/18 in the better seeing eye, suspected by examining ophthalmologist to be due to cataract.Results Among 613 persons with cataract identified on a population basis, 596 (97.2%) completed the household survey (mean (SD) age, 71.5 (10.0) years; 79.8% female). A total of 214 persons (35.9%) refused participation, while 382 (64.1%) took part in the vision screening. A total of 193 (50.5%) participants were found eligible for surgery, while 189 (49.5%) were not. Among 99 randomly selected participants who were offered immediate free surgery, surgery was accepted by 77 participants (77.8%) and refused by 22 (22.2%). In the multivariate model, being engaged in income-generating activities (p

Background The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset‐to‐puncture time remain unclear. Methods and Results This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non‐SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0–3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58–1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non‐SOTMD (OR, 1.67 [95% CI, 1.14–2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non‐SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. Conclusions No significant difference was observed in favorable outcomes between the SOTMD and non‐SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cells (e.g., dendritic cells and macrophages). In this project, we aimed at developing novel lipid-based nanoformulations for mRNA delivery to counteract the pandemic caused by SARS-CoV-2 virus. The formulations achieved a mRNA encapsulation efficiency of ~80.2% with chitosan-lipid nanoparticles, as measured by the RiboGreen assay. Furthermore, the evaluation of SARS-CoV-2 Spike (S) receptor-binding domain (RBD) expression via ELISA for our vaccine formulations showed transfection levels in human embryonic kidney cells (HEK 293), lung carcinoma cells (A549), and dendritic cells (DC 2.4) equal to 9.9 ± 0.1 ng/mL (174.7 ± 1.1 fold change from untreated cells (UT)), 7.0 ± 0.2 ng/mL (128.1 ± 4.9 fold change from UT), and 0.9 ± 0.0 ng/mL (18.0 ± 0.1 fold change from UT), respectively. Our most promising vaccine formulation was also demonstrated to be amenable to lyophilization with minimal degradation of loaded mRNA, paving the way towards a more accessible and stable vaccine. Preliminary in vivo studies in mice were performed to assess the systemic and local immune responses. Nasal bronchoalveolar lavage fluid (BALF) wash showed that utilizing the optimized formulation resulted in local antibody concentrations and did not trigger any systemic antibody response. However, if further improved and developed, it could potentially contribute to the management of COVID-19 through nasopharyngeal immunization strategies.

Virus genome recoding is an attenuation method that confers genetically stable attenuation by rewriting a virus genome with numerous silent mutations. Prior flavivirus genome recoding attempts utilised codon deoptimisation approaches. However, these codon deoptimisation approaches act in a species dependent manner and were unable to confer flavivirus attenuation in mosquito cells or in mosquito animal models. To overcome these limitations, we performed flavivirus genome recoding using the contrary approach of codon optimisation. The genomes of flaviviruses such as dengue virus type 2 (DENV2) and Zika virus (ZIKV) contain functional RNA elements that regulate viral replication. We hypothesised that flavivirus genome recoding by codon optimisation would introduce silent mutations that disrupt these RNA elements, leading to decreased replication efficiency and attenuation. We chose DENV2 and ZIKV as representative flaviviruses and recoded them by codon optimising their genomes for human expression. Our study confirms that this recoding approach of codon optimisation does translate into reduced replication efficiency in mammalian, human, and mosquito cells as well as in vivo attenuation in both mice and mosquitoes. In silico modelling and RNA SHAPE analysis confirmed that DENV2 recoding resulted in the extensive disruption of genomic structural elements. Serial passaging of recoded DENV2 resulted in the emergence of rescue or adaptation mutations, but no reversion mutations. These rescue mutations were unable to rescue the delayed replication kinetics and in vivo attenuation of recoded DENV2, demonstrating that recoding confers genetically stable attenuation. Therefore, our recoding approach is a reliable attenuation method with potential applications for developing flavivirus vaccines.

Abstract Background Oculomotor nerve palsy is a common and well-described disease with diverse etiologies. Clinicians should quickly and correctly diagnose and treat oculomotor nerve palsy according to its characteristics and the accompanying symptoms and signs. Intracranial aneurysm is an important and frequent cause of oculomotor nerve palsy. Considering the catastrophic consequences of rupture, the possibility of an urgent, life-threatening disease should always be considered. Case presentation A 63-year-old Chinese woman presented with intermittent left ptosis and diplopia and painless incomplete oculomotor nerve palsy without pupil involvement. She manifested no mydriasis or extraocular muscle weakness, and the light reflex was normal. Other cranial nerves and somatosensory and somatomotor examinations were normal. The neostigmine experiment and electromyography were normal, so the diagnosis of myasthenia gravis was excluded. Brain magnetic resonance angiography showed a 4-mm aneurysm located at the cavernous segment of the left internal carotid artery. Unfortunately, the patient refused digital subtraction angiography and was discharged home without further treatment. Conclusion Neuroimaging must be performed to exclude intracranial aneurysms in oculomotor nerve palsy regardless of whether the pupils are involved, as aneurysm rupture carries substantial morbidity and mortality.

Abstract Background Waardenburg syndrome is an autosomal dominant disorder with varying degrees of sensorineural hearing loss as well as abnormal pigmentation in hair, skin, and iris. There are four types of Waardenburg syndrome (1–4) with different characteristics. Mutations in six genes have been identified to be associated with the various types. Herein, we describe a case of Waardenburg syndrome type 4 combined with open-angle glaucoma. Case presentation A 43-year-old Han Chinese man had undergone trabeculectomy due to progression of visual field impairment and unstable intraocular pressure in both eyes. Slit-lamp examination revealed diffuse iris hypopigmentation in the left eye and hypopigmentation of part of the iris in the right eye. Fundus examination showed red, sunset-like fundus due to a lack of pigmentation in the retinal pigment epithelium layer, diffuse loss of the nerve fiber layer, and an excavated optic nerve head with advanced-stage glaucoma. Imaging was performed using anterior segment optical coherence tomography to detect the iris configuration. In the heterochromic iris portion, the normal part of the iris showed a clear hyperreflective signal of the anterior border layer, while atrophy of the pigmented anterior border layer showed a hyporeflective area of the anterior surface resulting in reduced light absorption. Two mutations of the endothelin receptor type B gene were recognized in this study. The first (c.1111G>A on exon 7) leads to an amino acid change from glycine to serine at codon 371. Sanger verification revealed that this mutation is inherited from the mother. The other mutation (c.553G>A) leads to an amino acid change from valine to methionine at codon 185. Sanger verification showed that this mutation was inherited from the father. Conclusion Waardenburg syndrome shows a remarkable diversity in clinical presentation and morphology. This disease can also present with open-angle glaucoma. Sequencing analysis revealed two heterozygous mutations in the EDNRB gene in this patient, inherited from his mother and father, respectively. These two sites constitute a compound heterozygous variation.

Nutrition poverty alleviation is an effective measure to improve the nutritional status of economically disadvantaged individuals, fundamentally improving their health and reducing poverty. Based on the Entitlement Theory and using the China Health and Nutrition Survey (CHNS) data, this paper examines the relationship between farmers’ nutritional intake, production structure and regional market conditions. Results show that farmers with diversified production have better nutritional intake than those who specialize. Furthermore, the correlation between regional market conditions and nutritional intake varies between economically disadvantaged and non-economically disadvantaged households. Market conditions significantly influence the carbohydrate and fat intake of economically disadvantaged households and are positively associated with the dietary structure and nutritional intake of non-economically disadvantaged ones. Moreover, income is positively correlated with the nutritional intake of non-economically disadvantaged households but not with economically disadvantaged ones.

Abstract Breastfeeding plays an important role in the growth and development of preterm infants, and exclusive breastfeeding (EBF) in the first 6 weeks post‐partum is the key to continuous breastfeeding. This study was designed to explore the influencing factors that contribute to breastfeeding attrition among mothers of preterm infants at Week 6 post‐partum based on the theory of planned behaviour (TPB). We herein adopted a prospective observational study design in which 97 mothers who exclusively breastfed at Week 6 post‐partum at a tertiary specialised hospital in Shanghai from June 2021 to February 2022 were taken as the EBF group, and 179 mothers without EBF were assigned to the EBF attrition group. Through an extensive literature review and expert consultation, we determined the possible factors influencing EBF attrition, analysed those factors that showed statistical significance in our univariate analysis by applying binary logistic regression, and constructed a nomogram model for predicting EBF attrition. The results revealed that negative breastfeeding sentiment (odds ratio [OR] = 1.006; 95% confidence interval [CI], 1.000–1.011) generated a greater risk of breastfeeding attrition. However, positive breastfeeding sentiment (OR = 0.991; 95% CI, 0.983–0.999), social and professional support (OR = 0.993; 95% CI, 0.987–0.999), breastfeeding control (OR = 0.945; 95% CI, 0.896–0.996), knowledge (OR = 0.893; 95% CI, 0.799–0.998), and intention to EBF at Week 6 post‐partum (OR = 0.522; 95% CI, 0.276–0.988) were the protective factors and facilitated the development of our nomogram model. The Hosmer–Lemeshow goodness‐of‐fit test generated a χ2 value of 11.344 (p = 0.183) and an area under the curve of 0.822 (95% CI, 0.771–0.873). The C‐index was 0.800 in the internal bootstrap validation, indicating that the nomogram model possessed favourable predictive accuracy and discrimination.

Abstract Background The leaves of the plant Ilex latifolia Thunb. can be made into Kuding tea, which is a drink rich in polyphenols. This study aimed to observe the effect of Ilex latifolia Thunb. polyphenols (ILTPs) on human lung cancer cell line A549 (A549 cells) by regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods In vitro cultured cells were treated with ILTPs; the proliferation of A549 cells and BEAS-2B human normal lung epithelial cells (Beas-2B cells) was observed using the 3-(4,5-dimethylazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the survival status of A549 cells was observed by fluorescence staining. The expression of A549 cells was observed by quantitative polymerase chain reaction (qPCR) assay and Western blot analysis, while the compound composition of ILTPs was detected using high-performance liquid chromatography (HPLC). Results The experimental results showed that the proliferation of Beas-2B cells was unaffected by treatment with 0–500 μg/mL of ILTPs, whereas the decreased proliferation of A549 cells was observed with the increasing concentrations of ILTPs. Additionally, ILTPs elevated the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) and promoted apoptosis in A549 cells. The results of qPCR experiments showed that ILTPs upregulated caspase-9 mRNA expression and downregulated phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma-2 (Bcl-2), nuclear factor-κB (NF-κB), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1α), and cyclooxygenase-2 (COX-2) expression in A549 cells. The Western blot analysis results also showed that ILTPs could reduce the protein expression of PI3K and Akt. The HPLC results showed that the main compounds present in the ILTPs were rutin, kaempferol, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C. Conclusions Thus, this study indicated that the polyphenols of I. latifolia act as a class of natural functional food materials that potently suppress cancer by exerting their inhibitory effects on A549 cell proliferation through five key polyphenolic compounds.

Objective: To investigate the safety and efficacy of selective intraarterial hypothermia combined with mechanical thrombectomy in the treatment of acute cerebral infarction based on microcatheter technology. Methods: A total of 142 patients with anterior circulation large vessel occlusion were randomly assigned to the hypothermic treatment group (test group) and the conventional treatment group (control group). National Institutes of Health Stroke Scale (NIHSS) scores, postoperative infarct volume, the 90-day good prognosis rate (modified Rankin Scale (mRS) score =2 points), and the mortality rate of the two groups were compared and analyzed. Blood specimens were collected from patients before and after treatment. Serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6), IL-10, and RNA-binding motif protein 3 (RBM3) were measured. Results: The 7-day postoperative cerebral infarct volume [(63.7 ± 22.1) ml vs. (88.5 ± 20.8) ml] and NIHSS scores at postoperative Days 1, 7, and 14 [(6.8 ± 3.8) points vs. (8.2 ± 3.5) points; (2.6 ± 1.6) points vs. (4.0 ± 1.8) points; (2.0 ± 1.2) points vs. (3.5 ± 2.1) points] in the test group were significantly lower than those in the control group. The good prognosis rate at 90 days postoperatively (54.9 vs. 35.2%, P = 0.018) was significantly higher in the test group than in the control group. The 90-day mortality rate was not statistically significant (7.0 vs. 8.5%, P=0.754). Immediately after surgery and 1 day after surgery, SOD, IL-10, and RBM3 levels in the test group were relatively higher than those in the control group, and the differences were statistically significant. Immediately after surgery and 1 day after surgery, MDA and IL-6 levels in the test group were relatively reduced compared with those in the control group, and the differences were statistically significant (P < 0.05). In the test group, RBM3 was positively correlated with SOD and IL-10. Conclusion: Mechanical thrombectomy combined with intraarterial cold saline perfusion is a safe and effectivemeasure for the treatment of acute cerebral infarction. Postoperative NIHSS scores and infarct volumes were significantly improved with this strategy compared with simple mechanical thrombectomy, and the 90-day good prognosis rate was improved. The mechanism by which this treatment exerts its cerebral protective effect may be by inhibiting the transformation of the ischaemic penumbra of the infarct core area, scavenging some oxygen free radicals, reducing inflammatory injury to cells after acute infarction and ischaemia-reperfusion, and promoting RBM3 production in cells. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the safety and efficacy of selective intraarterial hypothermia combined with mechanical thrombectomy in the treatment of acute cerebral infarction based on microcatheter technology.MethodsA total of 142 patients with anterior circulation large vessel occlusion were randomly assigned to the hypothermic treatment group (test group) and the conventional treatment group (control group). National Institutes of Health Stroke Scale (NIHSS) scores, postoperative infarct volume, the 90-day good prognosis rate (modified Rankin Scale (mRS) score ≤ 2 points), and the mortality rate of the two groups were compared and analyzed. Blood specimens were collected from patients before and after treatment. Serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6), IL-10, and RNA-binding motif protein 3 (RBM3) were measured.ResultsThe 7-day postoperative cerebral infarct volume [(63.7 ± 22.1) ml vs. (88.5 ± 20.8) ml] and NIHSS scores at postoperative Days 1, 7, and 14 [(6.8 ± 3.8) points vs. (8.2 ± 3.5) points; (2.6 ± 1.6) points vs. (4.0 ± 1.8) points; (2.0 ± 1.2) points vs. (3.5 ± 2.1) points] in the test group were significantly lower than those in the control group. The good prognosis rate at 90 days postoperatively (54.9 vs. 35.2%, P = 0.018) was significantly higher in the test group than in the control group. The 90-day mortality rate was not statistically significant (7.0 vs. 8.5%, P = 0.754). Immediately after surgery and 1 day after surgery, SOD, IL-10, and RBM3 levels in the test group were relatively higher than those in the control group, and the differences were statistically significant. Immediately after surgery and 1 day after surgery, MDA and IL-6 levels in the test group were relatively reduced compared with those in the control group, and the differences were statistically significant (P < 0.05). In the test group, RBM3 was positively correlated with SOD and IL-10.ConclusionMechanical thrombectomy combined with intraarterial cold saline perfusion is a safe and effective measure for the treatment of acute cerebral infarction. Postoperative NIHSS scores and infarct volumes were significantly improved with this strategy compared with simple mechanical thrombectomy, and the 90-day good prognosis rate was improved. The mechanism by which this treatment exerts its cerebral protective effect may be by inhibiting the transformation of the ischaemic penumbra of the infarct core area, scavenging some oxygen free radicals, reducing inflammatory injury to cells after acute infarction and ischaemia–reperfusion, and promoting RBM3 production in cells.

Abstract Long non-coding RNAs (lncRNAs) regulate numerous biological processes involved in both development and carcinogenesis. Hippo-YAP/TAZ signaling, a critical pathway responsible for organ size control, is often dysregulated in a variety of cancers. However, the nature and function of YAP/TAZ-regulated lncRNAs during tumorigenesis remain largely unexplored. By profiling YAP/TAZ-regulated lncRNAs, we identified SFTA1P as a novel transcriptional target and a positive feedback regulator of YAP/TAZ signaling. Using non-small cell lung cancer (NSCLC) cell lines, we show that SFTA1P is transcriptionally activated by YAP/TAZ in a TEAD-dependent manner. Functionally, knockdown of SFTA1P in NSCLC cell lines inhibited proliferation, induced programmed cell death, and compromised their tumorigenic potential. Mechanistically, SFTA1P knockdown decreased TAZ protein abundance and consequently, the expression of YAP/TAZ transcriptional targets. We provide evidence that this phenomenon could potentially be mediated via its interaction with TAZ mRNA to regulate TAZ translation. Our results reveal SFTA1P as a positive feedback regulator of Hippo-YAP/TAZ signaling, which may serve as the molecular basis for lncRNA-based therapies against YAP/TAZ-driven cancers.

Here, Yang et al. apply different RNA sequencing approaches to characterize the secondary structure of SARS-CoV-2 viral RNAs, report on long-range interactions along the viral genome, and uncover the virus-host RNA interactome in cells.