Extracellular vesicles reshape the tumor microenvironment to improve cancer immunotherapy: Current knowledge and future prospects.

Tumor immunotherapy has revolutionized cancer treatment, but limitations remain, including low response rates and immune complications. Extracellular vesicles (EVs) are emerging as a new class of therapeutic agents for various diseases. Recent research shows that changes in the amount and composition of EVs can reshape the tumor microenvironment (TME), potentially improving the effectiveness of immunotherapy. This exciting discovery has sparked clinical interest in using EVs to enhance the immune system's response to cancer. In this Review, we delve into the world of EVs, exploring their origins, how they're generated, and their complex interactions within the TME. We also discuss the crucial role EVs play in reshaping the TME during tumor development. Specifically, we examine how their cargo, including molecules like PD-1 and non-coding RNA, influences the behavior of key immune cells within the TME. Additionally, we explore the current applications of EVs in various cancer therapies, the latest advancements in engineering EVs for improved immunotherapy, and the challenges faced in translating this research into clinical practice. By gaining a deeper understanding of how EVs impact the TME, we can potentially uncover new therapeutic vulnerabilities and significantly enhance the effectiveness of existing cancer immunotherapies.

Rapidly progressive necrotizing enterocolitis: Risk factors and a predictive model.

BACKGROUND: Rapidly progressive necrotizing enterocolitis (RP-NEC) is a particular subtype of NEC known for its rapid progression and high mortality rate. The objective of this study was to establish a predictive model for RP-NEC. METHODS: This was a retrospective single-center cohort study. Patients were newborn infants with NEC (Bell's stage ≥ IIB) admitted from January 1, 2016 to December 31, 2023. The primary outcome was RP-NEC defined as the need for surgical intervention and/or death within 48 hours of the onset of NEC. RESULTS: Totally 334 newborn infants were included, among which 82 (24.6%) were RP-NEC cases with a gestation age 34.1 (31.0, 37.0) weeks and birth weight 2100 (1413, 2800) g. Plasma sodium <135 mmol/L, C-reactive protein ≥10 mg/L, platelet count <100 × 109/L, lymphocyte count <1.5 × 109/L, pH <7.2 in blood gas, and ascites at NEC onset were identified as independent risk factors for RP-NEC. The model established presented an AUC value of 0.983 (95% CI 0.97-0.99). The calibration curve for validation was applied revealing a slope close to unity while the Hosmer-Lemeshow test yielded χ2 = 2.550 (p = 0.636). CONCLUSION: The predictive model established on the above 6 items of RP-NEC is highly promising. IMPACT: Currently, there is a paucity of research on this specific type of severe necrotizing enterocolitis (NEC) characterized by rapid progression. Our study was to investigate the risk factors associated with surgical intervention and/or death within 48 hours following onset in infants with NEC, establish a predictive model for infants with rapidly progressive NEC. The new data presented in this study was the ROC curve combining the above factors as well as hyponatremia.

Fuzheng Huayu recipe inhibits bleomycin-induced pulmonary fibrosis in rats by inhibiting M2 polarization of macrophages via the oxidative phosphorylation pathway.

Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.

Biomaterials-mediated radiation-induced diseases treatment and radiation protection.

In recent years, the intersection of the academic and medical domains has increasingly spotlighted the utilization of biomaterials in radioactive disease treatment and radiation protection. Biomaterials, distinguished from conventional molecular pharmaceuticals, offer a suite of advantages in addressing radiological conditions. These include their superior biological activity, chemical stability, exceptional histocompatibility, and targeted delivery capabilities. This review comprehensively delineates the therapeutic mechanisms employed by various biomaterials in treating radiological afflictions impacting the skin, lungs, gastrointestinal tract, and hematopoietic systems. Significantly, these nanomaterials function not only as efficient drug delivery vehicles but also as protective agents against radiation, mitigating its detrimental effects on the human body. Notably, the strategic amalgamation of specific biomaterials with particular pharmacological agents can lead to a synergistic therapeutic outcome, opening new avenues in the treatment of radiation- induced diseases. However, despite their broad potential applications, the biosafety and clinical efficacy of these biomaterials still require in-depth research and investigation. Ultimately, this review aims to not only bridge the current knowledge gaps in the application of biomaterials for radiation-induced diseases but also to inspire future innovations and research directions in this rapidly evolving field.

Evaluation of the effects of health education interventions for hypertensive patients based on the health belief model.

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease and stroke, and its prevalence is increasing worldwide. Health education interventions based on the health belief model (HBM) can improve the knowledge, attitudes, and behaviors of patients with hypertension and help them control their blood pressure. AIM: To evaluate the effects of health education interventions based on the HBM in patients with hypertension in China. METHODS: Between 2021 and 2023, 140 patients with hypertension were randomly assigned to either the intervention or control group. The intervention group received health education based on the HBM, including lectures, brochures, videos, and counseling sessions, whereas the control group received routine care. Outcomes were measured at baseline, three months, and six months after the intervention and included blood pressure, medication adherence, self-efficacy, and perceived benefits, barriers, susceptibility, and severity. RESULTS: The intervention group had significantly lower systolic blood pressure [mean difference (MD): -8.2 mmHg, P < 0.001] and diastolic blood pressure (MD: -5.1 mmHg, P = 0.002) compared to the control group at six months. The intervention group also had higher medication adherence (MD: 1.8, P < 0.001), self-efficacy (MD: 12.4, P < 0.001), perceived benefits (MD: 3.2, P < 0.001), lower perceived barriers (MD: -2.6, P = 0.001), higher perceived susceptibility (MD: 2.8, P = 0.002), and higher perceived severity (MD: 3.1, P < 0.001) than the control group at six months. CONCLUSION: Health education interventions based on the HBM effectively improve blood pressure control and health beliefs in patients with hypertension and should be implemented in clinical practice and community settings.

Genome-wide identification and integrated analysis of TCP genes controlling ginsenoside biosynthesis in Panax ginseng.

Panax ginseng is an important medicinal plant, and ginsenosides are the main bioactive molecules of ginseng. The TCP (TBI, CYC, PCF) family is a group of transcription factors (TFs) that play an important role in plant growth and development, hormone signalling and synthesis of secondary metabolites. In our study, 78 PgTCP transcripts were identified from the established ginseng transcriptome database. A phylogenetic tree analysis showed that the 67 PgTCP transcripts with complete open reading frames were classified into three subfamilies, including CIN, PCF, and CYC/TB1. Protein structure analysis showed that PgTCP genes had bHLH structures. Chromosomal localization analysis showed that 63 PgTCP genes were localized on 17 of the 24 chromosomes of the Chinese ginseng genome. Expression pattern analysis showed that PgTCP genes differed among different lineages and were spatiotemporally specific. Coexpression network analysis indicated that PgTCP genes were coexpressed and involved in plant activities or metabolic regulation in ginseng. The expression levels of PgTCP genes from class I (PCF) were significantly downregulated, while the expression levels of PgTCP genes from class II (CIN and CYC/TB1) were upregulated, suggesting that TCP genes may be involved in the regulation of secondary metabolism in ginseng. As the PgTCP26-02 gene was found to be related to ginsenoside synthesis, its predicted protein structure and expression pattern were further analysed. Our results provide new insights into the origin, differentiation, evolution and function of the PgTCP gene family in ginseng, as well as the regulation of plant secondary metabolism.

SIRT3-Mediated Deacetylation of SDHA Rescues Mitochondrial Bioenergetics Contributing to Neuroprotection in Rotenone-Induced PD Models.

Mitochondrial dysfunction is critically involved in the degeneration of dopamine (DA) neurons in the substantia nigra, a common pathological feature of Parkinson's disease (PD). Previous studies have demonstrated that the NAD+-dependent acetylase Sirtuin 3 (SIRT3) participates in maintaining mitochondrial function and is downregulated in aging-related neurodegenerative disorders. The exact mechanism of action of SIRT3 on mitochondrial bioenergetics in PD pathogenesis, however, has not been fully described. In this study, we investigated the regulatory role of SIRT3-mediated deacetylation of mitochondrial complex II (succinate dehydrogenase) subunit A (SDHA) and its effect on neuronal cell survival in rotenone (ROT)-induced rat and differentiated MN9D cell models. The results revealed that SIRT3 activity was suppressed in both in vivo and in vitro PD models. Accompanying this downregulation of SIRT3 was the hyperacetylation of SDHA, impaired activity of mitochondrial complex II, and decreased ATP production. It was found that the inhibition of SIRT3 activity was attributed to a reduction in the NAD+/NADH ratio caused by ROT-induced inhibition of mitochondrial complex I. Activation of SIRT3 by icariin and honokiol inhibited SDHA hyperacetylation and increased complex II activity, leading to increased ATP production and protection against ROT-induced neuronal damage. Furthermore, overexpression of SDHA also exerted potent protective benefits in cells treated with ROT. In addition, treatment of MN9D cells with the NAD+ precursor nicotinamide mononucleotide increased SIRT3 activity and complex II activity and promoted the survival of cells exposed to ROT. These findings unravel a regulatory SIRT3-SDHA axis, which may be closely related to PD pathology. Bioenergetic rescue through SIRT3 activation-dependent improvement of mitochondrial complex II activity may provide an effective strategy for protection from neurodegeneration.

Efficacy and tolerability of oxcarbazepine in the treatment of focal epilepsy in neonates and infants under 3 months of age: A single-center retrospective analysis.

OBJECTIVE: The neonatal and infantile period is the age group with the highest incidence of epilepsy, in which gene variants in sodium and potassium channels are an important etiology, so the sodium channel blocker class of antiseizure medications may be effective in the treatment of early onset epilepsy. This study aimed to summarize the efficacy and tolerability of oxcarbazepine (OXC) in the treatment of focal epilepsy in neonates and infants under 3 months of age. METHODS: A retrospective analysis of children with focal epilepsy onset within 3 months of age and treated with OXC in a tertiary pediatric epilepsy center in China was conducted. The efficacy, tolerability and influencing factors of OXC were evaluated. RESULTS: A total of 50 patients were enrolled, with a median age of epilepsy onset of 11.5 (2, 42) days. There were 32 cases of early infantile developmental and epileptic encephalopathy, 10 cases of self-limited neonatal or neonatal-infantile epilepsy, and 8 cases of focal epilepsy that could not be classified as epileptic syndrome. The median age of application of OXC was 47 (31, 66) days. The median follow-up time was 16.5 (10, 25) months, with 7 deaths. Thirty-eight cases (76.0 %) were effective with OXC treatment, including 28 cases (56.0 %) achieved seizure freedom. Of the 34 cases whose pathogenesis involved genetic factors, 19 cases with sodium/ potassium channel gene variants had higher effective and seizure-free rates than those with other gene variants. The most common adverse event was transient hyponatremia. 2 cases had rash and 2 cases had abnormal electrocardiogram, 3 of which discontinued OXC. SIGNIFICANCE: This single-center retrospective study suggests that OXC is effective and tolerable for the treatment of focal epilepsy in neonates and infants under 3 months of age. The efficacy of OXC is better in patients with sodium/ potassium channel gene variants.

An outbreak of school influenza complicated with mycoplasma pneumoniae infection / 中国学校卫生

Objective@#To describe the clinical features, causal agent and transmission mode of a fever outbreak in a school in Shanghai.@*Methods@#Field epidemiological approaches including case definition development, searching for contacts, distribution of diseases description, environmental sampling and laboratory testing.@*Results@#A total of 16 influenza like cases were included, all concentrated in the one class of grade two, including 15 students and 1 teacher. Among student cases, the incidence rate was 36.59% (15/41), the average age was 7.4 years, the incidence rate was 36.84%(7/19) for boys, 36.36%(8/22) for girls. The clinical course was 5-15 days, with the median of 9 days, and 18.75%(3/16) of the cases stayed studying while sick. The nasopharyngeal swab specimens in 16 cases all tested positive for influenza B, of which 11 tested positive for mycoplasma pneumoniae and 1 case also tested positive for coronavirus OC43. Body temperature, number of mononuclear cells, and treatment time of patients infected with Influenza B and mycoplasma pneumoniae were higher than those of patients infected with influenza B alone( P <0.05). The outbreak lasted for 12 days, all sick students were treated and discharged from hospital, with no severe cases or death, and the outbreak was effectively controlled.@*Conclusion@#This campus cluster outbreak caused by influenza B and mycoplasma pneumoniae. Patients with influenza B with mycoplasma pneumoniae have severe symptoms and a long course of illness, suggesting the importance of early management of the epidemic.

Opening up Neat New Things: Exploring Understandings and Experiences of Social and Emotional Learning and Meaningful Physical Education Utilizing Democratic and Reflective Pedagogies.

When it comes to teaching social and affective outcomes pertaining to health and physical activity within Physical Education (PE) settings, such learning historically has been observed as manifesting itself as hoped-for-by-products rather than intentionally-taught-for curricular outcomes. The purpose of this study was to explore understandings and experiences of Social and Emotional Learning (SEL) and Meaningful Physical Education (MPE) utilizing democratic and reflective pedagogies. A qualitative case study design was implemented in an alternative high school setting in the USA across 10 months. Participants included the Teacher-Researcher (TR), one Physical Education (PE) teacher, a critical friend, two teaching assistants, and 16 ninth-grade alternative high school students aged 14-15 (eight girls/eight boys). Methods involved a TR journal, post-lesson teaching reflections, interviews, and focus groups, with inductive and deductive analysis applied. The following themes were constructed: It really made you think; making movement meaningful; being a better classmate; and doing things differently. Results demonstrate how utilizing democratic and reflective approaches grounded in social constructivist learning theory innovatively promoted SEL and MPE. It allowed students to reflect, interrogate and discuss how movement experiences inside and outside of PE influenced their pursuit of a physically active life. Participants articulated experiencing a more inclusive learning experience that challenged the purpose and subject matter of previous PE and physical activity. Teaching for SEL and MPE using common language and terminology around pre-identified and defined competencies, skills, and features drawn from these conceptual frameworks as demonstrated here, can help contribute to more concrete and uniform learning experiences within and across settings. Doing so led participants to demonstrate more holistic and broader understandings of what constituted participation in PE and physical activity, as well as how to promote and participate in meaningful movement and physical activity within and outside of school to promote healthy living. We call for further embedding of democratic and reflective pedagogies in PE teacher education and professional development that provides teachers and students with the opportunity to do so going forward.

Comparison of four neonatal transport scoring methods in the prediction of mortality risk in full-term, out-born infants: a single-center retrospective cohort study.

Neonatal transport scoring systems can assess severity before and after transport, improve transport efficiency, and predict the occurrence of critical illness. The aim of this study was to compare four neonatal transport scoring methods to predict mortality risk and clinical utility within the first week after transportation. This was a single-center retrospective cohort study. All patients were full-term, out-born neonates. Each patient was assessed by the Transport Risk Index of Physiologic Stability (TRIPS), Mortality Index for Neonatal Transportation (MINT), Transport-Related Mortality Score (TREMS), and Neonatal Critical Illness Score (NCIS) scoring methods. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) for each method were compared for their utility in predicting mortality risk within the 1st week after admission. In total, 368 full-term infants were included (368/770, 47.8% of all transported infants). Within the 1st week after admission, five infants (1.36%, 5/368) died while receiving advanced life support and full treatment, and 24 infants (6.52%, 24/368) died soon after they were discharged against medical advice. The areas under the curve (AUCs) for the MINT, TRIPS, TREMS, and NCIS for the prediction of mortality were 0.822, 0.827, 0.643, and 0.731, respectively (all p < 0.05). However, the clinical net benefits for the MINT and TRIPS were far superior than those for the NCIS and TREMS. CONCLUSION: It was concluded that the TRIPS and MINT might be more suitable for the prediction of mortality in full-term, out-born neonates in the neonatal intensive care unit (NICU) within the 1st week after transportation. WHAT IS KNOWN: • Neonatal transport scores can assess not only the mortality risk during transportation but also the mortality risk of critically ill newborns after admission to the NICU. • The effectiveness of neonatal transport scores in predicting mortality risk is different. WHAT IS NEW: • Our data indicate that the diagnostic efficacy of the MINT, TRIPS, and NCIS in the prediction of full-term infant mortality was high. • The TRIPS and MINT scores had better clinical utility and could be used to predict mortality within the 1st week after transportation in full-term out-born neonates.

"This Is Not Gym": Enacting Student Voice Pedagogies to Promote Social and Emotional Learning and Meaningful Physical Education.

The purpose of this study was to explore learners' experiences enacting youth/student voice pedagogies (SVP) to promote Social and Emotional Learning (SEL) and meaningful physical education (MPE) in an alternative education setting. Drawing on social constructivist learning theory in understanding and implementing a MPE approach, and a systemic framework for SEL, two research questions guided the research process: (1) How did students interpret and enact these pedagogies? (2) What contribution did the enactment of these pedagogies have in promoting SEL and MPE? This study implemented a qualitative case study design framed by a participatory action research (PAR) approach spanning 12 weeks from February to May 2021. Participants in this study included 16 ninth grade alternative high school students (eight girls/eight boys) aged 14-15 who had just returned to face-to-face learning in January 2021 for the first time following COVID-19. A range of traditional and innovative participatory qualitative research methods including focus group interviews, students' personal biographies, timelines, digital and written reflections, photovoice, and class artifacts were utilized. The Miles, Huberman, and Saldana Framework for Qualitative Data Analysis was implemented involving both deductive and inductive combinations of comparative and thematic analysis. The following themes were constructed: Making responsible decisions; unearthing and sharing mixed emotions; picturing physical activity beyond the classroom; recognizing the role of relationships; considering challenge and competence; and, pursuing meaning. Findings demonstrate how enacting SVP can lead to the development of students' SEL and MPE experiences complimenting multiple learning domains. We call for further embedding of SVP capturing students' physical activity and movement experiences inside and outside of PE in teacher education and professional development that helps teachers and their students make sense of, shape, influence, and enact more MPE and physical activity learning experiences.

Population pharmacokinetics-pharmacodynamics of ceftazidime in neonates and young infants: Dosing optimization for neonatal sepsis.

Ceftazidime is a third-generation cephalosporin with high activity against many pathogens. But the ambiguity and diversity of the dosing regimens in neonates and young infants impair access to effective treatment. Thus, we conducted a population pharmacokinetic study of ceftazidime in this vulnerable population and recommended a model-based dosage regimen to optimize sepsis therapy. Totally 146 neonates and young infants (gestational age (GA): 36-43.4 weeks, postnatal age (PNA): 1-81 days, current weight (CW): 900-4500 g) were enrolled based on inclusion and exclusion criteria. Ceftazidime bloods samples (203) were obtained using the opportunistic sampling strategy and determined by the high-performance liquid chromatography. The population pharmacokinetic-pharmacodynamic analysis was conducted by nonlinear mixed effects model (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic data. Covariate analysis showed the significance of GA, PNA, and CW on developmental pharmacokinetics. Monte Carlo simulation was performed based on above covariates and minimum inhibitory concentration (MIC). In the newborns with PNA ≤ 3 days (MIC=8 mg/L), the dose regimen was 25 mg/kg twice daily (BID). For the newborns with PNA > 3 days (MIC=16 mg/L), the optimal dose was 30 mg/kg three times daily (TID) for those with GA ≤ 37 weeks and 40 mg/kg TID for those with GA > 37 weeks. Overall, on the basis of the developmental population pharmacokinetic-pharmacodynamic analysis covering the whole range of neonates and young infants, the evidence-based ceftazidime dosage regimens were proposed to optimize neonatal early-onset and late-onset sepsis therapy.

Dendrobium nobile Lindl. alkaloids alleviate Mn-induced neurotoxicity via PINK1/Parkin-mediated mitophagy in PC12 cells.

Modern pharmacological studies have demonstrated that Dendrobium nobile Lindl. Alkaloids (DNLA), the main active ingredients of Dendrobium nobile, is valuable as an anti-aging and neuroprotective herbal medicine. The present study was designed to determine whether DNLA confers protective function over neurotoxicant manganese (Mn)-induced cytotoxicity and the mechanism involved. Our results showed that pretreatment of PC12 cells with DNLA alleviated cell toxicity induced by Mn and improved mitochondrial respiratory capacity and oxidative status. Mn treatment increased apoptotic cell death along with a marked increase in the protein expression of Bax and a decrease in the expression of Bcl-2 protein, all of which were noticeably reversed by DNLA. Furthermore, DNLA significantly abolished the decrease in protein levels of both PINK1 and Parkin, and mitigated the increased expression of autophagy marker LC3-II and accumulation of p62 caused by Mn. These results demonstrate that DNLA inhibits Mn induced cytotoxicity, which may be mediated through modulating PINK1/Parkin-mediated autophagic flux and improving mitochondrial function.

Endobronchial ultrasound-guided transbronchial needle aspiration combined with either endoscopic ultrasound-guided fine-needle aspiration or endoscopic ultrasound using the EBUS scope-guided fine-needle aspiration for diagnosing and staging mediastinal diseases: a systematic review and meta-analysis.

The present systematic review and meta-analysis aimed to evaluate the available evidence base on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) combined with either endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or endoscopic ultrasound using the EBUS scope-guided fine-needle aspiration (EUS-B-FNA) for diagnosing and staging mediastinal diseases. PubMed, Web of Science, and Embase were searched to identify suitable studies up to June 30, 2019. Two investigators independently reviewed articles and extracted relevant data. Data were pooled using random effect models to calculate diagnostic indices that included sensitivity and specificity. Summary receiver operating characteristic (SROC) curves were used to summarize the overall test performance. Data pooled from up to 16 eligible studies (including 10 studies of 963 patients about EBUS-TBNA with EUS-FNA and six studies of 815 patients with EUS-B-FNA) indicated that combining EBUS-TBNA with EUS-FNA was associated with slightly better diagnostic accuracy than combining it with EUS-B-FNA, in terms of sensitivity (0.87, 95%CI 0.83 to 0.90 vs. 0.84, 95%CI 0.80 to 0.88), specificity (1.00, 95%CI 0.99 to 1.00 vs. 0.96, 95%CI 0.93 to 0.97), diagnostic odds ratio (413.39, 95%CI 179.99 to 949.48 vs. 256.38, 95%CI 45.48 to 1445.32), and area under the SROC curve (0.99, 95%CI 0.97 to 1.00 vs. 0.97, 95%CI 0.92 to 1.00). The current evidence suggests that the combination of EBUS-TBNA with either EUS-FNA or EUS-B-FNA provides relatively high accuracy for diagnosing mediastinal diseases. The combination with EUS-FNA may be slightly better.

Regulation of SIRT3 on mitochondrial functions and oxidative stress in Parkinson's disease.

Sirtuin-3 (SIRT3) is a NAD+-dependent protein deacetylase that is located in mitochondria, regulating mitochondrial proteins and maintaining cellular antioxidant status. Increasing evidence demonstrates that SIRT3 plays a role in degenerative disorders including Parkinson's disease (PD), which is a devastating nervous system disease currently with no effective treatments available. Although the etiology of PD is still largely ambiguous, substantial evidence indicates that mitochondrial dysfunction and oxidative stress play major roles in the pathogenesis of PD. The imbalance of reactive oxygen species (ROS) production and detoxification leads to oxidative stress that can accelerate the progression of PD. By causing conformational changes in the deacetylated proteins SIRT3 modulates the activities and biological functions of a variety of proteins involved in mitochondrial antioxidant defense and various mitochondrial functions. Increasingly more studies have suggested that upregulation of SIRT3 confers beneficial effect on neuroprotection in various PD models. This review discusses the mechanism by which SIRT3 regulates intracellular oxidative status and mitochondrial function with an emphasis in discussing in detail the regulation of SIRT3 on each component of the five complexes of the mitochondrial respiratory chain and mitochondrial antioxidant defense, as well as the pharmacological regulation of SIRT3 in light of therapeutic strategies for PD.

Novel enhanced GFP-positive congenic inbred strain establishment and application of tumor-bearing nude mouse model.

Transgenic GFP gene mice are widely used. Given the unique advantages of immunodeficient animals in the field of oncology research, we aim to establish a nude mouse inbred strain that stably expresses enhanced GFP (EGFP) for use in transplanted tumor microenvironment (TME) research. Female C57BL/6-Tg(CAG-EGFP) mice were backcrossed with male BALB/c nude mice for 11 generations. The genotype and phenotype of novel inbred strain Foxn1nu .B6-Tg(CAG-EGFP) were identified by biochemical loci detection, skin transplantation and flow cytometry. PCR and fluorescence spectrophotometry were performed to evaluate the relative expression of EGFP in different parts of the brain. Red fluorescence protein (RFP) gene was stably transfected into human glioma stem cells (GSC), SU3, which were then transplanted intracerebrally or ectopically into Foxn1nu .B6-Tg(CAG-EGFP) mice. Cell co-expression of EGFP and RFP in transplanted tissues was further analyzed with the Live Cell Imaging System (Cell'R, Olympus) and FISH. The inbred strain Foxn1nu .B6-Tg(CAG-EGFP) shows different levels of EGFP expression in brain tissue. The hematological and immune cells of the inbred strain mice were close to those of nude mice. EGFP was stably expressed in multiple sites of Foxn1nu .B6-Tg(CAG-EGFP) mice, including brain tissue. With the dual-fluorescence tracing transplanted tumor model, we found that SU3 induced host cell malignant transformation in TME, and tumor/host cell fusion. In conclusion, EGFP is differentially and widely expressed in brain tissue of Foxn1nu .B6-Tg(CAG-EGFP), which is an ideal model for TME investigation. With Foxn1nu .B6-Tg(CAG-EGFP) mice, our research demonstrated that host cell malignant transformation and tumor/host cell fusion play an important role in tumor progression.

Anti-fibrotic effect of melittin on TRIM47 expression in human embryonic lung fibroblast through regulating TRIM47 pathway.

AIMS: To investigate the effect and underlying mechanism of melittin and tripartite motif (TRIM) family in human embryonic lung fibroblast (HELF). MATERIALS AND METHODS: Lentiviral RNA interference vector and lentiviral overexpression vector were constructed and packaged by transfecting 293T cells; the proliferation of HELF was examined using Cell Counting Kit 8; Western blot and qRT-PCR were performed to examine protein and mRNA expression; the interaction with protein phosphatase magnesium-dependent 1A (PPM1A) was examined by Co-immunoprecipitation. KEY FINDINGS: Compared with the control group, the mRNA expression of the TRIM6, TRIM8 and TRIM47 in the IPF group significantly increased. Melittin inhibited the mRNA expression and protein expression levels of TRIM47, the HELF proliferation, the hydroxyproline levels, and the phosphorylation of Smad2/3; the interference of TRIM47 inhibited the protein expression of Vimentin, α-SMA, CTGF, the phosphorylation of Smad2/3 and the synthesis of hydroxyproline; TRIM47 overexpression elevated the phosphorylation of Smad2/3, induced ubiquitination of PPM1A and decreased the expression level of PPM1A, while TRIM47 RNA interference reversed this result. SIGNIFICANCE: Melittin has anti-fibrotic effect in HELF by directly reducing the phosphorylation of Smad2/3 or indirectly reducing the phosphorylation of Smad2/3 by decreasing the expression levels of TRIM47 whose overexpression induces ubiquitination of PPM1A.

A Neonate With MuSK Congenital Myasthenic Syndrome Presenting With Refractory Respiratory Failure.

This was a Chinese neonatal congenital myasthenic syndromes case caused by muscle skeletal receptor tyrosine kinase gene mutations, which have not been recorded in the Human Gene Mutation Database. The newborn girl had refractory respiratory failure from birth to death, and failed extubation seven times. She had two heterozygous mutations: a non-sense mutation c.2062C>T (p.Q688X) inherited from father and a missense mutation c.2324T>C (p.F775S) inherited from mother, which was predicted pathogenic and harmful by bioinformatic softwares SIFT, PolyPhen_2 and REVEL. She positively responded to Neostigmine, but her parent quitted treatment when Pyridostigmine Bromide (2 mg/kg Q12 h) had been given for 8 days. She died 2 days after she was taken home by her parents on age of 56 days.

Effect of Weekly Antibiotic Round on Antibiotic Use in the Neonatal Intensive Care Unit as Antibiotic Stewardship Strategy.

Background: Antibiotics are commonly used in the neonatal intensive care unit (NICU). The objective was to observe the effect of weekly antibiotic round in NICU (WARN) to the antibiotic use in NICU. Methods: A retrospective observational study was performed. Departmental-level diagnosis categories and the parameters of antibiotic usage in NICU for the period of 2016-2017 (Phase 1) and 2018-2019 (Phase 2) were collected. WARN in NICU was started since January 2018. A time series forecasting was used to predict the quarterly antibiotic use in Phase 2, based on data from Phase 1. The actual antibiotic use of each quarter in Phase 2 was compared with the predicted values. Results: Totally 9297 neonates were included (4743 in Phase 1, 4488 in Phase 2). The composition of the disease spectrum between Phase 1 and Phase 2 was not different (P > 0.05). In Phase 1 and Phase 2, the overall antibiotic rate was 94.4 and 74.2%, the average accumulative defined daily dose per month was 199.00 ± 55.77 and 66.80 ± 45.64, the median antibiotic use density per month was 10.31 (9.00-13.27) and 2.48 (1.92-4.66), the median accumulative defined daily dose per case per month was 0.10 (0.09-0.13) and 0.03 (0.02-0.47), the number of patients who received any kind of antibiotic per 1000 hospital days per month was 103.45 (99.30-107.48) and 78.66 (74.62-82.77), rate of culture investigation before antibiotics was 64 to 92%, respectively, and all were better than the predicted values (P < 0.01). Conclusion: The implementation of periodical antibiotic rounds was effective in reducing the antibiotics use in the NICU.