Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy.

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus.

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.

Omega-3 polyunsaturated fatty acids and its metabolite 12-HEPE rescue busulfan disrupted spermatogenesis via target to GPR120.

Busulfan is an antineoplastic, which is always accompanied with the abnormal of spermatogonia self-renewal and differentiation. It has been demonstrated that the omega-3 polyunsaturated fatty acids (PUFAs) benefits mature spermatozoa. However, whether omega-3 can protect endogenous spermatogonia and the detailed mechanisms are still unclear. Evaluate of spermatogenesis function (in vivo) were examined by histopathological analysis, immunofluorescence staining, and western blotting. The levels of lipid metabolites in testicular tissue were determined via liquid chromatography. We investigated the effect of lipid metabolites on Sertoli cells provided paracrine factors to regulate spermatogonia proliferation and differentiation using co-culture system. In our study, we showed that omega-3 PUFAs significantly improved the process of sperm production and elevated the quantity of both undifferentiated Lin28+ spermatogonia and differentiated c-kit+ spermatogonia in a mouse model where spermatogenic function was disrupted by busulfan. Mass spectrometry revealed an increase in the levels of several omega-3 metabolites in the testes of mice fed with omega-3 PUFAs. The eicosapentaenoic acid metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) up-regulated bone morphogenic protein 4 (BMP4) expression through GPR120-ERK1/2 pathway activation in Sertoli cells and restored spermatogonia proliferation and differentiation. Our study provides evidence that omega-3 PUFAs metabolite 12-HEPE effectively protects spermatogonia and reveals that GPR120 might be a tractable pharmacological target for fertility in men received chemotherapy or severe spermatogenesis dysfunction.

Evaluation of the measles surveillance system performance in Jiading District， Shanghai from 2020 to 2022 / 上海预防医学

ObjectiveTo evaluate the measles surveillance system （MSS） in Jiading District， Shanghai from 2020 to 2022， and to provide evidence for the elimination of measles. MethodsDescriptive methods were used to analyze the MSS data and confirmed measles cases from 2020 to 2022 and to evaluate MSS performance indicators. ResultsA total of 120 suspected cases were reported through the MSS from 2020 to 2022， of which 12 were classified as measles， 9 as rubella， and 99 as non-measles /rubella. The incidence of reported non-measles /rubella was 1.44 per 100 000 population in 2020， 2.01 per 100 000 population in 2021， and 1.99 per 100 000 population in 2022. The rates of complete investigation within 48 hours， blood samples and etiology collection， timely delivery， and timely reporting were all 100%. Among the 12 confirmed measles cases from 2020 to 2022， seven routine immunization subjects completed the required doses of measles vaccines， while two out five adult cases had a history of measles vaccine-related immunization. The confirmed cases comprised six with fever accompanied by rash， five with rash alone， and one with fever alone. ConclusionThe MSS results in Jiading District， Shanghai are overall satisfactory. However， there is a need to improve sensitivity， especially in detecting and reporting cases with atypical symptoms. It is imperative to maintain high vaccination coverage for age-appropriate children， promote supplementary immunization activities， and elevate the overall immunity of the entire population.

Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients: a single-centre study / 中国天然药物

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.

Clinical practice and research advances in artificial liver support therapy / 临床肝胆病杂志

Artificial liver support system is one of the important therapies for liver failure， and in recent years， the role of non-bioartificial liver support system in the treatment of liver failure has been gradually recognized， with wide application in non-liver failure diseases. In clinical practice， various factors should be considered to reasonably select the timing and mode of non-bioartificial liver support therapy， and standardized， individualized， and precise treatment and optimal combination of different modes are the trend of the clinical application of artificial liver support therapy. There have been constant improvements in the key techniques of bioartificial liver support system such as seed cell source and bioreactor， and some of them have entered the stage of clinical trial. Although remarkable progress has been made in the clinical practice and research of artificial liver support therapy， there are still many challenges， and it is urgently needed to solve the problems of how to further improve its efficacy and safety through technological innovation and combination optimization and how to obtain higher-level evidence-based medical evidence through high-quality clinical trials.

Advances in mesenchymal stem cells therapy for tendinopathies / 中华创伤杂志(英文版)

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

IL-33 Suppresses the Progression of Atherosclerosis via the ERK1/2-IRF1-VCAM-1 Pathway.

PURPOSE: This study was designed to explore the effects of interleukin 33 (IL-33) on the progression of atherosclerosis and the possible mechanism. METHODS: The adhesion assay was performed on isolated peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The expression of proteins and messenger RNA (mRNA) were detected by western blot and quantitative real-time polymerase chain reaction (PCR), including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin. The effect of IL-33 on the interaction of growth stimulation expressed gene 2 (ST2) with myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) 1/4 were investigated using co-immunoprecipitation assay. An apolipoprotein (Apo) E-/- mice model was used to confirm the effect of IL-33 on atherosclerosis progression. Area of plaques was recorded by hematoxylin-eosin (H&E) staining. The severity of atherosclerosis plaque was evaluated using immunohistochemistry assay, and lipid accumulation was measured by an oil red O staining. In contrast, western blot was performed to detect the expression levels of VCAM-1, extracellular signal-regulated kinase (ERK) 1/2, and interferon regulatory factor 1 (IRF1). RESULTS: Our study observed that IL-33 suppressed cell adhesion and the expression of VCAM-1 in tumor necrosis factor-α (TNF-α) exposed HUVEC. Moreover, the addition of IL-33 significantly inhibited the expression of IRF1 and the binding level of IRF1 to VCAM-1 and also promoted the phosphorylation level of IRAK1/4 and ERK1/2 compared to TNF-α-stimulated HUVEC. The ST2 neutralizing antibody or ERK pathway inhibitor SCH772984 reversed the regulatory effects of IL-33 on HUVEC, suggesting that IL-33 suppressed IRF1 and VCAM-1 dependent on binding to ST2 and activating the ERK1/2 signaling pathway. Further investigation in vivo confirmed that IL-33 decreased the expressions of IRF1 and VCAM-1 by activating the phosphorylation of ERK1/2 in the thoracic aorta of Apo E-/- mice. CONCLUSION: In conclusion, our results demonstrated that IL-33 plays a protective role in the progression of atherosclerosis by inhibiting cell adhesion via the ERK1/2-IRF1-VCAM-1 pathway. This study may provide a potential therapeutic way to prevent the development of atherosclerosis.

Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1ß, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.

Age-related elevation of O-GlcNAc causes meiotic arrest in male mice.

In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.

TRIM40 ameliorates diabetic retinopathy through suppressing inflammation via Reelin/DAB1 signaling disruption: A mechanism by proteasomal degradation of DAB1.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Reelin, an extracellular matrix protein, and its effector protein Disabled1 (DAB1) have been linked to cellular events and retinal development. However, whether and how Reelin/DAB1 signaling causes DR remains to be investigated. In our study, significantly increased expression of Reelin, very low density lipoprotein receptor (VLDLR), ApoE receptor 2 (ApoER2) and phosphorylated DAB1 in retinas of streptozotocin (STZ)-induced DR mouse model was observed, along with enhanced expression of proinflammatory factors. Similar results are confirmed in high glucose (HG)-treated human retinal pigment epithelium cell line ARPE-19. Surprisingly, dysregulated tripartite motif-containing 40 (TRIM40), an E3 ubiquitin ligase, is found to be involved in DR progression by bioinformatic analysis. We observe a negative correlation between TRIM40 and p-DAB1 protein expression levels under HG conditions. Importantly, we find that TRIM40 over-expression markedly ameliorates HG-induced p-DAB1, PI3K, p-protein B kinase (AKT) and inflammatory response in HG-treated cells, but dose not affect Reelin expression. Of note, Co-IP and double immunofluorescence identify an interaction between TRIM40 and DAB1. Furthermore, we show that TRIM40 enhances K48-linked polyubiquitination of DAB1, thereby promoting DAB1 degradation. Finally, promoting TRIM40 expression by intravenous injection of the constructed adeno-associated virus (AAV-TRIM40) markedly ameliorates DR phenotypes in STZ-treated mice, as indicated by the decreased blood glucose and glycosylated hemoglobin (HbAlc) levels, and increased hemoglobin contents. Additionally, diabetes-related elevation of acellular capillaries was also meliorated in mice over-expressing TRIM40. The electroretinogram (ERG) deficits were strongly rescued in mice receiving AAV-TRIM40 injection. Moreover, AAV-TRIM40 attenuates the inflammation and p-DAB1 expression in retinal tissues of STZ-treated mice. Collectively, our findings disclose a mechanism through which TRIM40 limits DAB1 stability under physiological conditions and reveals TRIM40 as a potential therapeutic target for the intervention of Reelin/DAB1 signaling, contributing to DR treatment.

Chronic oral exposure to short chain chlorinated paraffins induced testicular toxicity by promoting NRF2-mediated oxidative stress.

As a widespread environmental contaminant, short chain chlorinated paraffins (SCCPs) has attracted great attention. However, the toxicity of SCCPs on male reproductive system remains ambiguous. In this study, we treated mice with SCCPs by gavage and investigated the toxic effects of SCCPs on testis. According to the results, the sperm parameters of mice were significantly reduced after exposure to 1, 10, 100 mg/kg body mass per day SCCPs for 35 days. SCCPs resulted in disorderly arranged seminiferous epithelium and increased apoptotic cells in testes. Both in vivo and in vitro experiments indicated that the oxidative stress was induced after SCCPs exposure, and dysfunction of nuclear factor erythroid-related factor (NRF2) signaling pathway played a role in this process. Moreover, resveratrol, an NRF2 activator, could alleviate the damage of SCCPs onmale reproductive system. Our study indicated that oxidative stress is the key point for explaining the testicular toxicity caused by SCCPs, and NRF2 could be used as a potential target for clinical treatment to alleviate the reproductive toxicity induced by SCCPs.

Genetic Analysis of a Case of Sotos Syndrome with Suspected Germinal Mosaicism in Mother.

This study is to identify the pathogenic mutation of a child with Sots syndrome and provide prenatal diagnosis for his pregnant mother. Chromosome microarray technology was used to detect whether there were minor deletions/duplication in patients' chromosomes. The gene mutation of patients was screened by next-generation sequencing technology, and it was verified by Sanger sequencing. Prenatal diagnosis of the fetus was conducted according to the selected pathogenic sites, and genetic counseling was conducted for her parents. Chromosome microarray results showed that there was no minor deletion in a chromosome 5q35 region, and the second-generation sequencing results showed that there was a c.4138delG heterozygous mutation in the patient's NSD1 gene, and the pathogenic of this mutation was not reported in related databases. Sanger sequencing found that there was a c.4138delG heterozygous mutation in the NSD1 gene of the patient and her parents' genotype at this locus was wild type. The prenatal gene test results indicated that there was heterozygous mutation of NSD1 gene c.4138delG in the fetus, so it was suggested to terminate the pregnancy. Gentling results indicated that the fetus and the patient inherited the same maternal chromosome 5. The heterozygous mutation of NSD1 gene c.4138delG is the pathogenic mutation of this Sots syndrome patient, and the mother may be germinal mosaicism.

The mediating role of professional commitment between the clinical learning environment and learning engagement of nursing students in clinical practice: A cross-sectional study.

BACKGROUND: Previous studies have shown that learning engagement can significantly predict nursing students' academic achievement. Nursing educators put considerable effort into assessing and promoting students' engagement in school. However, nursing students' learning engagement in clinical practice has seldom been explored. OBJECTIVES: To investigate nursing students' learning engagement and influencing factors in clinical practice and examine the effects of the clinical learning environment and professional commitment on learning engagement, specifically to verify the mediation effect of professional commitment. DESIGN: A cross-sectional study. SETTINGS: The participants were from five hospitals in Jining, Shandong, China. PARTICIPANTS: A total of 318 nursing students who were at the end of clinical practice training (>8 months) were included in this study. METHODS: The Utrecht Work Engagement Scale for Students, the Clinical Learning Environment for Nursing Scale, and the Professional Commitment Scale were used for data collection. Regression and mediating analyses were used to explore the influencing factors of clinical learning engagement and the potential mediating role of professional commitment. RESULTS: The participants experienced moderate levels of engagement in clinical learning. The clinical learning environment indirectly affected nursing students' learning engagement in clinical practice through professional commitment. Night shifts and educational background also contributed to learning engagement. CONCLUSIONS: The findings provide new perspectives on promoting nursing students' clinical learning engagement. Professional commitment might be an important mediating variable in nursing education. There is a need to take steps to improve professional commitment of nursing students.

Correlation between cognitive impairment and cortical atrophy in elderly patients with asymptomatic carotid artery stenosis / 中华健康管理学杂志

Objective:To analyze the correlation between cognitive impairment and cortical atrophy in elderly patients with asymptomatic carotid artery stenosis (ACAS).Methods:In this cross-sectional study, 40 consecutive elderly patients with ACAS treated in the Department of Neurology, Northern Jiangsu People′s Hospital from July 1, 2020 to June 30, 2021 (ACAS group), and 40 elderly healthy controls who accepted physical examination during the same period (control group) were included. Cognitive assessment was performed using the Mental State Examination Scale (MMSE) and the Montreal Cognitive Assessment Scale (MoCA), and brain magnetic resonance imaging scanning was performed in the ACAS group. The artificial intelligence technique was applied for brain lobe segmentation and cortical volume calculation. The χ2-test, independent sample t-test and Wilcoxon non-parametric test were used to analyze the difference of clinical data and cognitive scores between the two groups. In the ACAS group, the cortical volumes of the side with carotid stenosis was compared with that of the normal side, and Spearman′s correlation analysis was used to assess the correlation between cognitive scores and cortical atrophy. Results:Compared with the control group, the ACAS group got significantly lower scores of MMSE and MoCA, as well as lower scores of visuospatial executive function, attention and calculation, language function, abstraction ability and delayed recall [(25.60±2.49) vs (27.18±1.01), (22.05±3.59) vs (25.60±1.43), (2.73±1.04) vs (4.08±0.62), (4.53±0.93) vs (5.03±0.66), 2.00 (0.00) vs 3.00 (0.00), 1.00 (1.00) vs 2.00 (0.00), and (2.95±0.96) vs (3.35±0.62)] (all P<0.05). There was not significant differences in naming and orientation ability between the two groups (both P>0.05). The volume of cortical, temporal lobe, frontal lobe, parietal lobe and insular lobe on the side with carotid stenosis in the ACAS group were significantly smaller than those on the normal side [186.23 (177.97, 202.53) vs 194.67 (185.65, 204.82) cm 3, 54.74 (50.66, 56.95) vs 55.61 (51.24, 58.49) cm 3, 72.98 (70.76, 78.34) vs 75.27 (72.34, 80.66) cm 3, 53.66 (51.11, 57.86) vs 56.59 (52.80, 60.09) cm 3, 6.57 (6.35, 7.07) vs 6.72 (6.46, 7.34) cm 3] (all P<0.05). The MoCA score in the ACAS group was positively related to the cortical volume ratio of the two sides ( r=0.427, P<0.01). The attention ( r=0.353) and abstraction ( r=0.226) ability scores were positively correlated with the temporal lobe volume ratios of the two sides (both P<0.05). The visuospatial executive ( r=0.187) and language ( r=0.373) ability scores were positively correlated with frontal lobe volume ratios of the two sides (both P<0.05), and visuospatial executive ( r=0.386), naming ( r=0.344), language ( r=0.517), abstraction ( r=0.335) and delayed recall ( r=0.333) ability scores were positively correlated with parietal lobe volume ratios of the two sides (all P<0.05). Conclusion:In elderly patients with ACAS, the cognitive impairment and cortical atrophy on the sides with carotid stenosis are significant and a positive correlation is detected between them.

Applicability analysis of bone age assessment standards for children in rural areas of Beijing / 中华放射学杂志

Objective:To evaluate the applicability of bone age (BA) assessment methods and to investigate the difference between BA and chronological age (CA) based on the data of children in rural areas of Beijing.Methods:A total of 412 healthy children (226 boys, 186 girls) with the age 8.6 (6.8, 10.3) years old were included in this study. The data of the prospective study were from a subgroup of the project "National Nutrition and Health Systematic Survey for 0-18 Years Old Children in China", which included children with age of 3-12 years old in Beijing rural areas. The non-dominant hand-wrist radiographs of all participants were obtained in April 2021. The Dr.Wise BA detection and analysis system was used to assess the BA according to the Tanner Whitehouse 3 (TW3) radius-ulna-short bone score (TW3-RUS), TW3 carpal bone score (TW3-Carpal), China-05 TW3-Chinese RUS (TW3-C RUS), China-05 TW3-Chinese carpal (TW3-C Carpal), and Greulich-Pyle (G-P) standards. The cases were stratified by the sex and different CA in the statistical analysis. The estimated BA obtained using different methods were compared with the CA using Wilcoxon signed ranks test.Results:The sex-stratified results showed that no significant difference was found between the estimated BA using G-P standards and CA in boys ( Z=-0.694, P=0.488), while all the other estimated BA results were statistically significantly higher than CA ( P<0.05). Stratified by both sex and CA, the estimated BA using G-P standards in 4-6 years old boy groups, as well as the estimated BA using TW3-Carpal and TW3-C Carpal standards in 11-12 years old girl groups were lower than CA, while in the other groups, the estimated BA were higher than CA. Conclusions:There were varying degrees of deviations in the BA estimations using TW3, China 05, and G-P methods for children in rural areas of Beijing. It is imperative to establish a new standard for the BA evaluation of the contemporary Chinese children.

Sampling study design and radiography protocol of a large-sample investigation on skeletal maturation in 3 to 18-year-old children in China / 中华放射学杂志

Objective:To report the sampling study design and radiography protocol of a large-sample investigation on skeletal maturation of 3 to 18-year-old children in China.Methods:Multi-stage stratified random sampling was employed in this study. Two provinces, municipalities, or autonomous regions were randomly selected from each of the seven regions of China, including Northeast China, Northwest China, North China, Central China, East China, Southwest China, and South China. Then one rural and one urban investigation site were randomly selected from each province, municipality, or autonomous region. In total 28 sites were included. Among those sites, four residential districts were randomly selected from each urban site, and four townships from each rural site. For each residential district or township, 1-4 kindergartens, primary schools, and middle schools were chosen. Random cluster sampling was used to extract 3-<6-year-old children in kindergartens, and 6-18-year-old children in primary schools and middle schools. The investigation on skeletal maturation was sampled proportionate to the sampling of the whole study. The estimated simple size was 780 for each site, and 21 840 for all 28 sites in total. There were six groups of 3-<6-year-old children classified at 0.5-year intervals, and 12 groups of 6-18-year-old children classified at 1-year intervals. Posteroanterior position radiography of the left hand and wrist was achieved for all subjects.Results:The study was performed from August 26, 2019 to October 16, 2021. In total, 20 444 children received posteroanterior position radiography of the left hand and wrist, including 10 196 males and 10 248 females, 9 711 urban and 10 733 rural, respectively. The 3-<6-year-old group included 1 611 (male 819, female 792) subjects, and the 6 to 18-year-old group included 18 833 (male 9 377, female 9 456) subjects.Conclusion:This nationwide investigation on skeletal maturation of 3 to 18-year-old children in seven regions of China was successfully preformed. The results of this study can provide an important reference for establishing the current evaluation criteria of bone age in Chinese children and adolescents.

Apoptosis-promoting effect of temozolomide loaded nanoparticles combined with low intensity focused ultrasound on human glioma cells / 中华超声影像学杂志

Objective:To prepare liquid-gas phase modified nanoparticles (TMZ/PFP/PLGA NPs) of perfluoropentane (PFP) and temozolomide (TMZ) encapsulated by polylactic-glycolic acid copolymer (PLGA), combined with low intensity focused ultrasound (LIFU) irradiation, and to investigate its ultrasound imaging ability and intervention effect on human glioma cells in vitro.Methods:TMZ/PFP/PLGA NPs were prepared by compound emulsion method. The basic physical and chemical properties and drug loading ability of TMZ/PFP/PLGA NPs were detected. CCK-8 assay was used to detect the cytotoxicity of nanoparticles in vitro and the effect of synergistic intervention with LIFU on the survival rate of glioma cells. The expression levels of apoptosis related proteins Bcl-2, Bax and caspase-3 were detected by Western blot.Results:Under transmission electron microscope, TMZ/PFP/PLGA NPs showed a circular core-shell structure with regular morphology, particle size was (137.9±63.31)nm, encapsulation efficiency of TMZ was (83.01±5.57)%, drug loading was (3.19±0.22)%. The survival rate of U251 cells was still above 70% after 24 hours of co-incubation with nanoparticles. Under the synergistic effect of LIFU irradiation, the apoptosis of U251 cells was accelerated and the survival rate of U251 cells was significantly decreased. The results of Western blot showed that the synergic intervention could significantly down-regulate the expression of apoptosis related protein Bcl-2, and significantly up-regulate the expression of Bax protein and caspase-3 protein (all P<0.05). Conclusions:TMZ/PFP/PLGA NPs have good basic physical and chemical properties. TMZ/PFP/PLGA NPs have low cytotoxicity in vitro while efficiently loading chemotherapeutic drug timozolomide. Synergistic intervention under LIFU irradiation can significantly accelerate the apoptosis of U251 glioma cells, which has a good application prospect.