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.

PTBP1 promotes the progression of hepatocellular carcinoma by enhancing the oncogenic splicing switch of FGFR2.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer accounting for 90% of cases. It is a highly invasive and deadly cancer with a gradual onset. Polypyrimidine tract-binding protein 1 (PTBP1) is an important RNA-binding protein involved in RNA metabolism and has been linked to oncogenic splicing events. While the oncogenic role of PTBP1 in HCC cells has been established, the exact mechanism of action remains unclear. This study aimed to investigate the functional connection between PTBP1 and dysregulated splicing events in HCC. Through immunoprecipitation-mass spectrometry analyses, we discovered that the proteins bound to PTBP1 were significantly enriched in the complex responsible for the alternative splicing of FGFR2 (fibroblast growth factor receptor 2). Further RNA immunoprecipitation and quantitative PCR assays confirmed that PTBP1 down-regulated the FGFR2-IIIb isoform levels and up-regulated the FGFR2-IIIc isoform levels in HCC cells, leading to a switch from FGFR2-IIIb to FGFR2-IIIc isoforms. Subsequent functional evaluations using CCK-8, transwell, and plate clone formation assays in HCC cell lines HepG2 and Huh7 demonstrated that FGFR2-IIIb exhibited tumor-suppressive effects, while FGFR2-IIIc displayed tumor-promoting effects. In conclusion, this study provides insights into the PTBP1-mediated alternative splicing mechanism in HCC progression, offering a new theoretical basis for the prevention and treatment of this malignancy. Mechanistically, the isoform switch from FGFR2-IIIb to FGFR2-IIIc promoted epithelial-mesenchymal transformation (EMT) of HCC cells and activated the FGFR cascades ERK and AKT pathways.

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.

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.

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.

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.

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.

Association between cardiometabolic diseases and quality of life and the mediation effect of perceived stress / 中华心血管病杂志

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a2b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.

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.

Application of laparoscopic surgery skills training course in the standardized residency training of surgery / 中华医学教育探索杂志

Objective:To explore the application effect of laparoscopic surgery skills training course in the standardized residency training of surgery.Methods:A total of 40 standardized trainees of surgical residents rotating in general surgery were selected as the research objects, and randomly divided into the experimental group and the control group. The experimental group was offered laparoscopic surgery skills training course. The course content includes theoretical teaching module, simulated teaching module, virtual teaching module and clinical surgery practice teaching module. The control group was taught by traditional theory teaching and clinical surgery practice teaching. At the end of the courses, the two groups of students were assessed for their skills in laparoscopic grasping and pass, suture and knotting. At the same time, a questionnaire survey was conducted among the students and teachers. The t-test was performed using SPSS 22.0 statistical software. Results:The theoretical scores of the experimental and control groups were (67.90±13.24) and (69.70±13.46), respectively, with no statistically significant difference ( P > 0.05). After the courses, the performance of grasping and pass, suture and knotting of the experimental group (15.25±3.24 and 5.45±2.14) was higher than that of the control group (11.25±2.12 and 2.75±1.16), and the difference was statistically significant ( P < 0.01).The questionnaire survey showed that the proportion of "better" feedback from students and teachers on laparoscopic skills training courses was significantly higher than that of "general" and "poor". Conclusion:The laparoscopic surgery skills training course can improve the laparoscopic surgery skills of the trainees in the standardized residency training of surgery, shorten the learning curve, and make the training standardized and homogeneous. It is worthy of wide promotion and application in the standardized training base.

Postgraduate training system of biomedical science in the USA and its implications to China: taking the City of Hope National Medical Center as an example / 中华医学教育探索杂志

This paper, taking the City of Hope National Medical Center as an example, introduces the application and admission of biomedical science doctors in the USA, analyzes the curriculum system and teaching patterns, elaborates the requirement of degree awarding, and compares the differences in postgraduate training system between China and the USA, thereby providing valuable experience and reference for training biomedical science postgraduate students with Chinese characteristics in the domestic universities.

Predictive value of isoform -2 proprostate-specific antigen and its derived indexes for prostate cancer patients with PSA 4-20 ng/mL / 现代泌尿外科杂志

【Objective】 To evaluate the predictive value of isoform [-2] proprostate-specific antigen, p2 PSA (p2PSA) and its derived indexes for prostate cancer in a Chinese cohort with PSA 4-20 ng/mL. 【Methods】 A total of 139 males scheduled for biopsy were enrolled in the prospective study from Nov.2021 to Jun.2022. The total PSA (tPSA), free PSA (fPSA), fPSA/tPSA (f/t) and p2PSA were collected, and the percentage of p2PSA(%p2PSA) and prostate health index(PHI) were calculated. The predictive value of p2PSA and its derived indexes were compared with traditional indexes with receiver operating characteristic (ROC) curve and Logistic analysis. 【Results】 Prostate cancer was found in 54 cases (38.8%). There were significant statistical differences in tPSA(10.68 vs.8.14, P=0.021), f/t(0.13 vs.0.16, P=0.006), p2PSA(30.25 vs.19.81, P<0.001), %p2PSA(21.52 vs.13.15, P<0.001) and PHI(64.3vs.38.2, P<0.001) between prostate cancer patients and non-prostate cancer patients. The area under the ROC curve (AUC) of tPSA, fPSA, %fPSA, p2PSA, %p2PSA and PHI were 0.63, 0.51, 0.63, 0.71, 0.73, and 0.80, respectively. The inclusion of %p2PSA and PHI significantly increased the prediction efficiency of the basic prediction model (AUCbase+PHI=0.81, AUCbase+%p2PSA=0.78, AUCbase=0.67). With 35 as the recommended cut-off value of PHI, the incidence of meaningless puncture was reduced by 25.8%(36/139). 【Conclusion】 The application of p2PSA and its derived indexes have good predictive value for patients with PSA 4-20 ng/mL. The combined detection of %p2PSA and PHI can significantly increase the detection efficiency of prostate cancer and reduce the incidence of meaningless prostate puncture by 25.8%.

Association between dietary quality and bone mass among middle-aged and elderly people in Gansu Province / 西安交通大学学报(医学版)

【Objective】 To evaluate the dietary quality with the dietary balance index (DBI_16) and the association between dietary quality and bone mass among middle-aged and elderly people in Gansu Province so as to provide evidence for improving dietary quality and bone health status of Gansu population. 【Methods】 Based on the information of the type and quantity of food intake and the bone mass of middle-aged and elderly people aged 35 years and above collected by the Gansu Project in the Regional Ethnic Cohort Study in Northwest China, DBI_16 was used to evaluate the intake level of cereals, vegetables, fruits, milk, beans, fish and shrimp, eggs and other foods, and the degree of inadequate, excessive and unbalanced dietary intake of the participants. Multiple linear regression was used to evaluate the associations of three component indexes of DBI_16, high bound score (DBI_HBS), low bound score (DBI_LBS), diet quality distance (DBI_DQD), and seven single indexes of DBI_16 with bone mass. 【Results】 Analyses of the dietary and bone mass data of 11,840 participants showed that 44.8% of participants consumed excessive amounts of cereals compared to the dietary recommendation. 96.3%, 90.6%, 90.1%, 71.9%, 95.1% and 60.3% of participants’ intake of vegetables, fruits, milk, soybeans, fish and shrimp, and eggs, respectively, were inadequate. 47.7% participants consumed less than 10 types of food. 2.3% participants’ DBI_LBS levels were appropriate. 54.7% participants’ DBI_HBS levels were appropriate. Only 1.2% participants’ DBI_DQD reached a balanced level. The bone mass level in the study population was (2.5±0.6) kg [(2.8±0.5) kg for men and (2.3±0.5) kg for women]. After adjusting for sociodemographic characteristics, lifestyle, total dietary energy intake and body mass index, DBI_LBS and DBI_DQD were negatively associated with bone mass [β and 95% CI was -0.002 01 (-0.003 62--0.000 40) and -0.001 76 (-0.003 09--0.000 43), respectively]. 【Conclusion】 Dietary intake imbalance is common among middle-aged and elderly people in Gansu Province, and the more severe the dietary intake imbalance, the lower the bone mass level.