Tctp, a unique Ing5-binding partner, inhibits the chromatin binding of Enok in Drosophila.

The MOZ/MORF histone acetyltransferase complex is highly conserved in eukaryotes and controls transcription, development, and tumorigenesis. However, little is known about how its chromatin localization is regulated. Inhibitor of growth 5 (ING5) tumor suppressor is a subunit of the MOZ/MORF complex. Nevertheless, the in vivo function of ING5 remains unclear. Here, we report an antagonistic interaction between Drosophila Translationally controlled tumor protein (TCTP) (Tctp) and ING5 (Ing5) required for chromatin localization of the MOZ/MORF (Enok) complex and H3K23 acetylation. Yeast two-hybrid screening using Tctp identified Ing5 as a unique binding partner. In vivo, Ing5 controlled differentiation and down-regulated epidermal growth factor receptor signaling, whereas it is required in the Yorkie (Yki) pathway to determine organ size. Ing5 and Enok mutants promoted tumor-like tissue overgrowth when combined with uncontrolled Yki activity. Tctp depletion rescued the abnormal phenotypes of the Ing5 mutation and increased the nuclear translocation of Ing5 and chromatin binding of Enok. Nonfunctional Enok promoted the nuclear translocation of Ing5 by reducing Tctp, indicating a feedback mechanism between Tctp, Ing5, and Enok to regulate histone acetylation. Therefore, Tctp is essential for H3K23 acetylation by controlling the nuclear translocation of Ing5 and chromatin localization of Enok, providing insights into the roles of human TCTP and ING5-MOZ/MORF in tumorigenesis.

Prognosis and risk factor assessment of patients with advanced lung cancer with low socioeconomic status: model development and validation.

BACKGROUND: Lung cancer, a major global health concern, disproportionately impacts low socioeconomic status (SES) patients, who face suboptimal care and reduced survival. This study aimed to evaluate the prognostic performance of traditional Cox proportional hazards (CoxPH) regression and machine learning models, specifically Decision Tree (DT), Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost), in patients with advanced lung cancer with low SES. DESIGN: A retrospective study. METHOD: The 949 patients with advanced lung cancer with low SES who entered the hospice ward of a tertiary hospital in Wuhan, China, from January 2012 to December 2021 were randomized into training and testing groups in a 3:1 ratio. CoxPH regression methods and four machine learning algorithms (DT, RF, SVM, and XGBoost) were used to construct prognostic risk prediction models. RESULTS: The CoxPH regression-based nomogram demonstrated reliable predictive accuracy for survival at 60, 90, and 120 days. Among the machine learning models, XGBoost showed the best performance, whereas RF had the lowest accuracy at 60 days, DT at 90 days, and SVM at 120 days. Key predictors across all models included Karnofsky Performance Status (KPS) score, quality of life (QOL) score, and cough symptoms. CONCLUSIONS: CoxPH, DT, RF, SVM, and XGBoost models are effective in predicting mortality risk over 60-120 days in patients with advanced lung cancer with low SES. Monitoring KPS, QOL, and cough symptoms is crucial for identifying high-risk patients who may require intensified care. Clinicians should select models tailored to individual patient needs and preferences due to varying prediction accuracies. REPORTING METHOD: This study was reported in strict compliance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Gut microbiota, skin microbiota, and alopecia areata: A Mendelian randomization study.

BACKGROUND: Observational studies have shown an association between skin microbiota and alopecia areata (AA), but the causal connection remains ambiguous. METHODS: We obtained data on skin microbiota and AA from summary statistics of Genome-Wide Association Studies and applied statistical methods from Mendelian randomization (MR) to assess causal relationships. Additionally, we investigated whether the skin microbiota acts as a mediator in the pathway from gut microbiota to AA. RESULTS: In the MR analysis of KORA FF4 and AA, the inverse-variance weighting method indicated that Corynebacterium (odds ratio [OR] = 0.82, 95% confidence interval [CI]: 0.70-0.96, p = 0.02) and asv037 (OR = 0.87, 95% CI: 0.76-0.99, p = 0.05) exerted protective effects, while Betaproteobacteria (OR = 1.21, 95% CI: 1.01-1.44, p = 0.03), asv015 (OR = 1.27, 95% CI: 1.05-1.54, p = 0.02), and Burkholderiales (OR = 1.20, 95% CI: 1.04-1.38, p = 0.01) were identified as risk factors in AA. In the MR analysis of PopGen and AA, asv001 (OR = 1.12, 95% CI: 1.01-1.24, p = 0.04), asv054 (OR = 1.13, 95% CI: 1.01-1.25, p = 0.03), and asv059 (OR = 1.14, 95% CI: 1.02-1.27, p = 0.02) were found to potentially increase the risk in AA. Furthermore, in the influence of gut microbiota on AA, the skin microbiota did not act as a mediator. CONCLUSION: Our analysis suggests potential causal relationships between certain skin microbiota and AA, revealing insights into its pathogenesis and potential intervention strategies.

Community-based rehabilitation services implemented by multidisciplinary teams among adults with stroke: a scoping review with a focus on Chinese experience.

BACKGROUND: Despite the growing interest in hospital rehabilitation services for communities, studies on existing community-based rehabilitation (CBR) services remain scarce owing to limitations in the development of community health services and regional cultural diversity. As a guaranteed measure for ensuring the quality of rehabilitation services and achieving the desired service outcomes, clear roles and responsibilities in multidisciplinary teams and effective service delivery are particularly important. OBJECTIVE: This scoping review aimed to determine the scope of community stroke rehabilitation programs involving existing multidisciplinary teams and to analyze the implementation content and implementers' functional roles to provide guidance for future CBR programs. METHODS: The scoping review design followed the methodology of the Joanna Briggs Institute and was based on the normative scoping review framework proposed by Arksey and O'Malley. The comprehensive CBR framework was proposed by World Health Organization-guided data charting and analysis. RESULTS: Of the 22,849 identified citations, 74 studies were included, consisting of 6,809 patients with stroke and 49 primary caregivers, most of whom were from China. The most common working mode in CBR programs was a dual approach involving both healthcare professionals in medical institutions and community healthcare professionals. The number of programs in each discipline was in the following descending order: nursing, medical care, rehabilitation, psychology, nutrition, and public health. Among these, multidisciplinary teams comprising medical, nursing, and rehabilitation disciplines were the most common, with a total of 29 programs. Disciplinary members were mainly responsible for implementing their respective disciplinary content, with physicians providing guidance for the programs. More than 82.4% of the studies reported 2-4 intervention strategies. The intervention forms of rehabilitation content were the most diverse, whereas preventive interventions were more homogeneous than others. Physical function and socio-psychological measurements were the most commonly reported outcomes. CONCLUSION: CBR services implemented by multidisciplinary teams can effectively achieve functional and emotional improvement in patients with stroke, and nurses are the most involved in implementation, especially in community settings. The results further emphasize the importance of strengthening the exploration of nurses' maximum potential to implement CBR plans in future practice. TRIAL REGISTRATION: The registration information for this scoping review can be found at osf.io/pv7tg.

Living experiences of people with advance cancer with low socioeconomic status: A systematic review of qualitative evidence.

BACKGROUND: The number of patients with advanced cancer is rapidly increasing, and the subgroup of this population with low socioeconomic status has suffered more disease burden than others. However, there is no recent qualitative synthesis of primary research studies into advanced cancer patients with low socioeconomic status. OBJECTIVE: To synthesise qualitative research findings into advanced cancer patients' experiences with low socioeconomic status, and then to help provide targeted and effective strategies to improve their quality of life. DESIGN: A systematic review and meta-synthesis of qualitative evidence (PROSPERO: CRD42021250423). DATA SOURCES: PubMed, Web of Science Core Collection (ISI Web of Science), Cochrane Library, Embase, OVID LWW, CINAHL Complete (EBSCO), PsycINFO (EBSCO) and MEDLINE (ISI Web of Science), China National Knowledge Infrastructure (CNKI), WangFang, and Vip databases were systematically searched from their original dates to July 2022. Qualitative data were appraised using the Joanna Briggs Institute (JBI) qualitative assessment. FINDINGS: The findings were synthesised into the following three analytical themes: (1) multi-dimensional disease distresses; (2) barriers in coping with disease distresses; and (3) strategies for dealing with disease distresses. CONCLUSIONS: Patients with advanced cancer with low socioeconomic status experienced complicated and interactional distresses, unique life barriers, and a wide range of adaptation strategies. These findings will provide a comprehensive perspective to promote individual-centred health care systems and services to help these vulnerable people deal with the challenges of disease and improve their quality of life.

Prevalence and Trends of Thyroid Disease Among Adults, 1999-2018.

BACKGROUND: Thyroid disease is a prominent endocrine disorder, yet the clinical epidemiology of this condition remains unclear. This study aims to describe the recent trends in the prevalence of thyroid disease in US adults from 1999-2018. METHODS: This cross-sectional study used nationally representative data collected through the National Health and Nutrition Examination Survey (NHANES) from January 1, 1999 to December 31, 2018. Patients with thyroid disease were defined as patients who reported having a thyroid disease and were on thyroid-related treatment. Age-standardized prevalence of thyroid disease was calculated within 4-year survey periods (1999-2002, 2003-2006, 2007-2010, 2011-2014, and 2015-2018). RESULTS: During the NHANES 1999-2018, a total of 57 540 participants were examined. The age-standardized prevalence of thyroid disease was 5.05% (95% CI, 4.55%-5.60%) from 2015-2018, signifying a significant increase from the 1999-2002 period (P <.0002). However, prevalent thyroid disease remained steady between 2003 and 2014. The highest prevalence of thyroid disease was observed in non-Hispanic Whites (8.1%; 95% CI, 7.3%-9.0%), individuals aged ≥60 years (15.4%; 95% CI, 13.3%-17.8%), and tended to be higher in women (7.6%; 95% CI, 6.8%-8.5%). Multiple regression analysis revealed that age, women sex, non-Hispanic White and Mexican American, body mass index, higher education and incomes were independently associated with increased risks of thyroid disease. CONCLUSION: The age-standardized prevalence of thyroid disease among US adults increased from 1999-2003, remained stable between 2003 and 2014, and then saw an increase from 2014-2018, with the highest rate observed among elders, women, and non-Hispanic Whites.

Validation of the ADVIA Centaur® XP system for the determination of insulin and its application.

In this study, a direct chemiluminescent immunoassay for the determination of human serum insulin levels using the ADVIA Centaur® XP system was validated. Dilution recovery, linearity, precision, sensitivity, between analyzer variation, reference interval and stability were analyzed. The linear range of the insulin assay was from 0.64 to 277.27 mU/L. Intra- and inter-assay coefficients of variation were 3.67-7.96% and 4.66-8.69%, respectively. The lower and upper limits of quantification were 0.61 mU/L and 8872.64 mU/L, respectively. In terms of between analyzer variation, our study showed comparable results with a good correlation of r2 = 0.9934. The human serum insulin reference interval was in the range of 3.0-25.0 mU/L. Serum insulin can be kept for 7 days between 2-8 °C and 18-26 °C, and the corresponding results for -20 °C and -70 °C were 1 month and 6 months are reported. We proved that this insulin assay was robust and the analytical performance met the requirements. We successfully applied this insulin assay to a bioequivalence study of miglitol in 48 healthy Chinese subjects. The miglitol bioequivalence study was evaluated based on pharmacokinetic and pharmacodynamic parameter endpoints. The results demonstrated that the test formulation and the reference formulation were bioequivalent.

[Clinical effect of integrated sandplay therapy in children with Asperger syndrome].

OBJECTIVE: To study the clinical effect of integrated sandplay therapy in preschool children with Asperger syndrome (AS). METHODS: A total of 44 preschool children with AS were randomly divided into an experimental group and a control group, with 22 children in each group. The children in the control group were given routine training, and those in the experimental group were given integrated sandplay therapy in addition to the routine training. The treatment response was assess by the Social Responsiveness Scale (SRS), emotional recognition tools and changes in sandplay theme characteristics after 6 months of treatment. RESULTS: Before intervention, there were no significant differences between the two groups in the total score of SRS, the score of each factor of SRS, and correct rates of facial expression recognition of the upright position, inverted position, upper face and lower face (P>0.05). After 6 months of intervention, both groups had significant reductions in the total score of SRS and the score of each factor of SRS (P<0.01); the control group had significant increases in the correct rates of facial expression recognition of all positions except the upright position (P<0.05), while the experimental group had significant increases in the correct rates of facial expression recognition of all positions (P<0.05). Compared with the control group after intervention, the experimental group had significantly lower total score of SRS and scores of all factors of SRS except social perception (P<0.01) and significantly higher correct rates of facial expression recognition of all positions (P<0.01). The experimental group had a significant change in the number of sandplay theme characteristics after intervention (P<0.01). CONCLUSIONS: Integrated sandplay therapy can improve social responsiveness and emotion recognition ability in preschool children with AS.

Intravenous Administration of Multiwalled Carbon Nanotubes Aggravates High-Fat Diet-Induced Nonalcoholic Steatohepatitis in Sprague Dawley Rats.

Multiwalled carbon nanotubes (MWCNTs) have been explored in pharmaceutical applications such as tumor targeting and delivery of drugs, in which MWCNTs are given through intravenous injection. However, the biosafety of MWCNTs is of concern for such application. Therefore, in the current study, we used a fatty liver model to investigate the possible toxicity of MWCNTs to the liver, as MWCNTs were retained mainly in the liver of mice after intravenous injection. Male Sprague Dawley rats were used to generate the fatty liver model, and the effects of intravenous administration of MWCNTs on fatty liver were studied. Hematoxylin and eosin staining for hepatocellular anatomy and Masson trichrome staining for hepatic fibrosis were conducted. Histologically, MWCNTs aggravated steatohepatitis with higher nonalcoholic fatty liver disease scores. Analysis of liver injury markers indicated that MWCNTs administration resulted in chronic hepatitis, along with increased liver fat and altered liver oxidation, including the increase of P6 protein and the depletion of glutathione. In conclusion, our results suggest that MWCNTs can aggravate nonalcoholic steatohepatitis in Sprague Dawley rats, and oxidative injury may be involved in this process.

Ti3C2 MXene/MoS2@AuNPs ternary nanocomposite for highly sensitive electrochemical detection of phoxim residues in fruits.

Phoxim, extensively utilized in agriculture as an organothiophosphate insecticide, has the potential to cause neurotoxicity and pose human health hazards. In this study, an electrochemical enzyme biosensor based on Ti3C2 MXene/MoS2@AuNPs/AChE was constructed for the sensitive detection of phoxim. The two-dimensional multilayer structure of Ti3C2 MXene provides a robust framework for MoS2, leading to an expansion of the specific surface area and effectively preventing re-stacking of Ti3C2 MXene. Additionally, the synergistic effect of self-reduced grown AuNPs with MoS2 further improves the electrical conductivity of the composites, while the robust framework provides a favorable microenvironment for immobilization of enzyme molecules. Ti3C2 MXene/MoS2@AuNPs electrochemical enzyme sensor showed a significant response to phoxim in the range of 1 × 10-13 M to 1 × 10-7 M with a detection limit of 5.29 × 10-15 M. Moreover, the sensor demonstrated excellent repeatability, reproducibility, and stability, thereby showing its promising potential for real sample detection.

Prevalence of self-reported thyroid disease among adults with depression.

BACKGROUND: Thyroid disorders are a common comorbidity in patients with depression, yet there is limited information available about the clinical epidemiology of thyroid diseases in this specific population. This study aims to describe the prevalence of thyroid disease among US adults with depression from 2007 to 2018. METHODS: This cross-sectional study used nationally representative data collected through the National Health and Nutrition Examination Survey (NHANES) between January 1, 2007, to December 31, 2018. Age-standardized prevalence of thyroid disease among depressed patients was calculated within 4-year survey periods (2007-2010, 2011-2014, and 2015-2018), and adjusted to the 2000 U.S. standard population. RESULTS: In our weighed sample, 6.1% of depressed individuals and 4.3% of non-depressed individuals reported thyroid disease between 2007 and 2018 (P < 0.0001). The age-standardized prevalence of thyroid disease in patients with depression increased over time, from 5.4% (95%CI, 4.6%-6.2%) in 2007-2010 to 6.8% (95%CI, 5.8%-8.0%) in 2015-2018 (P for trend = 0.0270). Furthermore, thyroid disease prevalence was highest in non-Hispanic white individuals, increased with age, and tended to be higher in women. Mean depression scores in patients with thyroid disease (9.1; 95%CI, 8.7-9.5) did not significantly different from those without thyroid disease (9.1; 95%CI, 9.0-9.3) (P = 0.96). CONCLUSION: The age-standardized prevalence of thyroid disease among US adults with depression exhibited a consistent increase from 2007 to 2018, with the highest rate occurring in older, non-Hispanic white individuals, and women.

Preserved Ratio Impaired Spirometry and COPD Accelerate Frailty Progression: Evidence From a Prospective Cohort Study.

BACKGROUND: COPD has been found to be associated with frailty. However, longitudinal evidence for associations of COPD with frailty progression is inadequate. Furthermore, recent studies revealed a new phenotype of lung function impairment: preserved ratio impaired spirometry (PRISm) findings. Associations of PRISm findings and their transitions with frailty progression are unclear. RESEARCH QUESTION: What are the associations of PRISm findings, transitions of PRISm findings, and COPD with frailty progression? STUDY DESIGN AND METHODS: To analyze the associations of PRISm findings and COPD with frailty progression, 5,901 patients were included from the English Longitudinal Study of Ageing. Patients were classified into three lung function patterns of normal spirometry (NS) findings, PRISm findings, and COPD. Frailty progression was assessed by repeated measurements of the frailty index (FI) during follow-up. Among these 5,901 patients, 3,765 patients were included to analyze the associations of PRISm findings transitions with frailty progression. PRISm findings transitions were assessed based on the changes of lung function patterns after a 4-year interval. Linear mixed-effect models were used for statistical analyses. RESULTS: The median follow-up periods were 9.5 years for the analyses of PRISm findings and COPD with frailty progression and 5.8 years for PRISm findings transitions with frailty progression. When compared with participants with NS findings, patients with PRISm findings and COPD demonstrated accelerated FI progression with additional annual increases of 0.301 (95% CI, 0.211-0.392; P < .001) and 0.172 (95% CI, 0.102-0.242; P < .001), respectively. Patients who transitioned from NS findings to PRISm findings also demonstrated accelerated FI progression when compared with those with stable NS findings (ß = 0.242; 95% CI, 0.008-0.476; P = .042). However, no accelerated FI progression was found in patients with PRISm findings who transitioned to NS findings (ß = 0.119; 95% CI, -0.181 to 0.418; P = .438). INTERPRETATION: Our findings indicate that PRISm findings and COPD are associated with accelerated frailty progression. Further studies are needed to elucidate the causality of the association of PRISm findings and COPD with frailty.

Complete androgen insensitivity syndrome coexisting with müllerian duct remnants: a case report and literature review.

This study represents the first documentation of the coexistence of complete androgen insensitivity syndrome (CAIS) with Müllerian duct remnants (MDRs) in mainland China. Additionally, we provide a comprehensive review of the existing literature concerning CAIS with MDRs resulting from androgen receptor (AR) gene mutations. This study broadens the clinical spectrum of CAIS and offer novel insights for further exploration into Müllerian duct regression. A 14-year-old patient, initially raised as female, presented to the clinic with complaints of "primary amenorrhea." Physical examination revealed the following: armpit hair (Tanner stage 2), breast development (Tanner stage 4 with bilateral breast nodule diameter of 7 cm), sparse pubic hair (Tanner stage 3), clitoris measuring 0.8 cm × 0.4 cm, separate urethral and vaginal openings, and absence of palpable masses in the bilateral groin or labia majora. The external genital virilization score was 0 points. Serum follicle-stimulating hormone level was 13.43 IU/L, serum luteinizing hormone level was 31.24 IU/L, and serum testosterone level was 14.95 nmol/L. Pelvic magnetic resonance imaging (MRI) did not reveal a uterus or bilateral fallopian tubes, but nodules on both sides of the pelvic wall indicated cryptorchidism. The karyotype was 46,XY. Genetic testing identified a maternal-derived hemizygous variation c.2359C > T (p.Arg787*) in the AR gene. During abdominal exploration, dysplastic testicles and a dysplastic uterus were discovered. Histopathological analysis revealed the presence of fallopian tube-like structures adjacent to the testicles. The CAIS patient documented in this study exhibited concurrent MDRs, thus expanding the spectrum of clinical manifestations of AIS. A review of prior literature suggests that the incidence of CAIS combined with histologically MDRs is not uncommon. Consequently, the identification of MDRs in AIS cases may represent an integral aspect of clinical diagnosis for this condition.

Identification and Biological Characteristics of Mortierella alpina Associated with Chinese Flowering Cherry (Cerasus serrulata) Leaf Blight in China.

The Chinese flowering cherry (Cerasus serrulata), an ornamental tree with established medicinal values, is observed to suffer from leaf blight within Xi'an's greenbelts. This disease threatens both the plant's growth and its ornamental appeal. In this study, 26 isolates were obtained from plants with typical leaf blight, and only 3 isolates (XA-10, XA-15, and XA-18) were found to be pathogenic, causing similar symptoms on the leaves of the host plant. Based on sequence alignment, the ITS and LSU sequences of the three selected isolates were consistent, respectively. Following morphological and molecular analyses, the three selected isolates were further identified as Mortierella alpina. The three selected isolates exhibited similar morphological characteristics, including wavy colonies with dense, milky-white aerial mycelia on PDA medium. Therefore, isolate XA-10 was used as a representative strain for subsequent experiments. The representative strain XA-10 was found to exhibit optimal growth at a temperature of 30 °C and a pH of 7.0. Host range infection tests further revealed that the representative strain XA-10 could also inflict comparable disease symptoms on both the leaves and fruits of three different Rosaceae species (Prunus persica, Pyrus bretschneideri, and Prunus salicina). This study reveals, for the first time, the causative agent of leaf blight disease affecting the Chinese flowering cherry. This provides a deeper understanding of the biology and etiology of M. alpina. This study lays a solid foundation for the sustainable control and management of leaf blight disease in the Chinese flowering cherry.

Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS: The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.

Genotoxicity evaluation of stearic acid grafted chitosan oligosaccharide nanomicelles.

Stearic acid grafted chitosan oligosaccharide (CSO-SA) nanomicelles could be promptly internalized into cancer cells; therefore, it is regarded as a promising drug carrier for cancer therapy. However, the toxicity of CSO-SA is not clear. In the present study, the genotoxic effects of CSO-SA nanomicelles (with high substitution degree of SA, 42.6±3.8%) were evaluated with a battery of genotoxicity assays. Mutagenicity was not found in Ames Salmonella/microsome mutagenicity assay (Ames test), while mild but definite positive results were observed in mouse bone marrow micronucleus assay and single cell gel electrophoresis (SCGE or comet assay) in A549 cells. CSO-SA was also found to induce apoptosis and oxidative stress through the induction of reactive oxygen species (ROS) in a dose-dependent manner in A549 cells. Preincubation with the free radical scavenger N-acetyl-l-cysteine (NAC) decreased the intracellular ROS level and alleviated the DNA damage in A549 cells. Expression levels of cleaved poly ADP-ribose polymerase (PARP), caspase-9 and caspase-3, markers of apoptosis, were significantly higher in CSO-SA treated cells. In conclusion, these results suggested significant genotoxicity of high doses of CSO-SA nanomicelles in vivo and in vitro. Oxidative stress was, at least partially, the possible mechanism underlying the genotoxicity induced by CSO-SA.

Multiwall carbon nano-onions induce DNA damage and apoptosis in human umbilical vein endothelial cells.

Growing evidence has indicated the potential adverse effects on cardiovascular system of some nanomaterials, including fullerenes. In this study, we have evaluated the biological effects of multiwall carbon nano-onions (MWCNOs) (average size of 31.2 nm, ζ potential of 1.6 mV) on human umbilical vein endothelial cells (HUVECs). It was found that MWCNOs exhibited a dose-dependent inhibitory effect on cell growth; EC50 was 44.12 µg/mL. Thus, three concentrations were chosen (0.2, 1, and 5 µg/mL) for further experiments. Flow cytometry analysis revealed that 1 and 5 µg/mL MWCNOs could induce apoptosis in HUVECs, the apoptotic rates were 12% and 24% at 24 h after exposure. On the other hand, MWCNOs did not affect the cell cycle distribution during 24 h period. Using γH2AX foci formation as an indicator for DNA damage, it was shown that 5 µg/mL MWCNOs can induce γH2AX foci formation in HUVECs at 6, 12, and 24 h after treatment, whereas 0.2 µg/mL MWCNOs induced γH2AX foci formation only at 6 h after treatment. In addition, all three concentrations of MWCNOs induced the generation of reactive oxygen species (ROS), and inhibition of ROS generation can partially decrease the γH2AX foci formation induced by MWCNOs. Taken together, these data first suggested that MWCNOs can induce DNA damage and apoptosis in HUVECs, and that ROS might be involved in this process.

[The pulmonary toxicity study of nano-silica particles on rats through dynamic inhalation].

OBJECTIVE: To investigate the pulmonary toxicity of different concentrations of nano-silica (nano-SiO2) under continuous dynamic inhalation conditions in the rat. METHODS: 48 male Sprague-Dawley rats were randomly divided into four groups, including the dispersant control group (saline) and nano-SiO2 low-dose group (0.3%, w/v), the middle-dose group (1%) and the high-dose group (3%). Animals were sacrificed at 28 d after exposure under continuous dynamic inhalation conditions, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected. And following items were observed: body coefficient, BALF related items (leukocytes and classification, total protein content, LDH activity), lung tissue pathological changes (HE staining), and pulmonary fibrosis forming (collagen fiber VG staining). RESULTS: Compared to the dispersant control group, there was no significant change on lung organ coefficient in Nano-SiO2 group (P < 0.05). The BALF total WBC count in 1% and 3% in nano-SiO2 groups showed higher value than the dispersant control group (P < 0.05). No obvious changes were found on total protein content and LDH activity in nano-SiO2 groups compared to the dispersant control group (P > 0.05). For differential WBC counts, lymphocyte count in BALF in nano-SiO2 groups was significantly decreased (P < 0.05), monocyte and macrophage counts were significantly increased (P < 0.05), but there was no difference on the proportion of neutrophils (P > 0.05). HE staining results showed that the obvious thickening of alveolar wall in nano-SiO2 groups, inflammatory cell infiltration also increased around the bronchial and vascular wall. Lung fibrosis VG staining showed no significant change of collagen fiber distribution. CONCLUSION: Under our experimental conditions, the continuous dynamic inhalation of nano-SiO2 only caused the significant inflammation in rat lungs, pulmonary fibrosis phenomenon could not be observed significantly.

Relationship between complications of type 2 diabetes and thyroid nodules.

OBJECTIVE: Recent evidence suggests that diabetes is a risk factor for thyroid nodules. However, the relationship between complications of type 2 diabetes and the risk of thyroid nodules remains unclear. This present study aims to investigate the association between thyroid nodules and complications of type 2 diabetes. METHODS: This retrospective study collected 4696 adult inpatients with type 2 diabetes between January 2021 and December 2021. The complications examined in this paper included diabetic nephropathy, peripheral neuropathy, eye disorder, and peripheral vascular disease. RESULTS: A total of 4696 patients with type 2 diabetes participated in the study, of whom 19.6% had thyroid nodules. Among all the complications, eye disorder had the highest incidence of thyroid nodules (incidence rate, 29.4%; 95% CI, 26.23%-32.51%). The prevalence of thyroid nodules was lower among patients without complications (incidence rate, 14.1%; 95% CI, 12.48% -15.67%) compared to patients who had complications (incidence rate, 23.1%; 95% CI, 21.59%-24.68%) (p < 0.001). Logistic regression revealed that peripheral neuropathy (adjusted OR, 1.6; 95% CI, 1.4-1.9), eye disorder (adjusted OR, 1.8; 95% CI, 1.5-2.2), and peripheral vascular disease (adjusted OR, 1.8; 95% CI, 1.6-2.1) were all significantly associated with an increased risk of thyroid nodules. However, no significant correlation was found between diabetic nephropathy and the risk of thyroid nodules. CONCLUSION: One of the key findings of this study is that type 2 diabetes without complications is negatively correlated with the risk of thyroid nodules, while several complications are associated with a significantly increased risk of thyroid nodules.

Healthy lifestyle scores associate with incidence of type 2 diabetes mediated by uric acid.

BACKGROUND: Whether and to what extent serum uric acid (SUA) mediates the association between combined lifestyle behaviors and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to investigate the role of SUA in the relationship between healthy lifestyle scores (HLS) and the incidence of T2DM. METHODS: This prospective study used data from Zhejiang Metabolic Syndrome cohort. A HLS (5-point scale including healthy waist circumference (WC), never smoking, high physical activity, healthy diet and moderate alcohol intake) was estimated in 13,919 participants, who had SUA at baseline examination in 2009-2014, and were followed-up to 2021-2022 to ascertain incident of T2DM. Cox proportional hazards models and mediation analysis were used to examine the associations between HLS, SUA and T2DM. RESULTS: We included 13,919 participants aged 18 years or older without diabetes at baseline (mean age 54.6 [SD 13.9] years, 58.7% female). During a median follow-up of 9.94 years, 645 cases of T2DM occurred. Compared with participants with a poor HLS, those with 4-5 low-risk lifestyle factors showed a 60% reduction in the risk of developing T2DM (adjusted HR, 0.40; 95% CI: 0.28-0.57). Further, the population-attributable risk percent (95% CI) of T2DM for poor adherence to the overall healthy lifestyle (< 4 low-risk factors) was 43.24% (30.02%, 56.46%). The HLS was inversely associated with SUA level. With per score increased in HLS, the beta (95% CI) of SUA (log transformed) was - 0.03 (- 0.03, - 0.02), and the odds ratio (95% CI) of hyperuricemia was 0.82 (0.77, 0.86). The relationship between the HLS and risk of T2DM was mediated by SUA with a 13.06% mediation effect. There was no significant combined effect of HLS and SUA on risk of T2DM (P = 0.097). CONCLUSIONS: The relationship between overall healthy lifestyle behaviors and T2DM was reconfirmed and the association appeared to be mediated by SUA. The mediation effect of baseline SUA was more pronounced among women who were below 60 years old.