Background Tributyl phosphate (TBP) is widely used as an organophosphate flame retardant. However, there are limited studies on the toxicity of TBP to aquatic organisms at low levels of exposure. Objective To investigate the effects of TBP on early development of zebrafish (Danio rerio). Methods Zebrafish embryos were randomly divided into four groups at 2 h post-fertilisation (2 hpf), namely, the 0.01% dimethyl sulfoxide (DMSO) control group and TBP exposure groups (0.02, 0.2 and 2 μg·L⁻¹). The exposure time was from 2 hpf to 120 hpf and the hatching rate, malformation rate, heart rate and body length of zebrafish embryos at 72 hpf, the frequency of tail curling at 24-29 hpf, the locomotor ability at 96 hpf and the survival rate at 120 hpf were evaluated, respectively. The whole-body triiodothyronine (T₃) and tetraiodothyronine (T₄) levels of juvenile fish were measured by enzyme immunoassay at the end of the infection, and the expression levels of hypothalamic-pituitary-thyroid axis (HPT) and neurodevelopmental-related genes were detected by quantitative real-time PCR (q-PCR). Results The heart rates of zebrafish embryos were significantly decreased in all TBP-treated groups (P<0.001), the survival rates of the 0.02 and 2 μg·L⁻¹ TBP groups were significantly decreased (P<0.05), and the malformation rate of the 2 μg·L⁻¹ treated group was significantly increased (P<0.05), which was mainly manifested by pericardial oedema. The frequency of tail curling of zebrafish embryos in all groups reached the highest at 25 hpf, which was significantly lower (P<0.001) in all exposure groups than in the control group (P<0.001). In the locomotor behaviour experiments, the swimming speed of zebrafish larvae in the dark cycle was significantly decreased in the 0.02 and 0.2 μg·L⁻¹ TBP groups (P<0.05), and similar results were found for the light cycle in the 0.2 and 2 μg·L⁻¹ TBP groups (P<0.05). Compared with the control group, the T₃ level of zebrafish juveniles in the 0.2 μg·L⁻¹ TBP group increased significantly (P<0.05). The q-PCR results showed that the expression levels of HTP axis-related genes [thyroid hormone receptors (trα, \begin{document}$tr\beta $\end{document}), thyroglobulin (tg), and sodium/iodide co-transporter (nis)] were significantly down-regulated in the exposure groups, the expression level of transthyretin (ttr) was significantly up-regulated in the 0.02 μg·L⁻¹ TBP group, and the iodothyronine deiodinase 2 (dio2) expression level was significantly down-regulated in the 0.02 μg·L⁻¹ TBP group (P<0.05); the neurodevelopment-related gene acetylcholinesterase (ache) was significantly down-regulated in the exposure groups, and the expression levels of myelin basic protein (mbp) and Elav like neuron-specific RNA binding protein 3 (elavl3) were significantly down-regulated in the 0.02 μg·L⁻¹ TBP group (P<0.05). Conclusion TBP exposure can lead to early developmental abnormalities in zebrafish, manifested as developmental toxicity, thyroid endocrine disruption and neurotoxicity during hatching and early juvenile stages.

Objective To analyze the differences in serum amino acid levels between preeclampsia(PE)and normal pregnant women in Urumqi,and to explore the correlation between amino acids with statistically significant differences and PE severity,as well as their diagnostic value for PE patients.Methods A total of 49 normal pregnant women who visited Urumqi Maternal and Child Health Hospital from June 2021 to June 2023 were selected as the control group and 55 PE pregnant women were selected as the PE group,and the PE group was further divided into mild PE group(25 cases)and severe PE group(30 cases).Liquid chromatogra-phy-tandem mass spectrometry technology was used to determine the levels of 25 metabolites in pregnant women's serum.Spearman correlation analysis was used to analyze the correlation between the amino acid lev-els and PE severity.Logistic regression was used to correct for potential confounding factors,and receiver op-erating characteristic curve was used to analyze the diagnostic efficacy of amino acids with significant differ-ences in PE.Results There were statistically significant differences in the body mass index(BMI)and deliv-ery method between the PE group and the control group(P＜0.05).The serum levels of histidine,threonine,glutamine,ethanolamine,methylhistidine,and canine uric acid in the PE group were higher than those in the control group(P＜0.05).The serum levels of threonine,glutamine,methylhistidine,and canine uric acid in the severe PE group were higher than those in the mild PE group and control group(P＜0.05).The serum ethanolamine levels in the mild group and severe PE group were higher than those in the control group(P＜0.05).The serum histidine levels in the severe PE group were higher than those in the control group(P＜0.05).Correlation analysis showed that serum glutamine,ethanolamine,methylhistidine,and canine uric acid were positively correlated with the severity of PE(P＜0.05).After adjusting for BMI,there were still statisti-cally significant differences in the levels of threonine,glutamine,and methylhistidine between the PE group and the control group(P＜0.05).The area under the curve of the combined detection of serum threonine,glu-tamine,and methylhistidine for diagnosing PE was 0.734.Conclusion There is a certain correlation between serum levels of threonine,glutamine,and methylhistidine and the severity of PE,and the combined detection has high diagnostic value for patients with PE.

Objective:To explore the role of tripartite motif-containing protein 21(TRIM21)in chronic apical periodontitis(CAP)and its potential mechanism.Methods:Human CAP tissue and normal periodontal tissue were collected.The expression of inflamma-tory factors(IL-1 β,IL-6,TNF-a,TGF-β1),osteoclast related genes(TRAP,RANKL,CTSK),macrophage polarization related genes(CD86,iNOS,CD206,Arg1)and TRIM21 were detected by RT-qPCR.TRIM21 protein was detected by immunohistochemical staining,and the osteoclasts was detected by tartrate resistant acid phosphatase(TRAP)staining.The inflammation cell model was es-tablished by stimulating Raw264.7 cells with lipoteichoic acid(LTA)or lipopolysaccharide(LPS),and the expression of the above factors was detected.The bone marrow-derived macrophages(BMDMs)extracted from wild-type and TRIM21-/-mice stimulated by LPS were used to verify the expression of the above factors by RT-qPCR,the osteoclasts were detected by TRAP staining,and the po-larization of macrophages was detected by immunofluorescence staining.Results:In CAP tissue the expression of inflammatory factors,osteoclast related genes,CD86,iNOS and TRIM21 increased,while CD206 and Arg1 decreased,and osteoclasts were more than that in normal tissue.The stimulation of LTA/LPS promoted the proliferation of Raw264.7 cells,and the expression of these factors in cells was consistent with that in tissues.After LPS stimulation,BMDMs of TRIM21-/-mice had lighter inflammation,lower expression of os-teoclast specific genes,fewer osteoclasts and lower M1 polarization than those of wild type mice.Conclusion:TRIM21 might promote the progress of CAP by promoting M1 polarization of macrophages.

Objective:To systematically evaluate the life experiences of young-onset dementia (YOD) patients and provide a basis for healthcare professionals to develop effective support service strategies.Methods:Qualitative studies on the life experiences of YOD patients were retrieved from PubMed, Embase, Medline, CINAHL, PsycINFO, Scopus, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP, WanFang data, and China Biology Medicine disc. The search timeframe was from the establishment of the databases to December 10, 2023. A Meta-synthesis approach was used to integrate the results.Results:A total of 17 articles were included, from which 69 findings were extracted, forming 11 categories and synthesizing into four integrated results: the heavy physical and psychological burden borne by YOD patients, impairment in multiple roles and social isolation, unique needs of YOD patients, and various coping strategies of YOD patients.Conclusions:Healthcare professionals should focus on the personal stories of YOD patients, pay attention to their physiological, psychological, and social challenges, and continuously improve supportive care services to alleviate their psychological burden, promote social connections, assist in resuming life, and enhance their quality of life.

Cognitive reserve referred to the cumulative flexibility of an individual's cognitive processes,whereas accurately assessing an individual's cognitive reserve and intervening was important for preventing the occurrence of cognitive dysfunction as well as promoting cognitive health.This article reviewed the main contents and applications of cognitive reserve assessment tools,and compared the characteristics and limitations of each assessment tool.The purpose was to provide ideas for the development of cognitive reserve assessment tools suitable for China's cultural background and population characteristics,and to provide a basis for accurately assessing the current status of China's cognitive reserve and formulating targeted cognitive reserve enhancement programs.

Objective: To investigate the prevalence and influencing factors of comorbidity of chronic diseases among hypertensive patients with uncontrolled blood pressure in Huzhou City, so as to provide insights into community hypertension control. Methods: Hypertensive patients with uncontrolled blood pressure at ages of 35 to 74 years were sampled using a cluster random sampling method from 5 districts (counties) of Huzhou City. Participants' demographics, living behaviors, and development of chronic diseases were collected using questionnaires, and the height, body weight, waist circumference and blood pressure were measured. Blood glucose, blood lipid and other biochemical parameters were detected, and the number and combination of comorbidity of chronic diseases were descriptively analyzed. Factors affecting the comorbidity of chronic diseases were identified using a multivariable ordinal logistic regression model. Results: A total of 1 215 respondents were included, with a mean age of (60.83±7.76) years, and including 652 men (53.66%) and 563 women (46.34%). The prevalence of dyslipidemia, diabetes, hyperuricemia and cardiac encephalopathy was 45.10%, 30.95%, 23.05% and 5.10%, respectively. The prevalence of comorbidity of chronic diseases was 69.22% among respondents, and there were 497 respondents with one comorbidity (40.91%), 272 with two comorbidities (22.39%) and 72 with three and more comorbidities (5.93%). Hypertension+dyslipidemia (20.74%), hypertension+diabetes+dyslipidemia (9.96%) and hypertension+diabetes+dyslipidemia+hyperuricemia (4.36%) were predominant comorbid combinations. Multivariable ordinal logistic regression analysis showed that participants with overweight (OR=1.782, 95%CI: 1.390-2.286), obesity (OR=2.411, 95%CI: 1.802-3.222), grade 2 hypertension (OR=1.438, 95%CI: 1.077-1.919) had a higher risk of multiple comorbidities than those with normal body mass index and controlled blood pressure, and women (OR=0.563, 95%CI: 0.456-0.696) had a lower risk of multiple comorbidities than men. Conclusions The prevalence of comorbidity of chronic diseases was 69.22% among community hypertensive patients with uncontrolled blood pressure in Huzhou City, and the comorbidity of chronic diseases mainly included dyslipidemia and diabetes. Men, overweight, obesity and hypertension resulted in a high risk of comorbidity of chronic diseases.

Objective:To investigate the clinical and genetic characteristics of patients with late-onset subtypes (adolescent or adult) of Krabbe disease.Methods:The clinical data of 7 patients with Krabbe disease admitted to Shanghai Jiao Tong University Affiliated Sixth People′s Hospital and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2006 to June 2021 were analyzed and Sanger sequencing of the galactosylceramidase (GALC) gene (NM_000153) and detection of the activity of GALC were conducted. A total of 61 cases of Krabbe disease reported in domestic literature were reviewed and summarized.Results:Among the 7 patients with Krabbe disease, there were 4 males and 3 females. All of them had lower limb weakness or walking difficulty as the initial symptoms, and presented as spastic paraplegia. The symptoms were relatively mild in patients with late onset. There were 4 out of 5 patients undergoing magnetic resonance imaging examination, who showed abnormal signals: 2 had brain atrophy and the remaining 2 had white matter lesions. A total of 5 GALC gene mutations were detected by genetic analysis. Among these, c.1901T>C (p.L634S), c.908C>T(p.S303F) and c.461C>A(p.P154H) are known variants, while c.50_51insTT (p.M17Ifs) and c.1130delT(p.L337X) are novel variants reported for the first time in this paper.Conclusions:Krabbe disease is a rare neurodegenerative disease with phenotypic heterogeneity, which is inherited in an autosomal recessive mode. The severity of clinical manifestations of Krabbe disease is correlated with the age of onset.

Objective To investigate the protective effect of brain-derived neurotrophic factor (BDNF) on neuronal injury induced by ropivacaine (Rop) and its mechanism.Methods (1) Experiment one:0,1,2,3,4 and 5 mmol/L Rop was used to stimulate SH-SY5Y cells for 48 h to induce neuronal injury;the morphological changes of the cells were observed under microscope;MTT assay was used to detect the cell activity;flow cytometry was used to detect the cell apoptosis,and immunohistochemistry was used to detect the expressions of protein kinase B (Akt) and proliferating cell nuclear antigen (PCNA).(2) Experiment two:SH-SY5Y cells were treated with 0,1,3,5,7 mmol/L Rop,respectively;the cell activity was measured 48 h after Rop treatment;the semi inhibitory concentration (IC50) of Rop was calculated by MTT assay;the SH-SY5Y cells were divided into control group (PBS for 48 h),Rop group (Rop at IC50 for 48 h),BDNF+Rop group (20 μg/L BDNF for 2 h,and Rop at IC50 for 48 h),Akt pathway activator SC79+Rop group (5 mg/L SC79 for 2 h,and Rop at IC50 for 48 h),and BDNF+Akt pathway inhibitor API-2+Rop group (20 μg/L BDNF+10 μmol/L API-2 for 2 h,Rop at IC50 for 48 h);the morphological changes of the cells were observed under microscope;MTT assay was used to detect the cell activity;flow cytometry was used to detect the cell apoptosis,and immunohistochemistry was used to detect the expressions of Akt and PCNA;the expressions of B lymphoma-2 (Bcl-2),Bcl-2-associated X (Bax) and cysteine protease-3 (Caspase-3) were detected by reverse transcription (RT)-PCR and Western blotting.Western blotting was used to detect the expressions of Akt and phosphatidylinositol 3-kinase (PI3K).Results (1) As compared with the 0 mmol/L Rop group,the 1,2,3,4,and 5 mmol/L Rop group had significantly decreased cell activity,significantly increased apoptosis rate,and statistically smaller number of Akt and PCNA positive cells (P＜0.05).(2) As compared with the control group,the Rop group had significantly decreased cell activity,statistically increased apoptosis rate,significantly smaller number of Akt and PCNA positive cells,significantly decreased Bcl-2 mRNA and protein expressions,significantly increased Bax and caspase-3 mRNA and protein expressions,and significantly decreased phosphorylated-(p-) Akt and p-PI3K protein expressions;as compared with the Rop group,the BDNF+Rop group and SC79+Rop group had significantly higher cell activity,significantly decreased apoptosis rate,significantly larger number of Akt and PCNA positive cells,significantly increased Bcl-2 mRNA and protein expressions,statistically decreased mRNA and protein expressions of Bax and Caspase-3,and significantly increased p-Akt and p-PI3K protein expressions (P＜0.05);as compared with the BDNF+Rop group and SC79+Rop group,the BDNF+API-2+Rop group had significantly lower cell activity,significantly increased apoptosis rate,significantly smaller number of Akt and PCNA positive ceils,significantly decreased Bcl-2 mRNA and protein expressions,statistically increased mRNA and protein expressions of Bax and Caspase-3,and significantly decreased p-Akt and p-PI3K protein expressions (P＜0.05).Conclusion BDNF can alleviate ropivacaine-induced neuronal injury by activating Akt signaling pathway,consequently modulating the proliferation and apoptosis of neurons.

Objective To investigate the effect of hyperbaric oxygen (HBO) on malignant biological behavior of ovarian cancer SKOV3 cells and its related mechanism.Methods After the culture of human ovarian cancer cell line SKOV3 was completed,the effects of HBO on the proliferation,apoptosis and tumorigenicity of SKOV3 cells were respectively detected by CCK-8,flow cytometry and Western blotting in the HBO group and the control group,and the effects of HBO on PTEN/PI3K/AKT pathway activation were detected by Western blotting.After PTEN was knocked down,the effects of HBO on the proliferation and apoptosis of SKOV3 cells were detected by the above methods.The inhibition of HBO on the growth of ovarian cancer-bearing mice and the expression of related proteins were detected by tumor-bearing experiment in mice.Results Proliferation of SKOV3 cells in the HBO group was significantly decreased,while apoptosis was significantly improved (P ＜ O.05).In the HBO group,the expression of Bcl-2 was decreased,while the expression of Bax and caspase-3 were increased (P ＜ 0.05).HBO could significantly increase the expression of PTEN protein,and at the same time decrease the expressions of p-PI3K and p-AKT proteins in ovarian cancer SKOV3 cells (P ＜0.05 or P ＜0.01).In addition,the expression of HIF-1 in SKOV3 cells was decreased in the HBO group,however,after knock-down of PTEN,the inhibitory effect of HBO on the expression of HIV-1 in SKOV3 cells was significantly weakened (P ＜ 0.05).The proliferation and apoptosis of SKOV3 cells in the hyperbaric oxygen + si-PTEN group were significantly inhibited (all P ＜ 0.05).Compared with the control group,the tumor size and body mass of mice in the HBO group were significantly decreased (all P ＜ 0.05).The expression levels of HIF-1,p-PI3K,p-AKT and Bcl-2 proteins in the ovarian cancer tissues were decreased,while the expression levels of PTEN,caspase-3 and Bax were increased (all P ＜ 0.05).Conclusion HBO treatment could significantly inhibit malignant biological behavior of ovarian cancer SKOV3 cells,the mechanism of which might be related with the improvement of the hypoxic environment of cells through the regulation of PTEN/PI3K/AKT pathway.

Objective To investigate the effect of hyperbaric oxygen (HBO) on malignant biological behavior of ovarian cancer SKOV3 cells and its related mechanism.Methods After the culture of human ovarian cancer cell line SKOV3 was completed,the effects of HBO on the proliferation,apoptosis and tumorigenicity of SKOV3 cells were respectively detected by CCK-8,flow cytometry and Western blotting in the HBO group and the control group,and the effects of HBO on PTEN/PI3K/AKT pathway activation were detected by Western blotting.After PTEN was knocked down,the effects of HBO on the proliferation and apoptosis of SKOV3 cells were detected by the above methods.The inhibition of HBO on the growth of ovarian cancer-bearing mice and the expression of related proteins were detected by tumor-bearing experiment in mice.Results Proliferation of SKOV3 cells in the HBO group was significantly decreased,while apoptosis was significantly improved (P ＜ O.05).In the HBO group,the expression of Bcl-2 was decreased,while the expression of Bax and caspase-3 were increased (P ＜ 0.05).HBO could significantly increase the expression of PTEN protein,and at the same time decrease the expressions of p-PI3K and p-AKT proteins in ovarian cancer SKOV3 cells (P ＜0.05 or P ＜0.01).In addition,the expression of HIF-1 in SKOV3 cells was decreased in the HBO group,however,after knock-down of PTEN,the inhibitory effect of HBO on the expression of HIV-1 in SKOV3 cells was significantly weakened (P ＜ 0.05).The proliferation and apoptosis of SKOV3 cells in the hyperbaric oxygen + si-PTEN group were significantly inhibited (all P ＜ 0.05).Compared with the control group,the tumor size and body mass of mice in the HBO group were significantly decreased (all P ＜ 0.05).The expression levels of HIF-1,p-PI3K,p-AKT and Bcl-2 proteins in the ovarian cancer tissues were decreased,while the expression levels of PTEN,caspase-3 and Bax were increased (all P ＜ 0.05).Conclusion HBO treatment could significantly inhibit malignant biological behavior of ovarian cancer SKOV3 cells,the mechanism of which might be related with the improvement of the hypoxic environment of cells through the regulation of PTEN/PI3K/AKT pathway.