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 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.

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 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.

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 establish a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the determination of microcystin-LR (MC-LR) in drinking water, investigate its removal efficiency during tap water advanced treatment process and analyze its degradation products in the tap water. Methods: Two parallel water samples were collected from each point of tap water advanced treatment process in September 2015, November 2015 and January 2016, respectively, and treated by mixing, filtration, concentration, elution, nitrogen blow and re-dissolvement. The samples were analyzed by LC/MS/MS to determine the MC-LR concentration and its removal efficiency during treatment process. The combination of actual water enrichment (including source water enrichment of 50 times and 1 500 times concentrated, finished water enrichment of 50 times and 2 500 times concentrated) and laboratory simulated water (including the mixture of MC-LR and liquid chlorine in the mass ratio of 1∶10, 1∶20, 1∶100 and 1∶1 000, respectively) were used to qualitative analyze the MC-LR degradation products by Orbitrap mass spectrometry. Results: The linearity of MC-LR ranged from 2 to 200 μg/L with the detection limit of 0.007 9 μg/L and the limit of quantification of 0.026 3 μg/L. The recovery rate of MC-LR from different contration in drinking water were from 94.88%-101.47%. The intra-day precision was 2.51%-7.93% and the intra-day precision was 3.24%-8.41%. The average concentration of MC-LR in source water was (0.631±0.262) μg/L, 94.0% of which can be removed by ozone exposure while the concentrate was (0.038±0.016) μg/L, biological pre-treatment and chlorination. The remaining can hardly be removed by sand filtration, ozone exposure, activated carbon, ultrafiltration and other processes. The MC-LR average concentration in the finished water maintained at about (0.036±0.016) μg/L. Degradation products including hydroxy-microcystin, methyl-hydroxy-microcystin, methyl-microcystin were identified in the laboratory simulated water of the mixture of MC-LR and liquid chlorine in the mass ratio of 1∶10. Conclusion The established MC-LR detection method can be well applied to the monitoring of MC-LR in drinking water due to its simple pre-treatment process and good methodological validation parameters. The degradation products of treatment processes was different.

OBJECTIVETo investigate the mortality rates of hepatocellular carcinoma (HCC) in Nantong,China from 1999 to 2011, in order to uncover dynamic trends and provide reasoned advice on intervention strategies to decrease HCC incidence and mortality in Nantong in the future.

METHODSVersions 10 and 9 of the WHO International Classification of Diseases (ICD-10 and ICD-9) were used to determine the number of HCC deaths in Nantong,China for the study's range of years. Thex2 test was applied to compare the HCC mortality rates according to sex and age. The Grey system GM(1,1) model was used to predict the next-5-year HCC mortality for Nantong.

RESULTSAnalysis of the standardized mortality in Nantong showed a slight decreasing trend from 1999 to 2011 (x2=57 545.98, P less than 0.001),with males showing a steeper decrease than females. The total mortality of HCC during these years was 53.41 per 100,000 people,with mortality among males being significantly higher than that among females (80.81 per 100,000 people vs. 26.94 per 100,000 people; x2=13 625.42, P less than 0.001). In general, HCC mortality increased with increase in age (general trend:x2=57 545.98, P less than 0.001; male trend: x2=39 878.8, P less than 0.001; female trend: x2=20 105.3, P less than 0.001). However,HCC mortality increased significantly in women after the age of 40 and in men after the age of 35. The GM(1,1) equation was: Yt=-1265.28e(-0.0375t)+1315.5, which predicted that the HCC mortality will decrease to 25.56 per 100,000 people in 2016.

CONCLUSIONAlthough HCC mortality generally decreased from 1999 to 2011, the rate remained high. Public health intervention strategies may be more effective if they focus on males over the age of 35 and females over the age of 40.

Carcinoma, Hepatocellular ; mortality ; China ; epidemiology ; Female ; Humans ; Incidence ; Liver Neoplasms ; mortality ; Male

The enrollment scale of clinical medicine postgraduates with professional degree was expanded each year in order to meet the needs of the society.How to train high quality medical talents in line with modem medical education and people's health needs was the problem we were confronted with.The affiliated hospital of Inner Mongolia medical university lunched reform on training mode of clinical medicine postgraduates with professional degree; the concrete measures included increasing postgraduate pre-service training,implementing tutor responsible system,applying PBL teaching and focusing on the overall quality training.Students' clinical competence was improved after the reform.