OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group （0.5% carboxymethyl cellulose sodium solution）， model group （0.5% carboxymethyl cellulose sodium solution）， and BP low-dose and high-dose groups （50， 100 mg/kg）， with 10 mice in each group. Except for the normal control group， the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model； they were given relevant medicine/solution intragastrically， once a day， for consecutive 8 weeks. After the last medication， the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum were detected， and liver pathological changes were observed； the expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were detected in liver tissue； the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group， serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （P＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group， of which 18 substances were upregulated and 157 substances were downregulated； the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism， butanoate metabolism， fatty acid synthesis， tyrosine metabolism， β-alanine metabolism， nicotinic acid and nicotinamide metabolism， glutathione metabolism， etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism， butanoate metabolism， glutathione metabolism and so on in rats with liver fibrosis.

Objective To explore the characteristics of echolalic speech of children with moderate to severe autism spectrum disor-der(ASD)aged three to eight. Methods From January to March,2024,15 minutes rehabilitation course video of five children with moderate to severe ASD aged three to eight were collected in institutional and family settings,respectively.Language sample analy-sis and self-compiled coding were used to analyze the echo speech sample content,structure,and collect their oral language ability.The correlation between the echo speech and case oral language ability was analyzed. Results A total of 235 echoic speech-related speech rounds were recorded.Among them,the ratio of immediacy to de-layed echo speech was 7∶1;one echo speech was found in every two to three speech responses,with average sen-tence length of 2.97 and average word length of 2.23.The frequency of verbs and nouns was high,accounting for 45.03%and 38.48%,respectively;and there were many declarative words and sentences,accounting for 72.58%on average.The type of echo speech structure was the most frequently at the end of the reconstructed discourse,accounting for 29.98%on average.The type,frequency,sentence length,sentence pattern and structure of echoic speech were not significantly different in institutional and family settings.The language ability scores of imita-tion sentence length,word understanding and naming were significantly correlated with the number,frequency,sentence length and sentence type frequency of echoic speech(r>0.881,P<0.01). Conclusion Echoic speech activity in children with moderate to severe ASD aged three to eight shows transsituational stability,and is related with their understanding language and expressive language ability;characterized as instant echo speech,short sentence,the advantage of real words,declarative sentences,often repeat the end of the origi-nal sentence.

Objective To construct the evaluation index of physical restraint nursing quality for neurosurgical patients,which can guide nurses'clinical practice and continuously improve work flow and quality.Methods Under the guidance of three-dimensional quality structure model,the evaluation index of nursing quality of physical restraint in neurosurgery patients was established by reviewing literature,interviewing experts and using Delphi expert correspondence.Results The effective recovery rate of three rounds of expert enquiry was 100％,the expert authority coefficient was＞0.9,the first and second coordination co-efficients were 0.126 and 0.094(P＜0.001),and the final evaluation index included 3 first-level indicators and 31 second-level indicators.Conclusion The established evaluation indexes are scientific,standardized and comprehensive,which can guide the nursing quality of neurosurgery patients with physical restraint.

Objective To investigate the efficacy and safety of interventional therapy for bronchopleural fistula(BPF).Methods A total of 172 patients with confirmed BPF were treated with continuous negative pressure drainage(CNPD)and/or airway stent occlusion therapy.The clinical data were collected,and its effectiveness and safety were analyzed.Results In 5-7 days after interventional treatment,the pneumonia severity index(PSI)decreased significantly,and successful drainage was achieved in 166 patients(96.5％).One month after interventional therapy,the lung volume was remarkably increased.The median clinical healing time of interventional therapy was 9.0 months(95％CI=6.18-1 1.83).Multivariate analysis of the Cox proportional hazards model showed that the diagnosis time(HR=0.53,95％CI=0.38-0.74,P＜0.01)and fistula size(HR=0.74,95％CI=0.55-0.99,P=0.04)were significantly correlated with the clinical healing time.Conclusion For the treatment of BPF,CNPD and/or airway stent occlusion has several advantages such as accurate operation,minimally invasive,safe and effective.It can quickly improve the symptoms and quality of life,and prolong survival,therefore,it is worthy of clinical promotion and application.(J Intervent Radiol,2024,33:641-645)

Objective:To explore the influence of family function and personal characteristics on death anxiety in patients with advanced cancer, providing reference for finding methods and approaches to alleviate death anxiety in advanced cancer patients.Methods:From March to June 2023, convenience sampling was used to select 182 advanced cancer patients admitted to the Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University. The Chinese Version of Death and Dying Distress Scale and Family APGAR Index were used to investigate patients' death anxiety and family function. The Numerical Rating Scale and Kamofsky Performance Status were used to assess patients' pain and performance status. Single factor analysis and multiple linear regression were used to analyze the influencing factors of death anxiety in advanced cancer patients.Results:A total of 182 questionnaires were distributed, and 165 valid questionnaires were collected, with a valid response rate of 90.7%. The death anxiety score of advanced cancer patients was (22.52±15.27), and 10.3% (17/165) of patients had moderate or above death anxiety. The patients' total family function score was (8.62±1.97), and 86.7%(143/165) patients self-reported good family function. The death anxiety score was negatively correlated with the family function score ( P<0.05). Multiple linear regression analysis showed that Kamofsky Performance Status score, pre-illness employment, family function, place of residence, and pain score were the influencing factors of death anxiety in advanced cancer patients, and the differences were statistically significant ( R2=0.196, P<0.01) . Conclusions:The advanced cancer patients have low levels of death anxiety in our study. Advanced cancer patients with moderate family dysfunction, living in rural areas, working before illness, and high pain scores have high levels of death anxiety, while patients with good performance status have low levels of death anxiety. It is recommended that clinical workers strengthen the assessment of death anxiety and family function in patients with advanced cancer, take timely and effective measures based on influencing factors, and help alleviate death anxiety in patients with advanced cancer.

Objective:To analyze and summarize the key points of design and implementation of new drug clinical trials for ankylosing spondylitis.Methods:The platform for drug clinical trial registration and information published on the official website of center for drug review and evaluation of national medical products administration (CDE) was searched to obtain data and classified statistics was conducted then. The Mean±SD and M ( Q1, Q3) were used for quantitative data for statistical description, and the rate, composition or relative ratio of qualitative data were used for statistical description. Results:A total of 23 clinical trials meeting the requirements were screened, among which 19 were biological products included in nine phase Ⅲ clinical trials. Among the four chemical drugs, two were phase Ⅱ clinical trials. One of the clinical trials on AS adopted the 1966 New York classification criteria, accounting for 4%. Nineteen of the trials adopted the1984 New York classification criteria, accounting for 83%. Three other trials adopted unspecified classification criteria, accounting for 13%. In one of these clinical trials, the age of patients included was older than 16 years old, 9 trials were 18 to 65 years old, 6 were 18 years old but without upper limit. In the definition of active AS, 19 trials took BASDAI≥4 as the cut-off value for active disease, and BASDAI, total back pain, spinal pain and morning stiffness were regarded as active disease in 4.Conclusion:The number of dosestic AS clinical trial projects continnes to rise. The 1984 classification criteria is adopted as the classification criteria in clinical trials. The minimum age in the inclusion criteria is 18 years old, there is no upper limit in age for inclusion. Disease activity can be evaluated by BASDAI score, combined with comprehensive indicators such as night-time back pain, global spinal pain and morning stiffness.

Objective:To investigate the impact of exogenous lactate on the replication of dengue virus type 2 (DENV-2) in Raw264.7 cells, mouse bone marrow-derived macrophages (BMDMs) and THP-1 cells and explore its association with cell activation.Methods:BMDMs from BALB/c mouse bone marrow were prepared and evaluated by flow cytometry to detect the proportion of F4/80 + CD11b + cells. Glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), and monocarboxylate transporters 4 (MCT4) expression at mRNA level in BMDMs at different time points after DENV-2 infection were measured by qRT-PCR. The content of lactate in the culture supernatants was quantified via colorimetric assay. CCK-8 assay was used to evaluate the impacts of different concentrations of lactate on the viability of Raw264.7 cells, BMDMs, and THP-1 cells. qRT-PCR was used to detect the expression of DENV-2 E gene, TGF-β, CD86, retinoic acid-inducible gene Ⅰ (RIG-Ⅰ), IFN-β, interferon-stimulated gene 15 (ISG15), and ISG56 at mRNA level in cells infected with DENV-2 at different MOIs in the presence of different concentrations of lactate. Meanwhile, flow cytometry was used to analyze the expression of CD86 and CD206. Results:The percentage of BMDMs was (87.53±1.66)%. GLUT1 expression at mRNA level exhibited a decrease in BMDMs at 24 h after DENV-2 (MOI=3) infection following a transient increase at 12 h ( P<0.05), while HK2 expression at mRNA level was higher that than in blank control and inactivated DENV-2 infection groups at 12, 24, and 36 h ( P<0.01). Besides, there was an increase in both MCT4 mRNA level and the content of lactate in culture supernatants at 24 h after DENV-2 (MOI=1.5) infection ( P<0.05). The viability of the three types of cells remained above 80% when the concentration of lactate was 31.25 mmol/L. Lactate at the concentration of 35 mmol/L increased the expression of the DENV E gene at mRNA level in DENV-2-infected BMDMs at MOI=1 or MOI=2 ( P<0.05). Besides, it promoted the expression of DENV E gene at mRNA level in Raw264.7 and THP-1 cells ( P<0.001) as well as the expression of CD163, TGF-β, RIG-Ⅰ, IFN-β, ISG15 and ISG56 at mRNA level in BMDMs at MOI=1.5, but inhibited the expression of CD86 at mRNA level in BMDMs ( P<0.05). It also up-regulated CD206 protein expression ( P<0.01) and down-regulated CD86 protein expression ( P>0.05) in BMDMs. Conclusions:Exogenous lactate enhances DENV-2 replication in both human- and murine-derived macrophages and that might correlate with M2 macrophage polarization.

Abstract: Objective　To investigate the pollution characteristics of major heavy metals in PM2.5 in urban areas of Haikou City, and to assess their potential health risks to humans. Methods　From 2021 to 2022, samples of atmospheric PM2.5 were monthly collected from the typical urban areas of Haikou, and the concentrations of nine heavy metal elements including arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), nickel (Ni), copper (Cu), vanadium (V), and zinc (Zn) were measured using the inductively coupled plasma mass spectrometry (ICP-MS). The health risk assessment of these heavy metals was conducted using a health risk model. Results　The average mass concentration of PM2.5 in Haikou was (20.506±13.054) µg/m³, with a range of 4.000 to 64.000 µg/m³ during the year 2021 and 2022. The PM2.5 concentrations showed significant seasonal variations: highest in winter, followed by autumn and spring, and lowest in summer. The total concentration of the nine heavy metal elements ranged from 0.030 to 138.000 ng/m³, with Zn, Mn, and Pb having the highest concentrations, particularly notable during the autumn and winter seasons. Enrichment factor (EF) analysis indicated moderate enrichment (10 Cd > Cr > As > Pb > V > Zn > Cu > Ni. The total non-carcinogenic hazard index (HI) ranged from 0.171 to 0.361. The inhalation incremental lifetime carcinogenic risk values (ILCR) for the four elements Cr, As, Cd, and Ni ranged from 2.911×10-7 to 1.558×10-5, with ILCR decreasing in that order. The total carcinogenic risk index (TR) varied between 1.502×10-5 and 3.169×10-5, with risk intensities for HI and TR in the order: children > adult males > adult females. Conclusions　The average PM2.5 concentration in the Haikou urban area is lower than the 24-hour average concentration limit of Grade I (35 µg/m3) in the "Environmental Air Quality Standard" (GB 3095-2012), but still higher than the control standard recommended by the WHO in 2021 (15 µg/m3). The non-carcinogenic health risks of the nine heavy metal elements detected in PM2.5 are not significant, but Cr and As have potential carcinogenic risks, with children being more vulnerable than other populations.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective:To compare the efficacy and safety of different dosages of new drugs in the treatment of PsA by using network meta-analysis.Methods:Three medical databases (PubMed, Web of Science, Cochrane Library) were searched for the studies that compared the efficacy and safety of 4 new drugs (secukinumab, ixekizumab, apremilast, tofacitinib) with different dosages in the treatment of PsA. Data from included studies were analyzed by Stata 15.0.Results:A total of 16 RCTs were included. The results of the network meta-analysis showed that: (1) Among the overall patients, in terms of ACR20 response rate, the larger the surface under the cumulative ranking (SUCRA), the more effective it is. Secukinumab 300 mg Q4W(96.1%) had the best efficacy, followed by ixekizumab 80 mg Q4W(79.0%), ixekizumab 80 mg Q2W(75.1%), secukinumab 150 mg Q4W(73.2%), apremilast 30 mg BID(50.6%), apremilast 20 mg BID(38.6%), tofacitinib 5 mg BID(18.1%), tofacitinib 10 mg BID(17.7%) and placebo(2.0%). (2) In terms of PASI75 response rate, the larger the area under the SUCRA curve, the more effective it is. Ixekizumab 80 mg Q4W(96.1%) had the best efficacy, followed by ixekizumab 80 mg Q2W(88.7%), secukinumab 300 mg Q4W(75.6%), secukinumab 150 mg Q4W(63.3%), apremilast 30 mg BID(44.5%), apremilast 20 mg BID(38.4%), tofacitinib 10 mg BID(30.0%), tofacitinib 5 mg BID(12.5%) and placebo(1.0%). (3) Among the overall patients, in terms of safety, the smaller the area under the SUCRA curve, the higher the safety it is. Secukinumab 300 mg Q4W (17.3%) has the best safety. (4) The results of subgroup analysis showed that in terms of ACR20 response rate, ixekizumab 80 mg Q2W(85.3%) had the best efficacy in bDMARDs-na?ve patients, while in bDMARDs-IR patients, secukinumab 300 mg Q4W(83.9%) had the best efficacy.Conclusion:Among all patients, secukinumab 300 mg Q4W is the best in terms of ACR20 response rate and safety, but ixekizumab 80 mg Q4W is more effective in improving PsA lesions comparing yo other drugs.