Humans ; Parkinson Disease/diagnosis* ; Machine Learning

The study aims to observe the effects and explore the mechanisms of Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination in the treatment of the inflammatory response of mice with atherosclerosis(AS) via the Toll-like receptor 4(TLR4)/myeloid differentiation primary response protein 88(MyD88)/nuclear factor-κB(NF-κB) signaling pathway. Male ApoE~(-/-) mice were randomly assigned into a model group, a Buyang Huanwu Decoction group, an Astragali Radix-Angelicae Sinensis Radix combination group, and an atorvastatin group, and male C57BL/6J mice of the same weeks old were used as the control group. Other groups except the control group were given high-fat diets for 12 weeks to establish the AS model, and drugs were administrated by gavage. Aortic intimal hyperplasia thickness, blood lipid level, plasma inflammatory cytokine levels, M1/M2 macrophage markers, and expression levels of proteins in TLR4/MyD88/NF-κB pathway in the vessel wall were measured to evaluate the effects of drugs on AS lesions and inflammatory responses. The results showed that the AS model was successfully established with the ApoE~(-/-) mice fed with high-fat diets. Compared with the control group, the model group showed elevated plasma total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c) levels(P<0.05), thickened intima(P<0.01), and increased plasma tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) levels(P<0.01). Moreover, the model group showed increased expression of vascular cell adhesion molecule-1(VCAM-1) and inducible nitric oxide synthase(iNOS)(P<0.01), inhibited expression of endothelial nitric oxide synthase(eNOS) and cluster of differentiation 206(CD206)(P<0.01), and up-regulated mRNA and protein levels of TLR4, MyD88, NF-κB inhibitor alpha(IκBα), and NF-κB in the vessel wall(P<0.05). Compared with the model group, Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination lowered the plasma TC and LDL-c levels(P<0.01), alleviated the intimal hyperplasia(P<0.01), and reduced the plasma TNF-α and IL-6 levels(P<0.05). Moreover, the two interventions promoted the expression of eNOS and CD206(P<0.05), inhibited the expression of VCAM-1 and iNOS(P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, IκBα, and NF-κB(P<0.05) in the vessel wall. This study indicated that Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination could delay the progression of AS, inhibit the polarization of vascular wall macrophages toward M1 type, and attenuate vascular inflammatory response by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway in the vascular wall. Astragali Radix and Angelicae Sinensis Radix were the main pharmacological substances in Buyang Huanwu Decoction for alleviating the AS vascular inflammatory response.
Mice ; Male ; Animals ; NF-kappa B/metabolism* ; Toll-Like Receptor 4/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Cholesterol, LDL ; Hyperplasia ; Mice, Inbred C57BL ; Atherosclerosis/genetics* ; Apolipoproteins E/therapeutic use* ; RNA, Messenger

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

INTRODUCTION: We investigated the knowledge, attitudes and practice (KAP) towards coronavirus disease 2019 (COVID-19) and its related preventive measures in Singaporeans aged ≥60 years. METHODS: This was a population-based, cross-sectional, mixed-methods study (13 May 2020-9 June 2020) of participants aged ≥ 60 years. Self-reported KAP about ten symptoms and six government-endorsed preventive measures related to COVID-19 were evaluated. Multivariable regression models were used to identify sociodemographic and health-related factors associated with KAP in our sample. Associations between knowledge/attitude scores and practice categories were determined using logistic regression. Seventy-eight participants were interviewed qualitatively about the practice of additional preventive measures and data were analysed thematically. RESULTS: Mean awareness score of COVID-19 symptoms was 7.2/10. The most known symptom was fever (93.0%) and the least known was diarrhoea (33.5%). Most participants knew all six preventive measures (90.4%), perceived them as effective (78.7%) and practised 'wear a mask' (97.2%). Indians, Malays and participants living in smaller housing had poorer mean scores for knowledge of COVID-19 symptoms. Older participants had poorer attitudes towards preventive measures. Compared to Chinese, Indians had lower odds of practising three out of six recommendations. A one-point increase in score for knowledge and attitudes regarding preventive measures resulted in higher odds of always practising three of six and two of six measures, respectively. Qualitative interviews revealed use of other preventive measures, for example, maintaining a healthy lifestyle. CONCLUSIONS Elderly Singaporeans displayed high levels of KAP about COVID-19 and its related preventive measures, with a positive association between levels of knowledge/attitude and practice. However, important ethnic and socioeconomic disparities were evident, indicating that key vulnerabilities remain, which require immediate attention.
Humans ; Aged ; COVID-19/epidemiology* ; SARS-CoV-2 ; Health Knowledge, Attitudes, Practice ; Cross-Sectional Studies ; Singapore/epidemiology* ; Surveys and Questionnaires

Over the past half-century,the climate change,along with population growth,worsens the intensity and frequency of sand storms in China,and the environmental and health problems have become increasingly prominent.Sand and dust particles not only possess their own toxicity but also carry numerous pathogenic microorganisms and heavy metals.This can lead to high concentrations of local dust pollution,causing significant harm to the air environment and the health of residents in downwind areas during long-distance transportation sand and dust.Based on a comprehensive literature review on the health effects of dust storms,this paper aims to summarize the impact of various pathogenic factors presenting in dust storms on human health and the underlying mechanisms to provide a scientific foundation for the development of more effective control measures.In the future,amidst the backdrop of climate change,it is crucial to prioritize the research and analysis of dust source regions and dust control strategies in northern China.Additionally,there is a need to enhance the technology for simulating sand and dust environments in experiments,and to adopt a multidisciplinary approach to investigate the medical and toxicological aspects of sand and dust weather.

INTRODUCTION: Lifestyle activities, such as regular physical activity, are important for good metabolic health and the prevention of non-communicable diseases. Epidemiological studies highlight an increase in the proportion of overweight children in Singapore. A workgroup was formed to develop recommendations to encourage children and adolescents (aged 7-17 years) to adopt a holistic approach towards integrating beneficial activities within a daily 24-hour period for good metabolic and general health. METHODS: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework was employed to formulate the public health question, assess the evidence and draw conclusions for the guide. The evidence for international 24-hour movement guidelines, and guidelines for physical activity, sedentary behaviour, and sleep and eating habits were reviewed. An update of the literature review from August 2018 to end of September 2020 was conducted through an electronic search of Medline and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. RESULTS: Ten consensus statements were developed. The statements focused on the overall aim of achieving good metabolic health through integration of these activities and initiatives: light and moderate- to vigorous-intensity physical activity on a regular basis; muscle- and bone-strengthening activities; limiting sedentary behaviour; regular and adequate sleep; good eating habits and choosing nutritionally balanced foods and drinks; practise safety in exercise; and aiming to achieve more or all aforementioned recommendations for the best results. CONCLUSION This set of recommendations provides guidance to encourage Singapore children and adolescents to adopt health-beneficial activities within a 24-hour period.
Adolescent ; Child ; Exercise ; Humans ; Public Health ; Sedentary Behavior ; Singapore ; Sleep

OBJECTIVE: To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism. METHODS: Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq). RESULTS: Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level. CONCLUSION LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.
Acetylation ; Animals ; Inflammation Mediators ; Interleukin-6/metabolism* ; Lipopolysaccharides/pharmacology* ; Mice ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To investigate the effect of Xiaoyaosan on depressive behavioral phenotype in mice with vascular dementia （VaD） mice and its possible mechanism. Method:Sixty three-month-old male C57/BL6 mice were divided into the normal control group， model group， positive control group， as well as low-， medium-， and high-dose Xiaoyaosan groups. Mice in all groups except for the normal control group underwent bilateral carotid artery stenosis. Two weeks later， they were subjected to chronic restraint stress， 6 h per day， for inducing VaD complicated with depression. Mice in the low-， medium-， and high-dose Xiaoyaosan groups were treatment with intragastric administration of Xiaoyaosan decoction （5， 10， 20 g·kg^-1）， the ones in the positive control group with fluoxetine （10 mg·kg^-1）， and those in the normal control group and model group with an equal volume of normal saline for four weeks， during which the restraint stress was maintained. The depressive behavioral phenotype of mice was observed in sugar water preference test and tail suspension test. The fluorescence expression of myelin basic protein （MBP） in ventral hippocampus （vHIP） was detected by fluorescence immunoassay. The ultrastructure of myelin sheath in vHIP was observed by transmission electron microscopy. The protein expression levels of MBP， myelin oligodendrocyte glycoprotein （MOG）， myelin-associated glycoprotein （MAG）， triggering receptor expressed on myeloid cells-2 （TREM2）， inducible nitric oxide synthase （iNOS）， arginase 1 （Arg1）， interleukin-Iβ （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） were assayed by Western blot. Result:As revealed by behavioral test， compared with the normal control group， the model group exhibited prolonged immobility time and decreased percentage of sugar water preference （P<0.01）. Compared with the model group， Xiaoyaosan significantly shortened the immobility time of mice （P<0.05） and increased the percentage of sugar water preference （P<0.01）. Western blot results showed that the protein expression levels of MBP， MOG， and MAG in vHIP of the model group were remarkably decreased as compared with those of the normal control group （P<0.01）. The protein expression levels of MBP， MOG， and MAG in vHIP of the low-dose Xiaoyaosan group were increased in contrast to those in the model group （P<0.05， P<0.01）， while the protein expression of iNOS was decreased （P<0.01）. The protein expression levels of MBP， MOG， MAG， TREM2， Arg1， IL-4， and IL-10 in the medium- and high-dose Xiaoyaosan groups were up-regulated （P<0.05， P<0.01）， whereas those of iNOS， IL-1β， and TNF-α were down-regulated （P<0.01）. The immunofluorescence findings demonstrated that the mean fluorescence intensity of MBP in the model group declined in comparison with that in the normal control group （P<0.01）， while the mean fluorescence intensities of MBP in the low-， medium-， and high-dose Xiaoyaosan groups were enhanced to different degrees （P<0.01）. It was observed under the transmission electron microscope that the myelin structure of the model group was loosened and the dense layer was separated and irregularly arranged. Xiaoyaosan improved the structural integrity of myelin sheath and the looseness of lamellar structure. Conclusion:Xiaoyaosan ameliorates the depressive behavioral phenotype of VaD mice， which may be related to the up-regulation of TREM2， the induction of M2 polarization of microglia cells， the enhancement of their anti-inflammatory and phagocytic abilities， and the promotion of damaged myelin sheath regeneration.

Objective: Mulberry (Morus spp.) fruits and leaves have been proven to possess nutraceutical properties. Due to its fast and easy growing characteristics, mulberry fruits (MF) and leaves (ML) potentially emerge as a great source of functional foods. This study aims to enhance bioactivities (antioxidant, anti-inflammation, and hypoglycemic activity) of MF and ML via submerged fermentation using bacteria (Lactobacillus plantarum TAR 4), yeast (Baker's yeast and red yeast) and fungi (Tempeh and Tapai starter). Methods: In this study, 25% (mass to volume ratio) of MF and ML were fermented (48 h) with 1% (mass to volume ratio) of different microbial cultures, respectively. Effects of different fermentations on MF and ML were determined based on the changes of total phenolics (TPC), flavonoids (TFC), anthocyanins, total sugar, DPPH activity, ferric reducing antioxidant power (FRAP), albumin denaturation inhibition activity (ADI), anti-lipoxygenase activity and α-amylase inhibition activity (AI). Results: Generally, ML had higher AI than MF. However, MF exhibited higher DPPH, FRAP and anti-lipoxygenase activity than ML. After all forms of fermentation, DPPH and AI activity of MF and ML were increased significantly (P < 0.05). However, the effects of fermentation on TPC, FRAP, ADI and anti-lipoxygenase activity of MF were in contrast with ML. TPC, FRAP and anti-lipoxygenase activity of ML were enhanced, but reduced in MF after fermentation. Although the effects exerted by different microorganisms in MF and ML fermentation were different, the bioactivities of MF and ML were generally improved after fermentation. Fermentation by Tempeh starter enhanced TPC (by 2-fold), FRAP (by 2.3-fold), AI (at 10% increment) and anti-lipoxygenase activity (by 5-fold) of ML, whereas Tapai fermentation effectively enhanced the DPPH (at 17% increment) and ADI (by 2-fold) activity of MF. Conclusion: Findings of this study provide an insight into the future process design of MF and ML processing into novel functional foods.