ObjectiveThis paper aims to investigate the efficacy and related actions of Guizhi Fulingwan in intervening in the mice with colitis-associated colon cancer （CAC） based on the immunosuppressive microenvironment associated with myeloid-derived suppressor cells （MDSCs）. MethodsSixty male C57BL/6 mice were randomly assigned to a blank group， a model group， an aspirin group （0.04 g·kg^-1）， and low-， medium-， and high-dose Guizhi Fulingwan groups （4.87， 9.75， and 19.50 g·kg^-1）， with ten mice per group. The CAC mouse model was established via combined induction of azoxymethane （AOM）/dextran sulphate sodium （DSS）. Drug intervention commenced in week five， with continuous intragastric administration for nine weeks. The food intake， body weight， fecal characteristics， and haematochezia were observed and recorded， and disease activity index （DAI） scores were calculated according to scoring criteria. Hematoxylin and eosin （HE） staining was used to observe the histopathological changes in the colon tissues of the mice. Immunohistochemistry was used to determine proliferating cell nuclear antigen-67 （Ki67） expression in the colon tissues， and enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） in the serum of the mice. Flow cytometry was employed to determine the proportion levels of MDSCs， CD4⁺ T cells， and CD8⁺ T cells in the spleen tissues of the mice. The mRNA expressions of MDSC-associated effector molecules， including arginase 1 （Arg1） and inducible nitric oxide synthase （iNOS）， were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. After that， an in vitro co-culture model of MDSCs and CD8⁺ T cells was established， and drug-containing serum of Guizhi Fulingwan was used for intervention. The Flow cytometry was employed to assess the effects of drug-containing serum of Guizhi Fulingwan with different concentrations on the levels of reactive oxygen species （ROS） and iNOS in MDSCs and the proliferation of CD8⁺ T cells. The levels of granzyme B （GZMB） and interferon-γ （IFN-γ） in cell supernatant were detected by ELISA. ResultsCompared with those in the control group， the mice in the model group exhibited significantly reduced body weight， elevated DAI scores， shortened colon length （P<0.01）， increased number of tumors and Ki67 expression （P<0.01）， and significantly elevated contents of IL-6， IL-1β， and TNF-α in the serum （P<0.01）. Significant increases in the number of MDSCs were observed in mouse spleens， alongside marked reductions in the levels of CD4⁺ T and CD8⁺ T cells （P<0.01）. Furthermore， the mRNA expressions of MDSC function-associated effector molecules Arg1 and iNOS were significantly upregulated （P<0.01）. Compared with those in the model group， the mice in the middle-dose Guizhi Fulingwan group exhibited increased body weight and significantly decreased DAI scores （P<0.05， P<0.01）. The mice in the middle- and high-dose Guizhi Fulingwan groups exhibited significantly improved colon shortening， significantly decreased number of tumors and Ki67 expression （P<0.05， P<0.01）， and significantly decreased contents of IL-6， IL-1β， and TNF-α in the serum （P<0.05， P<0.01）. Furthermore， administration of Guizhi Fulingwan markedly reduced MDSC infiltration in the spleen of the mice， with different degrees of increase in the levels of both CD4⁺ T and CD8⁺ T cells （P<0.05， P<0.01）， alongside significant decreases in the mRNA expressions of Arg1 and iNOS （P<0.05， P<0.01）. In vitro cell co-culture shows that administration of drug-containing serum of Guizhi Fulingwan significantly decreases the activity levels of ROS and iNOS in MDSCs and promotes the proliferation of CD8⁺ T cells and the secretion of GZMB and IFN-γ （P<0.05， P<0.01）. ConclusionGuizhi Fulingwan can reduce pro-inflammatory cytokine secretion and inhibit tumor proliferation in the colon tissues of CAC mice. Its potential mechanism may involve reducing MDSC infiltration， enhancing effector T cells， particularly CD8⁺ T cell response， and improving the tumor immunosuppressive microenvironment.

It has been demonstrated that long-term space flights have a significantly greater impact on the cardiovascular, skeletal, and nervous systems of astronauts. The structural and functional alterations in the skeletal and muscular systems resulting from exposure to weightlessness can lead to the development of low back pain, significantly impairing the ability of astronauts to perform tasks and respond to emergencies. Both space flight and simulated microgravity have been shown to result in low back pain among astronauts, with the following factors identified as primary contributors to this phenomenon. The occurrence of intervertebral disc (IVD) edema results in the stimulation of type IV mechanoreceptors, which subsequently activate nociceptive afferents. The protrusion of an IVD causes compression of the spinal nerve roots. Furthermore, the elongation of the vertebral column and/or the diminished lumbar curvature of the spine exert traction on the dorsal root nerves. Paravertebral muscle degeneration leads to the inhibition of decreased nociceptive activity of the wide-dynamic range neurons of the spinal dorsal horn. Moreover, endogenous pain descending facilitation triggered by conditioning stimulation can be enhanced via the thalamic mediodorsal nuclei, while endogenous pain descending inhibition triggered by conditioning stimulation can be weakened via the thalamic ventromedial nuclei. Psychological factors may contribute to the development of low back pain. The mechanisms governing the generation, maintenance, and alleviation of low back pain in weightlessness differ from those observed in normal gravitational environments. This presents a significant challenge for space medicine research. Therefore, the elucidation of the occurrence and development mechanism of low back pain in weightlessness is important for the prevention and treatment during space flight. To reduce the incidence of low back pain during long-term missions on the space station, astronauts may choose to wear specialized space clothing that can provide axial physiological loads, designed to stimulate both musculature and skeletal structures, mitigating potential increases in vertebral column length, diminished lumbar curvature, and intervertebral disc edema and/or muscular atrophy. Additionally, assuming a “fetal tuck position” described as the knees to chest position may increase lumbar IVD hydrostatic pressure, subsequently reducing disc volume, rectifying diminished lumbar curvature, and alleviating dorsal root nerve tensions. Moreover, this position may reduce type IV mechanoreceptor facilitation and nerve impulse propagation from the sinuvertebral nerves of the annulus fibrosus. Elongated posterior soft tissues (apophyseal joint capsules and ligaments) with spinal flexion may potentially stimulate type I and II mechanoreceptors. It is also recommended to exercise the paraspinal muscles to prevent and alleviate the decrease in their cross-sectional area and maintain their structure and function. Photobiomodulation has been proved to be an effective means of activating the pain descending inhibition pathway of the central nervous system. In addition, astronauts should be encouraged to participate in mission-related activities and strive to avoid psychological problems caused by the long-term confinement in a small space station. The article presents a concise review of potential causes and targeted treatment strategies for low back pain induced by space flight or simulated microgravity in recent years. Its objective is to further elucidate the mechanisms underlying the occurrence and development of low back pain in weightless environments while providing scientific evidence to inform the development of guidelines for preventing, treating, and rehabilitating low back pain during long-term space flights.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

To investigate the phenotype and genomic characterization of a mucoid-type Salmonella Saintpaul ST50 isolate from a urinary tract infection patient,promoting clinical diagnosis and treatment for urinary tract infections caused by Salmo-nella spp.Culture-based quantitative counts of midstream urine sample from the patient were conducted,and further biochemi-cal identification,mass spectrometry detection,serum agglutination test and antimicrobial susceptibility test(AST)were con-ducted on Salmonella isolate(2024JD5).Whole-genome sequencing(WGS)was performed on isolate 2024JD5 to predict sero-type,multilocus sequence type(MLST),resistance genes,and virulence genes.Two smooth-type of Salmonella Saintpaul ST50 were selected as comparative genomic reference strains from the Chinese local Salmonella genome database.The literature reviews of global Salmonella serotype of urinary tract infection were summarized.Specific serum agglutination confir-mation of isolate 2024JD5 failed due to characterization of the mucus type.The strain 2024JD5 was predicted as Salmonella Saintpaul(4,5,12:e,h:1,2)ST50 using WGS,and was resistant to ciprofloxacin,nalidixic acid,chloramphenicol and tetracy-cline with carrying aminoglycoside resistance genes aac(6')-Ⅰaa and aph(3)-Ⅱa,chloramphenicol resistance gene floR,tetra-cycline resistance gene tet,quinolone resistance gene qnrS1,and S83Y substitution in the gyrA gene was found in the quinolo-ne resistance determination region(QRDR).In addition,the strain 2024JD4 carried six types of non-plasmid-based mobile ge-netic elements and 144 virulence genes,including 71 secretion transporter genes and 58 fimbriae adhesion genes,respectively.Four types of fimbriae regulatory genes(csgB,csgC,fimW,fimY)were absent in comparison with smooth-type Salmonella Saintpaul.The literature reviews showed Salmonella Saintpaul was currently a rare Salmonella serotype in cases of urinary tract infections worldwide.Salmonella Saintpaul ST50 with mucoid-type is the pathogen of urinary tract infection with multi-drug resistant phenotypic and genotypic characteristics,and the high mucoid expression may be related to the compensatory mechanism of fimbriae regulatory genes absence in urinary tract colonization and adaptation.WGS combined with the Chinese local Salmonella genome database can effectively solve the diagnosis and biosafety assessments of rare Salmonella phenotypes.

AIM To study the chemical constituents from Tylophora ovata(Lindl.)Hook.ex Steud.and their antibacterial activities.METHODS Ethanol extract was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.The inhibitory activities of each compound against Phomopsis sp.were determined by mycelial growth rate method.RESULTS Twenty-six compounds were identified as paeonol(1),stigmast-4-en-3-one(2),ergosta-4,6,8(14),22-tetraen-3-one(3),2,4-methoxyphenol(4),1,2,4-trimethoxybenzene(5),3-methoxyphenol(6),3,4-dimethoxyacetophenone(7),5α,8α-epidioxy-ergosta-6,22(E)-diene-3β-ol(8),kaempferol 3-O-β-D-galactopyranoside(9),glaucogenind C(10),glaucoge-nin A 3-O-β-D-cymaropyranoside(11),dibutyl phthalate(12),cynatratoside A(13),hirundigoside C(14),sublanceoside B2(15),cynanoside A(16),dipentyl phthalate(17),5-hydroxymethyl-2-furancarboxaldehyde(18),bis-(2-ethyl)hexylphthalate(19),p-hydroxybenzoic acid(20),syringic acid(21),β-hydroxypropiovanillone(22),3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(23),(+)-syringare sinol(24),(-)-syringare sinol(25),(+)-medioresinol(26).IC50 value of compound 12 was 37.27 μg/mL.CONCLUSION Compounds 1-26 are isolated from this plant for the first time.Compound 12 has inhibitory activity against Phomopsis sp.

Objective:To explore the distribution characteristics of HBsAg levels in treatment-na?ve and treatment-experienced patients with chronic hepatitis B (CHB) in China.Methods:Data were obtained from the China Registry of Hepatitis B (CR-HepB) platform from the establishment of the platform to April 11, 2024. Patients with CHB who were treatment-na?ve and treatment-experienced with nucleos(t)ide analogs (NAs) were included. Relevant clinical data were collected. The distribution of hepatitis B surface antigen (HBsAg) status, as well as the levels in populations of different age groups after different antiviral treatment durations, were retrospectively analyzed. Normally and non-normally distributed measured data were represented by Mean± SD, and M( Q1, Q3). Results:A total of 13 505 treatment-na?ve patients and 6 390 treatment-experienced patients were included in the analysis. The proportions of treatment-na?ve patients with HBsAg<100, <500, and <1 500 IU/mL were 10.51%, 28.47%, and 46.85%, and the corresponding proportions of treatment-experienced patients were 12.88%, 29.84%, and 52.07%. The proportions of treatment-na?ve patients with HBsAg levels≥1 500, ≥3 000, and≥8 000 IU/mL were 53.15%, 38.17%, and 15.62%, and the corresponding proportions of treatment-experienced patients were 47.93%, 31.77%, and 10.39%. HBsAg level showed a trend of gradual decrease with the increase of antiviral treatment time. The proportion of treatment-experienced patients with HBsAg<100 IU/mL increased from 12.73% when the treatment duration was less than three years to 26.92% when the treatment duration was≥10 years, while the proportion of patients with HBsAg levels≥3 000 IU/mL or≥8 000 IU/mL decreased from 34.66% to 23.08% and from 12.19% to 5.77%, respectively. The proportion of patients with HBsAg<100, <500, and<1 500 IU/mL increased with age, while the proportion of patients with HBsAg≥1 500, ≥3 000, and ≥8 000 IU/mL decreased sequentially.Conclusions:The CR-HepB platform provides a basis for clarifying the serum HBsAg levels in treatment-na?ve and treatment-experienced CHB patients in China. The HBsAg status indicates that with a prolonged antiviral treatment duration, there is a gradual decline trend in HBsAg level.

Objective:To dynamically assess liver fibrosis using magnetic resonance elastography (MRE) and explore factors associated with fibrosis reversal in patients with metabolic dysfunction-associated steatohepatitis (MASH).Methods:This study included data from patients diagnosed with MASH by liver biopsy who underwent at least two MRE examinations. Patients were divided into a fibrosis reversal group and a non-reversal group according to whether MRE values decreased by 20% during follow-up. Differences in clinical data between the groups were compared using analysis of variance, the Kruskal-Wallis test, and the chi-square test. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for fibrosis reversal in MASH.Results:A total of 46 cases were included in this study (mean age 50.1±12.3 years, BMI 26.1±3.1 kg/m2). Among them, the reversal group accounted for 26.1%. The rate of decrease in MRI proton density fat fraction (PDFF) was significantly higher in the reversal group (-50.0% vs. -8.1%, P=0.001) than in the non-reversal group between the two MRE examinations. The reversal group showed a more significant change rate of decreases in fasting insulin (-37.3% vs. -3.6%, P=0.011), insulin resistance index (-38.6% vs. -6.5%, P=0.044), and ALP (-24.9% vs. 0, P=0.004). Multivariate logistic regression analysis indicated that the rate of change in MRI PDFF was an independent predictor of fibrosis reversal ( OR=0.96, 95% CI: 0.92-1.00, P=0.046). Conclusion:A decrease in MRI proton density fat fraction levels is independently associated with liver fibrosis reversal in MASH, suggesting that intervention targeting liver fat content may be an effective treatment strategy.

Glycoengineering was carried out in the mammalian cell line CHO for the production of pro-tein-based drugs.Firstly,the genome sequence of the Rosa26 locus of CHO cells was determined,the gRNA sequences were designed,and the landing pad was integrated into the Rosa26 locus of CHO cells by CRISPR/Cas9 technology.Three targeting vectors co-expressed by glycosyltransferases,which are β-1,4 galactosyltransferase(B4GALT1),α-2,6-sialyltransferase 1(ST6GAL1)and N-acetaminoglycosyl-transferase Ⅲ(GnT Ⅲ),were constructed by overlapping PCR and seamless ligation technology,and the three glycosyltransferase genes were integrated into the CHO Rosa26 locus by Cre enzyme-mediated cassette exchange technology.PCR confirmed that three glycosyltransferases had been successfully site-directed integrated into the Rosa26 site.The mRNA expression levels of the three glycosyltransferases were more than 50 000-fold by qRT-PCR,and the protein expression levels of the three glycosyltrans-ferases were more than 4-fold via western blotting(P＜0.001).A CHO-engineered cell line with three glycosyltransferases integrated into Rosa26 site was successfully constructed.