Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Objective:To explore the value of dual-layer spectral CT virtual monoenergetic images (VMI) in contrast-enhanced abdominal CT scans with reduced contrast medium volume in pediatric tumor patients.Methods:The study is a self-matched case-control study. From January to October 2024, pediatric patients admitted to Shandong Cancer Hospital with abdominal tumors who underwent low contrast dose spectral CT contrast-enhanced scans during follow-up were prospectively included. A total of 47 patients aged (6.2±2.2) years (4-14 years) were enrolled. Usual contrast dose enhanced CT served as the conventional-dose group, while the follow-up low-dose spectral CT scans employed a protocol with half the contrast agent dose (low-dose group). Images were reconstructed as conventional CT images and VMI at 45, 55, and 65 keV. Using muscle as the reference background, differences in CT values and contrast-to-noise ratio (CNR) in the aorta, kidneys, liver, and spleen were compared between the low-dose group and conventional-dose group. Multi-group comparisons were performed using the Friedman test. Post-hoc pairwise comparisons were conducted with Bonferroni correction for P-values. Results:CT values and CNRs for all measured regions progressively increased with decreasing keV levels in spectral CT VMI. Significant overall differences were found in CT values and CNRs for the aorta, kidneys, liver, and spleen among the low-dose group (all VMIs) and the conventional-dose group (all P<0.001). At 65 keV VMI in the low-dose group, both CT values and CNRs (except for the liver CNR) were significantly lower than those in the conventional-dose group (all adjusted P<0.05). At 55 keV VMI in the low-dose group, CT values and CNRs for all regions did not show statistically significant differences compared to the conventional-dose group (all adjusted P>0.05). At 45 keV VMI in the low-dose group, CT values for all structures and CNR for the spleen were significantly higher than those in the conventional-dose group (all adjusted P<0.05). However, no statistically significant difference was found in CNRs for the aorta, kidneys, and liver (adjusted P=1.000, 0.313, and 0.503, respectively). Conclusion:When the contrast dose is halved, spectral CT 45 keV VMI enhances CT attenuation values and CNR in the abdomen of pediatric tumor patients, while 55 keV VMI provides image quality comparable to that of conventional-dose CT.

BACKGROUND:Some studies have shown a potential relationship between dietary intake and osteoarthritis,but whether there is a causal relationship between food preferences and osteoarthritis is still unknown.There is currently no large-scale genome-wide association study on dietary preferences and osteoarthritis in China.OBJECTIVE:To explore the causal association between dietary preferences and osteoarthritis in European populations,in order to provide a theoretical basis for the prevention of osteoarthritis and to provide reference data for the identification of high-risk groups for hip and knee osteoarthritis in China.METHODS:A total of 20 dietary preference genetic statistics datasets were selected to screen for exposure factor-related instrumental variables.The dataset for osteoarthritis was selected for the ending.After exclusion of the instrumental variables related to confounders,the two-sample Mendelian randomized causal association analysis was conducted mainly by inverse variance weighted analysis,and other four statistical methods were used as supplements.Sensitivity test was performed for the results.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighted analysis showed that preference for barbecue(OR=1.204,95％CI:1.058-1.370,P=0.005),beef(OR=1.167,95％CI:1.034-1.317,P=0.012),chicken(OR=1.399,95％CI:1.119-1.749,P=0.003),pork chops(OR=1.218,95％CI:1.039-1.427,P=0.015)and coffee(OR=1.133,95％CI:1.037-1.238,P=0.006)were risk factors for osteoarthritis of the knee and hip joints,vegetables(OR=0.893,95％CI:0.827-0.964,P=0.004),and vinegar(OR=0.897,95％CI:0.812-0.991,P=0.032)were protective factors for knee-hip osteoarthritis.(2)The results of the sensitivity analysis showed that the instrumental variables included in the analysis without horizontal pleiotropy and bias,and the corresponding inverse variance weighted analysis of effects model was used according to the results of the heterogeneity analysis.(3)The results of this study provide certain reference value in the research on the relationship between dietary preferences and hip and knee osteoarthritis,but only included human whole genome association study data from European populations,and the validity of the research results in other races remains to be tested.Moreover,no stratification was performed on gender,age and other health status.It is difficult to completely rule out the bias from population stratification in the research results.In the future,larger-scale and more finely classified sample data are still needed to carry out relevant causal relationship research.

BACKGROUND:Some studies have shown a potential relationship between dietary intake and osteoarthritis,but whether there is a causal relationship between food preferences and osteoarthritis is still unknown.There is currently no large-scale genome-wide association study on dietary preferences and osteoarthritis in China.OBJECTIVE:To explore the causal association between dietary preferences and osteoarthritis in European populations,in order to provide a theoretical basis for the prevention of osteoarthritis and to provide reference data for the identification of high-risk groups for hip and knee osteoarthritis in China.METHODS:A total of 20 dietary preference genetic statistics datasets were selected to screen for exposure factor-related instrumental variables.The dataset for osteoarthritis was selected for the ending.After exclusion of the instrumental variables related to confounders,the two-sample Mendelian randomized causal association analysis was conducted mainly by inverse variance weighted analysis,and other four statistical methods were used as supplements.Sensitivity test was performed for the results.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighted analysis showed that preference for barbecue(OR=1.204,95％CI:1.058-1.370,P=0.005),beef(OR=1.167,95％CI:1.034-1.317,P=0.012),chicken(OR=1.399,95％CI:1.119-1.749,P=0.003),pork chops(OR=1.218,95％CI:1.039-1.427,P=0.015)and coffee(OR=1.133,95％CI:1.037-1.238,P=0.006)were risk factors for osteoarthritis of the knee and hip joints,vegetables(OR=0.893,95％CI:0.827-0.964,P=0.004),and vinegar(OR=0.897,95％CI:0.812-0.991,P=0.032)were protective factors for knee-hip osteoarthritis.(2)The results of the sensitivity analysis showed that the instrumental variables included in the analysis without horizontal pleiotropy and bias,and the corresponding inverse variance weighted analysis of effects model was used according to the results of the heterogeneity analysis.(3)The results of this study provide certain reference value in the research on the relationship between dietary preferences and hip and knee osteoarthritis,but only included human whole genome association study data from European populations,and the validity of the research results in other races remains to be tested.Moreover,no stratification was performed on gender,age and other health status.It is difficult to completely rule out the bias from population stratification in the research results.In the future,larger-scale and more finely classified sample data are still needed to carry out relevant causal relationship research.

Objective:To explore the value of dual-layer spectral CT virtual monoenergetic images (VMI) in contrast-enhanced abdominal CT scans with reduced contrast medium volume in pediatric tumor patients.Methods:The study is a self-matched case-control study. From January to October 2024, pediatric patients admitted to Shandong Cancer Hospital with abdominal tumors who underwent low contrast dose spectral CT contrast-enhanced scans during follow-up were prospectively included. A total of 47 patients aged (6.2±2.2) years (4-14 years) were enrolled. Usual contrast dose enhanced CT served as the conventional-dose group, while the follow-up low-dose spectral CT scans employed a protocol with half the contrast agent dose (low-dose group). Images were reconstructed as conventional CT images and VMI at 45, 55, and 65 keV. Using muscle as the reference background, differences in CT values and contrast-to-noise ratio (CNR) in the aorta, kidneys, liver, and spleen were compared between the low-dose group and conventional-dose group. Multi-group comparisons were performed using the Friedman test. Post-hoc pairwise comparisons were conducted with Bonferroni correction for P-values. Results:CT values and CNRs for all measured regions progressively increased with decreasing keV levels in spectral CT VMI. Significant overall differences were found in CT values and CNRs for the aorta, kidneys, liver, and spleen among the low-dose group (all VMIs) and the conventional-dose group (all P<0.001). At 65 keV VMI in the low-dose group, both CT values and CNRs (except for the liver CNR) were significantly lower than those in the conventional-dose group (all adjusted P<0.05). At 55 keV VMI in the low-dose group, CT values and CNRs for all regions did not show statistically significant differences compared to the conventional-dose group (all adjusted P>0.05). At 45 keV VMI in the low-dose group, CT values for all structures and CNR for the spleen were significantly higher than those in the conventional-dose group (all adjusted P<0.05). However, no statistically significant difference was found in CNRs for the aorta, kidneys, and liver (adjusted P=1.000, 0.313, and 0.503, respectively). Conclusion:When the contrast dose is halved, spectral CT 45 keV VMI enhances CT attenuation values and CNR in the abdomen of pediatric tumor patients, while 55 keV VMI provides image quality comparable to that of conventional-dose CT.

Objective To investigate the effect of oral fish oil on wound healing and related indexes in patients with diabetic foot ulcer(DFU).Methods A randomized,double-blind,placebo-controlled design was used to recruit 68 patients with DFU aged 18-80 years old in the hospital,and the baseline clinical data of the patients were collected.The patients were randomly divided into experimental group(32 cases,fish oil soft capsule,3 g/d)and control group(33 cases,corn oil soft capsule,3 g/d)by random number generated by Ex-cel,and the intervention lasted for 12 weeks.The primary endpoints included the proportion of complete wound healing and healing area≥50%.The secondary endpoints included wound area,healing time,inflamma-tion index,glucose metabolism index,nutrition related index and wound reinfection.Additionally,the influen-cing factors of wound healing were analyzed.Results After intervention,the proportion of complete wound healing and healing area≥50%in the experimental group was significantly higher than that in the control group(P=0.007,0.039).In the subjects with complete wound healing,the mean healing time in the experi-mental group was shorter than that in the control group,but the difference was not statistically significant(P=0.132).The reduction area of wound area in the experimental group was significantly larger than that in the control group(P=0.045).The decrease of interleukin(IL)-6 and IL-8 in the experimental group was significantly higher than that in the control group(P<0.05).There was no significant difference in the reduc-tion of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),neutrophil-to-lymphocyte ratio(NLR),glycated hemoglobin A1c(HbA1c)and platelet-to-lymphocyte ratio(PLR)between the two groups(P>0.05).The improvement of prealbumin(PA)in the experimental group was higher than that in the control group,but the difference was not statistically significant(P>0.05).Multivariate logistic regression analysis showed that oral fish oil intervention(OR=6.771,95%CI:1.787-25.652),HbA1c(OR=4.149,95%CI:1.026-16.770)and ulcer type(OR=4.319,95%CI:1.026-18.173)were the influencing factors of wound healing(P<0.05).Conclusion Oral fish oil promotes wound healing in patients with DFU,which may be re-lated to improving the level of chronic inflammation in the body.

Rhamnogalacturonan Ⅱ(RG-Ⅱ)is one of the structural domains of pectin whose structure is highly conserved among species.The main chain of RG-Ⅱ consists of approximately nine galacturonic acids linked by α-1,4 glycosidic bonds,with six well-defined side chains replacing them(A-F).The structures of the disaccharide side chains C and D and the monosaccharide side chains E and F in RG-Ⅱ from different sources remain essentially the same.In contrast,the oligosaccharide side chains A and B showed slight variability.Structural characterization of RG-Ⅱ can be achieved by molecular weight,monosaccharide composition,and mass spectrometry.The polysaccharides containing RG-Ⅱ structural domains in traditional Chinese medicines(TCMs)have high medicinal value.Isolation of RG-Ⅱ can be achieved using endo-polygalacturonase(Endo-PG)and Penicillium oxalicum.A substantial number of RG-Ⅱ standards can be rapidly prepared from red wine for the development of new quantitative methods to realize the quality control of active polysaccharides from traditional Chinese medicines and to promote the research process of polysaccharides from traditional Chinese medicines.

Objective To summarize the research status and hotspots of Wumei Pills;To provide ideas and methods for the follow-up research of Wumei Pills.Methods Related literature about Wumei Pills was retrieved from CNKI,VIP,Wanfang Data and CBM from the establishment of the databases to January 12,2023.The publication time,author,author unit and keywords were collected and extracted through NoteExpress 3.0 software to manage bibliographic data.VOSviewer 1.6.18 software was used to conduct co-occurrence and clustering analysis,and construct keyword time superposition network.Results After screening,a total of 2 105 articles were included,involving 3 554 authors,such as Yan Shuguang,Fan Heng,and Hui Yi.They were from 1 135 units,such as Dongzhimen Hospital of Beijing University of Chinese Medicine,Shandong University of Traditional Chinese Medicine and Beijing University of Chinese Medicine.The included articles contained 2 565 keywords,which appeared 7 061 times,and the research involved 4 main directions:digestive system diseases(ulcerative colitis),study on TCM classics(Shang Han Za Bing Lun),medical cases and experience,and biliary ascariasis.The hotspots of Wumei Pills were scattered in recent years.Six meridian disease to appear,opening and closing pivots,intestinal microbiota,serum inflammatory factors and insomnia were research hotspots in recent 3 years.Conclusion The research of Wumei Pills mainly focus on the research of digestive system diseases,TCM classics,medical cases and experience,and biliary ascariasis.Theoretical research of TCM and mechanism research possibly become new hotspots of this field.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment

Metformin is one of the commonly used hypoglycemic drugs in clinical practice. In addition to hypoglycemia, there are a variety of medical biological values that have been constantly discovered and attracted much attention. In recent years, studies have shown that metformin through activation of AMPK inhibition of sterols regulating element binding protein 1 (SREBP-1) reduce lipid synthesis, in the treatment of liver steatosis, improve insulin sensitivity, prevention Metformin is one of the commonly used hypoglycemic drugs in clinical practice. In addition to hypoglycemia, there are a variety of medical biological values that have been constantly discovered and attracted much attention. In recent years, studies have shown that metformin through activation of AMPK inhibition of sterols regulating element binding protein 1 (SREBP-1) reduce lipid synthesis, in the treatment of liver steatosis, improve insulin sensitivity, prevention of atherosclerosis and cardiovascular dysfunction, tumor, polycystic ovary syndrome and adjuvant therapy of COVID-19 aspects play a role. Therefore, this article reviews the possible mechanism and clinical application of metformin in regulating glucose and lipid metabolism by inhibiting SREBP-1 through activating AMPK.