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 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.

The incidence and mortality of early-onset colorectal cancer (EOCRC) are increasing worldwide and have become a major issue in the field of public health. Dietary, environment and lifestyle factors are related to the incidence of EOCRC, and gut microbiota may play an important role in the development of EOCRC. This article reviewed the risk factors of EOCRC, the potential relationship between gut microbiota and EOCRC, and the prevention of EOCRC, which may provide new ideas for the prevention and treatment of EOCRC.

Objective:To compare the efficacies of MRI, X-ray mammography (XMG) and Ultrasound (US) in detecting and diagnosing breast ductal carcinoma in situ (DCIS).Methods:Two hundred and forty one consecutive patients with pathology-confirmed DCIS were retrospectively recruited from January 2011 to December 2017 in PLA General Hospital. The imaging examination modalities included MRI and/or XMG and/or US.The breast imaging reporting and data system (BI-RADS) categorizations by MRI, XMG and US were compared and their sensitivities of detecting DCIS were calculated. The causes of underestimation on MRI were interpreted with the information of XMG and US. Chi-square test was used to compare the differences.Results:The diagnostic sensitivity of XMG, US and MRI was 65.9% (29/44), 71.6% (101/141) and 91.2% (145/159), respectively, with statistical significant differences (χ2 =24.034, P<0.001). Breast density and lesion type would influence the sensitivity of XMG. And the sensitivity of US was decreased because of non-mass lesion. Of the 14 cases under-evaluated as BI-RADS category 1 to 3 on MRI, 5 were corrected by XMG and/or US to BI-RADS category 4. The cause of underestimation on MRI was the coexistence of DCIS with adenoma or other benign lesion. Conclusion:The retrospective comparison of MRI, XMG and US in this study showed that MRI had significant higher sensitivity in detecting breast DCIS, while the false negative rates of XMG and US were un-negligible.

Venous thromboembolism(VTE)is one of the common and serious complications of malignant tumors.In elderly lung cancer patients, problems such as decreased autonomic activity, bed rest, poor performance status(PS), combined underlying diseases and the use of chemoradiotherapy are often considered as risk factors for high incidence of VTE.This article is aimed to review the clinical features and pathogenesis of lung cancer in the elderly combined with VTE, to investigate the risk factors and explore feasible evaluation and prevention strategies.

Objective To analyse the clinical effect and safety of Alimta (Pemetrexed) combined with cisplatin treatment (PP) on elderly patients with non small cell lung cancer (NSCLC).Methods We retrospectively analyzed the clinical data of 40 cases of NSCLC patients treated with Pemetrexed combined with cisplatin for first-line chemotherapy,and 24 cases of them continually received single Pemetrexed for maintenance treatment (PP + C).Then we compared the results with 35 patients in the non-Pemetrexed regimen (control group) and 26 patients with best supportive care (BSC) in the same period.The adverse reactions and short-term efficacy [response rate (RR),disease control rate (DCR)] were evaluated.Time to progression (TTP),median survival time (MST),one-year and three-year survival rates and follow-up overall survival (OS) were calculated.Results Among 40 patients with Pemetrexed regimen,2 patients had complete remission (CR),and the RR was 47.8％,which was better than 42.8％ (P =0.026) in the control group.The main adverse reactions of pemetrexed regimen were myelosuppression,fatigue,nausea and vomiting,but all were tolerated and no treatment-related death occurred.24 patients received single Pemetrexed maintenance therapy.The MST of the PP + C group was superior to the other groups (P =0.03,P ≤0.05);the median OS of the PP + C group,the control group,and the BSC group reached 13.2,10.4 months and 8.6 months,respectively (P ≤ 0.001).Conclusions For elderly patients with advanced NSCLC,especially adenocarcinoma,the combination of Pemetrexed and cisplatin is a better treatment option.It is convenient to administer and has less toxicity and adverse reactions related to chemotherapy.Patients with better PS score after first-line treatment can obtain longer survival period after maintenance treatment.