ObjectiveTo observe the clinical efficacy and possible mechanisms of Xianglian Huazhuo Granules （香连化浊颗粒， XHG） in the treatment of chronic atrophic gastritis with intestinal metaplasia. MethodsA total of 140 patients with chronic atrophic gastritis and intestinal metaplasia were randomly divided into a treatment group and a control group， with 70 cases in each group. The treatment group received 12.5 g of XHG orally， twice daily. The control group received 12.5 g of placebo orally， twice daily. Both groups were treated for 6 months. The traditional Chinese medicine （TCM） symptom scores， pathological types， serum tumor markers of the digestive system， and serum bile acids （TBA）， interleukin-23 （IL-23）， and Dickkopf-related protein 1 （DKK-1） levels were observed before and after treatment. Safety indicators and adverse events were recorded. After treatment， TCM syndrome efficacy and pathological types were evaluated， and patients were followed up for 18 months with gastric endoscopy and pathological results， which were compared with the results after treatment finished. ResultsTwo patients dropped out in the control group， and a total of 168 cases were included in the final analysis， 70 in the treatment group and 68 in the control group. The treatment group showed a significant reduction in TCM symptom scores， serum TBA， IL-23， and DKK-1 levels， and a significant increase in alpha-fetoprotein （AFP）， carbohydrate antigen 125 （CA125）， carbohydrate antigen 199 （CA199） levels； in the control group， carcinoembryonic antigen （CEA）， CA125， CA199 levels significantly increased （P＜0.05 or P＜0.01）； and carbohydrate antigen 242 （CA242） level in both the treatment group and the control group decreased significantly （P＜0.01）. The treatment group had lower TCM symptom scores and lower levels of serum TBA， IL-23， and DKK-1 compared to the control group （P＜0.05）. The effective rate for TCM syndrome efficacy in the treatment group was 80.00% （56/70）， significantly higher than the 20.59% （14/68） in the control group （P < 0.05）. The effective rate for pathological classification in the treatment group was 72.73% （8/11） for mixed intestinal metaplasia， significantly better than 46.15% （6/13） in the control group （P＜0.05）. No adverse events were reported in either group. Among 40 patients who had a follow-up endoscopy after one year， 21 were from the treatment group， of whom 11 showed reduced intestinal metaplasia， 9 showed no significant changes， and 1 had worsened； while 19 patients in the control group had 4 with reduced intestinal metaplasia， 13 with no significant changes， and 2 with worsened conditions. No cancer was detected in either group. The treatment group showed significantly better improvement in intestinal metaplasia on follow-up gastric endoscopy pathology than the control group （P＜0.05）. ConclusionXHG can significantly improve the clinical symptoms in patients with chronic atrophic gastritis and intestinal metaplasia and reduce the degree of mixed intestinal metaplasia. The mechanism may involve lowering serum TBA， DKK-1， and IL-23 levles， thus delaying the progression from inflammation to cancer.

Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.

Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

Objective To investigate the effect and mechanism of transplantation of neuregulin1(NRG1)gene-modified bone marrow mesenchymal stem cells(BMSCs)on the repair of hemi-transected spinal cord injury(SCI)in rats.Methods Isolated and cultured rat BMSCs,followed by transfection with the NRG1 gene.The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method,and the proliferation activity of the BMSCs was detected by cell counting method.Forty-three healthy 8-week-old SD rats were randomly divided into control group(n=10),SCI model group(n=10),BMSCs group(n=10),and NRG1-BMSCs group(n=13).After establishing the spinal cord hemisection model,animals received in-situ transplantation of BMSCs or NRG1-BMSCs.On the 1,7,14,21,and 28 days after transplantation,the hind limb motor function was evaluated using BBB score and inclined plate test;on the 7th day after transplantation,the migration and distribution of transplanted cells was monitored using a fluorescence microscope;on the 28th day after transplantation,the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining;cell apoptosis using TUNEL staining,and levels of endoplasmic reticulum stress-related proteins[X-box binding protein 1(XBP1),C/EBP homologous protein(CHOP),activating transcription factor 4(ATF4),ATF6,glucose-regulated protein 78(GRP78)]and apoptosis-related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated protein X(Bax)]in rat spinal cord tissues using Western blotting.Results BMSCs were successfully isolated,cultured,and transfected with the NRG1 gene.ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner(P<0.05).The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs(P<0.05).On the 21 and 28 days after transplantation,the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group(P<0.05).However,it did not reverse to the level in control group(P<0.05).On the 28th day after transplantation,compared with the SCI model group and BMSCs group,neuronal pyknosis reduced,the Nissl body density increased,the expression levels of XBP1,CHOP,ATF4,ATF6,GRP78,and Bax,and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group(P<0.05),and the expression level of Bcl-2 significantly increased(P<0.05).Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats.The mechanism may be related to promoting the proliferation activity of BMSCs,inhibiting cell apoptosis,and mitigating endoplasmic reticulum stress.

Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P＜0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)