Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3⁺ (FOXP3⁺) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3⁺ Tregs and curbs pro-inflammatory pathways.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) represent a distinct subclass of specialized metabolites predominantly found in the plant kingdom, particularly within the Guttiferae (Clusiaceae) family. These compounds exhibit remarkable structural diversity and a wide range of biological activities. Seco- and nor-PPAPs, two unique variants of PPAPs with diverse skeletal structures, have been extensively investigated. As of June 2023, 200 compounds have been isolated from four genera, with Hypericum being the primary source. Notably, 115 of these compounds were identified in the past four years, indicating a significant increase in research activity. Seco- and nor-PPAPs can be categorized into six main subgroups based on the original PPAP scaffolds. Biological studies have revealed their potential in various therapeutic applications, including anti-cancer, anti-inflammatory, hepatoprotective, anti-Alzheimer's disease (anti-AD), multidrug resistance (MDR) reversal, anti-depressant, neuroprotective, and immunosuppressive effects. This review provides a comprehensive overview of the occurrence, structures, and bioactivities of natural seco- and nor-PPAPs, offering valuable insights for the further development of PPAPs.
Phloroglucinol/analogs & derivatives* ; Humans ; Molecular Structure ; Animals ; Clusiaceae/chemistry* ; Plant Extracts/pharmacology* ; Biological Products/pharmacology*

SIRT6,a member of the sirtuin family of histone deacetylases,belongs to the class Ⅲ longevity proteins and exhibits NAD+-dependent deacetylase and mono-ADP-ribosyltransferase activities.SIRT6 is primarily located in the cell nucleus and plays a pivotal role in regulating genomic stability and relative gene expression,participating in the control of key processes such as energy metabolism and aging.Given its crucial role in maintaining cellular homeostasis and organismal health,SIRT6 has emerged as a potential therapeutic target,sparking significant research interest in the development of targeted modulators.Activating the longevity protein with drugs may provide therapeutic strategies for age-associated diseases,including aging,metabolic syndrome,inflammation,and reproductive health issues.The review elaborates the structural characteristics,enzymatic activities,and biological functions of SIRT6,as well as the mechanisms of action,pharmacological activities,and clinical applications of various SIRT6 activators.

Objective:To explore which configuration schemes of proximal humerus internal locking system (PHILOS) fixation with endosteal augmentation can provide the optimal biomechanical stability for treatment of osteoporotic proximal humeral fractures by means of finite element analysis.Methods:Based on the CT data of the humerus of an old female volunteer (78 years old, with a bone density T-value of -3.0), a three-dimensional finite element model of the humerus was established by digital medical software such as Mimics 19.0, Geomagic Studio 12, and Creo 2.0 ANSYS Workbench2019. Next, a model of unstable proximal humerus fracture was established and subjected respectively to 5 different fixations: simple PHILOS fixation (PHILOS group), PHILOS plus 6-cm fibula fixation with calcar screws (PHILOS-F-C-6 group), PHILOS plus 6-cm fibula fixation without calcar screws (PHILOS-F-6 group), PHILOS plus 9-cm fibula fixation with calcar screws (PHILOS-F-C-9), and PHILOS plus 9-cm fibula fixation without calcar screws (PHILOS-F-9 group). After a stress mode of shoulder joint abduction at 25° was simulated, a compressive load of 200N was applied to the 5 fixation models. The stress distribution and displacement of fracture ends in different fixation models were tested, and the biomechanical stability was compared among the 5 different internal fixations.Results:Under a shoulder joint abduction at 25° and a load of 200 N, the maximum stress and the displacement of the fracture ends in PHILOS-F-C-9 group (38.678 Mpa and 0.012 mm) decreased by 30.08% and 45.45%, respectively, compared with PHILOS-F-C-6 group (55.321 Mpa and 0.022 mm), and decreased by 12.48% and 15.38%, respectively, in PHILOS-F-9 group (77.012 Mpa and 0.033 mm) compared with PHILOS-F-6 group (88.106 Mpa and 0.039 mm). The maximum stress and the displacement of the fracture ends in PHILOS-F-C-6 group decreased by 37.21% and 43.59%, respectively, compared with PHILOS-F-6 group while decreased by 49.83% and 63.63% in PHILOS-F-C-9 group compared with PHILOS-F-9 group, respectively.Conclusion:For treatment of osteoporotic proximal humeral fractures with medial instability, PHILOS fixation with longer fibula endosteal augmentation plus insertion of calcar screws is a more appropriate choice which can reduce the stress of internal fixation and reduce the displacement of the fracture ends.

Objective:To investigate the application value of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment of pancreaticobiliary maljunction (PBM) in children.Methods:The clinical data of 77 PBM children who underwent ERCP in General Surgery Department of Children's Hospital affiliated to Nanjing Medical University between January 2018 and December 2021 were retrospectively evaluated. Clinical characteristics, classification and post-operative nursing interventions were summarized, and vital signs, changes of biochemical markers and the occurrence of postoperative complications were compared and recorded.Results:77 patients were classified according to Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM), including 34 patients with type A, 18 patients with type B, 21 patients with type C, and 4 patients with type D. There were 68 patients with congenital bile duct dilation and 9 patients without congenital bile duct dialtion. 92 ERCP procedures were performed under general anesthesia, and 91 cases were successful with a success rate of 98.91%. Among these cases, including 7 cases of endoscopic sphincterotomy, 28 cases of endoscopic balloon dilation of the nipple, 22 cases of endoscopic probe dilation, 22 cases of endoscopic stone removal by balloon or basket, 35 cases of endoscopic retrograde biliary stent drainage, 4 cases of endoscopic pancreatic duct drainage, 18 cases of endoscopic nasobiliary drainage, 2 cases of endoscopic nasobiliary drainage, and 14 cases of biliary stent removal. In 77 children with PBM, body temperature, FLACC score, and laboratory-related biochemical indexes including direct bilirubin, serum amylase, ALT, AST and CGT decreased significantly after ERCP, and all the differences were statistically significant (all P value <0.001). The incidence of postoperative complications was 15.38%(14/91), including hyperamylasemia in 9 cases (9.89%) and abdominal pain in 5 cases (5.49%). Conclusions:ERCP is safe and effective in the treatment of abnormal confluence of pancreatic duct in children.

Objective:To analyze the functional connectivity (FC) characteristics of sensory motor network (SMN) in patients with bipolar disorder type Ⅰ (BD-Ⅰ) by independent component analysis (ICA), and explore the correlation between abnormal SMN and clinical symptoms.Methods:Eighteen patients with BD-Ⅰ (BD-Ⅰ group) and 20 matched normal controls (HC group) were included.Both groups received resting state fMRI (rs-fMRI) scanning.Based on ICA-fMRI data, one-sample t-test and two-sample t-test were used to analyze the components of SMN and to explore abnormal brain regions between the two groups.Functional network analysis (FNC) was also used to explore the functional connectivity between SMN and other brain networks.Pearson correlation analysis were conducted by SPSS 17.0 to measure the potential associations between intra-and inter-network functional connectivity and age, education, score of Bech-Rafaelsen mania rating scale (BRMS), score of positive and negative syndrome scale (PANSS) and other indicators. Results:In BD-Ⅰ group, the functional connection in the right paracentral lobule (MIN: x=8, y=-32, z=68, t=4.86, P<0.001) and the right postcentral gyrus (MIN: x=41, y=-26, z=53, t=3.33, P<0.001) in SMN were higher than those in HC group.Compared with HC group, the connectivity value in patients with BD-Ⅰ increased between SMN-DAN (0.247±0.073, -0.078±0.080, t=-2.974, P<0.01, FDR adjusted), while the connectivity value decreased between SMN-DMN(-0.037±0.054, 0.272±0.067, t=3.520, P<0.01, FDR adjusted) and between SMN-rFPN(-0.034±0.055, 0.231±0.070, t=2.939, P<0.01, FDR adjusted). Conclusion:The sensorimotor network of patients with BD-Ⅰ has abnormal functional connections within and between networks, and FC values in some networks are positively correlated with manic symptoms, which may be part of the neural mechanisms of patients with BD-Ⅰ.

Objective:To assess the relationship between serum total bilirubin and fundus arteriosclerosis in different genders.Methods:The physical examination data of Huadong Sanatorium in 2018 were analyzed, and a total of 26 275 people were included in this retrospective cross-sectional study. The age of this study was 18-86 (47.7±11.1) years old. Among them, there were 15 244 males (58.02%) and 11 031 females (41.98%). Participants were divided into 4 groups according to total bilirubin quartile values: Q1<11.50 μmol/L, Q2∶11.50-13.93 μmol/L, Q3∶13.94-17.14 μmol/L and Q4>17.14 μmol/L. The relationship between total serum bilirubin and fundus arteriosclerosis is determined using univariate and multivariate logistic regression analysis methods. The restricted cubic spline method was used to detect the dose-response relationship between total bilirubin and fundus arteriosclerosis. Results:In males, univariate analysis showed that high level of total bilirubin was a protective factor for fundus arteriosclerosis ( OR=0.87, 95% CI 0.78-0.97, P=0.012). After adjusting for other confounding factors, multivariate analysis showed that high level of total bilirubin remained as an independent protective factor for fundus arteriosclerosis ( OR=0.86, 95% CI 0.74-0.99, P=0.047). There was a linear dose-response relationship between total bilirubin level and fundus arteriosclerosis ( P=0.012). In females, univariate analysis showed that there were no statistically significant association between high level of total bilirubin and fundus arteriosclerosis ( OR=0.96, 95% CI 0.80-1.17, P=0.709). After adjusting for other confounding factors, multivariate analysis showed no statistically significant association between high level of total bilirubin and fundus arteriosclerosis ( OR=0.98, 95% CI 0.76-1.27, P=0.888). No linear dose-response relationship between total bilirubin level and fundus arteriosclerosis was found in females ( P=0.253). Conclusion:There are gender differences in the relationship between total bilirubin and fundus arteriosclerosis in this cohort. Elevated levels of total bilirubin are associated with fundus arteriosclerosis in males but not in females.

Breast cancer has become one of the major factors that threaten women's health. The spouse, as an intimate partner and its main caregiver, has many unmet needs during the care period, which indirectly reflects the quality of life and needs of the patient. This article reviews the measurement tools, content of needs and influencing factors of spouse needs of breast cancer patients, and so as to provide a basis for further exploring spouse needs in China and formulating personalized intervention plans for spouses of patients with different needs at different stages.

Objective To evaluate the efficacy of bare mental stent (BMS) and covered stent (CS) in the treatment of complete central venous occlusive disease (CVOD) in hemodialysis patients.Methods A total of 66 cases of CVOD who have been treated by endovascular methods successfully in the First Affiliated Hospital of Sun Yat-sen University from Jan 2015 to Jan 2017 were enrolled in this study.According to the type of stent,the patients were divided into two groups,BMS group (n=46)and CS group (n=20).The demographic data,clinical signs and symptoms,and pre-procedure and post-procedure imaging data were followed up and recorded.The primary patency rates were calculated at 1,3,6,9,and 12 months.Results The related symptoms were improved within 2 day post-procedure.The primary patency rates of BMS group in 1,3,6,9 and 12 months were 97.83％,95.65％,69.56％,41.3％,and 34.78％ respectively.The rates of CS group were 100％,100％,95％,65％,and 60％respectively.They did not reached statistical significance for primary patency rates between two groups in 1,3,and 6 months (P ＞ 0.05 respectively).However,from 9 months after procedure,it began to show the significant difference between two groups (P ＜ 0.05).The median patency time of the CS group was (10.30±5.32) months,while BMS group was (8.52±0.49) months.The difference between the two groups was statistically significant (P=0.046).Conclusions Stent implantation for complete occlusion of central venous in hemodialysis patients can get credible effect.The use of CS for CVOD provides superior patency as well as patency time in long period after procedure as compared with BMS.

Objective To evaluate the feasibility and value of multi-detector computed tomography venography (MDCTV) and three dimensional reconstruction image in the assessment of central venous occlusive disease in hemodialysis patients,and in the value of guiding interventional treatments.Methods Sixty hemodialysis patients with swelling of upper limbs were scanned by Toshiba 128-multislice spiral computed tomography (128-MSCT) and totally 80-100 ml non-ionic contrast media was injected into each of the patients via the peripheral veins of the contralateral limb with the rate of 4 ml/s.MSCT scanning was taken by the technique of intelligent triggering after setting scanning triggering threshold,with the monitoring point set in the development of the lumen of inferior vena cava,to detect the position and degree of vascular stenosis.The images were reformed as maximum intensity projection (MIP),volume rendering (VR),curved planar reformation and threedimensional image reconstruction technique.Results MDCTV clearly demonstrated the lesion location in all cases enrolled.Seventy-five occlusive lesions were detected in the total of 60 hemodialysis patients with swelling of upper limbs by MDCTV,of which the lesions of brachiocephalic vein was 47,superior vena cava 15 and subclavian vein 13.Among the 75 stenosis lesions,the number of complete occlusive,severe,moderate and mild stenosis was 31,24,19 and only 1,respectively.MDCTV provided information coincident with that of digital subtraction angiography (DSA),which the correlation index was 0.401,while DSA showed that number of complete occlusive,severe,moderate and mild stenosis was 49,7,14 and 5,respectively.Pereutaneous transluminal angioplasty was performed in 53 patients,and stent placement was done in 40 patients.After interventional treatments,swelling of upper limbs were obviously relieved and vascular accesses got functional recovery to the extent that they could meet the requirement of hemodialysis.Conclusions MDCTV is the first choice to evaluate the condition of central venous occlusive diseases of hemodialysis patients with advantages of non-invasion,high definition and three-dimensional reconstruction.It can provide accurate evaluations of the conditions of occlusive lesions,which can be of great clinical significance to subsequent interventional therapy.