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*

Objective To evaluate the clinical efficacy of Zhuanggu Kangsong Soft Extract combined with percutaneous vertebroplasty(PVP)in the treatment of osteoporotic vertebral compression fractures(OVCF).Methods A total of 90 eligible OVCF patients admitted to Guangzhou Integrated Chinese and Western Medicine Hospital between January 2023 and May 2024 were enrolled and randomly divided into an observation group(n=45)and a control group(n=45)using a random number table.Both groups underwent PVP.After treatment,the control group received conventional western medication orally(calcium carbonate D3 tablets+calcitriol soft capsules),while the observation group received additional Zhuanggu Kangsong Soft Extract treatment orally.Western medication was administered for 6 months,and herbal treatment lasted 3 months.Changes in Visual Analogue Scale(VAS)scores for pain,Oswestry Disability Index(ODI)scores for low back function,bone mineral density(BMD)T-values,and serum bone metabolism markers were observed before and after treatment.Results(1)At postoperative day 3,3 months,and 6 months,both groups showed significant improvements in VAS and ODI scores compared to those before treatment(P＜0.05).The observation group demonstrated superior improvements in VAS and ODI scores at 3 and 6 months compared to the control group(P＜0.05).(2)At 3,6,and 12 months postoperatively,BMD T-values were improved in both groups(P＜0.05),with the observation group exhibiting greater improvements at 6 and 12 months(P＜0.05).(3)Serum N-terminal osteocalcin and 25-hydroxyvitamin D3[25(OH)D3]levels increased in both groups at 1,3,and 6 months(P＜0.05).The observation group showed more pronounced elevations in these markers at 3 and 6 months(P＜0.05).Conclusion The combination of Zhuanggu Kangsong Soft Extract and PVP demonstrates significant therapeutic benefits for OVCF by effectively alleviating pain,enhancing BMD,and improving activities of daily living,which highlights its high clinical value.

Thalidomide(THA)is renowned for its potent anti-inflammatory properties.This study aimed to eluci-date 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 auto-phagy.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 modu-lates 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.

OBJECTIVE: To determine the carrier rate for thalassemia mutations in the ethnic Miao population of Qianxinan Prefecture. METHODS: Ethnic Miao people suspected for thalassemia trait at the People's Hospital of Qianxinan Prefecture, Guizhou Province between November 2020 to September 2024 were selected as the study subjects. Gap-PCR technology combined with high-throughput sequencing was used to screen a total of 666 individuals. ArcMap v10.8.2 was used to create a spatial distribution map of thalassemia based on the screening results. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2016-01). RESULTS: In total 254 positive cases were detected, with an overall positive rate of 38.14%. Among these, 173 cases were α-thalassemia (25.98%), 77 cases were β-thalassemia (11.56%), and 4 cases were αβ compound thalassemia (0.60%). The most common genotypes for α-thalassemia were αα/--^SEA (positive rate = 10.06%, accounting for 38.73%), αα/-α^3.7 (positive rate = 8.86%, accounting for 34.10%), and α^CSα/αα (positive rate = 4.95%, accounting for 19.08%). The most common genotypes for β-thalassemia were β^41/42(-TTCT)/β^A (positive rate = 5.11%, accounting for 44.16%) and β^{17 (A>T)}/β^A(positive rate = 4.20%, accounting for 36.36%), with these two genotypes accounting for as much as 80.52%. The spatial distribution map indicated that the highest overall detection rate of thalassemia and α-thalassemia in the Miao population of Qianxinan Prefecture was in Xingyi City. The highest detection rate of β-thalassemia was in Zhenfeng County, and the highest detection rate of αβ compound thalassemia was in Wangmo County. CONCLUSION The detection rate of thalassemia among the ethnic Miaos from Qianxinan Prefecture is relatively high, which primarily consisted of α-thalassemia. Regular monitoring and educational outreach should be conducted.
Humans ; China/ethnology* ; Female ; Male ; Genetic Testing ; Adult ; alpha-Thalassemia/genetics* ; Thalassemia/ethnology* ; Ethnicity/genetics* ; Genotype ; beta-Thalassemia/ethnology* ; Adolescent ; Mutation ; Middle Aged ; Child ; Asian People/genetics* ; Young Adult

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.