Objective:To evaluate the clinical efficacy of the operation treated of unilateral unstable sacral fracture with S 1 dysplasia by bi-perforative screws of the middle and posterior pelvic columns. Methods:A retrospective analysis was conducted on 18 patients with proximal S 1 dysplasia and unilateral unstable sacral fractures treated at Tianjin Hospital, from January 2018 to January 2023. The cohort included 10 males and 8 females, with an average age of 46.3±1.2 years (range, 18-56 years). The causes of injury were traffic accidents in 12 cases and falls in 6 cases. All patients had combined anterior pelvic ring injuries, including 14 cases of simple fractures and 4 cases of fractures combined with pubic symphysis injuries. Preoperative neuro-magnetic resonance imaging (MRI) confirmed that the lumbosacral nerves were not compressed by fracture fragments or displaced bone ends. According to the Dennis classification, there were 8 cases of type I and 10 cases of type II sacral fractures. Abnormalities in S 1 development included 9 cases of steep slopes, 6 cases of anterior rim depression, and 3 cases of both deformities simultaneously. There were 2 cases of nerve injury, both of which were Gibbons grade II. The average time from injury to surgery was 5.4±1.7 days (range, 4-14 days). All patients underwent combined anterior and posterior pelvic fixation in a single stage, with sacral fractures fixed using bi-perforative screws of posterior pelvic ring. The following parameters were recorded: screw placement time, intraoperative blood loss, fluoroscopy time, fracture healing time, accuracy of internal fixation placement, postoperative infection rate, and iatrogenic injury incidence. The Mears scoring system was used to evaluate the satisfaction rate of sacral fracture reduction, the Gibbons classification was used to assess neurological recovery, and the Majeed score was used to evaluate pelvic function. Results:The average screw placement time was 38.7±3.5 min for S 1 and 16.5±1.3 min for the posterior column. The average blood loss during screw placement was 30.53±1.61 ml, and the average fluoroscopy time was 11.3±3.2 s. No vascular or nerve injuries occurred in any case after the operation. All sacral fractures healed, with an average healing time of 7.6±2.2 months (range, 3-12 months). No cases of fracture re-displacement or internal fixation failure were observed. The Mears evaluation results showed anatomical reduction in 12 cases, satisfactory reduction in 4 cases, and unsatisfactory reduction in 2 cases. All internal fixations were accurately placed. All 18 patients were followed up with an average of 18.2±2.5 months (range, 12-36 months). At the last follow-up, the average Majeed score was 87.4±2.9, with 11 cases rated as excellent, 4 as good, and 3 as fair. The two patients with Gibbons grade II nerve injuries improved to grade I postoperatively. Conclusion:Bi-perforative screws fixation for the middle and posterior pelvic columns offers several advantages, including straightforward operation, precise minimally invasive placement, safety and efficacy, robust fixation, and low complication rates, resulting in satisfactory clinical outcomes.

OBJECTIVES: Metastasis is the primary cause of death in osteosarcoma, and current clinical treatments remain limited. BRD4, a key epigenetic regulator, has shown therapeutic promise in various cancers through its inhibition. However, the mechanistic role of BRD4 in osteosarcoma remains poorly understood. This study aims to elucidate the molecular mechanisms by which BRD4 regulate osteosarcoma progression and to explore novel therapeutic strategies. METHODS: Immunofluorescence was used to assess BRD4 expression levels in a tissue microarray containing 80 osteosarcoma samples from different patients. The Gene Expression Omnibus (GEO) dataset (GSE42352, containing survival data from 88 osteosarcoma patients) was downloaded to perform Kaplan-Meier survival analysis based on BRD4 gene expression levels. In vivo, an orthotopic intramedullary osteosarcoma model was established using HOS cells in C57 mice, followed by treatment with varying doses of the BRD4 inhibitor (+)-JQ1. Micro-CT, 3D reconstruction of bone tissue, and HE staining were employed to evaluate pathological changes in bone and intestinal lymph nodes. In vitro, cell viability was measured using the methyl thiazolyl tetrazolium (MTT) assay, while colony formation and Transwell assays assessed proliferative and invasive capacities. Chromatin-bound BRD4 was analyzed via co-immunoprecipitation combined with mass spectrometry (Co-IP/MS), and O-GlcNAc glycosylation sites and glycan chains of BRD4 were identified using Co-IP with Nano-LC MS/MS. Real-time PCR and Western blotting were used to analyze the relative mRNA and protein expression levels of target genes, respectively. RESULTS: BRD4 was positively expressed in 61.25% (49/80) of osteosarcoma tissues. Patients with high BRD4 expression exhibited significantly shorter survival times (P<0.05). In the orthotopic mouse model, intervention with (+)-JQ1, a potent and commonly used BETi, significantly inhibited tumor growth in vivo and reduced bone destruction (P<0.05). (+)-JQ1 treatment significantly suppressed the proliferation (P<0.001), invasion (P<0.001), and migration (P<0.05) of HOS cells. In osteosarcoma cells, BRD4 exhibited O-GlcNAc modifications at both N- and C- C-termini, particularly at Thr73, which is essential for protein stability. This modification also contributed to the activation of the EGFR tyrosine kinase inhibitor resistance pathway (KEGG Pathway: hsa01521). (+)-JQ1 treatment displaced BRD4 from enhancers and downregulated the transcription of pathway-related genes, such as EGFR and PDGFC, thereby suppressing the malignant behavior of osteosarcoma cells. CONCLUSIONS BRD4 promotes osteosarcoma progression via O-GlcNAc modification at Thr73 and plays a crucial role in tumor growth and metastasis.
Osteosarcoma/drug therapy* ; Humans ; Transcription Factors/metabolism* ; Animals ; Cell Cycle Proteins ; Mice ; Bone Neoplasms/drug therapy* ; Azepines/pharmacology* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Triazoles/pharmacology* ; Mice, Inbred C57BL ; Nuclear Proteins/metabolism* ; Gene Expression Regulation, Neoplastic ; Male ; Bromodomain Containing Proteins

Objective:To evaluate the clinical efficacy of the operation treated of unilateral unstable sacral fracture with S 1 dysplasia by bi-perforative screws of the middle and posterior pelvic columns. Methods:A retrospective analysis was conducted on 18 patients with proximal S 1 dysplasia and unilateral unstable sacral fractures treated at Tianjin Hospital, from January 2018 to January 2023. The cohort included 10 males and 8 females, with an average age of 46.3±1.2 years (range, 18-56 years). The causes of injury were traffic accidents in 12 cases and falls in 6 cases. All patients had combined anterior pelvic ring injuries, including 14 cases of simple fractures and 4 cases of fractures combined with pubic symphysis injuries. Preoperative neuro-magnetic resonance imaging (MRI) confirmed that the lumbosacral nerves were not compressed by fracture fragments or displaced bone ends. According to the Dennis classification, there were 8 cases of type I and 10 cases of type II sacral fractures. Abnormalities in S 1 development included 9 cases of steep slopes, 6 cases of anterior rim depression, and 3 cases of both deformities simultaneously. There were 2 cases of nerve injury, both of which were Gibbons grade II. The average time from injury to surgery was 5.4±1.7 days (range, 4-14 days). All patients underwent combined anterior and posterior pelvic fixation in a single stage, with sacral fractures fixed using bi-perforative screws of posterior pelvic ring. The following parameters were recorded: screw placement time, intraoperative blood loss, fluoroscopy time, fracture healing time, accuracy of internal fixation placement, postoperative infection rate, and iatrogenic injury incidence. The Mears scoring system was used to evaluate the satisfaction rate of sacral fracture reduction, the Gibbons classification was used to assess neurological recovery, and the Majeed score was used to evaluate pelvic function. Results:The average screw placement time was 38.7±3.5 min for S 1 and 16.5±1.3 min for the posterior column. The average blood loss during screw placement was 30.53±1.61 ml, and the average fluoroscopy time was 11.3±3.2 s. No vascular or nerve injuries occurred in any case after the operation. All sacral fractures healed, with an average healing time of 7.6±2.2 months (range, 3-12 months). No cases of fracture re-displacement or internal fixation failure were observed. The Mears evaluation results showed anatomical reduction in 12 cases, satisfactory reduction in 4 cases, and unsatisfactory reduction in 2 cases. All internal fixations were accurately placed. All 18 patients were followed up with an average of 18.2±2.5 months (range, 12-36 months). At the last follow-up, the average Majeed score was 87.4±2.9, with 11 cases rated as excellent, 4 as good, and 3 as fair. The two patients with Gibbons grade II nerve injuries improved to grade I postoperatively. Conclusion:Bi-perforative screws fixation for the middle and posterior pelvic columns offers several advantages, including straightforward operation, precise minimally invasive placement, safety and efficacy, robust fixation, and low complication rates, resulting in satisfactory clinical outcomes.

Objective:To investigate the difference of colectomy rate of acute severe ulcerative colitis (ASUC) treated with accelerated and standard infliximab (IFX) induction as salvage therapy.Methods:Relevant studies comparing accelerated and standard IFX induction in ASUC were systematically searched in PubMed, MEDLINE, EMBASE, Cochrane Library, Scopus from the establishment of the databases to Feb 7th, 2022. Two researchers screened the studies according to the established inclusion and exclusion criteria, evaluated the quality of included studies, and extracted the data. Meta-analysis was performed using R 4.0.3.Results:Ten studies were finally included, including 716 patients. The results of meta-analysis showed that there were no significant difference in colectomy rate of in-hospital ( OR = 0.56, 95% CI: 0.13 - 2.45, P = 0.446) , 3 months ( OR = 1.14, 95% CI: 0.54 - 2.42, P = 0.724) , 1 year ( OR = 0.85, 95% CI: 0.51 - 1.41, P = 0.528) , and 2 years ( OR = 1.01, 95% CI: 0.59 - 1.74, P = 0.962) between accelerated and standard IFX induction in ASUC patients, but there was significant heterogeneity among different studies. Covariate analysis revealed that baseline albumin ( MD = -1.27, 95% CI: -2.31 - -0.23, P = 0.017) and hemoglobin ( MD = -0.60, 95% CI: -1.01 - -0.20, P = 0.004) levels were significantly lower in the accelerated treatment group than those in the standard treatment group. Conclusions:There are no significant difference in short-term and long-term colectomy rates between ASUC patients treated with accelerated and standard infliximab induction, but there is significant difference in baseline disease severity between the two groups. Patients with severe disease activity should be treated with more aggressive accelerated IFX induction.

Objective:To explore the character of gut microbiota in inflammatory bowel disease (IBD) patients with Clostridium difficile infection (CDI) . Methods:A cross-sectional study was conducted. Fifty-four IBD patients were included consecutively in Peking Union Medical College Hospital from November 2017 to April 2018. The patients were divided into CDI group ( n = 20) and non-CDI group ( n = 34) according to whether the patient had CDI. Forty healthy people were recruited as the healthy control group. 16S rRNA sequencing was carried out in all the samples of 3 groups to analyze the diversity and composition of gut microbiota. Results:Compared with the healthy control group, α diversity (Chao1 index, Shannon index, Simpson index, Pielou index) was significantly lower and β diversity (microbiota structure) was significantly different in CDI and non-CDI groups (all P<0.05) . There was no significant difference in α and β diversities between CDI and non-CDI groups (all P>0.05) . Compared with healthy control group, relative abundance of Faecalibacterium was significantly lower in CDI and non-CDI groups, while relative abundances of Proteobacteria and Enterobacteriaceae were significantly higher (all P<0.05) . Compared with non-CDI group, relative abundances of Parabacteroides and Rothia were significantly lower, while relative abundance of Clostridioides was significantly higher in CDI group (all P<0.05) . Lefse analysis results showed that Ruminococcus gnavus, Clostridium innocuum, Clostridium paraputrificum, Lactobacillus farciminis, and Peptostreptococcaceae contributed greatly to the difference in CDI group. Conclusion:Compared with healthy control group and non-CDI group, IBD patients with CDI have specific alterations in composition of gut microbiota.

Objective:To compare the difference of chemical compositions of single decoction and mixed decoction of Gypsum Fibrosum - Anemarrhenae Rhizoma medicinal pair with different proportion.Methods:The Ultra Performance Liquid Chromatography (UPLC) and Ion Chromatography (IC) fingerprints of each sample were collected, and the independent sample t-test on the ratio of "peak area/weight" value of common peaks which was from the single decoction and mixed decoction samples was performed through SPSS 26.0.Results:In the UPLC fingerprint, there was significant difference in the "peak area/weight" values of peak 1, peak 2, peak 3, peak 6 and peak 13 between mixed decoction and single decoction with different compatibility ratios (1:1, 3:2, 2:1, 5:2, 3:1)( P<0.05), while peak 5 and peak 11 were without significant difference ( P>0.05). When the compatibility ratio of Gypsum Fibrosum and Anemarrhenae Rhizoma was 1:1, 3:2, 5:2, 3:1, there was significant difference in the "peak area/weight" values of peak 7 (neomangiferin) ( P<0.05). In the IC fingerprint, there was significant difference in the "peak area/weight" values of peak 1 between mixed decoction and single decoction with different compatibility ratios (1:1, 3:2, 2:1, 5:2, 3:1) ( P<0.05), while there was no significant difference in peak 5 (calcium ion) ( P>0.05). Conclusion:There are differences in the chemical component content of Gypsum Fibrosum-Anemarrhenae Rhizoma medicinal pair for single decoction and mixed decoction.

Objective:To explore the character of gut microbiota in inflammatory bowel disease (IBD) patients with Clostridium difficile infection (CDI) . Methods:A cross-sectional study was conducted. Fifty-four IBD patients were included consecutively in Peking Union Medical College Hospital from November 2017 to April 2018. The patients were divided into CDI group ( n = 20) and non-CDI group ( n = 34) according to whether the patient had CDI. Forty healthy people were recruited as the healthy control group. 16S rRNA sequencing was carried out in all the samples of 3 groups to analyze the diversity and composition of gut microbiota. Results:Compared with the healthy control group, α diversity (Chao1 index, Shannon index, Simpson index, Pielou index) was significantly lower and β diversity (microbiota structure) was significantly different in CDI and non-CDI groups (all P<0.05) . There was no significant difference in α and β diversities between CDI and non-CDI groups (all P>0.05) . Compared with healthy control group, relative abundance of Faecalibacterium was significantly lower in CDI and non-CDI groups, while relative abundances of Proteobacteria and Enterobacteriaceae were significantly higher (all P<0.05) . Compared with non-CDI group, relative abundances of Parabacteroides and Rothia were significantly lower, while relative abundance of Clostridioides was significantly higher in CDI group (all P<0.05) . Lefse analysis results showed that Ruminococcus gnavus, Clostridium innocuum, Clostridium paraputrificum, Lactobacillus farciminis, and Peptostreptococcaceae contributed greatly to the difference in CDI group. Conclusion:Compared with healthy control group and non-CDI group, IBD patients with CDI have specific alterations in composition of gut microbiota.

Objective:To investigate the difference of colectomy rate of acute severe ulcerative colitis (ASUC) treated with accelerated and standard infliximab (IFX) induction as salvage therapy.Methods:Relevant studies comparing accelerated and standard IFX induction in ASUC were systematically searched in PubMed, MEDLINE, EMBASE, Cochrane Library, Scopus from the establishment of the databases to Feb 7th, 2022. Two researchers screened the studies according to the established inclusion and exclusion criteria, evaluated the quality of included studies, and extracted the data. Meta-analysis was performed using R 4.0.3.Results:Ten studies were finally included, including 716 patients. The results of meta-analysis showed that there were no significant difference in colectomy rate of in-hospital ( OR = 0.56, 95% CI: 0.13 - 2.45, P = 0.446) , 3 months ( OR = 1.14, 95% CI: 0.54 - 2.42, P = 0.724) , 1 year ( OR = 0.85, 95% CI: 0.51 - 1.41, P = 0.528) , and 2 years ( OR = 1.01, 95% CI: 0.59 - 1.74, P = 0.962) between accelerated and standard IFX induction in ASUC patients, but there was significant heterogeneity among different studies. Covariate analysis revealed that baseline albumin ( MD = -1.27, 95% CI: -2.31 - -0.23, P = 0.017) and hemoglobin ( MD = -0.60, 95% CI: -1.01 - -0.20, P = 0.004) levels were significantly lower in the accelerated treatment group than those in the standard treatment group. Conclusions:There are no significant difference in short-term and long-term colectomy rates between ASUC patients treated with accelerated and standard infliximab induction, but there is significant difference in baseline disease severity between the two groups. Patients with severe disease activity should be treated with more aggressive accelerated IFX induction.

PURPOSE: . The present study compared the accuracy between digital and conventional implant impressions. MATERIALS AND METHODS: . The experimental models were divided into six groups depending on the implant location and the scanning span. Digital impressions were captured using the intraoral optical scanner TRIOS (3Shape, Copenhagen, Denmark). Conventional impressions were taken with the monophase impression material based on addition-cured silicones, Honigum-Mono (DMG, Hamburg, Germany). A highprecision laboratory scanner D900 (3Shape, Copenhagen, Denmark) was used to obtain digital data of resin models and stone casts. Surface tessellation language (STL) datasets from scanner were imported into the analysis software Geomagic Qualify 14 (3D Systems, Rock Hill, SC, USA), and scan body deviations were determined through two-dimensional and three-dimensional analyses. Each scan body was measured five times. The Sidak t test was used to analyze the experimental data. RESULTS: . Implant position and scanning distance affected the impression accuracy. For a unilateral arch implant and the mandible models with two implants, no significant difference was observed in the accuracy between the digital and conventional implant impressions on scan bodies; however, the corresponding differences for trans-arch implants and mandible with six implants were extremely significant (P <.001). CONCLUSION . For short-span scanning, the accuracy of digital and conventional implant impressions did not differ significantly. For long-span scanning, the precision of digital impressions was significantly inferior to that of the traditional impressions.

Eucommiae Folium(EF),a traditional Chinese medicine,has been used to treat secondary hypertension,including renal hypertension and salt-sensitive hypertension,as well as hypertension caused by thoracic aortic endothelial dysfunction,a high-fat diet,and oxidized low-density lipoprotein.The antihyperten-sive components of EF are divided into four categories:flavonoids,iridoids,lignans,and phenyl-propanoids,such as chlorogenic acid,geniposide acid and pinoresinol diglucoside.EF regulates the occurrence and development of hypertension by regulating biological processes,such as inhibiting inflammation,regulating the nitric oxide synthase pathway,reducing oxidative stress levels,regulating endothelial vasoactive factors,and lowering blood pressure.However,its molecular antihypertensive mechanisms are still unclear and require further investigation.In this review,by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology,we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension,the related components,and underlying mechanisms.The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component,multi-target and multi-pathway mechanism.In particular,we discussed the role of EF tar-gets in the treatment of hypertension,including epithelial sodium channel,heat shock protein70,rho-associated protein kinase 1,catalase,and superoxide dismutase.The relevant signal transduction path-ways,the ras homolog family member A(RhoA)/Rho-associated protein kinase(ROCK)and nicotinamide adenine dinucleotide phosphate(NADPH)oxidase/eNOS/NO/Ca2+pathways,are also discussed.