ObjectiveTo develop an exercise intervention program for patients undergoing total knee arthroplasty based on the daily goal management pathway, and preliminarily verify its clinical feasibility and effectiveness. MethodsThe intervention program was formulated based on the daily goal management pathway and hope theory, combined with literature analysis, qualitative interviews and expert consultation. Feasibility evaluation was conducted among orthopedic nurses and patients in Beijing Bo'ai Hospital from September to November, 2025. A controlled pilot study was performed with 15 patients in each group: the control group received routine rehabilitation care, while the experimental group received the developed intervention program. The Hospital for Special Surgery Knee Score (HSS), range of motion (ROM) of knee, functional exercise compliance score, Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were compared between two groups. ResultsThe program covered three themes from admission to three weeks postoperatively, including seven training methods and 32 specific recommendations. Feasibility results showed 100% patient recruitment rate, 93.75% retention rate and 96.94% program acceptance rate. A total of 21 orthopedic nurses scored ≥ 4.5 on all four dimensions of the program. After intervention, HSS score and knee ROM significantly increased (|t| > 6.205, P < 0.001), while WOMAC and VAS score decreased (t = 9.127, Z = -3.415, P < 0.01) in the experimental group; in the control group, VAS score decreased (Z = -3.122, P = 0.002), and knee ROM reduced (t = -2.622, P = 0.015), with no significant improvement in other indicators (P > 0.05); all the indexes were better in the experimental group than in the control group (|t| > 7.949, |Z| > 2.990, P < 0.01), including the functional exercise compliance (t = -8.565, P < 0.001). ConclusionThe exercise intervention program based on the daily goal management pathway is scientific, feasible and preliminarily effective, which can provide a new structured and humanized nursing for early exercise training of patients during hospitalization for total knee arthroplasty.

Objective To explore the application value of Laennec's membrane space in dealing with complex anatomical variations and dense adhesions during repeated liver transplantation (Re-LT). Methods The clinical data of 8 cases of Re-LT recipients treated in the Department of Hepatobiliary Surgery of the First Hospital Affiliated to Harbin Medical University were retrospectively analyzed. During the operation, based on the Laennec's membrane anatomical concept, the remaining Laennec space and the free technique within the hepatic portal plate were flexibly applied for dissection. Specifically, the first hepatic portal main ducts (biliary and portal veins) were dissected by lowering the hepatic portal plate inside the Laennec's membrane space, and the second hepatic portal was exposed to perform the modified piggyback liver transplantation to avoid the injury to the right adrenal gland and right kidney caused by the free inferior vena cava below the liver. Moreover, the dense adhesions between the liver and hollow organs were separated by a combination of blunt and sharp dissection within the subcapsular space of the liver capsule (Glisson capsule). Results All 8 cases of recipients successfully completed the surgery. Among them, 7 cases underwent end-to-end biliary anastomosis with a T-tube left in place, and 1 underwent choledochoenteric anastomosis, 2 cases underwent modified piggyback reconstruction, 2 cases used the subcapsular dissection technique to handle organ adhesions. One recipient died of generalized drug-resistant Klebsiella pneumoniae infection combined with septic shock after the operation, while the remaining 7 cases were discharged after the main complications (such as delayed graft function recovery, pulmonary infection, bile leakage, etc.) were cured or significantly improved. Two cases of recipients who used the subcapsular dissection technique effectively avoided the secondary injury of hollow organs, and no digestive tract leakage complications occurred after the operation. Conclusions By flexibly applying Laennec's membrane space and the intrahepatic portal plate free technique in Re-LT, it may effectively cope with the loss of anatomical layers and vascular dense adhesions, reducing the surgical difficulty and the risk of secondary injury, providing important technical support for improving the prognosis of recipients.

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 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 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.

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.