BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.

Objective:To investigate the prognosis of patients with cervical lymph node oligometastasis after esophageal cancer surgery who underwent different therapeutic modalities.Methods:The retrospective cohort study was conducted. The clinicopathological data of 5 692 pati-ents with esophageal cancer who were admitted to Sun Yat-sen University Cancer Center from May 2007 to June 2023 were collected. There were 4 473 males and 1 219 females, aged 61 (rang, 55-66)years. Of 5 692 patients, 127 patients developed cervical lymph node oligometastasis, including 23 cases undergoing surgery alone who were divided into the surgery along group, 74 cases under-going radiotherapy, chemotherapy, or combined chemoradiotherapy who were divided into the chemo-radiotherapy group, 30 cases undergoing surgery combined with radiotherapy, chemotherapy, or chemoradiotherapy who were divided into the combined treatment group, respectively. Measure-ment data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages, and comparisons between groups were performed using the chi-square test or Fisher exact probability. Baseline differences were adjusted using the inverse probability of treatment weighting (IPTW). The optimal cut-off value for prognosis was determined using X-tile software (v3.6.1). Median follow-up time was calculated using the inverse Kaplan-Meier method, and missing data were handled by multiple imputations. The Kaplan-Meier method was used to plot survival curve, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model, and clinicopathological factors with P<0.2 in the univariate analysis were included in the multivariate analysis. Results:(1) Survival situations. The median follow-up time for the 127 patients was 47 months, with a median progression-free survival time of 31 months and a median overall survival time of 53 months. The 1-, 3-, and 5-year progression-free survival rate were 61.5%, 43.0%, and 36.5%, respectively. The 1-, 3-, and 5-year overall survival rate were 85.6%, 60.2%, and 45.7%, respectively. After IPTW adjustment, the median progression-free survival time of the surgery along group, chemoradiotherapy group, and combined treatment group were 55, 23, and 61 months, respectively. The 1-, 3-, and 5-year progression-free survival rate of the surgery along group were 72.9%, 69.7%, and 43.6%, versus 61.1%, 37.3%, and 32.6% for the chemoradiotherapy group, and 60.9%, 52.9%, and 52.9% for the combined treatment group, showing no significant difference among the three groups ( χ2=0.34, P>0.05). The median overall survival time of the surgery along group, chemoradiotherapy group, and combined treatment group were not reached, 60 months, and 45 months, respectively. The 1-, 3-, and 5-year overall survival rate were 87.6%, 82.0%, and 55.1% for the surgery along group, versus 91.3%, 57.4%, and 46.8% for the chemoradiotherapy group, and 87.1%, 64.3%, and 32.2% for the combined treatment group, showing no significant difference among the three groups ( χ2=0.10, P>0.05). (2) Prognosis analysis. After IPTW adjustment, results of multivariate analysis showed that comorbidity and neoadjuvant therapy were independent risk factors affecting progression-free survival time for patients with cervical lymph node oligometastasis ( hazard ratio=2.25, 2.74, 95% confidence interval as 1.08-5.65, 1.49-5.06, P<0.05), and neoadjuvant therapy and oligometastasis occurring ≤24 months were independent risk factors affecting overall survival time for patients with cervical lymph node oligometastasis ( hazard ratio=2.85, 2.08, 95% confidence interval as 1.52-5.34, 1.04-4.17, P<0.05). Results of further analysis showed that the 1-, 3-, and 5-year overall survival rate were 83.7%, 35.3%, and 16.4% for patients with neoadjuvant therapy, versus 91.6%, 72.6%, and 56.2% for patients without neoadjuvant therapy, showing a significant difference between them ( χ2=9.26, P<0.05). The 1-, 3-, and 5-year overall survival rate were 84.9%, 53.9%, and 40.1% for patients with oligometastasis occurring ≤24 months, versus 97.8%, 80.5%, and 59.9% for patients with oligometastasis occurring>24 months, showing a signifi-cant difference between them ( χ2=9.20, P<0.05). Conclusions:There was no significant difference in prognosis of patients with cervical lymph node oligometastasis after esophageal cancer surgery who underwent surgery alone, chemoradiotherapy or combined treatment. Comorbidity is an inde-pendent risk factor affecting progression-free survival time for patients with cervical lymph node oligometastasis, oligometastasis occurring ≤24 months is an independent risk factor affecting overall survival time, and neoadjuvant therapy is an independent risk factor affecting both progression-free survival time and overall survival time.

Objective To observe the therapeutic efficacy and mechanism of Gushi Zaizao Pills for steroid-induced osteonecrosis of the femoral head(SONFH).Methods Male SD rats were randomly divided into normal group,model group,Xianling Gubao Capsules group and Gushi Zaizao Pills group.Except for the normal group,the rats in all other groups were replicated the SONFH model.After successful modeling,the continuous drug administration was carried out for six weeks.The thymus and spleen of the rats were taken to calculate the immune organ indices,the contents of interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)in rat synovial fluid were detected by enzyme-linked immunosorbent assay(ELISA),the percentage of empty lacunae and area ratio of trabecular bone was detected by hematoxylin-eosin(HE)staining,and the femoral head parameters[reduction of bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th)and trabecular separation(Tb.Sp)]were analyzed by Micro-CT,and bone strength of femoral head was detected by small animal bone strength tester.Results Compared with the normal group,the spleen and thymus indicators were significantly decreased in the model group,the levels of IL-1β and TNF-α in rat synovial fluid were significantly increased,the percentage of empty lacunae was increased,the area ratio of trabecular bone was decreased,the BV/TV,Tb.N and Tb.Th were decreased,the Tb.Sp was increased,the bone strength of femoral head was significantly decreased,the differences being all statistically significant(P＜0.05 or P＜0.01).Compared with the model group,the spleen and thymus indicators were significantly increased in Xianling Gubao Capsules group and Gushi Zaizao Pills group,the levels of IL-1β and TNF-α in rat synovial fluid were decreased,the percentage of empty lacunae was significantly decreased,the area ratio of trabecular bone was significantly increased,the BV/TV,Tb.N and Tb.Th were increased,the Tb.Sp was decreased,and the bone strength of femoral head was significantly increased,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Gushi Zaizao Pills can effectively prevent the further development of SONFH by regulating cellular immunity and reducing the secretion of inflammatory factors,thereby reducing the pathological damage of the femoral head and enhancing the bone strength.

Objective:To investigate the prognosis of patients with cervical lymph node oligometastasis after esophageal cancer surgery who underwent different therapeutic modalities.Methods:The retrospective cohort study was conducted. The clinicopathological data of 5 692 pati-ents with esophageal cancer who were admitted to Sun Yat-sen University Cancer Center from May 2007 to June 2023 were collected. There were 4 473 males and 1 219 females, aged 61 (rang, 55-66)years. Of 5 692 patients, 127 patients developed cervical lymph node oligometastasis, including 23 cases undergoing surgery alone who were divided into the surgery along group, 74 cases under-going radiotherapy, chemotherapy, or combined chemoradiotherapy who were divided into the chemo-radiotherapy group, 30 cases undergoing surgery combined with radiotherapy, chemotherapy, or chemoradiotherapy who were divided into the combined treatment group, respectively. Measure-ment data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages, and comparisons between groups were performed using the chi-square test or Fisher exact probability. Baseline differences were adjusted using the inverse probability of treatment weighting (IPTW). The optimal cut-off value for prognosis was determined using X-tile software (v3.6.1). Median follow-up time was calculated using the inverse Kaplan-Meier method, and missing data were handled by multiple imputations. The Kaplan-Meier method was used to plot survival curve, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model, and clinicopathological factors with P<0.2 in the univariate analysis were included in the multivariate analysis. Results:(1) Survival situations. The median follow-up time for the 127 patients was 47 months, with a median progression-free survival time of 31 months and a median overall survival time of 53 months. The 1-, 3-, and 5-year progression-free survival rate were 61.5%, 43.0%, and 36.5%, respectively. The 1-, 3-, and 5-year overall survival rate were 85.6%, 60.2%, and 45.7%, respectively. After IPTW adjustment, the median progression-free survival time of the surgery along group, chemoradiotherapy group, and combined treatment group were 55, 23, and 61 months, respectively. The 1-, 3-, and 5-year progression-free survival rate of the surgery along group were 72.9%, 69.7%, and 43.6%, versus 61.1%, 37.3%, and 32.6% for the chemoradiotherapy group, and 60.9%, 52.9%, and 52.9% for the combined treatment group, showing no significant difference among the three groups ( χ2=0.34, P>0.05). The median overall survival time of the surgery along group, chemoradiotherapy group, and combined treatment group were not reached, 60 months, and 45 months, respectively. The 1-, 3-, and 5-year overall survival rate were 87.6%, 82.0%, and 55.1% for the surgery along group, versus 91.3%, 57.4%, and 46.8% for the chemoradiotherapy group, and 87.1%, 64.3%, and 32.2% for the combined treatment group, showing no significant difference among the three groups ( χ2=0.10, P>0.05). (2) Prognosis analysis. After IPTW adjustment, results of multivariate analysis showed that comorbidity and neoadjuvant therapy were independent risk factors affecting progression-free survival time for patients with cervical lymph node oligometastasis ( hazard ratio=2.25, 2.74, 95% confidence interval as 1.08-5.65, 1.49-5.06, P<0.05), and neoadjuvant therapy and oligometastasis occurring ≤24 months were independent risk factors affecting overall survival time for patients with cervical lymph node oligometastasis ( hazard ratio=2.85, 2.08, 95% confidence interval as 1.52-5.34, 1.04-4.17, P<0.05). Results of further analysis showed that the 1-, 3-, and 5-year overall survival rate were 83.7%, 35.3%, and 16.4% for patients with neoadjuvant therapy, versus 91.6%, 72.6%, and 56.2% for patients without neoadjuvant therapy, showing a significant difference between them ( χ2=9.26, P<0.05). The 1-, 3-, and 5-year overall survival rate were 84.9%, 53.9%, and 40.1% for patients with oligometastasis occurring ≤24 months, versus 97.8%, 80.5%, and 59.9% for patients with oligometastasis occurring>24 months, showing a signifi-cant difference between them ( χ2=9.20, P<0.05). Conclusions:There was no significant difference in prognosis of patients with cervical lymph node oligometastasis after esophageal cancer surgery who underwent surgery alone, chemoradiotherapy or combined treatment. Comorbidity is an inde-pendent risk factor affecting progression-free survival time for patients with cervical lymph node oligometastasis, oligometastasis occurring ≤24 months is an independent risk factor affecting overall survival time, and neoadjuvant therapy is an independent risk factor affecting both progression-free survival time and overall survival time.

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA₂DS₂-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA₂DS₂-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.
Humans ; Female ; Male ; Atrial Fibrillation/drug therapy* ; Coronary Artery Disease/complications* ; Anticoagulants/therapeutic use* ; Platelet Aggregation Inhibitors/therapeutic use* ; Risk Factors ; China ; Administration, Oral ; Stroke

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.