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*

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

Value-based healthcare emphasizes the importance of taking patients′ needs and experiences into full consideration during the entire diagnosis and treatment process and providing patient-centered medical services, so as to improve population health and medical outcomes with manageable medical costs.From this perspective, it is particularly important to investigate how patients could take full advantage of their subjective value and central role to engage in healthcare-related activities. This article aims to summarize the concepts and specific pathways relevant to patient engagement in the entire healthcare process, and provide specific suggestions and recommendations on promoting participation in health self-monitoring, access to disease and consultation information, shared decision-making(SDM)between doctors and patients, patients for patient safety(PFPS), patient-reported outcomes(PROs), participation in self-management, and participation in patient organizations, etc. This article provided valuable reference and evidence on implementation of relevant medical practices and policies.

To investigate the degradation of polycyclic aromatic hydrocarbons (PAHs) and the changes of rhizosphere microorganisms in the rhizosphere soil of Leymus chinensis during the remediation of PAHs contaminated soil by Comamonas testosteroni (C.t)-assisted Leymus chinensis, we evaluated the removal of PAHs in the rhizosphere of Leymus chinensis using gas chromatography-mass spectrometry (GC-MS), analyzed the bacterial community and the diversity in Leymus chinensis rhizosphere soil by high-throughput sequencing technology, characterized the correlation among PAHs degradation and bacterial community components performing redundancy analysis (RDA) and network analysis, and predicted PAHs degradation potential via PICRUSt software in this paper. The degradation of PAHs in the rhizosphere of Leymus chinensis was promoted, the abundance and diversity of bacteria and the correlation among bacteria and PAHs were changed, and the degradation potential of PAHs in Leymus chinensis rhizosphere soil was enhanced in the later stage of phytoremediation (60-120 d) due to the incorporation of C.t. The accelerated degradation of three PAHs (Nap, Phe, BaP) was accompanied by the differ abundance and correlation of Proteobacteria (Sphingomonas, MND1, Nordella), Actinomycetes (Rubrobacter, Gaiella), Acidobacteria (RB41) and Bacteroides (Flavobacterium) affected by C.t. The results provide new insight into the microorganism choices for microbial assisted plant remediation of soil PAHs and the mechanisms of enhanced PAHs degradation via the combination of Comamonas testosteroni engineering bacteria and plants.
Biodegradation, Environmental ; Comamonas testosteroni/genetics* ; Polycyclic Aromatic Hydrocarbons/analysis* ; Rhizosphere ; Soil ; Soil Microbiology ; Soil Pollutants

The study is to establish the administrative ward round system and its effect evaluation system under the modern hospital management conditions, and explore the formation of a standardized, scientific and replicable standard mode of Administrative Ward round. According to the annual ward rounds plan, clinical departments and administrative departments were organized to decide the major issues of a department according to the procedures of " hearing-evaluation-discussion-decision " , and to ensure the implementation of management. Since 2016, administrative ward round has been carried out in 9 departments, and the medical quality and operational efficiency have been improved significantly. The closed-loop administrative ward rounds mode can effectively promote the modernization of hospital management system through the joint decision-making of clinical departments and functional departments.

Objective To evaluate the efficacy and adverse reactions of platinum-based combined chemotherapeutical regimens in treating relapsed or refractory non-Hodgkin lymphoma(NHL).Methods The clinical data of 68 patients with relapsed or refractory NHL treated with platinum-based combined chemotherapeutical regimens in the Affiliated Tumor Hospital of Guangxi Medical University from January 2008 to December 2014 were retrospectively analyzed.The curative effect of related regimens,adverse reactions and related influence factors were analyzed.Results Sixty-eight cases received 283 cycles of chemotherapy.In all cases,11 cases(16.18 ％) achieved the complete response(CR),31 cases(45.59 ％) achieved the partial response(PR),the overall response rate(ORR) was 61.76％;the median progression-free survival(PFS) was 6.51 months(95％CI:4.97-8.04 months).ORR and PFS in the cases of stage Ⅱ-Ⅲ,IPI score 0-2 and receiving only one chemotherapeutical regimen were superior to those in the cases of corresponding subgroup(P＜0.05);ORR and PFS had no statistical difference between the B cells lymphoma and Tcells lymphoma(P＞0.05).The medion PFS in the combined R group was 11.16 months,which was longer than 5.84 months in the non-combined R group(P =0.004).The major adverse events (stage Ⅱ-Ⅲ) included leukopenia (41.18 ％),thrombocytopenia (27.94％),hemoglobin decrease(11.76％),vomiting(8.82％) and diarrhea(1.47％).Conclusion The platinum-based combined chemotherapeutical regimens are effective with good safety in the treatment of relapsed or refractory NHL.

Fibroblast growth factor 21 (FGF21) is a multi-effect endocrine factor, mainly secreted in liver and adipose tissue, with the properties of lipid-lowering, anti-inflammatory, anti-oxidant and anti-atherosclerosis. Recent studies found that FGF21 can induce protective effect in cardiovascular disease, and plasma FGF21 levels in patients with disease cardiovascular are elevated. These studies have suggested the use of FGF21 as a biomarker for subclinical atherosclerosis and its potential role in the treatment of established atherosclerotic cardiovascular disease. This article will review the recent advances in the anti-atherosclerosis effect of FGF21.

Objective:To evaluate efficacy and safety of multiple-dose tropisetron plus dexamethasone (DXM) versus palonosetron plus DXM for chemotherapy-induced nausea and vomiting. (CINV) in patients received multiple day-based highly emetogenic chemotherapy. Methods:Cancer patients who were receiving multiday-based highly emetogenic chemotherapy were randomly assigned to AB or BA groups. A randomized, cross self-control ed method was applied. Patients in AB group received palonosetron (0.25 mg) 30 min before chemotherapy on day 1 and 3 or additional day 5 in the first cycle;and with tropisetron (5 mg) 30 min before chemotherapy on day 1, 2, and 3, or sup-plementary days (day 4 and 5) in the second cycle. Patients in BA group were treated with tropisetron in the first cycle and with palonosetron in the second cycle. Tropisetron and palonosetron were administered with DXM (10 mg) on day 1, followed by additional doses (5 mg) on days 2 to 5. Palonosetron group comprised patients in the AB group in the first cycle and BA group in the second cycle, whereas tropisetron group included patients in the AB group in the second cycle and BA group in the first cycle. Efficacy and safety of tropisetron versus palonosetron in preventing CINV were evaluated. Results:Ninety-one patients were included in analyses. At day 3, 4, and 5, incidence rates of nausea in the palonosetron group reached 28.6%, 30.8%, and 24.2%, respectively, and those of the tropisetron group totaled 42.8%, 47.3%, and 39.6%, respectively (P<0.05). At day 4, 5, and 6, incidence rates of vomiting in the palonosetron group measured 28.6%, 18.7%, and 5.5%, respectively, and those of the tropisetron group reached 42.9%, 34.1%, and 14.3%, respectively (P<0.05). From day 4 to day 5, day 6 to day 7, and day 1 to day 7, the palonosetron group yielded significantly lower incidence rates of nausea and vomiting than tropisetron group (P<0.05). Rate of rescue treatment in the palonosetron group was lower than that in tropisetron group (13.2%vs. 24.2%, P=0.057). No statistical difference in toxicities was observed between the two groups. Conclusion:Palonosetron plus DXM features better efficacy than that of tropisetron plus DXM against delayed CINV induced by multiple day-based highly emetogenic chemotherapy, which was well tolerated in the two treatments.