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*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective: To understand the prevalence of Lying Flat behaviors and its association with depressive symptoms among Chinese college students, so as to provide a scientific basis for promoting the physical and mental health development of adolescents. Methods: From July to October 2023, three universities were selected through convenient sampling from Jiangxi Province, Liaoning Province and Beijing City, respectively. Selfdesigned questionnaire links were distributed on campus to collect basic information and Lying Flat behaviors among college students, and the Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for students with depressive symptoms. Finally, a total of 4 225 valid questionnaires were obtained. Chisquare was used to compare of report rates of Lying Flat behaviors across different demographic characteristics. Ordered Logistic regression analysis was used to explore the association between Lying Flat behaviors and depressive symptoms, with Z test used to assess variations in the strength of associations. Results: The reporting rates of academic, life, and social Lying Flat were 32.7%, 17.8% and 17.5%, respectively. And 6.7% of the participants were found of all three Lying Flat behaviors simultaneously.Among college students with three Lying Flat behaviors, the constituent ratios of no, mild, moderate and above depressive symptoms were 9.9%, 30.5% and 59.6%, respectively. Additionally, college students who had three Lying Flat behaviors were more likely to show mild, moderate and above depressive symptoms [OR(95%CI)=2.49(1.60-3.87), 7.69(5.01-11.79), P<0.01]. Conclusions Academic Lying Flat behavior is most prevalent among college students. Academic, life and social Lying Flat behaviors are all significantly positively correlated with depressive symptoms. Attention should be paid to the Lying Flat behaviors and college students psychological health conditions to promote their physical and mental health development.

AIM:To investigate the molecular mechanism of a novel bromobenzene substituted trifluoromethylbenzo Cyclopentanone WW02 inhib-iting the viability and proliferation of human lung cancer A549 and H1299 cells.METHODS:The ef-fect of different concentrations of WW02(6.25,12.5,25,50 μg/mL)on cell viability and prolifera-tion of A549 and H1299 were measured using CCK-8 and EdU methods.After 24 hours of stimulation of A549 and H1299 cells with different concentra-tions of WW02,the changes in Akt and mTOR phos-phorylation levels under different concentrations of WW02 were detected through Western blot as-say.Macromolecular docking was carried out be-tween WW02,AKT and mTOR through MOE Dock.RESULTS:After treating A549 and H1299 cells with WW02 using different concentrations(6.25,12.5,25,50 μg/mL),the activity of A549 and H1299 cells decreased in a concentration dependent manner compared with the DMSO control group(P<0.05).The proliferation of cells showed a concentration dependent decrease compared to the DMSO con-trol group(P<0.05).Compared with the DMSO con-trol group,after 24 hours of WW02 stimulation,the phosphorylation levels of Akt and mTOR in A549 cells decreased under the concentration of WW02(12.5,25,50 μg/mL,P<0.05).Compared with the DMSO control group,the phosphorylation levels of Akt and mTOR in H1299 cells decreased af-ter 24 hours of WW02 stimulation(25,50 μg/mL,P<0.05).Based on pattern analysis,it was found that WW02 had a strong binding with Akt and mTOR,with the highest score of-8.3 kcal/mol for WW02 and mTOR,while the highest score for WW02 and Akt was-7.3 kcal/mol.CONCLUSION:WW02 inhib-its the activity and proliferation of lung cancer A549 and H1299 cells,and its mechanism of action may be achieved by directly binding to Akt and mTOR proteins to inhibit Akt and mTOR phosphory-lation.

Objective To explore the diagnostic value of magnetic resonance DKI parameters and serum levels of tumor necrosis factor-alpha(TNF-α)and interleukin-1α(IL-1α)in Alzheimer's disease(AD).Methods From July 2020 to July 2022,60 patients with Alzheimer's disease in our hospital were selected as the observation group and 60 healthy elderly people over 60 years old as the control group.All patients underwent routine MRI sequence examination,measured DKI parameters,and detected serum TNF-α and IL-1α levels by ELISA.Results The MD value of each brain area was significantly increased in alzheimer's disease patients.FA of white matter,hippocampus and substantia nigra decreased in temporal and parietal cortex,while FA of caudate nucleus,red nucleus and dentate nucleus increased.RK of white matter,hippocampus and thalamus in temporal and parietal cortex decreased significantly,while RK in substantia nigra increased significantly.AK of white matter,thalamus,dentate nucleus and substantia nigra in temporal and parietal cortex were significantly decreased.The MK in white matter,hippocampus and thalamus of temporal and parietal cortex decreased significantly,while the MK in caudate nucleus and substantia nigra increased significantly.The serum levels of homotype hemisoline and acetylcholinesterase increased significantly.Conclusion Combined magnetic resonance DKI parameters and detection of serum TNF-α and IL-1α levels have certain diagnostic and predictive value for the occurrence of Alzheimer's disease.

Objective:To analyze the imaging changes of patients with monophasic depression based on the changes in CT parameters of each cerebral lobe.Methods:A total of 100 patients with monophasic depression who received treatment in Department of Radiology, Shaoxing 7 th People's Hospital between June 2019 and June 2021 were included in the observation group. An additional 100 healthy individuals who concurrently received physical examination were included in the control group. CT scan of the brain was performed in all participants. CT value of each cerebral lobe was compared between the two groups. Results:CT values of the left frontal lobe and left temporal lobe in the observation group were (40.88 ± 2.01) HU and (40.21 ± 3.01) HU, respectively, which were significantly lower than those in the control group ( tleft frontal lobe = 2.94, P = 0.004; tleft temporal lobe = 3.29, P = 0.001). CT values of the right frontal lobe and right temporal lobe in the observation group were (40.09 ± 2.52) HU and (44.93 ± 3.03) HU, respectively. There were no significant differences in CT values of the right frontal lobe and right temporal lobe between the two groups ( tright frontal lobe = 1.89, P = 0.060; tright temporal lobe = 1.89, P = 0.060). There were no significant differences in CT values of the left and right occipital lobes and the left and right parietal lobes between the two groups (all P > 0.05). One-way analysis of variance revealed that the CT values of the left and right frontal lobes were negatively correlated with age (-0.441, -0.211) and course of disease (-0.445, -0.191) (both P < 0.05); the CT values of the left and right frontal lobes were not significantly correlated with 24-item Hamilton Depression Rating Scale score and the number of attacks (all P > 0.05). The CT values of the left and right temporal lobes (-0.207, -0.213), the left and right occipital lobes (-0.185, -0.195) and the left and right parietal lobes (-0.185, -0.180) were negatively correlated with age (all P < 0.05). The CT values of the left and right temporal lobes, the left and right occipital lobes, and the left and right parietal lobes were not significantly correlated with course of disease, 24-item Hamilton Depression Rating Scale score, and the number of attacks (all P > 0.05). Conclusion:The left and right frontal lobe and the left temporal lobe are atrophic in patients with monophasic depression. The degree of atrophy is closely related to the course of disease. Therefore, these findings can be used as a reference for imaging diagnosis of degenerative diseases of the central nervous system.

Objective To investigate the effect of atorvastatin on blood lipid and carotid atherosclerosis in patients with hyperlipidemia and cerebral infarction.Methods 98 patients with hyperlipidemia and cerebral in-farction in our hospital from September 2014 to February 2017 were selected and divided into observation group(49 cases)and control group(49 cases)according to the random number table method.The control group was treated with conventional treatment,the observation group was treated with atorvastatin on the ba-sis of the control group.The two groups were treated for 4 weeks.The ADL score,NIHSS score,blood lipid index,carotid IM T and carotid plaque area were compared between the two groups before and after treatment. Results ADL score of the patients in the observation group after treatment higher was than the control group (t=12.7783,P<0.05),NIHSS score was lower than the control group(t=10.941,P<0.05);LDL-C,TC and TG levels after treatment in the observation group were than in the control group(t= 17.239,9.216, 9.800,P<0.05),while the HDL-C level was higher than the control group(t=7.683.P<0.05);the patients in the observation group were treated by carotid artery IM T and carotid plaque area was higher than that of the control group(t=8.919,6.344,P<0.05).Conclusion Atorvastatin can improve hyperlipidemia in pa-tients with cerebral infarction and carotid atherosclerosis,dyslipidemia,has the important research signifi-cance.

A review of management problems found in lifesaving access to emergency care in healthcare organizations at all levels in China, and a reference international critical and emergency care systems and their quality and safety management standards were made by the authors. Based on such and special needs of such access, the paper studied the domestic lifesaving access to emergency care service workflow, and abstracted common management issues on the lifesaving access to emergency care. The study identified key elements of lifesaving access to emergency care management through case analysis, and formulated standard terms for such key elements. Hence a set of standards is developed for quality management fitting healthcare organizations at all levels in China′s lifesaving access to emergency care, serving as the guidance for their standardized management and evaluation.

OBJECTIVE: To study the relationship between fibrinogen level and pathogenesis of sudden sensorineural hearing loss(SSHI.). METHOD: Fifty patients (55 ears) with SSHL within 7 days of the onset were studied: a control group was consist of 50 normal-hearing people who were individually matched on a pairwise basis according to the same gender and age. Both the patients and the normal people were tested for the parameters of hemorheology, blood biochemistry, whole blood cell count and clotting function. RESULT: Fibrinogen level and plasma viscosity in patients with SSHL were significantly higher than that in control subjects. Prothrombin time and activated partial thromboplastic time were significantly less in the patients group than that in the control group (P < 0.05). There were statistical difference. The parameters of blood biochemistry, whole blood cell count and platelet adhesion test of two groups had no significant difference (P > 0.05). CONCLUSION Elevated plasma fibrinogen may be a major pathogenesis of SSHL. An increase in plasma fibrinogen level may lead to elevated plasma viscosity. All these may promote a prothrombin or hypercoagulable state and impair blood perfusion of cochlea.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Fibrinogen ; metabolism ; Hearing Loss, Sensorineural ; blood ; etiology ; Hearing Loss, Sudden ; blood ; etiology ; Hemorheology ; Humans ; Male ; Middle Aged ; Young Adult

Objective To study the relationship between the mammographic features and clinicopathologic characteristics in breast cancer.Methods Digital mammograms of 176 patients with pathologically proved breast cancer were reviewed.X-ray findings were analysed compared with clinical and pathologic data(histological types and axillary nodes status).Results The breast cancer simplely with micro-calcifications was common seen is the young women under 50 years old(27/32,84.4%) and microcalcifications with the mass was common seen in the aged women over 50 years old(53.8%,28/52).Microcalcifications in mammography occurred frequently occurred in 51.9%(14/27)in intra-ductal carcinoma and early invasive carcinoma.The breast cancer with expression of microcalcification cimbined with burr-like mass had a high metastatic rate to axillary lymph nodes(69.4%,25/36).A high metastatic rate of axillary lymph nodes could also be found in the patients with solitary worm-like microcalcification,solitary burr-like tumor and simple non-wormlike microcalcification.Conclusion The X-ray features of breast carcinoma are certainly related to the clinicopathological manifestations.