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*

OBJECTIVES: This study aimed to clarify the effects of Foxp3 silencing on the expression of inflammatory cytokines in human periodontal ligament cells (hPDLFs) in an inflammatory environment and on cell proliferation and invasiveness, as well as to explore the role of Foxp3 gene in the development of periodontitis. METHODS: An small interfering RNA (siRNA) construct specific for Foxp3 was transfected into hPDLFs. Foxp3 silencing efficiency was verified by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, and the siRNA with the optimum silencing effect of Foxp3 gene was screened. Using lipopolysaccharide to simulate an inflammatory environment in vitro, CCK-8 detected the effect of silencing Foxp3 on hPDLFs proliferation under inflammatory conditions. Wound-healing experiments and transwell assays were conducted to detect the effect of silencing Foxp3 on hPDLF migration under inflammatory conditions. The expression of the inflammatory cytokines interleukin (IL)-6 and IL-8 was detected by RT-PCR and Western blotting under inflammatory conditions. RESULTS: After siRNA transfection, RT-PCR and Western blotting analyses showed that the expression of Foxp3 mRNA in the Foxp3-si3 group decreased significantly (t=21.03, P<0.000 1), and the protein expression of Foxp3 also decreased significantly (t=12.8, P<0.001). In the inflammatory environment, Foxp3 gene silencing had no significant effect on hPDLFs proliferation (P>0.05), and Foxp3 gene silencing promoted hPDLFs migration (P<0.05). Moreover, the expression of IL-6 and IL-8 increased (P<0.05). CONCLUSIONS In an inflammatory environment, Foxp3 gene silencing promoted hPDLFs migration but had no significant effect on hPDLFs proliferation. The expression of inflammatory factors expressed in hPDLFs increased after Foxp3 gene silencing, indicating that Foxp3 gene inhibited inflammation in periodontitis.
Humans ; Cell Proliferation/genetics* ; Cells, Cultured ; Cytokines/metabolism* ; Fibroblasts/metabolism* ; Forkhead Transcription Factors/metabolism* ; Gene Silencing ; Interleukin-6/metabolism* ; Interleukin-8/metabolism* ; Periodontal Ligament/metabolism* ; Periodontitis/metabolism* ; RNA, Small Interfering/metabolism* ; Transcription Factors/metabolism*

Objective:To investigate the effect of ship-shaped expanded polytetrafluoroethylene (e-PTFE) nasal prosthesis in rhinoplasty.Methods:From February 2016 to June 2021, 86 patients, including 9 males and 77 females, aged 18-47 (24±5) years old, were admitted to Chengdu High-tech Zone Xinyuerong Medical Aesthetic Clinic for cosmetic treatment of rhinoplasty. All patients underwent rhinoplasty with the application of ship-shaped e-PTFE and autologous cartilage. The postoperative complications, glabellar fullness, inverted brow triangle, nasal polygon aesthetic shape and patient satisfaction were evaluated. These data were measured and analyzed, including the nasal length, nasal tip height, nasal frontal angle and nasal facial angle before and after the operation.Results:In 86 patients, the incision healed in one stage after surgery, and 8 cases had nasal vestibular scar hyperplasia. All patients were followed up for 1-5 years: 84 cases obtained satisfactory nasal morphology, and 2 cases recovered naturally after adjusting and lowering the prosthesis height half a year after surgery because the interbrow area was too full. 74 patients (86%) were very satisfied, 10 cases (11.6%) were satisfied. The nasal length was (4.07±0.20) cm, the nasal tip height was (2.66±0.36) cm, the nasal frontal angle was (106.42±8.04)°, and the nasal face angle was (15.90±0.85)°before operation. The nasal length was (4.23±0.20) cm, the nasal tip height was (2.59±0.26) cm, the naso-frontal angle was (113.69±6.34)°, and the naso-facial angle was (21.57±0.78)° at eighteen months after operation. There were statistically significant differences in nasal length, naso-frontal angle and naso-facial angle ( t=-5.51, -5.96, -52.31, P<0.01), but no statistically significant differences in nasal tip height ( t=1.47, P=0.146). Conclusions:The ship-shaped e-PTFE can be shaped to reflect the aesthetic of the nose dorsum, which is similar to the anatomical structure of the nose dorsum, increase the stability and authenticity of the prosthesis, and is worthy of clinical application.

Objective : To investigate the effect of transforming growth factor β1 (TGF-β1) on human periodontal ligament fibroblasts (hPDLFs) stimulated by lipopolysaccharide from Porphyromonas gingivalis (Pg-LPS). Methods: hPDLFs were obtained and identified by immunohistochemistry. The stimulating concentration of Pg-LPS was determined by qRT-PCR and CCK-8. The hPDLFs were divided into 4 groups: blank control group, 100 μg/mL pure Pg-LPS; low concentration group, 1 ng/mL TGF-β1+100 μg/mL Pg-LPS; medium concentration group, 10 ng/mL TGF-β1+100 μg/mL Pg-LPS; and high concentration group 100 ng/mL TGF-β1+100 μg/mL Pg-LPS. Cell proliferation was measured by CCK-8 assay at 72 hours, cell migration was measured by scratch and Transwell chamber assays at 24 hours, and the cell cycle of the hPDLFs was measured by flow cytometry at 72 hours. The expression of Forkhead/winged helix transcription factor p3 (Foxp3), interleukin-6 (IL-6) and Epstein-Barr virus-induced gene 3 (EBI3) mRNA in hPDLFs at 72 hours was measured by qRT-PCR, and the expression of Foxp3, IL-6 and EBI3 proteins in hPDLFs at 72 hours was detected by western blot. Results : The immunohistochemistry results showed that anti-vimentin was positive and anti-keratin was negative. At a concentration of 100 μg/mL Pg-LPS, the expression of IL-6 mRNA in hPDLFs was increased (P<0.000 1), and the proliferation of hPDLFs was decreased (P<0.000 1). Therefore, 100 μg/mL PG-LPS was selected to simulate the inflammatory state. 10, 100 ng/mL TGF-β1 could improve the proliferation ability of hPDLFs in inflammatory state (P<0.000 1) ; 1, 10 and 100 ng/mL TGF-β1 could promote the migration ability of hPDLFs in inflammatory state (P<0.000 1). 1, 10 and 100 ng/mL TGF-β1 could accelerate the cell cycle of hPDLFs in inflammatory state (P<0.000 1). 1, 10 and 100 ng/mL TGF-β1 could inhibit the expression of IL-6 gene and protein in hPDLFs in inflammatory state (P<0.000 1), 1 and 10 ng/mL TGF-β1 could increase the expression of EBI3 gene and protein in hPDLFs in inflammatory state (P<0.000 1). 1, 10 ng/mL TGF-β1 could increase the expression level of Foxp3 gene in hPDLFs in inflammatory state, and 10 ng/mL TGF-β1 could increase the expression level of Foxp3 protein (P<0.05). Conclusion TGF-β1 can promote the proliferation and migration of hPDLFs under inflammatory conditions, upregulate EBI3 and inhibit inflammation, which may be related to the expression of the transcription factor Foxp3.

Objective:To explore the epidemiological characteristics, clinical characteristics, treatment strategies and clinical results of non-dislocated hyperextension tibial plateau fracture.Methods:A total of 25 cases of non-dislocated hyperextension tibial plateau fracture patients were collected, including 12 males and 13 females, aged 27-79 years with an average age of 51±15 years. Causes of injury: 18 cases of traffic accident, 2 cases of heavy injury, 5 cases of falling injury. Schatzker classification of tibial plateau fracture: 4 cases of type II, 5 cases of type IV, 13 cases of type V, 3 cases of type VI. Three columns theoretical classification: 4 cases of simple lateral column, 5 cases of simple medial column, 7 cases of medial column+lateral columns, 9 cases of three columns. Preoperative tibial plateau posterior slope angle was -10-0 degrees, average-5.2 degrees. Preoperative MRI showed 5 cases of medial collateral ligament (MCL) injury, 3 cases of posterolateral complex (PLC) complex injury, 2 cases of PLC+ posterior cruciate ligament (PCL) injury and 10 cases of menisci injury. The change of tibial plateau posterior slope angle was more than 10 degrees in patients with ligament injury, 5 patients had a tibial plateau posterior slope angle change more than 15 degrees, 5 patients had a tibial plateau posterior slope angle change more than 10 degrees, and the patients with a tibial plateau posterior slope angle change less than 10 degrees had no ligament injury; 6 patients with simple lateral column or medial column fracture had a ligament injury, 2 patients with medial column+lateral column fracture had a ligament injury, and 2 patients with three column fracture had a ligament injury.Results:All patients were followed up for 12-24 months, with an average of 16.4 months. The operation time was 124±33 min (65-180 min), and the bleeding volume was 106±48 ml (20-200 ml). All patients were treated by open reduction and internal fixation. According to the characteristics of fracture, targeted reduction of articular surface and restoration of lower limb force line were carried out. The plate was placed on the anterior part of tibial plateau to fix the fracture fragment. Evaluation of postoperative fracture reduction: 20 cases were anatomic reduction, 5 cases were good reduction (between 2-5 mm articular surface collapse), and the excellent rate of fracture reduction was 100%. Internal fixation: 4 cases were treated with simple lateral plate, 2 cases with simple medial plate, 15 cases with medial+ lateral plate, 1 case with medial plate+ lateral anchor suture, 1 case with medial plate+ posterior screw, 1 case with lateral plate+ fibular screw, 1 case with medial plate + lateral plate+ lateral anchor suture. The meniscus was repaired in 8 patients, including 5 medial and 3 laterals. The fracture healing time was 3-6 months (mean 3.3 months). The postoperative knee Rasmussen score was 24.9±3.5 (18-29), and the postoperative knee joint mobility was 118°±9° (90°-130°). Superficial infection occurred in 2 patients.Conclusion:The main imaging characteristic of "non-dislocated hyperextension tibial plateau fracture" is the change of tibial plateau posterior slope angle. The injury of single anteromedial column/anterolateral column fracture is easy to combine with the "diagonal" injury, and when the tibial plateau posterior slope angle changes more than 10 degrees, it is easy to be associated with peripheral ligament injury. By using open reduction and internal fixation, restoring the joint articular surface and lower limb force line, repairing the soft tissue structure and ligament, and reconstructing the stability of knee joint, we can achieve satisfactory results.

Objective To evaluate the clinical efficacy of combined anteversion angle of femoral neck-acetabulam in Crowe Ⅳ developmental dysplasia of the hip (DDH) with Wagner Cone total hip arthroplasty. Methods From June 2013 to February 2016,45 cases of CroweⅣDDH were treated with no femoral shortening osteotomy in THA ,including 25 females and 20 males. The outcomes of anteversion angle of femoral neck and acetabulam were measured in CT scan of hip jiont. The outcomes of abduction angle ,hip center were measured radiologically in X-ray of pelvis. Postoperative function was scored by Harris scoring system. Results The mean follow-up time of the 45 patients was(3.2 ± 0.8)years. Using loosening or revision as the end point ,the survival rate was 100%. The outcomes of preoperative anteversion angle of acetabulam,femoral neck,acetabulam-femoral neck was(27.70 ± 5.35)°,(47.76 ± 7.25)°,and(74.90 ± 8.43)° in CroweⅣgroup,and those of postoperative anteversion angle was(19.82 ± 2.41)° ,(23.35 ± 3.84)° and(44.90 ± 5.18)° ,respectively. There was significant difference between the two groups(P < 0.05). The average height of preoperative dislocation in femoral head was (5.8 ± 1.2)cm and the postoperative average displacement of femoral lesser trochanter was (3.6 ± 0.8)cm. The Harris hip score was improved from preoperative(46.66 ± 7.28)to(90.36 ± 4.72). For most patients,hip pain were significantly relieved ,range of motion of the hip was improved ,and the gait returned to normal. Femoral nerve injury occurred in 2 cases and the case recovered after 3 months respectively. Conclusions The deformity of hip and the stability and matching degree of the prosthesis was evaluated with the combined anteversion angle of femoral neck-acetabulam in CroweⅣDDH. The Wagner Cone can effectively maintain the stability of the hip joint in the non-amputated total hip replacement.

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 explore the correlation between verbal memory and working memory in patients with alcohol dependence (AD).Methods A total of 40 patients with AD and 40 health controls were included in this study.N-back task was used to evaluate the verbal working memory.20 sets of phrases were used to evaluate long-term verbal memory.Results Correct number of verbal memory in AD group ((5.15±0.92)times) was lower than that of HC group ((7.35±3.07) times) after one-week baseline test,and the difference was statistically significant (t=4.344,P＜ 0.01).Compared with HC group ((1 436.37±192.50) ms,(1.08±0.89) times,(4.00±0.85) times,respectively),AD group((1 535.40± 192.50) ms,(1.90± 1.57)times,(2.60± 1.39)times) showed significantly impaired reply reaction time of 2-back,error number of 1-back and 2-back (t=-2.112,P=0.038;t=-2.899,P=0.005;t=-5.433,P＜0.01).The error number of 2-back task in AD group was negative correlated with verbal memory after one-week baseline test (r=-0.427,P=0.006).Conclusion The verbal memory is impaired in AD patients.Long-term verbal memory damage have a certain correlation with working memory.

Objective To investigate the attention network in patients with obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD).Methods 31 GAD patients,31 OCD patients and 30 healthy controls (HC) were tested with attention network test.Results There were significant differences in the main effects with respect to the alerting network(15.87±5.24,26.77±4.33,34.87±3.47) (F=4.619,P=0.012)) and the executive network(114.84±9.64,122.45±5.57,96.57±5.45) (F=3.388,P=0.038) among the OCD,GAD and HC groups.The three groups did significantly differ in RT of the attention network (F=19.808,P=0.000).For the HC group,there was significant main effects with respect to cue conditions(F=29.699,P=0.000).There was a significant correlation between the executive network and Hamilton anxiety scale (r=0.351) and also a significantly negative correlation between the alerting network and Hamilton depression scale (r=-0.267).Conclusion There are attention network damages in patients with OCD and GAD,which may be involved in the impairment of emotion.