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*

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective To identify symptom clusters in breast cancer patients undergoing chemotherapy and investigate the bridge symptoms that connect the symptom clusters,therefore to provide a guidance for precise intervention in the symptoms.Methods From October 2022 to October 2023,convenience sampling method was employed to selelct 340 breast cancer patients,who underwent postoperative chemotherapy,for investigation in the related symptom clusters and quality of life by using Anderson symptom assessment scale and breast cancer quality of life scale.Cluster analysis was performed to extract the symptom clusters by R software and the impacts of each symptom cluster on quality of life were analysed by stratified regression.A contemporaneous symptom network was constructed to identify the bridge symptoms.Results All 327 patients had completed the study.Three distinct symptom clusters were extracted:-gastrointestinal,psychological and neurological symptom clusters.The gastrointestinal cluster alone accounted for 10.2%of the variation in quality of life.Network analysis highlighted that distress(rbe=3.927,rbs=3.927,rbc=0.436),fatigue(rbe=3.907,rbs=3.907,rbc=0.434)and lack of appetite(rbe=3.842,rbs=3.842,rbc=0.427)were the bridging symptoms which had high expected influence coefficient,strength and closeness centrality index.Conclusion The gastrointestinal symptom cluster makes notably impact on the quality of life in breast cancer patients undergoing chemotherapy.Fatigue,lack of appetite and distress are the bridge symptoms in symptom management strategies in potentially improving the efficiency of intervention and reducing the costs to patient.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

A good integration of dental implants and the surrounding soft tissue is essential to ensure the long-term effect of implant. In this review, we summarized the research progress of peri-implant soft tissue integration of dental titanium implants, with emphasis on the modification of the gingival interface of implants based on immune microenvironment regulation. This method influences the immune response around the implant by promoting the surface properties of implants, so as to enhance the peri-implant soft tissue integration. The purpose of this review is to provide reference for the related research and clinical application in the field of dental implantation.

Objective:To explore the relationship between overweight and obesity, high blood pressure and left ventricular hypertrophy (LVH) in adolescents in Tangshan.Methods:Through cluster sampling, 1 023 adolescents aged 7-18 were selected from primary and secondary schools in Tangshan (January 2018 to January 2020). Questionnaire survey, blood pressure, weight, height measurement and ultrasound examination were performed. The incidence of LVH in 1 023 adolescents was statistically analyzed. 1 023 adolescents were divided into four groups according to whether they were overweight or obesity (overweight: weight for age Z score >2; obesity: height for age Z score >2) and whether blood pressure was high [high blood pressure: systolic blood pressure (SBP) or diastolic blood pressure (DBP)≥gender/age P 90 and

Objective:To evaluate the imaging features of CT scan in patients with COVID-19.Methods:Clinical data of 56 patients with COVID-19 from January 17 to 19, 2020 admitted to Wenzhou Central Hospital and the Second Affiliated Hospital of Wenzhou Medical University were retrospectively reviewed. The clinical manifestations, lung imaging characteristics and treatment outcomes of patients with different severity were analyzed with SAS software.Results:Fever (92.8%, 52/56), dry cough (75.0%, 42/56) and asthenia (58.9%, 33/56) were the first symptoms in most of the patients; some patients also had shortness of breath (25.0%, 14/56) and pharyngeal pain (10.7%, 6/56). Chest high-resolution CT scan showed that in 42 moderate patients, ground glass-like high-density shadows in the lung were observed in 30 cases (71.4%) ; localized plaque consolidation shadows and bronchial inflation signs were observed in 10 cases (23.8%). In 12 severe patients, 11 had high-density patches involving multiple lung lobes (≥3). In 2 critically ill patients the patches and stripes involving the entire lung were observed; and cord-like high-density shadow, local consolidation and fibrosis were also shown.Conclusion:The multiple ground-glass changes outside the lungs are early imaging manifestations of COVID-19 patients. The increase in pulmonary lobe consolidation and fibrosis may indicate the disease progression, and the degree of lung consolidation and fibrosis is closely related to the disease severity.

Objective: To analyze the prognostic value of baseline serum free light chain (sFLC) in immunoglobulin light-chain cardiac amyloidosis (AL-CA) . Methods: Thirty patients diagnosed with AL-CA from January 2012 to December 2016 at Beijing Chaoyang Hospital were included in this study to retrospectively evaluate the clinical data. The cut-off value of dFLC (involved sFLC minus uninvolved sFLC) was determined according to the receiver operator characteristic curve (ROC) and grouped, the prognoses of both groups were evaluated. Results: The onset age of all AL-CA patients was 57 years old. It occurred more commonly in men (21 cases, 70%) and the light chains of immunoglobulin composed mainly of type λ (22 cases, 73.3%) . Renal involvements occurred in 17 cases (56.7%) . The median value of difference between involved and uninvolved serum immunoglobulin free light chain levels (dFLC) was 162.9 (57.9-401.6) mg/L. More subjects in the high dFLC group had higher BNP (P=0.005) , and shorter median survival than those in the low dFLC group (15 months vs 47 months, P<0.001) . Similar results of median survival were observed when the patients were redivided by a new cut-off value of 180 mg/L for dFLC (high dFLC group: 22 months, low dFLC group: 40 months, P=0.001) , or a κ/λ ratio in which patients with κ type sFLC-ratio<3.79 and λ type sFLC-ratio≥0.06 were grouped into the low sFLC-ratio (37 months) , and the reverse the high sFLC-ratio ones (25 months, P=0.021) . In multivariate analysis, dFLC and New York Heart Association (NYHA) classification of cardiac function were two risk factors associated with all-cause mortality in patients, of them the hazard ratio for higher dFLC was 12.13 (95%CI 2.98-49.30, P<0.001) . Conclusion Measurement of the sFLC level could implicate the prognosis of AL-CA.

Objective    Through the perioperative outcome analysis of da Vinci robot-assisted sleeve lobectomy, to clarify its efficacy and safety. Methods    A retrospective analysis was performed on 10 patients with centrally located lung cancer undergoing robot-assisted sleeve lobectomy from March to December 2019 in our center, including 9 males and 1 female, aged 45-67 (55.0±8.9) years. Preoperative imaging and bronchoscopy showed central non-small cell lung cancer, involving the right upper lung in 3 patients, right lower lung in 2 patients, the left upper lung in 4 patients, and left lower lung in 1 patient. The operation time, Docking time, intraoperative blood loss volume, bronchial anastomosis time, number of dissected lymph nodes, drainage volume and postoperative hospital stay were analyzed. Results    The da Vinci robot-assisted bronchial sleeve lobectomy was completed smoothly on 10 patients. The operation time was 135-183 (157.8±14.3) min, Docking time 6-15 (10.0±2.9) min, intraoperative blood loss volume 55-250 (124.5±61.8) mL, bronchial anastomosis time 17-40 (27.7±7.3) min, the number of dissected lymph nodes 16-23 (19.7±2.8), the drainage volume 200-600 (348.0±148.4) mL and postoperative hospital stay 7-11 (8.7±1.6) d. All patients had no bronchopleural fistula, pulmonary infection or atelectasis, and there was no perioperative death. Postoperative pathological findings were all squamous cell carcinoma. Conclusion    Da Vinci robot-assisted sleeve lobectomy is safe and effective.

Objective: To describe the distribution characteristics of uric acid and associated factors among overweight and obese children in Tangshan City, so as to provide reference for the prevention of childhood hyperuricemia and related diseases. Methods: A total of 543 overweight and obese school-age children in Tangshan from 2018 to 2019 were selected, 503 children of normal weight were selected as the control group. Height, weight, waist circumference(WC), blood pressure(BP) were measured, then the Body mass index(BMI) and waist-to-height ratio(WHtR) were calculated. Uric acid(UA), fasting blood glucose(FPG), total cholesterol(TC), triglyceride(TG), high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C) were measured. The distribution characteristics of uric acid level were described by age groups, and the relationship between uric acid and related indicators were analyzed. Results: The mean uric acid of normal weight group,overweight and obese group were(278.15±89.68, 322.72±89.50)μmol/L respectively, the difference was statistically significant(t=-8.04, P<0.01). The detection rates of hyperuricemia in normal weight group, overweight and obesity group were 11.33% and 23.94% respectively, with statistically significant difference(χ2=28.28, P<0.01). UA level was positively correlated with age, BMI, body weight, TC, LDL-C(r=0.12，0.17，0.28，0.14，0.23，P<0.01), and negatively correlated with HDL-C(r=-0.25，P<0.01). Age, BMI, WHtR, TC, LDL-C were the influencing factors of hyper-uricemia[OR(95%CI)=0.82(0.72-0.94), 1.13(1.08-1.18), 0.38(0.23-0.64), 6.79(2.15-21.44), 0.04(0.01-0.14). Conclusion The urea level and high uric acid detection rate of overweight and obese children in Tangshan were higher than those of normal weight children. Age, obesity and dyslipidemia were influencing factors of hyperuricemia in obese and overweight children.