Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To investigate the relevant data on radiation dose in interventional radiodiagnosis and radiology of adults in Beijing and to provide a basis for establishing relevant diagnostic reference levels (DRLs) in this region.Methods:A total of 30 medical institutions in Beijing were surveyed, covering interventional radiodiagnosis and radiology surgeries for coronary artery, structural heart diseases, permanent cardiac pacemaker implantation, electrophysiological study and radiofrequency ablation, nervous systems, abdominal systems, and the blood vessels of the lower limbs. The primary parameters investigated included the air kerma area product ( PKA) and incident air kerma ( Ka, r). The 75 th percentiles of radiation dose were considered DRLs, which were analyzed at both the overall and individual medical institution levels. Results:A total of 3 331 cases of the abovementioned radiodiagnosis and radiology surgeries were collected. The DRLs (i.e., PKA and Ka, r) of various diagnostic examinations were 37.87 Gy·cm 2 and 509.00 mGy for coronary artery, 9.34 Gy·cm 2 and 48.00 mGy for electrophysiological study and radiofrequency ablation, 218.50 Gy·cm 2 and 901.70 mGy for nervous systems, 81.00 Gy·cm 2 and 302.20 mGy for the abdominal system, and 83.37 Gy·cm 2 and 214.69 mGy for the blood vessels of the lower limbs. In contrast, the DRLs (i.e., PKA and Ka, r) for interventional radiodiagnosis and radiology were determined at 135.00 Gy·cm 2 and 1 897.58 mGy for coronary artery, 26.91 Gy·cm 2 and 172.30 mGy for structural heart diseases, 27.77 Gy·cm 2 and 87.75 mGy for permanent cardiac pacemaker implantation, 34.46 Gy·cm 2 and 247.00 mGy for electrophysiological study and radiofrequency ablation, 214.36 Gy·cm 2 and 1 282.80 mGy for the nervous system, 196.64 Gy·cm 2 and 875.71 mGy for abdominal system, and 108.25 Gy·cm 2 and 523.25 mGy for the blood vessels of the lower limbs. Conclusions:The DRLs of radiation dose in interventional radiodiagnosis and radiology in Beijing were determined through a survey and statistic analysis. These findings suggest that for certain interventional procedures, the optimized radiation protection should be enhanced.

Objective:To systematically evaluate the incidence and influencing factors of postoperative stroke in patients with acute type A aortic dissection (ATAAD).Methods:Nine Chinese and English databases, including PubMed, Embase, CINAHL, JAMA, The Cochrane Library, CNKI, Wanfang, Vip and Chinese Biomedicine, were searched by computer to include literatures evaluating the incidence of postoperative stroke and its influencing factors in ATAAD patients. The search period was from the establishment of the database to September 2024. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 14.0 software was used to combine the prevalence rate, and descriptive analysis of influencing factors was performed.Results:A total of 22 articles were included, including 16 734 ATAAD patients, published from 2018 to 2024. Meta-analysis results showed that the incidence of postoperative stroke in ATAAD patients was 16% (14%-18%). Subgroup analyses showed a higher incidence of postoperative stroke in patients with ATAAD in Europe (19%, 95% CI: 15%-23%), with a sample size of 1 to 300 patients (18%, 95% CI: 14%-22%), and in 2024 (20%, 95% CI: 14%-28%). Descriptive analysis shows that the factors influencing the occurrence of postoperative stroke in ATAAD patients include preoperative history (preoperative hypotension, preoperative history of stroke, history of carotid artery disease, history of cardiac arrest), intraoperative measures (total arch replacement, femoral artery intubation, anterograde cerebral perfusion, intraoperative oxygen satiation), and various types of time (cryopreservation time, extracorporeal circulation time, operation time). Conclusion:The incidence of postoperative stroke is higher in ATAAD patients. Preoperative hypotension, history of stroke before surgery, history of carotid artery disease, history of cardiac arrest, total arch replacement, femoral artery intubation, anterograde cerebral perfusion, decrease of cerebral oxygen saturation during operation, and longer hypothermia stop time, cardiopulmonary bypass time and operation time may increase the risk of postoperative stroke in ATAAD patients.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

Objective: To investigate the role of murine double minute 2(MDM2) in dihydroartemisinin′s(DHA) inhibition of lung adenocarcinoma cell proliferation and migration. Methods: CCK8 assay was used to detect the inhibitory effect of gradient concentrations of DHA(0, 5, 10, 25, 50 and 100 μmol/L) and time gradients(0, 24, 48, and 72 h) on the proliferation of lung adenocarcinoma A549 and PC9 cells, and the half maximal inhibitory concentrate(IC50) were calculated respectively. Colony formation and scratch assays were used to detect the inhibitory effects of DHA on colony formation and migration of A549 and PC9 cells. Western blot was used to detect the inhibitory effects of DHA on MDM2 expression and epithelial-mesenchymal transition(EMT)-related proteins E-cadherin and N-cadherin. The promoting effects of MDM2 on proliferation, migration and EMT of lung adenocarcinoma cells were verified by small interfering RNA-mediated knockdown of MDM2(si-MDM2). The reversal effects of MDM2 overexpression on DHA′s inhibition on the proliferation and migration of A549 and PC9 cells were observed. Results: DHA inhibited the proliferation of A549 and PC9 cells in a dose⁃ and time⁃dependent manner,with IC50 values of 30. 57 and 78. 61 μmol/L , respectively. Compared with the Control group , A549 and PC9 cells had significantly decreased colony formation (both P < 0. 01) and migration (both P < 0. 01) upon treatment with DHA. Moreover, DHA significantly inhibited the protein expression levels of MDM2 and N ⁃cadherin in A549 and PC9 cells , and upregulated the expression of E ⁃cadherin protein (both P < 0. 05) . Compared with si⁃Control ,si⁃MDM2 significantly inhibited the protein levels of MDM2 and N ⁃cadherin in A549 and PC9 cells , and upregulat⁃(both P < 0. 01) of both cells. After overexpression of MDM2 in A549 and PC9 cells , the proliferation and migra⁃ tion ability were significantly enhanced (both P < 0. 05) , and the inhibitory effects of DHA were partially reversed by MDM2 overexpression (both P < 0. 05) . Conclusion DHA effectively inhibits the proliferation and migration of lung adenocarcinoma cells , and its mechanism is associated with the suppression of MDM2.

AIM To prepare the borneol-menthol eutectic mixture-loaded nanoemulsion gel of tetramethylpyrazine.METHODS The equilibrium solubilities of tetramethylpyrazine in different oil phases,emulsifiers and co-emulsifiers were determined,after which compatibility experiment was performed,and pseudo-ternary phase diagram was drawn.With Km value,oil phase proportion and water phase consumption as influencing factors,particle size,PDI and saturated drug loading as evaluation indices,the formulation was optimized by central composite design-response surface method.The drug-loaded nanoemulsion was dispersed into carbomer 940 gel matrix to prepare nanoemulsion gel,then the physicochemical properties,in vitro drug release and transdermal absorption properties were investigated.RESULTS The optimal formulation was determined to be 3.31∶6.16∶1.56∶88.97 for eutectic mixture-EL-40-1,2-propylene glycol-water ratio,the particle size,PDI and saturated drug loading were 37.85 nm,23.04 and 5.82 mg/g,respectively.The obtained white,semi-solid nanoemulsion gel demonstrated the average pH value and viscosity of 6.68±0.07 and(289.69±1.06)mPa·s,respectively,whose in vitro drug release accorded with Higuchi equation,and the accumulative permeability per unit area was(2 048.23±55.6)μg/cm2 within 24 h,which were 3.72 and 1.21 times higher than those of hydrogel and aqueous solution,respectively.CONCLUSION The borneol-menthol eutectic mixture-loaded nanoemulsion gel of tetramethylpyrazine meets preparation requirements,thus can achieve the effective transdermal delivery of raw medicine.

Objective:To investigate the relevant data on radiation dose in interventional radiodiagnosis and radiology of adults in Beijing and to provide a basis for establishing relevant diagnostic reference levels (DRLs) in this region.Methods:A total of 30 medical institutions in Beijing were surveyed, covering interventional radiodiagnosis and radiology surgeries for coronary artery, structural heart diseases, permanent cardiac pacemaker implantation, electrophysiological study and radiofrequency ablation, nervous systems, abdominal systems, and the blood vessels of the lower limbs. The primary parameters investigated included the air kerma area product ( PKA) and incident air kerma ( Ka, r). The 75 th percentiles of radiation dose were considered DRLs, which were analyzed at both the overall and individual medical institution levels. Results:A total of 3 331 cases of the abovementioned radiodiagnosis and radiology surgeries were collected. The DRLs (i.e., PKA and Ka, r) of various diagnostic examinations were 37.87 Gy·cm 2 and 509.00 mGy for coronary artery, 9.34 Gy·cm 2 and 48.00 mGy for electrophysiological study and radiofrequency ablation, 218.50 Gy·cm 2 and 901.70 mGy for nervous systems, 81.00 Gy·cm 2 and 302.20 mGy for the abdominal system, and 83.37 Gy·cm 2 and 214.69 mGy for the blood vessels of the lower limbs. In contrast, the DRLs (i.e., PKA and Ka, r) for interventional radiodiagnosis and radiology were determined at 135.00 Gy·cm 2 and 1 897.58 mGy for coronary artery, 26.91 Gy·cm 2 and 172.30 mGy for structural heart diseases, 27.77 Gy·cm 2 and 87.75 mGy for permanent cardiac pacemaker implantation, 34.46 Gy·cm 2 and 247.00 mGy for electrophysiological study and radiofrequency ablation, 214.36 Gy·cm 2 and 1 282.80 mGy for the nervous system, 196.64 Gy·cm 2 and 875.71 mGy for abdominal system, and 108.25 Gy·cm 2 and 523.25 mGy for the blood vessels of the lower limbs. Conclusions:The DRLs of radiation dose in interventional radiodiagnosis and radiology in Beijing were determined through a survey and statistic analysis. These findings suggest that for certain interventional procedures, the optimized radiation protection should be enhanced.