Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.

Objective:To systematically evaluate the psychological experience of financial toxicity in breast cancer patients.Methods:A computer search was conducted in Web of Science, PubMed, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang, and VIP for qualitative studies on the psychological experience of financial toxicity among breast cancer patients up to April 15, 2023. The Joanna Briggs Institute's quality assessment criteria for qualitative research were used for literature quality evaluation, and an aggregative integration method was applied for data analysis.Results:Ten studies were included, from which 56 distinct themes were extracted. These themes were consolidated into 11 new categories, forming three integrated results: multidimensional negative experiences in coping with financial toxicity, needs and expectations in dealing with financial toxicity, and strategies for dealing with financial toxicity.Conclusions:Breast cancer patients face varying degrees of financial toxicity, negatively impacting their physical and mental health. Healthcare professionals should pay close attention to the characteristics and needs of patients coping with financial toxicity. Continuous assessment of their financial status and implementation of comprehensive intervention strategies and measures through multiple channels and approaches are needed to help reduce the issues of financial toxicity.

[Objective] To explore the association between methyltransferase-like 3 (METTL3) and prostate cancer (PCa) prognosis, so as to establish a novel prognostic prediction model for PCa. [Methods] Public datasets and PCa tissue microarray were used to evaluate the gene and protein expressions of METTL3, the association between METTL3 and Gleason score (GS), and the ability of METTL3 to predict poor outcomes of PCa.A nomogram was constructed to quantitatively evaluate the prognosis of PCa. [Results] The gene and protein expressions of METTL3 were significantly upregulated in PCa tissues compared to normal tissues (P<0.05). Moreover, the expressions of METTL3 were significantly higher in high-risk PCa tissues (GS>7) compared to low-moderate risk PCa tissues (GS≤7) (P<0.05). Patients with elevated expressions of METTL3 exhibited poorer short-term and long-term progression-free and overall survival outcomes when compared to those with lower expressions of METTL3 (P<0.05). In addition, a risk model composed of 7 target genes regulated by METTL3 N6-methyladenine (m6A) modification was established.The 7 target genes were closely associated with the cell cycle process.The protein expression of METTL3 exhibited a significant positive correlation with the protein expression of cell cycle protein B1 (CCNB1) (r=0.30, P=0.002 5). [Conclusion] METTL3 exhibits the potential as a prognostic predictor for PCa, which may affect PCa prognosis through the regulation of the expressions of target genes closely associated with the cell cycle process via m6A modification.

Objective Given the extensive application of machine learning(ML)in medical models and its remarkable learning and generalization capabilities,this study employed automated ML(AutoML)combined with patient demographics and clinical conditions to early assess the risk of failure in bowel preparation prior to colonoscopy.Methods A retrospective analysis was conducted on patients who underwent colonoscopy examinations in Hospital 1 and Hospital 2 from January 2022 to January 2023,and their general and clinical information was collected.According to the Boston bowel preparation scale(BBPS),a BBPS of≤5 was defined as a failure in bowel preparation,>5 was deemed satisfactory.From the data of the two hospitals,we randomly divided the dataset into a training set(n=303)and a validation set(n=76)at an 8∶2 ratio.Least absolute shrinkage and selection operator(LASSO)logistic regression(LR)model was used for feature selection,a nomogram scoring system was constructed,and models were established using AutoML based on five algorithms.Model performance was evaluated through receiver operator characteristic curve(ROC curve),calibration curves,LR-based decision curve analysis(DCA),SHAP plots,and force plots.Results Among the 379 patients,105 cases(27.7%)experienced bowel preparation failure(BBPS≤5).21 study variables were narrowed down to 10 through LASSO with 5-fold cross-validation,resulting in the development of a Nomogram chart with demonstrated reliability via calibration curves.Using the H2O platform and five algorithms[gradient boosting machine(GBM),deep learning(DL),generalized linear model(GLM),Stacked Ensemble and distributed random forest(DRF)],67 models were developed.Stacked Ensemble outperformed the others with an area under the curve(AUC)of 0.871,LogLoss of 0.403,and RMSE of 0.354,surpassing traditional LR model and other models.Variable importance contribution plots indicated significant predictive influences from factors such as the interval between laxative ingestion and examination,history of constipation,completion of laxative regimen,age,and presence of a companion during the procedure.Finally,SHAP plots and force plots revealed variable distribution patterns in binary classification predictions and the impact of variables on predictive outcomes.Conclusion The AutoML model based on the Stacked Ensemble algorithm exhibits clear clinical utility in early prediction of bowel preparation failure risk.Moreover,a clinically applicable column chart scoring tool is constructed.

Objective:To systematically evaluate the qualitative research on human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients′experience of participating in advance care planning (ACP), so as to provide reference for the application of ACP in HIV/AIDS patients.Methods:Computer searched qualitative studies on HIV/AIDS patients′participation in ACP experience in Web of Science, PubMed, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, Wanfang, VIP, China Biomedical Literature Database. The search time limit was from inception to December 1, 2023, and the research results were integrated using Meta integration method after quality evaluation.Results:A total of 10 articles were included, and 58 research results were extracted, forming 12 new categories, and 4 integrated results were obtained: HIV/AIDS patients′understanding of ACP; attitudes of HIV/AIDS patients towards ACP; the influencing factors of HIV/AIDS patients′participation in ACP; suggestions for implementing ACP for HIV/AIDS patients.Conclusions:Medical staff should promptly identify the needs of HIV/AIDS patients for ACP, help them increase their awareness and acceptance of ACP. At the same time, based on China′s unique cultural background and healthcare system, relevant laws and regulations should be continuously improved to promote the development and improvement of ACP in China.

Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Renal cell carcinoma is a malignant tumor originating from renal tubular epithelial cells. Its pathogenesis is complicated, with no typical early clinical symptoms. Most patients are already in the advanced stage at the time of diagnosis and have a high mortality rate. The development mechanism and treatment strategy of renal cell carcinoma are the current research focus. In recent years, non-coding RNA has been proved to play a crucial role in regulating tumor progression. Among them, circular RNA plays a unique role in tumor development due to its nonlinear structure. The dysregulation of circular RNA is closely related to the progression of a series of diseases including metabolic diseases and cancer. Similarly, circular RNA plays a key role in the progression, treatment, and prognosis prediction of renal cell carcinoma. This article briefly reviews role of circular RNA in renal cell carcinoma, hoping to bring new research directions for the diagnosis and treatment of renal cell carcinoma.

Objective:To systematically analyze and evaluate the psychological experience of chemotherapy-induced alopecia (CIA) in breast cancer patients.Methods:The qualitative study on the CIA psychological experience of breast cancer patients was searched through computers in Web of Science, PubMed, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database, WanFang Data and VIP. The search period was from the establishment of the database to October 15, 2022. The quality evaluation of literature that met the criteria was conducted using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center in Australia, and the results of each study were further integrated and analyzed.Results:A total of 11 articles were included and 59 clear themes were extracted. The similar themes were summarized into 12 new categories and integrated into 4 synthesized results, namely, breast cancer patients' differential coping styles with alopecia, different psychological feelings, difficulties and challenges they faced, and desire for support and needs.Conclusions:CIA affects the physical and mental health and social interaction of breast cancer patients. Medical and nursing staff should pay attention to the cognition and experience of breast cancer patients on alopecia symptoms, establish effective communication between nurses and patients, strengthen health education on alopecia knowledge, encourage patients to actively respond, so as to reduce alopecia problems and improve the quality of life.

We present a case of a postmenopausal women with hyperandrogenic symptoms and virilization signs , such as hirsutism, alopecia, acne and clitoromegaly, which was pathologically confirmed to be an ovarian steroid cell tumor, not otherwise specified(NOS). The levels of testosterone, dehydroepiandrosterone sulfate and estradiol in serum were increased, while the levels of luteinizing hormone and follicle stimulating hormone were decreased. Computed tomography(CT) scan and magnetic resonance imaging(MRI) identified a solid, left ovarian tumor and detected an additional tumor of hypodensity in the left adrenal gland. ACTH stimulation test, hCG stimulation test, adrenal and ovarian vein sampling indicated that excessive androgens were derived from the ovary. After the injection of gonadotropin hormone analogues(GnRHa), testosterone levels dropped to the normal range. Laparoscopic bilateral adnexectomy was performed, and pathology indicated NOS. The purpose of this report is to improve the understanding of NOS with hyperandrogenic presentation.

OBJECTIVE: To investigate the effect of palbociclib on cell cycle progression and proliferation of human renal tubular epithelial cells. METHODS: Human renal tubular epithelial cell line HK-2 was treated with 1, 5, 10, and 20 μmol/L of palbociclib, and the changes in cell proliferation and viability were examined by cell counting and CCK8 assay. EDU staining was used to assess the proliferation of HK-2 cells following palbiciclib treatment at different concentrations for 5 days. The effect of palbociclib on cell cycle distribution of HK-2 cells was evaluated using flow cytometry. SA-β-Gal staining and C12FDG senescence staining were used to detect senescence phenotypes of HK-2 cells after palbociclib treatment at different concentrations for 5 days. The relative mRNA expression levels of P16, P21, and P53 and the genes associated with senescence-related secretion phenotypes were detected by RT-PCR, and the protein expressions of P16, P21 and P53 were detected by Western blotting. RESULTS: Palbociclib inhibited HK-2 cell proliferation and induced cell cycle arrest in G1 phase. Compared with the control cells, HK-2 cells treated with high-dose (10 μmol/L) palbociclib exhibited significantly suppressed cell proliferation activity, and the inhibitory effect was the most obvious on day 5 ( CONCLUSIONS Palbociclib induces HK-2 cell senescence by causing cell growth arrest and delaying cell cycle progression.
Cell Cycle ; Cell Cycle Checkpoints ; Cellular Senescence ; Epithelial Cells ; Humans ; Piperazines/pharmacology* ; Pyridines/pharmacology* ; Tumor Suppressor Protein p53/genetics*