Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.

Objective:To provide theoretical basis for the relevant mechanisms in diabetic retinopathy by bioinformatics methods.Methods:Proliferative diabetic retinopathy(PDR)datasets GSE60439 and GSE94019 were screened through GEO database.Expres-sion data of GSE60439 dataset was extracted using R language,and the differential genes were determined,with the screening condi-tions of P<0.05 and|log2FC|≥1;WGCNA was used to select the important modules related to PDR in GSE94019 dataset;key genes were obtained by intersecting differential genes and genes in important modules.Key genes were subjected to GO and KEGG enrich-ment analysis;PPI network was constructed to identify high-risk key proteins.Finally,CIBERSORTx was used to analyze the infiltra-tion of immune cells in PDR,and Pearson correlation analysis was used to screen key genes related to immune cells as core genes.Results:Three core genes were finally obtained,namely Col1a1,Col1a2 and Col3a1,their expressions were positively correlated with M2 macrophages,and the core genes were enriched in the AGEs-RAGE signaling pathway.Conclusion:Positive feedback may be formed between M2 macrophages,AGEs-RAGE signaling pathway and collagen genes(Col1a1,Col1a2,Col3a1),even without the stimulation of high glucose,this vicious circle may continue to damage retinal tissue.

Objective To establish the analysis method of 13 Paralytic shellfish toxins(PSTs)in human whole blood by high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Methods 13 kinds of PSTs were extracted from the whole blood using acetonitrile with 1%acetate(1︰3,v︰v)solution,and separated by UPLC BEH Amide chromatographic column(100mm×2.1mm,1.7μm).The samples were detected by an electrospray ionization source(ESI)and positive and negative ion multiple reaction monitoring(MRM)mode,and quantified by matrix matching curve external standard method.Results The results showed that 13 kinds of PSTs in blood samples were linear well in the ranges of 1～100 ng/mL,with the correlation coefficient(r2)>0.995.The limit of detection(LODs)of the method were 0.5～2 ng/mL,the limit of quantitation(LOQs)were 1～4 ng/mL,and the recoveries of the method were 65.55%～114.12%.Conclusion The method is highly sensitive,reproducible,and can qualify and quantify thirteen toxins at the same time,which is suitable for the rapid detection of PSTs in whole blood samples.

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
Animals ; Hematopoietic Stem Cells/cytology* ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Mice ; Cell Self Renewal ; Repressor Proteins/genetics* ; Mice, Inbred C57BL ; Mice, Knockout ; Humans ; Gene Expression Regulation

Shegan Mahuang Decoction is a classic formula for the treatment of asthma, which has the efficacy of dissipating cold and reducing phlegm, relieving cough and relieving asthma, and can be used clinically alone to control acute attacks, or to assist Western medical methods to improve the efficacy, and can also to combine with other classical prescriptions for the pathogenesis, which can improve the symptoms of cough and asthma, expectoration, and lung function indexes. The mechanism of Shegan Mahuang Decoction in the treatment of asthma is mainly related to reducing inflammatory response and inhibiting airway remodeling, and it mainly regulates immune inflammatory pathways to play a role.

We reported a 54-year-old female patient with severe tricuspid regurgitation, who received mechanic valve in the mitral position 15 years ago. The patient’s Society of Thoracic Surgeons score was 8.27%, and was intolerant to open heart surgery, so she was recommended for transcatheter tricuspid valve replacement via right vena jugularis interna. The procedures were guided by echocardiography and X ray fluoroscopy on November 13, 2021, the prosthesis was implanted successfully, and the patient was recoved without any adverse events. After 1 month follow-up, her general condition was apparently improved.

Objective:To explore the application effect of the ternary linkage continuation care model based on cognitive balance theory in patients with rheumatoid arthritis (RA), and to provide a reference for the continuation care model of RA patients.Methods:The convenience sampling method was adopted. A total of 72 RA patients who were treated in Huainan First People's Hospital, Anhui Province from January to December 2020 were selected as the research objects, and they were divided into observation group and control group by random number table method with 36 cases in each group. The control group was given regular discharge guidance and health education, and the observation group was given ternary continuous care based on cognitive balance theory on the basis of the control group. The intervention time was 3 months. The fatigue state, pain catastrophe, exercise self-efficacy and hope index was evaluated by the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the Pain Catastrophic Scale (PCS), the Self-Efficacy for Exercise Chinese version(SEE-C), and the Herth Hope Index Scale-Chinese version (HHI-C) and the results were compared between the two groups before and after the intervention.Results:There was no significant difference in the score of BRAF-MDQ, PCS, SEE-C, HHI-C before the intervention between the two groups( P>0.05). The scores of physical fatigue, life fatigue, cognitive fatigue and emotional fatigue of BRAF-MDQ in the observation group after the intervention were (10.02 ± 0.85), (6.33 ± 0.58), (3.31 ± 0.48), (4.25 ± 0.56) points, respectively, significantly lower than those in the control group (12.97 ± 1.89), (8.94 ± 0.97), (6.55 ± 0.97), (5.92 ± 0.87) points, and the differences were statistically significant ( t values were 8.54-17.96, all P<0.05). The scores of contemplation, exaggeration, and helplessness of PCS in the observation group after the intervention were (5.66 ± 0.43), (4.12 ± 0.36), (3.31 ± 0.41) points, respectively, which were significantly lower than those in the control group (8.41 ± 0.88), (5.74 ± 0.85), (5.52 ± 0.86) points, and the differences were statistically significant ( t=16.85, 10.53, 13.92, all P<0.05). The scores of SEE-C and HHI-C were (60.22 ± 7.89), (37.48 ± 5.79) points in the observation group after the intervention, which were significantly higher than those in the control group (46.98 ± 5.84), (34.21 ± 4.93) points, and the differences were statistically significant ( t=8.09, 2.58, both P<0.05). Conclusions:The ternary linkage continuation nursing model based on the cognitive balance theory has a significant effect on alleviating the fatigue state and pain catastrophe of RA patients, and helps to improve the patients' hope level and exercise self-efficacy.

Objective:To explore the surgical method and clinical effect of correcting lateral type alar retraction with intercartilaginous graft and lateral crural strut graft.Methods:A retrospective study was performed on the data of patients with moderate to severe lateral alar retraction treated in Shenzhen Mylike Medical Plastic Aesthetic Hospital from October 2018 to June 2020. During the operation, lower lateral cartilages was totally dissected and strengthened by lateral crural strut graft while scroll area was released and lengthened with intercartilaginous graft to correct lateral type alar retraction. The preoperative and postoperative distance from the nostril’s long axis to the alar rim was measured from the side view, the nasal measurements were expressed as Mean±SD, and paired t-test was used for statistical analysis. Results:A total of 32 patients were enrolled, including 5 males and 27 females, with an average age of 31 years (18-47 years). Twenty-three cases underwent primary rhinoplasty and 9 cases underwent second rhinoplasty. The preoperative data of distance from the nostril’s long axis to the alar rim was (4.1±0.5) mm (3.2-5.0 mm). The postoperative effect of nasal alar retraction defomity correction was obvious. After a follow-up period of 20 cases from 6 to 18 months, the distance from the nostril’s long axis to the alar rim was 1.5-2.8 mm [(2.1±0.3) mm on average]. Comparison of preoperative and postoperative measured values showed statistically significant difference ( P<0.01). There was 1 patient emerged complication alar flaring, and no contracture and deformation of the nasal rim occurred. All of patients were satisfied. Conclusions:The intercartilaginous graft combined with lateral crural strut graft is an effective new method for correction of lateral type alar retraction. It has stable clinical effect and high satisfaction.

Objective:To explore the surgical method and clinical effect of correcting lateral type alar retraction with intercartilaginous graft and lateral crural strut graft.Methods:A retrospective study was performed on the data of patients with moderate to severe lateral alar retraction treated in Shenzhen Mylike Medical Plastic Aesthetic Hospital from October 2018 to June 2020. During the operation, lower lateral cartilages was totally dissected and strengthened by lateral crural strut graft while scroll area was released and lengthened with intercartilaginous graft to correct lateral type alar retraction. The preoperative and postoperative distance from the nostril’s long axis to the alar rim was measured from the side view, the nasal measurements were expressed as Mean±SD, and paired t-test was used for statistical analysis. Results:A total of 32 patients were enrolled, including 5 males and 27 females, with an average age of 31 years (18-47 years). Twenty-three cases underwent primary rhinoplasty and 9 cases underwent second rhinoplasty. The preoperative data of distance from the nostril’s long axis to the alar rim was (4.1±0.5) mm (3.2-5.0 mm). The postoperative effect of nasal alar retraction defomity correction was obvious. After a follow-up period of 20 cases from 6 to 18 months, the distance from the nostril’s long axis to the alar rim was 1.5-2.8 mm [(2.1±0.3) mm on average]. Comparison of preoperative and postoperative measured values showed statistically significant difference ( P<0.01). There was 1 patient emerged complication alar flaring, and no contracture and deformation of the nasal rim occurred. All of patients were satisfied. Conclusions:The intercartilaginous graft combined with lateral crural strut graft is an effective new method for correction of lateral type alar retraction. It has stable clinical effect and high satisfaction.