1.Novel hormone therapies for advanced prostate cancer: Understanding and countering drug resistance.
Zhipeng WANG ; Jie WANG ; Dengxiong LI ; Ruicheng WU ; Jianlin HUANG ; Luxia YE ; Zhouting TUO ; Qingxin YU ; Fanglin SHAO ; Dilinaer WUSIMAN ; William C CHO ; Siang Boon KOH ; Wei XIONG ; Dechao FENG
Journal of Pharmaceutical Analysis 2025;15(9):101232-101232
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.
2.Risk factors for arrhythmia after robotic cardiac surgery: A retrospective cohort study
Wenjun WU ; Renzhong DING ; Jianming CHEN ; Ye YUAN ; Yi SONG ; Manrong YAN ; Yijie HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(05):745-750
Objective To investigate the risk factors for arrhythmia after robotic cardiac surgery. Methods The data of the patients who underwent robotic cardiac surgery under cardiopulmonary bypass (CPB) from July 2016 to June 2022 in Daping Hospital of Army Medical University were retrospectively analyzed. According to whether arrhythmia occurred after operation, the patients were divided into an arrhythmia group and a non-arrhythmia group. Univariate analysis and multivariate logistic analysis were used to screen the risk factors for arrhythmia after robotic cardiac surgery. Results A total of 146 patients were enrolled, including 55 males and 91 females, with an average age of 43.03±13.11 years. There were 23 patients in the arrhythmia group and 123 patients in the non-arrhythmia group. One (0.49%) patient died in the hospital. Univariate analysis suggested that age, body weight, body mass index (BMI), diabetes, New York Heart Association (NYHA) classification, left atrial anteroposterior diameter, left ventricular anteroposterior diameter, right ventricular anteroposterior diameter, total bilirubin, direct bilirubin, uric acid, red blood cell width, operation time, CPB time, aortic cross-clamping time, and operation type were associated with postoperative arrhythmia (P<0.05). Multivariate binary logistic regression analysis suggested that direct bilirubin (OR=1.334, 95%CI 1.003-1.774, P=0.048) and aortic cross-clamping time (OR=1.018, 95%CI 1.005-1.031, P=0.008) were independent risk factors for arrhythmia after robotic cardiac surgery. In the arrhythmia group, postoperative tracheal intubation time (P<0.001), intensive care unit stay (P<0.001) and postoperative hospital stay (P<0.001) were significantly prolonged, and postoperative high-dose blood transfusion events were significantly increased (P=0.002). Conclusion Preoperative direct bilirubin level and aortic cross-clamping time are independent risk factors for arrhythmia after robotic cardiac surgery. Postoperative tracheal intubation time, intensive care unit stay, and postoperative hospital stay are significantly prolonged in patients with postoperative arrhythmia, and postoperative high-dose blood transfusion events are significantly increased.
3.Changes in sleep and psychological characteristics of patients with insomnia under exposure to noise pollution
Journal of Apoplexy and Nervous Diseases 2023;40(7):647-651
Objective Exposure to nocturnal traffic noise at the same levels can produce different effects on sleep and psychological health in different populations. This study compared the electroencephalographic characteristics during sleep of people with insomnia and those with normal sleep quality under the same levels of nocturnal traffic noise exposure to elucidate the different effects of noise pollution on different populations,and to provide individualized precise treatment plans for people with insomnia who are sensitive to noise pollution. Methods We selected people who lived near highways,railways,and aircraft routes for more than six months where noise levels were relatively fixed(50-60 decibels,10-15 seconds per time) during the nighttime sleep period (22:00-6:00). We included 26 people with normal sleep quality and 30 people with insomnia based on the Pittsburgh Sleep Quality Index. The Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were administered. Polysomnography (PSG) was used to monitor the spindle density index during sleep. The sleep quality and psychological status of the two groups were compared. Results There were no significant differences in demographic characteristics between the two groups under the same nocturnal noise exposure conditions. The incidence of anxiety and depression was significantly lower in the people with normal sleep quality than in those with insomnia(P<0.01). Among the 26 people with normal sleep quality,5(19.23%) had mild anxiety,and no one had moderate to severe anxiety or depression. Among the 30 people with insomnia,6(20.00%) had mild anxiety,15 (50.00%) had moderate anxiety,and 4(13.33%) had severe anxiety;3(10.00%) had mild depression,9(30.00%) had moderate depression,and 3(10%) had severe depression. PSG showed that the sleep spindle index of the normal sleep group was significantly higher than that of the insomnia group(25.43 vs 16.60,P<0.05),with no significant differences in the average duration of sleep spindles during sleep between the two groups (P>0.05). Conclusion Under the same levels of nocturnal traffic noise exposure,people with insomnia have a higher incidence of anxiety and depression than people with normal sleep quality. Patients with insomnia with a reduced spindle density index have worse sleep quality under exposure to noise pollution.
5.Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer's Disease and Attenuate AD-type Pathology in a Mouse Model.
Jie-Ming JIAN ; Dong-Yu FAN ; Ding-Yuan TIAN ; Yuan CHENG ; Pu-Yang SUN ; Cheng-Rong TAN ; Gui-Hua ZENG ; Chen-Yang HE ; Ye-Ran WANG ; Jie ZHU ; Xiu-Qing YAO ; Yan-Jiang WANG ; Yu-Hui LIU
Neuroscience Bulletin 2022;38(9):1025-1040
Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aβ)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβ deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
Alzheimer Disease/pathology*
;
Amyloid beta-Peptides/metabolism*
;
Amyloid beta-Protein Precursor/metabolism*
;
Animals
;
Disease Models, Animal
;
Humans
;
Mice
;
Mice, Transgenic
6.Efficacy of Brief Behavioral Therapy for Insomnia (BBT-I) in patients suffering Paradoxical insomnia
Jingyi YE ; Wanying ZHANG ; Can JIANG
Journal of Apoplexy and Nervous Diseases 2022;39(3):210-214
To explore the effect of BBT-I on subjective insomnia and its influencing factors. Methods 60 primary insomnia patients were collected in outpatient department,and divided into two groups:Subjective insomnia group (SI group) and non-subjective insomnia group (NSI group) by sleep data collected by standard polysomnography monitoring and Pittsburgh Sleep Quality Index (PSQI),sleep diaries during the intervention were collected,and the Pre Sleep Arousal Scale(PSAS),Brief Version of Dysfunctional Beliefs and Attitudes About Sleep (DBAS) and the Sleep Hygiene Practice Scale(SHPS) were collected to evaluate the influencing factors related to sleep attitudes,beliefs and behaviors of patients. All patients received BBT-I for 4 weeks,and collected the sleep diaries and PSQI 1 week before and 1 week after treatment. Results Compared with NSI group,SI group had higher arousal index(P<0.05);compared with NSI group,SI group had lower scores in factor 3 indicated as drug belief and factor 4 representing anticipation of sleep in DBAS,that is,there were more irrational beliefs in SI (P<0.05).Intragroup comparison showed that there were statistically significant differences insleep latency、sleep efficiency,daytime function and PSQI score in SI group before and after treatment (P<0.05),and there were statistically significant differences in SE difference before and after intervention between SI group and NSI group (P<0.05).In the subjective insomnia group,daytime functional difference before and after intervention was negatively correlated with the first factor in DBAS(r=0.270,P=0.037). daytime functional difference before and after intervention was negatively correlated with PSAS(r=0.268,P=0.039);The difference of sleep latency before and after intervention was negatively correlated with physiological stimulation of PSAS(r =0.288,P=0.042). Conclusion Compared with nonsubjective patients,subjective insomnia patients have higher arousals and more irrational beliefs and attitudes.BBT-I may improve sleep latency/、sleep efficiency,daytime function and sleep sensation in subjective insomnia patients.
7.Recommendations from Experts in the Management of Adverse Reactions to ALK Inhibitors (2021 Version).
Ke WANG ; Juan LI ; Jianguo SUN ; Li LI ; Xi ZHANG ; Jianyong ZHANG ; Min YU ; Xianwei YE ; Ming ZHANG ; Yu ZHANG ; Wenxiu YAO ; Meijuan HUANG
Chinese Journal of Lung Cancer 2021;24(12):815-828
Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
.
Carcinoma, Non-Small-Cell Lung
;
Crizotinib
;
Humans
;
Lung Neoplasms/genetics*
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Protein Kinase Inhibitors/adverse effects*
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Receptor Protein-Tyrosine Kinases/antagonists & inhibitors*
8.Analysis of risk factors for arrhythmia in patients after heart valve replacement
Manrong YAN ; Qianjin ZHONG ; Yongchao GOU ; Jianming CHEN ; Yijie HU ; Yi SONG ; Ye YUAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(04):459-466
Objective To explore and analyze the risk factors for arrhythmia in patients after heart valve replacement. Methods A retrospective analysis of 213 patients undergoing cardiac valve replacement surgery under cardiopulmonary bypass in our hospital from August 2017 to August 2019 was performed, including 97 males and 116 females, with an average age of 53.4±10.5 year and cardiac function classification (NYHA) grade of Ⅱ-Ⅳ. According to the occurrence of postoperative arrhythmia, the patients were divided into a non-postoperative arrhythmia group and a postoperative arrhythmia group. The clinical data of the two groups were compared, and the influencing factors for arrhythmia after heart valve replacement were analyzed by logistic regression analysis. Results There were 96 (45%) patients with new arrhythmia after heart valve replacement surgery, and the most common type of arrhythmia was atrial fibrillation (45 patients, 18.44%). Preoperative arrhythmia rate, atrial fibrillation operation rate, postoperative minimum blood potassium value, blood magnesium value in the postoperative arrhythmia group were significantly lower than those in the non-postoperative arrhythmia group (P<0.05); hypoxemia incidence, hyperglycemia incidence, acidosis incidence, fever incidence probability were significantly higher than those in the non-postoperative arrhythmia group (P<0.05). The independent risk factors for postoperative arrhythmia were the lowest postoperative serum potassium value (OR=0.305, 95%CI 0.114-0.817), serum magnesium value (OR=0.021, 95%CI 0.002-0.218), and hypoxemia (OR=2.490, 95%CI 1.045-5.930). Conclusion Taking precautions before surgery, improving hypoxemia after surgery, maintaining electrolyte balance and acid-base balance, monitoring blood sugar, detecting arrhythmia as soon as possible and dealing with it in time can shorten the ICU stay time, reduce the occurrence of complications, and improve the prognosis of patients.
9.Preliminary application and efficacy analysis of transumbilical single-incision plus one port robotic total mesorectal excision.
Fan ZHANG ; Jing Wang YE ; De Wen TAN ; Zheng Yong LIU ; Wei Dong TONG ; Fan LI
Chinese Journal of Gastrointestinal Surgery 2021;24(3):269-271
Objective: To investigate the feasibility of transumbilical single-incision plus one port (SIPOP) robotic total mesorectal excision. Methods: Clinical data of a 70-year-old male patient with BMI 22.1 kg/m(2) who successfully underwent transumbilical single-incision plus 1 port robotic total mesorectal resection of upper rectal cancer at the General Surgery Department of Daping Hospital of Army Military Medical University on September 18, 2019 were retrospectively analyzed. Preoperative colonoscopy revealed that the distance of upper rectal cancer to anal edge was 14 cm, and the tumor size was 2.5 cm×1.5 cm×1 cm. Pathological result confirmed rectal moderately differentiated adenocarcinoma. The preoperative abdominal CT showed thickened bowel-wall of upper rectum and the blurred perirectal fat, suggesting tumor infiltration. Results: The operation was successful. There were no conversion to laparotomy or abdominal auxiliary incision, and the mesorectum of the specimen was intact. The operation time was 165 minutes, the blood loss was about 20 ml, and there were no complications such as injury to peripheral organs. Postoperative pathology showed ulcerative moderately differentiated adenocarcinoma of the upper rectum with TNM stage IVA (T4N2b). The postoperative recovery was smooth. Patient ambulated on the 1st day, the catheter was removed on the 7th day, and discharged from the hospital on the 8th day. Conclusion: The transumbilical SIPOP robotic total mesorectal excision is safe, effective and feasible.
Aged
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Humans
;
Laparoscopy
;
Male
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Rectal Neoplasms/surgery*
;
Rectum
;
Retrospective Studies
;
Robotic Surgical Procedures
;
Robotics
;
Treatment Outcome
10.CSF Brain-Reactive Autoantibodies are Elevated in Patients with Viral Encephalitis.
Zhong-Yuan YU ; Jian-Hong WANG ; Wei-Wei LI ; Ye-Ran WANG ; Noralyn B MAÑUCAT-TAN ; Jun WANG ; Ju WANG ; Gao-Yu CUI ; Jie-Xiang PAN ; Shui-Xian ZHANG ; Zu-Juan LIU ; Liang TAN ; Yu-Hui LIU
Neuroscience Bulletin 2020;36(8):942-946


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