1.Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.
Wanyu TANG ; Zhixue MA ; Bang LI ; Zhexiang YU ; Xiaobao ZHAO ; Huicui YANG ; Jian HU ; Sheng TIAN ; Linghan GU ; Jiaojiao CHEN ; Xing ZOU ; Qi WANG ; Fan CHEN ; Guangying LI ; Chaonan ZHENG ; Shuliu GAO ; Wenjing LIU ; Yue LI ; Wenhua ZHENG ; Mingmei WANG ; Na YE ; Xuechu ZHEN
Acta Pharmaceutica Sinica B 2025;15(10):5346-5365
Sigma-1 receptor (σ 1R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K i < 4 nmol/L) and selective σ 1R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ 1R in relation to σ 2R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ 1R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.
2.Clinical value of puncture biopsy in the diagnosis of hepatocellular carcinoma subtypes
Xueqin TIAN ; Jiapeng WU ; Lu LI ; Chuan PANG ; Chaonan CHEN ; Jie YU ; Ping LIANG
Chinese Journal of Hepatobiliary Surgery 2025;31(6):426-432
Objective:To investigate the clinical value of puncture biopsy for the diagnosis of vessels that encapsulate tumor clusters (VETC) and macrotrabecular-massive (MTM) subtypes of hepatocellular carcinoma (HCC).Methods:One hundred and eighty-four patients with HCC who underwent surgical resection at the Fifth Medical Centre of Chinses PLA General Hospital from November 2023 to July 2024 were prospectively collected, including 154 males and 30 females, aged (57.1±8.6) years. By simulating the clinical puncture procedure, puncture biopsy tissue specimens were obtained postoperatively from the patient's isolated tumors. The puncture biopsies and surgical resection specimens were stained with HE and CD34, and evaluated for VETC and MTM. Patients were divided into two groups based on the histopathological VETC results of surgically resected specimens: the VETC-positive group ( n=41) and the VETC-negative group ( n=143); and two groups based on the histopathological MTM results of surgically resected specimens: the MTM-positive group ( n=39) and the MTM-negative group ( n=145). Clinical data such as gender, age, tumor length, and alpha-fetoprotein (AFP) were recorded. Logistic regression analysis was performed to screen the risk factors of VETC and MTM. Evaluating the diagnostic efficacy of puncture biopsy for VETC and MTM. Results:The results of multivariable logistic analysis showed that puncture biopsy VETC-positive ( OR=63.97, 95% CI: 16.28-251.29), grade of M2 microvascular invasion ( OR=5.07, 95% CI: 1.31-19.59) and tumor length ≥5 cm ( OR=3.42, 95% CI: 1.11-10.52) were the risk factors for VETC-positive (all P<0.05); whereas the risk factors for MTM-positive were only puncture biopsy MTM-positive ( OR=34.78, 95% CI: 12.06-100.29, P<0.001). Puncture biopsy correctly diagnosed VETC subtype in 163 patients with a diagnostic accuracy of 0.89, sensitivity of 0.61, specificity of 0.97, positive predictive value (PPV) of 0.83, and negative predictive value (NPV) of 0.90; MTM subtype was correctly diagnosed in 164 patients with a diagnostic accuracy of 0.89, sensitivity of 0.72, specificity of 0.94, PPV of 0.76, and NPV of 0.93. Using the three indicators of puncture biopsy diagnosis, tumor length and AFP level as a combined indicator, the accuracy to diagnose VETC was 0.83, sensitivity was 0.71, specificity was 0.87, PPV was 0.60, and NPV was 0.91; and the combined indicator diagnosis of MTM had a diagnostic accuracy of 0.85, a sensitivity of 0.82, specificity of 0.86, PPV of 0.68 and NPV of 0.95. Conclusion:Puncture biopsy has high specificity and accuracy in the diagnosis of VETC and MTM subtypes, but the sensitivity is relatively limited, and the role of puncture combined with clinical factors in improving diagnostic efficacy is limited.
3.Management of 3D printing customized medical devices in a hospital
Xiaohua LIU ; Yun TIAN ; Chaonan XU ; Hanjing ZHANG ; Xinyun XUE
Chinese Journal of Hospital Administration 2025;41(3):245-248
3D printing technology customized medical devices can accurately adapt to the complex anatomical structure of the human body, and have become a new meaning to promote the development of precision medicine. In order to ensure the safety and effectiveness of the clinical use of 3D printed customized medical devices and standardize the management process of such products, a tertiary hospital had started the file-record management of 3D printed customized medical devices since March 2021, covering access approval management, production verification, surgical process management and postoperative traceability management. This practice had achieved standardized management of 3D printed customized medical devices and achieved good results. The 3D printed bone fixation fusion used by the hospital was officially approved as a medical device product registration certificate in March 2023; 109 orthopedic patients recorded the use of 3D printed custom medical devices in 2023, with a significant increase compared to 54 patients in 2022. This practice could provide references for other hospitals to carry out standardized management of the use of customized medical devices. In the future, hospital should further balance regulation and innovation, promote multi-party collaboration, strengthen data integration, ensure data security, and enhance the level of refined management of medical devices.
4.Management of 3D printing customized medical devices in a hospital
Xiaohua LIU ; Yun TIAN ; Chaonan XU ; Hanjing ZHANG ; Xinyun XUE
Chinese Journal of Hospital Administration 2025;41(3):245-248
3D printing technology customized medical devices can accurately adapt to the complex anatomical structure of the human body, and have become a new meaning to promote the development of precision medicine. In order to ensure the safety and effectiveness of the clinical use of 3D printed customized medical devices and standardize the management process of such products, a tertiary hospital had started the file-record management of 3D printed customized medical devices since March 2021, covering access approval management, production verification, surgical process management and postoperative traceability management. This practice had achieved standardized management of 3D printed customized medical devices and achieved good results. The 3D printed bone fixation fusion used by the hospital was officially approved as a medical device product registration certificate in March 2023; 109 orthopedic patients recorded the use of 3D printed custom medical devices in 2023, with a significant increase compared to 54 patients in 2022. This practice could provide references for other hospitals to carry out standardized management of the use of customized medical devices. In the future, hospital should further balance regulation and innovation, promote multi-party collaboration, strengthen data integration, ensure data security, and enhance the level of refined management of medical devices.
5.Clinical value of puncture biopsy in the diagnosis of hepatocellular carcinoma subtypes
Xueqin TIAN ; Jiapeng WU ; Lu LI ; Chuan PANG ; Chaonan CHEN ; Jie YU ; Ping LIANG
Chinese Journal of Hepatobiliary Surgery 2025;31(6):426-432
Objective:To investigate the clinical value of puncture biopsy for the diagnosis of vessels that encapsulate tumor clusters (VETC) and macrotrabecular-massive (MTM) subtypes of hepatocellular carcinoma (HCC).Methods:One hundred and eighty-four patients with HCC who underwent surgical resection at the Fifth Medical Centre of Chinses PLA General Hospital from November 2023 to July 2024 were prospectively collected, including 154 males and 30 females, aged (57.1±8.6) years. By simulating the clinical puncture procedure, puncture biopsy tissue specimens were obtained postoperatively from the patient's isolated tumors. The puncture biopsies and surgical resection specimens were stained with HE and CD34, and evaluated for VETC and MTM. Patients were divided into two groups based on the histopathological VETC results of surgically resected specimens: the VETC-positive group ( n=41) and the VETC-negative group ( n=143); and two groups based on the histopathological MTM results of surgically resected specimens: the MTM-positive group ( n=39) and the MTM-negative group ( n=145). Clinical data such as gender, age, tumor length, and alpha-fetoprotein (AFP) were recorded. Logistic regression analysis was performed to screen the risk factors of VETC and MTM. Evaluating the diagnostic efficacy of puncture biopsy for VETC and MTM. Results:The results of multivariable logistic analysis showed that puncture biopsy VETC-positive ( OR=63.97, 95% CI: 16.28-251.29), grade of M2 microvascular invasion ( OR=5.07, 95% CI: 1.31-19.59) and tumor length ≥5 cm ( OR=3.42, 95% CI: 1.11-10.52) were the risk factors for VETC-positive (all P<0.05); whereas the risk factors for MTM-positive were only puncture biopsy MTM-positive ( OR=34.78, 95% CI: 12.06-100.29, P<0.001). Puncture biopsy correctly diagnosed VETC subtype in 163 patients with a diagnostic accuracy of 0.89, sensitivity of 0.61, specificity of 0.97, positive predictive value (PPV) of 0.83, and negative predictive value (NPV) of 0.90; MTM subtype was correctly diagnosed in 164 patients with a diagnostic accuracy of 0.89, sensitivity of 0.72, specificity of 0.94, PPV of 0.76, and NPV of 0.93. Using the three indicators of puncture biopsy diagnosis, tumor length and AFP level as a combined indicator, the accuracy to diagnose VETC was 0.83, sensitivity was 0.71, specificity was 0.87, PPV was 0.60, and NPV was 0.91; and the combined indicator diagnosis of MTM had a diagnostic accuracy of 0.85, a sensitivity of 0.82, specificity of 0.86, PPV of 0.68 and NPV of 0.95. Conclusion:Puncture biopsy has high specificity and accuracy in the diagnosis of VETC and MTM subtypes, but the sensitivity is relatively limited, and the role of puncture combined with clinical factors in improving diagnostic efficacy is limited.
6.Qualitative study on psychosomatic experience of patients undergoing lumbar cistern drainage after transnasal endoscopic surgery
Rui ZHAO ; Pengwei LU ; Chaonan TIAN
Chinese Journal of Practical Nursing 2022;38(10):771-775
Objective:To understand the psychosomatic experience and needs of patients with lumbar cistern drainage after transnasal endoscopic sinus surgery in neurosurgery while lying in bed.Methods:Using the purposeful sampling method, one-to-on, face-to-face semi-structured interviews were conducted among 12 patients with lumbar cistern catheter drainage who were treated in Beijing Tiantan Hospital Affiliated to Capital Medical University from July to August 2020. Colaizzi phenomenology study was used to analyze the interview data, and summarized the themes.Results:The experience and needs of patients with lumbar cistern catheterization during the catheter placement were summarized into 3 themes. Obvious physical and mental discomfort: pain, discomfort of body position restriction, expectation minimization constraint scheme. Knowledge and cognitive needs: understand the reasons for intubation, intubation time and precautions. Affectionate and professional care needs: eager for professional care and more attention from medical staff, eager to be accompanied by family member to achieve greater improvement of comfort.Conclusions:Clinical nursing should be based on the patient′s psychosomatic feelings and needs, actively explore personalized intervention measures suitable for patients with lumbar cistern drainage, and formulate corresponding predictive care content to improve patients′ compliance, comfort and satisfaction.
7.Gold nanorods-mediated efficient synergistic immunotherapy for detection and inhibition of postoperative tumor recurrence.
Yingying ZHANG ; Tiange WANG ; Yu TIAN ; Chaonan ZHANG ; Kun GE ; Jinchao ZHANG ; Jin CHANG ; Hanjie WANG
Acta Pharmaceutica Sinica B 2021;11(7):1978-1992
Tumor recurrence after surgery is the main cause of treatment failure. However, the initial stage of recurrence is not easy to detect, and it is difficult to cure in the late stage. In order to improve the life quality of postoperative patients, an efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously. In this paper, two kinds of theranostic agents based on gold nanorods (AuNRs) platform were prepared. AuNRs and quantum dots (QDs) in one agent was used for the detection of carcinoembryonic antigen (CEA), using fluorescence resonance energy transfer (FRET) technology to indicate the occurrence of
8.Application of convolutional neural networks in the diagnosis of schizophrenia
Jin LIU ; Yong HE ; Jiuju WANG ; Wenxiang QUAN ; Ju TIAN ; Chaonan FENG ; Haokui YU ; Cai NAN ; Jun JI
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(7):622-626
Objective To explore the program of convolutional neural networks for the diagnosis of schizophrenia and evaluate its effects. Methods Using the convolutional neural network,the training model was trained in the lead data of 138 normal people and 183 schizophrenic patients,and the model was valida-ted by 20-fold cross-validation. Results The true positive rate of schizophrenia prediction using the convolu-tional neural network training model was 0. 749, the false positive rate was 0. 275, and the accuracy was 0. 738. Conclusion This model can achieve a strong diagnostic ability for patients with schizophrenia. Therefore,convolutional neural network for the diagnosis of schizophrenia will become an important research direction in the future.

Result Analysis
Print
Save
E-mail