1.Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension
Chen YU ; Songmei GENG ; Bin YANG ; Yunhua DENG ; Fuqiu LI ; Xiaojing KANG ; Mingye BI ; Furen ZHANG ; Yi ZHAO ; Weili PAN ; Zhongwei TIAN ; Jinhua XU ; Zhenghua ZHANG ; Nan YU ; Xinsuo DUAN ; Shuping GUO ; Qing SUN ; Weiquan LI ; Juan TAO ; Zhijun LIU ; Yuanyuan YIN ; Gang WANG
Chinese Medical Journal 2024;137(10):1190-1198
Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.
2.Research and application of TTK and its inhibition in malignant tumors
Xuzhen ZHENG ; Weiquan WANG ; Zhiyu GONG ; De HE
International Journal of Surgery 2024;51(2):138-144
Monopolar spindle 1, also known as threonine and tyrosine kinase (TTK), is a key component of spindle assembly checkpoint (SAC). It is considered to be a monitoring mechanism to ensure mitotic fidelity and genomic stability. TTK is overexpressed in a variety of malignant tumors, and patients with low expression of TTK tend to have a longer survival time, suggesting that it may be used as a biomarker for diagnosis and prognosis. Abnormal expression of TTK often impairs the function of SAC, resulting in irregular mitosis, increased aneuploidy and mitotic disaster, thus promoting the occurrence of tumors. Current studies have shown that TTK inhibitors can inhibit the proliferation of tumor cells and increase the sensitivity of tumor cells to therapy in combination with chemotherapy or radiotherapy to achieve sensitization and attenuated effects. This article will review the research and application of TTK and its inhibitors in malignant tumors.
3.Use of artificial intelligence in the management of T1 colorectal cancer: a new tool in the arsenal or is deep learning out of its depth?
James Weiquan LI ; Lai Mun WANG ; Katsuro ICHIMASA ; Kenneth Weicong LIN ; James Chi-Yong NGU ; Tiing Leong ANG
Clinical Endoscopy 2024;57(1):24-35
The field of artificial intelligence is rapidly evolving, and there has been an interest in its use to predict the risk of lymph node metastasis in T1 colorectal cancer. Accurately predicting lymph node invasion may result in fewer patients undergoing unnecessary surgeries; conversely, inadequate assessments will result in suboptimal oncological outcomes. This narrative review aims to summarize the current literature on deep learning for predicting the probability of lymph node metastasis in T1 colorectal cancer, highlighting areas of potential application and barriers that may limit its generalizability and clinical utility.
4.Exploring the effect of Tuina on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation based on NR2B/PSD-95 pathway
Huanzhen ZHANG ; Bingqian WANG ; Shuijin CHEN ; Lechun CHEN ; Jingjing JIANG ; Yu JIANG ; Jincheng CHEN ; Hongye HUANG ; Jiayu FANG ; Weiquan ZENG ; Zhigang LIN
Journal of Acupuncture and Tuina Science 2023;21(2):129-136
Objective: To investigate the analgesic mechanism of Tuina (Chinese therapeutic massage) by observing the effect of the N-methyl-D-aspartate receptor subunit 2B (NR2B)/postsynaptic density-95 (PSD-95) pathway on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation. Methods: Fifty Sprague-Dawley rats were randomly divided into a blank group, a model group, a Tuina group, a blocker agent group, and a blocker agent + Tuina group. The sciatic nerve chronic constriction injury (CCI) model was prepared by the sciatic nerve ligation method. From the 4th day after modeling, rats in the Tuina group and the blocker agent + Tuina group were subject to daily Tuina intervention, and those in the blocker agent group and the blocker agent + Tuina group were daily intrathecally injected with NR2B blocker agent (MK-801). The spontaneous pain score was used to observe the pain behavior of all rats. The expression levels of NR2B and downstream PSD-95 were measured by immunohistochemistry, and the dendritic structure changes were observed by Golgi staining for rat spinal cord dorsal horn after 14 d of continuous intervention. Results: Compared with the blank group, the degree of rat spontaneous pain after CCI was elevated in both the model and the Tuina groups (P<0.01) and was reduced in the Tuina group after the Tuina intervention compared with the model group (P<0.05). Compared with the model group, the rat spontaneous pain level after blocking NR2B was reduced in both the blocker agent group and the blocker agent + Tuina group (P<0.05). The NR2B and PSD-95 protein levels were significantly higher in the model group compared with the blank group (P<0.01); the total number of dendritic branches was increased (P<0.01), and the total dendritic length became longer (P<0.01) in the spinal cord dorsal horn. The rat NR2B and PSD-95 protein levels were significantly decreased in the Tuina group compared with the model group (P<0.01); the total dendritic branch number was reduced (P<0.01) and the total length was shortened (P<0.01) in the spinal cord dorsal horn. After blocking NR2B, the expression levels of NR2B and downstream PSD-95 protein were significantly lower in both the blocker agent group and the blocker agent + Tuina group compared to the model group (P<0.01). The total branch number was significantly reduced (P<0.01), and the total length was significantly shortened (P<0.01) of the dendrites in the spinal cord dorsal horn. Conclusion: Tuina may exert an analgesic effect by remodeling the dendritic structure in the spinal cord dorsal horn in rats with lumbar disc herniation, and its mechanism may be related to the inhibition of NR2B/PSD-95 signaling pathway.
5.EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study
Weiguang GU ; Hua ZHANG ; Yiyu LU ; Minjing LI ; Shuang YANG ; Jianmiao LIANG ; Zhijian YE ; Zhihua LI ; Minhong HE ; Xiaoliang SHI ; Fei WANG ; Dong YOU ; Weiquan GU ; Weineng FENG
Cancer Research and Treatment 2023;55(3):841-850
Purpose:
We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations.
Materials and Methods:
This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.
Results:
The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.
Conclusion
EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.
6.Mediating effect of life satisfaction between child neglect and problematic mobile phone use of middle school students
Xiuqin LIU ; Mingwan ZHOU ; Zhibin WANG ; Weiquan YOU ; Yun LI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(2):161-167
Objective:To explore whether life satisfaction has a mediating effect between child neglect and middle school student’ problematic mobile phone use.Methods:Totally 1 692 middle school students from four middle schools of Xiamen in June 2020 were selected by cluster stratified sampling.The self-rating questionnaire for adolescent problematic mobile phone use (SQAPMPU), child neglect scale (CNS) and quality of life scale for children and adolescents (QLSCA) were used for the survey. SPSS 23.0 software was used for descriptive statistics, correlation analysis, regression analysis and the mediating effect analysis.Results:The scores of CNS, QLSCA and SQAPMPU were (24.45±14.28), (134.44±19.34), (23.20±8.94)respectively.And the detection rate of problematic mobile phone use was 23.6%. There were significant differences in the scores of SQAPMPU scale in different grades, father's education degrees, mother's education degrees and monthly pocket money(all P<0.05). In SQAPMPU, high school students scored significantly higher than junior school students( t=-2.403, P=0.016), adolescents with undergrate education of their father and mother scored the lowest( F=3.411, P=0.017; F=2.729, P=0.043), adolescents with monthly pocket money of "500-1 000" and "1 000-2 000" scored significantly higher than those with monthly pocket money of "under 500". The total scores and sub scores of child neglect were significantly positively correlated with the total scores and sub scores of problematic mobile phone use ( r=0.177-0.360, all P<0.05). The total scores and sub scores of life satisfaction were significantly negative correlated with the total scores and sub scores of problematic mobile phone use ( r==-0.508--0.250, all P<0.05). Child neglect had a positive predictive effect on problematic mobile phone use ( t=15.598, R2=0.130, P<0.05), but had a negative predictive effect on life satisfaction ( t=-27.798, R2=0.321, P<0.05). There were the part intermediary role of life satisfaction between child neglect and problematic mobile phone use( t=-13.937, R2=0.222, P<0.05), and the mediating effect accounted for 58.29% of the total effect. Conclusion:The neglected experience in childhood of adolescents not only can directly affect problematic mobile phone use, but also can affect the problematic mobile phone use by affecting life satisfaction.
7.Clinical guidance on endoscopic management of colonic polyps in Singapore.
Tiing Leong ANG ; Jit Fong LIM ; Tju Siang CHUA ; Kok Yang TAN ; James Weiquan LI ; Chern Hao CHONG ; Kok Ann GWEE ; Vikneswaran S/O NAMASIVAYAM ; Charles Kien Fong VU ; Christopher Jen Lock KHOR ; Lai Mun WANG ; Khay Guan YEOH
Singapore medical journal 2022;63(4):173-186
Colonoscopy with endoscopic resection of detected colonic adenomas interrupts the adenoma-carcinoma sequence and reduces the incidence of colorectal cancer and cancer-related mortality. In the past decade, there have been significant developments in instruments and techniques for endoscopic polypectomy. Guidelines have been formulated by various professional bodies in Europe, Japan and the United States, but some of the recommendations differ between the various bodies. An expert professional workgroup under the auspices of the Academy of Medicine, Singapore, was set up to provide guidance on the endoscopic management of colonic polyps in Singapore. A total of 23 recommendations addressed the following issues: accurate description and diagnostic evaluation of detected polyps; techniques to reduce the risk of post-polypectomy bleeding and delayed perforation; the role of specific endoscopic resection techniques; the histopathological criteria for defining endoscopic cure; and the role of surveillance colonoscopy following curative resection.
Adenoma/surgery*
;
Colonic Neoplasms/surgery*
;
Colonic Polyps/surgery*
;
Colonoscopy/methods*
;
Colorectal Neoplasms/pathology*
;
Humans
;
Singapore
;
United States
8.Artificial intelligence-assisted colonoscopy: a narrative review of current data and clinical applications.
James Weiquan LI ; Lai Mun WANG ; Tiing Leong ANG
Singapore medical journal 2022;63(3):118-124
Colonoscopy is the reference standard procedure for the prevention and diagnosis of colorectal cancer, which is a leading cause of cancer-related deaths in Singapore. Artificial intelligence systems are automated, objective and reproducible. Artificial intelligence-assisted colonoscopy has recently been introduced into clinical practice as a clinical decision support tool. This review article provides a summary of the current published data and discusses ongoing research and current clinical applications of artificial intelligence-assisted colonoscopy.
Artificial Intelligence
;
Colonic Polyps/diagnosis*
;
Colonoscopy/methods*
;
Colorectal Neoplasms/diagnosis*
;
Diagnosis, Computer-Assisted
;
Humans
9.Academy of Medicine, Singapore clinical guideline on endoscopic surveillance and management of gastric premalignant lesions.
Vikneswaran NAMASIVAYAM ; Calvin J KOH ; Stephen TSAO ; Jonathan LEE ; Khoon Lin LING ; Christopher KHOR ; Tony LIM ; James Weiquan LI ; Aung Myint OO ; Benjamin C H YIP ; Ikram HUSSAIN ; Tju Siang CHUA ; Bin Chet TOH ; Hock Soo ONG ; Lai Mun WANG ; Jimmy B Y SO ; Ming THE ; Khay Guan YEOH ; Tiing Leong ANG
Annals of the Academy of Medicine, Singapore 2022;51(7):417-435
Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions.
Adenomatous Polyps
;
Endoscopy
;
Humans
;
Precancerous Conditions/therapy*
;
Singapore
;
Stomach Neoplasms/therapy*
10.Differential diagnosis and treatment of chylothorax and pseudochylothorax after lung cancer surgery
Jie YANG ; Zhuopeng WU ; Weiquan GU ; Jun YE ; Shengli YANG ; Fei WANG ; Ye XIAO ; Xiaowen ZHANG ; Ning ZHAO ; Lingling WU ; Dongsheng LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(8):481-486
Objective:To explore the differential diagnosis and different treatment methods of chylothorax and pseudochylothorax after lung cancer surgery.Methods:Clinical data of 1 584 surgical patients with non-small cell lung cancer from January 2016 to December 2021 were analyzed, 21 cases of chylothorax and 8 cases of pseudochylothorax were identified and analyzed to compare the differences in pleural fluid chyle test, pleural effusion biochemical values, total cholesterol, triglycerides, total cholesterol/triglyceride ratio, leukocyte count, bacterial culture and treatment.Results:The incidence of chylothorax after lung cancer surgery was 1.3%, and the incidence of pseudochylothorax was 0.5%; 80.9%% of chylothorax on the right side was significantly higher than 19.1% of chylothorax on the left side, and the difference was statistically significant( P<0.05). Pseudochylothorax occurred on the right side(100%). The difference between chylothorax and pseudochylothorax in pleural fluid tests for cholesterol and triglyceride was statistically significant( P<0.05), the leukocyte count was significantly higher in pseudochylothorax than chylothorax, and the difference was statistically significant( P<0.05). The differences in drainage before treatment, postoperative drainage time and postoperative hospitalization time between the two groups were statistically significant( P<0.05). The success rate was 61.9% in 13 cases of chylothorax treated conservatively and 38.1% in 8 cases of thoracic duct clamping; all cases of pseudochylothorax were treated conservatively with a success rate of 100%. Conclusion:In naddition to pleural fluid chyle test and pleural effusion biochemical values, total cholesterol, triglyceride and total cholesterol to triglyceride ratio in pleural fluid should be tested to identify chylothorax and pseudochylothorax, high triglyceride in pleural fluid diagnosed as chylothorax; Pseudochylothorax is diagnosed with a cholesterol/triglyceride ratio >1 in the pleural fluid, pseudochylothorax is usually treated conservatively. Chylothorax is treated conservatively and surgically according to different conditions. If the drainage flow is greater than 800 ml/day for 3 consecutive days or if it causes serious electrolyte disorders, it is recommended to perform thoracoscopic-assisted thoracic duct clamping via right-sided approach.

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