1.Preliminary application of sacral neuromodulation in patients with benign prostatic hyperplasia complicated with underactive bladder after transurethral resection of the prostate
Ning LIU ; Yan ZHANG ; Tao LI ; Qiang HU ; Kai LU ; Lei ZHANG ; Jianping WU ; Shuqiu CHEN ; Bin XU ; Ming CHEN
Journal of Modern Urology 2025;30(1):39-42
		                        		
		                        			
		                        			[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.
		                        		
		                        		
		                        		
		                        	
2.A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance.
Lei SUN ; Arabella H WAN ; Shijia YAN ; Ruonian LIU ; Jiarui LI ; Zhuolong ZHOU ; Ruirui WU ; Dongshi CHEN ; Xianzhang BU ; Jingxing OU ; Kai LI ; Xiongbin LU ; Guohui WAN ; Zunfu KE
Acta Pharmaceutica Sinica B 2024;14(1):223-240
		                        		
		                        			
		                        			Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.
		                        		
		                        		
		                        		
		                        	
3. The regulatory mechanism of physiological sleep-wake
Wei-Jie LU ; Kai LIU ; Xin-Ke ZHAO ; Qian-Rong LI ; Ying-Dong LI ; Guo-Tai WU
Chinese Pharmacological Bulletin 2024;40(3):421-426
		                        		
		                        			
		                        			 This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded. 
		                        		
		                        		
		                        		
		                        	
4.Exploration and Prospect of Quantitative Evaluation of Integrity Risk Prevention and Control in Public Hospitals
Yan CHEN ; Zhuoma JIAHUAN ; Kai WU ; Shiying LI ; Xinyu CUI ; Lu CENG ; Fang ZHU ; Juan XIE
Chinese Hospital Management 2024;44(3):80-83
		                        		
		                        			
		                        			Objective To explore the quantitative evaluation of integrity risk prevention and control in public hospitals,provide reference for improving the quality and efficiency of integrity risk prevention and control.Methods Self-designed"Inspection Standards for Integrity Risk Prevention and Control of Power Matters in Public Hospitals"was used to score and rate the power matters provided by each functional department/clinical department of West China Hospital of Sichuan University from three aspects:the clarity of power operation process,the accuracy of finding integrity risk points,the effectiveness of prevention and control measures.Results A total of 236 power matters of the hospital were inspected for integrity risk prevention and control,and according to the inspection criteria,57 items were rated as first grade,103 items were rated as second grade,and 76 items were rated as third grade,accounting for 24.15%,43.64%and 32.20%,respectively.The score for the special work of integrity risk prevention and control was 5.82±1.92 points,of which the process dimension score was 2.11±0.75 points,the risk points dimension score was 1.89±0.92 points,the prevention and control dimension score is 1.89± 0.79 points,which reflects the problems of unclear workflow,inaccurate finding of individual risk points,and unspecified prevention and control measures in some units.Conclusion Hospitals should focus on the concreteness,accuracy,salience and quantification in the long-term construction of integrity risk prevention and control from the aspects of thought,behavior,effectiveness and evaluation.
		                        		
		                        		
		                        		
		                        	
5.Research progress in the effectiveness and mechanism of hyperbaric oxygen therapy for depression
Lin XIAO ; Xiaomei ZHANG ; Kai WU ; Lu WANG
Sichuan Mental Health 2024;37(1):91-96
		                        		
		                        			
		                        			Hyperbaric oxygen therapy characterized by fewer side effects and simple operation has been explored as a potential therapy for depression. This article provides a review of researches relevant to current clinical application and mechanism of hyperbaric oxygen therapy for depression, aiming to provide valuable references for the formulation of new strategies for the treatment of depression. Hyperbaric oxygen therapy has been demonstrated to be useful as an adjunctive therapy for depression, which can effectively alleviate depression by regulating the homeostasis of hypothalamus-pituitary-adrenal axis, inhibiting inflammation and enhancing synaptic plasticity. And hyperbaric oxygen therapy as adjuvant to antidepressants for depression can contribute to increasing the treatment effectiveness to some extent. 
		                        		
		                        		
		                        		
		                        	
6.Efficacy of Pulmonary Artery Banding in Pediatric Heart Failure Patients:Two Cases Report
Zheng DOU ; Kai MA ; Benqing ZHANG ; Lu RUI ; Ye LIN ; Xu WANG ; Min ZENG ; Kunjing PANG ; Huili ZHANG ; Fengqun MAO ; Jianhui YUAN ; Qiyu HE ; Dongdong WU ; Yuze LIU ; Shoujun LI
Chinese Circulation Journal 2024;39(5):511-515
		                        		
		                        			
		                        			Two pediatric heart failure patients were treated with pulmonary artery banding(PAB)at Fuwai Hospital,from December 2021 to January 2022.In the first case,an 8-month-old patient presented with left ventricular non-compaction cardiomyopathy(LVNC),left ventricular systolic dysfunction,ventricular septal defect,and atrial septal defect.The second case was a 4-month-old patient with LVNC,left ventricular systolic dysfunction,and coarctation of the aorta.After PAB,the left ventricular function and shape of both patients were significantly improved,without serious surgery-related complications.In these individual cases of pediatric heart failure,pulmonary artery banding exhibited a more satisfactory efficacy and safety compared to pharmacological treatment,especially for those with unsatisfactory medication results.Future clinical data are needed to promote the rational and broader application of this therapeutic option for indicated patients.
		                        		
		                        		
		                        		
		                        	
7.Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma
Shou-Wu WU ; Shao-Kun LIN ; Zhong-Zhu NIAN ; Xin-Wen WANG ; Wei-Nian LIN ; Li-Ming ZHUANG ; Zhi-Sheng WU ; Zhi-Wei HUANG ; A-Min WANG ; Ni-Li GAO ; Jia-Wen CHEN ; Wen-Ting YUAN ; Kai-Xian LU ; Jun LIAO
Progress in Biochemistry and Biophysics 2024;51(9):2182-2193
		                        		
		                        			
		                        			ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC. 
		                        		
		                        		
		                        		
		                        	
8.Network meta-analysis for efficacy and safety of TACE combined with anti-angiogenic drugs in the treatment of unresectable primary liver cancer
Fenping LU ; Guangyan XING ; Bowen LIU ; Xiaobin LI ; Kai ZHAO ; Yun RAN ; Fenfang WU ; Shiping HU
China Pharmacy 2024;35(20):2533-2540
		                        		
		                        			
		                        			OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer (PLC). METHODS Retrieved from Chinese and English databases such as CNKI, the Cochrane Library, Google, and Baidu Academic, randomized controlled trial (RCT) about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27, 2024. After screening the literature, extracting data, and evaluating the quality of the literature, network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included, involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival (mOS) and median progression- free survival (mPFS), TACE+apatinib had the best efficacy, with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate (ORR) and disease control rate (DCR), TACE+donafenib had the best efficacy, with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety, TACE+donafenib was the best, with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC, and TACE+donafenib has the best safety profile.
		                        		
		                        		
		                        		
		                        	
9.Effect and mechanism of Mex3c gene knockout on embryonic neural tube development
Zhi-Guo LU ; Xiao-Ting WU ; Kai WANG ; Bo ZHANG ; Yong WANG ; Yong DU
Medical Journal of Chinese People's Liberation Army 2024;49(9):1029-1037
		                        		
		                        			
		                        			Objective To investigate the effect of Mex3c gene knockout on embryonic neural tube development and its possible mechanisms.Methods The NCBI database was used to analyze the expression of Mex3c gene in various tissues of mice.Fluorescence in situ hybridization(FISH)was employed to detect the expression of Mex3c in neural tubes of Mex3c+/+mice at different developmental stages(E12.5 d,E14.5 d).Sexual mature mice were mated at a ratio of Mex3c+/-male to female(1:1)in the same cage.Embryos were collected and genotyped using PCR.They were divided into 3 groups based on their genotype:wild-type group(Mex3c+/+,WT group),homozygous knockout group(Mex3c-/-,KO group),and heterozygous knockout group(Mex3c+/-).HE staining was employed to observe the development of neural tubes in the 3 groups of embryos.Immunofluorescence staining and Western blotting were performed to detect the proliferation and apoptosis of embryonic neural stem cells in the WT and KO groups.Transmission electron microscopy was used to observe the ultrastructure of the neural tubes and mitochondria in the WT and KO groups.RNA was extracted from the neural tubes of WT and KO groups for RNA-seq sequencing.The R.3.6.3 software was used to perform KEGG signaling pathway enrichment analysis on differentially expressed genes.RT-qPCR was used to validate the sequencing results.Results The NCBI database analysis and FISH detection results showed that the Mex3c gene was mainly expressed in the central nervous system of embryos.HE staining results showed that there was no significant difference in the development of embryonic neural tubes between KO group,WT group,and heterozygous knockout group at E12.5 d and E13.5 d.However,at E14.5 d,the embryonic neural tube development in KO group was delayed and the phenotype was significantly abnormal compared with those in WT group.Therefore,the embryonic neural tube tissues of KO group and WT group at E14.5 d were selected for subsequent experiments.The immunofluorescence staining results showed that the PCNA positive cell rate in KO group was significantly lower than that in WT group(P<0.001).The Western blotting results showed that the Bax/Bcl-2 ratio in KO group was higher than that in WT group(P<0.01).Transmission electron microscopy observation showed that compared with WT group,the synaptic gap in KO group disappeared,the mitochondrial of the embryonic neural tube in KO group were swollen,the mitochondrial cristae were disrupted,and the structure was significantly abnormal.The results of RNA-seq analysis showed that a total of 377 differentially expressed genes were obtained,including 101 up-regulated genes and 276 down-regulated genes.KEGG signaling pathway enrichment analysis revealed that the main signaling pathways of differentially expressed genes were enriched in the neuroactive ligand receptor interaction signaling pathways.The RT-qPCR validation results showed that the mRNA expression levels of Avpr1a,Drd1,Htr7,Sstr1,Oxtr and Gabra5 in this signaling pathway were down-regulated(P<0.05 or P<0.01),which was consistent with the RNA-seq results.Conclusion Mex3c plays an important role in the development of neural tubes in mouse embryos,which may participate in regulating the proliferation and apoptosis of neural stem cells through neural active ligand receptor interaction signaling pathways,thereby affecting the development of neural tubes.
		                        		
		                        		
		                        		
		                        	
10.Effect and mechanism of thyroid hormone T3 On the liver oxidative stress in alcoholic liver fibrosis mice
Ren-Li LUO ; San-Qiang LI ; Jia-Yang FENG ; Kai-Jie ZHANG ; Shan LU ; Jun-Fei WU
Acta Anatomica Sinica 2024;55(6):753-760
		                        		
		                        			
		                        			Objective To construct a mouse model of alcoholic liver fibrosis and explore the effect of supplementing exogenous thyroid hormone T3 on oxidative stress in liver.Methods Eighty mice were randomly divided into 6 groups,normal control group,alcoholic liver fibrosis(ALF)model group,and low concentration T3 intervention group(25 μg/kg),medium concentration T3 intervention group(50 μg/kg),high concentration T3 intervention group(100 μg/kg)and T3 control group(the concentration of T3 is 100 μg/kg).A model of mice alcoholic liver fibrosis was established by using alcoholic liquid feed combined with 31.5%ethanol gavage.From the sixth week,mice in the T3 intervention and T3 control group were injected with corresponding concentrations of T3 intraperitoneally for three weeks.Mice in the control and T3 control groups were fed with control liquid feed.The degree of mice liver injury and fibrosis was evaluated through the sirius red staining,Western blotting,and serum biochemical testing.The activity of superoxide dismutase(SOD),the content of glutathione(GSH)and malondialdehyde(MDA)in liver tissue were detected by ELISA,and the protein expressions of microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ)and p62 were detected by immunohistochemistry and Western blotting.Results The liver structure and function in the ALF group were severely damaged,autophagy was inhibited,and the oxidative stress response was significantly enhanced compared with the control group.Compared with the ALF group,the recovery of liver functional and structure and autophagy were showed in the T3 intervention group,and SOD activity and GSH content in the liver increased in the low and medium concentrations of T3 intervention groups,while MDA content significantly decreased.In the high concentration T3 intervention group,it showed the same increase in SOD activity,a significant decrease in MDA content,while the content of GSH was lower than that in the control group,which was not different with the ALF group.Conclusion Appropriate supplementation of T3 could affect the occurrence and development of alcoholic liver fibrosis by restoring the liver autophagy to inhibit the oxidative stress response.
		                        		
		                        		
		                        		
		                        	
            
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