1.The regulatory role of the RUS family in plant growth and development.
Yao HU ; Sirui LI ; Xinxin ZHANG ; Qinglin TANG ; Dayong WEI ; Shibing TIAN ; Yang YANG ; Zhimin WANG
Chinese Journal of Biotechnology 2024;40(1):81-93
		                        		
		                        			
		                        			The chloroplast genome encodes many key proteins involved in photosynthesis and other metabolic processes, and metabolites synthesized in chloroplasts are essential for normal plant growth and development. Root-UVB (ultraviolet radiation B)-sensitive (RUS) family proteins composed of highly conserved DUF647 domain belong to chloroplast proteins. They play an important role in the regulation of various life activities such as plant morphogenesis, material transport and energy metabolism. This article summarizes the recent advances of the RUS family proteins in the growth and development of plants such as embryonic development, photomorphological construction, VB6 homeostasis, auxin transport and anther development, with the aim to facilitate further study of its molecular regulation mechanism in plant growth and development.
		                        		
		                        		
		                        		
		                        			Female
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		                        			Pregnancy
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		                        			Humans
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		                        			Ultraviolet Rays
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		                        			Biological Transport
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		                        			Chloroplasts/genetics*
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		                        			Embryonic Development
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		                        			Plant Development/genetics*
		                        			
		                        		
		                        	
2.Exploring the Mechanism of Action of Guhuaisi Kangfu Pill for Treating Steroid-induced Osteonecrosis of the Femoral Head Based on WGCNA and Animal Experiment Validation
Wenxi LI ; Liangyu TIAN ; Jin ZHANG ; Caihong SHEN ; Zhimin YANG ; Jiaqiao GUO ; Yuju CAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1306-1318
		                        		
		                        			
		                        			Objective To investigate the main pharmacological basis and mechanism of action of Guhuaisi Kangfu Pill(GHSKF)in the treatment of steroid-induced osteonecrosis of the femoral head(SONFH).Methods The active constituents and targets of GHSKF were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases.The speculative targets of SONFH were screened out based on GeneCards and Online Mendelian Inheritance in Man(OMIM)databases.The gene modules and hub genes of SONFH were identified using a weighted gene co-expression network analysis(WGCNA).The intersection of the two targets and the result of WGCNA was taken to obtain the potential targets of GHSKF for the treatment of SONFH.The key active constituents were screened with the"active constituent-target"network,which was constructed by the Cytoscape software.Then,the STRING database was used to construct the protein interaction network to screen the key targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of key targets was performed,and the relationship between key active constituent,key targets and key signaling pathways was explored.Finally,the molecular docking between key active constituents and key targets was verified.In addition,the SONFH rat model was used for experimental verification.Results A total of 146 compounds and the corresponding 346 targets were identified based on the TCMSP database.A total of 4 187 targets of SONFH were obtained based on GeneCards and OMIM databases.In addition,twelve gene modules and 2 556 hub genes of SONFH were screened out based on WGCNA.Quercetin,luteolin and kaempferol were key active ingredients for the treatment of SONFH.Various signaling pathways such as PI3K/AKT were involved.Molecular docking showed the key active ingredients had good binding activity with the key targets.The results of animal experiments demonstrated that GHSKF could improve bone biological alterations by up-regulating AKT1,PI3K,RUNX2,and down-regulating the expression of Caspase-3 and IL-6(P<0.01),which verified some results of the network pharmacology prediction.Conclusion We analyzed the potential mechanism of action of GHSKF for the treatment of SONFH using network pharmacology and animal experiments,which may provide a reference for further research on its pharmacological basis and targets.
		                        		
		                        		
		                        		
		                        	
3.Cognition and coping of ICU nurses on post-ICU syndrome in family members of patients during hospitalisation:a qualitative study
Can CHEN ; Dandan LI ; Yanhong PENG ; Xuyan YANG ; Chaoli XIE ; Yujie TIAN ; Zhimin WANG
Modern Clinical Nursing 2024;23(9):24-30
		                        		
		                        			
		                        			Objective To understand the recognition and coping strategies of ICU nurses on post-ICU syndrome in family members of patients during hospitalisation so as to provide a reference for handling post-ICU syndrome of the family members of patients.Methods A phenomenological approach within qualitative research was adopted.Semi-structured in-depth interviews were conducted with 15 ICU nurses from 3 wards of the Second Affiliated Hospital of South China University.Colaizzi 7-step method was applied to analyse and refine the interview data themes.Results Three main themes and nine sub-themes were identified and they were insufficient cognition of post-ICU syndrome of the family members(limited understanding of post-ICU syndrome in family members,difficulty in recognising or ignoring symptoms,uncertainty about the impact of post-ICU syndrome),active coping with post-ICU syndrome of the family members(coping mainly through listening and explaining,coping mainly through verbal and physical actions,diligent patient care)and various factors hindering nurses'coping with post-ICU syndrome of the family members(compassion fatigue,high ICU work intensity,limited contact time with family members).Conclusion ICU nurses have insufficient understanding of post-ICU syndrome with the family members of patients during hospitalisation.It requires to enhance a comprehensive understanding in ICU nurses about post-ICU syndrome of the family members of patients and to optimise coping strategies to alleviate negative emotions of the family members.Additionally,efforts should be made to overcome factors that hinder nurses'coping with post-ICU syndrome of the family members of patients and to promote a harmonious relationship between medical staff and patients.
		                        		
		                        		
		                        		
		                        	
4.Reform and Development of Rare Diseases Drug Evaluation and Approval in China
Guo HUANG ; Zhimin YANG ; Ling TANG ; Jie ZHANG ; Xing AI ; Geleng SE RI ; Tian ZHAO
JOURNAL OF RARE DISEASES 2024;3(4):438-445
Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.
5.Consideration on"Patient-Centered"Drug Development for Rare Diseases
Ling TANG ; Xing AI ; Tian ZHAO ; Zhimin YANG
JOURNAL OF RARE DISEASES 2024;3(2):168-174
		                        		
		                        			
		                        			The unmet clinical needs of patients with rare diseases persist.Many rare diseases lack effec-tive treatments,and drug development for rare diseases faces greater challenges than that for common multiple diseases.In recent years,the concept of"patient-centered"drug development has been widely adopted.The Center for Drug Evaluation(CDE)of the National Medical Products Administration has successively issued a series of relevant guiding principles,such as the Technical Guidelines for the Implementation of Patient-Centered Clinical Trials,to promote a"patient-centered"drug development model.The implementation of the"patient-centered"approach in rare disease drug research and development,with a focus on patient perspectives and ac-tive engagement,can effectively facilitate a comprehensive understanding of rare diseases and patient needs among drug research and development enterprises,researchers,and regulatory agencies.This approach also en-hances the accuracy and efficiency of rare disease drug research and development.The CDE will continue to pri-oritize the integration of the"patient-centered"concept into rare disease drug research and development,effec-tively enhance the involvement of rare patients in the drug research and development process,and leverage the guiding role of patients'perspectives on drug research and development.
		                        		
		                        		
		                        		
		                        	
6.Analysis of Mechanism of Antidepressant Effect of Sophora flavescens Seed Extract
Tian ZHU ; Ru WANG ; Lihua BIAN ; Wenjing LI ; Jie LI ; Liangmian CHEN ; Zhimin WANG ; Huimin GAO ; Jianyou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):122-129
		                        		
		                        			
		                        			ObjectiveTo explore the antidepressant effect of Sophora flavescens seed extract and its molecular mechanism. MethodA mouse depression model was established by intraperitoneal injection of lipopolysaccharide(LPS), and normal group, model group, fluoxetine group(2.5 mg·kg-1), and S. flavescens seed low, medium and high dose groups(200, 400, 800 mg·kg-1) were set up for 7 d of consecutive gavage. Then the antidepressant effect of S. flavescens seed extract was evaluated by using open field test, elevated plus maze test and forced swimming test. Pathological morphological changes in the hippocampal tissue was observed by hematoxylin-eosin(HE) staining. Protein expression levels of G1/S-specific cyclin D1(Cyclin D1), Wnt1, β-catenin and phosphorylated glycogen synthase kinase-3β(p-GSK-3β) in mouse brain tissues were detected by Western blot. Hippocampal cell apoptosis was detected by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate(dUTP) nick end labeling(TUNEL). ResultThe results of mouse behavioral experiments showed that compared with the normal group, the speed of movement in the open field and the distance of movement in the central area of the open field, and the time spent on the open arms of the elevated plus maze were significantly reduced in the model group(P<0.01), while immobility time in the forced swimming test was significantly increased(P<0.05). Compared with the model group, the S. flavescens seed medium and high dose groups had increased speed of movement in the open field test and time spent on the open arms of the elevated plus maze test(P<0.05, P<0.01), and decreased immobility time in the forced swimming test(P<0.05), the distance of movement in the central area of the open field test increased in the high dose group(P<0.05). HE staining results showed that compared with the normal group, the hippocampal neuron structure of mice in the model group was damaged. Compared with the model group, after treatment of S. flavescens seed extract, the pathological state of the mouse hippocampal neuron structure was alleviated, and the neurons increased, were neatly arranged, and the cytoplasm was clear. Western blot results showed that the protein expression levels of Wnt1 and β-catenin in mouse brain tissue were significantly decreased(P<0.01), while the protein expression levels of Cyclin D1 and p-GSK-3β were significantly increased(P<0.01) after LPS injection. Compared with the model group, protein expression levels of Wnt1 and β-catenin in brain tissue of S. flavescens seed medium and high dose groups were significantly increased(P<0.01), while the protein expression levels of Cyclin D1 and p-GSK-3β were significantly decreased(P<0.01). TUNEL staining results showed that the hippocampal cell apoptosis rate in the model group was significantly increased compared with that of the normal group(P<0.01), while the hippocampal cell apoptosis rate in the S. flavescens seed medium and high dose groups was significantly decreased compared with that of the model group(P<0.01). ConclusionS. flavescens seed extract can effectively improve the severity of depression in LPS-induced depressed mice, and its molecular mechanism is related to the regulation of neuroinflammation and hippocampal neuronal apoptosis mediated by Wnt/β-catenin signaling pathway. 
		                        		
		                        		
		                        		
		                        	
7.Expression of pepsin in nasopharyngeal carcinoma and its correlation with quality of life after radiotherapy
Tian ZHANG ; Guodong YU ; Ying JIN ; Fangwei ZHOU ; Qiang TANG ; Zhipeng XIAN ; Zhimin WU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(6):699-705
		                        		
		                        			
		                        			Objective:By analyzing the expression of pepsin in nasopharyngeal carcinoma (NPC) tissues, to investigate the correlation between laryngeal reflux (LPR) and NPC, as well as the effect of LPR on the quality of life of patients with NPC after radiotherapy.Methods:A total of 133 patients with NPC who underwent radiotherapy at the Department of Otorhinolaryngology of the Affiliated Hospital of Guizhou Medical University and the Affiliated Cancer Hospital of Guizhou Medical University from 2005 to 2019 were enrolled consecutively, including 90 males and 43 females, aged (44.32±7.47) years old. At the same period, 58 patients with chronic nasopharyngitis who underwent nasopharyngeal biopsy were selected as the control group. Immunohistochemical method was used to detect the expression of pepsin in nasopharyngeal specimens of the two groups. In addition, 188 normal individuals were selected as the normal group in the same period. NPC patients before and within 6 months after radiotherapy were inverstigated by the General Information Questionnaire and the Quality of Life Scale, and the pepsin levels in saliva of NPC patients before and after radiotherapy and the individuals in normal group were measured. SPSS 21.0 software was used for statistical analysis.Results:Pepsin expression in 133 specimens of NPC patients was strongly positive in 24 cases (18.05%), positive in 21 cases (15.79%), weakly positive in 69 cases (51.88%), and negative in 19 cases (14.29%). The specimens of control group had 10 cases of weakly positive (17.24%), 48 cases of negative (82.76%), but no strong positive or positive pepsin expression. The rate of positive pepsin expression in the NPC group was higher than that in the control group, with a statistically significant (χ 2=83.15, P<0.001). The pepsin content in the saliva of NPC patients after radiotherapy ((30.31±7.82) ng/ml) was higher than that before radiotherapy ((20.47±8.21) ng/ml) and the normal group (5.11±2.13) ng/ml), and the pepsin content in saliva before radiotherapy was higher than that in the normal group, and all differences were statistically significant (all P<0.05). After radiotherapy, the five functional domains of quality of life and overall quality of life of NPC patients decreased, while the related symptom scores increased (all P<0.05). Multiple linear regression analysis showed that pepsin content in saliva was the influential factor of five functional domains of quality of life, related symptoms and overall quality of life in NPC patients after radiotherapy (all P<0.05). Conclusion:The positive rate of pepsin expression in NPC tissues is high, and the pepsin in saliva before and after radiotherapy of NPC patients is significantly higher than that in normal, suggesting that LPR may be involved in the process of NPC and affect the quality of life after radiotherapy in NPC patients.
		                        		
		                        		
		                        		
		                        	
8.Analysis of differential genes and metabolic pathway related to functional male sterility in eggplant.
Zhimin WANG ; Chao YUAN ; Zeqin DING ; Ruolin HU ; Yi NIU ; Qinglin TANG ; Dayong WEI ; Ming SONG ; Yongqing WANG ; Shibing TIAN
Chinese Journal of Biotechnology 2021;37(1):253-265
		                        		
		                        			
		                        			Based on observing the cytological characteristics of the flower buds of the functional male sterile line (S13) and the fertile line (F142) in eggplant, it was found that the disintegration period of the annular cell clusters in S13 anther was 2 days later than that of F142, and the cells of stomiun tissue and tapetum in F142 disintegrated on the blooming day, while it did not happen in S13. The comparative transcriptomic analysis showed that there were 1 436 differential expression genes (DEGs) (651 up-regulated and 785 down-regulated) in anthers of F142 and S13 at 8, 5 days before flowering and flowering day. The significance analysis of GO enrichment indicated that there were more unigene clusters involved in single cell biological process, metabolism process and cell process, and more catalytic activity and binding function were involved in molecular functions. Through KEGG annotation we found that the common DEGs were mainly enriched in the biosynthesis of secondary metabolites, metabolic pathway, protein processing in endoplasmic reticulum, biosynthesis of amino acids, carbon metabolism and plant hormone signal transduction. The fifteen genes co-expression modules were identified from 16 465 selected genes by weighted gene co-expression network analysis (WGCNA), three of which (Plum2, Royalblue and Bisque4 modules) were highly related to S13 during flower development. KEGG enrichment showed that the specific modules could be enriched in phenylpropanoid biosynthesis, photosynthesis, porphyrin and chlorophyll metabolism, α-linolenic acid metabolism, polysaccharide biosynthesis and metabolism, fatty acid degradation and the mutual transformation of pentose and glucuronic acid. These genes might play important roles during flower development of S13. It provided a reference for further study on the mechanism of anther dehiscence in eggplant.
		                        		
		                        		
		                        		
		                        			Flowers/genetics*
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		                        			Gene Expression Profiling
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		                        			Gene Expression Regulation, Plant
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		                        			Humans
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		                        			Infertility, Male
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		                        			Male
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		                        			Metabolic Networks and Pathways/genetics*
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		                        			Solanum melongena/genetics*
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		                        			Transcriptome/genetics*
		                        			
		                        		
		                        	
9.Optimization of Primary Processing Technology of Gentiana rigescens by Box-Behnken Design-response Surface Method
Xinyi WU ; Xiuwei LIU ; Yunhui QU ; Pingping SHI ; Yan YANG ; Zhimin LI ; Hao TIAN ; Liping GU
China Pharmacy 2020;31(15):1830-1835
		                        		
		                        			
		                        			OBJECTIVE:To optimize the primary processing technology of Gentiana rigesce ns. METHODS :HPLC method was adopted for content determination of loganic acid ,swertiamarin and gentiopicroside in G. rigescens ,and overall desirability value (OD value ) of the contents of above 3 components was taken as index to carry out single factor test on blanching temperature,blanching time and drying temperature. Based on that ,Box-Behnken design-response surface methodology was used to optimize primary processing technology of G. rigescens . Validation test was also performed. The samples prepared by optimized technology were compared with those dried in the shade. RESULTS :The optimal primary processing technology of G. rigescens included blanching time of 5 min,blanching temperature of 40 ℃ and drying temperature of 60 ℃. Validation test showed that the average OD value of the 3 components was 0.565 2,with a deviation of 0.94% from the predicted value (0.570 6). Compared with samples dried in the shade ,OD value of 3 components in samples prepared by optimized technology were increased significantly , indicating the quality of the samples prepared by the optimized technology was better. CONCLUSIONS :The optimal technology is stable and feasible ,and can be used for the primary processing of G. rigescens .
		                        		
		                        		
		                        		
		                        	
10.The efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation: a randomized, controlled, multi-center clinical trial with 2 years’ follow-up
Hao YU ; Kaiwen LI ; Hailong HU ; Xiang LI ; Nan LIU ; Jian ZHANG ; Xudong YAO ; Xiaodong ZHANG ; Wei LI ; Liqun ZHOU ; Xiangbo KONG ; Jinjian YANG ; Youhan CAO ; Junli WEI ; Jiacun CHEN ; Zhaoyang WU ; Dongwen WANG ; Xuhui ZHANG ; Jinkai SHAO ; Qingwen LI ; Huiqing ZHANG ; Xiaolin WANG ; Shaozhong WEI ; Ye TIAN ; Tie ZHONG ; Hongshun MA ; Kun LI ; Benkang SHI ; Jin YANG ; Yuhua QIAO ; Hongxing HUANG ; Liming LI ; Zhimin WANG ; Jianhua TIAN ; Tianxin LIN ; Jian HUANG
Chinese Journal of Urology 2020;41(10):724-730
		                        		
		                        			
		                        			Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.
		                        		
		                        		
		                        		
		                        	
            
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