1.Onco-metabolic surgery: the bridge between curative resection of gastric cancer and the remission of type 2 diabetes mellitus
Lyujia CHENG ; Zhenpeng WU ; Yuhan QIAO ; Yunsong JIANG ; Lin XIANG ; Lina WU ; Bingsheng GUAN ; Hanlin TANG ; Shifang HUANG ; Jingge YANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1178-1185
		                        		
		                        			
		                        			The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.
		                        		
		                        		
		                        		
		                        	
2.Expression,prognostic relevance of P4HB in glioblastoma and its biological effects on tumor cells
Guan-You HUANG ; Xiao-Hong HOU ; Xue-Cheng GE ; Hong-Chuan GAN ; Shu-Yu HAO ; Zhen WU
Medical Journal of Chinese People's Liberation Army 2024;49(4):459-467
		                        		
		                        			
		                        			Objective To investigate the expression of prolyl 4-hydroxylase β-polypeptide(P4HB)in glioblastoma multiforme(GBM)and its impact on clinical prognosis,as well as on the proliferation and migration of U87 cells.Methods(1)According to the Cancer Genome Atlas(TCGA)database,GTEx database and GEPIA2 database,the difference expression of P4HB in GBM and normal brain tissues were analyzed by R software.(2)A total of 52 patients with GBM who underwent surgical treatment from February 2017 to December 2019 were collected from Department of Neurosurgery,the Second People's Hospital of Guiyang.The normal brain tissues of 10 patients were selected as controls.Immunohistochemical method was used to detect the expression level of P4HB in tumor tissues and normal tissues.The Kaplan-Meier method with the log-rank test was employed for survival analysis.Receiver operating characteristic(ROC)curve was used to analyze the predictive valuable of P4HB expression in survival rate of GBM.Univariate and multivariate Cox regression analysis were used to identify the expression of P4HB and related clinicopathological factors affecting the survival and prognosis of the patients.(3)Human GBM U87 cells were randomly assigned into three groups:control group,NC-siRNA group and P4HB-siRNA group.P4HB expression was interfered with by the transfection of siRNA in P4HB-siRNA group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the content of P4HB mRNA in U87 cells.Cell counting kit-8(CCK-8)and immunofluorescence assay were used to analyze the effects of P4HB on the proliferation of U87 cells.Scratch test was used to analyze the effects of P4HB on cell migration.Results The expression of P4HB was significantly upregulated in GBM tissues compared with normal brain tissues(P<0.05).The γδ T cells(r=-0.227)and follicular helper T cells(r=-0.226)were negatively correlated with the expression of P4HB,while natural killer cell(r=0.417),macrophages(r=0.374),neutrophils(r=0.344),and immature dendritic cells(r=0.263)were positively correlated with the expression of P4HB.Kaplan-Meier survival analysis showed that the progression-free survival and disease-specific survival of GBM patients with high P4HB expression were significantly lower than those with low expression(P<0.05).ROC curve showed that the area under the curve(AUC)of P4HB in predicting overall survival rate of GBM patients was 0.982,and 1-year,3-year,and 5-year survival was 0.655,0.724,0.861,respectively.The immunohistochemistry results suggested that P4HB protein was significantly highly expressed in GBM tumors.Survival analysis indicated that high expression of P4HB was associated with bad prognosis in GBM patients(P<0.05).Multivariate Cox regression analysis indicated that high expression of P4HB and TERT promoter mutations were the independent prognostic risk factors for GBM(P<0.05).Compared with control group and NC-siRNA group,the expression levels of P4HB were decreased significantly after transfected with siRNA in U87 cells of P4HB-siRNA group(P<0.01),and the proliferation ability and the wound healing rate were decreased significantly in P4HB-siRNA group(P<0.001).Conclusions P4HB is significantly highly expressed in GBM,which indicates that the prognosis of patients is poor.Knockout of P4HB could inhibit cellular proliferation and migration of GBM U87 cells.P4HB may be used as the relevant predictive marker and potential therapeutic target in GBM.
		                        		
		                        		
		                        		
		                        	
3.Study on the construction of evaluation index system for multisectoral cooperation in chronic disease prevention and control under the strategy of Healthy China
Yu-Mei HUANG ; Li-Zheng GUAN ; Li-Guang SUN ; You-Li HAN ; Ning ZHANG ; Yan-Bing ZENG ; Cheng-Yu MA
Chinese Journal of Health Policy 2024;17(6):10-16
		                        		
		                        			
		                        			Objective:In order to construct a multisectoral cooperation evaluation index system for chronic disease prevention and control in the Healthy China strategy,so as to provide a reference for the evaluation and improvement of multisectoral cooperation work.Methods:The initial indicator system was constructed based on D'Amour's cooperative structure model.Fifteen public health experts were selected to refine the evaluation indicators through two rounds of expert consultation using the Delphi method.Then weights of indicators were assigned according to AHP.Results:Experts'positive coefficient,level of authority and coordination of opinions were confirmed.The finalized evaluation index system for multisectoral cooperation in chronic disease prevention and control contains 5 first-level indicators,12 second-level indicators and 34 third-level indicators.According to the weight,the indicators in first level were Shared Goals and Vision(0.222 8),Internalization(0.158 7),Formalization(0.252 3),Governance(0.154 5)and Cooperation effects(0.211 8).Conclusions:The evaluation index system applicable to multisectoral cooperation in the prevention and control of chronic diseases in counties(cities/districts)is preliminarily established,which is highly scientific and operable,and lays the foundation for the next step of application and promotion.
		                        		
		                        		
		                        		
		                        	
4.Onco-metabolic surgery: the bridge between curative resection of gastric cancer and the remission of type 2 diabetes mellitus
Lyujia CHENG ; Zhenpeng WU ; Yuhan QIAO ; Yunsong JIANG ; Lin XIANG ; Lina WU ; Bingsheng GUAN ; Hanlin TANG ; Shifang HUANG ; Jingge YANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1178-1185
		                        		
		                        			
		                        			The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.
		                        		
		                        		
		                        		
		                        	
5.Application progress on anti-skin aging effect of traditional Chinese medicine
Xin-min WANG ; Wei-cheng ZHOU ; Li-zhen HUANG ; Jing LI ; Ying-chong CHEN ; Yong-mei GUAN ; Peng-fei YUE
Acta Pharmaceutica Sinica 2023;58(5):1093-1102
		                        		
		                        			
		                        			 With the aging of population intensifies and the level of population health have improved, thus much attention has been directed to how to delaying or preventing skin aging. Skin aging is associated with age, ultraviolet and lifestyle, mainly characterized as skin sagging, wrinkles, pigmentation, so it is urgent to seek traditional Chinese medicine and related cosmetics to solve the problem of skin aging. Traditional Chinese medicine has the functions of anti-oxidation, enhancing human immunity, promoting body metabolism and regulating endocrine, therefore, it has become a research focus in anti-skin aging. This article reviews the skin aging mechanism and the research advances of traditional Chinese medicine anti-skin aging, in order to provide a reference for future research and development of anti-aging traditional Chinese medicine. 
		                        		
		                        		
		                        		
		                        	
6.Inhibition of Fatty Acid β-Oxidation by Fatty Acid Binding Protein 4 Induces Ferroptosis in HK2 Cells Under High Glucose Conditions
Jiasi CHEN ; Keping WU ; Yan LEI ; Mingcheng HUANG ; Lokyu CHENG ; Hui GUAN ; Jiawen LIN ; Ming ZHONG ; Xiaohua WANG ; Zhihua ZHENG
Endocrinology and Metabolism 2023;38(2):226-244
		                        		
		                        			 Background:
		                        			Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD. 
		                        		
		                        			Methods:
		                        			We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells. 
		                        		
		                        			Results:
		                        			In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe2+), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid β-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells. 
		                        		
		                        			Conclusion
		                        			Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid β-oxidation. 
		                        		
		                        		
		                        		
		                        	
7.Pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual in infants and young children undergoing daytime surgery
Hao LUO ; Yao LIU ; Junxiang HUANG ; Yanping GUAN ; Cheng FAN ; Guoping ZHONG ; Xingrong SONG ; Bilian LI
Chinese Journal of Anesthesiology 2023;43(8):966-971
		                        		
		                        			
		                        			Objective:To investigate the pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual in infants and young children undergoing daytime surgery.Methods:One hundred and four pediatric patients of either sex, aged 3-36 months, of American Society of Anesthesiologists Physical Status classification Ⅱ, with body mass index of 18.5-28.0 kg/m 2, diagnosed with oblique inguinal hernia and/or hydrocele, scheduled for laparoscopic high ligation of hernia sac and/or high ligation of sphingoid surgery, were included in the study. Intraoperative neuromuscle relaxation was assessed by transdermal stimulation of the ulnar nerve in the wrist using a TOF Guard monitor. Rocuronium 0.9 mg/kg, propofol 3 mg/kg, and sufentanyl 0.5 μg/kg were intravenously injected for anesthesia induction, and propofol 6-8 mg·kg -1·h -1 was intravenously infused to maintain anesthesia. The pediatric patients were divided into Ⅰgroup and Ⅱ group according to the degree of postoperative neuromuscular block. In group Ⅰ, sugammadex 2 mg/kg was intravenously injected when TOF returned to T 2 recurrence. In group Ⅱ, sugammadex 4 mg/kg was intravenously injected when the single stimulation count was 1 or 2 after tetanic stimulation. At 2 and 10 min after rocuronium administration, at the end of operation, 2 and 10 min after sugammadex administration, and when the children met the standard of leaving the resuscitation room, venous blood samples were collected for determination of plasma concentrations of rocuronium and sugammadex using ultra-high performance liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined using the Pheonix WinNonlin software. The onset of rocuronium and time for recovery of TOF ratio to 90% were recorded. Results:The pharmacokinetics of sugammadex was fitted to the nonlinear mixed-effect satrioventricular model.There was no significant difference in the peak concentration, area under the drug concentration-time curve, elimination half-life, apparent clearance, apparent volume of distribution, mean retention time, and time for TOF ratio returning to 90% between the two groups ( P> 0.05). Conclusions:The pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual is fitted to a nonlinear mixed-effect satrioventricular model, and sugammadex 2 and 4 mg/kg have similar pharmacokinetics in infants and young children undergoing daytime surgery.
		                        		
		                        		
		                        		
		                        	
8.Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development.
Hu LIN ; Hao YANG ; Jun Fen FU ; Jin Na YUAN ; Ke HUANG ; Wei WU ; Guan Ping DONG ; Hong Juan TIAN ; De Hua WU ; Da Xing TANG ; Ding Wen WU ; Li Ying SUN ; Ya Lei PI ; Li Jun LIU ; Li Ping SHI ; Wei GU ; Lu Gang HUANG ; Yi Hua WANG ; Lin Qi CHEN ; Hong Ying LI ; Yang YU ; Hai Yan WEI ; Xin Ran CHENG ; Xiao Ou SHAN ; Yu LIU ; Xu XU ; Shu LIU ; Xiao Ping LUO ; Yan Feng XIAO ; Yu YANG ; Gui Mei LI ; Mei FENG ; Xiu Qi MA ; Dao Xiang PAN ; Jia Yan TANG ; Rui Min CHEN ; Mireguli MAIMAITI ; De Yun LIU ; Xin Hai CUI ; Zhe SU ; Zhi Qiao DONG ; Li ZOU ; Yan Ling LIU ; Jin WU ; Kun Xia LI ; Yuan LI
Chinese Journal of Pediatrics 2022;60(5):435-441
		                        		
		                        			
		                        			Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
		                        		
		                        		
		                        		
		                        			3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics*
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			China/epidemiology*
		                        			;
		                        		
		                        			Cryptorchidism/genetics*
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		                        			Disorders of Sex Development/genetics*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Genital Diseases, Male
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypospadias/genetics*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Membrane Proteins/genetics*
		                        			;
		                        		
		                        			Penis/abnormalities*
		                        			;
		                        		
		                        			Phenotype
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Steroid 21-Hydroxylase/genetics*
		                        			
		                        		
		                        	
9.Inhibition of the CDK9-cyclin T1 protein-protein interaction as a new approach against triple-negative breast cancer.
Sha-Sha CHENG ; Yuan-Qing QU ; Jia WU ; Guan-Jun YANG ; Hao LIU ; Wanhe WANG ; Qi HUANG ; Feng CHEN ; Guodong LI ; Chun-Yuen WONG ; Vincent Kam Wai WONG ; Dik-Lung MA ; Chung-Hang LEUNG
Acta Pharmaceutica Sinica B 2022;12(3):1390-1405
		                        		
		                        			
		                        			Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.
		                        		
		                        		
		                        		
		                        	
10.Application of Matrix-assisted Laser Desorption Ionization Mass Spectrometry in Analysis of Traditional Chinese Medicine:A Comprehensive Review
Guan-hua ZHANG ; Xiao-li LIU ; Lu-qi HUANG ; Xiao WANG ; Wei LIU ; Cheng-long SUN ; Hua-min ZHANG ; Chun-xia MA
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(12):247-255
		                        		
		                        			
		                        			Traditional Chinese medicine (TCM), which owns abundant chemical components and complex action pathways, has been widely recognized in the prevention and treatment of diseases. Some analysis methods have been emerged in order to ensure the quality of TCM and to develop new TCM drugs. Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) is a soft ionization mass spectrometric technique with the advantages of high throughput, high sensitivity, low cost and so on. It provides technical support for the molecular level study on TCM. At present, this technique has been used in the field of composition analysis and metabonomics research of TCM, and plays an important role in the identification of Chinese herbal medicines, real-time molecular screening and the construction of metabolic network pathway of active ingredients. Among them, the selection of appropriate matrix and sample preparation technology is the key to ensure the detection effect of MALDI-MS. With the development and optimization of new matrix, the continuous improvement of sample preparation technology and the combination of MALDI-MS with various analytical methods will greatly improve the detection effect. Based on this, this paper discusses the application of MALDI-MS in TCM, including high-throughput detection of active ingredients in TCM, monitoring of the original medicines and their metabolites in vivo, and in situ visualization and characterization of tissue distribution information of active ingredients in TCM. It also discusses the application prospect and existing problems of MALDI-MS in TCM, so as to provide technical support for the identification of active ingredients in TCM, drug utilization and metabolism. 
		                        		
		                        		
		                        		
		                        	
            
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