1. Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy
Ying-Dong ZHOU ; Meng-Xian ZHANG ; Qing-Ling WANG ; Hao-Ran KANG ; Zhi-Cheng ZHANG ; Xiang-Dong GUO ; Qing-Lin WANG ; Ya-Min LIU
Chinese Pharmacological Bulletin 2024;40(3):455-461
		                        		
		                        			
		                        			 Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by 
		                        		
		                        		
		                        		
		                        	
2.Modified Xiaoyaosan Alleviates Depression-like Behaviors by Regulating Activation of Hippocampal Microglia Cells in Rat Model of Juvenile Depression
Jiayi SHI ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Feng QIU ; Chang LEI ; Hongyu ZENG ; Kaimei TAN ; Hongqing ZHAO ; Dong YANG ; Yuhong WANG ; Pengxiao GUO ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):46-56
		                        		
		                        			
		                        			ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction (Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex) in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control, model, fluoxetine, and low-, medium-, and high-dose (5.36, 10.71, 21.42 g·kg-1, respectively) Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress (CUMS). The sucrose preference test (SPT) was carried out to examine the sucrose preference of rats. Forced swimming test (FST) was carried out to measure the immobility time of rats. The open field test (OFT) was conducted to measure the total distance, the central distance, the number of horizontal crossings, and the frequency of rearing. Morris water maze (MWM) was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase (iNOS, the polarization marker of M1 microglia) and CD206 (the polarization marker of M2 microglia). Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS, CD206, pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] and anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group, the model rats showed a reduction in sucrose preference (P<0.05), an increase in immobility time (P<0.05), decreased motor and exploratory behaviors (P<0.05), and weakened learning and spatial memory (P<0.05). In addition, the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β, IL-6, and TNF-α (P<0.05). Compared with the model group, Baihuan Xiaoyao decoction increased the sucrose preference value (P<0.05), shortened the immobility time (P<0.01), increased the motor and exploratory behaviors (P<0.05), and improved the learning and spatial memory (P<0.01). Furthermore, the decoction down-regulated the positive expression and protein level of iNOS, lowered the levels of TNF-α, IL-1β, and IL-6 (P<0.01), promoted the positive expression of CD206, and elevated the levels of IL-4 and IL-10 (P<0.01) in the hippocampus of the high dose group. Moreover, the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value (P<0.01), shorter immobility time (P<0.01), longer central distance (P<0.01), stronger learning and spatial memory (P<0.01), higher positive expression and protein level of iNOS (P<0.01), lower levels of TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), lower positive expression and mRNA level of iNOS (P<0.05), and higher levels of IL-4 and IL-10 (P<0.05, P<0.01) than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus. 
		                        		
		                        		
		                        		
		                        	
3.The value of high-throughput sequencing data reanalysis in identifying ERBB2 amplification in colorectal cancer patients
Min-Na SHEN ; Li ZHANG ; Xin-Ning CHEN ; Fei HUANG ; Chao-Gang BAI ; Li-Meng CHEN ; Hai-Xiang PENG ; Yan ZHOU ; Bei-Li WANG ; Bai-Shen PAN ; Wei GUO
Fudan University Journal of Medical Sciences 2024;51(2):166-171
		                        		
		                        			
		                        			Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.
		                        		
		                        		
		                        		
		                        	
4.Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China
Haozhuo GUO ; Meng NIU ; Haibo SHAO ; Xinwei HAN ; Jianbo ZHAO ; Junhui SUN ; Zhuting FANG ; Bin XIONG ; Xiaoli ZHU ; Weixin REN ; Min YUAN ; Shiping YU ; Weifu LYU ; Xueqiang ZHANG ; Chunqing ZHANG ; Lei LI ; Xuefeng LUO ; Yusheng SONG ; Yilong MA ; Tong DANG ; Hua XIANG ; Yun JIN ; Hui XUE ; Guiyun JIN ; Xiao LI ; Jiarui LI ; Shi ZHOU ; Changlu YU ; Song HE ; Lei YU ; Hongmei ZU ; Jun MA ; Yanming LEI ; Ke XU ; Xiaolong QI
Chinese Journal of Radiology 2024;58(4):437-443
		                        		
		                        			
		                        			Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.
		                        		
		                        		
		                        		
		                        	
5.Protective effects of Ginkgo biloba extract on presbycusis in the rat model via autophagy pathway
Qing-Ling WANG ; Meng-Xian ZHANG ; Ying-Dong ZHOU ; Hao-Ran KANG ; Xiang-Dong GUO ; Qing-Lin WANG
Chinese Traditional Patent Medicine 2024;46(1):65-71
		                        		
		                        			
		                        			AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.
		                        		
		                        		
		                        		
		                        	
6.Focusing on the evaluation of resectability of bile ducts-Application of medical imaging technology and 3D recon-struction in preoperative planning for radical resection of hi-lar cholangiocarcinoma
Xiang-Min DING ; Dou-Sheng BAI ; Guo-Qing JIANG ; Sheng-Jie JIN ; Chi ZHANG ; Qian WANG ; Bao-Huan ZHOU ; Ao-Qing WANG ; Ren-Jie LIU
Chinese Journal of Current Advances in General Surgery 2024;27(10):789-793
		                        		
		                        			
		                        			Hepatohilar cholangiocarcinoma is a common malignant tumor of the biliary system,and radical surgery is one of the important treatment methods.Due to the narrow space at the hi-lum and the high rate of anatomical variation,radical surgery is challenging.By using medical imag-ing technology and 3D reconstruction,surgeons can accurately determine the stage and classifica-tion of hilar cholangiocarcinoma preoperatively.They can assess the tumor's resectability by Ac-cording to the bile duct separation limit points(U point,P point)and anticipate the impact of portal vein,bile duct,and arterial variations on the surgical plan,thereby improving the rate of radical re-section and reducing complication rates.
		                        		
		                        		
		                        		
		                        	
7.Prognostic values of 18F-FDG PET/CT metabolic parameters combined with clinical pathological indicators in cutaneous malignant melanoma
Rongchen AN ; Yunhua WANG ; Xinyu LU ; Lianbo ZHOU ; Xiaowei MA ; Chuning DONG ; Xin XIANG ; Xuan YIN ; Honghui GUO ; Jiaying YUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(7):396-400
		                        		
		                        			
		                        			Objective:To discuss the relationship between 18F-FDG PET/CT metabolic parameters and clinical pathological indicators and prognosis in cutaneous malignant melanoma (CMM). Methods:A total of 100 CMM patients (62 males, 38 females, age (56.5±2.5) years) who underwent 18F-FDG PET/CT scans at the Second Xiangya Hospital of Central South University from August 2013 to November 2022 were retrospectively enrolled. Clinical pathological indicators (such as primary site, TNM staging, sentinel lymph node (SLN) status) and metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG), whole-body MTV (wb-MTV), and whole-body TLG (wb-TLG)) were collected. ROC curve analyses were used to determine the PET parameters thresholds for progression-free survival (PFS) and melanoma-specific survival (MSS). Kaplan-Meier survival analysis, univariate and multivariate Cox proportional hazards regression models were used to analyze the prognosis of patients′ PFS and MSS, and a nomogram survival prediction model was constructed. Results:Results of ROC curve analyses showed that the thresholds of SUV max of primary tumor (p-SUV max), MTV of primary tumor (p-MTV), TLG of primary tumor (p-TLG), wb-MTV and wb-TLG for predicting PFS and MSS were 7.13, 2.24 cm 3, 6.98 g, 2.57 cm 3, 8.04 g and 9.09, 2.34 cm 3, 7.44 g, 2.24 cm 3, 9.17 g, respectively. Results of univariate analysis indicated that several clinical pathological indicators and metabolic parameters were prognostic risk factors for PFS and MSS. Results of multivariate analysis indicated that metastases of SLN (hazard ratio( HR)=2.54, 95% CI: 1.09-5.90; P=0.030) and wb-TLG>8.04 g( HR=2.58, 95% CI: 1.17-5.72; P=0.019) were independent prognostic risk factors for PFS, while metastases of SLN ( HR=4.53, 95% CI: 1.54-13.35; P=0.006) and wb-TLG>9.17 g ( HR=2.48, 95% CI: 1.26-4.89; P=0.009) were independent risk prognostic factors for MSS. A nomogram survival prediction model based on PET metabolic parameter (wb-TLG) and clinical pathological indicator (SLN status) can effectively predict the prognosis of CMM patients. Conclusions:Clinical pathological parameters and PET parameters are associated with the prognosis of CMM patients. SLN status is critical for prognosis.
		                        		
		                        		
		                        		
		                        	
8.Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis
Huixing WU ; Zhenhua ZHANG ; Changrui LONG ; Guifen GUO ; Yanyu WANG ; Yanchun CHEN ; Juxiong FU ; Shijian XIANG ; Benjie ZHOU ; Chengyu LU
China Pharmacy 2024;35(13):1570-1575
		                        		
		                        			
		                        			OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group (0.5% carboxymethyl cellulose sodium solution), model group (0.5% carboxymethyl cellulose sodium solution), and BP low-dose and high-dose groups (50, 100 mg/kg), with 10 mice in each group. Except for the normal control group, the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model; they were given relevant medicine/solution intragastrically, once a day, for consecutive 8 weeks. After the last medication, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver pathological changes were observed; the expressions of α-smooth muscle actin (α-SMA) and Collagen Ⅰ were detected in liver tissue; the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group, serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups (P<0.05), while liver fibrosis was improved significantly. Meanwhile, metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group, of which 18 substances were upregulated and 157 substances were downregulated; the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism, butanoate metabolism, fatty acid synthesis, tyrosine metabolism, β-alanine metabolism, nicotinic acid and nicotinamide metabolism, glutathione metabolism, etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism, butanoate metabolism, glutathione metabolism and so on in rats with liver fibrosis.
		                        		
		                        		
		                        		
		                        	
9.Assessment and preliminary clinical application of a domestic nucleic acid detection reagent for hepatitis D virus
Yongcong LI ; Rongchen YUAN ; Kuanhui XIANG ; Guomin OU ; Tianxun HUANG ; Fangming CHENG ; Zhenchao TIAN ; Xiongwei LIU ; Xiaozhong WANG ; Feng GUO ; Yahong MA ; Jing ZHOU ; Erhei DAI ; Bangning CHENG ; Tong LI ; Tao SHEN ; Chungen QIAN
Chinese Journal of Laboratory Medicine 2024;47(3):239-244
		                        		
		                        			
		                        			Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.
		                        		
		                        		
		                        		
		                        	
		                				10.Two new isocoumarins from cave-derived Metarhizium anisopliae  NHC-M3-2
		                			
		                			Rong-xiang WU ; Jie-lan GUO ; Hua HUANG ; Jing-jing LIAO ; Yi HAO ; Fan-dong KONG ; Li-man ZHOU ; Chao-jun ZHANG
Acta Pharmaceutica Sinica 2024;59(9):2588-2593
		                        		
		                        			
		                        			 Extracting extracts of secondary metabolites from the karst cave fungus 
		                        		
		                        	
            
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