1.Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
Xinqiao CHU ; Yaning BIAO ; Ying GU ; Meng LI ; Tiantong JIANG ; Yuan DING ; Xiaping TAO ; Shaoli WANG ; Ziheng WEI ; Zhen LIU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):35-42
ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease (NAFLD) and explore the underlying mechanism based on the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows: control, model, Yishanfu (0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, and 9.76 g·kg-1, respectively) Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling, rats were treated with corresponding agents for 4 weeks. Then, the body weight and liver weight were measured, and the liver index was calculated. At the same time, serum and liver samples were collected. The levels or activities of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fe2+ in the serum and TC, TG, free fatty acids (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species (ROS) content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFR1), and divalent metal transporter 1 (DMT1) in the liver were determined by Western blot. ResultsCompared with the control group, the model group showed increases in the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), and decreases in the activities of SOD, GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.05, P<0.01). Meanwhile, the liver tissue in the model group presented steatosis, iron deposition, mitochondrial shrinkage, and blurred or swollen mitochondrial cristae. Compared with the model group, all doses of Danggui Shaoyaosan reduced the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), while increasing the activities of SOD and GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.01). Furthermore, Danggui Shaoyaosan alleviated steatosis, iron deposition, and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.
2.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
3.Current status of pubertal sexual characteristics development of 2 704 girls aged 6-18 years in Tongzhou District of Beijing
Yaqin ZHANG ; Huahong WU ; Wen SHU ; Yang LI ; Chengdong YU ; Tao LI ; Guimin HUANG ; Dongqing HOU ; Fangfang CHEN ; Junting LIU ; Shaoli LI ; Xinnan ZONG
Chinese Journal of Pediatrics 2024;62(5):430-437
Objective:To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese.Methods:A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ 2 test was applied to compare the counting data between two or multiple groups. Results:A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95% CI 8.9-9.1), 10.5 (95% CI 10.4-10.6), and 11.4 (95% CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95% CI 4.6-4.8) years, between P2 and P5 was 4.5 (95% CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95% CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95% CI 9.5-10.6), 9.3 (95% CI 9.2-9.4), and 8.6 (95% CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95% CI 12.4-13.7), 11.6 (95% CI 11.4-11.7), and 11.1 (95% CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions:The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.
4.Establishment and application of fluorescence PCR method for genotyping of Mycoplasma pneumoniae based on specimen nucleic acid
Yiwei ZHANG ; Liyong LIU ; Lihua HE ; Fanliang MENG ; Ruixue GU ; Jie GONG ; Shaoli LI ; Fei ZHAO
Chinese Journal of Microbiology and Immunology 2024;44(8):653-659
Objective:To establish a nucleic acid detection and genotyping method for Mycoplasma pneumoniae ( Mp) based on nucleic acid in clinical samples. Methods:Through genomic comparison, the specific target sequences of Genotype 1 and Genotype 2 Mp strains were selected to design synthetic primers and probes, and a PCR detection and classification method for Mp dual fluorescent probe was established, and the specificity, accuracy, detection limit and repeatability of the method were evaluated. The established fluorescence PCR method was used to detect the nucleic acid of clinical specimens and compared with the reported fluorescent PCR methods. Results:The nucleic acid of 18 pathogens, including other species of Mycoplasma and common respiratory bacteria and viruses, which were closely related to the Mp species, were detected, and the results showed that there was no cross-reactivity. The accuracy of detection and typing of 90 Mp nucleic acid was 100%. The detection limits of Genotype 1 and Genotype 2 Mp samples were 1.0 copy/μl, and the experimental coefficient of variation of repeatability within groups and between groups was less than 2.5%. In the detection of 88 nucleic acid of clinical specimens, the Kappa value was 0.675 and the P value was 0.267 compared with the reported real-time PCR method, showing a high degree of agreement. Conclusions:The method for detecting and genotyping Mp in this study has high sensitivity, specificity, and accuracy, which can be applied to the monitoring and prevention and control of Mp in the disease control system of provinces and cities at all levels in China. This method promotes the improvement of the Mp prevention and control system in China, strengthens the surveillance ability, and is of great significance for the early warning and prediction of Mp.
5.Prevalence of Mycoplasma pneumoniae among children undergoing physical examination
Shaoli LI ; Liyong LIU ; Lele HUANG ; Jie LIU ; Lei WANG ; Li DANG ; Caixin XIANG ; Ying YANG ; Fei ZHAO
Chinese Journal of Microbiology and Immunology 2023;43(7):555-558
Objective:To investigate the prevalence of Mycoplasma pneumoniae ( Mp) in children undergoing physical examination. Methods:This study randomly enrolled 1 303 children at the age of 6-12 years who underwent physical examination in 2023. Their oral and pharyngeal swabs as well as venous blood samples were collected. The prevalence of Mp in these subjects was detected using isolation and culturing, nucleic acid detection and serological test. Chi-square test was used for statistical analysis. Results:Among the 1 303 children, the detection rate of Mp was 4.1% (53/1 303) by culturing, 7.3% (95/1 303) by nucleic acid detection and 13.6% (177/1 303) by serological test. Statistical analysis showed that there were significant differences in the the detection rates of Mp among children undergoing physical examination between the three methods ( P<0.05). Conclusions:The detection rate of Mp in children undergoing physical examination in 2023 was about 4.1%. Isolation and culturing was more accurate than nucleic acid detection and serological test in the detection of Mp in healthy population as the latter two methods would overestimate the rate.
6.Expanded Applications of Traditional Chinese Medicine Four Examination Techniques in Asymptomatic Spleen-Stomach Diseases
Jingwen YU ; Taicheng LU ; Meng LI ; Yuan DING ; Kexin QIN ; Shaoli WANG ; Zhen LIU
Journal of Traditional Chinese Medicine 2023;64(24):2511-2515
Asymptomatic spleen-stomach diseases refer to diseases without related symptoms and signs of abdo-minal pain, bloating, diarrhea an others in patients, but showing lesions or pathological changes discovered by modern medical techniques such as endoscopy, CT, MRI. The four examination techniques of traditional Chinese medicine (TCM) are based on symptoms and signs of patients, which are the advantage of TCM but also have certain limitations. In the context of the increasingly modernized diagnosis and treatment in TCM, it is proposed to expand the application of the four examination techniques from three aspects including microcosmic syndrome differentiation, data sharing, and artificial intelligence in asymptomatic spleen-stomach diseases, in order to achieve the goals of dynamically observing the disease process, collecting disease data in multiple dimensions, and intelligently processing disease data. This will strengthen the modern requirements of early diagnosis and treatment in TCM, and highlight the advantages of TCM in “treating disease before it arises and treating the symptoms beforehand”.
7.Difference analysis of 18F-FMISO PET/CT hypoxia imaging in response to heavy ion radiotherapy in patients with non-small cell lung cancer
Mingyu LIU ; Ningyi MA ; Jian CHEN ; Caiyue REN ; Fuquan ZHANG ; Jingfang MAO ; Kailiang WU ; Guoliang JIANG ; Yun SUN ; Shaoli SONG ; Jingyi CHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(1):11-15
Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.
8.Application value of 68Ga-PSMA-11 PET/CT in newly diagnosed prostatic cancer patients
Wei LIU ; Chang LIU ; Xiaoping XU ; Shaoli SONG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(2):97-101
Objective:To explore the value of 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT in newly diagnosed prostate cancer patients with different risk stratifications, and to compare the performance of this modality with conventional imaging in detecting metastases. Methods:From June 2019 to July 2020, the clinical and imaging data of 60 patients (age range: 44-88 years, median age 69 years) who underwent 68Ga-PSMA-11 PET/CT imaging in Fudan University Shanghai Cancer Center were retrospectively analyzed. Spearman rank correlation analysis was used to explore the correlation of SUV max in primary foci with prostate specific antigen (PSA) and Gleason score (GS). Based on the D′Amico risk stratification (PSA>20 μg/L and ≤20 μg/L, GS>7 and ≤7), the detection rates of 68Ga-PSMA-11 PET/CT for metastases were evaluated by χ2 test, and the differences of SUV max were analyzed by Mann-Whitney U test. Patients were divided into high-risk (PSA>20 μg/L and GS>7), medium-risk (PSA>20 μg/L and GS≤7, or PSA≤20 μg/L and GS>7), and low-risk (PSA<20 μg/L and GS<7) groups according to PSA levels and GS. Compared with conventional imaging (bone imaging, CT or MRI), the ability of 68Ga-PSMA-11 PET/CT to detect metastatic tumors, and the utility to change the prostate cancer stage were evaluated by Fisher′s exact test. Results:High uptake of 68Ga-PSMA-11 was observed in primary lesions of 60 patients, and SUV max was positively correlated with GS or PSA ( rs values: 0.42, 0.38; P values: 0.001, 0.002). The detection rates of lymph node and bone metastases in the group with PSA>20 μg/L were 11/18 and 13/18, respectively, which were higher than those in the group with PSA≤20 μg/L (28.57%(12/42) and 35.71%(15/42); χ2 values: 6.56, 7.56, P values: 0.010, 0.006. However, there was no statistical significance in the SUV max of these lesions( z values: -1.04, -0.96; P values: 0.299, 0.337). There was a statistical difference in the detection rates of lymph node and bone metastases between the group with GS>7 and the group with GS≤7 (lymph node: 54.05%(20/37) vs 13.04%(3/23), χ2=10.09, P=0.001; bone metastases: 59.46%(22/37) vs 26.09%(6/23), χ2=8.19, P=0.004), as well as the SUV max of bone metastases( z=-2.02, P=0.044). In the high-risk group, 68Ga-PSMA-11 PET/CT had the higher detection rate of metastases than conventional imaging (16/17 vs 10/17; P=0.039) and it changed 25.0%(15/60) of the patients′ staging. Conclusions:PSA and GS affect the detection rate of 68Ga-PSMA-11 PET/CT. In patients with high-risk prostate cancer, 68Ga-PSMA-11 PET/CT is superior to conventional imaging in detecting metastases. When PSA>20 μg/L and GS>7, it is better to use 68Ga-PSMA-11 PET/CT in prostate cancer staging.
9.Clinical features of Mycoplasma pneumoniae infection complicated by coagulation dysfunction in children
Lele HUANG ; Zhengli LI ; Ling CAO ; Xiuwei WANG ; Junting LIU ; Shaoli LI
Chinese Journal of Microbiology and Immunology 2023;43(12):932-938
Objective:To compare the clinical features, laboratory test results and imaging findings between cases of Mycoplasma pneumoniae ( Mp) infection complicated by coagulation dysfunction and isolated Mp infection, and analyze the predictive value of related indicators for Mp infection with coagulation dysfunction. Methods:A total of 65 cases of Mp infection complicated by coagulation dysfunction (case group) and 92 cases of isolated Mp infection (control group) treated in the Children′s Hospital Affiliated to Capital Institute of Pediatrics in 2021 were enrolled. Clinical data of the two groups were compared, and receiver operating characteristic (ROC) curves were drawn to analyze the predictive value of differential indicators to the case group. Results:There were no significant differences in the general clinical features or imaging findings between the case group and the control group. The levels of fibrinogen (FIB), D-Dimer, fibrinogen degradation product (FDP), IgE, lactic dehydrogenase (LDH), alanine transaminase (ALT), aspartate aminotransferase (AST), adenosine deaminase (ADA) and C-reactive protein (CRP), activated partial thromboplastin time (APTT), thrombin time (TT), blood platelet count (PLT), neutrophil count, length of hospital stay, peak body temperature, and duration of cough and fever in the case group were higher than those in the control group, and the differences were statistically significant ( P<0.05). The areas under ROC curves of LDH, CRP, peak body temperature, ADA, ALT, neutrophil count, AST and IgE for predicting Mp infection complicated by coagulation dysfunction were 0.855, 0.810, 0.730, 0.716, 0.692, 0.648, 0.631 and 0.603, respectively. The area under ROC curve of LDH, CRP and peak body temperature used in combination was 0.901. Conclusions:LDH, CRP, peak body temperature, ADA, ALT, neutrophil count, AST and IgE had predictive value for Mp infection complicated by coagulation dysfunction, among which LDH, CRP and peak body temperature had higher predictive value. LDH, CRP and peak body temperature used in combination had the highest diagnostic value (AUC=0.901).
10.Characteristics of endometriosis in 18F-FDG PET/CT imaging
Mingzhen XU ; Shuai LIU ; Shaoli SONG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(10):599-603
Objective:To explore the 18F-FDG PET/CT imaging features in endometriosis (EMS), in order to provide valuable information for accurate clinical diagnosis. Methods:The clinical and imaging data of 21 patients (age range 23-72 (44.0±11.4) years) who underwent 18F-FDG PET/CT imaging in Fudan University Shanghai Cancer Center between December 2016 and May 2021, and were pathologically confirmed to be EMS, were retrospectively collected. The symptoms and signs, carbohydrate antigen (CA)125 levels, and the characteristics of the lesions on PET/CT images were analyzed. According to the intraoperative lesion invasion score, patients were divided into group A with lesion confined to the adnexal region (the score ≤4), and group B with multiple sites invaded (the score >4). The differences in age, CA125, SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were analyzed by independent-sample t test or Mann-Whitney U test. Results:About 42.9%(9/21) had a history of dysmenorrhea. CA125 was elevated in 95.2%(20/21) of the patients. CA125 levels of the group A and group B were 88.4(42.0, 351.5) and 619.8(72.3, 1 420.0) kU/L, respectively, which meant the higher the CA125 and the wider the lesion involvement ( z=-2.32, P=0.041). The older the patients, the more likely the lesions were confined to the adnexal region ( t=-2.10, P=0.049). The SUV max of the two groups were 3.67±1.78 and 3.93±1.88, respectively ( t=0.33, P=0.746). The other metabolic parameters (SUV mean, MTV and TLG) of the 2 groups were not significantly different either ( t=0.79, both z=-1.16, P values: 0.446, 0.245, 0.245). About 23.8%(5/21) of patients were with SUV max greater than 5, and 4 of them had inflammation. Conclusions:EMS patients are often accompanied by abdominal pain and increased CA125. The older the age, the more prone to focal involvement of appendages. The higher the CA125 level, the wider the lesion involvement. The 18F-FDG metabolism level has nothing to do with the scope of the lesion, but when the SUV max of the lesion >5, it is often accompanied by acute inflammation, which is easy to be misdiagnosed.

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