1.Zuoguiwan Treats Cyclophosphamide-induced Premature Ovarian Failure by Regulating SLC7A11/GPX4 Pathway to Inhibit Ferroptosis
Min ZHAO ; Jinrong ZHANG ; Jianghuan HUA ; Min XIAO ; Zhihua ZHANG ; Biran ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):60-66
ObjectiveTo investigate the effect of Zuoguiwan on the ovarian function in the rat model of cyclophosphamide-induced premature ovarian failure (POF) based on the changes of ferroptosis pathway. MethodForty SD rats were randomized into blank, model, and low- and high-dose (2, 8 g·kg-1, respectively) Zuoguiwan groups, with 10 rats in each group. The rats in the other groups except the normal group were intraperitoneally injected with CTX at a dose of 50 mg·kg-1 on the first day and 8 mg·kg-1 from the second day to the fifteenth day for the modeling of POF. After modeling, the rats were administrated with corresponding drugs or normal saline by gavage for four weeks. Hematoxylin-eosin staining was performed to observe the pathological changes in the ovarian tissue. The mitochondria of the ovarian tissue was observed by electron microscopy. The serum levels of follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), anti-Mullerian hormone (AMH), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and iron ion were measured by biochemical methods and enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain (FTH1), and acyl-CoA synthetase long chain family member 4 (ACSL4). ResultCompared with the blank group, the model group showcased significantly increased atretic follicles, atrophied, fragmented, and vacuolated mitochondria, and reduced, loose, and disordered cristae in mitochondria. Compared with the model group, high-dose Zuoguiwan increased mature follicles, the volume of mitochondria in the ovary, alleviated the vacuolation, and improved the number and arrangement of mitochondrial cristae. Compared with the blank group, the modeling elevated the levels of iron, MDA, FSH, and LH, up-regulated the expression of GPX4, SLC7A11, and FTH1 (P<0.05, P<0.01), decreased the activities of SOD and CAT, lowered the levels of E2 and AMH, and down-regulated the expression of ACSL4 (P<0.05, P<0.01). Compared with the model group, drug interventions lowered the levels of iron, MDA, FSH, and LH, down-regulated the expression of GPX4, SLC7A11, and FTH1 (P<0.05, P<0.01), increased the activity of CAT, elevated the levels of E2 and AMH, and up-regulated the expression of ACSL4 (P<0.05, P<0.01). ConclusionZuoguiwan may inhibit the occurrence of ferroptosis by regulating the SLC7A11/GPX4 axis, thereby improving the ovarian function of POF rats.
2.Analysis on clinical efficacy of ureteroscope-assisted laparoscopic ureteroplasty at lying and running position of healthy side in the treatment of postoperative ureteral stenosis
Hua CHEN ; Tairong LIU ; Qiuhua ZHU ; Leming SONG ; Qiliang ZHAI ; Jiaqi GE ; Jiansheng XIAO
Chinese Journal of Urology 2024;45(1):29-33
Objective:To explore the safety and efficacy of ureteroscopy-assisted laparoscopic ureteroplasty in the healthy side-lying running position for the treatment of ureteral stenosis after pelvic surgery.Methods:The data of 92 patients with ureteral stenosis after surgery admitted to Ganzhou People’s Hospital from June 2017 to February 2023 were retrospectively analysed. There were 31 male patients and 61 female patients, with an average age of (46.4±23.3) years. Of the 92 patients, 53 patients had previously undergone stone fragmentation or stone retrieval surgery for urinary system stones, 35 patients had undergone gynecologic laparoscopic surgery for gynecologic diseases, 2 patients had previous intestinal surgery, and 2 patients had undergone laparoscopic ureteral reconstruction surgery. The mean preoperative serum creatinine was (120.33±16.52) μmol/L, the mean blood urea nitrogen was (14.28 ± 2.47) mmol/L, and the mean renal pelvis dilation was (3.23±2.47) cm. All patients were placed in healthy side-lying running position with general anesthesia. The patient's lower limbs were in the oblique supine position, and the angle of the lower limbs was 60-80°. By using a transabdominal approach, the narrow section of the ureter was mobilized and excised under the guidance of ureteroscopy. The posterior wall of the ureter was sutured and a zebra guidewire was placed into the renal pelvis. An F7 double-J stent was then retrogradely advanced over the guidewire. Then the anterior wall of the ureter was anastomosed to complete the surgery. The operation time, average length of hospital stay, perioperative complications, preoperative and postoperative pyelectasis and renal function changes were recorded, and the clinical efficacy were evaluated by comparative analysis.Results:Of the 92 patients, 90 patients were successfully treated with ureterovesical anastomosis. Two patients underwent ureterovesical reimplantation because of the low position and heavy adhesion of the stenosis segment. There were no cases of conversion to open surgery or intraoperative death. The mean surgery duration was (121.52±22.35) min, the mean drainage tube indwelling time was (3.16±1.23) d, and the mean hospital stay was (6.46±2.37) d. A patient with moderate hydronephrosis exhibited postoperative urinary leakage. Two patients developed symptoms of hematuria after ambulation. Following treatment with bed rest, adequate drainage, and appropriate hemostatic medication, all patients recovered smoothly and were discharged. The double J tube was removed 3 months after operation, and the CT reexamination after extubation showed that the degree of pyelectasis was (2.52±1.54) cm, the average serum creatinine was (89.64±15.21) μmol/L, and urea nitrogen was (9.42±1.36) mmol/L, which was all significantly different from that before operation ( P<0.05). The patients were followed up for 6 to 12 months, and there was no ureteral restenosis. Conclusions:Ureteroscopic-assisted laparoscopic ureteroplasty in the healthy side-lying running position is a safe and effective surgical method for the treatment of short segment (narrow segment <3 cm) ureteral cicatrix stenosis after surgery. And this surgical method has the advantages of accurate positioning of the narrow segment, safe and convenient ureteral free, exact ureteral anastomosis, and easy placement of double J tube.
3.A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement
Hua ZHENG ; Yunfei ZHI ; Lujing YING ; Lan ZHU ; Mingliang JI ; Ze LIANG ; Jiangshan WANG ; Haifeng SHI ; Weihong ZHANG ; Mengsu XIAO ; Yushi ZHANG ; Kaifeng XU ; Zhaohui LU ; Yaping LIU ; Ruiyi XU ; Huijuan ZHU ; Li WEN ; Yan ZHANG ; Gang CHEN ; Limeng CHEN
JOURNAL OF RARE DISEASES 2024;3(1):79-86
Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.
4.Relationship between GLI1 expression and tumor immune infiltration and clinical prognosis of gastric cancer
Wen-Shuai ZHU ; Jing-Guo SUN ; Yi LU ; Mu-Hua LUAN ; Xiao-Li MA ; Yan-Fei JIA
Chinese Journal of Current Advances in General Surgery 2024;27(1):8-13
Objective:To investigate the correlation between the expression of GLI1 and im-mune invasion and clinical prognosis in gastric cancer.To study the effect of GLI1 expression on drug resistance in gastric cancer.Methods:The expression difference of GLI1 in gastric cancer and normal tissues was analyzed by using TCGA database,and the effect of clinical features and GLI1 gene ex-pression level on prognosis of patients with gastric cancer was analyzed.The correlation between GLI1 gene expression and tumor immune cell infiltration in gastric cancer tissues was analyzed to explore its influence on drug resistance of chemotherapy drugs and targeted drugs.Clinical samples were collect-ed to analyze the difference of GLI1 expression in gastric cancer and paracancer tissues.Results:The expression of GLI1 in gastric cancer tissues was 1.7 times that in normal tissues,and the overall sur-vival and disease-free survival of patients with high expression are shorter than those with low ex-pression(P<0.05).The interstitial score,immune score and abundance of immunoinfiltrating cells were higher in the high expression of GLI1 in gastric cancer tissues.High expression of GLI1 reduces drug sensitivity and is positively correlated with the expression of immune checkpoint markers PDCD1(P<0.05).GLI1 expression was significantly increased in patients with subdifferentiated gastric cancer.Conclusions:GLI1 expression is associated with the prognosis and immune infiltration of patients with gastric cancer,and it may lead to poor prognosis of patients by regulating chemotherapy resis-tance,which may be a potential therapeutic target and molecular marker for gastric cancer.
5.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.
6.Effects of emodin modulation of the HIF-1α/VEGF pathway on vascular endothelial cells damage in diabetic macroangiopathy rats
Qiu-Xiao ZHU ; Hui-Yao HAO ; Zi-Bo LIU ; Ming GAO ; Fang ZHANG ; Jing ZHOU ; Zhi-Hua HAO ; Li-Hui ZHANG ; Yong-Mei HAO
The Chinese Journal of Clinical Pharmacology 2024;40(6):859-863
Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)%,(6.28±0.20)%,(24.96±1.18)%,(12.36±0.49)%,(18.76±0.68)%and(4.59±0.26)%;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P<0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.
7.Role of problem chain and course ideological and political cases teaching method in enhancing clinical medication ability research
Zhi-Hua QIN ; Long-Xi PENG ; Gao-Shuang LAN ; Xiao-Bin ZHANG ; Jiao-Jiao YANG ; Liang ZHU ; Xi-Long QIU ; Yun-Long CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(11):1650-1653
Nowadays,with the continuous deepening and development of vocational education teaching reform,medical higher vocational education always takes moral education as the fundamental task.As an independent type of education,vocational education should always deepen the integration of industry and education and the integration of science and education.Through the teaching research of"problem chain+course ideological and political case",this study innovates the coordinated education team of drug nursing curriculum,the collaborative education method and the collaborative education evaluation,and improves the teaching effect.
8.Study on neuronal protection of Gualou Guizhi decoction via inhibiting M1 microglia polarization
Xing-Hua ZHONG ; Hai-Xia HU ; Xin-Jun LIN ; Xiao-Qin ZHU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2197-2201
Objective To explore the molecular mechanism of Gualou Guizhi decoction which regulates the interferon regulator factor 5(IRF5)signaling pathway to inhibit M1 type microglia activation and reduce the inflammatory response to protect damaged nerve cells.Methods Microglia(BV2)cells were randomly divided into BV2-control,BV2-model,BV2-experimental-L,-M,-H groups.The BV2-control group was given routine culture;the BV2-model group used 100 ng·mL-1 lipopolysaccharide(LPS)to stimulate BV2 which establish an inflammatory model;the BV2-experimental-L,-M,-H groups were cultured in 50,100,200 μg·mL-1 GLGZD and 100 ng·mL-1 LPS.The HT22 cells were divided into the HT-22-blank group,HT-22-model group,HT-22-control group and HT-22 experimental group.HT-22-blank group were conventional culture;HT-22-model group were oxygen glucose deprivation was performed for 2 h,then the complete medium was replaced for 24 h;HT-22-control group were after 2 h of oxygen glucose deprivation,the 100 ng·mL-1 LPS conditioned medium was replaced and incubated for 24 h;HT-22-experimental group were after 2 h of oxygen glucose deprivation,the 200 μg·mL-1 GLGZD conditioned medium was added for 24 h.Interleukin-12(IL-12)and IL-23 were detected by enzyme-linked immunosorbent assay(ELISA);the protein of IRF5,cluster differentiation 16(CD1 6)and MHC class Ⅱ(MHC-Ⅱ)was detected by Western blot;the expression of the synaptic marker protein class Ⅲ β-Tubulin(Tuj-1)was observed by immunofluorescence.Results IL-12 contents in the BV2-control,BV2-model and BV2-experimental-L,-M,-H groups were(2.62±1.02),(10.67±3.22),(6.87±1.61),(3.96±1.22)and(3.36±1.04)pg·mL-1;IL-23 contents were(20.40±2.04),(77.08±3.25),(76.28±3.75),(63.96±4.94)and(54.48±3.34)pg·mL-1;relative expression levels of IRF5 protein were 0.80±0.41,2.22±0.69,1.11±0.11,0.92±0.39 and 0.65±0.29;relative expression levels of CD16 protein were 0.69±0.45,1.91±0.52,1.42±0.22,1.04±0.15 and 0.67±0.30;relative expression levels of MHC-Ⅱ protein were 0.89±0.27,1.96±0.19,1.34±0.38,1.15±0.19 and 0.68±0.24.BV2-experimental-M,-H groups were compared with the BV2-model group,the differences were statistically significant(all P<0.05).The Tuj-1 protein expression levels were 28.85±6.69,14.44±1.98,7.75±1.12 and 20.05±3.54,determined in the HT22-blank,HT22-model,HT22-control and HT22-experimental groups.The HT22-experimental group was compared with the HT22-control group,the difference was statistically significant(P<0.05).Conclusion GLGZD may reduces the activation of microglia M1 phenotype through IRF5 signaling pathway,and then inhibits inflammatory response to protect damaged nerve cells.
9.Effects of moxifloxacin in reducing lung injury in mice with Mycoplasma pneumoniae pneumonia
Xiao-Hua GUO ; Wei ZHU ; Qian ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(19):2853-2857
Objective To investigate the protective effect of moxifloxacin(Moxi)on Mycoplasma pneumoniae pneumonia by down-regulating long non-coding RNA growth inhibition specific gene(lncRNA GAS5)through non-receptor protein tyrosine kinase(JAK)/signaling and transcriptional activator protein(STAT)signaling pathways.Methods BALB/c mice were randomly divided into control group,model group,experimental group and combined group.Mice in model group,experimental group and combined group were treated with nasal drops of Mycoplasma pneumoniae fluid to establish Mycoplasma pneumoniae pneumonia model.By intraperitoneal injection of the experimental group and the combined group of 100 mg·kg-1 moxifloxacin treatment;on the basis,the overexpressed plasmid pc-GAS5 was injected into the tail vein of the combined group.The control group and model group were injected with the same amount of 0.9%NaCl intraperitoneally.The serum levels of interleukin-1 β(IL-1β)and IL-6 were detected by enzyme-linked immunosorbent assay(ELISA);the serum levels of superoxide dismutase(SOD)were detected by biochemical method;and the expression of lncRNA GAS5 in lung tissue was detected by real-time fluorescence quantitative polymerase chain reaction;the protein expression levels of B-cell lymphoma-2(Bcl-2),JAK2 and STAT3 in mouse lung were detected by Western blot.Results The serum IL-1 β content in control group,model group and experimental group were(64.03±14.19),(254.85±63.79)and(157.46±42.93)pg·mL-1,respectively;IL-6 contents were(22.61±5.01),(184.14±39.50)and(132.64±25.47)pg·mL-1;SOD activities were(50.38±11.75),(28.17±6.71)and(37.67±8.09)U·mL-1,respectively;the relative expression levels of lncRNA GAS5 in lung tissues were 1.00±0.16,3.78±0.69 and 2.41±0.54,respectively.The relative expression levels of Bcl-2 protein in control group,model group,experimental group and combined group were 1.00±0.17,0.65±0.14,0.82±0.16 and 0.62±0.13,respectively;phospherylated JAK2/JAK2 ratios were 1.00±0.20,4.98±1.01,2.13±0.52 and 4.21±0.92,respectively;phospherylated STAT3/STAT3 ratios were 1.00±0.18,3.77±0.78,2.65±0.64 and 3.49±0.75,respectively.Compared with the control group,the above indexes in the model group had statistical significance(P<0.05,P<0.001).The above indexes in the experimental group were statistically significant compared with those in the model group(P<0.05,P<0.01,P<0.001).There were significant differences between combined group and experimental group(P<0.05,P<0.001).Conclusion Moxifloxacin can effectively improve the lung tissue morphology of mice with Mycoplasma pneumoniae pneumonia,regulate the levels of inflammatory factors and oxidative stress damage,and affect apoptosis and JAK/STAT pathway protein expression by down-regulating lncRNA GAS5.
10.Clinical trial of N-acetyl cysteine effervescent tablets combined with budesonide and formoterol fumarate powder for inhalation in the treatment of patients with moderate to severe COPD
Xiao-Hua HE ; Qing-Hua ZHU ; Jun-Kai FU
The Chinese Journal of Clinical Pharmacology 2024;40(20):2929-2933
Objective To explore clinical effect and safety of N-acetyl cysteine(NAC)effervescent tablet combined with budesonide and formoterol fumarate powder for inhalation in the treatment of patients with moderate to severe chronic obstructive pulmonary disease(COPD).Methods Patients with moderate to severe COPD were randomly divided into NAC group,ST group and combination group.NAC group was treated with NAC effervescent tablets[NAC effervescent tablets 0.6 g was dissolved in warm water(≤40 ℃),one tablet/once,qd,take medicine at night],ST group was treated with budesonide and formoterol fumarate powder for inhalation(a inhalation/once,bid),combination group was treated with NAC effervescent tablets and budesonide and formoterol fumarate powder for inhalation.All patients were treated for 7 d.The clinical curative effect,peak expiratory flow(PEF),forced expiratory volume in 1 s(FEV1),FEV1/forced vital capacity(FVC),serum CRP,PCT,SAA,6 min walking test(6MWT)and safety in the three groups were evaluated.Results There were 40 cases in each group.After 7 d of treatment,total response rates of NAC group,ST group and combination group were 77.50%(31 cases/40 cases),80.00%(32 cases/40 cases)and 95.00%(38 cases/40 cases),the differences between combination group and NAC group or between combination group and ST group were statistically significant(P<0.05),but the difference between NAC group and ST group was not statistically significant(P>0.05).After 7 d of treatment,FVC levels in NAC group,ST group and combination group were(2.51±0.72),(2.59±0.76)and(3.01±0.82)L,PaO2 levels were(2.24±0.61),(2.29±0.64)and(2.87±0.72)L,FEV1/FVC levels were(89.24±4.28)%,(88.42±4.19)%and(95.35±4.27)%,levels of serum CRP were(19.52±2.12),(19.34±2.09)and(11.85±2.24)mg·L-1,PCT levels were(0.83±0.22),(0.87±0.24)and(0.51±0.13)μg·L-1,SAA levels were(28.95±3.48),(29.23±3.75)and(17.70±2.73)mg·L-1,the differences between combination group and NAC group or between combination group and ST group were statistically significant(all P<0.05),but the difference between NAC group and ST group was not statistically significant(all P>0.05).The adverse drug reactions were mainly on abdominal pain,diarrhea,headache,nausea and vomiting in the three groups.The total incidence of adverse drug reactions in NAC group,ST group and combination group was 2.50%,5.00%and 12.50%,the difference among the three groups was not statistically significant(all P>0.05).Conclusion The curative effect of NAC effervescent tablet combined with budesonide and formoterol fumarate powder for inhalation is significant in patients with moderate to severe COPD,which can effectively improve pulmonary function,reduce levels of serum CRP,PCT and SAA,with good safety.

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