1.Analysis of operative approaches and their curative effect in gastric stromal tumor
Cancer Research and Clinic 2016;28(1):40-42,47
Objective To explore the operative approaches of gastric stromal tumor,and to evaluate the treatment effect of various operation methods. Methods The clinical and pathological data of 96 cases of gastric stromal tumor treated in People's Hospital of Shanxi Medical University from Jan 2011 to Jun 2015 were analyzed retrospectively. 16 cases got laparoscopic resection, 48 cases got gastroscope and laparoscopic combined resection, and 42 cases got open resection. Results For patients with tumor diameter < 2 cm and 2-5 cm, the operation time, intraoperative bleeding and postoperative hospitalization days in the laparoscopic group were better than those in the laparotomy group (P < 0.05), but the postoperative complications and metastasis or mortality in the laparoscopic group didn't have the advantage compared with the laparotomy group (P > 0.05). For patients with tumor diameter > 5 cm, the operation time, intraoperative blood loss, postoperative hospitalization days, postoperative complications, and postoperative metastasis of mortality in the laparoscopic group didn't have the advantage compared with the laparotomy group (P > 0.05). Conclusion Different diameter of gastric stromal tumor should adopt different surgical methods and ways, the indication is strict, otherwise easy to cause tumor residual or disseminated planting.
2.Comparison of the Therapeutic Characteristics of Anterior Hybrid Decompression and Posterior Decompression in the treatment of Multilevel Cervical Spondylotic Myelopathy
Yongbiao SUN ; Yan ZHAO ; Zhongshuang ZHANG ; Ketao MA ; Lei CHEN ; Zhongpeng QIU ; Haoruo JIA
Progress in Modern Biomedicine 2017;17(22):4262-4267
Objective:To compare the therapeutic characteristics of anterior hybrid decompression and posterior cervical posterior laminectomy in the treatment of multilevel cervical spondylotic myelopathy.Methods:Thirty six cases of multilevel cervical spondylotic myelopathy patients treated by anterior hybrid decompression and thirty three cases of multilevel cervical spondylotic myelopathy patients treated by posterior cervical posterior laminectomy were involved.The general information,bleeding amount,operative time,cervical curvature D value,JOA score and incidence of postoperative complications of the two groups before and after surgery were compared.Results:There was no significant difference in the general information among the two groups(P>0.05),including age (anterior group:56.23± 7.64 years old,posterior group:55.76± 8.18 years old),sex (anterior group:22 males/14 females,posterior group:20 males/13 females),cervical curvature D value (anterior group:7.41± 3.14,posterior group:8.19± 2.74),JOA score (anterior group:9.08± 1.09 scores,posterior group:8.82± 1.26 scores),disease course (anterior group:17.24± 7.36 months,posterior group:15.75± 5.78 months) and affected segment (anterior group:3.11 ± 0.26 segments,posterior group:3.24± 0.39 segments).The the amount of bleeding in the anterior group (anterior approach:221.79± 178.02 ml,posterior group:483.07± 434.25 ml) was lower than that of the posterior group(P<0.05).The operative time (anterior group:196.54± 51.88 mins,posterior group:175.12± 54.93 mins) was longer,but there was no significant difference (P>0.05).The cervical curvature D value and JOA score of posterior group were increased with the extension of surgery time.However,the cervical curvature D value of posterior group was decreased,but JOA score was increased.The incidence of bone unfinished,hoarseness and cerebrospinal fluid leakage were found in the anterior group,and axial pain and C5 nerve root paralysis were found in the posterior group.But there was no significant difference in the incidence of complications between the two groups (anterior group 14.89%,posterior group:12.12%)(P>0.05).Conclusions:Anterior hybrid decompression and posterior cervical posterior laminectomy had their own advantages in the treatment of multilevel cervical spondylotic myelopathy.,The appropriate treatment should be taken according to the condition of patients.
3.Clinical observation of total laparoscopic radical gastrectomy for locally advanced esophagogastric junction carcinoma
Qingyao CHANG ; Jun XU ; Kai JIA ; Wenhui YANG ; Yidi WANG ; Haoruo ZHANG
Cancer Research and Clinic 2021;33(8):606-611
Objective:To investigate the efficacy of total laparoscopic radical gastrectomy for locally advanced esophagogastric junction carcinoma and its effect on patient's immune function and levels of tumor markers.Methods:A total of 106 patients who underwent total laparoscopic radical gastrectomy (total endoscopic group) in the Affiliated Cancer Hospital of Shanxi Medical University from January 2016 to April 2020 were collected, and 98 patients who underwent open radical gastrectomy (open group) in the same period were selected. The short-term efficacy, preoperative and postoperative immune function and tumor markers were compared between the two groups.Results:The operative time of the total endoscopic group was longer than that of the open group [(214±49) min vs. (165±32) min, t = 8.87, P < 0.01], the intraoperative blood loss was less than that of the open group [(86±50) ml vs. (113±53) ml, t = 3.59, P < 0.01], the postoperative first exhaust time was shorter than that of the open group [3.0 d (3.0 d, 4.0 d) vs. 3.5 d (3.0 d, 4.5 d), Z = 2.89, P < 0.01], and the incision length was shorter than that of the open group [(4.6±0.6) cm vs. (17.6±2.0) cm, t = 68.63, P < 0.01]. The postoperative proportion of CD4 + T cells, CD4 +/CD8 + and proportion of NK cells in the total endoscopic group were higher than those in the open group [(41±8)% vs.(36±8)%, t = 4.710, P < 0.01; 1.63 (1.19, 2.30) vs. 1.15 (0.87, 1.63), Z = 4.165, P < 0.01; 24.60 % (17.77 %, 32.50 %) vs. 19.25 % (13.35 %, 25.80 %), Z = 3.440, P < 0.01], while the postoperative proportions of CD8 + T cells and regulatory T cells in the total endoscopic group were lower than those in the open group [(26±11)% vs. (30±10)%, t = 2.375, P = 0.018; 3.37% (5.00%, 6.70%) vs. 4.48% (5.70%, 7.20%), Z = 3.057, P = 0.002]. Postoperative carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) in the total endoscopy were lower than those in the open group group [0.96 μg/L (0.54 μg/L, 1.50 μg/L) vs. 1.27 μg/L (0.70 μg/L, 2.98 μg/L), Z = 2.745, P = 0.036; 8.07 U/ml (5.48 U/ml, 13.07 U/ml) vs. 10.80 U/ml (6.54 U/ml, 19.93 U/ml), Z = 2.690, P = 0.043]. Conclusion:Compared with open surgery, total laparoscopic radical gastrectomy has less trauma and stress response, and has less impact on the gastrointestinal and immune function of patients, and the levels of tumor markers CEA and CA199 are low.
4.Comparative study of exosome-mimetic nanovesicles and exosomes derived from human adipose mesenchymal stem cells on the biological function of human umbilical vein endothelial cells
Haoruo ZHANG ; Aizhen CHEN ; Caixiang CHEN ; Shijie TANG ; Junjing LI ; Xiangyu LI ; Xiaosong CHEN
Chinese Journal of Plastic Surgery 2022;38(5):517-527
Objective:To investigate the effect of different concentrations of human adipose-derived mesenchymal stromal cells (hADMSCs) derived exosome-mimetic nanovesicles (NVs)and exosomes (EXOs) on the biological function of human umbilical vein endothelial cells (HUVECs) .Methods:(1) Through hydrodynamic liposuction, adipose tissue was obtained from the thighs of 10 women (aged 18-65 years) in Fujian Medical University Union Hospital from June 2019 to August 2020. The hADMSCs were isolated by enzymatic hydrolysis, cultured to passage 4 and induced into adipocytes and osteocytes. The surface protein markers were identified by flow cytometry. (2) hADMSCs-NVs and hADMSCs-EXOs were prepared and observed under an electron microscope. Their surface protein markers were analyzed with particle size analyzer, particle size was analyzed with nanoparticle tracker. Protein quantitative analysis and nanoparticle tracking were used to detect the total protein and particle number of NVs and EXOs produced by 1×10 6 hADMSCs. (3) The control group (DMEM basic medium), 40, 60, 80 μg/ml NVs groups and 20, 40, 60 μg/ml EXOs groups were set to compare the proliferation, migration and angiogenesis of HUVECs through CCK-8 proliferation test, cell scratch test and angiogenesis test respectively. Graphpad Prism 7.0 was used for statistical analysis, and the measurement data were expressed as Mean±SD. Repeated measurement analysis of variance was applied to the comparison between multiple groups, and Tukey test was applied to pairwise comparison. P<0.05 represented statistical significance. Results:(1) The fourth generation of hADMSCs were slender spindle-shaped cells under optical microscope. After 21 days of adipogenesis induction, the transparent lipid droplets inside the cells were stained red by oil red O staining. After 14 days of osteogenesis induction, a large proportion of brown black staining area was observed by alkaline phosphatase calcium cobalt staining. The surface protein markers CD90 and CD29 of hADMSCs were positive. (2) Under transmission electron microscope, the structures of hADMSCs-NVs and EXOs were similar, both were discoid vesicles. The expression levels of CD9, CD81 and IgG were similar between NVS and EXOs. The particle sizes of NVs and EXOs were about the same, which were (72.0 ± 21.51) nm and (81.27±22.37) nm. The total protein content of NVs produced by 1×10 6 hADMSCs was (140.7±5.1) μg, about 100 times that of EXOs, which was (1.3±0.3) μg. The number of NVs [(644.5 ± 17.1)×10 8/ml] particles was about 90 times that of EXOs [(7.1±0.1)×10 8/ml]. (3) In CCK-8 proliferation assay, at 12, 24 and 48 hours after culture, the growth trend of HUVECs in the groups were generally consistent, and the difference in absorbance value was statistically significant ( P<0.01); at 48 hours after culture, the absorbance values of 60 μg/ml NVs and 40 μg/ml EXOs were higher than those in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). At 8 and 24 hours after cell scratch assay, the changes of scratch width in each group were different, and the difference was statistically significant ( P<0.01); at 24 hours after scratch, the change of scratch width in 60 μg/ml NVs and 40 μg/ml EXOs groups were greater than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). In the angiogenesis assay, the number of branch points and the length of blood vessels in each group were different, and the difference was statistically significant ( P<0.01). The number of capillary branches formed by HUVECs in 60 μg/ml NVs and 40 μg/ml EXOs groups were higher than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups (all P>0.05). The capillary length of 60 μg/ml NVs and 40 μg/ml EXOs groups were longer than that of the control group ( all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). Conclusions:The shape and size of NVs were similar to EXOs, while the total protein content of NVs was about 100 times that of EXOs. The effects of hADMSCs-NVs and EXOs on the biological functions of HUVECs are similar and the optimum concentrations of NVs and EXOs are 60 μg/ml and 40 μg/ml, respectively.
5.Comparative study of exosome-mimetic nanovesicles and exosomes derived from human adipose mesenchymal stem cells on the biological function of human umbilical vein endothelial cells
Haoruo ZHANG ; Aizhen CHEN ; Caixiang CHEN ; Shijie TANG ; Junjing LI ; Xiangyu LI ; Xiaosong CHEN
Chinese Journal of Plastic Surgery 2022;38(5):517-527
Objective:To investigate the effect of different concentrations of human adipose-derived mesenchymal stromal cells (hADMSCs) derived exosome-mimetic nanovesicles (NVs)and exosomes (EXOs) on the biological function of human umbilical vein endothelial cells (HUVECs) .Methods:(1) Through hydrodynamic liposuction, adipose tissue was obtained from the thighs of 10 women (aged 18-65 years) in Fujian Medical University Union Hospital from June 2019 to August 2020. The hADMSCs were isolated by enzymatic hydrolysis, cultured to passage 4 and induced into adipocytes and osteocytes. The surface protein markers were identified by flow cytometry. (2) hADMSCs-NVs and hADMSCs-EXOs were prepared and observed under an electron microscope. Their surface protein markers were analyzed with particle size analyzer, particle size was analyzed with nanoparticle tracker. Protein quantitative analysis and nanoparticle tracking were used to detect the total protein and particle number of NVs and EXOs produced by 1×10 6 hADMSCs. (3) The control group (DMEM basic medium), 40, 60, 80 μg/ml NVs groups and 20, 40, 60 μg/ml EXOs groups were set to compare the proliferation, migration and angiogenesis of HUVECs through CCK-8 proliferation test, cell scratch test and angiogenesis test respectively. Graphpad Prism 7.0 was used for statistical analysis, and the measurement data were expressed as Mean±SD. Repeated measurement analysis of variance was applied to the comparison between multiple groups, and Tukey test was applied to pairwise comparison. P<0.05 represented statistical significance. Results:(1) The fourth generation of hADMSCs were slender spindle-shaped cells under optical microscope. After 21 days of adipogenesis induction, the transparent lipid droplets inside the cells were stained red by oil red O staining. After 14 days of osteogenesis induction, a large proportion of brown black staining area was observed by alkaline phosphatase calcium cobalt staining. The surface protein markers CD90 and CD29 of hADMSCs were positive. (2) Under transmission electron microscope, the structures of hADMSCs-NVs and EXOs were similar, both were discoid vesicles. The expression levels of CD9, CD81 and IgG were similar between NVS and EXOs. The particle sizes of NVs and EXOs were about the same, which were (72.0 ± 21.51) nm and (81.27±22.37) nm. The total protein content of NVs produced by 1×10 6 hADMSCs was (140.7±5.1) μg, about 100 times that of EXOs, which was (1.3±0.3) μg. The number of NVs [(644.5 ± 17.1)×10 8/ml] particles was about 90 times that of EXOs [(7.1±0.1)×10 8/ml]. (3) In CCK-8 proliferation assay, at 12, 24 and 48 hours after culture, the growth trend of HUVECs in the groups were generally consistent, and the difference in absorbance value was statistically significant ( P<0.01); at 48 hours after culture, the absorbance values of 60 μg/ml NVs and 40 μg/ml EXOs were higher than those in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). At 8 and 24 hours after cell scratch assay, the changes of scratch width in each group were different, and the difference was statistically significant ( P<0.01); at 24 hours after scratch, the change of scratch width in 60 μg/ml NVs and 40 μg/ml EXOs groups were greater than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). In the angiogenesis assay, the number of branch points and the length of blood vessels in each group were different, and the difference was statistically significant ( P<0.01). The number of capillary branches formed by HUVECs in 60 μg/ml NVs and 40 μg/ml EXOs groups were higher than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups (all P>0.05). The capillary length of 60 μg/ml NVs and 40 μg/ml EXOs groups were longer than that of the control group ( all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). Conclusions:The shape and size of NVs were similar to EXOs, while the total protein content of NVs was about 100 times that of EXOs. The effects of hADMSCs-NVs and EXOs on the biological functions of HUVECs are similar and the optimum concentrations of NVs and EXOs are 60 μg/ml and 40 μg/ml, respectively.
6.Quercetin Attenuates Ferroptosis Against LPS-induced Acute Kidney Injury Rats via Modulating Keap1/Nrf2/ARE Pathway
Haoruo YANG ; Dajun YU ; Yu ZHANG ; Bin YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):65-75
ObjectiveTo investigate the effect and therapeutic role of quercetin on ferroptosis in lipopolysaccharide (LPS)-induced acute kidney injury (AKI) rats based on the Kelch-like epichlorohydrin-related protein-1 (Keap1)/nuclear factor erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. MethodsSixty male SD rats were randomly divided into normal group, model group, quercetin high-dose (100 mg·kg-1) and low-dose (10 mg·kg-1) groups, ferroptosis inhibitor Ferrostatin 1 (FER1) group (5 mg·kg-1), and quercetin high-dose + Nrf2 inhibitor group (ML385, 30 mg·kg-1). Except for the normal group, the AKI rat model was established in each group by intraperitoneal injection of LPS (10 mg·kg-1). Following successful modeling, each treatment group received the corresponding dose of drug intervention, while the normal and model groups were administered an equal volume of normal saline. The intervention lasted for 3 weeks. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured biochemically to assess renal function. Serum tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). The levels of Fe2+, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in renal tissue were detected. Hematoxylin-eosin (HE), Masson, and periodic acid-Schiff (PAS) staining were employed to observe pathological morphological changes in renal tissue. Mitochondrial morphological changes were observed using transmission electron microscopy. Reactive oxygen species (ROS) levels in renal tissue were detected by immunofluorescence (IF). The protein and mRNA expression levels of Keap1, Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), transferrin receptor (TFR1), and kidney injury molecule-1 (KIM-1) were assessed by immunohistochemistry (IHC) and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the normal group, the model group exhibited significantly elevated serum levels of SCr, BUN, TNF-α, IL-1β, IL-6, Fe2+ and MDA in renal tissue, and significantly reduced SOD and GSH levels (P<0.01). Pathological injury in renal tissue was severe, with evident mitochondrial damage characteristic of ferroptosis and a reduced mitochondrial count. ROS levels in renal tissue were significantly increased. The protein and mRNA expression levels of Keap1, TFR1, and KIM-1 in renal tissue were significantly elevated, while those of Nrf2, HO-1, and GPX4 were significantly decreased (P<0.01). Compared with the model group, serum levels of SCr, BUN, TNF-α, IL-1β, IL-6, Fe2+ and MDA in renal tissue in the quercetin dosage groups and FER1 group showed varying degrees of reduction, while SOD and GSH levels were significantly increased (P<0.05). Pathological injury in renal tissue was markedly alleviated, mitochondrial damage improved, and mitochondrial counts increased. ROS levels in renal tissue were significantly reduced. The protein and mRNA levels of Keap1, TFR1, and KIM-1 in renal tissue were significantly decreased, while those of Nrf2, HO-1, and GPX4 were significantly increased, with the most notable improvement in the high-dose quercetin group (P<0.05). In comparison to the high-dose quercetin group, the ML385 group significantly weakened the protective effect of quercetin on AKI rats (P<0.05). ConclusionQuercetin effectively inhibits ferroptosis, improves renal tissue injury, and repairs renal function in AKI rats, and its mechanism may be related to the activation of the Keap1/Nrf2/ARE pathway.