1.Effect of Modified Xiangsha Liujunzitang on Hepatic Kupffer Cell Inflammation Mediated by Intestinal-derived LPS in Rats with Hyperlipidemia and Spleen Deficiency Syndrome
Mengzhu CHE ; Lianqun JIA ; Dongyu MIN ; Guoyuan SUI ; Qi ZHANG ; Guanlin YANG ; Yunhao CUI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):77-86
ObjectiveThe study aims to investigate the intervention effect of modified Xiangsha Liujunzitang (M-XSLJZ) on intestinal-derived lipopolysaccharide (LPS)-activated Kupffer cell inflammation in rats with hyperlipidemia spleen deficiency syndrome. MethodsSeventy male SD rats were randomly divided into seven groups (n=10): blank control (CON), high-fat diet without spleen deficiency (HFD), high-fat diet with spleen deficiency (SD-HFD), M-XSLJZ low-, medium-, and high-dose groups (XS-L, XS-M, XS-H), and western medicine control (R). Spleen deficiency was induced in SD-HFD, XS-L, XS-M, XS-H, and R groups via irregular diet combined with exhaustive swimming for 15 days. The CON group received a standard diet, while other groups were fed a high-fat diet for 10 weeks to establish the hyperlipidemia model. After successful modeling, rats were treated for 8 weeks: M-XSLJZ was administered at 3.51, 7.02, 14.04 g·kg-1 in XS-L, XS-M, and XS-H groups, respectively. The R group received 9×10-4 g·kg-1 of a reference drug. D-xylose excretion rate was measured by the phloroglucinol method. Blood lipids were assessed using an automated biochemical analyzer. Hematoxylin-eosin (HE) staining was used to evaluate the pathological conditions of the liver, and oil red O staining was used to observe the lipid deposition in the liver. The levels of LPS, portal vein serum LPS, LPS-binding protein (LBP), serum interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to evaluate CD86 expression and CD68/TLR4 co-localization in the liver. Protein levels of TLR4, MyD88, NF-κB p65, and p-NF-κB p65 in Kupffer cells were analyzed via Western blot automated protein analysis. Hepatic IL-6, TNF-α, and IL-1β mRNA and protein levels were measured using Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared with the CON group, the SD-HFD group showed a decrease in D-xylose excretion (P<0.01). TC, TG, HDL-C, and LDL-C increased (P<0.05, P<0.01). A large number of hepatic lipid vacuoles and orange-red lipid droplet deposition appeared in the liver. Ileal LPS, portal LPS, and LBP increased (P<0.05, P<0.01). The levels of serum IL-6, TNF-α, and IL-1β increased (P<0.01). The expression of CD86 was upregulated (P<0.01), and the co-expression of CD68 and TLR4 was enhanced. The protein levels of TLR4, MyD88, and p-p65 in Kupffer cells increased (P<0.01). The mRNA and protein levels of IL-6, TNF-α, and IL-1β increased (P<0.05, P<0.01). Compared with the HFD group, the SD-HFD group exhibited decreased D-xylose excretion (P<0.01), higher HDL-C, LDL-C (P<0.05), increased portal LBP and LPS (P<0.05), increased serum IL-6 and TNF-α (P<0.01), upregulated CD86 (P<0.01), enhanced CD68/TLR4 co-expression, and higher TNF-α mRNA/protein (P<0.05). Compared with the SD-HFD group, all M-XSLJZ treatment groups showed reduced TC, TG, and LDL-C (P<0.05, P<0.01). XS-H and R groups displayed improved hepatic lipid deposition. XS-H and R groups had lower ileal LPS, portal LPS, and LBP levels (P<0.05, P<0.01). All M-XSLJZ treatment groups exhibited reduced serum IL-6, IL-1β, and TNF-α (P<0.01). The XS-H group showed downregulated CD86 (P<0.01) and weakened CD68/TLR4 co-expression. The XS-H group had reduced TLR4, MyD88, and p-NF-κB p65 in Kupffer cells (P<0.01). XS-H and R groups showed lower IL-6, TNF-α, and IL-1β mRNA/protein (P<0.05, P<0.01). ConclusionM-XSLJZ may exert its lipid-lowering effects by inhibiting intestinal-derived LPS and alleviating Kupffer cell inflammation in the liver.
2.Visualization of Brain Abnormal β-Amyloid Deposition in Alzheimer's Disease Based on 18F-Florbetaben PET Imaging
Huamei LIN ; Yunhao YANG ; Jiaying LU ; Zhengwei ZHANG ; Shufen CHEN ; Jingjie GE ; Yihui GUAN ; Chuantao ZUO
Chinese Journal of Medical Imaging 2024;32(5):420-425
Purpose To investigate the characteristics of 18F-Florbetaben(18F-FBB)β-amyloid(Aβ)PET imaging in different brain regions of Alzheimer's disease(AD)patients with different degrees of cognitive impairment,and to explore the correlation between Aβ deposition and cognitive dysfunction.Materials and Methods A total of eighteen patients with a clinical diagnosis of probable AD from August 2022 to October 2023 were retrospectively included in Huashan Hospital.All patients had Aβ abnormal deposition in the brain as confirmed by 18F-FBB PET imaging.According to the severity of symptoms,they were divided into the AD-induced mild cognitive impairment(MCI)group(8 cases)and the dementia group(10 cases).In addition,12 healthy controls were included.First,the standardized uptake value ratio of abnormal Aβ deposition in the frontal lobe,lateral parietal lobe,lateral temporal lobe,anterior and posterior cingulate gyrus,and compound cortex was semi-quantitatively calculated and compared among the three groups based on the subjects'brain MRI and automated anatomical labeling template.The correlation between the degree of Aβ deposition in the brains of AD patients and cognitive scale scores(mini-mental state examination,Montreal cognitive assessment)was then further analyzed.Results The standardized uptake value ratio values of Aβabnormal deposition in the frontal lobe,lateral temporal lobe,lateral parietal lobe,anterior and posterior cingulate cortex and compound cortex in the AD-induced MCI and dementia groups were significantly higher than those in the healthy controls(t=7.442-9.151,all P<0.05).However,there was no significant difference in the standardized uptake value ratio values of Aβ abnormal deposition in the above brain regions between the MCI and dementia groups(t=0.312-0.996,all P>0.05).In addition,there was no significant correlation between the degree of Aβ deposition in the brain and the cognitive scale scores(mini-mental state examination,Montreal cognitive assessment)in the AD-induced MCI and dementia groups(r=-0.049-0.050,all P>0.05).Conclusion Aβ deposition in the brains of AD-induced MCI and dementia is significantly higher than in the healthy controls.However,Aβ deposition cannot identify AD patients with different degrees of cognitive impairment,reflecting that Aβ deposition has certain limitations in assessing the severity of clinical symptoms of AD.
4.The short-term outcomes of congenital radioulnar synostosis patients treated with modified reverse Sauvé-Kapandji technique
Lu LIU ; Qipei WEI ; Chen YANG ; Yunhao XUE ; Shanlin CHEN
Chinese Journal of Orthopaedics 2023;43(12):863-868
Objective:To evaluate the short-term outcomes of modified reverse Sauvé-Kapandji technique in treating the congenital radioulnar synostosis.Methods:A retrospective analysis was performed on the data of 46 congenital radioulnar synostosis patients were treated with modified reverse Sauvé-Kapandji technique in Beijing Jishuitan Hospital from December 2018 to January 2020, including 38 males (45 sides), 8 females (9 sides), average age 6.6 (3.2, 8.1) years old. All the patients were classified as type III according to Cleary-Omer classification and were followed up for at least 1 year. All the patients were treated with same operation, in which 1.5 cm shaft was resected at the proximal radius, allogeneic graft tendon was used as interposition, and rotational osteotomy was performed in the middle of the ulnar shaft, with intramedullary needle or Kirschner wire fixation, depending on the intramedullary width of ulnar shaft. The radiological features were collected and recorded preoperatively and at the latest follow-up, together with the following evaluation indexes: modified Morrey tasks score, subjective function score, active forearm rotation range without compensation, active forearm rotation range with wrist joint compensation, and active forearm rotation range with wrist and shoulder joint compensation.Results:All patients were followed up for 14.6±3.4 months (range, 11.2-19.5 months). The uncompensated forearm rotation Angle was 0.0°±0.0° before surgery and 62.3°±23.7° after surgery. The forearm rotation angles before and after surgery with wrist compensatory surgery were 86.9°±29.4° and 133.2°±27.9°, respectively. The forearm rotation angles before and after surgery with wrist and shoulder joint compensatory surgery were 205.2°±42.7° and 245.2°±35.8°, respectively. There were statistically significant differences in the above indexes before and after surgery ( t=8.71, P<0.001; t=2.54, P=0.030; t=5.05, P<0.001). Ulnar union was observed in 31 patients (37 sides) after the operation, and the union duration was 6.1±2.3 months. There were 15 patients (17 sides) ulnar shafts faced with postoperative delayed union, the union duration was 8.4±1.6 months and were recovered after prolonging brace fixation and orthopedic shock wave treatment. The scores of subjective function and improved Morrey tasks of the 43 sides with good pseudo-joint were 12.1 (0.0, 20.8) and 0.7 (0.0, 1.0) points, respectively, which were improved compared with 33.9 (25.0, 41.6) and 3.2 (2.0, 4.0) points before surgery. The differences were statistically significant ( Z=-2.44, P=0.015; Z=-2.83, P=0.005). There were 11 forearms with postoperative pseudo-joint re-ankylosis, the average forearm rotation ranges without compensation was 11.4°±10.5°(range, 0°-30°), the average forearm rotation ranges with wrist compensation was 98.6°±15.9° (range, 80°-120°), the average forearm rotation ranges with wrist and shoulder compensation was 231.7°±16.9° (range, 210°-255°). The average subjective function scores was 26.7 (8.3, 39.6). The average modified Morrey tasks scores was 1.2 (0, 2), and there were no other postoperative complications. Conclusion:The reverse Sauvé-Kapandji technique showed a satisfying short-term outcome, and can be a new choice of treatment for type III congenital radioulnar synostosis.
5.Establishment and clinical verification of brain template for analyzing 11C-CFT PET imaging data
Chengfeng JIANG ; Ping WU ; Jingjie GE ; Zhemin HUANG ; Jianfei XIAO ; Yunhao YANG ; Xiuming LI ; Qian XU ; Huiwei ZHANG ; Yihui GUAN ; Chuantao ZUO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(4):216-220
Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.
6.Ferroptosis is involved in testicular injury induced by TDCIPP in adolescent male mice
Chuanzhen XIONG ; Ling ZHANG ; Yang ZHANG ; Ruiwen LI ; Yu SUN ; Yunhao LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(8):562-568
Objective:To investigate the role of ferroptosis in testicular injury in adolescent male mice induced by TDCIPP.Methods:In December 2021, 30 healthy 3-week-old male C57BL/6 mice, with a body weight of (13±2) g, were selected and fed adaptive for one week. They were divided into control group, low-dose group, medium-dose group, high-dose group and iron death inhibitor group according to a random number table, with 6 mice in each group. Mice in low, medium and high dose groups were treated with 5, 25 and 125 mg/ (kg·d) TDCIPP for 28 days, respectively, while the control group was treated with the same amount of corn oil for 28 days. The iron death inhibitor group was given 125 mg/ (kg·d) TDCIPP intragastric administration for 28 days, and 30 mg/kg DFO saline solution was intraperitoneally injected three times a week. After the treatment, the mice were killed, the epididymis was separated, and sperm count was performed. HE staining was used to observe the morphological changes of mouse testis, and iron content in testis was detected by tissue iron detection kit. The level of reactive cxygen species, MDA content, and the mitochondrial membrane potential level of mice were detected. Western blot analysis of testicular glutathione peroxidase (GPX4) and internal cyclooxygenase-2 (COX2) protein expression.Results:Compared with the control group, the spermatogenic cells in the testes of mice treated with medium-and high-dose of TDCIPP were disorderly arranged, showing a vacuolar structure. the number of sperm in the epididymis was significantly reduced ( P=0.009, 0.004), while the sperm deformity rate was significantly increased ( P=0.010, 0.000). Moreover, the content of ROS, iron ion and MDA in the testes increased significantly ( P<0.05), and the mitochondrial membrane potential of mouse testicular cells decreased significantly ( P<0.05). The expression of GPX4 proteins decreased ( P<0.05). while the expression of COX2 increased significantly ( P<0.01). Compared with high-dose group group, spermatogenic cells in ferroptosis inhibitor group were closely arranged and normal, and ROS and Fe contents in testicular tissue were significantly decreased ( P<0.01) ; GPX4 protein expression was significantly increased while COX2 protein expression was significantly decreased ( P<0.05) . Conclusion:Ferroptosis is involved in TDCIPP-induced testicular damage in male pubertal mice.
7.Ferroptosis is involved in testicular injury induced by TDCIPP in adolescent male mice
Chuanzhen XIONG ; Ling ZHANG ; Yang ZHANG ; Ruiwen LI ; Yu SUN ; Yunhao LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(8):562-568
Objective:To investigate the role of ferroptosis in testicular injury in adolescent male mice induced by TDCIPP.Methods:In December 2021, 30 healthy 3-week-old male C57BL/6 mice, with a body weight of (13±2) g, were selected and fed adaptive for one week. They were divided into control group, low-dose group, medium-dose group, high-dose group and iron death inhibitor group according to a random number table, with 6 mice in each group. Mice in low, medium and high dose groups were treated with 5, 25 and 125 mg/ (kg·d) TDCIPP for 28 days, respectively, while the control group was treated with the same amount of corn oil for 28 days. The iron death inhibitor group was given 125 mg/ (kg·d) TDCIPP intragastric administration for 28 days, and 30 mg/kg DFO saline solution was intraperitoneally injected three times a week. After the treatment, the mice were killed, the epididymis was separated, and sperm count was performed. HE staining was used to observe the morphological changes of mouse testis, and iron content in testis was detected by tissue iron detection kit. The level of reactive cxygen species, MDA content, and the mitochondrial membrane potential level of mice were detected. Western blot analysis of testicular glutathione peroxidase (GPX4) and internal cyclooxygenase-2 (COX2) protein expression.Results:Compared with the control group, the spermatogenic cells in the testes of mice treated with medium-and high-dose of TDCIPP were disorderly arranged, showing a vacuolar structure. the number of sperm in the epididymis was significantly reduced ( P=0.009, 0.004), while the sperm deformity rate was significantly increased ( P=0.010, 0.000). Moreover, the content of ROS, iron ion and MDA in the testes increased significantly ( P<0.05), and the mitochondrial membrane potential of mouse testicular cells decreased significantly ( P<0.05). The expression of GPX4 proteins decreased ( P<0.05). while the expression of COX2 increased significantly ( P<0.01). Compared with high-dose group group, spermatogenic cells in ferroptosis inhibitor group were closely arranged and normal, and ROS and Fe contents in testicular tissue were significantly decreased ( P<0.01) ; GPX4 protein expression was significantly increased while COX2 protein expression was significantly decreased ( P<0.05) . Conclusion:Ferroptosis is involved in TDCIPP-induced testicular damage in male pubertal mice.
8.Cadmium promotes apoptosis of mouse spermatogenic cells via regulation of JNK/c-Jun signaling pathway
Li YANG ; Dingyu HUANG ; Lan MA ; Ling ZHANG ; Yunhao LIU
Journal of Public Health and Preventive Medicine 2021;32(3):37-40
Objectives To study the effect of cadmium (Cd) on the proliferation and apoptosis of mouse spermatocyte (GC-2 spd) cells and explore the underlying molecular mechanism. Methods GC-2 spd cells were cultured with 0, 5, 10, 15, 20 and 30 μM CdCl2, respectively, for 24 hours. The cell viability and IC50 of Cd were estimated based on CCK-8 data. The apoptosis of GC-2 spd cells and cellular concentration of ROS were analyzed by flow cytometry after treatment of the cells with different concentrations of CdCl2 (0, 5, 10 μM) for 24 hours. The expression levels of JNK/c-Jun signaling pathway regulatory proteins, pro-apoptotic factor Bax and anti-apoptotic factor Bcl-2, were determined by Western blot. Results Cd inhibited the proliferation of GC-2 spd cells with IC50 value of 12.99 μM, 95% CI [11.95, 14.00]. Exposure to 5 and 10 μM CaCl2 resulted in increases in apoptosis and cellular ROS generation in a dose-dependent manner, which was statistically significant compared with the control (P < 0.05). Although there was no difference in the expression level of c-Jun (P > 0.05), the phosphorylation level of JNK and c-Jun in Cd group was highly increased as compared to the control (P < 0.05). In addition, Cd exposure significantly increased the expression of Bax protein but decreased the expression Bcl-2 protein (P < 0.05). Conclusions Cadmium induces GC-2 spd cell apoptosis by increasing concentration of ROS and regulating the JNK/c-Jun signaling pathway.
9.Comparison of the clinical features and therapeutics of COVID-19 in cardio-cerebrovascular disease (CCVD) and non-CCVD patients.
Yu WANG ; Lan LI ; Yuanjiang PAN ; Yu HE ; Zuhua CHEN ; Yunhao XUN ; Yuhan XU ; Yilei GUO ; Jiehong YANG ; Jianchun GUO ; Haitong WAN
Frontiers of Medicine 2021;15(4):629-637
Cardio-cerebrovascular disease (CCVD) is a major comorbidity of Coronavirus disease 2019 (COVID-19). However, the clinical characteristics and outcomes remain unclear. In this study, 102 cases of COVID-19 from January 22, 2020 to March 26, 2020 in Xixi Hospital of Hangzhou were included. Twenty cases had pre-existing CCVD. Results showed that compared with non-CCVD patients, those with CCVD are more likely to develop severe disease (15% versus 1%), and the proportion of pneumonia severity index grade IV was significantly higher (25% versus 3.6%). Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group (90% versus 63.4%). Compared with non-CCVD group, the levels of C-reactive protein, fibrinogen, D-dimer, and serum amyloid-A were higher, whereas the total protein and arterial partial PaO
COVID-19
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Cerebrovascular Disorders/epidemiology*
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Comorbidity
;
Humans
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SARS-CoV-2
;
Tomography, X-Ray Computed
10.Clinical application of enlarging greater ischiatic notch by ilium osteotomy to expose the sacral plexus via the gluteal approach
Shufeng WANG ; Feng LI ; Yunhao XUE ; Wenjun LI ; Pengcheng LI ; Yaobin YIN ; Chen YANG ; Bin LI
Chinese Journal of Surgery 2021;59(9):744-749
Objectives:To observe the possibility of enlarging the greater sciatic notch by illium osteotomy through the posterior gluteal approach for reaching the intrapelvic upper sacral plexus as well as the covergence level of sacral plexus,and performing the nerve graft for surgical repairing the sacral plexus ruptured injuries or sacral plexus nerve tumor resection.Methods:The clinical data of 10 patients with sacral plexus injury or sacral plexus nerve tumor underwent the surgical operation via the expanded greater sciatic notch at Department of Hand Surgery,Beijing Jishuitan Hospital from July 2016 to November 2020 were retrospectively analyzed.There were 4 male and 6 female patients,with an age of (38.0±9.3)years (range:26 to 56 years).There were 8 cases with sacral plexus injury at the intrapelvic or covergence level (deep to the piriformis). Out of this 8 cases,4 cases with intrapelvic pan-sacral plexus injury,1 case with upper sacral plexus injury and 3 cases with convergence level pan sacral plexus injury.Another 2 cases were sacral plexus neoplasm.The average time from injury or onset to operation was 10.4 months (range:1.5 to 60.0 months). All cases were performed surgery for reaching the intrapelvic upper sacral plexus as well as the covergence level of sacral plexus with enlarging the greater sciatic notch by illium osteotomy through the posterior gluteal approach.Intraoperation the sacral plexus ruptured injurie was repaired and the sacral plexus nerve tumor was resected.Intraoperative findings,postoperative complications and healing of incision and osteotomy of patients were recorded.Results:All the 10 patients underwent the sacral plexus surgical exploration and cutaneous nerve graft for sacral plexus nerve repairing or neurolysis or neoplasm resection through the posterior gluteal approach successfully.The length and width of illium osteotomy mass were (2.9±0.4)cm (range:2.5 to 3.8 cm) and (2.5±0.5)cm (range:1.5 to 3.4 cm) respectively.The median intraoperative bleeding volume was ( M( Q R))800(800)ml (range:400 to 2 000 ml).There were no complication with major vascular injury and hematoma formation,and all incisions healed.The postoperative follow-up was 29.8 months (range:1.5 to 54.0 months).Nine cases of iliac osteotomy were healed,and 1 case was not healed because the follow-up was only 1.5 months. Conclusions:The intrapelvic upper sacral plexus and the convergence level of sacral plexus deep to the piriformis can be exposed clearly through this posterior gluteal approach via illium osteotomy for enlarging the greater sciatic notch,and there was enough operative space that surgical exploration and nerve graft or nerve transfer or neoplasm resection can be performed.


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