1.Aberrant Increase in Lipid Synthesis Exacerbates Diabetic Nephropathy and Folic Acid-induced Kidney Injury.
Yuzhi CHEN ; Xiaoyun JIANG ; Qihui DAI ; Gonghua HUANG ; Xinguang LIU ; Meng YANG
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(1):119-132
ObjectiveTo investigate the changes and effects of fatty acid metabolism in folic acid (FA)-induced kidney injury and diabetic nephropathy (DN) mouse models. MethodsThe FA-induced kidney injury model was established via intraperitoneal injection of FA. Nine adult C57BL/6J mice were randomly allocated to two groups: saline control group (Saline, n=5) and FA intervention group (n=4). Mice in the FA group received a single intraperitoneal injection of FA (250 mg/kg), whereas those in the Saline group were administered an equivalent volume of normal saline. The DN model was constructed using a high-fat diet combined with streptozotocin (STZ) injection. Eleven adult C57BL/6J mice were randomly divided into two groups: normal diet control group (ND, n=6) and DN model group (DN, n=5). The ND group was fed a normal diet throughout the experiment; the DN group was maintained on a high-fat diet for 8 weeks, followed by a single intraperitoneal injection of STZ (100 mg/kg), and then continued on the high-fat diet until week 16. (1) Hematoxylin and eosin (HE) and sirius red staining were used to observe pathological changes in the kidneys of the four groups of mice. (2) RNA-Seq was performed on mouse kidney tissues to screen for differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). RT-qPCR was used to detect the mRNA levels of fatty acid synthesis and fibrosis-related genes. Lipid droplet accumulation was assessed by Oil Red O staining on frozen kidney sections. (3) Human renal cortical proximal tubular epithelial cells (HK-2) and proximal tubular epithelial cells (PTECs) were treated with 10 ng/mL recombinant human TGF-β1 or high glucose. RT-qPCR was used to measure the mRNA levels of fatty acid synthesis and fibrosis-related genes in HK-2 cells. Lipid droplet accumulation in HK-2 cells and PTECs was detected using Bodipy 493/503 staining. (4) HK-2 cells were treated with 100 µmol/L palmitic acid (PA). Bodipy 493/503 staining was used to evaluate lipid droplet accumulation. (5) SA-β-gal staining was used to assess senescence in kidney tissues from all four mouse groups. Cellular senescence and the expression of senescence-associated secretory phenotype (SASP) factors in PA-treated HK-2 cells were assessed using SA-β-gal staining, Western blot, and RT-qPCR. The effect of PA-treated PTECs on renal fibroblast activation was assessed by immunofluorescence. Results(1) Both FA and DN groups showed pathological changes in kidney tissue, including renal tubular structural damage and collagen fiber deposition. (2) DEGs in both FA and DN groups were significantly enriched in metabolism-related pathways, especially lipid metabolism pathways. Compared to the Saline control, the expression of fatty acid synthesis genes Srebp1 and Fasn was significantly upregulated in the FA group (Srebp1: t=2.445, P=0.044 4; Fasn: t=2.571, P=0.037 0). Compared to the ND group, Srebp1, Acc1, and Fasn gene expression was upregulated in the DN group (Srebp1: t=3.354, P=0.010 0; Acc1: t=2.602, P=0.031 5; Fasn: t=2.358, P=0.046 1). The fibrosis-related gene Col1a1 was also upregulated in both FA and DN groups (FA: t=2.628, P=0.034 0; DN: t=3.602, P=0.007 0), accompanied by pathological signs of lipid accumulation. (3) In HK-2 cells treated with TGF-β1 or high glucose, the mRNA expression levels of SREBP1 (F=15.41, P=0.004 3; TGFβ: P=0.002 9; HG: P=0.045 2), ACC1 (F=30.30, P=0.000 7; HG: P=0.001 4), and FASN (F=18.76, P=0.002 6; TGFβ: P=0.001 7; HG: P=0.031 0) were significantly upregulated. Both treatments also induced lipid accumulation in HK-2 cells and PTECs. (4) There was an increase in senescent cells in the kidneys of both the FA and DN groups. PA treatment induced lipid accumulation, accelerated senescence, and activated fibroblasts in renal tubular epithelial cells. ConclusionsTranscriptional abnormalities of lipid metabolism-related genes were observed in the kidneys of both FA-induced kidney injury and diabetic nephropathy models. Excessive fatty acid synthesis leads to lipid accumulation, which induces senescence in PTECs and ultimately promotes the development and progression of fibrosis.
2.Lipidomics driven biomarker discovery in chronic lung disease
Ang ZHANG ; Yan DU ; Yang XIE ; Xinguang LIU
Chinese Journal of Comparative Medicine 2024;34(7):131-141
Chronic lung diseases(CLD)include chronic obstructive pulmonary disease,asthma,and idiopathic pulmonary fibrosis.Studies have shown that CLD are closely related to disorders in lipid metabolism.Therefore,lipids,as biomarkers of CLD,may be of great value in the diagnosis,prevention,and monitoring of disease treatment.This review discusses lipidomics from four major aspects:the technical methods of lipidomics,the selection of clinical samples for lipidomics,the discovery of biomarkers for CLD,and the differentiation of traditional Chinese medicine syndromes from CLD.
3.Comparison of short-term clinical outcomes and patient satisfaction between robotic-assisted and conventional total hip arthroplasty
Xinguang WANG ; Yizhen HE ; Ziyang DONG ; Xiao GENG ; Cheng WANG ; Yang LI ; Zijian LI ; Hua TIAN
Chinese Journal of Orthopaedics 2023;43(8):492-499
Objective:To compare short-term clinical outcomes and patient satisfaction between robotic-assisted total hip arthroplasty (THA) and conventional THA.Methods:Patient data of unilateral primary THA with the same prosthesis by the same operator due to osteoarthritis, osteonecrosis of the femoral head, and other diseases in Peking University Third Hospital from September 2019 to February 2022 was retrospectively analyzed. Patients were divided into robot-assisted THA group and conventional THA group according to surgical methods. The preoperative general data, operation time, intraoperative complications and other intraoperative data were collected. Anteroposterior X-ray of pelvis and cross-table X-ray of hip were taken. Main outcome measures consisted of total blood loss, blood transfusion rate, hospitalization stay, postoperative complications, and the inclination and anteversion angle of the acetabular cup, while the dislocation rate outside the Lewinnek and Callanan safe zone was also analyzed. Other outcomes measures included visual analogue scale, Harris score, quality of life score (QOL) and satisfaction score.Results:There was no significant difference in gender, age, height, weight, body mass index (BMI), operation side, preoperative blood volume and Harris score between the two groups ( P>0.05); Loosening of positioning screws occurred in 2 patients due to osteoporosis in robot-assisted THA group, so conventional THA was performed. Therefore, 84 cases in robot-assisted THA group and 87 cases in conventional THA group were enrolled in this study at last. There was no significant difference in follow-up time between conventional THA group and robot-assisted THA group (19.7±6.8 months vs. 18.6±5.4 months, t=1.16, P=0.249); The operation time of robot-assisted THA group was longer than that of conventional THA group (106.99±31.91 min vs. 73.79±29.48 min, t=7.07, P<0.001), but there was no significant difference in hospitalization stay between conventional THA group and robot-assisted THA group (6.40±2.40 d vs. 6.49±1.95 d, t=0.26, P=0.796). There was also no significant difference in total blood loss and blood transfusion rate between the two groups ( P>0.05). There was no significant difference in inclination angle (38.79°±6.93° vs. 39.41°±3.01°, t=0.58, P=0.449) and anteversion angle (14.81°±6.49° vs. 13.33°±4.32°, t=3.06, P=0.082) between conventional THA group and robot-assisted THA group, while the percentage in Lewinnek safe zone (96.4% vs. 73.6%, χ 2=15.60, P<0.001) and Callanan safe zone (92.9% vs. 65.5%, χ 2=17.61, P<0.001) was significantly higher in conventional THA than that of robot-assisted THA. There were no significant differences in postoperative VAS, Harris score and QOL score between the two groups ( P>0.05), but the excellent and good rate of Harris score of conventional THA group was lower than that of robot-assisted THA group (83.91% vs. 95.24%, χ 2=5.83, P=0.016); The overall satisfaction of patients in robot-assisted THA group was better than that in conventional THA group ( Z=-3.47, P=0.001), and 95.2% (80/84) of patients in robot-assisted THA group were very satisfied, which was higher than that in conventional THA group (75.86%, 66/87). The satisfaction of patients in robot-assisted THA group on pain relief ( Z=-2.44, P=0.015) and improvement of leisure activity ( Z=-2.12, P=0.034) was better than that in conventional THA group, but there was no significant difference in the satisfaction of ability of doing house work between the two groups ( Z=-0.49, P=0.626). Conclusion:Compared with conventional THA, robot-assisted THA has longer operation time but better short-term clinical outcomes and higher patient satisfaction after surgery.
4.The role and value of surgeon-engineer interaction during preoperative planning of patient-specific instrumentation assisted total knee arthroplasty
Liang YUAN ; Xiaohua WANG ; Bin SUN ; Xing XIN ; Xinguang LIU ; Ke ZHANG ; Jie YAO ; Bin YANG
Chinese Journal of Orthopaedics 2023;43(15):1031-1040
Objective:To investigate the significance and importance of the interaction between surgeons and engineers during the preoperative planning phase of total knee arthroplasty (TKA) when utilizing patient-specific instrumentation (PSI).Methods:A retrospective review was conducted on 202 knees of PSI-assisted TKA performed on 178 patients between June 2018 and August 2022. The patients' mean age was 68.4±6.2 years, ranging from 53 to 86 years. Among the participants, there were 149 females and 29 males, 93 left knees and 109 right knees. The study involved 171 patients of osteoarthritis (193 knees) and 7 patients of rheumatoid arthritis (9 knees), with 194 knees presenting varus knees and 8 knees with valgus knees. The preoperative plan documents, from the initial engineer-designed plan to the final plan approved by the surgeon, were analyzed to assess the frequency, parameters, and reasons for adjustments made during the planning process.Results:The planning of the 202 PSI-assisted TKA was subjected to at least one round of surgeon-engineer interaction. Among the 202 TKA planning, 117 knees (57.9%) underwent modifications after discussion, with most plans (100 knees, 49.5%) being confirmed after one round of modification. Two rounds of modifications were performed on 10 knees (5.0%), and three rounds on 5 knees (2.5%). A maximum of four rounds of modifications were made on two knees (0.9%). Furthermore, in the case of the remaining 85 knees (42.1%), the surgeons promptly consented to the engineers' initial planning following the discussions. Specific adjustments were made in 106 knees (52.5%) regarding femoral parameters, 57 knees (28.2%) concerning tibial parameters, and 46 knees (22.8%) requiring adjustments to both femoral and tibial parameters. Notably, the most frequently adjusted parameter was the osteotomy thickness of the posterior femoral condyles, which was modified in 94 knees (80.3%). The reasons for adjusting femoral or tibial parameters were summarized, revealing the main factors as follows: 1) Discrepancy between the mediolateral and anteroposterior diameters of the femoral condyle; 2) Twisted deformity of the proximal tibia; 3) Severe flexion contracture deformity of the knee; 4) Collapse of the medial or lateral tibial plateau; 5) Evident anterior arch deformity of the femur.Conclusion:The interaction between surgeons and engineers plays a pivotal role in the preoperative phase of PSI-assisted TKA. Effective collaboration allows surgeons to accurately analyze the unique anatomical characteristics and pathological changes of each patient in a three-dimensional perspective, facilitating the formulation of individualized surgical plans.
5.Effects of exposure to low-dose ionizing radiation on changing platelets: a prospective cohort study.
Ning LIU ; Yang PENG ; Xinguang ZHONG ; Zheng MA ; Suiping HE ; Ying LI ; Wencui ZHANG ; Zijun GONG ; Zhenjiang YAO
Environmental Health and Preventive Medicine 2021;26(1):14-14
BACKGROUND:
Numerous studies have concentrated on high-dose radiation exposed accidentally or through therapy, and few involve low-dose occupational exposure, to investigate the correlation between low-dose ionizing radiation and changing hematological parameters among medical workers.
METHODS:
Using a prospective cohort study design, we collected health examination reports and personal dose monitoring data from medical workers and used Poisson regression and restricted cubic spline models to assess the correlation between changing hematological parameters and cumulative radiation dose and determine the dose-response relationship.
RESULTS:
We observed that changing platelet of 1265 medical workers followed up was statistically different among the cumulative dose groups (P = 0.010). Although the linear trend tested was not statistically significant (P
CONCLUSION
We concluded that although the exposure dose was below the limit, medical workers exposed to low-dose ionizing radiation for a short period of time might have increased first and then decreased platelets, and there was a dose-response relationship between the cumulative radiation dose and platelets changing.
Adult
;
Aged
;
Blood Platelets/radiation effects*
;
Female
;
Health Personnel/statistics & numerical data*
;
Humans
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Male
;
Middle Aged
;
Occupational Exposure/adverse effects*
;
Prospective Studies
;
Radiation Dosage
;
Radiation Exposure/adverse effects*
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Radiation, Ionizing
;
Young Adult
6.Safety and short-term efficacy analysis of breast-conserving surgery combined with intraoperative radiotherapy for early-stage breast cancer
Yang ZHANG ; Yang YANG ; Xinguang WANG ; Jian TIE ; Yingjian HE ; Jinfeng LI ; Yuntao XIE ; Tianfeng WANG ; Tao OUYANG ; Zhaoqing FAN
Chinese Journal of Oncology 2020;42(8):682-686
Objective:To analyze the safety and short-term efficacy of breast-conserving surgery combined with intraoperative radiotherapy for early-stage breast cancer.Methods:A total of 101 consecutive patients who received breast-conserving surgery plus intraoperative radiotherapy were recruited to summarize the recent follow-up results and clinicopathological data. Univariate analysis and Logistic regression model were used to evaluate the factors affecting the postoperative adverse reactions and cosmetic effects.Results:Among 101 patients, 4 patients had recurrence or metastasis. The 3-years disease free survival rate was 94.9%, and the 3-years cumulative recurrence rate was 5.1%. Univariate analysis showed that the menstrual status and postoperative whole breast radiotherapy were associated with the postoperative adverse reactions ( P<0.05). The T stage and applicator diameter were associated with the cosmetic effect ( P<0.05). Multivariate analysis indicated that the diameter of the applicator ( OR=3.701, P=0.026) and postoperative whole breast radiotherapy ( OR=5.962, P=0.005) were independent factors for the postoperative adverse reactions, and the diameter of the applicator ( OR=2.522, P=0.037) was an independent factor for the cosmetic effect. Conclusion:Breast-conserving surgery combined with intraoperative radiotherapy shows safety and good short-term efficacy in low-risk early-stage breast cancer.
7.Safety and short-term efficacy analysis of breast-conserving surgery combined with intraoperative radiotherapy for early-stage breast cancer
Yang ZHANG ; Yang YANG ; Xinguang WANG ; Jian TIE ; Yingjian HE ; Jinfeng LI ; Yuntao XIE ; Tianfeng WANG ; Tao OUYANG ; Zhaoqing FAN
Chinese Journal of Oncology 2020;42(8):682-686
Objective:To analyze the safety and short-term efficacy of breast-conserving surgery combined with intraoperative radiotherapy for early-stage breast cancer.Methods:A total of 101 consecutive patients who received breast-conserving surgery plus intraoperative radiotherapy were recruited to summarize the recent follow-up results and clinicopathological data. Univariate analysis and Logistic regression model were used to evaluate the factors affecting the postoperative adverse reactions and cosmetic effects.Results:Among 101 patients, 4 patients had recurrence or metastasis. The 3-years disease free survival rate was 94.9%, and the 3-years cumulative recurrence rate was 5.1%. Univariate analysis showed that the menstrual status and postoperative whole breast radiotherapy were associated with the postoperative adverse reactions ( P<0.05). The T stage and applicator diameter were associated with the cosmetic effect ( P<0.05). Multivariate analysis indicated that the diameter of the applicator ( OR=3.701, P=0.026) and postoperative whole breast radiotherapy ( OR=5.962, P=0.005) were independent factors for the postoperative adverse reactions, and the diameter of the applicator ( OR=2.522, P=0.037) was an independent factor for the cosmetic effect. Conclusion:Breast-conserving surgery combined with intraoperative radiotherapy shows safety and good short-term efficacy in low-risk early-stage breast cancer.
8.Co-expression of GRP78 and Myocilin in trabecular meshwork cells of primary open angle glaucoma
Fang, CHAI ; Hua, AI ; Juan, LI ; Xinguang, YANG
Chinese Journal of Experimental Ophthalmology 2017;35(4):300-305
Background Misfolding of Myocilin protein plays an important role in the pathogenesis of primary open angle glaucoma (POAG).GRP78 can transfer the misfolded proteins out endocytoplasmic reticulum and keep the protein synthesis function of endoplasmic reticulum.However the relationship between GRP78 and Myocilin in the pathogenesis of POAG has not been elucidated.Objective This study was to investigate and analyze the coexpressions of GRP78 and Myolicin in trabecular meshwork cells (TMCs) of POAG.Methods The trabecular meshwork tissues were obtained during the surgery of POAG and healthy donor for the isolated and in vitro culture of TMCs,and the morphology of the cells was compared between POAG-derived TMCs and donor-derived TMCs.The expression of specific factors for TMCs were detected by immunochemistry.The cells were divided into normal control group,tunicamycin (Tm)-treated group and staurosporine (STS)-treated group,and the cells were cultured by regular medium,the 1 μ mol/L Tm medium or 0.1 μmol/L STS medium for 24 hours respectively.The co-expression of GRP78 and Myocilin in the cells were detected using immunofluorescence assay.This study was approved by Ethics Committee of Xi'an No.4 Hospital,and written informed consent was obtained from each patient before surgery.Results Primarily cultured cells showed the fiat star-like and irregular appearance with 3-5 processes,round nuclei,abundant cytoplasm and black engulf particles.The 3-7 generations of POAG-derived cells grew well,showing positive expressions of laminin (LN),fibronectin (FN),neuronal specific enolase (NSE) and Vimentin.Immunofluorescence assay showed positive expressions of GRP78 and Myocilin in the cells of the Tm group,STS group and normal control group,with the reddish and green fluorescence separately.Incomplete co-expression of GRP78 and Myocilin was seen in donor-derived TMCs,and complete co-expression of GRP78 and Myocilin was found in the POAG-derived TMCs in the normal control group.Complete co-expression of GRP78 and Myocilin was exhibited in both donor-and POAG-derived TMCs in the Tm group and STS group.In addition,accumulation of GRP78 protein around nucleus was seen in both donor-and POAG-derived TMCs in the Tm group.Conclusions GRP78 and Myocilin proteins are completely co-expressed in POAG-derived TMCs,inferring that GRP78 and Myocilin play an interaction role in the pathogenesis and development of POAG.GRP78 may play a cytoprotective role against the apoptosis of TMCs caused by endoplasmic reticulum stress.
9.Clinical Curative Effect of Vitreous Cavity Injection Combined with Transconjunctival Sutureless Vitrectomy on the Patients with Poliferative Diabetic Retinopathy
Lianyi SUN ; Meisheng ZHAO ; Fengzhi LI ; Qian YAO ; Zhongqiao ZHU ; Xinguang YANG
Progress in Modern Biomedicine 2017;17(23):4579-4582
Objective:To investigate the clinical curative effect of vitreous cavity injection combined with transconjunctival sutureless vitrectomy on the patients with poliferative diabetic retinopathy.Methods:80 patients with diabetic retinopathy were enrolled in our hospital from January 2014 to January 2016,in which contained 83 sicked eyes,and randomly divided into two groups.Group A (n=40,42 sicked eyes) accepted 25G transconjunctival sutureless vitrectomy,and Group B (n=40,41 sicked eyes) adopted intravitreal injection of conbercept based on patients in Group A.The operative conditions,best-corrected visual acuity (BCV) and retinal thickness were compared between two groups,and the incidence of adverse reactions within postoperative 1 month were recorded and analyzed.Results:The operation time of group B was significantly shorter than that of group A (P<0.05).The percentage of using electric coagulation,operative bleeding and iatrogenic fracture space in group B were significantly lower than of those group A (P<0.05).The percentage of neovascularization vanish in group B was significantly higher than that of group A (P<0.05).The BVCA of patients in group B in postoperative 1 month and 3 month were higher than those of group A (P<0.05).And the thickness of retinal in group B were significantly thinner than those of Group A (P<0.05).The incidence of vitreous hemorrhage and hyphema in group B were significantly lower than those of Group A (P<0.05).Conclusions:Vitreous cavity injection combined with transconjunctival sutureless vitrectomy improved the operative conditions and contributed to the recovery of postoperative visual acuity and retinal in the treatment of patients with poliferative diabetic retinopathy.
10.Crocin inhibits glutamate-induced apoptosis of retinal ganglion cells
Bochang Lü ; Xiaojie DANG ; Zhiguo XU ; Fuquan HUO ; Ting ZHANG ; Xinguang YANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(3):445-452
Objective To evaluate the effects and underlying mechanisms of crocin on glutamate-induced apoptosis of retinal ganglion cells (RGCs) by affecting extracellular calcium influx.Methods Primary rat retinal ganglion cells were isolated and stimulated with glutamate at concentrations of 0.1 mmol/L and 1 mmol/L for 24 h or 48 h,respectively,to establish apoptosis model of RGCs.Afterwards,crocin of different doses (0.1,1.0 and 3.0 μmol/L) was used to treat the glutamate-induced RGCs for 12 h;then cell apoptosis was detected by Annexin V-FITC/PI staining.The intracellular calcium concentration was determined by FIuo-3/AM fluorescent labeling.Western blot was used to examine the effect of crocin on Ca2+-mediated apoptotic signal molecules calpain and CaMKII.The mitochondrial membrane potential was detected by JC-1 staining and mitochondrial apoptosis-related signaling molecules Caspase-3,Caspase-9 and Bcl-2/Bax were evaluated by Western blot,respectively.Results In comparison with the untreated controls,the cell apoptosis of RGCs exposed to 0.1 mmol/L of glutamate for 24 h did not significantly change (P> 0.05).However,apoptosis rate of the cells reached (43.050 ± 2.616) % when the stimulation time lasted for 48 h and showed a significant increase (P<0.01).Treatment with higher-dose glutamate (1 mmol/L) significantly increased apoptosis of RGCs at 24 h (46.450±1.061)% and 48 h (45.500±3.253)% compared with the controls (P<0.01).RGCs were induced by 1 mmol/L of glutamate for 12 h,followed by the treatment with crocin at concentrations of 0.1,1.0 and 3.0 μmol/L,respectively.Each dose of crocin could significantly inhibit cell apoptosis in the dose-dependent manner (P<0.01).In addition,crocin at 1.0 μmol/L blocked glutamate-induced extracellular calcium influx,inhibited the expression of calcium-dependent proteins Calpainl and CaMK Ⅱ.Moreover,crocin at the dose of 1.0 μmol/L also increased mitochondrial membrane potential,suppressed the expressions of Caspase-3 and Caspase-9,and elevated Bcl-2/Bax ratio.Cornclusion Crocin inhibits glutamate-induced apoptosis of retinal ganglion cells through suppressing extracellular calcium influx,thereby blocking calcium-dependent and mitochondria-dependent apoptosis signaling pathways.

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