1.Sulodexide alleviates renal fibrosis following prolonged ischemia-reperfusion injury by protecting vascular endothelial glycocalyx
Chaoyu HU ; Peng ZHANG ; Chao SUN ; Shuyong MO ; Yanfeng WANG
Organ Transplantation 2025;16(3):404-415
Objective To investigate the protective effects and mechanisms of sulodexide on renal fibrosis induced by prolonged warm ischemia. Methods An in vivo ischemia-reperfusion injury (IRI) model was established in rats, which were randomly divided into Sham group, IRI 60 min group (IRI group), and IRI 60 min + sulodexide group (IRI+SDX group), with 20 rats in each group. Pathological examination was used to evaluate renal tissue injury and fibrosis levels in each group. Immunohistochemistry was performed to detect the expression levels of kidney injury molecule (KIM)-1, intercellular adhesion molecule (ICAM)-1, von Willebrand factor (vWF), transforming growth factor (TGF)-β, α-smooth muscle actin (SMA), and type I collagen (COL-1). Immunofluorescence staining was used to detect CD31 expression. Real-time quantitative polymerase chain reaction was employed to measure the expression of KIM-1, ICAM-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in renal tissues. Transmission electron microscopy was used to observe the structure of the renal glycocalyx. Evans blue dye was injected to assess renal vascular permeability. Rat survival was recorded, and serum levels of syndecan (SDC)-1, heparan sulfate (HS) and serum creatinine were measured. An ex vivo perfusion model was also established, with rats randomly assigned to either the hypothermic oxygenated machine perfusion (HOPE) group or the HOPE+SDX group (five rats per group). Perfusion parameters were recorded after 2 hours of ex vivo perfusion. Results One day after reperfusion, compared with the Sham group, the IRI group exhibited more severe renal tissue injury, higher tubular injury scores, increased expression of KIM-1, ICAM-1 and vWF, decreased CD31 expression, elevated serum levels of SDC-1 and HS, increased vascular permeability, and higher expression of TNF-α, IL-1β and IL-6. Compared with the IRI group, the IRI+SDX group showed reduced renal tissue injury, lower tubular injury scores, decreased expression of KIM-1, ICAM-1 and vWF, increased CD31 expression, lower serum levels of SDC-1 and HS, decreased vascular permeability, and reduced expression of TNF-α, IL-1β and IL-6 (all P < 0.05). Ten days after reperfusion, renal tissue injury was further alleviated in the IRI+SDX group. Twenty-five days after reperfusion, the IRI+SDX group exhibited decreased expression of TGF-β, α-SMA, and COL-1, as well as reduced collagen deposition area (all P < 0.05). Compared with the HOPE group, the HOPE+SDX group showed increased renal perfusion flow and decreased intrarenal vascular resistance (both P < 0.01). Conclusions Sulodexide may alleviates renal IRI and fibrosis caused by prolonged warm ischemia by inhibiting inflammatory responses and protecting vascular endothelial glycocalyx.
2.Mechanism of Tibetan Medicine Sanguo Decoction Prevent High-Fat Diet-induced Hyperlipidemia Rats by Regulating Nrf2/HO-1 Signal Pathway
Yan JIANG ; Linlin ZHAO ; Jing MA ; Yanfeng PENG ; Jiyu XU ; Dejun ZHANG
Chinese Journal of Modern Applied Pharmacy 2024;41(6):743-749
OBJECTIVE
To investigate the protective effect of Tibetan medicine Sanguo decoction on hyperlipidemic rats based on the Nrf2/HO-1 signaling pathway and its related mechanisms.
METHODS
Forty-eight male SD rats were randomly divided into six groups: the normal control group, the model control group, the simvastatin group(3.5 mg·kg−1), and the Tibetan medicine Sanguo decoction low, medium, and high dose groups(0.43 , 0.86 , 1.72 g·kg−1), with eight rats in each group. The normal control group was fed a basal diet, and the remaining groups were fed the H10060 high-fat diet to prepare a hyperlipidemic rat model. At the same time, each treatment group was given corresponding drugs by gavage once a day. The normal control group and model control group were given an equal volume of physiological saline(once a day) by gavage for 6 consecutive weeks. After 6 weeks, serum levels of lipids[totalcholesterol(TC), triglyceride(TG), low density lipoprotein(LDL) and high density lipoprotein(HDL)] and oxidative parameters[malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH)] were measured by reagent kit. Nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase 1(HO-1), Keap1, and quinone oxidoreductase(NQO1) protein expression in liver tissues were analyzed by Western blotting. The correlation of lipid and oxidative indices was investigated by person correlation.
RESULTS
Compared with the normal control group, the model control group showed a significant increase in body weight, significantly higher serum levels of TC, TG, LDL, and MDA, significantly lower serum levels of HDL, and significantly lower SOD and GSH activity. Compared with the model control group, each administration group showed a decrease in body weight and serum TC, TG, LDL, and MDA levels. In comparison with the model control group, the body weight was reduced, the serum levels of TC, TG, LDL, and MDA were significantly lower, the serum levels of HDL were significantly higher, and the SOD and GSH activities were significantly higher. Keap1 protein level expression was significantly up-regulated compared with the normal control group, and Nrf2, HO-1, and NQO1 protein level expression were significantly down-regulated in the model control group. Keap1 protein level expression was significantly down-regulated compared to the model control group, and Nrf2, HO-1, and NQO1 protein level expression were significantly up-regulated in the liver tissues of low and high doses of Sanguo decoction. The expressions of Nrf2, HO-1, and NQO1 were significantly up-regulated. Correlation analysis showed that TG was negatively correlated with SOD, HO-1, and NQO1, and positively correlated with Keap1, while TC was negatively correlated with SOD, HO-1, GSH, and Nrf2, and positively correlated with Keap1 and MDA.
CONCLUSION
The Tibetan medicine Sanguo decoction can improve body weight and blood lipid levels in hyperlipidemic rats, and the mechanism may be related to the regulation of the Nrf2/HO-1 signaling pathway and the improvement of oxidative stress.
3.Triple negative breast cancer:a study based on histological and immunohistochemical classification
Jing LIAN ; Li HUANG ; Peng BU ; Hong SU ; Yanfeng XI
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):268-273
Purpose To evaluate the classification criteria of triple negative breast cancer(TNBC)based on histomorphol-ogy and immunohistochemistry(IHC),and to provide theoreti-cal basis for the classification and treatment of TNBCs.Methods TNBC subtyping was performed according to the histomorphologi-cal characteristics and the expression of immune markers AR,CD8 and FOXC1,and the clinicopathological features and prog-nostic differences were compared.Results Among 93 cases of TNBC,there were 23 cases(24.7%)of luminal androgen re-ceptor subtypes,24 cases(25.8%)of immunomodulatory type,39 cases(42.0%)of basal immunosuppressive type,and 7 ca-ses(7.5%)of mesenchymal type.There were significant differ-ences in the clinicopathological features of subtypes,including pT stage(P=0.030),histological grade(P<0.001),intersti-tial lymphocyte infiltration pattern(P<0.001),expression of PD-L1(P<0.001),and HER2-low(P=0.024).There was no significant difference in disease-free survival among the sub-types(P>0.05).Univariate survival analysis showed there was significant difference in disease-free survival among the subtypes at pT1 stage(P=0.011),and other clinicopathological features were not independent prognostic factors.Conclusion The clini-copathological characteristics of TNBC subtypes are different,which are expected to be an alternative choice for complex gene expression profile analysis and to provide theoretical basis for subtypic therapy and targeted therapy.
4.Microscopic electric rotary grinding combined with graft repairing in patients with Peyronie's disease:a report of 21 cases
Dachun JIN ; Yong LUO ; Peng WANG ; Yong ZHANG ; Gang BI ; Dali TONG ; Yihe WANG ; Wanyi ZHOU ; Yanfeng LI
Journal of Army Medical University 2024;46(11):1291-1297
Objective To explore the surgical techniques and experiences in the treatment of Peyronie's disease using electric rotary grinding of tunica albuginea plaques followed by graft repair with tunica vaginalis or bovine pericardium under a microscope.Methods A retrospective cohort study was performed on 21 patients with severe penile curvature due to Peyronie's disease admitted in our department from January 2021 and May 2023.All of them underwent microscopic electric rotary grinding of tunica albuginea plaques followed by graft repair surgery.Short-term and mid-term outcomes were observed.Results For the 21 enrolled patients,12(57.1%)underwent repair using unilateral tunica vaginalis,3(14.3%)underwent repair using bilateral tunica vaginalis,and 6(28.6%)underwent repair using bovine pericardium.The operation time was 170~385(average 272±69)min,and the average postoperative follow-up duration was3~24(average 12.1±7.2)months.Seventeen patients(81.0%)had their penis fully extended,while 4 patients(19.0%)had slight dorsal curvature,which was less than 10°.All patients were satisfied with the shape of their penis during erection.The change in penile length was+(1.1±0.5)cm,and 9 patients(42.9%)reported early postoperative penile head numbness,which spontaneously resolved after an average duration of 3.2±1.9 months.All patients were able to successfully engage in sexual activity,with an average penile erection hardness score of 3.8.The overall satisfaction rate was 90.5%post operatively.Conclusion Meticulous dissection of Buck's fascia under a microscope is advantageous in reliably preserving dorsal neurovascular structures.Application of an electric grinding drill for plaque ablation allows for more precise release of the tunica.Graft repair of tunica albuginea defects with testicular tunica vaginalis or bovine pericardium for Peyronie's disease yields overall favorable clinical outcomes and obtains high satisfaction.It is worthy of promotion in clinical practice.
5.Application effect and economic benefit analysis of total parathyroidectomy+thymectomy+forearm subcutaneous implantation in patients with secondary hyperparathyroidism
Zhenyu WU ; Yanfeng TIAN ; Peng DAI ; Yaolei YE ; Hengzhe JIA ; Fangjian SHANG
Journal of Clinical Surgery 2024;32(9):918-922
Objective To analyze the application effect and economic benefit of total parathyroidectomy(TPTX)+subcutaneous implantation of forearm(AT)+thymectomy in patients with secondary hyperparathyroidism(SHPT).Methods The clinical data of 110 patients with SHPT who were treated in our hospital from March 2018 to January 2021 were retrospectively analyzed.They were divided into medication group(50 cases,receiving cinacalcet combined with low-dose calcitriol)and operation group(60 cases,receiving TPTX+AT+thymectomy)according to different treatment regimens.The biochemical indexes,cardiac structure and function,clinical symptoms and quality of life of the two groups were compared before and after treatment for 24 months,and the complications,cost-effectiveness and recurrence rate of the two groups after operation were counted.Results After treatment,the levels of serum iPTH[(206.45±152.59)pg/ml],calcium[(2.05±0.26)mmol/L],phosphorus[(1.48±0.21)mmol/L],calcium-phosphorus product(3.02±0.69)and ALP[(102.03±30.25)U/L]in operation group were all lower Drug group[(721.32±325.36)pg/ml,(2.22±0.18)mmol/L,(1.91±0.22)mmol/L,(4.22±0.74),(140.62±27.15)U/L](P<0.05);LVEF[(60.85±4.02)%]in operation group was higher than that in drug group[(55.58±3.84)%].LVED[(48.03±2.58)mm]and LVST[(9.85±0.76)mm]were lower than those in drug group[(51.02±3.65)mm,(11.12±0.86)mm](P<0.05).The scores of bone pain,skin pruritus and restless legs syndrome in the operation group were lower than those of the medication group,and the KDTA score was higher than that of the medication group(P<0.05).The total cost of treatment in the operation group[(4.06±1.42)million yuan]was not significantly different from that in the drug group[(3.46±1.85)million yuan](P>0.05).The effective rate of iPTH reduction in operation group was 90.00%(54/60),which was higher than that in drug group(48.00%,24/50)(P<0.05).The cost-effectiveness analysis showed that the CER of the drug group and the operation group were 7.21 and 4.51 respectively,and the operation treatment had more cost-effectiveness advantages.The incremental cost-effectiveness analysis shows that compared with the drug group,the operation group needs to increase the cost by 14,800 yuan for each additional patient effectively treated for SHPT(P>0.05).There was no significant difference in the incidence of complications(13.33%VS 12.00%)and the recurrence rate(8.33%VS 4.00%)at 2 4 months after treatment between the operation group and the drug group(P>0.0 5).Conclusion TPTX+AT+thymectomy can relieve the bone pain,reduce the iPTH level,correct the disorder of calcium and phosphorus metabolism,improve the heart function and structure,and improve the quality of life,and the cost-effectiveness is higher than SHPT of drug treatment,without increasing short-term recurrence rate.
6.Biological characteristics of triple negative breast cancer with low expression of HER2
Jing LIAN ; Ruoqi LI ; Lei YAN ; Peng BU ; Huiwen WANG ; Yanfeng XI
Chinese Journal of Pathology 2024;53(9):898-904
Objective:To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low).Methods:A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups.Results:Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different ( P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group ( P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions:There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.
7.Urinary iodine characteristics of children aged 8 to 10 in Jiangxi Province in 2022
Jun SHANGGUAN ; Binghua ZHOU ; Qiang HU ; Meiqin HUANG ; Guai TANG ; Yanfeng GONG ; Zifen LI ; Wenfang PENG
Chinese Journal of Endemiology 2024;43(10):823-825
Objective:To study the urinary iodine levels of children in Jiangxi Province and provide a basis for prevention and treatment of iodine deficiency disorders and scientific iodine supplementation.Methods:From March to July in 2022, a systematic sampling method was used in 99 counties (cities, districts, abbreviated as counties) in Jiangxi Province. One township (street) was selected from each county in five directions: east, west, south, north and middle. One primary school was selected from each township (street), and 40 non boarding children aged 8 - 10 (half male and half female) were selected from each primary school. One random urine sample was collected to test urinary iodine, and the distribution of urinary iodine in different regions, genders, and ages were compared.Results:A total of 19 842 urine samples were collected from children, with a median urinary iodine level of 181.90 μg/L. The median urinary iodine levels of children in different cities ( H = 1 014.05, P < 0.001), genders ( Z = 6.44, P < 0.001) and ages groups ( H = 29.82, P < 0.001) were compared, and the differences were statistically significant. Conclusion:The urinary iodine level of children in Jiangxi Province is at an appropriate level, but the distribution of urinary iodine is uneven among different regions, genders, and ages, indicating that scientific and precise iodine supplementation is necessary for the prevention and treatment of iodine deficiency disorders.
8.Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques.
Dali TONG ; Mei ZHANG ; Yunru YANG ; Han XIA ; Haiyang TONG ; Huajun ZHANG ; Weihong ZENG ; Muziying LIU ; Yan WU ; Huan MA ; Xue HU ; Weiyong LIU ; Yuan CAI ; Yanfeng YAO ; Yichuan YAO ; Kunpeng LIU ; Shifang SHAN ; Yajuan LI ; Ge GAO ; Weiwei GUO ; Yun PENG ; Shaohong CHEN ; Juhong RAO ; Jiaxuan ZHAO ; Juan MIN ; Qingjun ZHU ; Yanmin ZHENG ; Lianxin LIU ; Chao SHAN ; Kai ZHONG ; Zilong QIU ; Tengchuan JIN ; Sandra CHIU ; Zhiming YUAN ; Tian XUE
Protein & Cell 2023;14(1):69-73
9.The relationship between shear wave elastography and pathological classification in nephrotic syndrome
Yingchen LUO ; Chaomei WEN ; Linqian PENG ; Yajuan LI ; Yanfeng YAO
Journal of Chinese Physician 2023;25(8):1144-1146,1152
Objective:To explore the clinical value of shear wave elastography in the diagnosis and pathological classification of nephrotic syndrome.Methods:A retrospective analysis was conducted on the clinical data of 43 patients with primary nephrotic syndrome (primary nephrotic syndrome group) diagnosed through renal biopsy at the Yongchuan Hospital Affiliated to Chongqing Medical University from June 2022 to March 2023. They were further divided into three subgroups: mesangial proliferative glomerulonephritis group, membranous nephropathy group, and minimal change nephropathy group. Another 30 healthy individuals were selected as the control group. We applied shear wave elastography to measure the shear wave velocity of the right renal lower pole parenchyma and statistically analyzed the differences in shear wave velocity between each group.Results:There was a statistically significant difference in shear wave velocity between the primary nephrotic syndrome group [(1.76±0.41)m/s] and the control group [(1.55±0.34)m/s] ( P<0.05); The shear wave velocity in the membranous nephropathy group [(1.97±0.36)m/s] was the highest, and there was a statistically significant difference ( P<0.05) compared to the small lesion nephropathy group [(1.54±0.42)m/s]; There was no statistically significant difference in shear wave velocity between the membranous nephropathy group and the mesangial proliferative glomerulonephritis group [(1.74±0.38)m/s], as well as between the mesangial proliferative glomerulonephritis group and the small lesion nephropathy group (all P>0.05). Conclusions:Shear wave elastography is a non-invasive examination that provides valuable clinical clues for the diagnosis and pathological classification of nephrotic syndrome by detecting the shear wave velocity of the kidney.
10.Liver transplantation for liver metastasis of unresectable rectal cancer: one case report
Chao SUN ; Peng ZHANG ; Shuyong MO ; Yanfeng WANG
Chinese Journal of Organ Transplantation 2023;44(6):366-369
This report described one case of applying liver transplantation (LT) in for liver metastases of unresectable rectal cancer.The recipient had multiple intrahepatic metastases upon a diagnosis of colorectal cancer.FOLFOX chemotherapy plus bevacizumab targeted therapy were offered after a resection of primary lesion.Two years later, intrahepatic metastases expanded while no extrahepatic metastasis or in situ recurrence was noted.After LT, tacrolimus + sirolimus immunosuppression regimen and chemotherapy of rhatitrexed were prescribed.Tumor recurred at 3 years after LT and the survival time was 6 years.For patients with unresectable liver metastases of colorectal cancer, LT in the absence of orthotopic recurrence and other distant metastases may improve patient quality-of-life and achieve better outcomes.


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