1.Pharmacological inhibition of ENaC or NCX can attenuate hepatic ischemia-reperfusion injury exacerbated by hypernatremia.
Yabin CHEN ; Hao LI ; Peihao WEN ; Jiakai ZHANG ; Zhihui WANG ; Shengli CAO ; Wenzhi GUO
Journal of Zhejiang University. Science. B 2025;26(5):461-476
Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na+/Ca2+ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals
;
Reperfusion Injury/drug therapy*
;
Hypernatremia/complications*
;
Rats
;
Liver/metabolism*
;
Rats, Inbred Lew
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Male
;
Apoptosis
;
Sodium-Calcium Exchanger/antagonists & inhibitors*
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Reactive Oxygen Species/metabolism*
;
Oxidative Stress
;
Epithelial Sodium Channel Blockers/pharmacology*
;
Epithelial Sodium Channels
;
Cell Line
;
Liver Transplantation
2.Efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator in the treatment of Sanders types II and III calcaneal fractures
Xiaohui HAO ; Yongqing WANG ; Zhanmin XU ; Xinan ZHANG ; Zhihui ZHAO ; Jingtao SUN ; Zhiqiang YANG ; Meiyue LIU ; Weiyong WU ; Baoxi HAO ; Juwen CHEN
Chinese Journal of Trauma 2025;41(5):463-470
Objective:To evaluate the efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator (short for "3M fixator") for Sanders types II and III calcaneal fractures.Methods:A retrospective case series study was conducted to analyze the clinical data of 26 patients (26 feet) with calcaneal fractures admitted to Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to June 2024, including 21 males and 5 females, aged 27-69 years [(46.5±2.5)years]. Among them, 10 patients had fractures in the left foot and 16 in the right. According to the Sanders classification, the fractures were classified as type II in 16 patients and type III in 10. All the patients were treated with the close reduction with reduction robot system combined with 3M fixator in a minimally invasive procedure. The surgical waiting time, operative duration, and fracture healing time were recorded. The length, width and height of the calcaneus, B?hler′s angle and Gissane′s angle were compared before operation and at 1, 3 months after operation. The visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score before operation and at 1, 3 months after operation and at the last follow-up were detected. The postoperative complications were recorded.Results:All the patients were followed up for 6-12 months [(9.7±1.1)months]. The surgical waiting time was 1-4 days [(2.0±0.8)days]. The operative duration was 36-66 minutes [(53.2±9.5)minutes]. All the fractures achieved primary union with a healing period of 3-4 months [(3.2±0.4)months]. At 1, 3 months after operation, the length of the calcaneus [(83.3±3.7)mm and (83.6±3.6)mm], width of the calcaneus [(44.3±5.8)mm and (44.3±5.7)mm], height of the calcaneus [(50.1±3.8)mm and (50.3±3.6)mm], B?hler′s angle [(29.8±2.9)° and (29.8±3.0)°], and Gissane angle [(121.1±6.7)° and (123.9±5.9)°] were significantly improved compared with those before operation [(79.3±4.5)mm, (53.6±4.1)mm, (46.2±3.7)mm, (18.9±3.8)°, (109.0±7.5)°, respectively] ( P<0.05), with no significant differences between those indicators at 1, 3 months after operation ( P>0.05). The VAS scores were (3.2±0.6)points, (1.9±0.5)points, and (1.6±0.3)points at 1, 3 months after operation and at the last follow-up, which were lower than (7.1±0.5)points preoperatively and decreased with the prolongation of follow-up time ( P<0.05). The AOFAS scores were (73.5±6.9)points, (90.1±4.3)points, and (92.0±3.6)points, which were higher than (32.0±4.6)points preoperatively and increased with the follow-up time ( P<0.05). One patient had lateral calcaneal pain after operation, and was alleviated after rehabilitation. No complications such as infection or nonunion were found after operation. Conclusion:The reduction robot system combined with 3M fixator for Sanders types II and III calcaneal fractures demonstrates significant clinical advantages, such as reduced surgical waiting time and operative duration, promoted fracture healing, early alleviated pain, enhanced ankle joint functional recovery, and decreased complication occurrence.
3.Biomarkers affecting the progression of mild to moderate cognitive impairment after stroke:a non-targeted metabolomics analysis
Zhifeng WANG ; Jiao YANG ; Yujiang XI ; Shuangfeng XU ; Ting SHI ; Junfeng LAN ; Zhihui HAO ; Pengfen HE ; Aiming YANG ; Pan PAN ; Jian WANG
Chinese Journal of Tissue Engineering Research 2025;29(24):5116-5126
BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.
4.Nanoparticles preparation from ethanol extracts of Euphorbia helioscopia L.and antibacterial mechanism
Zhiying SHI ; Fengting LANG ; Li ZHAO ; Yangyang RU ; Jintao SUN ; Zhihui HAO
Chinese Journal of Veterinary Science 2025;45(9):1990-1998
In order to explore the potential of nanoparticles from ethanol extracts of Euphorbia he-lioscopia L.(ZQNPs)in antibacterial application.In this study,ZQNPs were prepared by the self-assembly method using alcohol extract of Euphorbia helioscopia L.,polylysine and polyethylene glycol 1 000 as raw materials.The morphology and structure of ZQNPs were characterized by transmission electron microscopy,UV-vis spectrophotometer,and Fourier transform infrared spec-troscopy.The growth and biofilm inhibition of ZQNPs against methicillin-resistant Staphylococcus aureus(MRSA)were tested by broth microdilution,crystal violet,and checkerboard assays.The broad-spectrum antibacterial activity and antibacterial activity of ZQNPs against three clinical strains were evaluated by broth microdilution method.Finally,the antibacterial mechanism of ZQNPs was preliminarily explored by morphological observation and soluble protein detection of MRSA.The results showed that ZQNPs were self-assembled and cross-linked multi-faceted spheres with an average diameter of 67 nm.The MIC of ZQNPs against MRSA was 8 mg/L,and the antibacterial effect was much better than that of Euphorbia helioscopia L.mongolicum alcohol extract(MIC>32 mg/L).The time killing curve again showed that ZQNPS had a good antibacteri-al effect on MRSA(8 mg/L)biofilm inhibition rate of 89%,and the antibacterial effect of ZQNPS combined with cefquinome sulfate showed additive results.The mics of ZQNPs against Gram-posi-tive bacteria(S.aureus)and gram-negative bacteria(E.coli)were 16 mg/L and 8 mg/L,respec-tively.The mics of ZQNPS against E.coli clinical strains were stable between 8 and 16 mg/L.The MIC of Salmonella clinical strains was 32-64 mg/L,and the MIC of S.aureus clinical strains was 8-64 mg/L.Preliminary antibacterial mechanism showed that ZQNPs could destroy the membrane structure of MRSA,lead to the release of intracellular substances,and affect the growth of MRSA.These results indicate that ZQNPs have a good antibacterial effect and have potential application value in antimicrobial therapy.
5.Nanoparticles preparation from ethanol extracts of Euphorbia helioscopia L.and antibacterial mechanism
Zhiying SHI ; Fengting LANG ; Li ZHAO ; Yangyang RU ; Jintao SUN ; Zhihui HAO
Chinese Journal of Veterinary Science 2025;45(9):1990-1998
In order to explore the potential of nanoparticles from ethanol extracts of Euphorbia he-lioscopia L.(ZQNPs)in antibacterial application.In this study,ZQNPs were prepared by the self-assembly method using alcohol extract of Euphorbia helioscopia L.,polylysine and polyethylene glycol 1 000 as raw materials.The morphology and structure of ZQNPs were characterized by transmission electron microscopy,UV-vis spectrophotometer,and Fourier transform infrared spec-troscopy.The growth and biofilm inhibition of ZQNPs against methicillin-resistant Staphylococcus aureus(MRSA)were tested by broth microdilution,crystal violet,and checkerboard assays.The broad-spectrum antibacterial activity and antibacterial activity of ZQNPs against three clinical strains were evaluated by broth microdilution method.Finally,the antibacterial mechanism of ZQNPs was preliminarily explored by morphological observation and soluble protein detection of MRSA.The results showed that ZQNPs were self-assembled and cross-linked multi-faceted spheres with an average diameter of 67 nm.The MIC of ZQNPs against MRSA was 8 mg/L,and the antibacterial effect was much better than that of Euphorbia helioscopia L.mongolicum alcohol extract(MIC>32 mg/L).The time killing curve again showed that ZQNPS had a good antibacteri-al effect on MRSA(8 mg/L)biofilm inhibition rate of 89%,and the antibacterial effect of ZQNPS combined with cefquinome sulfate showed additive results.The mics of ZQNPs against Gram-posi-tive bacteria(S.aureus)and gram-negative bacteria(E.coli)were 16 mg/L and 8 mg/L,respec-tively.The mics of ZQNPS against E.coli clinical strains were stable between 8 and 16 mg/L.The MIC of Salmonella clinical strains was 32-64 mg/L,and the MIC of S.aureus clinical strains was 8-64 mg/L.Preliminary antibacterial mechanism showed that ZQNPs could destroy the membrane structure of MRSA,lead to the release of intracellular substances,and affect the growth of MRSA.These results indicate that ZQNPs have a good antibacterial effect and have potential application value in antimicrobial therapy.
6.Biomarkers affecting the progression of mild to moderate cognitive impairment after stroke:a non-targeted metabolomics analysis
Zhifeng WANG ; Jiao YANG ; Yujiang XI ; Shuangfeng XU ; Ting SHI ; Junfeng LAN ; Zhihui HAO ; Pengfen HE ; Aiming YANG ; Pan PAN ; Jian WANG
Chinese Journal of Tissue Engineering Research 2025;29(24):5116-5126
BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.
7.Efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator in the treatment of Sanders types II and III calcaneal fractures
Xiaohui HAO ; Yongqing WANG ; Zhanmin XU ; Xinan ZHANG ; Zhihui ZHAO ; Jingtao SUN ; Zhiqiang YANG ; Meiyue LIU ; Weiyong WU ; Baoxi HAO ; Juwen CHEN
Chinese Journal of Trauma 2025;41(5):463-470
Objective:To evaluate the efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator (short for "3M fixator") for Sanders types II and III calcaneal fractures.Methods:A retrospective case series study was conducted to analyze the clinical data of 26 patients (26 feet) with calcaneal fractures admitted to Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to June 2024, including 21 males and 5 females, aged 27-69 years [(46.5±2.5)years]. Among them, 10 patients had fractures in the left foot and 16 in the right. According to the Sanders classification, the fractures were classified as type II in 16 patients and type III in 10. All the patients were treated with the close reduction with reduction robot system combined with 3M fixator in a minimally invasive procedure. The surgical waiting time, operative duration, and fracture healing time were recorded. The length, width and height of the calcaneus, B?hler′s angle and Gissane′s angle were compared before operation and at 1, 3 months after operation. The visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score before operation and at 1, 3 months after operation and at the last follow-up were detected. The postoperative complications were recorded.Results:All the patients were followed up for 6-12 months [(9.7±1.1)months]. The surgical waiting time was 1-4 days [(2.0±0.8)days]. The operative duration was 36-66 minutes [(53.2±9.5)minutes]. All the fractures achieved primary union with a healing period of 3-4 months [(3.2±0.4)months]. At 1, 3 months after operation, the length of the calcaneus [(83.3±3.7)mm and (83.6±3.6)mm], width of the calcaneus [(44.3±5.8)mm and (44.3±5.7)mm], height of the calcaneus [(50.1±3.8)mm and (50.3±3.6)mm], B?hler′s angle [(29.8±2.9)° and (29.8±3.0)°], and Gissane angle [(121.1±6.7)° and (123.9±5.9)°] were significantly improved compared with those before operation [(79.3±4.5)mm, (53.6±4.1)mm, (46.2±3.7)mm, (18.9±3.8)°, (109.0±7.5)°, respectively] ( P<0.05), with no significant differences between those indicators at 1, 3 months after operation ( P>0.05). The VAS scores were (3.2±0.6)points, (1.9±0.5)points, and (1.6±0.3)points at 1, 3 months after operation and at the last follow-up, which were lower than (7.1±0.5)points preoperatively and decreased with the prolongation of follow-up time ( P<0.05). The AOFAS scores were (73.5±6.9)points, (90.1±4.3)points, and (92.0±3.6)points, which were higher than (32.0±4.6)points preoperatively and increased with the follow-up time ( P<0.05). One patient had lateral calcaneal pain after operation, and was alleviated after rehabilitation. No complications such as infection or nonunion were found after operation. Conclusion:The reduction robot system combined with 3M fixator for Sanders types II and III calcaneal fractures demonstrates significant clinical advantages, such as reduced surgical waiting time and operative duration, promoted fracture healing, early alleviated pain, enhanced ankle joint functional recovery, and decreased complication occurrence.
8.Genetic polymorphism of ACOX1 gene and its correlation with milk quality traits in China Holstein dairy cows
Yurong HAO ; Zhihui ZHAO ; Tao YOU ; Haibin YU ; Guanghui LI ; Ping JIANG ; Ziwei LIN
Chinese Journal of Veterinary Science 2024;44(10):2260-2265
The SNP loci of ACOX1 gene in 83 China Holstein cows were detected by PCR amplifica-tion and direct sequencing,and the association between the genetic polymorphism loci of ACOX 1 gene and milk quality traits of China Holstein cows was analyzed by SPSS 25.0 software.The re-sults showed that a SNP locus I3-2 267 G→C was found in the third intron of ACOX1 gene,it was moderately polymorphic and in Hardy Weinberg equilibrium in the population.By correlation anal-ysis,it was found that the SNP locus was significantly related to the somatic cell content and cor-rected milk quantity of dairy cows.The I3-2 267 G→C locus of ACOX1 gene can be used as a mo-lecular marker of quality traits of Holstein cows in China,and provide reference for the study of quality traits of Holstein cows in China.
9.Surgical strategies and efficacy analysis for aortic dissection complicating intractable mesenteric artery ischemia
Lingwei ZOU ; Yifan LIU ; Hao LIU ; Bin CHEN ; Junhao JIANG ; Yun SHI ; Daqiao GUO ; Xin XU ; Zhihui DONG ; Weiguo FU
Chinese Journal of Surgery 2024;62(3):235-241
Objective:To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia.Methods:This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded.Results:Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%.Conclusions:Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.
10.Endovascular treatment for Stanford type B aortic dissection in Marfan syndrome patients: a series of 23 cases
Xiaolang JIANG ; Hao LIU ; Lingwei ZOU ; Bin CHEN ; Junhao JIANG ; Daqiao GUO ; Xin XU ; Zhihui DONG ; Weiguo FU
Chinese Journal of Surgery 2024;62(5):438-442
Objective:To evaluate the clinical outcomes of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B aortic dissection (TBAD) in Marfan syndrome patients who had no history of aortic arch replacement.Methods:This is a retrospective case-series study. From January 2009 to December 2019,the clinical data of Marfan syndrome patients who underwent TEVAR for TBAD at the Department of Vascular Surgery were collected. A total of 23 patients were enrolled,including 15 males and 8 females. The age was (38.0±11.0) years (range:24 to 56 years). Among them,12 patients had history of ascending aortic surgery. Details of TEVAR,perioperative complications and reintervention were recorded and survival rate was analyzed by Kaplan-Meier curve.Results:Technical success was 91.3% (21/23). Two patients with technical failure were as follows:one patient had type Ⅰa endoleak at the completion angiography,which healed spontaneously during the follow-up,and the other patient suffered aortic intimal intussusception after the deployment of the first stent-graft, and the second stent-graft was deployed. However, type Ⅲ endoleak was detected,which disappeared during the follow-up. One patient died during hospitalization. The median follow-up time ( M(IQR)) was 60 (48) months (range:12 to 132 months). Reintervention was performed on 7 patients,including 3 distal stent-graft-induced new entry,2 distal aortic dilation,1 Ⅰa endoleak and 1 retrograde type A aortic dissection,respectively. Five-year cumulative survival rate was 86.7% (95% CI:86.6% to 86.8%) and the 5-year freedom from reintervention rate was 81.8% (95% CI:61.8% to 92.8%). Conclusions:TEVAR is feasible in the treatment of TBAD in Marfan syndrome patients who has no history of aortic arch replacement. It has high technical success rate and low perioperative complication.

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