1.New research direction of organ dysfunction caused by hemorrhagic shock: mechanisms of mitochondrial quality control
Zheng ZHANG ; Hongjie DUAN ; Jiake CHAI ; Xiaofang ZOU ; Shaofang HAN ; Hailiang BAI ; Yufang ZHANG ; Huiting YUN ; Ran SUN
Chinese Critical Care Medicine 2024;36(1):93-97
Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.
2.Different transplantation models of hepatocellular carcinoma in mice
Rui PAN ; Kun YU ; Hailiang ZHANG ; Yongren ZHENG ; Xiaoyu ZHAO ; Junze TANG ; Jianming WU ; Xin CHENG
Acta Laboratorium Animalis Scientia Sinica 2024;32(3):329-336
Objective To explore the otherness of orthotopic injection of cell suspensions and transplantation of tumor tissue blocks to establish orthotopic implantation models of hepatocellular carcinoma in mice,and to provide a technical reference for the establishment of an orthotopic implantation model.Methods Healthy KM mice were divided into four groups:group A,direct injection of H22 cells;group B,direct injection of H22 ascitic cells;group C,transplantation of tissues;and group D,direct injection of saline.Activity and weight changes were observed regularly in each group and survival times were recorded.Liver tumor formation,tumor size,abdominal organ adhesion degree,and metastasis were observed in all groups.B-ultrasound imaging was performed,concentrations of alpha fetoprotein(AFP)and abnormal prothrombin(DCP)were detected,and liver histopathological changes were detected by hematoxylin and eosin staining.Results Mice molding operation time in groups A,B,and C were(3.36±0.44)min,(3.30±0.41)min,and(5.68±0.65)min,respectively.After modeling for 25 days,the rates of model formation in groups A,B,and C were all 100.0%.Severe abdominal adhesions occurred in 40.0%of mice in group A and 60.0%in group B,but in no mice in group C or D.Ascites occurred in 40.0%,100.0%,and 0.0%and abdominal wall tumors in 30.0%,60.0%,and 0.0%of mice in groups A,B,and C,respectively,while 40.0%of mice in group B also had liver metastasis.B-ultrasound imaging,detection of serum AFP and DCP levels,and histopathological result showed smooth liver margins,uneven echo and slightly lower echo mass,maintained high AFP and DCP secretion,and large numbers of inflammatory cells and tumor cells in mice in groups A,B,and C.Conclusions At day 25,all three methods can thus be used to establish orthotopic transplantation models of HCC.Among these,inj ection of cell suspensions demonstrated the advantage of simplicity in operation and the presence of multiple metastatic nodules within the liver,compared to transplantation of tumor tissue.Conversely,transplantation of tumor tissue showed the advantage of causing less impact on the abdomen and other organs when compared to inj ection of cell suspensions.
3.Hemorrhagic shock-induced vascular endothelial glycocalyx damage: progress on mechanism of damage and preventive and therapeutic strategies
Yufang ZHANG ; Hongjie DUAN ; Hailiang BAI ; Ran SUN ; Huiting YUN ; Zheng ZHANG
Chinese Journal of Trauma 2023;39(9):847-856
Hemorrhagic shock, a life-threatening organ hypoperfusion caused by rapid, massive blood loss, is the leading cause of traumatic death in peacetime and wartime. The vascular endothelial glycocalyx (vEG) plays an important role in maintaining microcirculatory homeostasis. Severe ischemia and hypoxia of hemorrhagic shock can damage the vEG, leading to endothelial dysfunction and exacerbated microcirculatory and organ impairments. Therefore, early prevention and treatment of vEG damage in hemorrhagic shock can improve microcirculation dysfunction, which is of paramount importance for therapeutic efficacies and outcomes. There have been many studies on the prevention and treatment of vEG damage in hemorrhagic shock, but none is based on the management of vEG damage. The authors reviewed the progress on the mechanism and preventive and therapeutic strategies of vEG damage caused by hemorrhagic shock, hoping to provide reference for the further research of hemorrhagic shock-induced vEG damage.
4.Clinical efficacy of radiofrequency ablation guided by CT hepatic arteriography in the treatment of multiple nodular liver metastases of colorectal cancer
Xiang GENG ; Hailiang LI ; Chenyang GUO ; Hongtao HU ; Hongtao CHENG ; Quanjun YAO ; Lin ZHENG ; Ke ZHAO
Chinese Journal of Hepatobiliary Surgery 2023;29(6):423-427
Objective:To evaluate the safety and efficacy of radiofrequency ablation guided by CT hepatic arteriography (CTHA) in the treatment of multiple nodular liver metastases of colorectal cancer.Methods:Clinical data of 32 patients with liver metastasis of colorectal cancer who underwent femoral arterial catheterization and percutaneous radiofrequency ablation guided by CT hepatic arteriography (CTHA) at the Affiliated Cancer Hospital of Zhengzhou University from March 2020 to September 2021 were retrospectively analyzed, including 21 males and 11 females, aged (53.2±9.9) years old. Before ablation, the angiography catheter were placed in the common or proper hepatic artery under the digital subtraction angiography (DSA). The patients were then transferred to a CT operating room. Under general anesthesia, contrast agent was injected into the indwelling angiography catheter and percutaneous radiofrequency ablation guided by CTHA was performed. The presentation of lesions, the dosage of contrast agent and complications during ablation were analyzed, and the treatment outcome was followed up outpatient or inpatient review.Results:All 32 patients uneventfully underwent DSA-guided angiography catheter placement, and CTHA-guided radiofrequency ablation was successfully performed in 97 lesions, with a technical success rate of 100% (97/97). The difference between CT values at the lesion enhancement site and peri-tumor hepatic parenchyma were greater than 25 HU. The total amount of contrast agent used during the procedure was 63.9±14.7 ml. All ablation-related complications were graded as A or B according to the Society of Interventional Radiology classification system. The complete ablation rate assessed by CTHA after the ablation was 100% (97/97). The rate of lesion necrosis was 100% evaluated by MRI one month after ablation. All patients were followed up and no recurrence was observed in 97 ablated lesions by the end of follow-up period.Conclusion:Radiofrequency ablation guided by CTHA is safe and feasible for the treatment of multiple nodular liver metastases of colorectal cancer, which could reduce the local recurrence of lesions after ablation.
5.CT texture analysis for predicting pseudoprogression in metastatic clear cell renal cell carcinoma during PD-1 inhibitor therapy
Bingjie ZHENG ; Wenjuan XU ; Lingdi ZHAO ; Chunmiao XU ; Hailiang LI
Chinese Journal of Internal Medicine 2023;62(9):1114-1120
Objective:To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy.Methods:A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis.Results:A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included“original_ngtdm_Strength”(0.49 vs. -0.61, P=0.006), “wavelet-HLH_glszm_ZonePercentage”(0.67 vs. -0.22, P=0.024),“wavelet-LHL_ngtdm_Strength”(1.20 vs. -0.51, P=0.002), “wavelet-HLL_gldm_LargeDependenceEmphasis”(-0.84 vs. 0.19, P=0.002), “wavelet-HLH_glcm_Id” (-0.30 vs. 0.43, P=0.037),“wavelet- HLH_glrlm_RunPercentage”(0.45 vs. -0.01, P=0.032),“wavelet-LHH_firstorder_Skewness”(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95% CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95% CI 0.817-0.997) according to ROC curve analysis. Conclusions:Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.
6.Clinical study of the CT hepatic arteriography guided percutaneous radiofrequency ablation of hypervascular hepatocellular carcinoma
Hongtao CHENG ; Chenyang GUO ; Xiang GENG ; Hongtao HU ; Lin ZHENG ; Chengshi CHEN ; Jincheng XIAO ; Dengwei ZONG ; Hailiang LI
Chinese Journal of Radiology 2022;56(7):800-804
Objective:To investigate the feasibility of CT hepatic arteriography(CTHA) guided percutaneous radiofrequency ablation of hepatocellular carcinoma (HCC).Methods:Forty-four patients diagnosed with hepatocellular carcinomas were enrolled in this prospective study from September 2019 to May 2021 in Henan Cancer Hospital. Thirty-three out of the 44 patients were treatment naive, 8 cases recurred after radiofrequency ablation, and the other 3 patients recurred after surgery. The mean size of HCC nodules was 5-44(17±8)mm measured on enhanced MRI images. Each patient was implanted a 5-French Cobra catheter or a 5-French RH angiographic catheter, then was catheterized into common hepatic artery or proper hepatic artery, under DSA monitoring via right femoral artery. Then the patient was transferred to CT operation room. Percutaneous radiofrequency ablation was performed by CTHA guidance using contrast agent injected via the catheter indwelled in hepatic artery. The endpoint of a complete ablation was a non-enhancing ablation necrosis zone in the target tumor and the target tumor margin at least 5 mm on CTHA. At the end of the procedure, the probe was retracted using tract ablation, and the arterial catheter and sheath were removed. The number of HCC lesions showed on the enhanced MRI and CTHA imaging were compared using Wilcoxon rank-sum test. The technical success rate and volume of contrast agent used during the CTHA ablation procedures were summarized.Results:Additional tumors were founded in 13 out of the 44 patients during the CT hepatic arteriography compared with enhanced MRI. The tumors founded by enhanced MRI and CTHA were 64 and 91 respectively, with statistical significance ( Z=-3.24, P=0.001). One patient dropped out of the study after palliative ablation and was transferred to transaterial chemoembolization treatment because the number of lesions showed by CTHA scan was more than 5. The other 43 patients got complete ablation verified by immediate postoperative assessment using CTHA. The technical success rate was 100%. The average volume of contrast agent used in CTHA guided radiofrequency ablation was 30-80(42±14)ml. There was no complications occurred related to the CTHA guided percutaneous radiofrequency ablation procedures. Conclusions:CTHA can demonstrate additional lesions that can not be detected by the enhanced MRI images, which improves the lesion conspicuity and verifies the optimal position of radiofrequency probe. The complete tumor ablation can be verified by CTHA performed immediately after ablation.
7.Comparison of Radiological Tumor Response Based on iRECIST and RECIST 1.1 in Metastatic Clear-Cell Renal Cell Carcinoma Patients Treated with Programmed Cell Death-1 Inhibitor Therapy
Bingjie ZHENG ; Ji Hoon SHIN ; Hailiang LI ; Yanqiong CHEN ; Yuan GUO ; Meiyun WANG
Korean Journal of Radiology 2021;22(3):366-375
Objective:
To evaluate the radiological tumor response patterns and compare the response assessments based on immunebased therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1 in metastatic clear-cell renal cell carcinoma (mccRCC) patients treated with programmed cell death-1 (PD-1) inhibitors.
Materials and Methods:
All mccRCC patients treated with PD-1 inhibitors at Henan Cancer Hospital, China, between January 2018 and April 2019, were retrospectively studied. A total of 30 mccRCC patients (20 males and 10 females; mean age, 55.6 years; age range, 37–79 years) were analyzed. The target lesions were quantified on consecutive CT scans during therapy using iRECIST and RECIST 1.1. The tumor growth rate was calculated before and after therapy initiation. The response patterns were analyzed, and the differences in tumor response assessments of the two criteria were compared. The intra- and inter-observer variabilities of iRECIST and RECIST 1.1 were also analyzed.
Results:
The objective response rate throughout therapy was 50% (95% confidence interval [CI]: 32.1–67.9) based on iRECIST and 30% (95% CI: 13.6–46.4) based on RECIST 1.1. The time-to-progression (TTP) based on iRECIST was longer than that based on RECIST 1.1 (median TTP: not reached vs. 170 days, p = 0.04). iRECIST and RECIST 1.1 were discordant in 8 cases, which were evaluated as immune-unconfirmed PD based on iRECIST and PD based on RECIST 1.1. Six patients (20%, 6/30) had pseudoprogression based on iRECIST, of which four demonstrated early pseudoprogression and two had delayed pseudoprogression.Significant differences in the tumor response assessments based on the two criteria were observed (p < 0.001). No patients demonstrated hyperprogression during the study period.
Conclusion
Our study confirmed that the iRECIST criteria are more capable of capturing immune-related atypical responses during immunotherapy, whereas conventional RECIST 1.1 may underestimate the benefit of PD-1 inhibitors. Pseudoprogression is not rare in mccRCC patients during PD-1 inhibitor therapy, and it may last for more than the recommended maximum of 8 weeks, indicating a limitation of the current strategy for immune response monitoring.
8.Effects of magnetic thermotherapy mediated by magnetic nanocomposite PEG-APTESMNP on proliferation of liver cancer cells.
Quan ZHENG ; Peng GAO ; Xiaofeng LI ; Hailiang LI
Journal of Southern Medical University 2019;39(8):891-897
OBJECTIVE:
To observe the inhibitory effects of PEG-APTES-MNP magnetic heating on liver cancer cells.
METHODS:
The magnetic nanoparticle complex PEG-APTES-MNP was synthesized and its physiochemical properties and biocompatibility were characterized. HepG2 cells were incubated with the PEG-APTES-MNP nanoparticles for magnetic heating or nanoparticle therapy. Prussian blue staining was used to detect the uptake efficiency of the magnetic nanoparticles by HepG2 cells. MTT assay and flow cytometry were used to evaluate the inhibitory effect of the nanoparticles on HepG2 cells, and laser scanning confocal microscopy was used to detect the production of reactive oxygen species (ROS) in the cells. Fifteen nude mice bearing HepG2 cell xenografts were randomized equally into PEG-APTES-MNP injection group (with nanocomposite injection only), PEG-APTES-MNP magnetic heating group and control group (with PBS injection), and the tumor growth were observed in the mice after the treatments.
RESULTS:
The synthesized PEG-APTES-MNP nanoparticles showed good physicochemical properties and biocompatibility. Incubation of HepG2 with the nanoparticles resulted in significantly increased ROS production, obvious inhibition of the cell growth through the synergetic effects of magnetic heating ( < 0.05), and significantly enhanced cell apoptosis. In the tumor-bearing nude mice, the nanoparticles strongly inhibited the tumor growth by magnetic heating ( < 0.05).
CONCLUSIONS
The magnetic nanocomposite PEG-APTES-MNP has good physicochemical properties and bioavailability and can strongly inhibit the growth of liver cancer cells both and in nude mice through magnetic heating, demonstrating its potential as a candidate nanomedicine for liver cancer treatment.
Animals
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Cell Line, Tumor
;
Cell Proliferation
;
Humans
;
Hyperthermia, Induced
;
Liver Neoplasms
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Magnetics
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Mice
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Mice, Nude
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Nanocomposites
9.Interventional treatment for hepatocellular carcinoma with hepatic arterio-portal shunts:comparision of ethanol-soaked gelatin sponge and gelatin sponge
Jing LI ; Hailiang LI ; Chenyang GUO ; Jincheng XIAO ; Hongtao HU ; Dengwei ZONG ; Lin ZHENG ; Junli MA
Chinese Journal of Radiology 2019;53(2):127-132
Objective To investigate the effect of embolization with ethanol-soaked gelatin sponge for the treatment of arterioportal shunting (APS) in patients with hepatocellular carcinoma (HCC). Methods From January 2016 to June 2017, a total of 78 patients with unresectable HCC were enrolled in this study. These patients were randomly divided into two groups by digital random method. The experimental group (n=39) received transarterial embolization of the shunt with ethanol-soaked gelatin sponge, while the control group (n=39) received only gelatin sponge shunt. Both of the two groups underwent transarterial chemoembolization if available. Changes in APS, tumor response (according to modified response evaluation criteria in solid tumor), changes in Eastern Cooperative Oncology Group (ECOG), and haemodynamics changes of the portal vein were analyzed. χ2 test and t test were used to compare the differences of qualitative and quantitative parameters between two groups. The APS grades were compared between the two groups before treatment and 2 months after treatment using rank sum test. Results Six patients were lost during the 2-month follow-up, and 72 patients were followed up, which include 38 patients in the experimental group and 34 patients in the control group. Compared to (14/34), the experimental group (25/38) has higher The APS improvement rates of the experimental group and the control group were 65.8%(25/38) and 41.2%(14/34), and there was significant difference (χ2=4.379, P<0.05). Of the 72 patients, 66 cases were conform to modified response evaluation criteria in solid tumor, which include 35 patients in the experimental group and 31 patients in the control group. Tumor response at 2 months of the experimental group and the control group were 57.1%(20/35) and 32.3%(10/31), and there was significant difference (χ2=4.106, P<0.05). The ECOG score was significantly decreased from 2 points to ≤1 point in 19 cases in the experimental group, while 12 cases in the control group (χ2=6.894, P<0.05). Compared with the control group, the diameter of the portal vein dropped significantly (t=2.082, P<0.05), while the blood flow velocity of portal vein increased (t=2.219, P<0.05) obviously in the experimental group 1 month after treatment. Conclusion Tansarterial embolization with ethanol-soaked gelatin sponge can effectively improve APS improvement rate, and quality of life of patients with unresectable HCC accompanied with APS.
10.Clinical analysis of transcatheter closure of patent foramen ovale in migraine
Xiaoqing LI ; Wenjian MA ; Peng YUAN ; Li WANG ; Hailiang ZHENG
Chinese Journal of Neurology 2018;51(1):45-48
Objective To investigate the effect of the transcatheter closure of patent foramen ovale (PFO) on the treatment of migraine.Methods This prospective clinical trial enrolled 43 consecutive migraine patients with PFO from Department of Neurology,Beijing Anzhen Hospital from March 2014 to March 2015,in which PFO was diagnosed by transesophageal echocardiography (TEE) and contrast-enhanced transcranial Doppler (c-TCD).We grouped subjects according to their selection or refusal of PFO closure.Nine patients were allocated to treatment with PFO closure.Thirty-four patients were given with medical treatment and were assigned to control group.Basal clinical data,frequency of migraine,duration of migraine and scores of Headache Impact Test-6 (HIT-6) were collected.c-TCD was performed after procedure of PFO closure transthoracic echocardiography.Changes of HIT-6 scores were analyzed after closure of PFO in the follow-up period.Results Successful PFO procedure was achieved in all patients without any complications both in hospital and in follow-up period.Only one patient had residual Ⅱ-grade right-to-left shunt (RLS) tested by c-TCD.Mean scores of HIT-6 in the surgical group were reduced significantly (49.3 ± 3.6 vs 67.5 ± 4.9,t =15.129,P =0.000).There were statistically significant differences in mean reduction of HIT-6 scores in the following one year for the female (48.8 ± 3.1 vs 69.8 ± 2.6,t =15.674,P=0.002),constant RLS (47.8 ±2.1 vs 67.9 ±3.5,t =8.572,P=0.043),RLS Ⅲ (50.6±2.3 vs65.4±2.7,t=7.663,P=0.039)/RLS 1V(48.2 ±1.9 vs 68.5 ±3.9,t=8.924,P=0.028)as well as migraine with aura subgroup (47.9± 1.6 vs 68.3 ±3.8,t=13.532,P=0.001).Conclusion Our results suggest that transcatheter PFO closure is a safe and effective approach for the treatment of migraine,espeecially for female migraineur with aura and with constant serious RLS.

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