1.Liver tolerogenic dendritic cells and liver transplantation immunity
Chinese Journal of Hepatobiliary Surgery 2021;27(2):149-152
Dendritic cells are the key cells to regulate immunity. Tolerogenic dendritic cells (Tol-DC) with immunosuppressive function play an important role in inducing and maintaining immune tolerance. In recent years, a class of liver Tol-DC with low level of presenting antigen and inhibition of T cell activation and proliferation has become a research hotspot to reduce the rejection of liver transplantation. At the same time, there are many strategies to induce phenotypic stable Tol-DC, which lays a foundation for its clinical application. This article introduces the current understanding of liver Tol-DC and its mechanism of regulating the immunity of liver transplantation, in order to provide new ideas for immunotherapy of liver transplantation.
2.18F-FLT and 18F-FDG PET/CT Scan in Diagnosing Lung Cancer:A Meta-analysis
Longlong WANG ; Jingjian WANG ; Bing HAN ; Yanzhong GAO ; Qing ZHAO ; Minjuan WU
Chinese Journal of Medical Imaging 2015;(1):50-55
Purpose To assess the diagnostic value of 18F-FLT and 18F-FDG PET/CT scan in patients with lung cancer. Materials and Methods Computer-based retrieval was performed on Medline, PubMed, EMbase, Wanfang data, CNKI and the Cochrane Library to search reports on diagnostic value of lung cancer with 18F-FLT and 18F-FDG PET/CT scan. The quality of included studies was evaluated according to quality assessment of diagnostic accuracy studies (QUADAS), and MetaDisc software was adopted to conduct meta-analysis. The pooled specificity, sensitivity, and diagnostic odds ratio (DOR) were calculated. The heterogeneity was tested. The summary receiving operating characteristic (SROC) curve was drawn, and the areas under the curve (AUC) as well as Q* were measured. Results Ten studies were included. Meta-analysis showed pooled sensitivity was 0.88, pooled specificity was 0.56, DOR was 9.10, AUC was 0.8102, Q*was 0.7448 for FDG group;pooled sensitivity was 0.79, pooled specificity was 0.78, DOR was 12.50, AUC was 0.8440, Q*was 0.7756 for FLT group. Conclusion Both 18F-FDG and 18F-FLT have well diagnostic value for lung cancer, but the specificity of 18F-FLT is higher than that of 18F-FDG in the diagnosis of lung cancer.
3. Effect of benazepril on nuclear factor E2 related factor 2, nicotinamide adenine dinucleotide phosphate oxidase and reactive oxygen species in rats with hepatic fibrosis
Yingying XU ; Fengjun SHEN ; Longlong WU
Chinese Journal of Hepatology 2019;27(9):677-680
Objective:
To study the effect of benazepril on the expression of nuclear factor E2 related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and reactive oxygen species (ROS) concentration in rats with hepatic fibrosis and to explore the possible antifibrotic mechanism of benazepril.
Methods:
Twenty-two healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (6 rats), model group (8 rats) and benazepril treatment group (8 rats). Two rats died during modeling and treatment in the model group and the benazepril treatment group, and a model of hepatic fibrosis induced by carbon tetrachloride (CCL4) was established. The rats in benazepril group were given benazepril for 8 weeks by gastric gavage. The assessment of liver tissue damage in each group was measured using conventional hematoxylin-eosin and Masson staining. The mRNA level of Nrf2, NOX4 in liver tissue was detected by RT-PCR, and serum ROS concentration was determined by colorimetry. All data were expressed in mean ± standard deviations, and were analyzed using SPSS21.0 statistical software. The data were compared using one-way analysis of variance, and the LSD-t method was used for pairwise comparison between the two groups. The correlation analysis was performed by Spearman’s correlation analysis.
Results:
In the liver of the model group, with the aggravation of liver fibrosis the expression of Nrf2mRNA, NOX4 mRNA and ROS concentration were higher than control group [(4.01 ± 3.40), (31.78 ± 3.96), (1.82 ± 0.46) μg/ ml vs. (0.12 ± 0.11), (2.03 ± 0.31), (1.56±0.84) μg/ml,
4. Effect of valsartan on the expression of leptin, leptin receptor and collagen in rats with hepatic fibrosis
Huifang HUANG ; Xinmei HUO ; Lijuan HUO ; Fengjun SHEN ; Longlong WU
Chinese Journal of Hepatology 2018;26(2):119-124
Objective:
To investigate the effects of angiotensin II type 1 receptor antagonist valsartan on leptin, leptin receptor and collagen in rats with hepatic fibrosis.
Methods:
Thirty-six male wistar rats were randomly divided into control group, model group and drug-treated group, with 12 rats in each group. Liver fibrosis models were made by subcutaneous injection of carbon tetrachloride on the dorsal of the rats, simultaneously gastric gavage with Valsartan and were killed at the end of 8th week. The degree of liver fibrosis was observed by HE and Masson staining. The serum leptin (LP) and TGFβ1 were determined by ELISA. Liver LP mRNA and leptin receptor mRNA (OB-R mRNA) were detected by RT-PCR. Liver LP, OB-R and collagen I were detected by Western blot. The data of multiple groups were analyzed by one-way analysis variance (ANOVA), and linear correlation was performed between serum LP and TGF β1.
Results:
After the intervention of valsartan, HE and Masson staining showed that the degree of liver fibrosis was significantly reduced. The levels of serum LP and TGFβ1 in the control group were (18.92 ± 7.10) ng/ml and (9.13 ± 1.58) pg/ml respectively, which were significantly lower than those in the model group (46.92 ± 28.54) ng/ml and (16.39 ± 3.56) pg/ml, And (29.27 ± 7.27) ng/ml and (12.24 ± 2.94) pg/ml in the drug-treated group, respectively. The
5.Clinical study of transperitoneal and retroperitoneal robot-assisted partial nephrectomy for renal hilar tumors
Jianlin YUAN ; Ping MENG ; Xiaojian YANG ; Yanzhu WANG ; Weijun QIN ; Yuntao ZHANG ; Longlong ZHANG ; Bo YANG ; Peng WU ; Yuming JING ; Wanxiang ZHENG
Chinese Journal of Urology 2017;38(7):502-506
Objective To investigate the clinical value and experience of transperitoneal and retroperitoneal robot-assisted partial nephrectomy for renal hi1 ar tumors.Methods We evaluated 48 patients who had partial nephrectomy for renal hilar tumor by robotic surgical syestem from January 2013 to March 2017.In those cases,35 were male and 13 were female,with an average age of 57.3 (range from 41 to 75 ),27 cases were ventral tumor and 21 cases were dorsal tumor.3 cases were totally confined to the renal parenchyma,the other 45 cases were partially confined to the renal parenchyma.18 cases were performed surgery by retroperitoneal route,the rest 30 cases were performed by peritoneal route.Results A total of 48 patients underwent successful robotic partial nephrectomy for renal hilar tumors.The mean warm ischemia time was 22 minutes (range from 16 to 33 minutes) and the mean estimated blood loss was 88 md (range from 50 to 350 ml).No bleeding-related complications were found.Histopathology confirmed 39 cases of ccRCC,7 cases of angioleiomyolipoma,2 cases of renal oncocytoma.There was one case in this review was positive surgical margin (2.1%) and found no sign of recurrence during the short term post-operation follow-up.All cases in this review are following up after surgery to date from 2 months to 4 years,no cases of tumor recurrence or metastasis were found.Conclusions The application of transperitoneal and retroperitoneal RAPN is the effective and safe way for renal hilar tumor resection,and it has a clear advantage of renal surgical incision stitching and tumor complete resection.The choice of surgical approaches depends on the size and location of tumor and the clinical experience of the surgeon.
6.Mechanisms of bone marrow mesenchymal stem cells plus normothermic mechanical perfusion alleviating hepatocyte apoptosis after donation after cardiac death transplantation in rats
Longlong WU ; Mengshu YUAN ; Ling LIN ; Xuan TIAN ; Weiping ZHENG ; Huan CAO ; Hongli SONG
Chinese Journal of Organ Transplantation 2022;43(4):228-234
Objective:To explore the effect and possible mechanism of normal temperature mechanical perfusion(NMP)plus bone marrow mesenchymal stem cells(BMMSCs)on early endoplasmic reticulum stress(ERs)and cellular apoptosis after donation after cardiac death(DCD)donor liver transplantation.Methods:BMMSCs were isolated and cultured by adherence method.Sixty Sprague-Dawley(SD)rats were randomly divided into five groups of sham operation(sham), static cold storage(SCS), NMP, BMMSC and NMP plus BMMSCs(BP)( n=12 each). Liver tissue and serum sample of each group were harvested at Day 1/7 post-operation.Hematoxylin-eosin(HE)staining was employed for observing pathological changes of liver tissue; TdT-mediated dUTP nick end labeling(TUNNEL)staining for detecting cellular apoptosis; immunohistochemistry for detecting the expression of hepatocyte transcription factor C/EBP homologous protein(CHOP); Western blot for detecting the expressions of GRP-78, p-PERK, ATF4, CHOP and cleaved caspase-3. Results:Compared with SCS group, hepatic injury and inflammation significantly declined in NMP, BMMSC and BP groups and improvement of hepatic injury was the most pronounced in BP group.Cellular apoptosis lessened markedly in BP group at Day 1/7 as compared with SCS group and the difference was statistically significant.The expressions of ERs-related proteins GRP-78, p-PERK and ATF4 spiked in SCS group and the expressions of pro-apoptotic proteins CHOP and cleaved caspase-3 were significantly elevated and declined markedly in BP group.And the difference was statistically significant.Conclusions:BMMSCs plus NMP can significantly improve hepatocyte apoptosis and inflammatory response after DCD donor liver transplantation.And its mechanism may be correlated with suppressing early endoplasmic reticulum stress of hepatocytes.
7.Randomized controlled study of olanzapine oral soluble film versus intramuscular haloperidol against agitated behaviour in male inpatients with schizophrenia
Longlong SUN ; Yanhai WU ; Yexin LI ; Chenchen TAN ; Shu CUI ; Jinghua ZHAO
Sichuan Mental Health 2024;37(5):409-413
Background Agitated behaviour in male patients with schizophrenia can lead to serious consequences for the individual and the society.Non-invasive drug delivery may help to rapidly control agitation and improve the overall patient satisfaction,but there are limited studies on the efficacy of olanzapine oral soluble film for the treatment of agitated behaviour in patients with schizophrenia.Objective To compare the efficacy and safety profile of olanzapine oral soluble film versus intramuscular haloperidol against agitated behaviour in male patients with schizophrenia,so as to provide a reference for the treatment of agitated behaviour.Methods From May 2022 to July 2023,a consecutive sample of schizophrenic patients(n=44)with agitated behaviour who met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)were recruited in the male psychiatric closed ward of the Third People's Hospital of Fuyang.Patients were assigned into two groups using the random number table method,each with 22 cases.Study group was treated with olanzapine oral soluble film 10 mg/d,while control group was given intramuscular haloperidol 8 mg/d.The severity of agitated behaviour was determined using Positive and Negative Syndrome Scale-Excited Component(PANSS-EC)and Agitation Calmness Evaluation Scale(ACES)at the baseline and after 6 h of drug administration.The treatment response rate was calculated based on the reduction of PANSS-EC score,and the drug side effects were assessed using Rating Scale for Extrapyramidal Side Effects(RSESE)and Barnes Akathisia Rating Scale(BARS)after 6 h of drug administration.Results After 6 h of drug administration,no statistical difference was reported in PANSS-EC score and ACES score between two groups(F=0.039,0.082,P>0.05),and the treatment response rate yielded no statistical difference between two groups(χ2=0.419,P=0.517),while study group reported a lower incidence rate of adverse reactions compared with control group,with statistically significant difference(P=0.031).BARS scores noted no statistical significant difference between two groups(t=0.587,P=0.561),whereas study group scored lower on RSES compared to control group,with a statistical difference(t=-7.367,P<0.01).Conclusion In the treatment of agitation in male patients with schizophrenia,the efficacy of olanzapine oral soluble film is comparable to that of intramuscular haloperidol,while the safety profile of the former is superior to that of the latter.
8.Effect of amifostine on proliferation and differentiation of human megakaryocyte Dami cells
Haitao WANG ; Bo YANG ; Xuechun LU ; Bo HU ; Hongqi YANG ; Longlong LUO ; Jie LIN ; Suxia LI ; Hui FAN ; Chunxia QIAO ; Wei WANG ; Xiaoling LANG ; Jing GENG ; Yan LI ; Xiaoxiong WU ; Ming LYU ; Hongli ZHU
Chinese Journal of Pharmacology and Toxicology 2016;30(7):723-727
OBJECTIVE To investigate the effect of amifostine(Amf)on the differentiation of human megakaryocyte cell line-Dami. METHODS Dami cells were treated with Amf 0.01-5.0 mmol · L-1 for 12 d. Dami cells were counted every day for the growth curve:only cells with a diameter>20μm. The platelet demarcation membrane system was observed by transmission electron microscopy. The expression of CD33,CD34,CD41a and DNA ploidy was detected by flow cytometry. RESULTS Amf 0.1-1.0 mmol · L-1 promoted the differentiation of Dami cells ,but inhibited their proliferation at a concentration>1.0 mmol · L-1. When these cells were treated with Amf 1.0 mmol · L-1 for 12 d,the platelet demarcation membrane system was observed,the percentage of cells with a diameter >20 μm was increased by 24.6%(P<0.01),the expression of CD41a was increased by 11.9%,while the expression of CD33 was decreased by 13.6%(P<0.05). Polyploidy cells(16N)were observed,and 4N,8N and 16N cells were increased to 31.56%,8.83% and 3.43%,respectively(P<0.05). CONCLUSION Amf 0.1-1.0 mmol · L-1 can promote the differentiation of Dami cells,but inhibit their proliferation at a high concentration(>1.0 mmol·L-1).
9.Preliminary evaluation of sunitinib as first line therapy in treating patients with metastatic renal cell carcinoma
Jianlin YUAN ; Fuli WANG ; Weijun QIN ; Jun QIN ; Xiaojian YANG ; Chunjuan TIAN ; Rongliang QIN ; Chen SHAO ; Lijun YANG ; Fei LIU ; Geng ZHANG ; Ping MENG ; Longlong ZHANG ; Yu ZHENG ; Guojun WU
Chinese Journal of Urology 2015;(10):742-745
[Abstact] Objective To investigate the efficacy and safety of sunitinib as first line therapy in treating those patients with metastatic renal cell carcinoma ( mRCC ) .Methods A total of 66 patients , including 42 male and 24 female cases ,with metastatic renal cell carcinoma were enrolled from January 2009 to June 2014.The median age was 52 years (range 26-75 years).According to American Joint Committee On Cancer (AJCC) staging,there were 35 cases of T3 stage,31 cases of T4 stage.All patients had distant metastasis ,including single organ metastasis in 52 patients and multiple organ metastasis in 14 cases.Sixty-one patients received prior radical nephrectomy ,5 patients received biopsy .Sixty-two patients were diagnosed as renal clear cell carcinoma and 4 patients were diagnosed as renal papillary cell carcinoma .Sunitinib was administered in standard 4/2 regimens.Briefly, patient takes 50 mg once a day orally for 4 weeks.Then the sunitinib will be stopped for 2 weeks.Six weeks was defined as 1 cycle.It should be continued until disease progression or occurrence of intolerable adverse reactions .The efficacy of sunitinib should be evaluated within 2 cycles.Results The duration of following-up ranged from 5 to 66 months.The efficacy could be evaluated in 63 patients.Two patients ( 3.2%) achieved complete remission .Twelve patients ( 19.0%) achieved partial remission.Forty-five patients (71.4%) demonstrated stable disease and 4 patients (6.3%)
developed progressive disease .The disease control rate was 93.7%(59/63) and the objective response rate was 22.2%(14/63).2 (3.2%) patients died due to the progression of disease .The most commonⅠ-Ⅱadverse events included fatigue in 36 cases ( 57.1%) , thrombocytopenia in 36 cases ( 57.1%) , hand-foot syndrome in 32 cases (50.8%),hypertension in 27 cases (42.9%),neutropenia in 15 cases (23.8%), hypothyroidism in 12 cases (19.0%), diarrhea in 6 cases (9.5%) and alopecia in 4 cases (6.3%).Ⅲ-Ⅳ adverse events were hand-foot syndrome in 4 cases ( 6.3%) , hypertension in 2 cases ( 3.2%) , neutropenia in 5 cases (7.9%) and thrombocytopenia in 5 cases (7.9%).Most mild adverse reactions after symptomatic treatment could be alleviated ,did not affect the medication .When the adverse events returned to the Ⅰ-Ⅱdegree, the 37.5 mg sunitinib was resumed once daily by orally.NoⅢ-Ⅳadverse events were reported again.Conclusions Sunitinib was efficacious in the treatment of advanced renal cell carcinoma.Most mild adverse events were tolerable ,and severe adverse events need medical treatment .
10.Effect of BMMSCs on steatosis of DCD donor liver in SD rats by normothermic machine perfusion
Xiang LI ; Longlong WU ; Xuan TIAN ; Weiping ZHENG ; Huan CAO ; Mengshu YUAN ; Hongli SONG
Chinese Journal of Hepatobiliary Surgery 2022;28(1):56-62
Objective:To investigate the role of ferroptosis in bone marrow mesenchymal stem cells (BMMSCs) combine with normothermic machine perfusion (NMP) in repairing steatotic liver donor after cardiac death (DCD) in SD rats.Methods:BMMSCs were derived from SD rats to establish the DCD model of rats steatotic liver. A total of 24 rats were randomly divided into four groups: simple steatotic liver model group (Sham), static cold storage group (SCS), NMP, BMMSCs combine with NMP preservation group (BNMP), and the preservation time was 4 hours. The donor liver function was evaluated by liver structure, liver enzymes and lactic acid content of perfusion fluid, bile secretion and inflammatory cytokines; furthermore, in order to evaluate the occurrence of liver ferroptosis, the content of Fe 2+, malondialdehyde and glutathione (GSH) in liver tissue, as well as the mRNA or protein expression changes of cyclooxygenase-2 (COX-2), prostaglandin-endoperoxide synthase 2 (Ptgs2), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) were detected. Results:After DCD steatotic donor liver was preserved for 4 hours, the liver injury, pro-inflammatory and anti-inflammatory cytokines expression in the BNMP and NMP groups were better than those in the SCS group. During the machine perfusion preservation period, alanine aminotransferase [(189.0±12.5)U/L vs. (227.7±16.2)U/L], aspartate aminotransferase [(207.3±18.6)U/L vs. (247.0±11.8)U/L] and lactic acid [(2.3±0.3)mmol/L vs. (2.9±0.2)mmol/L] in the BNMP group is lower than those in NMP group, moreover, the amount of hepatic bile secretion in the BNMP group [(1 245.7±46.8) μl vs. (1 014.3±67.9) μl] was more than that in NMP group, the difference was statistically significant (all P<0.05). The content of Fe 2+ and malondialdehyde in the liver tissue of BNMP group was significantly lower than those of SCS and NMP groups, on the contrary, the content of GSH was significantly higher than those of SCS and NMP groups. In addition, in the BNMP group, the mRNA level of Ptgs2 and protein level of COX-2 in the liver were significantly reduced, and expression of GPX4 and FTH1 were significantly higher than those of NMP and SCS groups, the differences were statistically significant (all P<0.05). Conclusion:BMMSCs combine with normothermic machine perfusion can better repair SD rats DCD steatotic donor liver and its mechanism of action may be related to its regulation on liver ferroptosis.