BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Objective To observe neuroprotective effects of Ca2+/calmodulin-dependent kinase Ⅱ(CaMKⅡ)γ and CaMkⅡ δ against acute neuronal ischemic reperfusion injury in mice and explore the underlying mechanism.Methods Primary cultures of brain neurons isolated from fetal mice(gestational age of 18 days)were transfected with two specific siRNAs(si-CAMK2G and si-CAMK2D)or a control sequence(si-NT).After the transfection,the cells were exposed to oxygen-glucose deprivation/reperfusion(OGD/R)conditions for 1 h followed by routine culture.The expressions of phosphatidylinositol-3-kinase/extracellular signal-regulated kinase(PI3K/Akt/Erk)signaling pathway components in the neurons were detected using immunoblotting.The expressions of the PI3K/Akt/Erk signaling pathway proteins were also detected in the brain tissues of mice receiving middle cerebral artery occlusion(MCAO)or sham operation.Results The neuronal cells transfected with si-CAMK2G showed significantly lower survival rates than those with si-NT transfection at 12,24,48,and 72 h after OGD/R(P<0.01),and si-CAMK2G transfection inhibited OGD/R-induced upregulation of CaMKⅡγ expression.Compared to si-NT,transfection with si-CAMK2G and si-CAMK2D both significantly inhibited the expressions of PI3K/Akt/Erk signaling pathway components(P<0.01).In the mouse models of MCAO,the expressions of CaMKⅡδ and CaMKⅡγ were significantly increased in the brain,where activation of the PI3K/Akt/Erk signaling pathway was detected.The expression levels of CaMKⅡδ,CaMKⅡγ,Erk,phosphorylated Erk,Akt,and phosphorylated Akt were all significantly higher in MCAO mice than in the sham-operated mice at 24,48,72,and 96 h after reperfusion(P<0.05).Conclusion The neuroprotective effects of CaMKⅡδ and CaMKⅡγ against acute neuronal ischemic reperfusion injury are mediated probably by the PI3K/Akt/Erk pathway.

Objective To observe neuroprotective effects of Ca2+/calmodulin-dependent kinase Ⅱ(CaMKⅡ)γ and CaMkⅡ δ against acute neuronal ischemic reperfusion injury in mice and explore the underlying mechanism.Methods Primary cultures of brain neurons isolated from fetal mice(gestational age of 18 days)were transfected with two specific siRNAs(si-CAMK2G and si-CAMK2D)or a control sequence(si-NT).After the transfection,the cells were exposed to oxygen-glucose deprivation/reperfusion(OGD/R)conditions for 1 h followed by routine culture.The expressions of phosphatidylinositol-3-kinase/extracellular signal-regulated kinase(PI3K/Akt/Erk)signaling pathway components in the neurons were detected using immunoblotting.The expressions of the PI3K/Akt/Erk signaling pathway proteins were also detected in the brain tissues of mice receiving middle cerebral artery occlusion(MCAO)or sham operation.Results The neuronal cells transfected with si-CAMK2G showed significantly lower survival rates than those with si-NT transfection at 12,24,48,and 72 h after OGD/R(P<0.01),and si-CAMK2G transfection inhibited OGD/R-induced upregulation of CaMKⅡγ expression.Compared to si-NT,transfection with si-CAMK2G and si-CAMK2D both significantly inhibited the expressions of PI3K/Akt/Erk signaling pathway components(P<0.01).In the mouse models of MCAO,the expressions of CaMKⅡδ and CaMKⅡγ were significantly increased in the brain,where activation of the PI3K/Akt/Erk signaling pathway was detected.The expression levels of CaMKⅡδ,CaMKⅡγ,Erk,phosphorylated Erk,Akt,and phosphorylated Akt were all significantly higher in MCAO mice than in the sham-operated mice at 24,48,72,and 96 h after reperfusion(P<0.05).Conclusion The neuroprotective effects of CaMKⅡδ and CaMKⅡγ against acute neuronal ischemic reperfusion injury are mediated probably by the PI3K/Akt/Erk pathway.

Objective To explore the determinants of serum uric acid (UA) levels and the relationship between UA and cardiovascular disease in elderly patients.Methods A cross-sectional design was used.A total of 1 066 elderly patients were consecutively recruited in the study.Anthropometric measurement and lifestyle survey were performed,and serum UA,lipid profile,glucose,homocysteine (Hcy) and superoxide dismutase (SOD) were measured.The determinants of serum UA levels and correlation between UA and cardiovascular disease were analyzed by regression.Results The prevalence of hyperuricemia was 21.9％ (25.9％ in men and 18.7％ in women).Partial correlation analysis showed the level of serum UA was positively correlated with Hcy (r=0.163,P=0.000),body mass index (r=0.128,P=0.004) and triglyceride (r=0.133,P=0.003),and negatively correlated with HDL-C (r=-0.103,P=0.021).After adjustment for potential confounding factors,multivariate analysis showed eGFR (β =-2.044,t =-10.544,P =0.000),gender (β =42.065,t=4.700,P=0.000),Hcy (β=1.367,t=3.714,P=0.000),BMI (β=3.370,t=2.706,P=0.007),TG (β=14.120,t=2.589,P=0.010) and SOD (β=-0.636,t=-3.079,P=0.002) were independent determinants for UA levels in elderly patients.Logistic regression analysis indicated that mild elevation of UA levels was a risk factor of hypertension (OR=1.925,95％ CI=1.124-3.295) in women and OR=1.780 (95％ CI=1.010-3.136) in men].High UA levels increased the risk of coronary heart disease in women [OR=1.710 (95％ CI=1.157-2.526)],but decreased the risk of ischemic stroke in men [OR=0.524 (95％ CI=0.335-0.820)].Conclusions In elderly patients,serum UA levels were affected by renal function,gender,BMI and serum Hcy,TG and SOD.Mildly elevated UA levels increased the risk of hypertension.High UA levels increased the risk of coronary heart disease in women and decreased the risk of ischemic stroke in men.

Clinical studies had demonstrated that early diagnosis of lesion could significantly reduce the risk of cancer. Magneto-acoustic-electrical tomography (MAET) is expected to become a new detection method due to its advantages of high resolution and high contrast. Based on thinking of modular design, a low-cost, digital magneto-acoustic conductivity detection system was designed and implemented in this study. The theory of MAET using chirp continuous wave excitation was introduced. The results of homogeneous phantom experiment with 0.5% NaCl clearly showed that the conductivity curve of homogeneous phantom was highly consistent with the actual physical size, which indicated that the chirp excitation theory in our proposed system was correct and feasible. Besides, the resolution obtained by 1 000 μs sweep time was better than that obtained by 500 μs and 1 500 μs, which means that sweep time is an important factor affecting the detection resolution of the conductivity. The same result was obtained in the experiments carried out on homogeneous phantoms with different concentrations of NaCl, which demonstrated the repeatability of our proposed MAET system.

Objective To evaluate the value of acoustic radiation force impulse (ARFI) elastography in assessment of nonalcoholic fatty liver disease (NAFLD) and hepatic fibrosis in rats.Methods Models with various degrees of NAFLD severity were conducted in 110 rats by feeding high fat emulsion.The right liver lobe of rat models were processed and embedded in a fabricated gelatin solution to measure the shear wave velocity (SWV) by ARFI.And the other liver lobes were used for histologic assessment.Based on NAFLD activity score (NAS),the final pathologic NAFLD diagnosis were considered as normal group (NAS=0),simple steatosis (SS) group (1≤NAS≤2),borderline (3≤NAS≤4) group and nonalcoholic steatohepatitis (NASH) group (NAS≥5).The diagnostic accuracy of the SWV parameters in evaluating NAFLD severity and fibrosis stages was studied using ROC curves.Results The difference of SWV values among normal group,SS group,borderline group and NASH group was statistically significant (F=31.53,P＜0.001).Taking SWV≥ 2.54 m/s as the diagnostic standard to differentiate normal rats from rats with SS,and SWV≥2.90 m/s to differentiate SS from NASH in rats,the area under ROC curve (AUC) was 0.922 (95％CI [0.871,0.973],P＜0.001) and 0.882 (95％ CI [0.807,0.956],P＜0.001) respectively.The sensitivity and specificity were 93.5 ％ and 100 ％ for differentiating normal and SS groups,83.3 ％ and 84.2 ％ for differentiating SS and NASH groups.Taking SWV≥3.48 m/s as cutoff to predict fibrosis (≥F2 stage),the AUC was 0.963 (95％CI [0.909,1.000],P＜0.001),the sensitivity was 92.9％ and the specificity was 97.6％.Taking SWV≥3.61 m/s as cutoff to predict severe fibrosis (≥F3 stage),the AUC was 0.997 (95％CI [0.990,1.000],P＜0.001),sensitivity was 100％ and specificity was 98.9％.The same high validity was maintained as in the prediction of cirrhosis (F4 stage) with the cutoff as SWV≥4.50 m/s,and the AUC was 0.993 (95％CI [0.982,1.000],P＜0.001),the sensitivity was 100 ％ and the specificity was 96.8％.Conclusion ARFI elastography is a promising method for differentiating the different severity of NAFLD and staging the degree of hepatic fibrosis with NAFLD in rat models.

reference index of lymph node in central region.

OBJECTIVETo compare the outcomes of hand-assisted laparoscopic liver surgery (HALS) and pure laparoscopic liver surgery (PLS).

METHODSThe clinical data were analyzed for 64 patients undergoing major hepatectomy with HALH (23 cases) and PLS (41 cases) between January, 2010 and December, 2012.

RESULTSThe general data of the two groups were comparable. Compared with PLS, HALS was associated with a significantly shorter operative time (240 vs 191 min), less intraoperative blood loss (430 vs 220 ml, P<0.05), and a lower cost (P<0.05). There was no significant difference between the two groups in postoperative hospital stay, complication rates or recurrence rate of hepatocellular carcinoma.

CONCLUSIONHALS is safe for major liver resection with such advantages over PLS as causing less trauma and a lower cost.

Blood Loss, Surgical ; Carcinoma, Hepatocellular ; surgery ; Hepatectomy ; methods ; Humans ; Laparoscopy ; methods ; Length of Stay ; Liver Neoplasms ; surgery ; Neoplasm Recurrence, Local

Objective To compare the outcomes of hand-assisted laparoscopic liver surgery (HALS) and pure laparoscopic liver surgery (PLS). Methods The clinical data were analyzed for 64 patients undergoing major hepatectomy with HALH (23 cases) and PLS (41 cases) between January, 2010 and December, 2012. Results The general data of the two groups were comparable. Compared with PLS, HALS was associated with a significantly shorter operative time (240 vs 191 min), less intraoperative blood loss (430 vs 220 ml, P<0.05), and a lower cost (P<0.05). There was no significant difference between the two groups in postoperative hospital stay, complication rates or recurrence rate of hepatocellular carcinoma. Conclusions HALS is safe for major liver resection with such advantages over PLS as causing less trauma and a lower cost.