Identification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice.

(-)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3 µM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections.

Differences between exhausted CD8+ T cells in hepatocellular carcinoma patients with and without uremia.

The purpose of this study was to explore the differences between exhausted CD8+ T cells in hepatocellular carcinoma (HCC) patients with and without uremia. We enrolled 45 uremic patients who were recently diagnosed with HCC into the HCC + uremia cohort and similar patients with HCC but without uremia into the HCC-only cohort. Lymphocytes were obtained from the two cohorts, and exhausted CD8+ T cells, comprising PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ T cells, were sorted and expanded in vitro. After expansion, the proportions of PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ T cells were significantly higher in the HCC-only cohort than in the HCC + uremia cohort. CD8+ T cells expressing PD-1, TIM-3, or LAG-3 showed increased tumor reactivity and release of interferon-γ in vitro; however, these cells demonstrated weaker anti-tumor activity in HCC + uremia patients than in HCC-only patients. Among the expanded lymphocytes, only the decreased proportion of PD-1+CD8+ T cells significantly correlated with the HCC + uremia cohort (odds ratio of 2.731, p = 0.009). We concluded that peripheral CD8+ T cells expressing PD-1, TIM-3, or LAG-3 from the HCC + uremia cohort were dysfunctional in vitro. Among these populations, PD-1+CD8+ T cells were most evident in HCC patients with uremia.

Association of trimethylamine N-Oxide with cardiovascular and all-cause mortality in hemodialysis patients.

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

Elevated serum soluble interleukin-2 receptor levels increase malignancy-related risk in patients on chronic hemodialysis.

BACKGROUND: Patients on chronic hemodialysis (HD) have an increased incidence of malignancy due to decreased immunity. Soluble interleukin-2 receptor (sIL-2R), as an immunomodulator, seemed to have an effect in the process of malignancy. In this study, we aimed to evaluate the clinical significance of increased sIL-2R in the course of malignancy among HD patients. METHODS: Patients who undergoing chronic hemodialysis were followed for 24 months. Risk factors for malignancy events and malignancy-related mortality during the 2-year follow-up period were investigated among various clinicopathological variables. RESULTS: Of the 363 patients included in this research, 47 patients (12.95%) had a prior history of treated malignancy. During the 2-year follow-up period, malignancy events were detected in 15 (4.12%) patients. Sixty-seven patients died during the study period, of which nine patients (13.43%) were died of malignancy. Malignancy events reduced 2-year mortality significantly (log-rank = 23.02, P < 0.0001). Both high sIL-2R levels ( ≥ 2-fold upper limit of the normal value) (OR 6.6, P = 0.006) and a prior history of treated malignancy (OR 4.12, P = 0.018)were identified by multivariate logistic analysis as independent determinants for malignancy events. However, only the levels of sIL-2R (used as a continuous variable) had the significantly predictive effect on malignancy events and malignancy-related mortality in the following 2 years. CONCLUSIONS: Elevated sIL-2R levels was commonly seen in serum of HD patients. And this elevated level increased the risk of malignancy. Aside from its role as a biomarker, sIL-2R may also exert biological effects in the course of malignancy.

Association of indoxyl sulfate with heart failure among patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up. RESULTS: In total, 258 patients (145 men) with a mean age of 57.0 ± 14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤ 2.35 µg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 µg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5-48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan-Meier analysis revealed the incidence of first heart failure event in the high-indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001). CONCLUSIONS: Plasma indoxyl sulfate was associated with first heart failure event in patients on hemodialysis. Whether indoxyl sulfate is only a biomarker or involved in the pathogenesis of heart failure in hemodialysis warrants additional study.

Inappropriately elevated endothelin-1 plays a role in the pathogenesis of intradialytic hypertension.

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty-four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10 mmHg during or immediately after a hemodialysis session), while 17 age-matched and sex-matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N-terminal fragment brain natriuretic peptide, renin, angiotensin-II, aldosterone (ALD), angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post-dialysis serum ET-1 concentrations were significantly higher (4.09 ± 2.06 vs. 2.75 ± 1.34 pg/mL, P < 0.05), while the post-dialysis ratio of NO to ET-1 was lower (17.79 ± 5.65 vs. 24.78 ± 12.04, P < 0.05) in IDH patients compared with the control group. Post-dialysis ALD and NOR values were significantly lower (P < 0.01) and ACE levels were significantly higher (P < 0.01) than the pre-dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre-dialysis and post-dialysis determinations. Compared with blood angiotensin-II, ALD, ACE, NOR, adrenomedullin, N-terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET-1 plasma concentrations may play a predominant role in the pathogenesis of IDH.

ELISA examining urinary angiotensinogen as a potential indicator of intrarenal renin-angiotensin system (RAS) activity: a clinical study of 128 chronic kidney disease patients.

In the current study, we measured urinary angiotensinogen (AGT) through enzyme-linked immunoadsordent assay (ELISA) and analyzed its correlation with intrarenal renin-angiotensin system (RAS) activity in 128 chronic kidney disease (CKD) patients. Urinary and plasma renin activity, AGT, angiotensin II (Ang II) and aldosterone levels were also measured by radioimmunoassay (RIA) or ELISA in these participants. Further, the expression level of intrarenal renin, AGT, Ang II and Ang II receptors were examined by immunohistochemistry staining (IHCS) in 72 CKD patients. Their correlations with urinary AGT were also analyzed. We found that the urinary AGT level was positively correlated with hypertension (ρ = 0.28, P < 0.01), urinary protein (r = 0.38, P < 0.01), urinary Ang II (r = 0.29, P < 0.05), urinary type IV collagen (Col IV) (r = 0.56, P < 0.01), and was negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.28, P < 0.01), urinary sodium (r = -0.22, P < 0.05) and serum AGT (r = -0.27, P < 0.01). Multiple regression analysis indicated low serum AGT (P < 0.01), high urinary protein (P < 0.01), high urinary Ang II (P < 0.05) and high urinary Col IV (P < 0.01) were correlated significantly with high urinary AGT. Urinary AGT level was positively correlated with intrarenal expression level of AGT (ρ = 0.46, P < 0.01), Ang II (ρ = 0.56, P < 0.01) and Ang II type 1 receptor (ρ = 0.32, P < 0.01), as detected by IHCS. Together, these data suggest that urinary AGT might be a potential biomarker of intrarenal RAS and Ang II activities in CKD patients.

Association of residual renal function at initiation of dialysis with prognosis in maintenance dialysis patients / 中华肾脏病杂志

Objective To examine the association between residual renal function at initiation of dialysis and prognosis in maintenance dialysis patients.Methods Incident patients with end-stage renal diseases initiating dialysis between 1 January 2005 and 30 September 2009,followed up to 31 March 2010 were enrolled in this study.Residual renal function was evaluated using eGFR estimated by the abbreviated MDRD equation.Patients were classified into four groups according to eGFR of ≥10.5,8 to ＜10.5,6 to ＜8,＜6 ml·min-1·(1.73 m2)-1.The outcome was all-cause and cardiocerebral vascular mortality.Results (1) A total of 562 patients were included.The median eGFR at initiation of dialysis was 5.60 (2.26-12.62) ml·min-1·(1.73 m2)-1.The median follow-up time was 17 (0-58) months from initiation of dialysis and 141 patients died within this period.The median survival time was 45.48 (43.05-47.90) months.With eGFR declined,Scr,BUN,serum uric acid,serum prealbumin,phosphorus,calcium and phosphate product,iPTH,mean arterial pressure (MAP) at initiation of dialysis increased (P＜0.05),and hemoglobin,proportion of male,proportion of diabetes comorbidity,proportion of the Charlson comorbidity index ≥5 decreased (P＜0.05).Though there was no significant difference among the four groups,the proportion of left ventricular hypertrophy comorbidity increased when eGFR declined.(2) There was no significant difference of all-cause mortality among four groups using Kaplan-Meire survival curve.Cox regression model indicated no significant difference of all-cause mortality in levels of eGFR (HR=1.012,95％CI 0.961-1.065,P=0.654).Without patients died in the first 3 months,the multivariate Cox regression model indicated eGFR at initiation of dialysis was the protective factor to 1 year survival (HR=0.791,95％CI 0.669-0.935,P＜0.01).(3) The multivariate Cox regression model indicated the risk of overall and 1 year cardiocerebral vascular death decreased with eGFR at initiation of dialysis increased (HR=0.868,95％CI 0.777-0.971,P＜0.05; HR=0.937,95％CI 0.851-0.992,P＜0.05,respectively).(4) The multivariate Cox regression model indicated eGFR at initiation of dialysis was benefit to survival of patients treated by peritoneal dialysis,with all-cause death risk decreased by 10％ when eGFR increased by 1 ml·min-1·(1.73 m2)-1 (HR=0.90,95％CI 0.81-0.99,P＜0.05).In hemodialysis patients,Kaplan-Meire survival curve was significantly different among the four groups (Log-rank test,P=0.047); the survival of the group of 8 to ＜10.5 ml·min-1·(1.73 m2)-1 was lower as compared to the groups of 6 to ＜8 (Log-rank test,P=0.033) and ＜6 ml·min-1(1.73 m2)-1 (Log-rank test,P=0.005); but the multivariate Cox regression model indicated no relationship between survival and eGFR.In the subgroup of chronic glomerulonephritis as primary renal disease,the eGFR at initiation of dialysis was the benefit factor,with all-cause death risk decreased by 16.6％ (HR=0.834,95％CI 0.736-0.946,P＜0.01) and cardiocerebral vascular death risk decreased by 18.2％ (HR=0.818,95％CI 0.669-0.999,P＜0.05) when eGFR increased by 1 ml ·min-1 ·(1.73 m2)-1.In the subgroup of chronic glomerulonephritis treated by peritoneal dialysis,the all-cause death risk decreased by 32.1％ with eGFR increased by 1 ml·min 1·(1.73 m2)-1 (HR=0.679,95％CI 0.535-0.862,P＜0.01).Conclusions Early initiation of dialysis may not be associated with improved overall survival,but may reduce cardiocerebral vascular and 1 year all-cause mortality,improve the survival of chronic glomerulonephritis patients and peritoneal dialysis patients.

NT-proBNP as a predictor of intradialytic-hypotension among maintaining hemodialysis patients / 中华肾脏病杂志

Objective To assess the risk factors of intradialytic-hypotension (IDH) among maintaining hemodialysis (MHD) patients and to explore the relation between NT-proBNP and IDH,thus to provide clinical evidence for the prevention and treatment of IDH.Methods A total of 202 MHD patients during March 2009 to May 2009 in our dialysis center were enrolled in the study.Intradialytic blood pressure (BP) was measured during a 3-month period.IDH was defined as an event characterized by a sudden drop in systolic BP more than 20 mm Hg or in mean artery pressure (MAP) more than l0 mm Hg.Logistic regression analysis was used to assess the risk factors of IDH.ROC curve was used to evaluate the diagnostic efficacy of serum NT-proBNP.Results The incidence of IDH was 42.1％.One hundred and seventeen patients with no-IDH (＜1/10 hypotensive events per 3 months) were served as controls.Fifty-five patients with o-IDH (≥ 1/ 10 but ≤1/3 hypotensive events per 3 months) and 30 patients with f-IDH (＞1/3 hypotensive events per 3 months) were identified among 202 patients.Multivariate regression analysis showed that age,gender,ultrafiltration rate,serum NT-proBNP,serum albumin,aortic root dimension (AoRD) were associated with IDH among MHD patients.Serum NT-proBNP was positively correlated with IDH.The area under the ROC curve (AUC) of NT-proBNP was 0.76 (95％ CI 0.69 to 0.83,P＜0.01).The cut-off value of serum NT-proBNP for IDH was 1746.5 ng/L,with a sensitivity of 88.61％ and a specificity of 51.10％.Furthermore,the AUC of NT-proBNP for f-IDH was 0.65 (95％ CI 0.53 to 0.763,P＜0.01).The cut-off value of serum NT-proBNP for f-IDH was 8208.0 ng/L,with a sensitivity of 33.33％ and a specificity of 91.30％.Conclusions Elderly,female,high ultrafiltration rate,high level of serum NT-proBNP,hypoalbuminemia,shorter AoRD are independent risk factors of IDH among MHD patients.Serum NT-proBNP can be used as a predictor of IDH.

Investigation of death events caused by infection in end-stage renal disease patients undergoing hemodialysis / 中华肾脏病杂志

Objective To explore the clinical characteristics and prevention management of death events caused by infections in end-stage renal disease (ESRD)patients undergoing hemodialysis. Methods Clinical data of ESRD patients undergoing hemodialysis in Nephrology Department of Zhongshan Hospital from 1998 to 2008 were retrospectively studied.Death causes,primary diseases,complications,infections,and survival time were analyzed. Results A total of 252 patients died including 162 males(64.29%)and 90 females(35.71%).Average death age was (63.48±14.77)years.In death events,emergency dialysis accounted for 59.52%,and primary glomerular disease was the major primary diseases(27.23%),then diabetic nephropathy(16.90%)and hypertensive nephrosclerosis (14.55%).34.8%death was caused by infections or promoted by infections,secondly by cerebrovascular events(23.6%).The elderly accounted for the majority of infection-associated deaths.48.15%and 38.71%patients with deaths caused or promoted by infections respectively had shorter dialysis duration(75 years)and hemodialysis duration within 3 months,which may result in shorter survival.Pulmonary infection and gram negative bacillus combined with fungal infection should be considered in the treatment.Prophylaxis of nosocomial infection and pulmonary infection in hemodialysis patients should be more emphasized.

Expression of intrarenal angiotensin Ⅱ is correlated with kidney fibrosis in primary IgA nephropathy patients / 中华肾脏病杂志

Objective To analyze the expression and regulation of components of intrarenal renin-angiotensin system (RAS) and the correlation between intrarenal angiotensin Ⅱ (Ang Ⅱ) expression and clinicopathological injury index in primary IgA nephropathy patients. Methods Expressions of intrarenal RAS components were assessed by immunohistochemistry staining (IHCS). Correlation among intrarenal RAS components and of intrarenal Ang Ⅱ expression with blood pressure, estimated glomerular filtration rate (eGFR), 24-h urinary protein and Katafuchi score in 36 primary IgA nephropathy patients were examined. Results There were positive correlations between positive IHCS area of intrarenal renin and Ang Ⅱ (r=0.43, P＜0.01), angiotensiongen and Ang Ⅱ (r=0.34, P＜0.05). There was negative correlation between positive IHCS area of intrarenal Ang Ⅱ and eGFR (r=-0.61, P＜0.01). There was positive correlation between positive IHCS area of intrarenal Ang Ⅱ and pathological chronicity index (ρ=0.39, P＜0.05), index of interstitial cell infiltration (ρ =0.52, P ＜0.05). Conclusion Expression of intrarenal Ang Ⅱ is positively correlated with expression of intrarenal renin and angiotensinogen, and plays an important role in kidney fibrosis in primary IgA nephropathy.

Correlation between urinary angiotensinogen and intrarenal renin-angiotensin system activity in chronic kidney disease patients / 中华肾脏病杂志

Objective To analyze the correlation of urinary angiotensinogen (AGT) with clinical index of kidney injury and intrarenal renin-angiotensin system (RAS) activity in chronic kidney disease (CKD) patients. Methods Urinary or plasma renin activity, AGT, angiotensin Ⅱ (Ang Ⅱ ), aldosterone were measured by RIA or ELISA in 129 CKD patients. Expression of intrarenal renin, AGT, Ang Ⅱ and angiotensinⅡ receptor was examined by immunohistochemistry staining (IHCS) in 73 CKD patients undergoing renal biopsy. Correlation of urinary AGT with other indexes was performed. Results Average urinary AGT in 129 CKD patients was (159.08 ± 125.18) μg/g Cr, Scr was (113.20± 105.05)μmol/L, and urinary AGT was positively correlated with Scr (r=0.51, P<0.01). Average estimated glomerular filtration rate (eGFR) was (58.52±27.15) ml·min-1·(1.73 m2)-1, which was negatively correlated with urinary AGT (r=-0.55, P<0.01). Average urinary protein was (2.03±2.65) g/24 h, which was positively correlated with urinary AGT (r=0.30, P<0.01). Average urinary Ang Ⅱ was (164.71 ±139.25) ng/g Cr, which was positively correlated with urinary AGT (r=0.20, P<0.05). Average urinary type Ⅳ collagen was (447.60± 800.66) μg/g Cr, which was positively correlated with urinary AGT (r=0.47, P<0.01). Average urinary soduim was (162.17±81.61) mmol/24 h, which was negatively correlated with urinary AGT (r=-0.20, P<0.05). Multiple regression analysis indicated that low eGFR (P<0.01), high Scr (P< 0.01), high urinary protein (P<0.05), high urinary Ang Ⅱ (P<0.05) and high urinary type Ⅲ collagen (P<0.01) were significantly correlated with high urinary AGT. In renal tissues of CKD patients, there was positive correlation of urinary AGT with positive IHCS area of AGT (r=0.45, P< 0.01), Ang Ⅱ (r=0.52, P<0.01) and angiotensin Ⅱ type 1 receptor (r =0.28, P <0.05). Conclusions Urinary AGT level may indicate the kidney injury severity, especially in chronic kidney injury, and may be used as a non-invasive marker of intrarenal Ang Ⅱ activity in CKD patients.

Adjuvant hepatic chemotherapy after resection of solitary hepatocellular carcinoma associated with hepatitis B virus cirrhosis.

BACKGROUND: Although resection is the major treatment for patients with hepatocellular carcinoma (HCC), the high intrahepatic recurrence remains a cardinal cause of death. This study was undertaken to evaluate the effect of hepatic arterial infusion chemotherapy on the survival and recurrence of HCC patients with hepatitis B virus (HBV) cirrhosis after resection. METHODS: Twenty-eight patients who had undergone placement of a hepatic arterial pump at the time of liver wedge resection for HCC from 1998 through 2004 were reviewed retrospectively. These patients aged 23-71 years had HBV cirrhosis (Child-Pugh class A or B). They were given floxuridine (FUDR)(250 mg), doxorubicin (10 mg) and mitomycin C (4 mg) alternatively every 2 or 3 days through arterial pumps for 8 cycles each year in the first two years after resection. Meanwhile, traditional Chinese herbal medicine was prescribed to the patients. When the leukocyte count was as low as 3X10(9)/L or asparate aminotransferase (AST) level was significantly increased, the regimen of chemotherapy was delayed for the normalization of leukocyte count and AST level (below 80 U/L). RESULTS: Of the 28 patients, 23 received 8 or 16 cycles of the set regimen of chemotherapy. These patients are alive with no evidence of recurrence. Among them, 5, 7, and 11 patients are alive beyond 5 years, 3 years, and 1 year respectively. In the remaining 5 patients, 3 who had had a HCC 10 cm or more in diameter showed tumor recurrence within 1 year, in whom, 8 cycles of chemotherapy were not completed because of their low leukocyte count (<3 x 10(9)/L) and poor liver function. One patient who had received 8 cycles of chemotherapy demonstrated recurrence at 16 months after resection. One patient who had received 16 cycles of chemotherapy had intrahepatic recurrence at 58 months after surgery. No recurrence was observed in 17 patients who had received 16 cycles of chemotherapy. CONCLUSION: Adjuvant hepatic arterial chemotherapy may be feasible to improve the survival of patients after resection of solitary HCC associated with HBV cirrhosis.

[Application of sleeve anastomosis in development of cervical heart transplantation in rats].

OBJECTIVE: To simplify surgical technique and increase postoperative survival rate, sleeve anastomosis technique combined cuff technique was used in developing the model of cervical heart transplantation in rats. METHODS: In this model, the hearts from 25 male SD rats were transplanted into the neck of Wistar rats by anastomosing the donor innominate artery to the recipient right common carotid artery by use of sleeve technique, and the donor pulmonary artery to the recipient right external jugular vein by use of cuff technique. After operation, the rats were treated with cyclosporine A (1.5 mg/kg, q.d.), transplanted hearts were followed by daily inspection or palpation and the allograft survival time was more than 3 days as the standard of successful operation. RESULTS: The mean operative time was (48.7 +/- 3.4) min, with a successful rate of 88% (22/25). Complications were anastomotic hemorrhage (1 case) and thrombosis(2 cases). During the follow-up period, 6 rats died of pulmonary infection, abscess in the neck, liver or bladder tumor. The remaining 16 transplanted hearts survived more than 3 months. CONCLUSION: The modified operation have advantages of less operative procedure, shorter operation and ischemia time and easier monitoring of graft function.

Transcatheter arterial chemoembolization and delayed surgery for infant hepatoblastoma / 实用儿科临床杂志

Objective To evaluate the effect of transcatheter arterial chemoembolization (TACE) and delayed surgery for infant hepatoblastoma.Methods TACE was performed with the initial digital subtractive angiography (DSA) under general anesthesia 1-3 times in 8 infants with huge hepatoblastoma, whose age was 2 to 12 months. DSA was done via arterials in hepatoblastoma each time before chemoembolization. The arterials were perfused with chemodrugs and suspensions in ultrasome iodized oil , and were blocked with spring rings. DSA findings indicated that the tumor shrank without new tumorous arterials after 1 month in 6 cases, and 4 of them showed no tumorous staining, and the delayed surgery was performed successfully 1 week later in 6 infants. One boy underwent systemic chemotherapy alone during 6 months after 3 times of TACE. Results TACE therapy did not encounter any major technical problem or toxic reaction caused by chemotherapy. The following DSA test 4 weeks later did not detect any new tumorous vessels in 6 cases. Six children received TACE and surgery had been followed-up with no tumor recurrence for months averagely. The boy underwent TACE and venous chemotherapy for 6 months , without surgery , had been followed-up for 48 months until the present report. CT, AFP and DSA did not show any hints of tumor recurrence. Six cases receiving 3 times TACE combined with surgery survived without tumor recurrence. Conclusions TACE is a very effective, safe and helpful therapy for hepatoblastoma, which stressed the repeated use of spring ring to block tumor vessels lastingly if necessary. If surgery is required, DSA test is needed beforehand to detect new tumorous vessels or neoplasm. If there is any , TACE is repeated. TACE combined with surgery may provide an additional promising choice in the treatment of hepatoblastoma, and repeated TACE alone may cure hepatoblastoma in infants.