[Clinical application of split liver transplantation: a single center report of 203 cases].

Objective: To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application. Methods: This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group (χ2=5.560,P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group (χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion: SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

[Clinical application of the simultaneous detection of methotrexate and 7-hydroxymethotrexate in the delayed elimination for pediatric acute lymphoblastic leukemia].

Objective: To discuss the application value of the simultaneous determination of methotrexate (MTX) and 7-hydroxymethotrexate (7-OHMTX) in the delayed elimination of MTX for pediatric acute lymphoblastic leukemia (ALL). Methods: Cross sectional study. A total of 97 children who received 192 high-dose MTX treatments cycles in Lu Daopei Hospital from April to August 2019 were enrolled. The peripheral blood was collected at 0,24,48 h after the end of MTX infusion and analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). One hundred and ninety-two MTX treatments were divided into a normal MTX elimination group (n=149) and delayed elimination group (n=43) according to the standard of delayed elimination and divided into 0-9 year old group (n=95), 10-14 group (n=50), 15-18 group (n=47) according to age. The comparisons of the C(MTX), C(7-OHMTX) between normal and delayed group was conducted as well as among different age groups. Receiver operator characteristic curve (ROC) of C(MTX-0h) and C(7-OHMTX-0h) was analyzed and the concentration corresponding to the maximum of the Youden index on the ROC was set as the warning value for delayed elimination. Correlation between the delayed elimination after the end of MTX infusion and toxicity was investigated and the percentage of delayed elimination was also analyzed. Results: The concentrations of MTX and 7-OHMTX were significantly higher in the delayed elimination group than the normal group. Immediately after infusion (0 h), a C(7-OHMTX-0h) of >17.8 µmol/L (sensitivity 97.7%, specificity 54.4%) and a C(MTX-0h) of >148.8 µmol/L (sensitivity 72.1%, specificity 84.6%) were found to be warning predictors of delayed elimination under the MTX treatment protocol. MTX delayed elimination was positively correlated with methotrexate-induced toxicities (r=0.58, P<0.01). The percentage of hepatotoxicity and nephrotoxicity was 32.6% and 37.2% in the delayed elimination group, which was significantly higher than normal group of 12.8% and 3.4% (P<0.05). No significant difference was found in other toxicities. There was significant difference in C(MTX) among different age groups but no significant difference in C(7-OHMTX). Conclusion: Simultaneously determination of MTX and 7-OHMTX in plasma by HPLC-MS/MS in childhood ALL patients can provide a reference for clinical individualized medicine and pharmacokinetic research.

[Prevalence and risk factors of hypertension among residents of 30 years or above years old in Pengzhou city of Sichuan province].

OBJECTIVE: To investigate the prevalence and risk factors of hypertension among residents in Pengzhou city of Sichuan province. METHODS: Among 20 townships in Pengzhou city of Sichuan Province, 14 townships were selected using a clustered sampling based on the economic level and distance. The registered residents in the selected townships aged 30-79 years were recruited for a comprehensive survey from 2004 to 2007. A total of 55 687 residents (21 315 males and 34 372 females) were selected based on a face to face questionnaire interview and physical examination; the patient group included 14 151 residents with hypertension and the control group had 41 536 residents without hypertension were selected. Multivariate logistic regression model was used to investigate the influence factors for hypertension. OR (95%CI) values were calculated. Different levels of risk exposure factors were transformed into the risk scores using a statistical model. RESULTS: The prevalence rate of hypertension was 25.41% among residents aged 30 years or above in Pengzhou (14 151/55 687), 28.95% (6 170/21 315) for male residents and 23.22% (7 981/34 372) for female residents. Multivaraite logistic regression analysis showed that main risk factors for hypertension in male residents were age, low educational level, widower, low household income, no medical insurance, no fresh fruits intake, high body mass index (BMI), high waist to hip ratio, and low physical activity, which was less than 3 metabolic equivalent of task (MET) level, among which the highest three riskswere (not including the social demographic characteristics) BMI≥28 kg/m(2), waist to hip ratio ≥0.90, and not consuming fresh fruits. OR (95% CI) values for these three key factors were 3.74 (3.27-4.28), 1.34 (1.24-1.44), and 1.27 (1.14-1.41), respectively. The corresponding risk scores for these factors were 2.993, 1.102, and 1.237, respectively. Main risk factors for hypertension in female residents were age, working hours, no medical insurance, fewer number of family members, no fresh fruits intake, smoking, never drinking tea, no dairy products intake, high BMI, highwaist to hip ratio and low physical activity, among which the highest three risks were (not including the social demographic characteristics) BMI ≥28 kg/m(2), MET level, and waist to hip ratio ≥0.85. OR (95% CI) values for these three key factors were 3.30 (3.02-3.60), 1.35 (1.22-1.51), and 1.33 (1.23-1.44), respectively. The corresponding risk scores for these factors were 2.390, 1.263, and 1.051, respectively. CONCLUSION: The prevalence rate of hypertension among the residents over 30 years of age in Pengzhou city was 25.41%. The main risk factors were age, not consuming fresh fruits, high BMI, high waist to hip ratio, and low MET level.

[Prevalence of diabetes and related factors in Pengzhou city, Sichuan province].

OBJECTIVE: To study the prevalence, treatment and related risk factors of diabetes in Pengzhou city, so as to provide reference for the three-tier related prevention programs. METHODS: Baseline survey of population of Sichuan province from the China Kadoorie Biobank, was used to analyze the prevalence and treatment of diabetes in Pengzhou city. Logistic regression model was used to analyze the influencing factors on diabetes. RESULTS: The prevalence rate of diabetes was 3.7% in the 30-79 year-old groups in Pengzhou with the awareness rate, treatment rate and control rate as 45.2%, 36.6% and 17.6%, respectively. The prevalence rate, awareness rate and control rate appeared in the older age groups, high education level group, high income group and non-farming population group, were higher than that seen in the other groups. Factors as older age (OR=5.50, 95%CI: 4.77-6.34), low education (OR=0.43, 95%CI: 0.38-0.49), family with low income (OR=0.86, 95%CI: 0.82-0.90), family history of diabetes (OR=3.15, 95%CI: 2.72-3.65), hypertension (OR=2.94, 95%CI: 2.70-3.21), smoking (OR=2.11, 95% CI: 1.84-2.42), low fruit intake (OR=3.62, 95% CI: 3.23-4.07), sedentary leisure time (OR=1.28, 95% CI: 1.16-1.41), physical activities (OR=2.11, 95% CI: 1.89-2.35), overweight or obesity (OR=2.33, 95% CI: 2.04-2.65), etc. were the risk factors of diabetes. CONCLUSIONS: Rates related to the awareness, treatment and control of diabetes in Pengzhou city were low. Programs on health education should be strengthened in all the population with contents focusing on healthy lifestyle. Special attention should be paid on the treatment and control of diabetes in the elderly population. Patients with diabetes should follow the standardized management programs.

Dexamethasone stimulates proteasome- and calcium-dependent proteolysis in cultured L6 myotubes.

The effect of dexamethasone on protein degradation and the involvement of different proteolytic pathways were examined in cultured L6 myotubes. Treatment of the cells with dexamethasone resulted in an approximately 20% increase in protein degradation at a hormone concentration of 10(-7) to 10(-6) M. By using various proteolytic blockers, evidence was found that the dexamethasone-induced increase in protein breakdown mainly reflected energy-proteasome-dependent proteolysis and to a lesser extent calcium-dependent protein breakdown. In contrast, the hormone treatment did not increase lysosomal proteolysis. mRNA levels for cathepsin B, ubiquitin, and the proteasome subunit C3 were increased by dexamethasone. The results suggest that glucocorticoids stimulate calcium and energy-proteasome-dependent muscle proteolysis and that changes in mRNA levels for proteolytic enzymes do not necessarily reflect the involvement of different proteolytic pathways.

The transcription factor activator protein-1 is activated and interleukin-6 production is increased in interleukin-1beta-stimulated human enterocytes.

The intestinal mucosa is an active participant in the inflammatory and metabolic response to sepsis, endotoxemia, and other critical illness. The genes for various cytokines, e.g., interleukin 6 (IL-6), are regulated by multiple transcription factors, including nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1). In recent studies, treatment with IL-1beta of cultured Caco-2 cells, a human intestinal epithelial cell line, resulted in increased NF-kappaB DNA binding. The effect of IL-1beta on AP-1 activity in the enterocyte and the potential role of AP-1 in enterocyte IL-6 production are not known. We treated Caco-2 cells with IL-1beta and determined AP-1 activity by electrophoretic mobility shift assay (EMSA) and IL-6 production by enzyme-linked immunosorbent assay (ELISA). Treatment of Caco-2 cells with IL-1beta resulted in a dose- and time-dependent increase in AP-1 DNA binding. Supershift analysis suggests that activated AP-1 contained c-Jun, JunD, c-Fos, FosB, and Fra1 subunits. When Caco-2 cells were transiently transfected with an AP-1 luciferase reporter plasmid, stimulation with IL-1beta resulted in increased luciferase activity, suggesting that AP-1 DNA binding increased gene activation. Additional luciferase assays were performed with a plasmid containing a wild-type or AP-1-mutated IL-6 promoter. Stimulation of these cells with IL-1beta gave rise to results supporting the role of AP-1 in the regulation of IL-6 production. Geldanamycin, which has been shown in studies to inhibit AP-1 activation, blocked IL-1beta-induced AP-1 luciferase gene activation and IL-6 production. These results suggest that the AP-1 family of transcription factors is activated by IL-1beta in human enterocytes and that AP-1 may at least in part regulate IL-6 production in these cells.

Hyperthermia stimulates energy-proteasome-dependent protein degradation in cultured myotubes.

Previous studies suggest that elevated temperature stimulates protein degradation in skeletal muscle, but the intracellular mechanisms are not fully understood. We tested the role of different proteolytic pathways in temperature-dependent degradation of long- and short-lived proteins in cultured L6 myotubes. When cells were cultured at different temperatures from 37 to 43 degrees C, the degradation of both classes of proteins increased, with a maximal effect noted at 41 degrees C. The effect of high temperature was more pronounced on long-lived than on short-lived protein degradation. By using blockers of individual proteolytic pathways, we found evidence that the increased degradation of both long-lived and short-lived proteins at high temperature was independent of lysosomal and calcium-mediated mechanisms but reflected energy-proteasome-dependent degradation. mRNA levels for enzymes and other components of different proteolytic pathways were not influenced by high temperature. The results suggest that hyperthermia stimulates the degradation of muscle proteins and that this effect of temperature is regulated by similar mechanisms for short- and long-lived proteins. Elevated temperature may contribute to the catabolic response in skeletal muscle typically seen in sepsis and severe infection.