Enzyme-mediated green synthesis of glycosaminoglycans and catalytic process intensification.

Glycosaminoglycans (GAGs) are a family of structurally complex heteropolysaccharides that play pivotal roles in biological functions, including the regulation of cell proliferation, enzyme inhibition, and activation of growth factor receptors. Therefore, the synthesis of GAGs is a hot research topic in drug development. The enzymatic synthesis of GAGs has received widespread attention due to their eco-friendly nature, high regioselectivity, and stereoselectivity. The enhancement of the enzymatic synthesis process is the key to its industrial applications. In this review, we overviewed the construction of more efficient in vitro biomimetic synthesis systems of glycosaminoglycans and presented the different strategies to improve enzyme catalysis, including the combination of chemical and enzymatic methods, solid-phase synthesis, and protein engineering to solve the problems of enzyme stability, separation and purification of the product, preparation of structurally defined sugar chains, etc., and discussed the challenges and opportunities in large-scale green synthesis of GAGs.

Adjuvant chemotherapy combined with immunotherapy in patients with cholangiocarcinoma after radical resection.

BACKGROUND: The malignancy of cholangiocarcinoma is highly pronounced, and it exhibits a propensity for recurrence and metastasis even in the presence of standard chemotherapy. The efficacy of adjuvant chemotherapy combined with immunotherapy in patients with resected cholangiocarcinoma needs to be substantiated. METHODS: Data from 101 patients with cholangiocarcinoma treated at the Sun Yat-sen University Cancer Center between 2015 and 2020 were studied. RESULTS: After propensity score matching, there were no significant differences in baseline characteristics between patients in the combined adjuvant chemotherapy and immunotherapy group (AC + IM group) and the adjuvant chemotherapy alone group (AC group) (all p > 0.05). The AC + IM group demonstrated a statistically significant improvement in relapse-free survival (RFS) compared to the AC group (p = 0.032). Likewise, the AC + IM group exhibited a significantly superior overall survival (OS) outcome when compared to the AC group (p = 0.044). Multivariate Cox analysis unveiled perineural invasion (p = 0.041), lymph node metastasis (p = 0.006), and postoperative immunotherapy (p = 0.008) as independent prognostic factors exerting a significant impact on the OS of patients. In the cohort of patients with perineural invasion, the AC + IM group exhibited significantly improved OS compared to the AC group (p = 0.0077). Similarly, within the subset of patients with lymph node metastasis, the AC + IM group exhibited a significantly superior OS outcome when compared to the AC group (p = 0.023). CONCLUSION: Combining postoperative adjuvant chemotherapy with immunotherapy extends the RFS and OS of patients with cholangiocarcinoma following radical resection.

IL20RB signaling enhances stemness and chemotherapy resistance in pancreatic cancer.

OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness. MATERIALS AND METHODS: Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored. RESULTS: IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects. CONCLUSION: Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.

Adjuvant chemotherapy in pancreatic cancer at different AJCC stages: a propensity score matching analysis.

OBJECTIVE: In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. MATERIALS AND METHODS: Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. RESULTS: 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). CONCLUSIONS: The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.

Association of placental PPARα/γ and miR-27b expression with macrosomia in healthy pregnancy.

BACKGROUND: Peroxisomal proliferator-activated receptors (PPARs) and microRNAs (miRNAs) play important roles in the development of fetuses, whereas expression changes of PPARs and three miRNAs (miR-17, miR-27b and miR-34a) and whether these miRNAs regulate PPARs in non-GDM macrosomia placenta is unclear. METHODS: A case-control study was performed to collect information and placental tissues on mothers and newborns of non-GDM macrosomia and normal-birth-weight infants. In vitro HTR8-SVneo cellular model was used to detect the effects of miRNAs on PPARs expression. Quantitative real-time PCR (qRT-PCR) and western blot was applied to examine the expression levels of PPARs, miR-17, miR-27b, and miR-34a in placental tissues and cells. RESULTS: The PPARα/γ mRNA and protein levels were significantly up-regulated and miR-27b was down-regulated in the placenta of macrosomia group compared with in the control group, while no difference was observed in PPARß, miR-17, and miR-34a. After adjusting for confounding factors, low miR-27b and high PPARα/γ mRNA expression still increased the risk of macrosomia. The PPARα/γ protein levels presented a corresponding decrease or increase when cells were transfected with miR-27b mimic or inhibitor. CONCLUSIONS: Placental PPARα/γ and miR-27b expression were associated with non-GDM macrosomia and miR-27b probably promotes the occurrence of non-GDM macrosomia by regulating PPARα/γ protein. IMPACT: Low miR-27b and high PPARα/γ mRNA expression in the placenta were associated with higher risk of macrosomia. In vitro HTR8-SVneo cell experiment supported that miR-27b could negatively regulate the expression of PPARα and PPARγ protein. MiR-27b was probably involved in non-GDM macrosomia through negative regulation of PPARα/γ protein.

Efficacy and safety of adjuvant chemotherapy in T1N0M0 intrahepatic cholangiocarcinoma after radical resection.

OBJECTIVE: Adjuvant chemotherapy is necessary for radical resection of intrahepatic cholangiocarcinoma (ICC) with a high risk of recurrence (T2-4, N1). However, its use in the treatment of early-stage ICC remains controversial. This study aimed to investigate the role of adjuvant chemotherapy after radical resection in patients with early-stage ICC (T1N0M0). DATA AND METHODS: The data of 148 patients with pathologically diagnosed ICC (T1N0M0) who underwent radical resection from January 2012 to January 2018 at the Sun Yat-sen University Cancer Center were retrospectively analyzed. Using consistent baseline data, Kaplan-Meier survival curves were constructed to compare relapse-free survival (RFS) and overall survival (OS) between patients who received postoperative adjuvant chemotherapy (AC group) and those who received only surgical treatment (non-AC group). Univariate and multivariate Cox regression analyses were used to screen for independent prognostic factors affecting survival. The RFS and OS of patients were analyzed after the administration of three adjuvant chemotherapy regimens (gemcitabine + capecitabine [GX], gemcitabine + cisplatin [GP], and capecitabine monotherapy [X]). Finally, the safety of adjuvant chemotherapy was evaluated based on the incidence of grade 1-4 adverse events. RESULTS: The median RFS was 18 months in the non-AC group and 25 months in the AC group. The median OS was 34 months in the non-AC group; however, it was not reached in the AC group. The OS of the AC group was significantly higher than that of the non-AC group (P = 0.005). Multivariate Cox analysis demonstrated that nerve invasion (P = 0.001), preoperative elevation of cancer antigen 19-9 (CA 19-9) levels (P = 0.009), and postoperative adjuvant chemotherapy (P = 0.009) were independent prognostic factors for early-stage ICC after radical resection. The OS rates of the GX, GP, X, and non-AC groups were significantly different (P = 0.023) and were higher in the GX group than in the non-AC group (P = 0.0052). Among patients with elevated preoperative CA 19-9 levels, the OS rate was higher in the AC group than in the non-AC group (P = 0.022). In terms of safety, the incidence of grade 3 or 4 adverse reactions was < 18.2% in the GX, GP, and X groups, without the occurrence of death owing to such reactions. CONCLUSION: Adjuvant chemotherapy can prolong OS among patients with early-stage ICC who have undergone radical resection. Preoperative elevation of CA 19-9 levels and nerve invasion are independent prognostic factors for poor survival outcomes for early-stage ICC after radical resection. All chemotherapy regimens used in the study are safe.

Extracellular histones induce inflammation and senescence of vascular smooth muscle cells by activating the AMPK/FOXO4 signaling pathway.

BACKGROUND: Sepsis is an abnormal immune-inflammatory response that is mainly caused by infection. It can lead to life-threatening organ dysfunction and death. Severely damaged tissue cells will release intracellular histones into the circulation as damage-related molecular patterns (DAMPs) to accelerate the systemic immune response. Although various histone-related cytotoxicity mechanisms have been explored, those that affect extracellular histones involved in vascular smooth muscle cell (VSMC) dysfunction are yet to be determined. METHODS: Mouse aortic vascular smooth muscle cells (VSMCs) were stimulated with different concentrations of histones, and cell viability was detected by CCK-8 assay. Cellular senescence was assessed by SA ß-gal staining. C57BL/6 mice were treated with histones with or without BML-275 treatment. RT-qPCR was performed to determine the expression of inflammatory cytokines. Western blotting was used to analyze the expression of NLRP3, ASC and caspase-1 inflammasome proteins. The interaction of NLRP3 and ASC was detected by CoIP and immunofluorescence staining. RESULTS: In this study, we found that extracellular histones induced senescence and inflammatory response in a dose-dependent manner in cultured VSMCs. Histone treatment significantly promoted apoptosis-associated speck-like protein containing CARD (ASC) as well as NACHT, LRR and PYD domains-containing protein 3 (NLRP3) interaction of inflammasomes in VSMCs. Forkhead box protein O4 (FOXO4), which is a downstream effector molecule of extracellular histones, was found to be involved in histone-regulated VSMC inflammatory response and senescence. Furthermore, the 5'-AMP-activated protein kinase (AMPK) signaling pathway was confirmed to mediate extracellular histone-induced FOXO4 expression, and blocking this signaling pathway with an inhibitor can suppress vascular inflammation induced by extracellular histones in vivo and in vitro. CONCLUSION: Extracellular histones induce inflammation and senescence in VSMCs, and blocking the AMPK/FOXO4 pathway is a potential target for the treatment of histonemediated organ injury.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

Placental mtDNA copy number and methylation in association with macrosomia in healthy pregnancy.

INTRODUCTION: Fetal growth and development depend on metabolic energy from placental mitochondria. However, the impact of placental mitochondria on the occurrence of macrosomia remains unclear. We aimed to explore the association between macrosomia without gestational diabetes mellitus (non-GDM) and changes in placental mitochondrial DNA (mtDNA) copy number and methylation. METHODS: Fifty-four newborns with macrosomia and 54 normal birthweight controls were enrolled in this study. Placental mtDNA copy number and mRNA expression of nuclear genes related to mitochondrial replication or ATP synthesis-related genes were measured by real-time quantitative polymerase chain reaction (qPCR). Methylation levels of the non-coding regulatory region D-loop and ATP synthesis-related genes were detected by targeted bisulfite sequencing. RESULTS: Newborns with macrosomia had lower placental mtDNA copy number and higher methylation rates of the CpG15 site in the D-loop region (D-CpG15) and CpG6 site in the cytochrome C oxidase III (COX3) gene (COX3-CpG6) than normal birth weight newborns. After adjusting for potential covariates (gestational age, prepregnancy BMI, and infant sex), decreased placental mtDNA copy number (adjusted odds ratio [aOR] = 2.09, 95% confidence interval [CI] 1.03-4.25), elevated methylation rate of D-CpG15 (aOR = 2.06, 95% CI 1.03-4.09) and COX3-CpG6 (aOR = 2.13, 95% CI 1.08-4.20) remained significantly associated with a higher risk of macrosomia. DISCUSSION: Reduced mtDNA copy number and increased methylation levels of specific loci at mtDNA would increase the risk of macrosomia. However, the detailed molecular mechanism needs further identification.

Comparison of clinical characteristics in patients with coronavirus disease and influenza A in Guangzhou, China.

BACKGROUND: This study aims to compare the epidemiological, clinical and laboratory characteristics between patients with coronavirus disease (COVID-19) and influenza A (H1N1), and to develop a differentiating model and a simple scoring system. METHODS: We retrospectively analyzed the data from patients with COVID-19 and H1N1. The logistic regression model based on clinical and laboratory characteristics was constructed to distinguish COVID-19 from H1N1. Scores were assigned to each of independent discrimination factors based on their odds ratios. The performance of the prediction model and scoring system was assessed. RESULTS: A total of 236 patients were recruited, including 20 COVID-19 patients and 216 H1N1 patients. Logistic regression revealed that age >34 years, temperature ≤37.5 °C, no sputum or myalgia, lymphocyte ratio ≥20% and creatine kinase-myocardial band isoenzyme (CK-MB) >9.7 U/L were independent differentiating factors for COVID-19. The area under curves (AUCs) of the prediction model and scoring system in differentiating COVID-19 from H1N1 were 0.988 and 0.962, respectively. CONCLUSIONS: There are certain differences in clinical and laboratory features between patients with COVID-19 and H1N1. The simple scoring system may be a useful tool for the early identification of COVID-19 patients from H1N1 patients.

Clinical practice of basin-shaped hepaticojejunostomy following hilar resection of stage III/IV hilar cholangiocarcinoma.

BACKGROUND: Radical surgery for Bismuth type III/IV hilar cholangiocellular carcinoma, which was usually considered unresectable, seems to improve prognosis by increasing the surgical curability rate. However, the dilemma of multiple billiary stumps and high postoperative complication rate caused by hepato-enteric anastomosis has been the main impediment. Thus, we practiced and introduce a new technique called "basin-shaped" hepaticojejunostomy to improve the treatment. METHODS: Thirty-two cases with Bismuth type III/IV hilar cholangiocarcinoma admitted to our department from Aug. 2013 to Dec. 2015 and who underwent hilar resection and resection segment 4(or plus resection segment 1) were reconstructed by "basin-shaped" hepaticojejunostomy. The clinical data were collected and analyzed. RESULTS: All patients underwent successful R0 high hilar resection following basin-shaped hepaticojejunostomy and were discharged from the hospital without severe postoperative complications. The average operation time for hepato-enteric anastomosis was 42.1 ± 8.5 min. The postoperative bile leakage rate was 3.1% (1/32), and the biliary infection rate was 6.2% (2/32). Within a median follow-up of 25.6 months, none of the patients developed local recurrence around the hepato-enteric anastomosis. CONCLUSIONS: For patients with Bismuth type III/IV hilar cholangiocellular carcinoma who underwent resection segment 4(or plus resection segment 1), basin-shaped hepaticojejunostomy was a safe, simple and valid method for bile duct reconstruction, with a relatively low incidence of postoperative complications.

The impact of surgery in metastatic pancreatic neuroendocrine tumors: a competing risk analysis.

Aim The role of surgery in the treatment of metastatic pancreatic neuroendocrine tumors (PNETs) was controversial. The objectives of this study were to illustrate the impact of surgery in improving the prognosis of patients with metastatic PNETs and build nomograms to predict overall survival (OS) and cancer-specific survival (CSS) based on a large population-based cohort. Methods Patients diagnosed with metastatic PNETs between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Nomograms for estimating OS and CSS were established based on Cox regression model and Fine and Grey's model. The precision of the nomograms was evaluated and compared using concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). Results The study cohort included 1966 patients with metastatic PNETs. It was shown that the surgery provided survival benefit for all groups of patients with metastatic PNETs. In the whole study cohort, 1-, 2- and 3-year OS and CSS were 51.5, 37.1 and 29.4% and 53.0, 38.9 and 31.1%, respectively. The established nomograms were well calibrated, and had good discriminative ability, with C-indexes of 0.773 for OS prediction and 0.774 for CSS prediction. Conclusions Patients with metastatic PNETs could benefit from surgery when the surgery tolerance was acceptable. The established nomograms could stratify patients who were categorized as tumor-node-metastasis (TNM) IV stage into groups with diverse prognoses, showing better discrimination and calibration of the established nomograms, compared with 8th TNM stage system in predicting OS and CSS for patients with metastatic PNETs.

Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety.

BACKGROUND: The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma (HCC) patients with solitary tumor and microvascular invasion (MVI) is controversial. This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization (TACE) after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor ≥ 5 cm and MVI. METHODS: In this randomized, open-labeled, phase III trial, HCC patients with a solitary tumor ≥ 5 cm and MVI were randomly assigned (1:1) to receive either 1-2 cycles of adjuvant TACE after hepatectomy (Hepatectomy-TACE) or hepatectomy alone (Hepatectomy Alone). The primary endpoint was disease-free survival (DFS); the secondary endpoints included overall survival (OS) and adverse events. RESULTS: Between June 1, 2009, and December 31, 2012, 250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group (n = 125) or the Hepatectomy Alone group (n = 125). Clinicopathological characteristics were balanced between the two groups. The median follow-up time from randomization was 37.5 months [interquartile range 18.3-48.2 months]. The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [17.45 months (95% confidence interval [CI] 11.99-29.14) vs. 9.27 months (95% CI 6.05-13.70), hazard ratio [HR] = 0.70 (95% CI 0.52-0.95), P = 0.020], respectively. The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [44.29 months (95% CI 25.99-62.58) vs. 22.37 months (95% CI 10.84-33.91), HR = 0.68 (95% CI 0.48-0.97), P = 0.029]. Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group, although these were generally mild and manageable. The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction. CONCLUSION: Hepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor ≥ 5 cm and MVI, with acceptable toxicity.

Effect of Cesarean Section on the Severity of Postpartum Hemorrhage in Chinese Women: The Shanxi Study.

Postpartum hemorrhage (PPH) is one of the most adverse obstetric outcomes. Our aim is to detect the risks of multilevel PPH in different cesarean section (CS) groups [including nulliparous CS with indications, nulliparous CS without indications, repeat cesarean (RC), vaginal birth after cesarean (VBAC), cesarean after vaginal birth (CAVB)]. We conducted a retrospective cohort study, and the data on 127 145 women collected from January 2014 to May 2016 and from 35 tertiary hospitals in Shanxi province, China, were reviewed. Based on the measuring results of PPH, an ordered logistic regression model was used to analyze the adjusted PPH risks for each of the CS groups, and comparisons were drawn between them. Finally, a total of 99 066 nulliparous (77.92%) and 28 079 multiparous (22.08%) women were observed. The number of CS cases was 61 117, and the rate for CS was 48.07%. A total of 10 029 women did not show indications for CS and accounted for 16.41% of the CS parturient, whereas 9103 women underwent a repeated cesarean, with a CS frequency of 14.89%. The number of VBAC cases was 989, whose rate was 9.88% in prior CS women. The number (proportions) of PPH was 3658 (2.88%) in LI (PPH volume: ≥900 and <1500 mL), 520 (0.41%) in 12 (PPH volume: >1500 and <2100 mL), and 201 (0.16%) in L3 (PPH volume: ≥2100 mL). The Ln (n=l, 2,3, etc.) represented the increasing order of PPH severity. In the adjusted results, compared with spontaneous vaginal delivery (SVD) as the reference group, in the adjusted result for nulliparous, there was a decreased PPH risk in CS with indications (OR: 2.32; CI: 2.04-2.62), which was lower than that of CS without indications (OR: 2.50; CI: 2.01-2.96). The highest PPH risk in all subgroups (i.e. nulliparous and multiparous groups) was observed in the RC (OR: 3.61; CI: 3.16-4.17), which was nearly twice higher than that of the VBAC (OR: 1.82; CI: 1.33-2.52). CAVB (OR: 1.03; CI: 0.65-1.62) showed no significant difference with the reference group. Thus, we deemed that CS should be avoided in nulliparous pregnancies unless indicated, to prevent or reduce the rates for the use of RC or VBAC which are high risks of severe PPH to the parturient women.

Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial.

PURPOSE: To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS: In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS: Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.

Bootstrapping data envelopment analysis of efficiency and productivity of county public hospitals in Eastern, Central, and Western China after the public hospital reform.

China implemented the public hospital reform in 2012. This study utilized bootstrapping data envelopment analysis (DEA) to evaluate the technical efficiency (TE) and productivity of county public hospitals in Eastern, Central, and Western China after the 2012 public hospital reform. Data from 127 county public hospitals (39, 45, and 43 in Eastern, Central, and Western China, respectively) were collected during 2012-2015. Changes of TE and productivity over time were estimated by bootstrapping DEA and bootstrapping Malmquist. The disparities in TE and productivity among public hospitals in the three regions of China were compared by Kruskal-Wallis H test and Mann-Whitney U test. The average bias-corrected TE values for the four-year period were 0.6442, 0.5785, 0.6099, and 0.6094 in Eastern, Central, and Western China, and the entire country respectively, with average non-technical efficiency, low pure technical efficiency (PTE), and high scale efficiency found. Productivity increased by 8.12%, 0.25%, 12.11%, and 11.58% in China and its three regions during 2012-2015, and such increase in productivity resulted from progressive technological changes by 16.42%, 6.32%, 21.08%, and 21.42%, respectively. The TE and PTE of the county hospitals significantly differed among the three regions of China. Eastern and Western China showed significantly higher TE and PTE than Central China. More than 60% of county public hospitals in China and its three areas operated at decreasing return scales. There was a considerable space for TE improvement in county hospitals in China and its three regions. During 2012-2015, the hospitals experienced progressive productivity; however, the PTE changed adversely. Moreover, Central China continuously achieved a significantly lower efficiency score than Eastern and Western China. Decision makers and administrators in China should identify the causes of the observed inefficiencies and take appropriate measures to increase the efficiency of county public hospitals in the three areas of China, especially in Central China.

Transarterial chemoembolization combined with recombinant human adenovirus type 5 H101 prolongs overall survival of patients with intermediate to advanced hepatocellular carcinoma: a prognostic nomogram study.

BACKGROUND: Patients with intermediate to advanced hepatocellular carcinoma (HCC) are most commonly treated with transarterial chemoembolization (TACE). Previous studies showed that TACE combined with recombinant human adenovirus type 5 (H101) may provide a clinical survival benefit. In the present study, we aimed to determine the survival benefit of TACE with or without H101 for patients with intermediate to advanced HCC and to develop an effective nomogram for predicting individual survival outcomes of these patients. METHODS: We retrospectively collected data from 590 patients with intermediate to advanced HCC who were treated at Sun Yat-sen University Cancer Center between January 2007 and July 2015. After propensity score matching, 238 patients who received TACE with H101 (TACE with H101 group) and 238 patients who received TACE without H101 (TACE group) were analyzed. Overall survival (OS) was evaluated using the Kaplan-Meier method; the nomogram was developed based on Cox regression analysis. Discrimination and calibration were measured using the concordance index (c-index) and calibration plots. RESULTS: Clinical and radiologic features were similar between the two groups. OS rates were significantly lower in the TACE group than in the TACE with H101 group (1-year OS rate, 53.8% vs. 61.3%; 2-year OS rate, 33.4% vs. 44.2%; 3-year OS rate, 22.4% vs. 40.5%; all P < 0.05). Multivariate Cox regression analysis for the entire cohort showed that alpha-fetoprotein level, alkaline phosphatase level, tumor size, metastasis, vascular invasion, and TACE with or without H101 were independent factors for OS, all of which were included in the nomogram. Calibration curves showed good agreement between nomogram-predicted survival and observed survival. The c-index of the nomogram for predicting OS was 0.716 (95% confidence interval 0.686-0.746). CONCLUSIONS: TACE plus H101 extends the survival of patients with intermediate to advanced HCC. Our proposed nomogram provides individual survival prediction and stratification for patients with intermediate to advanced HCC who receive TACE with or without H101.

Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101.

BACKGROUND: The systemic inflammatory response plays an important role in cancer development and progression. An original inflammation-based staging system for predicting survival in patients undergoing transarterial chemoembolization (TACE) combined with recombinant human type-5 adenovirus H101 is not available. This study aimed to validate the prognostic value of inflammation scores for patients with hepatocellular carcinoma (HCC) who were treated with TACE combined with H101. METHODS: The data from 216 patients with HCC who underwent TACE combined with H101 from January 2007 to July 2015 were retrospectively collected, and the association of the inflammation scores with overall survival (OS) was analyzed. Univariate and multivariate analyses were performed to identify variables associated with OS. The prognostic value of the inflammation scores, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil/ platelet-to-lymphocyte ratio (NLR-PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), prognostic index (PI), tumor-node-metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) staging systems were analyzed and compared using the areas under the receiver operating characteristic curves (AUROCs). RESULTS: The estimated 1-, 2-, and 3-year OS rates were 61.3%, 44.2%, and 40.5% for the entire study cohort, respectively; the median OS was 17 months. According to the multivariate Cox proportional hazards model, the pretreatment NLR, tumor diameter and pretreatment alpha-fetoprotein (AFP) levels were independent predictors of OS. The CLIP score had superior discriminative abilities compared with other staging systems, and the NLR-PLR score consistently displayed a higher AUROC value than the other inflammation-based prognostic scores. The combination of the NLR-PLR and CLIP scores exhibited a superior prognostic ability for OS compared to the NLR-PLR or CLIP scores alone. CONCLUSIONS: The NLR-PLR score is a more powerful predictive system than the other inflammation-based scores for patients with HCC who were treated with TACE and H101. The predictive ability may be improved by utilizing a combination of the NLR-PLR and CLIP scores.

Bootstrapping Data Envelopment Analysis of Efficiency and Productivity of County Public Hospitals in Eastern, Central, and Western China after the Public Hospital Reform / 华中科技大学学报（医学）（英德文版）

China implemented the public hospital reform in 2012.This study utilized bootstrapping data envelopment analysis (DEA) to evaluate the technical efficiency (TE) and productivity of county public hospitals in Eastern,Central,and Western China after the 2012 public hospital reform.Data from 127 county public hospitals (39,45,and 43 in Eastern,Central,and Western China,respectively) were collected during 2012-2015.Changes of TE and productivity over time were estimated by bootstrapping DEA and bootstrapping Malmquist.The disparities in TE and productivity among public hospitals in the three regions of China were compared by Kruskal-Wallis H test and Mann-Whitney U test.The average bias-corrected TE values for the four-year period were 0.6442,0.5785,0.6099,and 0.6094 in Eastern,Central,and Western China,and the entire country respectively,with average non-technical efficiency,low pure technical efficiency (PTE),and high scale efficiency found.Productivity increased by 8.12％,0.25％,12.11％,and 11.58％ in China and its three regions during 2012-2015,and such increase in productivity resulted from progressive technological changes by 16.42％,6.32％,21.08％,and 21.42％,respectively.The TE and PTE of the county hospitals significantly differed among the three regions of China.Eastern and Western China showed significantly higher TE and PTE than Central China.More than 60％ of county public hospitals in China and its three areas operated at decreasing return scales.There was a considerable space for TE improvement in county hospitals in China and its three regions.During 2012-2015,the hospitals experienced progressive productivity;however,the PTE changed adversely.Moreover,Central China continuously achieved a significantly lower efficiency score than Eastern and Westem China.Decision makers and administrators in China should identify the causes of the observed inefficiencies and take appropriate measures to increase the efficiency of county public hospitals in the three areas of China,especially in Central China.

Changes of HBV DNA After Chemoembolization for Hepatocellular Carcinoma and the Efficacy of Antiviral Treatment.

Unlike systemic chemotherapy for hematological malignancies with hepatitis B virus (HBV) infection, transarterial chemoembolization (TACE) for HBV-related hepatocellular carcinoma (HCC) has only recently been reported to cause HBV reactivation and subsequent hepatitis. Most patients with HBV-related HCC have an underlying disease with liver fibrosis or cirrhosis, and TACE may potentially induce HBV reactivation and liver decompensation. Currently, there are no clinical guidelines for managing TACE-caused HBV reactivation. In this review, we summarize the changes of HBV status and liver function after TACE and the effect of antiviral treatment before, during, or after TACE.