Integrated analysis of intratumoral biomarker and tumor-associated macrophage to improve the prognosis prediction in cancer patients.

BACKGROUND: The lack of effective and accurate predictive indicators remains a major bottleneck for the improvement of the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Hepatitis B virus X (HBx) has been widely suggested as a critical pathogenic protein for HBV-driven liver carcinogenesis, while tumor-associated macrophage (TAM) infiltration is also closely related to the tumorigenesis and progression of HCC. However, few studies have determined whether combining HBx expression with TAM populations could increase the accuracy of prognostic prediction for HBV-related HCC. METHODS: The study cohort enrolling 251 patients with HBV-related HCC was randomly split into a training and a validation group (ratio 1:1). The expression levels of HBx and TAM marker CD68 in HCC samples were detected by immunohistochemistry. Kaplan-Meier curves, Cox regression and Harrell's concordance index (C-index) analysis were conducted to evaluate the prognostic significance of these indicators alone or in combination. RESULTS: The expression level of HBx was strongly correlated with CD68+ TAM infiltration in HCC tissues. Elevated HBx or CD68 expression indicated poorer overall survival (OS) and progression-free survival (PFS) after hepatectomy, and both of them were independent risk factors for postoperative survival. Meanwhile, patients with both high HBx and CD68 levels had worst clinical outcomes. Moreover, integrating HBx and CD68 expression with clinical indicators (tumor size and micro-vascular invasion) showed the best prognostic potential with highest C-index value for survival predictivity, and this proposed model also performed better than several conventional classifications of HCC. CONCLUSION: Combining the expression of intratumoral HBx, CD68+ TAM population and clinical variables could enable better prognostication for HBV-related HCC after hepatectomy, thus providing novel insights into developing more effective clinical prediction model based on both molecular phenotypes and tumor-immune microenvironment.

Dielectric Relaxation and Beyond Limiting Behavior of Alternating-Current Conductivity in a Supermolecular Ferroelectric.

A cyclen-based hybrid supermolecule crystal, [(FeCl2 )(cyclen)]Cl (1), where cyclen=1,4,7,10-tetraazacyclododecane, was prepared using a liquid-liquid diffusion approach. The variable crystal structures exhibit that compound 1 belongs to an orthorhombic crystal system, Pna21 space group (point group C2V ) in the temperature range of 150-400 K. This hybrid supermolecule shows a dielectric relaxation behavior around room temperature, and the ferroelectric nature of 1 has been directly verified by hysteresis measurements. In addition, the AC (alternating current) conductivity study reveals that the 1 displays a beyond limiting behavior. These interesting findings are for the first time reported in the field of supermolecular ferroelectrics. This study may open a new way to construct supermolecular ferroelectrics and give insights into their conductor behavior.

Comparison of the Efficacy of Ultra-Mini PCNL, Flexible Ureteroscopy, and Shock Wave Lithotripsy on the Treatment of 1-2 cm Lower Pole Renal Calculi.

OBJECTIVE: To compare the efficacy of new percutaneous technique ("ultra-mini PCNL", UMP), shock wave lithotripsy (SWL) and flexible ureteroscopy (FURS) on the treatment of 1-2 cm lower pole kidney stones, and to determine the advantages and disadvantages of each method. MATERIALS AND METHODS: This prospective study was based on data collected from the files of patients between March 2015 and March 2017. This study recruited a total of 180 patients with single radio-opaque lower caliceal calculi of 1-2 cm. All patients were randomly divided into 3 groups: group A was treated with UMP, group B was treated with FURS by using holmium laser and group C was treated with SWL by using the electromagnetic lithotripter. The average age, sex, size of the stone, the time of operation, the rate of no stone, the time of hospitalization, the rate of retreatment, the cost and the complications of the 3 groups were compared. The success of the operation was defined as no residual stone or < 0.3 cm on computed tomography at 3 months postoperatively. RESULTS: The stone burdens of the groups were equivalent. The re-treatment rate in group C was significantly higher than that in group A and B (30 vs. 1.6%, 5%). The average operating time in group B (93.35 ± 21.64 min) was statistically significantly longer than that in group A and C (68.58 ± 15.82 min, 46.33 ± 5.81 min). Although the time of hospitalization of group A (5.32 ± 1.20 day) was longer than that of group B (3.22 ± 0.52 day) and C (1.08 ± 0.28 day; p < 0.05). The stone-free rate (SFR) in UMP, FURS, SWL were 98, 92, and 73% respectively; the highest SFR was in the UMP group (p < 0.05). The complication rates were evaluated by using the Clavien grading system, which were determined to be 16.67% in UMP, 6.67% in SWL and 8.33% in FURS. In particular, the complications of GI and GII were more common in group A (p < 0.05). CONCLUSIONS: UMP, FURS, and SWL are all safe and effective in the treatment of 1-2 cm lower pole kidney stones. UMP and FURS had a better SFR than SWL, but the time of hospitalization in UMP group was longer and there were more complications in the UMP group. In addition, the operation time of FURS is longer as compared to UMP and SWL, and there is a higher rate of postoperative fever. The invasiveness and cost of SWL were lower than that of UMP and FURS, but the re-treatment rate was higher.

Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinoma.

BACKGROUND: In the clinic, how to stratify renal cell carcinoma (RCC) patients with different risks and to accurately predict their prognostic outcome remains a crucial issue. In this study, we assessed the expression and prognostic value of gankyrin in RCC patients. METHODS: The expression of gankyrin was examined in public databases and validated in specimens from two independent centers. The clinical practice and disease correlation of gankyrin in RCC were evaluated in RCC patients, various cell lines and an orthotopic RCC model. FINDINGS: Upregulation of gankyrin expression in RCC was corroborated in two independent cohorts. High gankyrin expression positively associated with disease progression and metastasis of RCC patients. A positive correlation between gankyrin and sunitinib-resistance was also observed in RCC cell lines and in an orthotopic RCC model. Kaplan-Meier analysis revealed that patients with higher gankyrin expression presented worse prognosis of RCC patients in the two cohorts. Gankyrin served as an independent prognostic factor for RCC patients even after multivariable adjustment by clinical variables. Time-dependent AUC and Harrell's c-index analysis presented that the incorporation of the gankyrin classifier into the current clinical prognostic parameters such as TNM stage, Fuhrman nuclear grade or SSIGN score achieved a greater accuracy than without it in predicting prognosis of RCC patients. All results were confirmed in randomized training and validation sets from the two patient cohorts. INTERPRETATION: Gankyrin can serve as a reliable biomarker for disease progression and for prognosis of RCC patients. Combining gankyrin with the current clinical parameters may help patient management. FUND: National Natural Science Foundation of China (No. 81773154, 81772747 and 81301861), Medical Discipline Construction Project of Pudong New Area Commission of Health and Family Planning (PWYgf2018-03), the Shanghai Medical Guidance (Chinese and Western Medicine) Science and Technology Support Project (No. 17411960200), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (No. PWR12016-05).

[(18-Crown-6)K][Fe(1)Cl(1)4 ]0.5 [Fe(2)Cl(2)4 ]0.5 : A Multifunctional Molecular Switch of Dielectric, Conductivity and Magnetic Properties.

Multifunctional materials that exhibit different physical properties in a single phase have potential for use in multifunctional devices. Herein, we reported an organic-inorganic hybrid compound [(18-crown-6)K][Fe(1)Cl(1)4 ]0.5 [Fe(2)Cl(2)4 ]0.5 (1) by incorporating KCl and FeCl3 into a 18-crown-6 molecule, which acts as a host of the six O atoms providing a lone pair of electrons to anchor the guest potassium cation, and [FeCl4 ]- as a counterion for charge balance to construct a complex salt. This salt exhibited a one-step reversible structural transformation giving two separate high and low temperature phases at 373 K, which was confirmed by systematic characterizations including differential scanning calorimetry (DSC) measurements, variable-temperature structural analyses, and dielectric, impedance, variable-temperature magnetic susceptibility measurements. Interestingly, the structural transformation was coupled to both hysteretic dielectric phase transition, conductivity switch and magnetic-phase transition at 373 K. This result gives an idea for designing a new type of phase-transition materials harboring technologically important magnetic, conductivity and dielectric properties.