Precision therapy for intrahepatic cholangiocarcinoma: A case report on adjuvant treatment in a recurrent patient after surgery and literature review.

A 37-year-old female patient was diagnosed with intrahepatic cholangiocarcinoma (ICC), with the lesion located in the right lobe of the liver. Despite radical resection, postoperative adjuvant chemotherapy and a combination of adjuvant chemotherapy and immunotherapy, the patient continued to experience multiple instances of intrahepatic tumor metastases. Furthermore, the patient exhibited significant adverse reactions to systemic chemotherapy and had poor treatment tolerance. Guidance from paraffin section fluorescence in situ hybridization gene sequencing was used to select a combination of immunotherapy and targeted therapy treatments with programmed cell death 1 (PD-1)/PD-1 ligand 1 antibody durvalumab and the targeted drug pemigatinib. The patient tolerated the treatment and has continued to survive for 28 months. According to imaging evaluations, the lesions continued to decrease, with some disappearing completely. The tumor marker carbohydrate antigen 19-9 remained normal for >9 weeks during the treatment. This report described the patient's treatment process in detail and briefly reviewed relevant literature on the treatment progress of postoperative patients with ICC.

High-throughput and controllable manufacturing of liquid crystal polymer planar microlens array for compact fingerprint imaging.

The microlens array (MLA) with a small geometric footprint and unique performances, is the key enabler to push the development of photonic devices toward miniaturization, multi-function and large-scale integration. However, the realization of 100% fill-factor (FF) MLAs with high controllability and its mass manufacturing without complex steps has always been a difficult issue. Here, we propose an efficient, highly flexible and low-cost manufacturing approach for MLAs with a high FF via snapshot polarization patterning. The digitalized linear polarization pattern was distributed across the photo-alignment layer with both high efficiency and accuracy, enabling large-area liquid crystal MLA with parameter controllability from element to element. The MLA manufacturing process does not involve developing, etching and deposition steps and is suitable for industry up-scaling. We further proposed a novel compact compound-eye imaging system for biometrics with the obtained MLAs. The 100% FF MLA enables high light utilization efficiency and low background crosstalk, yielding compact biometrics indentation with high recognition accuracy. The realization of such planar optics would lead to a plethora of different miniaturized multiaperture imaging systems in the future.

Madecassoside impedes invasion of rheumatoid fibroblast-like synoviocyte from adjuvant arthritis rats via inhibition of NF-κB-mediated matrix metalloproteinase-13 expression.

Fibroblast-like synoviocytes (FLS) play a pivotal role in Rheumatoid arthritis (RA) pathogenesis through aggressive migration and invasion. Madecassoside (Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis (AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase (MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec (10 and 30 µmol·L-1) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1ß (IL-1ß), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1ß-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.

Id4 promotes cell proliferation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in the world, especially in China. As a member of the inhibitor of differentiation (Id) family, Id4 has been reported to function in many cancer types, but relatively little is known about its role in HCC. The purpose of this study was to investigate the potential relationship between Id4 and HCC development and the underlying mechanism involving the function of Id4 in HCC. METHODS: We used quantitative real-time polymerase chain reaction and Western blotting to examine the RNA and protein expression of Id4. In addition, we used Cell Counting Kit-8 assay and colony formation assay to identify the function of Id4 in the regulation of cell proliferation in human HCC. RESULTS: We found that the expression of Id4 protein was up-regulated in tumor tissues from HCC patients. Overexpression of Id4 promoted HCC cell proliferation, clonogenicity in vitro, and tumorigenicity in vivo. Id4 knockdown experiments showed that silencing Id4 blocked the proliferation and colony formation ability of HCC cells in vitro. Furthermore, overexpression of CCAAT/enhancer-binding protein ß inhibited Id4 expression in HCC cells. CONCLUSION: Id4 may be developed as a potent therapeutic agent for the treatment of HCC, but more details about the underlying mechanisms of action are needed.

Inhibitory effects of transcription factor Ikaros on the expression of liver cancer stem cell marker CD133 in hepatocellular carcinoma.

CD133 is a cellular surface glycoprotein that has been reported as a marker for the enrichment of cancer stem cells (CSCs). However, the regulatory mechanism of CD133 remains unknown. CSCs have been proposed to contribute to radioresistance and multi-drug resistance. The elucidation of key regulators of CD133 and CSCs is critical for the development of CSC-targeted therapy. In this study, we showed that Ikarosinhibited the expression of CD133 via direct binding to the CD133 P1 promoter and repressed the tumorigenic and self-renewal capacity of CD133(+) cancer stem-like cells in hepatocellular carcinoma (HCC). We found that Ikaros interacted with CtBP as a transcription repressor complex, which inhibited CD133 expression in HCC. We also demonstrated that Ikaros expression was up-regulated by ETS1 which activity was regulated by MAPKs pathway. Furthermore, decreased expression of Ikaroswas significantly associated with poor survival in HCC patients. Overall, our study identifies that Ikaros plays a role as a transcription repressor in HCC and is a new reactivated therapeutic target for the treatment of HCC. Meanwhile, our findings provide evidence that Ikaros could be an attractive inhibitor of the target gene CD133, which reactivates anticancer mechanisms in targeted CSC therapy.

Enhancement of survivin-specific anti-tumor immunity by adenovirus prime protein-boost immunity strategy with DDA/MPL adjuvant in a murine melanoma model.

As an ideal tumor antigen, survivin has been widely used for tumor immunotherapy. Nevertheless, no effective protein vaccine targeting survivin has been reported, which may be due to its poor ability to induce cellular immunity. Thus, a suitable immunoadjuvant and optimized immunization strategy can greatly enhance the cellular immune response to this protein vaccine. DDA/MPL (monophosphoryl lipid A formulated with cationic dimethyldioctadecylammonium) has been reported to enhance the antigen uptake and presentation to T cells as an adjuvant. Meanwhile, a heterologous prime-boost strategy can enhance the cellular immunity of a protein vaccine by applying different antigen-presenting systems. Here, DDA/MPL and an adenovirus prime-protein boost strategy were applied to enhance the specific anti-tumor immunity of a truncated survivin protein vaccine. Antigen-specific IFN-γ-secreting T cells were increased by 10-fold, and cytotoxic T lympohocytes (CTLs) were induced effectively when the protein vaccine was combined with the DDA/MPL adjuvant. Meanwhile, the Th1 type cellular immune response was strongly enhanced and tumor inhibition was significantly increased by 96% with the adenovirus/protein prime-boost strategy, compared to the protein homologous prime-boost strategy. Moreover, this adjuvanted heterologous prime-boost strategy combined with oxaliplatin could significantly enhance the efficiency of tumor growth inhibition through promoting the proliferation of splenocytes. Thus, our results provide a novel vaccine strategy for cancer therapy using an adenovirus prime-protein boost strategy in a murine melanoma model, and its combination with oxaliplatin may further enhance the anti-tumor efficacy while alleviating side effects of the drug.

Changes in the proportions of CD4(+)T cell subsets defined by CD127 and CD25 expression during HBV infection.

CD4(+)T cell counts are closely related to the progression of HBV infection. Here, we investigated how the proportions of three CD4(+)T cell subsets - CD127(-)CD25(-), CD127(+)CD25(low/-) and CD127(low)CD25(high) - changed during HBV infection, as is little known. Compared with healthy controls, the proportions of CD127(-)CD25(-) in chronic hepatitis B (CHB) patients and HBV carriers significantly increased, while that of CD127(+)CD25(low/-) significantly decreased. The proportion of CD127(low)CD25(high) in CHB patients was significantly higher than those in HBV carriers or healthy controls. Compared with HBV-DNA negative group, the proportion of CD127(-)CD25(-) in positive group significantly decreased and that of CD127(+)CD25(low/-) significantly increased. In the follow-up study for CHB patients treated with interferon-α2b for 12 weeks or 24 weeks, the proportions of CD127(-)CD25(-) significantly decreased, while that of CD127(low/-)CD25(high) significantly increased. The results suggested that specific changes in the fraction of CD4(+)T cell subsets expressing CD127 and/or CD25 were associated with hepatitis B progression.

[Clinical significance and detection of the expression of CD25- CD127- on CD4+ T cells in peripheral blood in patients with hepatitis B].

OBJECTIVE: To investigate the clinical significance and detection of the expression of CD25- CD127- on CD4+ T cells in peripheral blood in patients with hepatitis B. METHODS: The expression of CD25- CD127- on CD4+ T cells were measured by using flow cytometry in 53 patients with chronic hepatitis B, 53 carrier with hepatitis B virus and 26 healthy blood donors, and follow up 20 patients with HBV-DNA positive treated with interferon. RESULTS: (1) Compared with healthy controls, the expression of CD25- CD127- on CD4+ T cells in patients and carrier with hepatitis B virus were lower (Q = 4.559, P < 0.05; Q = 6.230, P < 0.05). (2) The expression of CD25- CD127- on CD4+ T cells in patients with HBV-DNA positive (n = 77) was lower than that of negative (n = 29) (t = 2.290, P = 0.024). (3) Compared with the prior treatment,the expression of CD25- CD127- on CD4+ T cells in patients with B hepatitis were lower after interferon treated with 12 weeks (t = 2.469, P = 0.024). CONCLUSION: It suggested that the CD25- CD127- expression on CD4+ T cells correlated with viral infections and cleared,exogenous interferon could decrease CD25- CD127- expression on CD4+ T cells.

[Laser resonance ionization spectroscopy of even-parity autoionization states of cerium atom].

This paper describes the investigation of even-parity autoionization states of cerium atoms by three-step three-color resonance ionization spectroscopy (RIS). Twenty-seven odd-parity highly excited levels, whose transition probability is high, were used in this research. One hundred and forty-one autoionization states were found by these channels with the third-step laser scanning in the wavelength range of 634-670 nm. The ionization probabilities of different channels, which had higher cross sections, were compared. On the basis of this, eight optimal photoionization schemes of cerium atom have been given.

[Study on recovery of ethyl acetate after extracting tripterygium wifordii extractum with ethyl acetate].

OBJECTIVE: To increase the recovery rate of ethyl acetate after extracting tripterygium wifordii extractum and to decrease product cost. METHOD: After extracting tripterygium wifordii extractum with ethyl acetate, 3 times saturated salt water was added in it so as to recovery ethyl acetate distilled under normal atmospheric pressure. Ethyl acetate containing salt water was purified through Na2SO4 column. RESULT: Ethyl acetate purified could be used repeatedly and the recovery rate was up to 85%. CONCLUSION: This method is completely adapted for mass production.

Tuberculosis control priorities defined by using cost-effectiveness and burden of disease.

OBJECTIVE: To define TB control priorities using cost-effectiveness and burden of disease. METHODS: An assumed cohort of 2,000 cases was set up based on age-specific incidence of 794 newly registered smear-positive cases in Beijing in 1994. Prognostic trees and model diagrams of infectivity with natural history and DOTS intervention were constructed based on the epidemiological parameters. RESULTS: DOTS reduced 89.19% of YLL, 78.90% of YLD, and 99.98% of infectivity BOD. One DALY could be saved with 45.70 Yuan by DOTS with 3% discount. Sensitivity analysis showed that discount had effect on CER. Weight of age was insensitive to CER. The higher the DOTS cured rate, the more the cost-effectiveness. CONCLUSIONS: DOTS is a good cost-effectiveness TB control strategy. Cost-effectiveness and burden of disease can be used to define TB control priorities.

Methodology for the assessment of burden of smear-positive pulmonary TB and its infectivity.

OBJECTIVE: The study investigated the burden of smear-positive pulmonary TB and its infectivity using DALY (disability-adjusted life year) as an indicator. METHODS: An assumed cohort of 2,000 cases was set up based on the age-specific incidence of 794 newly registered smear-positive cases in Beijing in 1994. Prognostic trees and model diagrams of infectivity under natural history and DOTS(directly observed treatment, short-course) strategy were established according to the epidemiological evidence. RESULTS: The results showed that 29.6% of DALYs would be neglected if the burden caused by the infectivity was not considered. CONCLUSION: DOTS strategy may reduce 97.3% of the number of potential cases infected, 92.9% of DALYs related to TB-patients themselves, and 99.9% of DALYs caused by TB's infectivity as well.

[Identification of odd-parity high-lying lever of Ce I by laser resonance ionization spectroscopy (I): 32,042-34,575 cm-1].

Laser resonance ionization spectroscopy (RIS) is an excellent technique for investigating the complicated atomic structure of heavy elements especially in their higher-energy region. In order to obtain the optimal photoionization scheme of cerium atom, odd-parity high-lying states were studied using this technique. The 83 odd-parity high-lying levers have been firstly observed by two-step resonance laser excitation followed by non-resonance photoionization in the 32,042-34,575 cm-1 energy region. These high-lying states have been measured. The possible angular momentum quantum numbers J are assigned for these levels.