The purpose of this study was to evaluate whether vitamin D receptor (VDR) genes BsmI polymorphisms were markers for susceptibility to or severity of systemic lupus erythematosus (SLE) in Chinese patients in Taiwan. The study included 47 Chinese patients with SLE. In addition, 90 unrelated, healthy individuals living in central Taiwan served as control subjects. Each polymorphism was detected as a result of polymerase chain reaction (PCR)-based restriction analysis. A PCR product length was determined to be 580bp (BB) whereas two fragments of 405 and 175bp were determined to be excisable lengths (bb) by BsmI endonuclease. The relationship between Bsm polymorphisms and clinical manifestations of SLE was evaluated. We found that BB was significantly more common and bb less common in SLE than in control group (chi2 = 54.2, P < 0.0001). In addition, the frequency of B allele was also significantly more common in patients with SLE than in the healthy control subjects (chi2 = 38.7, P < 0.0001), giving an odds ratio of 7.14 (95% confidence interval 3.53-14.4). In the SLE patients, we did not detect any associations of VDR genotype with the clinical, laboratory profiles, or lupus nephritis (chi2 = 2.34, P = 0.3). This study indicated an increased distribution of VDR BB genotype and B allelic frequencies in the Chinese SLE patients in Taiwan. However, there were no associations between the frequency of VDR allelic variations and clinical manifestations, laboratory profiles, or lupus nephritis.

Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. In Caucasians, four variant TPMT alleles have been detected in over 80% of individuals with low or intermediate TPMT activity. The wild-type allele is designated as TPMT*1 and the mutant alleles are designated TPMT*2 through TPMT*8. The frequency of these alleles in different ethnic groups has not been well defined. In this study, one hundred individuals, from each of the Indonesian, Thai and Philippine populations, together with 249 Taiwanese, were analysed by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing methods. The results showed that the allelic frequencies of TPMT*3C were 0.6% for Taiwanese and 1% for Filipino, Thai and Indonesian populations, respectively. One Filipino with a Caucasian parent was found to be heterozygous for the TPMT*2 allele. This study provides the first analysis of the allele frequency distribution of all known TPMT mutations in South-east Asian populations.

Superparamagnetic iron oxide nanoparticles (SPION) are potential drug carriers and a magnetic resonance imaging (MRI) contrast agent for cancer therapy and diagnosis. In this study, dechlorinated cisplatin (CMDP) is tethered to maghemite nanoparticles modified with 4-oxo-4-(3-(triethoxysilyl)propylamino)butanoic acid (OTPBA-SPION) through the surface carboxylate groups. The nanocomposite (CMDP-OTPBA-SPION) was characterized by TEM, XPS, EDX, SQUID, ICP-AES, and zeta potential. A relatively high Pt loading capacity (ca. 13%) is achieved with this drug delivery system. The DNA binding ability of CMDP-OTPBA-SPION is prominent in acidic medium (pH 5.2) but is insignificant under normal physiological conditions (pH 7.4), suggesting that an acidic cancerous environment is favourable for the release of the platinum pharmacophore from the composite. The transverse relaxivity of CMDP-OTPBA-SPION in phosphate-buffered saline is 141.9 mM À1 s À1 in terms of Fe concentration, implying that the composite could be used as a negative-contrast agent for MRI. The cytotoxicity of the composite toward MCF-7 and HeLa cancer cells displays slow and time-dependent characteristics, reaching a level comparable to that of cisplatin at 72 h. The diagnostic capability and tumor-specific accumulation of the composite are verified in vitro and in vivo by the time-dependent negative-contrast enhancement effect in MRI using MCF-7 cells and tumor-bearing mice, respectively. The results demonstrate that CMDP-OTPBA-SPION can potentially be used as an anticancer theranostic agent for simultaneous targeted therapy and MRI under an external magnetic field.

We aimed to evaluate the relationship between two polymorphisms of the IL4 gene (-590T/C and intron 3) and systemic lupus erythematosus in Chinese patients in Taiwan. This study included 91 patients with systemic lupus erythematosus (SLE) and 163 unrelated, age matched healthy controls living in the same area. The typing of -590T/C and intron 3 VNTR (variable number of tandem repeats) polymorphisms were performed by PCR-RFLP and PCR, respectively. Allelic frequencies and carriage rates between SLE patients and controls were compared, and the relationship between allelic frequencies and clinical manifestations of SLE was evaluated. The genotype frequencies of IL-4 intron 3 were found to differ significantly between SLE patients with and without discoid rash (chi-square test, P = 0.03 5). The allelic frequency of intron 3 RP1 was significant different in the patients with discoid rash when compared to patients without this clinical feature (OR = 3.70, 95% CI 2.04-6.72, chi2 test, P = 0.029). The RP1/RP1 homozygous carriage was significantly associated with patients with discoid rash when compared to patients without this clinical feature (OR = 6.04, 95% CI 2.81-12.95, P = 0.01). The allelic frequency of -590T was significant different in the patients with discoid rash when compared to patients without this clinical feature (OR = 3.44, 95% CI 1.88-6.31, chi-square test, P=0.04). The T/T homozygous carriage was significantly associated with patients with discoid rash when compared to patients without this clinical feature (OR = 5.41, 95% CI 2.50-11.68, P = 0.02). We describe a novel association between RPI/RPI and T/T homozygous carriage and patients with discoid rash. The role of the intron 3 polymorphism of the IL4 gene in SLE remains unclear and further substantiation based on larger patient samples is needed.

Cholangiocarcinoma (CCA) is a rare cancer biliary tract malignancy which accounts for less than 3% of all gastrointestinal cancers diagnosed worldwide (1). The incidence of CAA is highest in Thailand, China, and other Asian populations, but is lowest in the western world, presumably reflecting differences in the exposure of genetic and other risk factors (2). Anatomically, CCA can be divided into intrahepatic or extrahepatic subtypes choosing second-order bile ducts as the point of separation (3). The majority of CCA are extrahepatic cholangiocarcinoma (eCCA), whereas Summary Immunotherapy might be an effective treatment in extrahepatic cholangiocarcinoma (eCCA), a tumor with extremely limited therapeutic options. Our study is to characterize the programmed death ligand-1 (PD-L1) protein expression and cancer microenvironment profiles in surgically resected eCCA samples. PD-L1 positivity was observed on tumor cells (32.3%) as well as on tumor-associated macrophages (74.2%). PD-L1 expression by eCCA correlated significantly with immune parameters such as intra-tumoral CD3+ tumor infiltrating lymphocytes (TILs) density (P = 0.002), intra-tumoral CD8+ TILs density (P < 0.001), and the expression pattern of human leukocyte antigen (HLA) class I (P < 0.001). Immunofluorescence showed that PD-L1 positive tumor cells were adjacent to PD-1 positive cells and the stroma covered with interferon-γ. Correlation with clinicopathological parameters and survival analyses revealed that PD-L1 positivity in eCCA was related to the absence of venous invasion (P = 0.030), improved overall survival (P = 0.020) and progressionfree survival (P = 0.011). HLA class I molecules defect, which is an important mechanism of immune evasion, was frequently observed in eCCA (50.0%) and was associated with a decreased number of intra-tumoral CD8+ TIL density (P = 0.028). Additionally, the presence of unusually high numbers of tumor-associated macrophages (TAMs) subsets M2 in most of eCCA (74.2%) was noted. Our study indicated that PD-L1 expression in association with intra-tumoral TILs infiltration and HLA class I expression in 32.3% of the eCCA reflects an active immune microenvironment potentially responsive to PD-1/PD-L1 inhibitors. In addition, the combination of macrophage-targeting agents may provide therapeutic synergy for future immunotherapy.

Interleukin-1 (IL-1) might play a role in the process of bone loss and hypercalciuria and is therefore considered to be involved in the formation of urinary stones. The aim of this study is to test whether the IL-1beta promoter region, exon 5 region and IL-1 receptor antagonist gene intron 2 polymorphisms could be genetic markers for the susceptibility to the formation of urinary stones. A control group of 152 healthy people and a group of 105 patients with recurrent calcium oxalate stone were examined in this study. Polymerase chain reaction (PCR) analyzed the variable number tandem repeats at intron 2 of the IL-1Ra gene for the polymorphisms. PCR-based restriction analysis was done for the IL-1beta gene polymorphisms of the promoter region and exon 5 by the endonucleases Ava I and Taq I, respectively. The polymorphisms studied in the IL-1beta genes did not reveal a strong association with calcium oxalate stone disease when compared with the control group (promoter region by chi-square test, P=0.627: exon 5 region by Fisher's exact test, P = 0.403). Only two frequent alleles of the IL-1Ra gene corresponding to one and two copies of an 86-bp sequence repeat were identified by PCR. The result revealed significant differences between control individuals and stone patients (P < 0.01. Fisher's exact test). In addition, the frequency of the type I allele in the stone group (99.0%) was higher than in the control group (94.0%). The odds ratio for the type I allele of the IL-1Ra gene in calcium oxalate stone disease is 6.041 (95% CI: 1.683 approximately 21.687). There is an association between urolithiasis and polymorphism in the IL-1Ra gene. No significant difference was found when dividing the stone patients into groups with normocalciuria and hypercalciuria in relation to these genetic polymorphisms. Further studies of the type I allele of the IL-IRa gene are worthwhile because of its correlation with stone disease. In our study, neither the IL-1beta promoter region nor the exon 5 polymorphisms were significantly different when comparing control subjects and calcium oxalate stone patients.

The exploration of highly efficient materials for the degradation of chemical warfare agents has been a longstanding task for preventing human exposure. Herein, we report a series of metal−organic frameworks (MOFs) M-TCPP-La based on metallo-tetra(4-carboxyphenyl)porphyrin and La III , which were applied to selectively oxidize 2-chloroethyl ethyl sulfide (CEES, a sulfur mustard simulant) as heterogeneous photocatalysts. After irradiation from a commercial blue light-emitting diode (LED), both superoxide ion and singlet oxygen were generated by M-TCPP-La and involved in selective oxidization of CEES to 2-chloroethyl ethyl sulfoxide (CEESO). Notably, a very short half lifetime (2.5 min) was achieved using Fe-TCPP-La as the photocatalyst. In comparison to currently utilizing singlet oxygen and hydrogen peroxide as oxidizing agents, this work employing both singlet oxygen and superoxide ion represents a new and effective strategy of detoxification of mustard gas.

Photodynamic therapy (PDT) is an approved and promising treatment approach that utilizes photosensitizer (PS) to produce cytotoxic reactive oxygen species (ROS) through irradiation to achieve tumor noninvasive therapy. Whereas, the...