In vitro characteristics of Epirubicin-loaded thermosensitive liquid embolic agent.

OBJECTIVE: To investigate the drug loading and release rate of epirubicin-loaded thermosensitive liquid embolic agents in vitro. MATERIALS AND METHODS: The drug loading and stability of epirubicin-loaded thermosensitive liquid embolic agents with or without iopromide were determined by high-performance liquid chromatography, and the same method was used to determine the drug release rate of thermosensitive liquid embolic agents at different time points. RESULTS: For epirubicin-loaded thermosensitive liquid embolic agents without iopromide, the average drug loading after filtration by membrane was (0.78 ± 0.02) mg and the drug loading rate was (16.1 ± 0.35)%, while the average drug loading without membrane was (0.73 ± 0.06) mg and the drug loading rate was (15.07 ± 1.17)%. After adding iopromide, the drug loading capacity was measured from 0 h-24 h solution and the drug loading was calculated indirectly and conclude that the drug loading capacity of thermosensitive liquid embolic agents decreased or disappeared. The sustained release rate of epirubicin from 0 to 48 hours was 42.65% in 48 hours. CONCLUSION: Epirubicin can be successfully loaded into the thermosensitive liquid embolic agents with good stability and sustained release. After adding iopromide, the drug loading capacity of thermosensitive liquid embolic agents decreased or disappeared.

Comprehensive germline and somatic genomic profiles of Chinese patients with biliary tract cancer.

Background: Biliary tract cancer (BTC) is an uncommon but highly lethal malignancy with poor clinical outcomes. To promote the development of precision medicine for BTC, uncovering its genomic profile becomes particularly important. However, studies on the genomic feature of Chinese BTC patients remain insufficient. Methods: A total of 382 Chinese patients with BTC were enrolled in this study, including 71 with intrahepatic cholangiocarcinoma (ICC), 194 with extrahepatic cholangiocarcinoma (ECC), and 117 with gallbladder carcinoma (GBC). Genetic testing was performed by utilizing the next-generation sequencing (NGS) of 499 cancer-related genes and the results were compared to those of Western BTC patients (MSKCC cohorts). Results: The most prevalent genes were TP53 (51.6%), ARID1A (25.9%), KMT2C (24.6%), NCOR1 (17%), SMAD4 (15.2%), KRAS (14.9%), KMT2D (14.9%), ATM (14.1%), and APC (13.9%) in Chinese BTC patients. TP53, SMAD4, and APC were more prevalent in GBC, ECC, and ICC, respectively. In addition, 10.5% of Chinese BTC patients harbored pathogenic or likely pathogenic (P/LP) germline alterations in 41 genes, which were mainly related to DNA damage repair (DDR). Additionally, the genomic features of Chinese and Western BTC tumors were similar, with the exception of the notable difference in the prevalence of TP53, KRAS, IDH1, KMT2C, and SMAD4. Notably, Chinese BTC patients had high prevalence (57.1%) of actionable alterations, especially for those with ECC, and half (192/382) of them had somatic DDR alterations, with the prevalence of deleterious ones being significantly higher than their Western counterparts. Twenty-three percent of patients had a higher tumor mutational burden (TMB-H, over 10 mutations/MB), and TMB was significantly higher in those with deleterious DDR alterations and/or microsatellite instability-high. The most common mutational signature in BTC patients was Signature 1, and interestingly, Signatures 1, 4, and 26 were significantly associated with higher TMB level, but not with the survival of patients who had received immunotherapy in pan-cancer. Conclusion: Our study elaborated the distinct germline and somatic genomic characteristics of Chinese BTC patients and identified clinically actionable alterations, highlighting the possibility for the development and application of precision medicine.

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma: A bibliometric and knowledge-map analysis.

Background: In recent years, hepatic arterial infusion chemotherapy (HAIC) has gained popularity in the treatment of hepatocellular carcinoma. Although several studies have been published, no bibliometric analysis have been conducted on this topic. Objectives: To understand the development status and future trends in the application of HAIC, we conducted bibliometric analysis to examine the cooperation and influence among countries, institutions, authors, and journals. Methods: All relevant articles and reviews on the use of HAIC in HCC treatment were retrieved from the Web of Science database. A bibliometric analysis of countries, institutions, journals, authors, and keywords related to this field was performed using R and VOSviewer software. The main aspects analyzed were the research status and key fields of HAIC in HCC treatment. Results: A total of 1026 articles published in 292 journals by 4937 authors from 959 institutions between 1974 and 2021 were retrieved. A rapid increase in articles published after 1990 was observed, which reached the peak in 2021. Japan had the most publications and citations. Yonsei University, Sun Yat-sen University, and Hiroshima University were the three leading institutions in research on this topic. Kwang-Hyub Han and Masatoshi Kudo have the greatest academic influence in this field. Most publications were made in the Hepato-Gastroenterology, whereas cancer had the most citations. The main aspects of HAIC treatment of HCC include HAIC and TACE, chemotherapy drug selection, HAIC and targeted therapy and immunotherapy, HAIC and surgery, and hepatotoxicity. Keywords such as FOLFOX, lenvatinib, hepatic arterial infusion chemotherapy are hot words in this field in recent years. Conclusion: The research on the use of HAIC in the treatment of HCC has been on the rise. Currently, HAIC combined with targeted therapy or immunotherapy has attracted significant attention.

Comparative analysis of bile culture and blood culture in patients with malignant biliary obstruction complicated with biliary infection.

OBJECTIVE: This study is aimed to provide a clinical basis for the identification and treatment of patients with malignant biliary obstruction (MBO) complicated with biliary infection by comparing pathogenic bacteria detected in bile and blood cultures from these patients. MATERIALS AND METHODS: A total of 380 patients with MBO who received percutaneous transhepatic cholangic drainage from January 2004 to January 2019 were included in the study. A total of 90 patients were diagnosed with having MBO complicated with biliary infection, and bile and blood culture were simultaneously performed on these patients. The patients included 58 men and 32 women, ranging in age from 33 to 86 years old, with a mean age of 60.69 years. RESULTS: The detection rate using bile bacterial culture in patients with MBO complicated with biliary infection was significantly higher than that using blood culture, and there were significant differences in the two kinds of bacterial culture found positive bile and blood cultures from the same patients. Gram-positive cocci were dominant in the bile cultures and Gram-negative bacilli were dominant in the blood cultures. Therefore, it is necessary to conduct simultaneous bile bacterial culture and blood culture for patients with MBO complicated with biliary infection, especially those with severe or critical diseases. CONCLUSIONS: It is vital to enable simultaneous bile bacterial culture and blood culture in patients with MBO complicated with biliary infection. Existing guidelines for the diagnosis and treatment of benign biliary infection are not applicable to patients with MBO complicated with biliary infection.

[Application of SPR protein chip in screening for imported malaria].

Imported malaria has become a major risk factor for malaria prevention and control in China. How to screen malaria quickly for people entering China is an urgent problem to be solved. Protein microarrays are widely used in high-throughput screening and diagnosis. In this study, surface plasmon resonance (SPR) technique for malaria detection was established by using the specific adsorption surface treated by polyethylene glycol polymer, and the malaria specific antigen HRP2 was used as capture probe. The optimal concentration of antigen, sensitivity and specificity of detection, as well as anti-interference ability of the chip were analyzed. The SPR protein chip was applied to detect specific antibodies of malignant malaria in serum with the advantage of label-free, instant and fast. Compared with fluorescence quantitative PCR, there were no significant difference in sensitivity and specificity between the two methods. This study lays a foundation for further development of protein microarray for malaria typing identification, and it is conducive to the rapid screening of malaria for people entering.

Development of peptide-based chemiluminescence enzyme immunoassay (CLEIA) for diagnosis of dengue virus infection in human.

Dengue is the most prevalent mosquito-borne viral disease in tropical and subtropical regions worldwide. Since its clinical symptoms are non-specific and easily mistaken as other kinds of infection, laboratory diagnosis is required to confirm dengue infections. In this study, ten peptides (E1-E10) from the envelope protein of dengue virus (DENV) were first identified using bioinformatic tool. The screened peptides were then synthesized for the peptide-based chemiluminescence enzyme immunoassay (CLEIA). Two peptides, E1 and E7, were found as the best candidate antigen and therefore used as downstream application in the development of low-cost peptide-based anti-DENV immunoglobulin M antibodies (IgM) indirect CLEIA. 176 serum samples were used to study the presence of anti-DENV IgM antibodies to evaluate the diagnostic ability of IgM-CLEIA. Receiver operating characteristic curve (ROC) was used to estimate the diagnostic cut-off value. The sensitivity and the specificity reached 82.5% and 94.6% respectively when peptide E1 was used, but declined to 79.2% and 92.9% respectively when peptide E7 was used. Therefore, the combination of E1 and E7 was used to improve the sensitivity and the specificity to 85.0% and 96.4% respectively in 1.5 h assay time, providing a potentially practical use for the diagnosis of DENV infections in patients' serum.

Development of SPR biosensor for simultaneous detection of multiplex respiratory viruses.

A surface plasmon resonance (SPR)-based biosensor was developed for specific detection of nine common respiratory virus, including influenza A and influenza B, H1N1, respiratory syncytial virus (RSV), parainfluenza virus 1-3 (PIV1, 2, 3), adenovirus, and severe acute respiratory syndrome coronavirus (SARS). The SPR biosensor was developed by immobilizing nine respiratory virus-specific oligonucleotides in an SPR chip. To increase the biosensor sensitivity, biotin was used to label the PCR primer and further amplify the signal by introducing streptavidin after hybridization. Throat swab specimens representing nine common respiratory viruses were tested by the innovative SPR-based biosensor to evaluate the sensitivity, specificity and reproducibility of this method. Results suggest that this biosensor has the potential to simultaneously identify common respiratory viruses.

Chimeric peptide constructs comprising linear B-cell epitopes: application to the serodiagnosis of infectious diseases.

Linear B-cell epitopes are ideal biomarkers for the serodiagnosis of infectious diseases. However, the long-predicted diagnostic value of epitopes has not been realized. Here, we demonstrated a method, diagnostic epitopes in four steps (DEIFS), that delivers a combination of epitopes for the serodiagnosis of infectious diseases with a high success rate. Using DEIFS for malaria, we identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide constructs. Along with 4 other peptides, we developed a rapid diagnostic test (RDT), which is able to differentiate Plasmodium falciparum (P. falciparum) from Plasmodium vivax (P. vivax) infections with 95.6% overall sensitivity and 99.1% overall specificity. In addition to applications in diagnosis, DEIFS could also be used in the diagnosis of virus and bacterium infections, discovery of vaccine candidates, evaluation of vaccine potency, and study of disease progression.