Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Comprehensive analysis of the significance of METTL7A gene in the prognosis of lung adenocarcinoma.

Background: The most common subtype of lung cancer, called lung adenocarcinoma (LUAD), is also the largest cause of cancer death in the world. The aim of this study was to determine the importance of the METTL7A gene in the prognosis of patients with LUAD. Methods: This particular study used a total of four different LUAD datasets, namely TCGA-LUAD, GSE32863, GSE31210 and GSE13213. Using RT-qPCR, we were able to determine METTL7A expression levels in clinical samples. Univariate and multivariate Cox regression analyses were used to identify factors with independent effects on prognosis in patients with LUAD, and nomograms were designed to predict survival in these patients. Using gene set variation analysis (GSVA), we investigated differences in enriched pathways between METTL7A high and low expression groups. Microenvironmental cell population counter (MCP-counter) and single-sample gene set enrichment analysis (ssGSEA) methods were used to study immune infiltration in LUAD samples. Using the ESTIMATE technique, we were able to determine the immune score, stromal score, and estimated score for each LUAD patient. A competing endogenous RNA network, also known as ceRNA, was established with the help of the Cytoscape program. Results: We detected that METTL7A was down-regulated in pan-cancer, including LUAD. The survival study indicates that METTL7A was a protective factor in the prognosis of LUAD. The univariate and multivariate Cox regression analyses revealed that METTL7A was a robust independent prognostic indicator in survival prediction. Through the use of GSVA, several immune-related pathways were shown to be enriched in both the high-expression and low-expression groups of METTL7A. Analysis of the tumor microenvironment revealed that the immune microenvironment of the group with low expression was suppressed, which may be connected to the poor prognosis. To explore the ceRNA regulatory mechanism of METTL7A, we finally constructed a regulatory network containing 1 mRNA, 2 miRNAs, and 5 long non-coding RNAs (lncRNAs). Conclusion: In conclusion, we presented METTL7A as a potential and promising prognostic indicator of LUAD. This biomarker has the potential to offer us with a comprehensive perspective of the prediction of prognosis and treatment for LUAD patients.

[Effects of Roxithromycin on Reproduction,Growth, and Anti-oxidation System of Daphnia magna].

Roxithromycin (ROX) is widespread in the water environment and has been reported to have ecotoxicological effects on aquatic organisms. To improve our understanding of these effects, we selected Daphnia magna as a test organism to study acute and chronic ROX toxicity on reproduction, growth, and antioxidant systems. The acute ROX toxicity was low, with 48 h-LC50 and 96h-LC50ROX values of 60.26 mg·L-1 and 39.81 mg·L-1, respectively. Furthermore, ROX concentrations of 0.5 µg·L-1 and 50 µg·L-1 significantly increased the frequency of egg laying, total number of eggs, and number of eggs per fetus. In the early exposure stages, ROX altered the sexual maturation time of Daphnia magna, affecting the frequency of egg laying and the number of eggs per fetus to cope with environmental stress. The intrinsic growth rate was also significantly increased by 50 µg·L-1 ROX. In both treatment groups, Daphnia magna had a shorter body length, abnormal heart rate, and inhibited swimming activity. Moreover, 50 µg·L-1 ROX inhibited the activities of POD, CAT, and GSH-Px by approximately 50% and induced MDA by more than 100%, resulting in the accumulation of reactive oxygen species in the body, which could potentially damage the cell membrane. In the 50 µg·L-1 ROX treatment, per 06 was up-regulated, enhancing the immune response of Daphnia magna. In contrast. gst and gst-theta were down-regulated, suggesting that ROX could weaken the detoxification effect of Daphnia magna. jhe, ecra, ecrb, rxr, vg1, vg2, and vit-2 were also down-regulated. ROX affected the secretion of juvenile and thyroid hormones, inhibiting the synthesis of vitellogenin. Finally, ROX also affected the growth and disturbed the population stability of Daphnia magna. This study provides a reference for the effects of ROX on the reproduction and growth of aquatic organisms and their responses at protein and gene levels.

Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Cerebral Venous Thrombosis : A Meta-Analysis.

OBJECTIVE: A role of diffusion-weighted imaging (DWI) in the diagnosis of cerebral venous thrombosis (CVT) is not wellunderstood. This study evaluates the effectiveness of DWI in the diagnosis of CVT. METHODS: Literature search was conducted in electronic databases for the identification of studies which reported the outcomes of patients subjected to DWI for CVT diagnosis. Random-effects meta-analyses were performed to achieve overall estimates of important diagnostic efficiency indices including hyperintense signal rate, the sensitivity and specificity of DWI in diagnosing CVT, and the apparent diffusion coefficient (ADC) of DWI signal areas and surrounding tissue. RESULTS: Nineteen studies (443 patients with 856 CVTs; age 40 years [95% confidence interval (CI), 33 to 43]; 28% males [95% CI, 18 to 38]; symptom onset to DWI time 4.6 days [95% CI, 2.3 to 6.9]) were included. Hyperintense signals on DWI were detected in 40% (95% CI, 26 to 55) of the cases. The sensitivity of DWI for detecting CVT was 22% (95% CI, 11 to 34) but specificity was 98% (95% CI, 95 to 100). ADC values were quite heterogenous in DWI signal areas. However, generally the ADC values were lower in DWI signal areas than in surrounding normal areas (mean difference-0.33×10-3 mm2/s [95% CI, -0.44 to -0.23]; p<0.00001). CONCLUSION: DWI has a low sensitivity in detecting CVT and thus has a high risk of missing many CVT cases. However, because of its high specificity, it may have supporting and exploratory roles in CVT diagnosis.

[SSR linkage map construction and QTL mapping for leaf area in maize].

Maize (Zea mays L.) leaf is the main organ for photosynthesis. The area of leaves (especially the ear-leaf and the two leaves above and below the ear-leaf) plays a vital role in dry matter accumulation and grain yield. Therefore, genetic information on leaf area has a theoretical significance for breeding maize with high yield. In this study, a genetic linkage map composing of 184 simple sequence repeat (SSR) markers was constructed based on an F8 recombinant inbred line (RIL) population, which was derived from a cross between 478 and W312. The parents showed a significant difference in leaf area. The map covers 2084.1 cM with an average interval of 11.3 cM. QTLs for leaf area were identified under two-year's field experiments. Totally 7 QTLs were detected in two years, among which 4 QTLs were detected in 2006 and 3 QTLs in 2007. A major QTL on chromosome 2 (between umc1542 and umc1518) were detected in both 2006 and 2007. It explains 12.5% and 17.3% of the phenotypic variation, respectively. This locus can be used as a potental marker for improving maize leaf growth through marker assisted selection (MAS) approach.

[Occurrence and Ecological Risk of Eight Typical PhACs in Surface Water and Its Impact on Daphnia magna].

The occurrence and risk assessment of eight typical pharmaceutical active compounds (PhACs) in a receiving water body of wastewater treatment plant effluent were investigated. The results showed that the total concentrations of eight PhACs in summer and winter ranged from 27.6 to 226.4 ng·L-1 and 56.6 to 368.8 ng·L-1, respectively. The concentration of caffeine (16.2-125.8 ng·L-1) was highest, followed by roxithromycin (3.3-89.2 ng·L-1) and ibuprofen (3.6-59.2 ng·L-1). The total ecological risks (mixture risk quotients, MRQ) of eight PhACs to green algae, daphnia, and fish were 1.51, 0.08, and 5.68 in summer and 8.34, 0.22, and 6.45 in winter, respectively. The contribution rates of ketoconazole, erythromycin, and ibuprofen exceeded 49%, 85%, and 92% for MRQ in green algae, daphnia, and fish, respectively. In terms of sensitive species, green algae and fish are the most sensitive to PhACs in winter and summer, respectively. The results of 21 d chronic toxicity showed that mixed PhACs effect normal development and reproduction of Daphnia magna, resulting in an increase in reproductive capacity and swimming activity, and a reduction in heart rate and thoracic limb activity.

Medical cost and healthcare utilization of amyotrophic lateral sclerosis in China: A cohort study based on hospital data from 2015 to 2018.

Amyotrophic lateral sclerosis (ALS), a specific neurodegenerative disease, imposed increased economic and utilizations burden on the healthcare system, especially with the progress of the diseases severity. However, the economic burden on Chinese ALS patients remained unclear. This study therefore was aimed to investigate medical cost and healthcare utilization for Chinese ALS patients.Longitudinal health data of over 20 million individuals, including military personnel and civilians, was collected from all Chinese military hospitals. We identified 480 patients with a first major diagnosis for ALS from 2015 to 2018, while matched 400 controlled patients on age, gender, ethnic group, geographic region, length of stay, year of diagnosis and comorbidity. Their medical cost and healthcare utilizations were then measured 1 year before, and 1 year after ALS diagnosis.The median annual medical cost of ALS patients was about 2-fold higher, 17,087 CNY during the index year than 1 year before, 7859 CNY. The highest increase in utilizations may account for medical costs on ALS patients, which was represented by hospitalizations (Odd Ratio (OR) = 4.26, 95% confidence interval (CI) 3.52, 5.15), electromyography (OR = 4.14, 95% CI 2.37, 7.22), nerve conduction velocity (OR = 3.26, 95% CI 2.23, 4.77).This study is the first one reporting direct economic burden on Chinese ALS patients. Efforts should be made to develop cost-effective diagnostic tools in order that sources of medical cost were more effectively allocated, and this disease was detected earlier.

Total synthesis of scutellarin and apigenin 7-O-ß-d-glucuronide.

A general protocol for direct glucuronic linkages formation featuring Au(I)-catalyzed appropriately protected glucuronyl o-alkynylbenzoate-involved glycosylation reaction, as well as a concise approach for easy access of scutellarein prominent for the mild and efficient hydroxyl group installation via borylation-oxidation sequence from flavanone derivative, has been established, based on which a novel route for scutellarin derivatives preparation has been devised. The developed strategies, among which the stepwise deprotection process was also included, guarantee the high whole synthetic efficiency, and definitely will find broad application in diversity-oriented synthesis of bioactive flavonoid glycosides.

[Distribution and Environmental Risk of Pharmaceutically Active Compounds in the Traditionally Aqueous Phase of Effluent-receiving Rivers].

Colloid media are not only an important "sink" for pollutants in the aquatic environment, but also a crucial regulating unit for the biogeochemical cycle of pollutants. In this study, the distribution and environmental risk levels of ten typical pharmaceutically active compounds (PhACs) in the water phase of effluent-receiving rivers were investigated using cross-flow ultrafiltration, solid-phase extraction, and liquid chromatography-tandem mass spectrometry as the pretreatment and analysis methods. The results showed that the total concentrations of the ten PhACs in the dissolved phase and colloidal phase ranged from 27.2 to 168.1 ng·L-1 and 164.5 to 751.1 ng·g-1, respectively. Ibuprofen (IPF), roxithromycin (ROX), and erythromycin (ETM) are the dominating pollutants in the dissolved phase and colloidal phase, accounting for more than 80% of the total concentration. Strong adsorption properties for ROX, ketoconazole, ETM, and sertraline were found in the colloid phase, their colloid/water distribution coefficients (lgKcol) ranged from 3.2 to 4.0, and the percentage of PhACs absorbed to the colloidal phase reached 21.1%-34.5%. The risk assessment of acute and chronic toxicity to algae, daphnia, and fish showed that only IPF presented a high chronic risk to fish, while the risk levels of the other PhACs were at or below medium risk. It is worth noting that, in comparison with their acute risk, most PhACs have chronic negative effects on higher aquatic organisms.

Synthesis and in vitro antiproliferative evaluation of pyrimido[5,4-c]quinoline-4-(3H)-one derivatives.

A series of pyrimido[5,4-c]quinoline-4-(3H)-one derivatives variously substituted at positions 2 and 3 were synthesized and evaluated for their in vitro antiproliferative activities against a panel of six human cancer cell lines. Biological evaluation revealed that the vast majority of derivatives exhibited moderate tumor growth inhibitory activities. In particular, compound 7e showed effective anti-tumor activity with broad-spectrum toward numerous cell lines and the most active member in this study. This derivative displaying significant activity against KB (IC(50): 4.9 µM), CNE2 (IC(50): 13.8 µM), MGC-803 (IC(50): 4.8 µM), GLC-82 (IC(50): 7.88 µM), MDA-MB-453 (IC(50): 18.2 µM) and MCF-7 (IC(50): 10.1 µM) cell lines could be considered as the most promising and useful template for future development to obtain more potent anti-tumor agent(s).