RT-SRTS: Angle-agnostic real-time simultaneous 3D reconstruction and tumor segmentation from single X-ray projection.

Radiotherapy is one of the primary treatment methods for tumors, but the organ movement caused by respiration limits its accuracy. Recently, 3D imaging from a single X-ray projection has received extensive attention as a promising approach to address this issue. However, current methods can only reconstruct 3D images without directly locating the tumor and are only validated for fixed-angle imaging, which fails to fully meet the requirements of motion control in radiotherapy. In this study, a novel imaging method RT-SRTS is proposed which integrates 3D imaging and tumor segmentation into one network based on multi-task learning (MTL) and achieves real-time simultaneous 3D reconstruction and tumor segmentation from a single X-ray projection at any angle. Furthermore, the attention enhanced calibrator (AEC) and uncertain-region elaboration (URE) modules have been proposed to aid feature extraction and improve segmentation accuracy. The proposed method was evaluated on fifteen patient cases and compared with three state-of-the-art methods. It not only delivers superior 3D reconstruction but also demonstrates commendable tumor segmentation results. Simultaneous reconstruction and segmentation can be completed in approximately 70 ms, significantly faster than the required time threshold for real-time tumor tracking. The efficacies of both AEC and URE have also been validated in ablation studies. The code of work is available at https://github.com/ZywooSimple/RT-SRTS.

Co-infusion of CAR T cells with aAPCs expressing chemokines and costimulatory ligands enhances the anti-tumor efficacy in mice.

Chimeric antigen receptor-modified T (CAR-T) cell therapy has shown curable efficacy for treating hematological malignancies, while in solid tumors, the immunosuppressive microenvironment causes poor activation, expansion and survival of CAR-T cells, accounting mainly for the unsatisfactory efficacy. The artificial antigen-presenting cells (aAPCs) have been used for ex vivo expansion and manufacturing of CAR-T cells. Here, we constructed a K562 cell-based aAPCs expressing human epithelial cell adhesion molecule (EpCAM), chemokines (CCL19 and CCL21) and co-stimulatory molecular ligands (CD80 and 4-1BBL). Our data demonstrated that the novel aAPCs enhanced the expansion, and increased the immune memory phenotype and cytotoxicity of CAR-T cells recognizing EpCAM, in vitro. Of note, co-infusion CAR-T and aAPC enhances the infiltration of CAR-T cells in solid tumors, which has certain potential for the treatment of solid tumors Moreover, IL-2-9-21, a cytokine cocktail, prevents CAR-T cells from entering the state of exhaustion prematurely after continuous antigen engagement and boosts the anti-tumor activity of CAR-T cells co-infused with aAPCs. These data provide a new strategy to enhance the therapeutic potential of CAR-T cell therapy for the treatment of solid tumors.

[Efficient production of L-asparaginase in Bacillus licheniformis by optimizing expression elements and host].

L-asparaginase (L-ASN) is widely applied in the treatment of malignant tumor and low-acrylamide food production, however, the low expression level hampers its application. Heterologous expression is an effective strategy to increase the expression level of target enzymes, and Bacillus is generally used as the host for efficient production of enzymes. In this study, the expression level of L-asparaginase in Bacillus was enhanced through optimization of expression element and host. Firstly, five signal peptides (SPSacC, SPAmyL, SPAprE, SPYwbN and SPWapA) were screened, among which SPSacC showed the best performance, reaching an activity of 157.61 U/mL. Subsequently, four strong promoters (P43, PykzA-P43, PUbay and PbacA) from Bacillus were screened, and tandem promoter PykzA-P43 showed the highest yield of L-asparaginase, which was 52.94% higher than that of control strain. Finally, three Bacillus expression hosts (B. licheniformis Δ0F3 and BL10, B. subtilis WB800) were investigated, and the maximum L-asparaginase activity, 438.3 U/mL, was reached by B. licheniformis BL10, which was an 81.83% increase compared with that of the control. This is also the highest level of L-asparaginase in shake flask reported to date. Taken together, this study constructed a B. licheniformis strain BL10/PykzA-P43-SPSacC-ansZ capable of efficiently producing L-asparaginase, which laid the foundation for industrial production of L-asparaginase.

Injectable and photocurable CAR-T cell formulation enhances the anti-tumor activity to melanoma in mice.

The chimeric antigen receptor-T cells (CAR-T) therapy, as a novel personalized immunotherapy, has shown prominent clinical efficacy in the treatment of B-cell malignancies. However, the progress in solid tumors was hindered by multiple elements in the tumor immunosuppressive microenvironment. In this study, an injectable and photocurable Gelatin Methacryloyl (GelMA) hydrogel was applied to be a depot of CAR-T cells, thus forming an injectable CAR-T Gelatin Methacryloyl hydrogels Delivery (i-GMD) system. According to our results, CAR-T cells in this system could be normally amplified, sustained released, and play an anti-tumor role in vitro. When compared with local or intravenously injection of CAR-T solution, injection of i-GMD matrix around tumor demonstrated enhanced anti-tumor effect and markedly extended survival of mice. Our research outcomes indicated that this therapeutic strategy might hopefully provide a treatment for patients with unresectable tumors.

Cost-effectiveness of enfortumab vedotin in previously treated advanced urothelial carcinoma.

BACKGROUND: Antibody-drug conjugates have recently been introduced as a treatment for advanced urothelial carcinoma. The EV-301 study demonstrated that enfortumab vedotin (EV) improved overall survival compared with conventional chemotherapy. To assess the cost-effectiveness of EV for the treatment of advanced urothelial carcinoma (UC) from a payer perspective in middle- and high-income countries. METHODS: A decision analysis model was developed to assess the efficacy and economic viability of EV as a subsequent-line treatment following disease progression in patients with advanced urothelial carcinoma already treated with PD-1 or PD-L1 inhibitors. Clinical and utility values were obtained from the published literature and available databases. Cost data were obtained from payer perspectives in the United States, United Kingdom, and China. Quality-adjusted life-years (QALYs) were used to measure health outcomes, and incremental cost-effectiveness ratios (ICERs) used to evaluate cost-effectiveness in comparison to willingness-to-pay in the United States, United Kingdom, and China. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. RESULTS: Compared with chemotherapy, EV increased the benefit by 0.16-0.17 QALYs, resulting in ICERs of $2,168,746.71, $2,164,494.38, and $1,775,576.56 per QALY in the United States, United Kingdom, and China, respectively. One-way sensitivity analysis indicated that the largest effect on outcome was the utility value for progression-free survival. Probabilistic sensitivity analysis demonstrated that the probability of EV being cost-effective was 0%. CONCLUSIONS: EV provides an additional health benefit over chemotherapy for patients with advanced urothelial carcinoma but is not cost-effective from a payer perspective in the United States, United Kingdom, or China.

Biosynthesis and Genetic Incorporation of 3,4-Dihydroxy-L-Phenylalanine into Proteins in Escherichia coli.

While 20 canonical amino acids are used by most organisms for protein synthesis, the creation of cells that can use noncanonical amino acids (ncAAs) as additional protein building blocks holds great promise for preparing novel medicines and for studying complex questions in biological systems. However, only a small number of biosynthetic pathways for ncAAs have been reported to date, greatly restricting our ability to generate cells with ncAA building blocks. In this study, we report the creation of a completely autonomous bacterium that utilizes 3,4-dihydroxy-L-phenylalanine (DOPA) as its 21st amino acid building block. Like canonical amino acids, DOPA can be biosynthesized without exogenous addition and can be genetically incorporated into proteins in a site-specific manner. Equally important, the protein production yields of DOPA-containing proteins from these autonomous cells are greater than those from cells exogenously fed with 9 mM DOPA. The unique catechol moiety of DOPA can be used as a versatile handle for site-specific protein functionalizations via either oxidative coupling or strain-promoted oxidation-controlled cyclooctyne-1,2-quinone (SPOCQ) cycloaddition reactions. We further demonstrate the use of these autonomous cells in preparing fluorophore-labeled anti-human epidermal growth factor 2 (HER2) antibodies for the detection of HER2 expression on cancer cells.

Comprehensive analysis of EMT-related genes and lncRNAs in the prognosis, immunity, and drug treatment of colorectal cancer.

BACKGROUND: EMT is an important biological process in the mechanism of tumor invasion and metastasis. However, there are still many unknowns about the specific mechanism of EMT in tumor. At present, a comprehensive analysis of EMT-related genes in colorectal cancer (CRC) is still lacking. METHODS: All the data were downloaded from public databases including TCGA database (488 tumor samples and 52 normal samples) as the training set and the GEO database (GSE40967 including 566 tumor samples and 19 normal samples, GSE12945 including 62 tumor samples, GSE17536 including 177 tumor samples, GSE17537 including 55 tumor samples) as the validation sets. One hundred and sixty-six EMT-related genes (EMT-RDGs) were selected from the Molecular Signatures Database. Bioinformatics methods were used to analyze the correlation between EMT-RDGs and CRC prognosis, metastasis, drug efficacy, and immunity. RESULTS: We finally obtained nine prognostic-related EMT-RDGs (FGF8, NOG, PHLDB2, SIX2, SNAI1, TBX5, TIAM1, TWIST1, TCF15) through differential expression analysis, Unicox and Lasso regression analysis, and then constructed a risk prognosis model. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high-risk and low-risk groups and the different states of the nine prognostic-related EMT-RDGs. The methylation level and mutation status of nine prognostic-related EMT-RDGs all affect their regulation of EMT. The Cox proportional hazards regression model was also constructed by the methylation sites of nine prognostic-related EMT-RDGs. In addition, the expression of FGF8, PHLDB2, SIX2, and SNAIL was higher and the expression level of NOG and TWIST1 was lower in the non-metastasis CRC group. Nine prognostic-related EMT-RDGs also affected the drug treatment response of CRC. CONCLUSIONS: Targeting these nine prognostic-related EMT-RDGs can regulate CRC metastasis and immune, which is beneficial for the prognosis of CRC patients, improve drug sensitivity in CRC patients.

A Nomogram for the Determination of the Necessity of Concurrent Chemotherapy in Patients With Stage II-IVa Nasopharyngeal Carcinoma.

BACKGROUND: The efficiency of concurrent chemotherapy (CC) remains controversial for stage II-IVa nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT). Therefore, we aimed to propose a nomogram to identify patients who would benefit from CC. METHODS: A total of 434 NPC patients (stage II-IVa) treated with IC followed by IMRT between January 2010 and December 2015 were included. There were 808 dosimetric parameters extracted by the in-house script for each patient. A dosimetric signature was developed with the least absolute shrinkage and selection operator algorithm. A nomogram was built by incorporating clinical factors and dosimetric signature using Cox regression to predict recurrence-free survival (RFS). The C-index was used to evaluate the performance of the nomogram. The patients were stratified into low- and high-risk recurrence according to the optimal cutoff of risk score. RESULTS: The nomogram incorporating age, TNM stage, and dosimetric signature yielded a C-index of 0.719 (95% confidence interval, 0.658-0.78). In the low-risk group, CC was associated with a 9.4% increase of 5-year locoregional RFS and an 8.8% increase of 5-year overall survival (OS), whereas it was not significantly associated with an improvement of locoregional RFS (LRFS) and OS in the high-risk group. However, in the high-risk group, patients could benefit from adjuvant chemotherapy (AC) by improving 33.6% of the 5-year LRFS. CONCLUSIONS: The nomogram performed an individualized risk quantification of RFS in patients with stage II-IVa NPC treated with IC followed by IMRT. Patients with low risk could benefit from CC, whereas patients with high risk may require additional AC.

The role of non-apoptotic cell death in the treatment and drug-resistance of digestive tumors.

Tumor cell apoptosis evasion is one of the main reasons for easy metastasis occurrence, chemotherapy resistance, and the low five-year survival rate of digestive system tumors. Current research has shown that non-apoptotic cell death plays an important role in tumors of the digestive system. Therefore, increasing the proportion of non-apoptotic tumor cells is one of the effective methods of improving therapeutic efficacies for digestive system tumors. Non-apoptotic cell death modes mainly include autophagic cell death, pyroptosis, ferroptosis, in addition to other cell death modes. This review covers a systematic review relating to the research progress made into autophagic cell death, pyroptosis, ferroptosis, and other cell death modes in the treatment of digestive system tumors. It also highlights how treatment is a reasonable prospect based on clinical experience and provides reliable guidance for the further development of digestive system tumor treatments.

Coordination Polymer Glasses with Lava and Healing Ability for High-Performance Gas Sieving.

Coordination polymer (CP) glasses offer a way to tackle the fabrication challenges encountered by inorganic porous membranes and show great potentials for size-exclusive gas separation. However, their processability and performance still cannot simultaneously meet the requirements for high-performance membrane separation. Herein, we have developed a series of CP glasses (M-P-dmbIm, M=Zn, Cd, Cu, and Mn), which possess low vitrification temperature as well as low viscosity (η) and lave capability above the transition temperatures. The derived glass (ag M-P-dmbIm) membranes show outstanding performances for H2 /CO2 , H2 /N2 , and H2 /CH4 separation, which all far surpass the Robeson upper bound and even rival against the best of the state-of-the-art gas separation membranes. The low viscosities not only allow us to hot-cast or hot-press the CP glasses into thin membranes within 5 min without sacrificing their selectivity and permeability, but also endow the resulted glass membranes with healing ability.

The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer.

Cellular autophagy plays an important role in the occurrence and development of colorectal cancer (CRC). Whether autophagy-related genes and lncRNAs can be used as ideal markers in CRC is still controversial. The purpose of this study is to identify novel treatment and prognosis markers of CRC. We downloaded transcription and clinical data of CRC from the GEO (GSE40967, GSE12954, GSE17536) and TCGA database, screened for differentially autophagy-related genes (DEAGs) and lncRNAs, constructed prognostic model, and analyzed its relationship with immune infiltration. TCGA and GEO datasets (GSE12954 and GSE17536) were used to validate the effect of the model. Oncomine database and Human Protein Atlas verified the expression of DEAGs. We obtained a total of 151 DEAGs in three verification sets collaboratively. Then we constructed a risk prognostic model through Lasso regression to obtain 15 prognostic DEAGs from the training set and verified the risk prognostic model in three verification sets. The low-risk group survived longer than the high-risk group. Age, gender, pathological stage, and TNM stage were related to the prognostic risk of CRC. On the other hand, BRAF status, RFS event, and tumor location are considered as most significant risk factors of CRC in the training set. Furthermore, we found that the immune score of the low-risk group was higher. The content of CD8 + T cells, active NK cells, macrophages M0, macrophages M1, and active dendritic cells was noted more in the high-risk group. The content of plasma cells, resting memory CD4 + T cells, resting NK cells, resting mast cells, and neutrophil cells was higher in the low-risk group. After all, the Oncomine database and immunohistochemistry verified that the expression level of most key autophagy-related genes was consistent with the results that we found. In addition, we obtained six lncRNAs co-expressed with DEAGs from the training set and found that the survival time was longer in the low-risk group. This finding was verified in the verification set and showed same trend to the results mentioned above. In the final analysis, these results indicate that autophagy-related genes and lncRNAs can be used as prognostic and therapeutic markers for CRC.

Effect of forkhead box O1 in renal tubular epithelial cells on endotoxin-induced acute kidney injury.

Mitochondrial damage in renal tubular epithelial cells (RTECs) is a hallmark of endotoxin-induced acute kidney injury (AKI). Forkhead box O1 (FOXO1) is responsible for regulating mitochondrial function and is involved in several kidney diseases. Here, we investigated the effect of FOXO1 on endotoxin-induced AKI and the related mechanism. In vivo, FOXO1 downregulation in mouse RTECs and mitochondrial damage were found in endotoxin-induced AKI. Overexpression of FOXO1 by kidney focal adeno-associated virus (AAV) delivery improved renal function and reduced mitochondrial damage. Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1-α), a master regulator of mitochondrial biogenesis and function, was reduced in endotoxin-induced AKI, but the reduction was reversed by FOXO1 overexpression. In vitro, exposure to LPS led to a decline in HK-2 cell viability, mitochondrial fragmentation, and mitochondrial superoxide accumulation, as well as downregulation of FOXO1, PGC1-α, and mitochondrial complex I/V. Moreover, overexpression of FOXO1 in HK-2 cells increased HK-2 cell viability and PGC1-α expression, and it alleviated the mitochondrial injury and superoxide accumulation induced by LPS. Meanwhile, inhibition of FOXO1 in HK-2 cells by siRNA treatment decreased PGC1-α expression and HK-2 cell viability. Chromatin immunoprecipitation assays and PCR analysis confirmed that FOXO1 bound to the PGC1-α promoter in HK-2 cells. In conclusion, downregulation of FOXO1 in RTECs mediated endotoxin-induced AKI and mitochondrial damage. Overexpression of FOXO1 could improve renal injury and mitochondrial dysfunction, and this effect occurred at least in part as a result of PGC1-α signaling. FOXO1 might be a potential target for the prevention and treatment of endotoxin-induced AKI.

Cost-effectiveness of Capecitabine + Irinotecan Versus Leucovorin + Fluorouracil + Irinotecan in the Second-line Treatment of Metastatic Colorectal Cancer in China.

PURPOSE: The AXEPT trial demonstrated that modified XELIRI (mXELIRI; capecitabine + irinotecan) was noninferior to standard treatment with FOLFIRI (fluorouracil + leucovorin + irinotecan), both ± bevacizumab, in the treatment of metastatic colorectal cancer (mCRC). The present study was designed to evaluate the cost-effectiveness of mXELIRI versus FOLFIRI as a second-line treatment of mCRC. METHODS: We developed a Markov model to estimate the costs and health outcomes of mXELIRI and FOLFIRI in patients with mCRC from the Chinese payer perspective. Survival data, transition probabilities, and health utility values were obtained from published studies. The costs of drugs were obtained from the West China Hospital. Life-years (LYs), quality-adjusted life-years (QALYs) gained, incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER) values were regarded as the primary end points. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the impact of uncertainty of parameters in the analysis. FINDINGS: The effectiveness was found to be 0.48 QALYs (1.14 LYs) in the mXELIRI arm and 0.41 QALYs (1.05 LYs) in the FOLFIRI arm, with total costs of 29,896.41 US dollars (USD) in the mXELIRI arm and 28,894.68 USD in the FOLFIRI arm. The ICER and ICUR with mXELIRI versus FOLFIRI were 11,130.33 USD/LY and 14,310.43 USD/QALY gained, which were less than the willingness-to-pay threshold in China (25,840.88 USD/QALY). IMPLICATIONS: Based on the results of this study, mXELIRI was found to be a cost-effective alternative to FOLFIRI as a second-line treatment of mCRC in patients in China.

Cost-Effectiveness of Tucatinib in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer From the US and Chinese Perspectives.

Background: The clinical evaluation of HER2CLIMB trial showed a 21. 9-month median overall survival with the triplet regimens of tucatinib, capecitabine, and trastuzumab (TXT) for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. From the payer's perspective of the United States and China, a cost-effectiveness analysis was conducted to evaluate the costs and benefits of adding tucatinib in this study. Methods: We constructed a Markov model for the economic evaluation of adding tucatinib to trastuzumab plus capecitabine in patients with HER-2 positive metastatic breast cancer in the United States and China. The model was conducted with a 10-year time horizon, and the health status was divided into three states: progression-free survival, progressing disease, and death. The health utility scores were consistent with published literature with similar patient status. The transition probabilities were derived from the survival data of the HER2CLIMB study. The unit prices of medicines were obtained from the West China Hospital, Red Book, and published literature. Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. Results: Compared with the two-drug regimen of trastuzumab plus capecitabine (TX), the addition of tucatinib increased 0.21 QALY, with an increasing cost of $146,995.05 and $19,022.97 in the United States and China, respectively. The incremental cost-effectiveness ratios (ICERs) for the TXT versus TX was $699,976.43 in the U.S. and $90,585.57 in China, both of which are higher than their respective threshold of willingness to play. Deterministic sensitivity analysis shows that the price of tucatinib is the parameter that has the most significant impact on ICERs, but it does not change the results of the model. Probability sensitivity analysis shows that the probability of cost-effective for TXT is 0 in the base case. Conclusion: In the United States and China, tucatinib combined with trastuzumab and capecitabine is not cost-effective for patients with HER-2 positive metastatic breast cancer.

Pembrolizumab alone or with chemotherapy for squamous cell carcinoma of the head and neck: A cost-effectiveness analysis from Chinese perspective.

OBJECTIVES: The KEYNOTE-048 trial indicated pembrolizumab plus chemotherapy is an appropriate first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), while pembrolizumab monotherapy is optimal for PD-L1 positive patient. This study was powered to determine the most cost-effective strategy for patient with different combined positive score (CPS). MATERIALS AND METHODS: A Markov model was developed to predict progression-free survival, disease progression, or death in patients with recurrent or metastatic HNSCC based on data from the KEYNOTE-048 trial. Cost was obtained from West China Hospital, while utilities were referred to published studies. By using Monte Carlo simulations, acceptability curves were depicted to address the uncertainty of model inputs. RESULTS: Compared with cetuximab plus chemotherapy, pembrolizumab monotherapy resulted in an incremental cost-effectiveness ratio (ICER) of $14,995 per quality adjusted life year (QALY) in total population and $22,779 per QALY in patients with CPS ≥ 1. Comparing pembrolizumab plus chemotherapy with standard therapy led to an ICER of $43,230 per QALY in total population and $26,157 per QALY in patients with CPS ≥ 1. For patients with CPS ≥ 20, ICERs yield by immunotherapy with or without chemotherapy exceeded the threshold of willingness to pay we set, when compared with standard therapy. Pembrolizumab plus chemotherapy was dominated by pembrolizumab alone in this patient population. CONCLUSION: For HNSCC patients with different CPS, pembrolizumab alone was the optimal choice for total population and patients with CPS ≥ 1. Among patients with high CPS, immunotherapy with or without chemotherapy was not preferred over the standard therapy.

Cost-Effectiveness Analysis of Bevacizumab plus Paclitaxel versus Bevacizumab plus Capecitabine for HER2-Negative Locally Recurrent or Metastatic Breast Cancer.

BACKGROUND: The aim of the current study was to estimate two protocols for HER2-negative locally recurrent or metastatic breast cancer patients, bevacizumab combined with paclitaxel versus bevacizumab combined with capecitabine, from the economic view. METHODS: The process of HER2-negative locally recurrent or metastatic breast cancer treated with bevacizumab combined with paclitaxel or bevaciz-umab combined with capecitabine made up the decision model in our analysis. The primary objective was to show the incremental cost-effectiveness ratio (ICER). The critical parameters and the robustness of the model on the results of the analysis were assessed by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS: In the analysis, quality-adjusted life year (QALY) increased by 0.4 with bevacizumab plus paclitaxel compared with bevacizumab plus capecitabine, and incremental cost of USD 4,340.46. Therefore, the ICER was USD 27,252.875. The ICER exceeded the commonly accepted willingness to pay on the recommendation of the World Health Organization, which is defined as 3 times of the gross domestic product per capita of China in the model (USD 25,840.88 per QALY). On univariate analysis, it is found that the most significant affecting factor is the cost of progression-free survival state in the bevacizumab plus paclitaxel group. Besides, bevacizumab plus paclitaxel had a 47.8% probability of being cost-effective versus bevacizu-mab plus capecitabine according to probabilistic sensitivity analysis. CONCLUSIONS: Based on the results of the analysis, bevacizumab plus paclitaxel is unlikely to be a cost-effective option for patients with HER2-negative locally recurrent or metastatic breast cancer compared with bevacizumab plus capecitabine.

Efficient removal of formaldehyde by polyethyleneimine modified activated carbon in a fixed bed.

Polyethyleneimine modified activated carbon (PEI-AC) was prepared through a treatment of immersion, and used for the adsorption of formaldehyde. The adsorption capacity of formaldehyde by unmodified AC is 190.1 mg g-1, and the adsorption capacity of formaldehyde can reach to 317.6 mg g-1 after 10 g L-1 of PEI modified, being about 1.67 times than unmodified activated carbon (AC: 191.2 mg g-1). And the 10 g L-1 of PEI modified AC (PAC-30) has the highest adsorption capacity of formaldehyde, reached to 650 mg g-1, with an increasing magnitude of 240% in comparison with that without modified AC. This is mainly due to changes in the pore structure and surface functional groups after modification. However, as the PEI concentration increases, the adsorption performance is inhibited. Through kinetic studies, it was found that all adsorption curves follow the second-order kinetics, and the breakthrough curves follow the Boltzmann model, and the adsorption process can also be described by the intraparticle diffusion model.

Remarkable Response of Metastatic Gallbladder Carcinoma to Apatinib After Failed Multiline Chemotherapies: A Case Report and Literature Review.

Gallbladder carcinoma (GBC) is a relatively rare and aggressive malignant tumor with a poor prognosis. A systematic review of current clinical studies illustrates an extreme paucity of second-line therapeutic options following the failure of standard-of-care cisplatin-gemcitabine chemotherapy. The efficacy of apatinib, an highly potent and selective oral inhibitor of VEGFR-2 tyrosine kinase, for refractory advanced GBC has not yet been clarified. Herein, we report a case of advanced GBC that presented a durable partial response to apatinib used as monotherapy after the failure of multiline chemotherapies including S-1 monotherapy, capecitabine monotherapy, gemcitabine plus capecitabine, and irinotecan plus oxaliplatin. The patient achieved an efficacy of partial response within 2 months. By September 23, 2019, the duration of treatment had extended for almost 1 year with a satisfactory quality of life, and the administration of apatinib was continued. Dose reduction of apatinib occurred at week four due to grade 2 hypertension and hand-foot skin reaction (HFSR). No fatigue, proteinuria, mucositis, or thrombocytopenia occurred. To the best of our knowledge, this is the first case of a successful use of apatinib monotherapy for heavily pretreated GBC. Further prospective studies are warranted to confirm the efficacy and safety of apatinib in GBC.

Adjuvant Chemoradiotherapy for Gastric Cancer: Efficacy and Cost-Effectiveness Analysis.

Purpose: The benefit of adjuvant chemotherapy (CT) for localized gastric cancer (GC) after D2-gastrectomy has been clearly demonstrated. However, adjuvant chemoradiotherapy (CRT) remains controversial. This study aimed to assess the efficacy and cost-effectiveness of treatment for GC after D2-gastrectomy. Materials and methods: Stage IB-IIICGC patients who had received adjuvant CRT or CT, or who had just been observed after D2-gastrectomy were retrospectively selected. Therapeutic strategy after surgery, disease-free survival (DFS), overall survival (OS), adverse events and costs were recorded retrospectively. A Markov model was developed to simulate the process of GC after D2-gastrectomy. Health outcomes were measured using quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was regarded as the primary outcome. Results: A total of 254 patients were selected. Three year OS and DFS were 83.02 and 64.15% in the adjuvant CRT group, 74.19 and 63.54% in the adjuvant CT group, and 45.45 and 43.35% in the observation group. Total grade 3 or 4 toxicity was higher in the CRT group than in the CT group (54.72% vs. 37.10%, p < 0.05). The ICER of the CT and CRT groups vs. the observation group were $10,571.55 and $11,467.41/QALY, respectively. The probability of CT, CRT and observation being cost-effective were 28.9, 37.9, and 33.2%, respectively, when a willingness-to-pay threshold (WTP) of $25,648.45/QALY was used. Conclusions: Adjuvant CRT was associated with improved OS and DFS compared with adjuvant CT and postoperative observation. Both adjuvant CRT and CT are likely to be cost effective compared with postoperative observation. However, adjuvant CRT was the optimal choice for a WTP threshold of $25,648.45/QALY.

p53-cyclophilin D mediates renal tubular cell apoptosis in ischemia-reperfusion-induced acute kidney injury.

Ischemia-reperfusion (I/R)-induced acute kidney injury (I/R-AKI) favors mitochondrial permeability transition pore (mPTP) opening and subsequent cell death. Cyclophilin D (CypD) is an essential component of the mPTP, and recent findings have implicated the p53-CypD complex in cell death. To evaluate the role of p53-CypD after I/R-AKI, we tested the hypothesis that the p53-CypD complex mediates renal tubular cell apoptosis in I/R-AKI via mPTP opening. Expression of p53 and cleaved caspase-3 was significantly increased in rats subjected to I/R-AKI compared with normal controls and sham-operated controls. The underlying mechanisms were determined using an in vitro model of ATP depletion. Inhibition of mPTP opening using the CypD inhibitor cyclosporin A or siRNA for p53 in ATP-depleted HK-2 cells prevented mitochondrial membrane depolarization and reduced apoptosis. Furthermore, p53 bound to CypD in ATP-depleted HK-2 cells. These results suggest that the p53-CypD complex mediates renal tubular cell apoptosis in I/R-AKI via mPTP opening.