Ultrahigh Energy Storage Performance of BiFeO3-BaTiO3 Flexible Film Capacitor with High-Temperature Stability via Defect Design.

Nanoengineering polar oxide films have attracted great attention in energy storage due to their high energy density. However, most of them are deposited on thick and rigid substrates, which is not conducive to the integration of capacitors and applications in flexible electronics. Here, an alternative strategy using van der Waals epitaxial oxide dielectrics on ultra-thin flexible mica substrates is developed and increased the disorder within the system through high laser flux. The introduction of defects can efficiently weaken or destroy the long-range ferroelectric ordering, ultimately leading to the emergence of a large numbers of weak-coupling regions. Such polarization configuration ensures fast polarization response and significantly improves energy storage characteristics. A flexible BiFeO3-BaTiO3 (BF-BT) capacitor exhibits a total energy density of 43.5 J cm-3 and an efficiency of 66.7% and maintains good energy storage performance over a wide temperature range (20-200 °C) and under large bending deformation (bending radii ≈ 2 mm). This study provides a feasible approach to improve the energy storage characteristics of dielectric oxide films and paves the way for their practical application in high-energy density capacitors.

Combinational zimberelimab plus lenvatinib and chemotherapy for alpha-fetoprotein elevated, advanced gastric cancer patients (AFPGC): a phase 1 dose-escalation study.

BACKGROUND: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC. METHODS: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate. RESULTS: Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07-11.27) and 13.17 months (95% CI 2.78-23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183. CONCLUSIONS: GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment.

Erratum: Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis: Erratum.

[This corrects the article DOI: 10.7150/thno.44419.].

Dihydroxyl modified UiO-66 as dispersive solid-phase extraction sorbent coupled with ultra-high performance liquid chromatography tandem mass spectrometry for detection of neonicotinoid insecticides.

The extensive usage of neonicotinoid insecticides (NIs) has raised many concerns about their potential harm to environment and human health. Thus, it is of great importance to develop an efficient and reliable method to determine NIs in food samples. In this work, three Zr4+-based metal-organic frameworks functionalized with various numbers of hydroxyl groups were fabricated with a facile one-pot solvothermal method. Among them, dihydroxy modified UiO-66 (UiO-66-(OH)2) exhibited best adsorption performance towards five target NIs. Then, a sensitive and efficient method for detection of NIs from vegetable and fruit samples was established based on dispersive solid phase extraction (dSPE) with UiO-66-(OH)2 as adsorbent coupled with ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Key parameters affecting the dSPE procedure including amounts of adsorbent, adsorption time, eluent solvents and desorption time were investigated. Under the optimal conditions, rapid adsorption of NIs within five minutes was achieved due to the high affinity of UiO-66-(OH)2 towards NIs. The developed method exhibited high sensitivity with limits of detection (LODs) varied from 0.003 to 0.03 ng/mL and wide linearity range over 3-4 orders of magnitude from 0.01 to 500 ng/mL. Furthermore, the established method was applied for determining trace NIs from complex matrices with recoveries ranging from 74.6 to 99.6 % and 77.0-106.8 % for pear and tomato samples, respectively. The results indicate the potential of UiO-66-(OH)2 for efficient enrichment of trace NIs from complex matrices.

Anti-PD-L1 antibody TQB2450 combined with tyrosine kinase receptor inhibitor AL2846 for immunotherapy-refractory advanced hepatocellular carcinoma and esophageal squamous cell carcinoma: A prospective phase 1b cohort study.

BACKGROUND: Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity. METHODS: In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response. RESULTS: Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC. CONCLUSIONS: Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study.

BACKGROUND: There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. METHODS: Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher's exact test. ROC curve and surv_cutpoint function of 'survminer' package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. RESULTS: A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. CONCLUSIONS: Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

Combined score based on plasma fibrinogen and platelet-lymphocyte ratio as a prognostic biomarker in esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has showed that inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and fibrinogen can be used as predictors in the prognosis of esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore prognostic value of these biomarkers and evaluate the clinicopathological and prognostic significance of combined score based on plasma fibrinogen and platelet-lymphocyte ratio (F-PLR score). METHODS: A total of 506 patients with ESCC were enrolled in this study. Harrell's concordance index (c-index) was used to determine the optimal cut-off values of these markers and evaluate their prognostic significance. The relationship between factors with survival rates (including overall survival [OS] and disease-free survival [DFS]) was explored by Kaplan-Meier curve, univariate analysis and multivariate cox hazard analysis. RESULTS: Our result indicated that high F-PLR score was significantly associated with longer tumor length and deeper depth of tumor invasion (p < 0.01). The result of Cox multivariable analysis showed that F-PLR score was an independent prognostic factor for OS (p = 0.002) and DFS (p = 0.003). In addition, F-PLR score presented the greater c-index values for OS and DFS compared with NLR, PLR and fibrinogen level. Our result also showed that the c-index values for OS and DFS were both greater in TNM + F-PLR than those in TNM stage alone. CONCLUSIONS: In conclusion, F-PLR score is a predictive biomarker for prognosis in patients with ESCC.

Prusogliptin (DBPR108) monotherapy in treatment-naïve patients with type 2 diabetes: A randomized, double-blind, active and placebo-controlled, phase 3 study.

AIM: This study aimed to assess the efficacy and safety of prusogliptin (DBPR108), a novel and highly selective dipeptidyl peptidase-4 inhibitor, in individuals with type 2 diabetes who had not been using glucose-lowering agents regularly for the 8 weeks before the screening period. MATERIALS AND METHODS: In this multicentre, randomized, double-blind, phase 3 study, adult patients with type 2 diabetes were randomly assigned to receive either DBPR108 100 mg, sitagliptin 100 mg, or placebo once daily during the initial 24-week double-blind treatment period, followed by a 28-week open-label extension period during which all patients received DBPR108 100 mg once daily. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) levels from baseline to week 24. RESULTS: In total, 766 patients were enrolled and received DBPR108 100 mg (n = 462), sitagliptin 100 mg (n = 152), or placebo (n = 152). The mean age of all patients was 54.3 ± 10.5 years, with 58% being men. The median duration of type 2 diabetes was 0.38 (0.02, 2.65) years, and the mean HbA1c (SD) at baseline was 7.94% (0.62), 7.88% (0.61) and 7.83% (0.59) for DBPR108, sitagliptin and placebo groups, respectively. At week 24, the least square mean (SE) changes from baseline in HbA1c were -0.63% (0.04%) for DBPR108, -0.60% (0.07%) for sitagliptin and -0.02% (0.07%) for placebo. The mean treatment difference between DBPR108 and placebo was -0.61% (95% CI -0.77% to -0.44%), and between DBPR108 and sitagliptin was -0.03% (95% CI -0.19% to 0.13%). These results indicate that DBPR108 was superior to placebo and non-inferior to sitagliptin. DBPR108 also significantly reduced fasting and postprandial plasma glucose levels and had little effect on body weight. The mean (SD) changes in HbA1c from baseline to week 52 were -0.50% (0.97%) for the DBPR108 group, -0.46% (0.96%) for the sitagliptin group and -0.41% (0.95%) for the placebo group. The incidence of adverse events was comparable across all three groups. CONCLUSIONS: DBPR108 showed superiority to placebo and non-inferiority to sitagliptin in terms of glycaemic control over the initial 24 weeks in treatment-naïve patients with type 2 diabetes. Furthermore, its efficacy was sustained for up to 52 weeks.

[Retracted] Effects of miR­138­5p and miR­204­5p on the migration and proliferation of gastric cancer cells by targeting EGFR.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the numerous immunohistochemical images shown in Fig. 1D on p. 2626 exhibited a number of overlaps comparing among the data panels, such that data which were intended to show the results from differently performed experiments were likely to have been derived from a smaller number of original sources. A subsequent independent investigation of the data in this paper in the Editorial Office also revealed that certain of the cell migration and invasion assay data shown in Fig. 4A on p. 2629 were strikingly similar to data that had previously appeared in a couple of already published papers written by different authors at different research institutes.  Owing to the fact that the contentious data in Fig. 4 in the above article had already been published prior to its submission to Oncology Reports, in addition to the matter of several panels in Fig. 1D showing overlapping data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 2624-2634, 2018; DOI: 10.3892/or.2018.6389].

BRD4 facilitates osteogenic differentiation of human bone marrow mesenchymal stem cells through WNT4/NF-κB pathway.

BACKGROUND: Human bone marrow mesenchymal stem cells (hBMSCs) are a major source of osteoblast precursor cells and are directly involved in osteoporosis (OP) progression. Bromodomain-containing protein 4 (BRD4) is an important regulator for osteogenic differentiation. Therefore, its role and mechanism in osteogenic differentiation process deserve further investigation. METHODS: hBMSCs osteogenic differentiation was evaluated by flow cytometry, alkaline phosphatase assay and alizarin red staining. Western blot was used to test osteogenic differentiation-related proteins, BRD4 protein, WNT family members-4 (WNT4)/NF-κB-related proteins, and glycolysis-related proteins. Metabolomics techniques were used to detect metabolite changes and metabolic pathways. BRD4 and WNT4 mRNA levels were determined using quantitative real-time PCR. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to detect BRD4 and WNT4 interaction. Glycolysis ability was assessed by testing glucose uptake, lactic acid production, and ATP levels. RESULTS: After successful induction of osteogenic differentiation, the expression of BRD4 was increased significantly. BRD4 knockdown inhibited hBMSCs osteogenic differentiation. Metabolomics analysis showed that BRD4 expression was related to glucose metabolism in osteogenic differentiation. Moreover, BRD4 could directly bind to the promoter of the WNT4 gene. Further experiments confirmed that recombinant WNT4 reversed the inhibition effect of BRD4 knockdown on glycolysis, and NF-κB inhibitors (Bardoxolone Methyl) overturned the suppressive effect of BRD4 knockdown on hBMSCs osteogenic differentiation. CONCLUSION: BRD4 promoted hBMSCs osteogenic differentiation by inhibiting NF-κB pathway via enhancing WNT4 expression.

A study on table tennis landing point detection algorithm based on spatial domain information.

To address the limitations of computer vision-assisted table tennis ball detection, which heavily relies on vision acquisition equipment and exhibits slow processing speed, we propose a real-time calculation method for determining the landing point of table tennis balls. This novel approach is based on spatial domain information and reduces the dependency on vision acquisition equipment. This method incorporates several steps: employing dynamic color thresholding to determine the centroid coordinates of all objects in the video frames, utilizing target area thresholding and spatial Euclidean distance to eliminate interference balls and noise, optimizing the total number of video frames through keyframe extraction to reduce the number of operations for object recognition and landing point detection, and employing the four-frame difference slope method and polygonal area determination to detect the landing point and area of the target object, thereby obtaining precise coordinates and their corresponding areas. Experimental results on the above method on the Jetson Nano development board show that the dynamic color thresholding method achieves a detection speed of 45.3 fps. The keyframe extraction method correctly identifies the landing point frames with an accuracy rate exceeding 93.3%. In terms of drop point detection, the proposed method achieves 78.5% overall accuracy in detecting table tennis ball drop points while ensuring real-time detection. These experiments validate that the proposed method has the ability to detect table tennis ball drop points in real time and accurately in low frame rate vision acquisition devices and real environments.

Distribution of multidrug-resistant bacterial infections in diabetic foot ulcers and risk factors for drug resistance: a retrospective analysis.

Objective: To investigate the distribution, drug resistance and risk factors of multi-drug resistant bacterias (MDROs) in patients with Type 2 diabetic foot ulcers (DFU). Method: The clinical data, foot secretions, pathogenic microorganisms and drug sensitivity tests of 147 patients with type 2 diabetes admitted to our department from January 2018 to December 2021 were analyzed. Patients were divided into two groups according to whether they had been infected with MDROs or not. Seventy-one cases were infected with MDROs as the case group, and the remaining 76 cases were the control group. Chi-square test and t-test were used to analyze the results of MDROs infection and DFU, and logistic multivariate regression was used to evaluate the risk factors of MDROs infection. Results: A total of 71 strains were isolated from the MDROs-positive group, with the top three being Staphylococcus aureus (46.48%), Escherichia coli (22.53%), and Pseudomonas aeruginosa (18.31%), respectively. Logistic multifactorial regression analysis showed that history of previous antimicrobial exposure, neuroischemic wound, Wagner grade 3-5, and combined osteomyelitis were associated with Type 2 diabetic foot infection MDROs (P < 0.05). Conclusion: Previous history of antimicrobial exposure, neuroischemic wounds, Wagner grade 3-5, and combined osteomyelitis are independent risk factors for MDROs, which can identify the risk factors for MDROs at an early stage and help to identify people at high risk of MDROs infection and take relevant comprehensive treatment in time to slow down the development of the disease.

A Modified Negative Pressure Wound Therapy Reduces the Occurrence of Tension Blisters Around Negative Pressure Dressings.

Background: To date, there is no effective solution for preventing the formation of blisters around negative-pressure wound dressings. In this study, we aim to address this problem and identify techniques to improve the negative-pressure drainage technique. Methods: A total of 129 patients from 2021.11 to 2022.11 who were previously treated in Fuyang People's Hospital were included in this retrospective analysis. All patients had negative-pressure drainage dressings applied to their wounds after undergoing thorough wound debridement. The patients were divided into the following groups: a traditional treatment group and a modified treatment group. The traditional treatment group comprised 60 patients who received negative-pressure wound therapy (NPWT) and a modified treatment group comprised 69 patients who received NPWT plus Vaseline gauze. The dressing coverage area, wound location, incidence of blisters around the dressing 3 days after NPWT, wound infection rate, and length of hospitalization were recorded. The incidence of blisters, wound infection rate, and wound location in the 2 groups were included as the categorical data and were compared using a chi-squared test. The dressing coverage area and length of hospitalization in the 2 groups were included as the quantitative data and were compared using an independent samples t test or with the Mann-Whitney test if the data were abnormally distributed. Results: The incidence rates of blisters in the traditional and modified treatment groups were 33.3% (20/60) and 13.0% (9/69), respectively, displaying a statistically significant difference (χ2 = 7.581, P = .006). The infection rates of the 2 groups were 38.3% (23/60) and 20.3% (14/69), respectively, showing a statistically significant difference (χ2 = 5.108; P = .024). The lengths of hospitalization in the 2 groups were 26.05 ± 14.74 days and 18.17 ± 7.54 days, respectively, showing a statistically significant difference (t = 3.892; P = .000). The dressing coverage areas were 150 cm2 (88.75 cm2, 600 cm2) and 150 cm2 (124 cm2, 600 cm2), respectively, showing no statistical difference (P = .759). Conclusion: Modified NPWT can effectively reduce the incidence of blisters, length of hospitalization, and infection rate of patients.

Third-line treatment patterns and clinical outcomes for metastatic colorectal cancer: a retrospective real-world study.

Background: There are multiple recommendations on the third-line therapy of metastatic colorectal cancer (mCRC); however, no consensus has been reached. Objectives: This study aimed to explore the patient demographics and the real-world third-line treatment landscape of mCRC. Design: A retrospective real-world cohort study. Methods: Electronic medical records of mCRC patients from Tianjin Medical University Cancer Institute and Hospital between 2013 and 2020 were collected. Upon descriptive, comparative, and survival analyses, a retrospective study was conducted to describe demographics and clinical outcomes of mCRC patients receiving third-line treatment. Results: Among 218 mCRC patients receiving third-line therapy, 65.5% received chemotherapy combined with or without targeted drugs, followed by anti-angiogenic monotherapy (18.4%), anti-epidermal growth factor receptor drugs (6.9%) and immunotherapy (6.4%). The overall response rate and disease control rate reached 10.2% and 59.2%, respectively; and median progression-free survival (PFS) and overall survival were 4.0 m and 10.7 m, respectively. After Cox multivariate analysis, we found that therapeutic regime was an independent prognostic factor. Compared to patients receiving anti-angiogenic monotherapy, those receiving chemotherapy combined with or without targeted drugs exhibited better prognosis. For patients whose PFS were longer in the front-line treatment, the PFS of third-line therapy was also relatively longer (p = 0.023). Multiple types of therapies (>3, p = 0.002) or multiple drugs (>5, p = 0.024) in the whole-course management of mCRC are indicators of longer survival. Conclusion: Chemotherapy combined with or without targeted therapy remained dominated third-line choice and showed favorable efficacy compared with anti-angiogenic monotherapy. With the application of more types and quantities of effective drugs, patients would achieve better survival.

Treatment of Morel-Lavallée Lesions (MLLs) with Mesh Incisions Combined with Quilting Sutures and Negative Pressure Wound Therapy (NPWT).

Purpose: The objective of this retrospective study was to evaluate the clinical effects of a novel treatment approach for Morel-Lavallée lesions (MLL) using a combination of suturing techniques and Negative Pressure Wound Therapy (NPWT) with mesh incisions. To summarize the clinical effects of a combination of suturing techniques and (Negative Pressure Wound Therapy) NPWT on the wall of Morel-Lavallée lesions (MLL) fibrotic pseudocapsules with mesh incisions in the treatment of MLLs. A retrospective analysis was performed on MLL patients from April 2017 to March 2021. Methods: This a retrospective case-control study and thirteen MLL patients were included in this retrospective analysis conducted between April 2017 and March 2021, who were treated with mesh incisions on the wall of the pseudocapsule, quilting suturing to degloved soft tissues, and NPWT. Physical examination, MRI, or ultrasound before surgery confirmed the diagnosis. Wound healing, secondary infection, recurrence, visual analog scale (VAS) scores before and after surgery, and skin and soft tissue condition were observed and evaluated. Results: The combination of mesh incisions, quilting sutures, and NPWT led to successful wound healing in 11 out of 13 cases without recurrent hematoma or secondary infection. Visual analog scale (VAS) scores significantly decreased after the operation, and the aesthetic and tactile qualities of the injured area improved. One case of skin and soft tissue necrosis infection before the operation, which healed after second-stage full-thickness skin grafting, 1 case healed after a dressing change, and the remaining 11 cases had wounds that healed by the first stage without secondary infection or recurrent hematoma formation. VAS scores decreased significantly after the operation, the appearance of the injured area was as expected, and the skin feel and elasticity recovered satisfactorily. Conclusion: The study demonstrates that the mesh incision technique, along with mattress sutures and NPWT, presents a feasible and effective approach for treating MLL with fibrotic pseudocapsules. This could shorten healing times, reduce risk of complications, and improve patient satisfaction.

The optimal time of starting adjuvant chemotherapy after curative surgery in patients with colorectal cancer.

BACKGROUND: Postoperative adjuvant chemotherapy (AC) is now well-accepted as standard for high-risk stage II and stage III colorectal cancer (CRC) patients, however the optimal time to initiate AC remains elusive. METHODS: A comprehensive literature search was performed using the PubMed and Embase databases. The Hazard ratio (HR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate primary endpoints. All analyses were conducted using Stata software version 12.0 with the Random-effects model. RESULTS: A total of 30 studies were included in our study. Upon comparison on overall survival (OS), we identified that delaying the initiation of AC for > 8 weeks after operation was significantly associated with poor OS (HR: 1.37; 95% CI: 1.27-1.48; P < 0.01). The poor prognostic value of AC delay for > 8 weeks was not undermined by subgroup analysis based on region, tumor site, sample size and study quality. No obvious differences were observed in survival between AC within 5-8 weeks and ≤ 4 weeks (HR: 1.03; 95% CI: 0.96 -1.10; P = 0.46). Moreover, two studies both highlighted that the survival benefit of AC was still statistically significant when AC was applied 5-6 months after surgery compared with the non-chemotherapy group. CONCLUSIONS: Delaying the initiation of AC for > 8 weeks after surgery was significantly associated with poor OS. AC started within 8 weeks after surgery brought more benefits to CRC patients. There were no obvious differences in survival benefits between AC within 5-8 weeks and ≤ 4 weeks. Compared to patients not receiving AC after surgery, a delay of approximately 5-6 months was still useful to improve prognosis.

Sintilimab Plus Apatinib and Chemotherapy as Second­/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial.

BACKGROUND: The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients. METHODS: In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator's choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety. RESULTS: From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9-72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4-11.5) and 12.5 months (95% CI, 3.7-21.3), respectively. Grade 3-4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3-4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred. CONCLUSION: Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05025033, 27/08/2021.

Room temperature fabrication of magnetic covalent organic frameworks for efficient enrichment of parabens in water.

A novel 4 + 2 covalent magnetic organic framework (COF) with core-shell structure was synthesized for the first time with N, N, N', N'-Tetrakis (4-aminophenyl)-1, 4- benzenediamine (TPDA) and 2, 6-Pyridinedicarboxaldehyde (PCBA) at room temperature. The synthesized magnetic TPDA-PCBA-COF has a large specific surface area and superparamagnetism, which makes it an ideal sorbent for trace analytes enrichment. To this end, we combined it with magnetic solid phase extraction (MSPE) to enrich trace parabens in environmental water. The parameters affecting the enrichment efficiency of magnetic solid phase extraction, such as the amount of Fe3O4@TPDA-PCBA-COF, extraction time, pH of samples, salt concentration, desorption solvent volume and desorption time, were optimized. A simple method for extraction and determination of parabens in water samples by MSPE combined with high performance liquid chromatography (HPLC) was established under optimized conditions. The validation results revealed that the linear ranges were at 1.0-5.0 × 102 ng mL-1 with R value between 0.9915 and 0.9999, the spiked recoveries were in the range of 82.8% to 99.9% and RSDs were lower than 10%. The method was further applied to the determination of parabens in water samples, with recoveries in the range of 82.2% to 110.0% and RSDs ≤ 7.7%. These results suggest that the magnetic TPDA-PCBA-COF could be used as a promising adsorbent for efficient extraction and quantitation of parabens in environmental water samples.