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Background: Few data are available on metastatic colorectal cancer (mCRC) treated with late-line regorafenib monotherapy or combined with other therapies. This study thus aimed to examine regorafenib combined with immune checkpoint inhibitors (ICIs) compared with regorafenib monotherapy in patients with advanced CRC., Methods: This single-center retrospective cohort study included patients with advanced CRC who experienced recurrence and progression after standard first- and second-line treatments treatment from November 2018 to December 2021. The patients received regorafenib plus ICIs or regorafenib monotherapy. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed via multivariate analysis., Results: The combined group and the monotherapy group included 30 and 43 patients, respectively. The median OS (13.7 vs . 10.1 months; P=0.10) and PFS (4 vs . 3.6 months; P=0.32) were not significantly different between the two groups. In males, the median OS was significantly longer in the combined group compared with the monotherapy group (not reached vs . 8.03 months; P=0.02), but the median PFS showed no significant difference (7.23 vs . 3.90 months; P=0.16). There was no significant difference in OS (P=0.71) or PFS (P=0.89) in females. Eastern Cooperative Oncology Group performance status (ECOG PS) 1 [ vs . 0; hazard ratio (HR) =3.13, 95% confidence interval (CI): 1.61-6.10; P<0.001] was independently associated with PFS. ECOG PS 1 ( vs . 0; HR =3.63, 95% CI: 1.54-8.56; P=0.003) and combined therapy ( vs . monotherapy; HR =0.47, 95% CI: 0.22-0.99; P=0.048) were associated with OS., Conclusions: Regorafenib combined with ICIs led to numerically longer PFS and significantly prolonged OS in patients with mCRC compared to regorafenib monotherapy, especially in male patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-468/coif). J.M.P. reports honoraria and support for attending meetings and travel from MSD, Bristol-Myers Squibb, and Merck. The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Ultrawide-bandgap semiconductors, possessing bandgaps distinctly larger than the 3.4 eV of GaN, have emerged as a promising class capable of achieving deep ultraviolet (UV) light detection. Based on first-principles calculations, we propose an unexplored two-dimensional (2D) InTeClO 3 layered system with ultrawide bandgaps ranging from 4.34 eV of bulk to 4.54 eV of monolayer. Our calculations demonstrate that 2D InTeClO 3 monolayer can be exfoliated from its bulk counterpart and maintain good thermal and dynamic stability at room temperature. The ultrawide bandgaps may be modulated by the small in-plane strains and layer thickness in a certain range. Furthermore, the 2D InTeClO 3 monolayer shows promising electron transport behavior and strong optical absorption capacity in the deep UV range. A two-probe InTeClO 3 -based photodetection device has been constructed for evaluating the photocurrent. Remarkably, the effective photocurrent (5.7 A m -2 at photon energy of 4.2 eV) generation under polarized light has been observed in such a photodetector. Our results indicate that 2D InTeClO 3 systems have strong photoresponse capacity in the deep UV region, accompanying the remarkable polarization sensitivity and high extinction ratio. These distinctive characteristics highlight the promising application prospects of InTeClO 3 materials in the field of deep UV optoelectronics.

Objective: To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations., Methods: A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis., Results: The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2&#95;Supporting+PP3)., Conclusion: The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.

Tunneling electroresistance (TER) is the change in tunneling resistance induced by ferroelectric polarization reversal in ferroelectric tunnel junctions (FTJs), and how to achieve a giant TER has always been a central topic in the study of FTJs. In this work, by considering the NaTiO3/BaTiO3/LaTiO3 junction with asymmetric polar interfaces as an example, we propose a novel scheme to realize a giant TER based on the reversible partial metallization of ferroelectric barrier upon the switching of ferroelectric polarization. Density functional theory calculations indicate that high on-state and low off-state conductances are obtained and the TER ratio is as high as 3.20 × 108% due to the reversible partial barrier metallization, which leads to a great difference in the effective tunneling barrier widths. The reversible partial barrier metallization, accompanied by the ferroelectric polarization reversal, is driven by the parallel or anti-parallel alignment of the depolarization electrical field of the ferroelectrical barrier and a strong built-in electrical field cooperatively contributed by the asymmetric polar interfaces and the difference in the work functions of the two leads. The findings suggest a feasible scheme for constructing promising high performance FTJ memory devices by combining both asymmetric polar interfaces and substantially different work functions.

Acute lung injury (ALI) severely impairs gas exchange and results in high mortality. Insulin-like growth factor binding protein 3 (IGFBP-3) plays a crucial role in diverse lung diseases;however, the expression and function of IGFBP-3 in ALI remain unclear. In the present study, mice were injected with lipopolysaccharide to establish ALI, and IGF and IGFBP3 expression was measured using ELISA, western blotting, and immunohistochemical staining. Mice with ALI were then treated with recombinant human IGFBP-3 (rhIGFBP-3), and treatment was evaluated using survival analysis, histological staining analysis, and inflammatory cytokine expression in lung tissues and bronchoalveolar lavage fluid (BALF). The expression of NF-κB and VEGF was also measured using western blotting and ELISA in ALI mice. Our results demonstrated the upregulation of IGF expression in lung tissues and BALF of ALI mice, accompanied by downregulation of IGFBP-3. Administration of rhIGFBP-3 prolonged the survival time and attenuated LPS-induced lung injury. The expression of TNF-α, IL-6, IL-1β, and IFN-γ both in lung tissues and BALF decreased after rhIGFBP-3 treatment, whereas IL-10 expression increased. These results suggest that rhIGFBP-3 inhibits the expression of NF-κB and VEGF in lung tissues. Collectively, our study demonstrates a protective role of rhIGFBP-3 in ALI by regulation of lung inflammation., Competing Interests: None., (IJCEP Copyright © 2020.)

Objective: To explore the genetic basis for a neonate with bloody stool and thrombocytopenia., Methods: Clinical data of the neonate was collected. Peripheral venous blood samples were extracted from the neonate and his parents. Next generation sequencing through target capturing was carried out to detect potential mutations of genes associated with thrombocytopenia. Suspected mutation was validated by Sanger sequencing., Results: The 14-day-old male neonate was admitted to hospital for bloody stool for 8 days, decreased platelet count and reduced platelet volume. His liver function and blood coagulation were both normal. Genetic testing revealed a novel deletional mutation in c.1221delG (G407fsX444) of the WAS gene in the patient, which was inherited from his mother., Conclusion: The c.1221delG (G407fsX444) mutation of the WAS gene probably underlies the X-linked thrombocytopenia in the proband. Next generation sequencing can facilitate the diagnose and genetic counseling of such diseases.

Vav1 play key roles in the progression of human cancer. However, the role of Vav1 in gastric cancer (GC) remains to be elucidated. The present study aimed to investigate the potential relevance of the clinicopathological characteristics and prognostic significance of Vav1 in GC patients., Methods: The protein expression of Vav1 was analyzed by immunohistochemistry in formalin-fixed samples obtained from 105 GC patients., Results: Positive Vav1 expression was correlated with larger tumor size and more lymph node metastasis ( P <0.05) in GC tissues. Serosal invasion (hazard ratio [HR] = 2.764, P = 0.007), lymph node metastasis (HR = 1.298, P = 0.002) and Vav1 expression (HR = 0.436, P = 0.006) were identified as independent factors of the overall survival (OS) of GC patients. For advanced GC patients, lymph node metastasis (HR = 1.310, P = 0.003) and Vav1 expression (HR = 0.443, P = 0.010) were the independent prognostic factors of OS., Conclusion: Vav1 performs important functions in the aggressiveness of GC, and Vav1 may serve as a novel prognostic factor in GC., Competing Interests: None., (IJCEP Copyright © 2018.)

Objective: This study aimed to investigate mRNA and protein expression levels of RABEX-5 and matrix metalloproteinase-9 (MMP-9), their mutual correlation, and biological behavior in gastric cancer (GC) patients., Methods: The expression levels of RABEX-5 and MMP-9 were determined by real-time quantitative PCR and Western blotting in cell lines, GC tissues, and adjacent normal tissues. In addition, RABEX-5 and MMP-9 expression was analyzed by immunohistochemistry in formalin-fixed tissues from 113 GC patients., Results: The mRNA and protein expression levels of RABEX-5 and MMP-9 in GC cell lines and GC tissues were higher than those in normal gastric mucosa cell line and adjacent normal tissues. RABEX-5 expression and MMP-9 expression in GC tissues were significantly and positively correlated. In addition, the size of tumor (p<0.001), Lauren's classification (p=0.009), and N stage (p<0.001) were identified as the relative factors of RABEX-5 expression, whereas the expression of MMP-9 was correlated with N stage (p=0.003). The results of the multivariate analysis revealed that the independent predictive factors of overall survival were T stage (hazard ratio (HR)=2.382; p=0.028), N stage (HR=1.755; p<0.001), RABEX-5 expression (HR=0.452; p=0.004), and MMP-9 expression (HR=0.561; p=0.032)., Conclusions: RABEX-5 and MMP-9 expression levels were elevated in GC tissues and were associated with tumor invasion, metastasis, and prognosis. Therefore, they may be promising prognostic indicators of survival in GC patients.

Objective: The phase information of magnetic resonance (MR) phase image can be used in many MR imaging techniques, but phase wrapping of the images often results in inaccurate phase information and phase unwrapping is essential for MR imaging techniques. In this paper we analyze the causes of errors in phase unwrapping with the commonly used Goldstein Brunch-cut algorithm and propose an improved algorithm. During the unwrapping process, masking, filtering, dipole- remover preprocessor, and the Prim algorithm of the minimum spanning tree were introduced to optimize the residues essential for the Goldstein Brunch-cut algorithm. Experimental results showed that the residues, branch-cuts and continuous unwrapped phase surface were efficiently reduced and the quality of MR phase images was obviously improved with the proposed method.

Objective: To establish the method for quantitative determination of sibricose A5 and sibricose A6 in Polygalae Radix by HPLC., Method: The ultrasonic extracting method was applied in sample pre-treatment. The HPLC procedure was performed on the chromatographic column of Agela Promosil C18 (4.6 mm x 250 mm, 5 microm), the mobile phase was acetonitrile-0.1% phosphoric acid water solution (10:90). The detection wavelength was 330 nm and flow velocity was 1 mL x min(-1). The column temperature was 30 degrees C., Result: The method has good linearity in the ranges of 0.0087-0.0694 g x L(-1) (r = 0.9993) for sibricose A5, 0.0090-0.0723 g x L(-1) (r=0.9991) for sibricose A6. The average recoveries of sibricose A5 and sibricose A6 were 101.7%, 97.87%, with the RSD of 1.7%, 1.6%, respectively., Conclusion: The method was simple, quick accurate and reliable. It is appropriate for the quantitative determination of sibricose A5 and sibricose A6 in Polygalae Radix.