Combination kinase inhibitors and immunotherapy for unresectable anaplastic thyroid carcinoma: A retrospective single-center study.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is rare but has a very poor prognosis. New therapeutic options such as multikinase inhibitors and selective tyrosine kinase inhibitors have revolutionized the treatment of ATC, with immunotherapy also showing encouraging effects. This study evaluated the efficacy and safety of kinase inhibitors combined with an anti-PD-1 inhibitor as first-line treatment, as well as in the neoadjuvant setting for patients with unresectable ATC. MATERIALS & METHODS: This retrospective single-center study recruited consecutive patients with stage IVB and IVC ATC who received first-line kinase inhibitors plus immunotherapy between June 2021 and June 2023. The patients were treated with either selective or multi-kinase inhibitors (dabrafenib/trametinib, lenvatinib, or anlotinib) in combination with one immune checkpoint inhibitor (pembrolizumab, sintilimab, or camrelizumab). The endpoints included overall survival (OS), progression-free survival (PFS), response evaluation, and feasibility of R0/R1 resection. RESULTS: Eighteen patients were included in this analysis. The median OS (mOS) was 14.0 months and the 12-month survival rate was 55.6 %. The mOS in BRAF V600E mutated ATC was not reached, significantly longer than non-BRAF V600E mutated ATC (4.0 months [95 %CI, 1.1-6.9], p = 0.049). Among evaluable patients, 5 achieved a complete response (CR) and 6 patients achieved partial response (PR). The best ORR was 61.1 %. Surgical resection was feasible in 7/18 (38.9 %) patients. One grade 5 adverse event (AE) occurred. Most AEs were well tolerated. CONCLUSIONS: Combination kinase inhibitors with immunotherapy as first-line therapy are safe and effective for the treatment of unresectable ATC, especially with BRAF V600E mutation.

Impact of Lumbar Fusion Internal Fixation on Lumbar Disc Herniation in Young Patients: A Retrospective Study.

BACKGROUND Lumbar fusion and internal fixation techniques have shown promise in treating lumbar disc herniation (LDH), yet the impact on lumbar function in young patients remains unclear. This study aimed to investigate the impact of lumbar fusion on lumbar function in young patients. MATERIAL AND METHODS A retrospective analysis was conducted on 330 patients diagnosed with LDH admitted to our hospital. Patients were divided into 2 groups: a control group (n=264) that underwent a minimally invasive procedure with a keyhole lens, and a research group (n=66) that underwent lumbar fusion internal fixation. Clinical features and therapeutic outcomes were assessed using Oswestry Disability Index (ODI) and Japanese Orthopedic Association (JOA) Lumbar Scores before surgery and 12 months postoperatively. Additionally, intervertebral space height, degree of vertebral spondylolisthesis (grades I, II, and III), incidence of adverse effects, and treatment efficacy were measured pre-and post-surgically. RESULTS No significant difference in ODI and JOA scores was found between the groups before surgery (P>0.05). Postoperatively, the research group had lower ODI scores, higher JOA scores, and lower intervertebral space heights compared to the control group (P=0.001). While grade 1 and 2 spondylolisthesis showed slight improvement (P>0.05), a significant difference was observed in grade III spondylolisthesis between the 2 groups (P=0.001). Additionally, the research group had a lower incidence of adverse effects (P=0.049) and higher treatment efficacy, although the difference was not statistically significant (P>0.05). CONCLUSIONS Lumbar fusion with internal fixation produced better postoperative outcomes and fewer adverse effects than minimally invasive procedures in young patients with lumbar disc herniation.

Negative prognostic impact of tumor deposits in stage III colorectal cancer patients.

BACKGROUND: The prognostic value of tumor deposits (TDs) in stage III colorectal cancer (CRC) patients is poorly described based on the current tumor node metastasis (TNM) stage system. MATERIALS AND METHODS: Based on the data from the Surveillance, Epidemiology, and End Result (SEER) database between 2010 to 2020 and local hospital between 2006 to 2022, the clinicopathological features of stage III CRC patients with TDs were screened by Chi-square test. Kaplan-Meier curves were performed to describe the significant difference in overall survival (OS) among the different groups, and log-rank tests were used to compare the cumulative survival distributions. RESULT: Patients with TDs exhibited more aggressive tumors, characterized by advanced T staging (T3&T4), N staging (N2), perineural invasion, and more advanced TNM stage. The presence of TDs was identified as a negative prognostic factor in stage III CRC patients, with the co-existence of TDs and lymph node metastasis associated the poorest prognosis. A pairwise comparison revealed no statistically significant difference between TD+N1a/b and N1c groups, while the OS of TD-LN+ (TD- N1a/b) patients was the most favorable within the N1 stage. Notably, patients with a single lymph node positive had a significantly better OS than those with a single TD positive. CONCLUSION: The presence of tumor deposits was a negative prognostic factor in stage III colorectal cancer patients, and the significance of tumor deposits was underestimated in the current TNM staging system.

Efficacy of robot-assisted gait training on lower extremity function in subacute stroke patients: a systematic review and meta-analysis.

BACKGROUND: Robot-Assisted Gait Training (RAGT) is a novel technology widely employed in the field of neurological rehabilitation for patients with subacute stroke. However, the effectiveness of RAGT compared to conventional gait training (CGT) in improving lower extremity function remains a topic of debate. This study aimed to investigate and compare the effects of RAGT and CGT on lower extremity movement in patients with subacute stroke. METHODS: Comprehensive search was conducted across multiple databases, including PubMed, Web of Science, Cochrane Library, EBSCO, Embase, Scopus, China National Knowledge Infrastructure, Wan Fang, SinoMed and Vip Journal Integration Platform. The database retrieval was performed up until July 9, 2024. Meta-analysis was conducted using RevMan 5.4 software. RESULTS: A total of 24 RCTs were included in the analysis. The results indicate that, compared with CGT, RAGT led to significant improvements in the Fugl-Meyer Assessment for Lower Extremity [MD = 2.10, 95%CI (0.62, 3.59), P = 0.005], Functional Ambulation Category[MD = 0.44, 95%CI (0.23, 0.65), P < 0.001], Berg Balance Scale [MD = 4.55, 95%CI (3.00, 6.11), P < 0.001], Timed Up and Go test [MD = -4.05, 95%CI (-5.12, -2.98), P < 0.001], and 6-Minute Walk Test [MD = 30.66, 95%CI (22.36, 38.97), P < 0.001] for patients with subacute stroke. However, it did not show a significant effect on the 10-Meter Walk Test [MD = 0.06, 95%CI (-0.01, 0.14), P = 0.08]. CONCLUSIONS: This study provides evidence that RAGT can enhance lower extremity function, balance function, walking ability, and endurance levels compared to CGT. However, the quality of evidence for improvements in gait speed remains low.

[Corrigendum] Omi/HtrA2 pro-apoptotic marker differs in various hepatocellular carcinoma cell lines owing to ped/pea-15 expression level.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the control western blots shown for Fig. 1A and B on p. 908 and Fig. 8A and C on p. 911 were apparently the same, where different experiments were intended to have been portrayed. After having re­examined their original data files, the authors realized that these figures had been published with the control western blots shown incorrectly for Fig. 1A and 8C. The  corrected versions of this pair of figures are shown on the next page. Note that the corrections made to these figures do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 33: 905­912, 2015; DOI: 10.3892/or.2014.3656].

Genome-wide identification of the WRKY gene family in blueberry (Vaccinium spp.) and expression analysis under abiotic stress.

Introduction: The WRKY transcription factor (TF) family is one of the largest TF families in plants and is widely involved in responses to both biotic and abiotic stresses. Methods: To clarify the function of the WRKY family in blueberries, this study identified the WRKY genes within the blueberry genome and systematically analyzed gene characteristics, phylogenetic evolution, promoter cis-elements, expression patterns, and subcellular localization of the encoded products. Results: In this study, 57 VcWRKY genes were identified, and all encoding products had a complete WRKY heptapeptide structure and zinc-finger motif. The VcWRKY genes were divided into three subgroups (I-III) by phylogenetic analysis. Group II was divided into five subgroups: IIa, IIb, IIc, IId, and IIe. 57 VcWRKY genes were distributed unevenly across 32 chromosomes. The amino acids ranged from 172 to 841, and molecular weights varied from 19.75 to 92.28 kD. Intra-group syntenic analysis identified 12 pairs of duplicate segments. Furthermore, 34 cis-element recognition sites were identified in the promoter regions of VcWRKY genes, primarily comprising phytohormone-responsive and light-responsive elements. Comparative syntenic maps were generated to investigate the evolutionary relationships of VcWRKY genes, revealing the closest homology to dicotyledonous WRKY gene families. VcWRKY genes were predominantly expressed in the fruit flesh and roots of blueberries. Gene expression analysis showed that the responses of VcWRKY genes to stress treatments were more strongly in leaves than in roots. Notably, VcWRKY13 and VcWRKY25 exhibited significant upregulation under salt stress, alkali stress, and saline-alkali stress, and VcWRKY1 and VcWRKY13 showed notable induction under drought stress. Subcellular localization analysis confirmed that VcWRKY13 and VcWRKY25 function within the nucleus. Conclusion: These findings establish a foundation for further investigation into the functions and regulatory mechanisms of VcWRKY genes and provide guidance for selecting stress-tolerant genes in the development of blueberry cultivars.

Assembly and comparative analysis of the complete mitochondrial genome of Vaccinium carlesii Dunn.

Vaccinium L. is an important fruit tree with nutritional, medicinal, and ornamental values. However, the mitochondrial (mt) genome of Vaccinium L. remains largely unexplored. Vaccinium carlesii Dunn is an endemic wild resource in China, which is crucial for blueberry breeding. The V. carlesii mt genomes were sequenced using Illumina and Nanopore, which total length was 636,904 bp with 37 protein coding genes, 20 tRNA genes, and three rRNA genes. We found four pairs of long repeat fragments homologous recombination mediated the generation of substructures in the V. carlesii mt genome. We predicted 383 RNA editing sites, all converting cytosine (C) to uracil (U). According to the phylogenetic analysis, V. carlesii and V. macrocarpon of the Ericaceae exhibited the closest genetic relationship. This study provides a theoretical basis for understanding the evolution of higher plants, species classification and identification, and will also be useful for further utilization of Vaccinium germplasm resources.

Genetic and epigenetic signatures for improved breeding of cultivated blueberry.

Blueberry belongs to the Vaccinium genus and is a highly popular fruit crop with significant economic importance. It was not until the early twentieth century that they began to be domesticated through extensive interspecific hybridization. Here, we collected 220 Vaccinium accessions from various geographical locations, including 154 from the United States, 14 from China, eight from Australia, and 29 from Europe and other countries, comprising 164 Vaccinium corymbosum, 15 Vaccinium ashei, 10 lowbush blueberries, seven half-high blueberries, and others. We present the whole-genome variation map of 220 accessions and reconstructed the hundred-year molecular history of interspecific hybridization of blueberry. We focused on the two major blueberry subgroups, the northern highbush blueberry (NHB) and southern highbush blueberry (SHB) and identified candidate genes that contribute to their distinct traits in climate adaptability and fruit quality. Our analysis unveiled the role of gene introgression from Vaccinium darrowii and V. ashei into SHB in driving the differentiation between SHB and NHB, potentially facilitating SHB's adaptation to subtropical environments. Assisted by genome-wide association studies, our analysis suggested VcTBL44 as a pivotal gene regulator governing fruit firmness in SHB. Additionally, we conducted whole-genome bisulfite sequencing on nine NHB and 12 SHB cultivars, and characterized regions that are differentially methylated between the two subgroups. In particular, we discovered that the ß-alanine metabolic pathway genes were enriched for DNA methylation changes. Our study provides high-quality genetic and epigenetic variation maps for blueberry, which offer valuable insights and resources for future blueberry breeding.

Release of PAHs from sediments to seawater under wave: Indoor microcosms and level IV fugacity models.

Estuaries and coasts are located at the land-sea interface, where sediment liquefaction due to strong wave action results in significant material exchange at the sediment-seawater system. Polycyclic aromatic hydrocarbons (PAHs), as organic pollutants, are distributed across various media. Herein, the impact of wave was studied on the release of PAHs through indoor microcosmic experiments combined with a level IV fugacity model. Comparison revealed that the release amount and rate of PAHs during static consolidation stage were minimal, whereas wave action substantially enhanced the release. Particularly the sediments in a liquefied state, the PAHs release in Stage III was 1.55-1.86 times that in Stage II, reaching 84.73 µg/L. The loss of soil strength and strong hydrodynamic effects resulted in a substantial release of PAHs into seawater along with suspended solids. Due to volatility of 2-ring PAHs and difficult desorption of 6-ring PAHs, 3-5-ring PAHs are the main contributors to releases into seawater. The model results also indicated that the three PAHs had different fates in the sediment-seawater system, with sediment serving as an important "reservoir" for benzo[a]pyrene entering seawater, while functioning as both a "sink" and a "source" for pyrene.

Molecular mechanisms of EGCG-CSH/n-HA/CMC in promoting osteogenic differentiation and macrophage polarization.

2. This research investigates the impact of the EGCG-CSH/n-HA/CMC composite material on bone defect repair, emphasizing its influence on macrophage polarization and osteogenic differentiation of BMSCs. Comprehensive evaluations of the composite's physical and chemical characteristics were performed. BMSC response to the material was tested in vitro for proliferation, migration, and osteogenic potential. An SD rat model was employed for in vivo assessments of bone repair efficacy. Both transcriptional and proteomic analyses were utilized to delineate the mechanisms influencing macrophage behavior and stem cell differentiation. The material maintained excellent structural integrity and significantly promoted BMSC functions critical to bone healing. In vivo results confirmed accelerated bone repair, and molecular analysis highlighted the role of macrophage M2 polarization, particularly through changes in the SIRPA gene and protein expression. EGCG-CSH/n-HA/CMC plays a significant role in enhancing bone repair, with implications for macrophage and BMSC function. Our findings suggest that targeting SIRPA may offer new therapeutic opportunities for bone regeneration.

The Causes Behind the Survival Paradox in Non-Metastatic Colorectal Cancer Patients and its Impact on the Treatment Regimen: A Retrospective Cohort Study.

BACKGROUND: The survival paradox (ie, the prognosis of the population at earlier tumor stages is worse than that of the population at later stages) has been observed in colorectal cancer based on the American Joint Committee on Cancer Tumor-Nodes-Metastases staging system. We aimed to clarify the reason for the survival paradox and its impact on patient treatment. METHODS: We conducted a retrospective study analyzing eligible patients with colorectal cancer from the Surveillance, Epidemiology, and End Results database and Zhejiang Cancer Hospital between 2010 and 2019. Adjusting for confounders using propensity score matching allowed confirmation of the effect of staging on the survival paradox. RESULTS: Based on the Surveillance, Epidemiology, and End Results database, the subgroups with survival paradox might be IIB/C versus IIIA, IIA versus IIIA, and T4N0 (IIB/C) versus T3N1 (IIIB). After propensity score matching, stage IIB/C still had a worse prognosis than stage IIIA (5-year overall survival: 69.3% vs 78.5%, P < .001). Interestingly, the proportion of stage IIIA people receiving chemotherapy was higher than that of stage IIB/C (P < .001), and logistic regression models showed that staging was the reason for deciding whether a patient receives chemotherapy or not. These phenomena between stage IIB/C and IIIA were verified in the local database. CONCLUSION: These results suggested that the survival paradox was mainly due to underestimation of stage T4 weights or overestimation of stage N1 weights, and the low proportion of chemotherapy in patients with T4N0M0 colorectal cancer (proven to be more malignant than stage IIIA) might be related to the assignment to earlier stages, resulting in a lack of attention and poor compliance to chemotherapy in these patients.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Efficacy and safety of Wuhu oral liquid in treating acute soft tissue injuries: a multicenter, randomized, double-blind, double-dummy, parallel-controlled trial.

Background: Wuhu Oral Liquid (WHOL) is a modified preparation derived from the famous Wuhu Powder, which has a long history of use in treating traumatic injuries. This preparation has anti-inflammatory and analgesic properties and accelerates recovery following acute soft tissue injuries. Aims: To evaluate the efficacy and safety of WHOL in treating acute soft tissue injury associated with qi stagnation and blood stasis syndrome and to provide a basis for applying for the protection of varieties of Chinese medicine for WHOL. Methods: This study was a randomized, controlled, double-blind, multicenter clinical trial in which Fufang Shang Tong Capsule (FFSTC) was selected as the control drug. A total of 480 subjects with acute soft tissue injury associated with qi stagnation and blood stasis syndrome were randomly divided into a test and control group in a 3:1 ratio. The duration of drug treatment was 10 days. The primary outcome was Visual Analogue Scale (VAS) score for pain (including pain at rest and pain on activity). Secondary outcomes included the disappearance time of the pain at rest and on activity; the curative effect of TCM syndrome and improvement in the individual symptoms of TCM (swelling, ecchymosis, and dysfunction); and changes in C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Safety was assessed using vital signs, laboratory examinations, electrocardiograms, and physical examinations. Results: Patient compliance was satisfactory in both groups (all between 80% and 120%). After 4 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain at rest (-1.88 ± 1.13 vs. -1.60 ± 0.93, p < 0.05) and on activity (-2.16 ± 1.18 vs. -1.80 ± 1.07, p < 0.05). After 7 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain on activity (-3.87 ± 1.60 vs. -3.35 ± 1.30, p < 0.01) and improving swelling (cure rate: 60.4% vs. 46.2%, p < 0.05; obvious effective rate: 60.7% vs. 47.0%, p < 0.05). After 10 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the levels of CRP (-0.13 ± 2.85 vs. 0.25 ± 2.09, p < 0.05) and improving the TCM syndrome (cure rate: 44.1% vs. 30.8%, p < 0.05) and swelling (cure rate: 75.6% vs. 67.5%, p < 0.01; obvious effective rate: 75.6% vs. 68.4%, p < 0.05; effective rate: 77.0% vs. 71.8%, p < 0.05). The disappearance time of pain at rest was 8 days in both groups and 9 days on activity in both groups. In addition, there was no statistical difference between the incidence of adverse events (4.5% vs. 2.6%, p > 0.05) and adverse reactions (0.3% vs. 0%, p > 0.05) between the WHOL group and the FFSTC group. No serious adverse events occurred in either group, and no subjects were withdrawn because of adverse events. Conclusion: WHOL relieves the symptoms caused by acute soft tissue injury associated with qi stagnation and blood stasis syndrome more rapidly than FFSTC, and it is effective and safe in the treatment of acute soft tissue injury. Future studies still need a larger sample size to verify its efficacy and safety. Clinical Trial Registration: https:// www.chictr.org.cn/showproj.html?proj=149531, Identifier ChiCTR2200056411.

Mechanisms of intermittent theta-burst stimulation attenuating nerve injury after ischemic reperfusion in rats through endoplasmic reticulum stress and ferroptosis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) exerts neuroprotective effects early in cerebral ischemia/reperfusion (I/R) injury. Intermittent theta-brust stimulation (iTBS), a more time-efficient modality of rTMS, improves the efficiency without at least decreasing the efficacy of the therapy. iTBS elevates cortical excitability, and in recent years it has become increasingly common to apply iTBS to patients in the early post-IS period. However, little is known about the neuroprotective mechanisms of iTBS. Endoplasmic reticulum stress (ERS), and ferroptosis have been shown to be involved in the development of I/R injury. We aimed to investigate the potential regulatory mechanisms by which iTBS attenuates neurological injury after I/R in rats. METHODS: Rats were randomly divided into three groups: sham-operated group, MCAO/R group, and MCAO/R + iTBS group, and were stimulated with iTBS 36 h after undergoing middle cerebral artery occlusion (MCAO) or sham-operated. The expression of ERS, ferroptosis, and apoptosis-related markers was subsequently detected by western blot assays. We also investigated the mechanism by which iTBS attenuates nerve injury after ischemic reperfusion in rats by using the modified Neurological Severity Score (mNSS) and the balance beam test to measure nerve function. RESULTS: iTBS performed early in I/R injury attenuated the levels of ERS, ferroptosis, and apoptosis, and improved neurological function, including mNSS and balance beam experiments. It is suggested that this mode of stimulation reduces the cost per treatment by several times without compromising the efficacy of the treatment and could be a practical and less costly intervention.

Efficacy and Safety of Transarterial Chemoembolization Plus Donafenib with or without Immune Checkpoint Inhibitors as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

Purpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus donafenib with immune checkpoint inhibitors (ICIs) (T+D+I) versus TACE plus donafenib (T+D) as the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). Methods: This retrospective study included patients with unresectable HCC who received T+D+I or T+D between June 2021 and February 2023. The tumor response was analyzed according to the modified Response Evaluation Criteria in Solid Tumors. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) in the two groups were compared before and after propensity score matching (PSM). Cox's proportional-hazards regression model was used to analyze factors affecting PFS and OS. Results: This study included 69 patients: 41 patients in the T+D group and 28 patients in the T+D+I group. After PSM, 26 patients in each group were analyzed. Patients in the T+D+I group had a higher DCR (96.2% vs 73.1%, P = 0.021), longer median PFS (13.1 vs 7.2 months, P = 0.017), and longer median OS (23.1 vs 14.7 months, P = 0.021) than those in the T+D group. The ORR in the two groups was similar (53.8% vs 50.0%, P = 0.781). Multivariate analyses revealed that T+D+I treatment and total bilirubin levels of <20 µmol/L were independent prognostic factors for long PFS. T+D+I treatment, Child-Pugh class A, and single-lobe tumor distribution were independent prognostic factors for long OS. The incidence of TRAEs in the two groups was similar (P > 0.05). Conclusion: In comparison with TACE plus donafenib, TACE plus donafenib with ICIs could significantly improve DCR, PFS, and OS as a potential first-line treatment for unresectable HCC with an acceptable safety profile.

The potential role of CDC20 in tumorigenesis, cancer progression and therapy: A narrative review.

The cell division cycle 20 homologue (CDC20) is known to regulate the cell cycle. Many studies have suggested that dysregulation of CDC20 is associated with various pathological processes in malignant solid tumors, including tumorigenesis, progression, chemoradiotherapy resistance, and poor prognosis, providing a biomarker for cancer diagnosis and prognosis. Some researchers have demonstrated that CDC20 also regulates apoptosis, immune microenvironment, and tumor angiogenesis. In this review, we have systematically summarized the biological functions of CDC20 in solid cancers. Furthermore, we briefly synthesized multiple medicines that inhibited CDC20. We anticipate that CDC20 will be a promising and effective biomarker and therapeutic target for the treatment of human cancer.

An Efficient Transformation System for Fast Production of VcCHS Transgenic Blueberry Callus and Its Expressional Analysis.

The Agrobacterium tumefaciens-mediated transformation for blueberries remains less efficient than is desirable. A new leaf callus regeneration and genetic transformation system was investigated in blueberries in this study. The leaf explants of cv. 'Legacy' and 'Northland' were used to establish the stable callus induction system when placed on the woody plant medium (WPM) supplemented with 1.0 mg·L-1 2, 4-D, 0.4 mg·L-1 6-BA for 30 d; then, the callus was sub-cultured in the proliferation medium supplemented with 1.5 mg·L-1 2, 4-D, 0.4 mg·L-1 6-BA in the darkness at 25 °C every 30 days. The co-cultivation of callus with A. tumefaciens was operated on WPM plus 100 µM acetosyringone for 4 days; then, the transferred callus was grown in WPM supplemented with 1.5 mg·L-1 2,4-D, 0.4 mg·L-1 6-BA, 50 mg·L-1 hygromycin, and 200 mg·L-1 cefotaxime. The VcCHS transgenic blueberry callus with both GFP signal and Hyg resistance was obtained from the transformed callus of cv. 'Northland'. The rate of GFP signal detected in the transformed callus was as high as 49.02%, which was consistent with the PCR assay. Collectively, this study provides a highly efficient genetic transformation system in blueberry callus and a powerful approach for the molecular breeding of blueberries.

Comparative analysis of the difference in flavonoid metabolic pathway during coloring between red-yellow and red sweet cherry (Prunus avium L.).

The color of a fruit is an important contributor to the perception of its nutritional value. It is widely acknowledged that the color of sweet cherry changes obviously during ripening. Variations in anthocyanins and flavonoids account for the heterogeneous color of sweet cherries. In this study, we showed that anthocyanins but not carotenoids determine the color of sweet cherry fruits. The difference between red-yellow and red sweet cherry may be attributed to seven anthocyanins, including Cyanidin-3-O-arabinoside, Cyanidin-3,5-O-diglucoside, Cyanidin 3-xyloside, Peonidin-3-O-glucoside, Peonidin-3-O-rutinoside, Cyanidin-3-O-galactoside, Cyanidin-3-O-glucoside (Kuromanin), Peonidin-3-O-rutinoside-5-O-glucoside, Pelargonidin-3-O-glucoside and Pelargonidin-3-O-rutinoside. The content of 85 flavonols differed between red and red-yellow sweet cherries. The transcriptional analysis identified 15 key structural genes involved in the flavonoid metabolic pathway and four R2R3-MYB transcription factors. The expression level of Pac4CL, PacPAL, PacCHS1, PacCHS2, PacCHI, PacF3H1, PacF3H2, PacF3'H, PacDFR, PacANS1, PacANS2, PacBZ1 and four R2R3-MYB were positively correlated with anthocyanin content (ps < 0.05). PacFLS1, PacFLS2 and PacFLS3 expression was negatively correlated with anthocyanin content but positively correlated with flavonols content (ps < 0.05). Overall, our findings suggests that the heterogeneous expression of structural genes in the flavonoid metabolic pathway accounts for the variation in levels of final metabolites, leading to differences between red 'Red-Light' and red-yellow 'Bright Pearl'.

MS-FANet: Multi-scale feature attention network for liver tumor segmentation.

Accurate segmentation of liver tumors is a prerequisite for early diagnosis of liver cancer. Segmentation networks extract features continuously at the same scale, which cannot adapt to the variation of liver tumor volume in computed tomography (CT). Hence, a multi-scale feature attention network (MS-FANet) for liver tumor segmentation is proposed in this paper. The novel residual attention (RA) block and multi-scale atrous downsampling (MAD) are introduced in the encoder of MS-FANet to sufficiently learn variable tumor features and extract tumor features at different scales simultaneously. The dual-path feature (DF) filter and dense upsampling (DU) are introduced in the feature reduction process to reduce effective features for the accurate segmentation of liver tumors. On the public LiTS dataset and 3DIRCADb dataset, MS-FANet achieved 74.2% and 78.0% of average Dice, respectively, outperforming most state-of-the-art networks, this strongly proves the excellent liver tumor segmentation performance and the ability to learn features at different scales.