Trend of robot-assisted surgery system in gastrointestinal and liver surgery: A bibliometric analysis.

BACKGROUND: Robot-assisted gastrointestinal and liver surgery has been an important development direction in the field of surgery in recent years and it is also one of the fastest developing and most concerning fields in surgical operations. AIM: To illustrate the major areas of research and forward-looking directions over the past twenty-six years. METHODS: Using the Web of Science Core Collection database, a comprehensive review of scholarly articles pertaining to robot-assisted gastrointestinal and liver surgery was researched out between 2000 and 2023. We used Citespace (Version 6.2.4) and Bibliometrix package (Version 4.3.0) to visualize the analysis of all publications including country, institutional affiliations, authors, and keywords. RESULTS: In total, 346 articles were retrieved. Surgical Endoscopy had with the largest number of publications and was cited in this field. The United States was a core research country in this field. Yonsei University was the most productive institution. The current focus of this field is on rectal surgery, long-term prognosis, perioperative management, previous surgical experience, and the learning curve. CONCLUSION: The scientific interest in robot-assisted gastrointestinal and liver surgery has experienced a significant rise since 1997. This study provides new perspectives and ideas for future research in this field.

Revisiting the association between pretreatment thrombocytosis and cancer survival outcomes: an umbrella review of meta-analyses.

BACKGROUND: Although associations have been reported linking pretreatment thrombocytosis to cancer survival outcomes, the validity and strength of existing observational evidence have been contested. This study aimed to conduct an umbrella review to comprehensively appraise the strength, validity and credibility of these reported associations. METHODS: We searched Medline, Embase and Cochrane Database of Systematic Reviews from inception to 8 April 2023 to retrieve meta-analyses of observational studies. Meta-analyses were re-performed using a random-effect model and the strength of evidence was graded as convincing, highly suggestive, suggestive and weak according to seven pre-defined quantitative criteria reflecting statistical significance, amount of data, heterogeneity, and evidence of bias. The quality of review was appraised using the AMSTAR2 checklist. The umbrella review was reported adhering to the PRISMA guideline and was registered on PROSPERO (CRD42023455391). RESULTS: A total of 21 unique meta-analyses investigating ten cancer subtypes were included. All meta-analyses reported inferior survival outcome in cancer patients with pretreatment thrombocytosis, and 18 of them (85.7%) yielded statistically significant results (P < 0.05). Consistent effects were observed across meta-analyses that adopted different cut-off values (i.e. platelet count > 300 or 400 × 109 /L) to define thrombocytosis. Although evidence appraisal did not identify convincing evidence (Class I), the associations of thrombocytosis with inferior overall survival of lung, gastric, colorectal cancer and malignant mesothelioma were classified as highly suggestive evidence (Class II). According to AMSTAR2 ratings, no meta-analysis was identified with high or moderate quality. CONCLUSIONS: Our findings consolidated the association between pretreatment thrombocytosis and poor survival outcomes in various cancers. Nonetheless, the absence of convincing associations indicates a need for further large-scale, high-quality evidence to confirm whether platelets can serve as a prognostic predictor or a therapeutic target.

Tuberculosis to lung cancer: application of tuberculosis signatures in identification of lung adenocarcinoma subtypes and marker screening.

Background: There is an association between LUAD and TB, and TB increases the risk of lung adenocarcinogenesis. However, the role of TB in the development of lung adenocarcinoma has not been clarified. Methods: DEGs from TB and LUAD lung samples were obtained to identify TB-LUAD-shared DEGs. Consensus Clustering was performed on the TCGA cohort to characterize unique changes in TB transcriptome-derived lung adenocarcinoma subtypes. Prognostic models were constructed based on TB signatures to explore the characterization of subgroups. Finally, experimental validation and single-cell analysis of potential markers were performed. Results: We characterized three molecular subtypes with unique clinical features, cellular infiltration, and pathway change manifestations. We constructed and validated TB-related Signature in six cohorts. TB-related Signature has characteristic alterations, and can be used as an effective predictor of immunotherapy response. Prognostically relevant novel markers KRT80, C1QTNF6, and TRPA1 were validated by RT-qPCR. The association between KRT80 and lung adenocarcinoma disease progression was verified in Bulk transcriptome and single-cell transcriptome. Conclusion: For the first time, a comprehensive bioinformatics analysis of tuberculosis signatures was used to identify subtypes of lung adenocarcinoma. The TB-related Signature predicted prognosis and identified potential markers. This result reveals a potential pathogenic association of tuberculosis in the progression of lung adenocarcinoma.

Cross-sectional investigation of the distribution characteristics and prognostic significance of lateral lymph nodes in patients with rectal cancer.

BACKGROUND: Information about the distribution characteristics and prognostic significance of lateral lymph nodes (LLNs) on primary computed tomography (CT) scan in rectal cancer patients is lacking. METHODS: Between January 2013 and December 2016, patients with pathologically proved rectal cancer and pretreatment abdominal enhanced CT in our department were screened. We firstly redivided LLNs into seven categories based on their locations. Then, the number and distribution of all measurable LLNs and the characteristics of the largest LLN in each lateral compartment were recorded. Furthermore, we investigated the long-term outcomes in patients with different LLN characteristics and LLN risk scoring. RESULTS: A total of 572 patients were enrolled in this study. About 80% of patients had measurable LLNs, and most patients developed measurable LLNs in the obturator cranial compartment. Lateral local recurrence (LLR) was observed in 20 patients, which accounted for 83.3% of the local recurrence (LR). Patients with the largest LLN short-axis diameter >10 mm had a poor prognosis, which was similar to that in patients with simultaneous distant metastasis (SDM). Patients with LLN risk scoring ≥2 had a worse prognosis than those with LLN risk scoring <2, while better than those with SDM. CONCLUSION: This study suggests that LLR is the main locoregional recurrence pattern. Most rectal cancer patients have measurable LLNs on primary CT scan. However, patients with enlarged LLNs <10 mm or LLN risk scoring <2 still have a significantly better prognosis than patients with SDM, which indicated the potential value of locoregional treatment for these LLNs.

Extent of Lymphadenectomy for Surgical Management of Right-Sided Colon Cancer: The Randomized Phase III RELARC Trial.

PURPOSE: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. METHODS: This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). RESULTS: Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group). CONCLUSION: This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

Primary tumor resection for asymptomatic colorectal cancer patients with synchronous unresectable metastases: a meta-analysis of randomized controlled trials and case-matched studies.

PURPOSE: The value of upfront primary tumor resection (PTR) for asymptomatic unresectable metastatic colorectal cancer (mCRC) patients remains contentious. This meta-analysis aimed to assess the prognostic significance of upfront PTR for asymptomatic unresectable mCRC. METHODS: A systematic literature search was performed on June 21st, 2024. To minimize the bias and ensure robust evidence, only randomized controlled trials (RCTs) and case-matched studies (CMS) that compared PTR followed by chemotherapy to chemotherapy alone were included. The primary outcome was overall survival (OS), while cancer-specific survival (CSS) served as the secondary outcome. RESULTS: Eight studies (three RCTs and five CMS) involving 1221 patients were included. Compared to chemotherapy alone, upfront PTR followed by chemotherapy did not improve OS (hazard ratios [HR] 0.91, 95% confidence interval [CI] 0.79-1.04, P = 0.17), but was associated with slightly better CSS (HR 0.59, 95% CI 0.40-0.88, P = 0.009). CONCLUSIONS: The current limited evidence indicates that upfront PTR does not improve OS but may enhance CSS in asymptomatic unresectable mCRC patients. Ongoing trials are expected to provide more reliable evidence on this issue.

Dual Hydrogen Production System: Synergistic Effect of Ru and Ce Over Cu2O Nanotubes Drives Hydrogen Evolution and Formaldehyde Oxidation.

Water splitting for hydrogen production is limited by high cell voltage and low energy conversion efficiencies due to the slow kinetic process of the oxygen evolution reaction (OER). Here, an electrolytic system is constructed in which the cathode and anode co-release H2 at ultra-low input voltage using formaldehyde oxidation reaction (FOR) instead of OER. The prepared RuCe co-doped Cu2O nanotubes on copper foam (RuCe-Cu2O/CF) are used as electrode materials for the HER-FOR system. A current density of 0.8 A cm-2 is achieved at 0.55 V, and a stable hydrogen production process is realized at both the cathode and anode. Density functional theory (DFT) studies show that the synergistic effect of Ru and Ce drives: i) the d-band center of RuCe-Cu2O/CF away from the Fermi energy level; ii) the energy barrier for the C─H cracking of the H2C(OH)O* intermediate in FOR is lowered, which promotes the formation of H2 from H*, and iii) ΔGH* tends to 0 (-0.1 eV), optimizing the reaction kinetics of HER. This work provides a new design for an efficient catalyst for dual hydrogen production systems from water splitting.

Construction and Application of a Multienzyme System for Synthesis of L-malate.

This study aimed to develop a multienzymatic system for synthesis of L-malate. First, recombinant Escherichia coli strains were constructed expressing maleic acid cis-trans isomerase (MaiA) or fumarase C (FumC) from different sources. Serratia marcescens MaiA (SMaiA) and E. coli FumC (ECFumC) showed good catalytic performance. Next, six co-expression systems for SMaiA and ECFumC were constructed. E. coli BL21 (DE3)-pRSFDuet-1-ecfumC-smaiA (named strain pFM2) had the highest L-malate catalytic activity. In 7-L fed-batch fermentation, the SMaiA and ECFumC activities of strain pFM2 wet cells were 43.4 and 154.5 U/g, respectively, 2.4- and 10.7-fold the values that were obtained in shaken flasks. Finally, a whole-cell catalytic process was established for the production of L-malate by strain pFM2 with maleate as the substrate. When the dose of pFM2 wet cells was 0.5 g/100 mL and 1 mol/L maleate was the substrate, the catalytic process was completed within 4 h. Notably, the intermediate fumarate was almost absent during the conversion process. The concentration of L-malate reached 143.8 g/L with a yield of 0.60 g/(L·min). The molar conversion rate of the substrate was 98.4%. These findings lay a foundation for the industrial application of multienzymatic synthesis of L-malate.

Identification and validation of tryptophan-related gene signatures to predict prognosis and immunotherapy response in lung adenocarcinoma reveals a critical role for PTTG1.

Introduction: Tryptophan metabolism is strongly associated with immunosuppression and may influence lung adenocarcinoma prognosis as well as tumor microenvironment alterations. Methods: Sequencing datasets were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Two different clusters were identified by consensus clustering, and prognostic models were established based on differentially expressed genes (DEGs) in the two clusters. We investigated differences in mutational landscapes, enrichment pathways, immune cell infiltration, and immunotherapy between high- and low-risk scoring groups. Single-cell sequencing data from Bischoff et al. were used to identify and quantify tryptophan metabolism, and model genes were comprehensively analyzed. Finally, PTTG1 was analyzed at the pan-cancer level by the pan-TCGA cohort. Results: Risk score was defined as an independent prognostic factor for lung adenocarcinoma and was effective in predicting immunotherapy response in patients with lung adenocarcinoma. PTTG1 is one of the key genes, and knockdown of PTTG1 in vitro decreases lung adenocarcinoma cell proliferation and migration and promotes apoptosis and down-regulation of tryptophan metabolism regulators in lung adenocarcinoma cells. Discussion: Our study revealed the pattern and molecular features of tryptophan metabolism in lung adenocarcinoma patients, established a model of tryptophan metabolism-associated lung adenocarcinoma prognosis, and explored the roles of PTTG1 in lung adenocarcinoma progression, EMT process, and tryptophan metabolism.

MRI Tumor Regression Response to Neoadjuvant Chemotherapy Alone without Radiation for Rectal Adenocarcinoma.

Background Neoadjuvant chemotherapy (NCT) is gaining acceptance for the management of locally advanced rectal cancer (LARC) in patients without negative prognostic factors. However, the value of MRI in evaluating tumor response after NCT remains unclear. Purpose To investigate the accuracy of MRI in assessing pathologic complete response in participants with LARC who underwent surgery after NCT without radiation. Materials and Methods A retrospective imaging substudy was conducted within two consecutive prospective clinical trials: the expanded phase II trial (from December 2017 to May 2021) and the COPEC trial (comparison of tumor response to two or four cycles of neoadjuvant chemotherapy alone, ongoing from August 2021). All included participants received four cycles of capecitabine combined with oxaliplatin (or CAPOX) before surgery. Three radiologists who were blinded to the clinicopathologic data independently evaluated the tumor response using five methods, namely, MR tumor regression grade (MR-TRG) alone, diffusion-weighted imaging (DWI) alone, DWI-modified MR-TRG (DWImodMR-TRG), MRI complete response, and radiologic neoadjuvant response score. With pathologic assessment serving as the reference standard, the positive and negative predictive values, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined to evaluate the accuracy and performance of these models. The AUCs of the models were compared using the DeLong test. Results A total of 224 participants were included, comprising 119 from the expanded phase II trial (median age, 61 years [IQR, 53-67]; 89 male) and 105 from the COPEC trial (median age, 59 years [IQR, 53-67]; 65 male). MR-TRG, DWI, DWImodMR-TRG, MRI complete response, and the radiologic neoadjuvant response score were associated with pathologic complete response. DWImodMR-TRG achieved the highest AUC of 0.90 (95% CI: 0.85, 0.95), with a specificity of 89% (162 of 182) and a negative predictive value of 93% (162 of 174). Conclusion MRI-based models were accurate for determining pathologic complete response in participants with LARC following NCT. DWI improved the predictive performance of MRI-based assessment. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Santiago and Shur in this issue.

Electrocatalytic Valorization of Nitrate and Polyester Plastic for Simultaneous Production of Ammonia and Glycolic Acid.

Electrochemical upcycling of nitrate and polyester plastic into valuable products is an ideal solution to realize the resource utilization. Here, the co-production of ammonia (NH3) and glycolic acid (GA) via electrochemical upcycling of nitrate and polyethylene terephthalate (PET) plastics over mesoporous Pd3Au film on Ni foam (mPd3Au/NF), which is synthesized by micelle-assisted replacement method, is proposed. The mPd3Au/NF with well-developed mesoporous structure provides abundant active sites and facilitated transfer channels and strong electronic effect. As such, the mPd3Au/NF exhibits high Faraday efficiencies of 97.28% and 95.32% at 0.9 V for the formation of NH3 and GA, respectively. Theoretical results indicate that the synergistic effect of Pd and Au can optimize adsorption energy of key intermediates *NOH and *OCH2-CH2OH on active sites and increase bond energy of C─C band, thereby improving the activity and selectivity for the formation of NH3 and GA. This work proposes a promising strategy for the simultaneous conversation of nitrate and PET plastic into high-value NH3 and GA.

Unraveling Mechanism for Microstructure Engineering toward High-Capacity Nickel-Rich Cathode Materials.

Microstructural engineering on nickel-rich layered oxide (NRLO) cathode materials is considered a promising approach to increase both the capacity and lifespan of lithium-ion batteries by introducing high valence-state elements. However, rational regulation on NRLO microstructures based on a deep understanding of its capacity enhancement mechanism remains challenging. Herein for the first time, it is demonstrated that an increase of 14 mAh g-1 in reversible capacity at the first cycle can be achieved via tailoring the micro and nano structure of NRLO through introducing tungsten. Aberration-corrected scanning transmission electron microscopy (STEM) characterization reveals that the formation of a modified microstructure featured as coherent spinel twin boundaries. Theoretical modeling and electrochemical investigations further demonstrate that the capacity increase mechanism is related to such coherent spinel twin boundaries, which can lower the Li+ diffusion barrier and thus allow more Li+ to participate in deeper phase transitions. Meanwhile, the surface and grain boundaries of NRLOs are found to be modified by generating a dense and uniform LiWxOy phase, which further extends its cycle life by reducing side reactions with electrolytes. This work enables a comprehensive understanding of the capacity-increased mechanism and endows the remarkable potential of microstructural engineering for capacity- and lifespan-increased NRLOs.

Elucidating the mechanism of action of Isobavachalcone induced autophagy and apoptosis in non-small cell lung cancer by network pharmacology and experimental validation methods.

BACKGROUND: Lung cancer is the leading cause of cancer deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer-related mortality. In recent years, there have been numerous treatments for non-small cell lung cancer, but the cure and survival rates are still extremely low. Isobavachalcone (IBC) belongs to the chalcone component of the traditional Chinese medicine Psoralea corylifolia L., and is a unique Protein kinase B (AKT) pathway inhibitor with significant anticancer effects. Previous studies have shown that IBC possess a variety of biological properties, including anti-cancer, anti-inflammatory, and antioxidant properties. This study focused on the use of network pharmacology analysis, molecular docking technology and experimental validation to elucidate the potential mechanisms of IBC for the treatment of NSCLC. METHODS: Screening key genes and pathways of IBC action in NSCLC using network pharmacology. The IBC target genes were from The Encyclopedia of Traditional Chinese Medicine (ETCM) and BATMAN-TCM databases, the NSCLC target genes were from GeneCards, Online Mendelian Inheritance in Man (OMIM) and The Therapeutic Target database (TTD) databases, both of which were taken as intersecting genes for protein-protein interaction network analysis and enrichment analysis, and the binding energies of the compounds to the core targets were further verified by molecular docking. Cell lines in vitro experiments were then performed to further unravel the mechanism of IBC for NSCLC. RESULTS: A total of 279 potential targets were retrieved by searching the intersection of IBC and NSCLC targets. Protein-protein interaction (PPI) network analysis indicated that 6 targets, including AKT1, RXRA, NCOA1, RXRB, RARA, PPARG were hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that IBC treatment of NSCLC mainly involves steroid binding, transcription factor activity, Pathways in cancer, cAMP signaling pathway, Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Among them, the AMPK signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of NSCLC. Then, the results of in vitro experiment indicated that IBC could inhibit proliferation of NSCLC cells and induce cell autophagy and apoptosis. The results also showed that IBC could increase the protein expression of AMPK and decrease the protein expression of AKT and mammalian target of rapamycin (mTOR), suggesting that IBC can treat NSCLC by inducing cellular autophagy and apoptosis as well as modulating AMPK and AKT signaling pathways. CONCLUSIONS: In summary, this study provided a new insight into the protective mechanism of IBC against NSCLC through network pharmacology and experimental validation.

Head-to-head comparison of the diagnostic performance between 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer: a systematic review and meta-analysis.

This study aimed to compare the detection rates of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer. A systematic search of major medical databases was conducted to identify studies up to September 2023. The primary outcome assessed was the detection rate of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in the primary tumor. Pooled risk ratios with a 95% CI were calculated using random-effect models to adjust for heterogeneity. Eight studies were included in the meta-analysis. 68Ga-FAPI-04 PET/CT has higher uptakes in lymph nodes, bone, and peritoneal metastasis compared with 18F-FDG PET/CT. The detection rate of 68Ga-FAPI-04 PET/CT based on lesion was better for lymph node metastasis (RR = 0.63, 95% CI 0.47-0.84, P = 0.002) and peritoneal metastasis (RR = 0.52, 95% CI 0.32-0.85, P = 0.009), both imaging modalities had essentially the same diagnostic efficacy in primary tumor (RR = 0.99, 95% CI 0.96-1.02, P = 0.49). 68Ga-FAPI-04 as a highly promising PET/CT tracer was superior to 18F-FDG PET/CT in colorectal cancer, especially in detecting lymph node metastases and peritoneal metastases.

Targeting CXCR4/CXCL12 axis via [177Lu]Lu-DOTAGA.(SA.FAPi)2 with CXCR4 antagonist in triple-negative breast cancer.

PURPOSE: Radiopharmaceutical therapies targeting fibroblast activation protein (FAP) have shown promising efficacy against many tumor types. But radiopharmaceuticals alone in most cases are insufficient to completely eradicate tumor cells, which can partially be attributed to the protective interplay between tumor cells and cancer-associated fibroblasts (CAFs). The C-X-C chemokine receptor type 4/C-X-C motif chemokine 12 (CXCR4/CXCL12) interaction plays an important role in orchestrating tumor cells and CAFs. We hereby investigated the feasibility and efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2, a FAP-targeting radiopharmaceutical, in combination with AMD3100, a CXCR4 antagonist, in a preclinical murine model of triple-negative breast cancer (TNBC). METHODS: Public database was first interrogated to reveal the correlation between CAFs' scores and the prognosis of TNBC patients, as well as the expression levels of FAP and CXCR4 in normal tissues and tumors. In vitro therapeutic efficacy regarding cell proliferation, migration, and colony formation was assessed in BALB/3T3 fibroblasts and 4T1 murine breast cancer cells. In vivo therapeutic efficacy was longitudinally monitored using serial 18F-FDG, [18F]AlF-NOTA-FAPI-04, and [68Ga]Ga-DOTA-Pentixafor PET/CT scans and validated using tumor sections through immunohistochemical staining of Ki-67, α-SMA, CXCR4, and CXCL12. Intratumoral abundance of myeloid-derived suppressive cells (MDSCs) was analyzed using flow cytometry in accordance with the PET/CT schedules. Treatment toxicity was evaluated by examining major organs including heart, lung, liver, kidney, and spleen. RESULTS: CAFs' scores negatively correlated with the survival of TNBC patients (p < 0.05). The expression of CXCR4 and FAP was both significantly higher in tumors than in normal tissues. The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 significantly suppressed cell proliferation, migration, and colony formation in cell culture, and exhibited synergistic effects in 4T1 tumor models along with a decreased number of MDSCs. PET/CT imaging revealed lowest tumor accumulation of 18F-FDG and [18F]AlF-NOTA-FAPI-04 on day 13 and day 14 after treatment started, both of which gradually increased at later time points. A similar trend was observed in the IHC staining of Ki-67, α-SMA, and CXCL12. CONCLUSION: The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 is a feasible treatment against TNBC with minimal toxicity in main organs.

Nuclear miRNAs as transcriptional regulators in processes related to various cancers (Review).

MicroRNAs (miRNAs) are noncoding small nucleic acids that contain ~22 nucleotides and are considered to promote the degradation or inhibit the translation of mRNA by targeting its 3'­untranslated region. However, growing evidence has revealed that nuclear miRNAs, combined with gene promoters or enhancers, are able to directly mediate gene transcription. These miRNAs exert a critical influence on cancer progression by affecting cell growth, migration and invasion. In this review, the direct regulation of gene expression by nuclear miRNAs at the transcriptional level was discussed and summarized, and their mechanisms of action in cancers were highlighted with reference to the various body systems.

Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

Underlying effect of SMAD4 gene polymorphism on risk prediction of papillary thyroid carcinoma in Chinese population.

Objective: This research intends to explore how variations in the SMAD4 gene impact papillary thyroid carcinoma (PTC) among patients in China. Methods: The rs10502913 and rs12968012 polymorphisms were genotyped in 405 subjects using SNP-scan high-throughput technology. Differential mRNA expression of SMAD4 was analyzed using data from TCGA and GSE33630, and protein level expression differences were analyzed using immunohistochemistry. Results: The results showed that SMAD4 mRNA expression was lower in thyroid cancer (THCA) tissues than in normal tissues. Immunohistochemical results showed that the expression level of SMAD4 in normal tissue, thyroid papillary carcinoma tissue and poorly differentiated tissue was significantly different. We found that SMAD4 mismatch variants (rs10502913 and rs12968012) were associated with PTC susceptibility. Specifically, the SMAD4-rs10502913 genotypes (GA and AA) showed a notable correlation with a lower likelihood of PTC in comprehensive and segmented studies (genotype GA: OR (95% CI) = 0.270 (0.077-0.950), p = 0.041; genotype AA: OR (95% CI) = 0.103 (0.025-0.416), p = 0.001). We categorized the immunohistochemical results according to genotype and found that rs10502913-GG protein level was expressed at the lowest level, and both GA and AA were higher than GG (GG vs. AA, P < 0.05), and rs12968012-CG protein level was expressed at the lowest level, and both GG and CC were higher than CG (GG vs. CG, P < 0.01). Conclusion: Two missense variants of SMAD4 (rs10502913 and rs12968012) are associated with reduced risk of papillary thyroid carcinoma, possibly by reducing protein expression leading to susceptibility to papillary thyroid carcinoma.