Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Two-dimensional Janus Polarization Functioned by Mechanical Force.

Two-dimensional (2D) polarization materials have emerged as promising candidates for meeting the demands of device miniaturization, attributed to their unique electronic configurations and transport characteristics. Although the existing inherent and sliding mechanisms have been increasingly investigated in recent years, strategies for inducing 2D polarization with innovative mechanisms remain rare. In this study, we introduce a novel 2D Janus state by modulating the puckered structure. Combining scanning probe microscopy, transmission electron microscopy, and density functional theory calculations, we realized force-triggered out-of-plane and in-plane dipoles with distorted smaller warping in GeSe. The Janus state is preserved after removing the external mechanical perturbation, which could be switched by modulating the sliding direction. Our work offers a versatile method to break the space inversion symmetry in a 2D system to trigger polarization in the atomic scale, which may open an innovative insight into configuring novel 2D polarization materials. This article is protected by copyright. All rights reserved.

Microcystin-LR (MC-LR) inhibits green algae growth by regulating antioxidant and photosynthetic systems.

Microcystins release from bloom-forming cyanobacteria is considered a way to gain competitive advantage in Microcystis populations, which threaten water resources security and aquatic ecological balance. However, the effects of microcystins on microalgae are still largely unclear. Through simulated culture experiments and the use of UHPLC-MS-based metabolomics, the effects of two microcystin-LR (MC-LR) concentrations (400 and 1,600 µg/L) on the growth and antioxidant properties of three algae species, the toxic Microcystis aeruginosa, a non-toxic Microcystis sp., and Chlorella vulgaris, were studied. The MC-LR caused damage to the photosynthetic system and activated the protective mechanism of the photosynthetic system by decreasing the chlorophyll-a and carotenoid concentrations. Microcystins triggered oxidative stress in C. vulgaris, which was the most sensitive algae species studied, and secreted more glycolipids into the extracellular compartment, thereby destroying its cell structure. However, C. vulgaris eliminated reactive oxygen species (ROS) by secreting terpenoids, thereby resisting oxidative stress. In addition, two metabolic pathways, the vitamin B6 and the sphingolipid pathways, of C. vulgaris were significantly disturbed by microcystins, contributing to cell membrane and mitochondrial damage. Thus, both the low (400 µg/L) and the high (1,600 µg/L) MC-LR concentration inhibited algae growth within 3 to 7 days, and the inhibition rates increased with the increase in the MC-LR concentration. The above results indicate that the toxin-producing Microcystis species have a stronger toxin tolerance under longer-term toxin exposure in natural water environments. Thus, microcystins participates in interspecific interaction and phytoplankton population regulation and creates suitable conditions for the toxin-producing M. aeruginosa to become the dominant species in algae blooms.

Long-term 4-nonylphenol exposure drives cervical cell malignancy through MAPK-mediated ferroptosis inhibition.

4-NP (4-nonylphenol), a prevalent environmental endocrine disruptor with estrogenic properties, is commonly detected in drinking water and food sources. It poses a significant risk of endocrine disruption, thereby influencing the onset and progression of diverse diseases, including tumorigenesis. However, its specific impact on cervical cancer remains to be fully elucidated. Our study focused on the biological effects of sustained exposure to low-dose 4-NP on human normal cervical epithelial cells (HcerEpic). After a continuous 30-week exposure to 4-NP, the treated cells exhibited a significant malignant transformation, whereas the solvent control group showed limited malignant phenotypes. Subsequent analyses of the metabolomic profiles of the transformed cells unveiled marked irregularities in glutathione metabolism and unsaturated fatty acid metabolism. Analyses of transcriptomic profiles revealed significant activation of the MAPK signaling pathway and suppression of ferroptosis processes in these cells. Furthermore, the expression of MT2A was significantly upregulated following 4-NP exposure. Knockdown of MT2A restored the aberrant activation of the MAPK signaling pathway, elevated antioxidant capacity, ferroptosis inhibition, and ultimately the development of malignant phenotypes that induced by 4-NP in the transformed cells. Mechanistically, MT2A increased cellular antioxidant capabilities and facilitated the removal of toxic iron ions by enhancing the phosphorylation of ERK1/2 and JNK MAPK pathways. The administration of activators and inhibitors of the MAPK pathway confirmed that the MAPK pathway mediated the 4-NP-induced suppression of ferroptosis and, ultimately, the malignant transformation of cervical epithelial cells. Overall, our findings elucidated a dynamic molecular transformation induced by prolonged exposure to 4-NP, and delineated comprehensive biological perspectives underlying 4-NP-induced cervical carcinogenesis. This offers novel theoretical underpinnings for the assessment of the carcinogenic risks associated with 4-NP.

Pain symptoms are associated with two-point discrimination threshold in patients with temporomandibular disorders.

OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.

Current understanding of subjective tinnitus in adults.

PURPOSE: An up-to-date overview of epidemiology, etiology and pathophysiological mechanisms, diagnostic and evaluation methods, current treatment status and future directions of subjective tinnitus in adults. METHODS: Review of current evidence-based literature on subjective tinnitus in adults. RESULTS: The prevalence of subjective tinnitus in the adult population is estimated to be around 14%, and it tends to increase with age. Subjective tinnitus is a complex condition with multiple factors contributing to its origin. However, the exact causes and underlying mechanisms remain unknown. Potential causes may include hearing loss, dysfunction in the somatosensory system, and auditory cortical dysfunction, although severe underlying pathology is rare. Currently, diagnosis primarily relies on patient self-reported medical history and physician-based clinical assessment due to the lack of objective testing. Various treatment and management options have been proposed, but their effectiveness varies, and there is no universally agreed-upon treatment option. CONCLUSIONS: Tinnitus is a complex and heterogeneous disease with a high incidence rate and a tendency to increase with age. A holistic perspective is needed to understand the generation, perception, and emotional responses to tinnitus. Diagnosis requires a comprehensive assessment based on medical history and relevant examinations, identification of concurrent psychosomatic comorbidities, and active pursuit of objective diagnostic methods. At the same time, on the basis of existing treatment plans and combining emerging technologies, we will develop new personalized, precise, and combined treatment plans.

Comparison of [18F]FDG and [68 Ga]pentixafor PET/CT in Nasopharyngeal Carcinoma.

PURPOSE: This study aimed to explore the feasibility of [68 Ga]pentixafor positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma (NPC). PROCEDURES: This prospective study included patients with NPC who underwent [68 Ga]pentixafor PET/CT and 2-[18F]fuoro-2-deoxy-D-glucose ([18F]FDG) PET/CT within one week between November 2022 and March 2023. The [68 Ga]pentixafor and [18F]FDG uptakes in primary and metastatic lesions were measured and compared. RESULTS: Twenty-five participants (21 patients for initial stage and four patients for recurrence detection) were enrolled in our study. The participants underwent [18F]FDG PET/CT and [68 Ga]pentixafor PET/CT. [68 Ga]pentixafor PET/CT had the same detection rate as [18F]FDG for primary tumor (96% vs. 96%). The [68 Ga]pentixafor maximum standard uptake value (SUVmax) and target-to-background ratio (TBR) of primary tumors were lower than those of [18F]FDG (SUVmax: 8.13 ± 2.78 vs. 14.25 ± 6.45; P < 0.01; TBR: 5.17 ± 2.14 vs. 9.81 ± 5.30, P < 0.01). The difference between tumor volume of [68 Ga]pentixafor (TVpentixafor) and tumor volume of [18F]FDG (TVFDG) showed no significance (median: 16.01 vs. 9.56, P = 0.332). In the detection of suspected metastatic cervical lymph nodes (CLNs), [68 Ga]pentixafor PET possessed a lower SUVmax than [18F]FDG PET/CT (SUVmax: 6.86 ± 2.63 vs. 10.39 ± 5.28, P < 0.01), but there was no significant difference in the detection rate between [68 Ga]pentixafor and [18F]FDG PET/CT (96 vs. 98, P = 0.613). CONCLUSIONS: [68 Ga]pentixafor is a promising imaging tracer for detecting primary and metastatic NPC. [68 Ga]pentixafor PET/CT is comparable to [18F]FDG PET/CT in the detection rate of primary tumors and metastatic cervical lymph nodes in nasopharyngeal carcinoma, but [68 Ga]pentixafor uptake was heterogeneous. [68 Ga]pentixafor PET/CT may help select patients most likely to benefit from CXCR4-directed endoradiotherapy. CLINICAL TRIAL REGISTRATION NO: ChiCTR2200065902.

Analysis and monitoring of drug therapy in a patient with peptic ulcer complicated by infection: A case report.

BACKGROUND: The role of primary-level medical pharmacists in medical institutions in China is limited; therefore, it is necessary to explore the role of pharmacists in the process of drug treatment. CASE SUMMARY: A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer. The rationale for drug treatment was evaluated, and adjustments were made to the antacid and anti-infective regimen, as well as the dose and frequency of administration. Body temperature, routine blood examination, and adverse drug reactions were strictly monitored. During treatment, the pharmacist recommended anti-infective therapy with ampicillin-sulbactam, which effectively controlled the infection. Additionally, the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment, combined with Chinese patent medicine such as Kangfuxin Liquid. This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection. CONCLUSION: A pharmacist participated in the treatment process, provided individualized medication adjustment, and achieved good clinical results.

Mechanisms of the Accelerated Li+ Conduction in MOF-based Solid-State Polymer Electrolytes for All-Solid-State Lithium Metal Batteries.

Solid polymer electrolytes (SPEs) for lithium metal batteries have garnered considerable interests owing to their low cost, flexibility, lightweight, and favorable interfacial compatibility with battery electrodes. Their soft mechanical nature compared to solid inorganic electrolytes give them a large advantage to be used in low pressure solid-state lithium metal batteries (SSLMBs), which can avoid the cost and weight of the pressure cages. However, the application of SPEs has been hindered by their relatively low ionic conductivity. In addressing this limitation, enormous efforts have been devoted to the experimental investigation and theoretical calculations/simulation of new polymer classes. Recently, metal-organic frameworks (MOFs) have been shown to be effective in enhancing ion transport in SPEs. However, the mechanisms in enhancing Li+ conductivity have rarely been systematically and comprehensively analyzed. Therefore, this review provides an in-depth summary of the mechanisms of MOF-enhanced Li+ transport in MSPEs in terms of polymer, MOF, MOF/polymer interface (MPI) and solid electrolyte interface (SEI) aspects, respectively. Moreover, the understanding of Li+ conduction mechanisms through employing advanced characterization tools, theoretical calculations and simulations are also reviewed in this review. Finally, the main challenges in developing MSPEs are deeply analyzed and the corresponding future research directions are also proposed. This article is protected by copyright. All rights reserved.

Demonstration of hypergraph-state quantum information processing.

Complex entangled states are the key resources for measurement-based quantum computations, which is realised by performing a sequence of measurements on initially entangled qubits. Executable quantum algorithms in the graph-state quantum computing model are determined by the entanglement structure and the connectivity of entangled qubits. By generalisation from graph-type entanglement in which only the nearest qubits interact to a new type of hypergraph entanglement in which any subset of qubits can be arbitrarily entangled via hyperedges, hypergraph states represent more general resource states that allow arbitrary quantum computation with Pauli universality. Here we report experimental preparation, certification and processing of complete categories of four-qubit hypergraph states under the principle of local unitary equivalence, on a fully reprogrammable silicon-photonic quantum chip. Genuine multipartite entanglement for hypergraph states is certificated by the characterisation of entanglement witness, and the observation of violations of Mermin inequalities without any closure of distance or detection loopholes. A basic measurement-based protocol and an efficient resource state verification by color-encoding stabilizers are implemented with local Pauli measurement to benchmark the building blocks for hypergraph-state quantum computation. Our work prototypes hypergraph entanglement as a general resource for quantum information processing.

Synergistic Combination of Sb2Si2Te6 Additives for Enhanced Average ZT and Single-Leg Device Efficiency of Bi0.4Sb1.6Te3-based Composites.

Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride-based alloys are still the best for near-room-temperature applications. In this work, a ≈38% enhancement of the average ZT (300-473 K) to 1.21 is achieved by mixing Bi0.4Sb1.6Te3 with an emerging thermoelectric material Sb2Si2Te6, which is significantly higher than that of most BiySb2-yTe3-based composites. This enhancement is facilitated by the unique interface region between the Bi0.4Sb1.6Te3 matrix and Sb2Si2Te6-based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high-density dislocations in the same region can effectively scatter the phonons, decoupling the electron-phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single-leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb2Si2Te6 compositing strategy and the importance of the precipitate-matrix interface microstructure in improving the performance of materials for relatively low-temperature applications.

Correction: Huang et al. Systemic Anticoagulation and Inpatient Outcomes of Pancreatic Cancer: Real-World Evidence from U.S. Nationwide Inpatient Sample. Cancers 2023, 15, 1985.

In the original publication [...].

Automatic recognition of depression based on audio and video: A review.

Depression is a common mental health disorder. With current depression detection methods, specialized physicians often engage in conversations and physiological examinations based on standardized scales as auxiliary measures for depression assessment. Non-biological markers-typically classified as verbal or non-verbal and deemed crucial evaluation criteria for depression-have not been effectively utilized. Specialized physicians usually require extensive training and experience to capture changes in these features. Advancements in deep learning technology have provided technical support for capturing non-biological markers. Several researchers have proposed automatic depression estimation (ADE) systems based on sounds and videos to assist physicians in capturing these features and conducting depression screening. This article summarizes commonly used public datasets and recent research on audio- and video-based ADE based on three perspectives: Datasets, deficiencies in existing research, and future development directions.

Repurposing cinacalcet suppresses multidrug-resistant Staphylococcus aureus by disruption of cell membrane and inhibits biofilm by targeting IcaR.

BACKGROUND: MDR Staphylococcus aureus infections, along with the severity of biofilm-associated infections, continue to threaten human health to a great extent. It necessitates the urgent development of novel antimicrobial and antibiofilm agents. OBJECTIVES: To reveal the mechanism and target of cinacalcet as an antibacterial and antimicrobial agent for S. aureus. METHODS: Screening of non-antibiotic drugs for antibacterial and antibiofilm properties was conducted using a small-molecule drug library. In vivo efficacy was assessed through animal models, and the antibacterial mechanism was studied using quantitative proteomics, biochemical assays, LiP-SMap, BLI detection and gene knockout techniques. RESULTS: Cinacalcet, an FDA-approved drug, demonstrated antibacterial and antibiofilm activity against S. aureus, with less observed development of bacterial resistance. Importantly, cinacalcet significantly improved survival in a pneumonia model and bacterial clearance in a biofilm infection model. Moreover, the antibacterial mechanism of cinacalcet mainly involves the destruction of membrane-targeted structures, alteration of energy metabolism, and production of reactive oxygen species (ROS). Cinacalcet was found to target IcaR, inhibiting biofilm formation through the negative regulation of IcaADBC. CONCLUSIONS: The findings suggest that cinacalcet has potential for repurposing as a therapeutic agent for MDR S. aureus infections and associated biofilms, warranting further investigation.

[Preparation and effectiveness evaluation of placebo of Jiawei Ermiao Granules].

This study explored the preparation process of the placebo of Jiawei Ermiao Granules and evaluated the placebo effect, aiming to provide qualified placebo samples for clinical trials of Jiawei Ermiao Granules and a reference for the preparation and quality evaluation of placebos of traditional Chinese medicine granules. On the basis of the comprehensive analysis results of Jiawei Ermiao Granules, the orthogonal experiment was conducted to optimize the flavoring agents and colorants. After manual evaluation, the placebo formula was determined as dextrin 10 g, Codonopsis Radix extract 5.0 g, bitter melon extract 1.6 g, Mume Fructus extract 0.3 g, stevioside 0.1 g, sucrose octaacetate 0.004 g, indigo 0.004 g, lemon yellow 0.003 1 g, sunset yellow 0.001 8 g, bitter tea powder 0.001 8 g, caramel 0.001 3 g. Pilot trials were conducted on the placebo formula. The simulation effect of placebo was evaluated independently and comparatively, and the objectively evaluated by electronic nose and electronic tongue. The results showed that the independent manual evaluation of the placebo formula had higher error rate, and the placebo and Jiawei Ermiao Granules showed the similarity of 99.61% in the comparative manual evaluation. The smell similarity between the placebo and Jiawei Ermiao Granules was 99.19%, and the electronic tongue test showed little difference in the taste. In conclusion, the placebo prepared in this study shows a high similarity to Jiawei Ermiao Granules, which is not easy to break the blindness when being applied to clinical trials. This study provides a reference for the preparation and quality evaluation and promotes the large-scale production of placebos of traditional Chinese medicine granules, playing a role in improving the persuasiveness and acceptance of the efficacy of traditional Chinese medicines.

The sucker-like end-to-side arterial anastomosis for free flap in extremities reconstruction: a retrospective study of 78 cases.

BACKGROUND: The application of end-to-side (ETS) anastomosis for flap transfer poses challenges, particularly in cases of significant size discrepancy between the donor and flap arteries. Herein, a novel ETS anastomosis technique, termed "sucker-like ETS anastomosis", is developed to mitigate and rectify such vessel discrepancies. This study aims to evaluate the efficacy of this technique in tissue defect reconstruction through free flap transfer. METHODS: Between September 2018 and March 2023, the medical records and follow-up data of 78 patients who underwent free flap transfer using sucker-like ETS anastomosis for significant artery size discrepancies were collected and retrospectively analyzed. RESULTS: Among the 78 cases that received free flap transfer, the range of artery size discrepancy (flap artery vs donor artery) was 1:1.6-1:4 (mean: 1:2.5). Following anastomosis with the sucker-like ETS technique, 75 cases achieved flap survival without requiring additional surgical intervention, yielding a one-stage success rate of 96.2%. Three cases experienced post-operative venous crises, with two cases surviving after vein exploration and one case undergoing flap necrosis, necessitating a secondary skin graft. Seven cases faced delayed wound healing but eventually achieved complete healing following dressing changes. No arterial crisis was observed during hospitalization. With an average follow-up of 13 months, the surviving flaps exhibited excellent vitality without flap necrosis or pigment deposition. Overall, the application of sucker-like ETS arterial anastomosis for flap transfer resulted in a high overall surgical success rate of 98.7% (77/78). CONCLUSION: The application of sucker-like ETS anastomosis for free flap transfer is highly effective, particularly in cases with significant size discrepancy between the recipient and donor arteries.

Improved lung cancer classification by employing diverse molecular features of microRNAs.

MiRNAs are edited or modified in multiple ways during their biogenesis pathways. It was reported that miRNA editing was deregulated in tumors, suggesting the potential value of miRNA editing in cancer classification. Here we extracted three types of miRNA features from 395 LUAD and control samples, including the abundances of original miRNAs, the abundances of edited miRNAs, and the editing levels of miRNA editing sites. Our results show that eight classification algorithms selected generally had better performances on combined features than on the abundances of miRNAs or editing features of miRNAs alone. One feature selection algorithm, i.e., the DFL algorithm, selected only three features, i.e., the frequencies of hsa-miR-135b-5p, hsa-miR-210-3p and hsa-mir-182_48u (an edited miRNA), from 316 training samples. Seven classification algorithms achieved 100% accuracies on these three features for 79 independent testing samples. These results indicate that the additional information of miRNA editing is useful in improving the classification of LUAD samples.

Watch-and-wait strategy vs. resection in patients with radiologic complete response after conversion therapy for initially unresectable hepatocellular carcinoma: a propensity score-matching comparative study.

BACKGROUND: The optimal subsequent management for patients with initially unresectable hepatocellular carcinoma (uHCC) who have achieved complete response (CR) following conversion therapy remains unclear. This study aims to evaluate the feasibility and outcomes of the watch-and-wait (W-W) strategy versus surgical resection (SR) for these patients. MATERIALS AND METHODS: This retrospective study reviewed patients with initially uHCC who underwent conversion therapy employing transarterial therapies combined with or without systemic therapies. Radiologic CR (rCR), clinical CR (cCR), and pathologic CR (pCR) were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared between the W-W and SR groups. RESULTS: Among 1880 patients with uHCC who underwent conversion therapy, 207 (11.0%) achieved rCR. Finally, we enrolled 149 patients meeting the inclusion criteria, including 74 receiving W-W strategy and 75 undergoing SR. Among the 149 patients with rCR, the W-W group demonstrated comparable 3-year OS rates to the SR group (80.9 vs 83.1%, P =0.77), but demonstrated inferior PFS rates (14.4 vs 46.5%, P =0.002). These results remained consistent after propensity score matching. For the 57 patients who achieved cCR, the W-W group exhibited comparable 3-year OS (88.1 vs 87.9%, P =0.89) and PFS rates (27.8 vs 40.8%, P =0.34) compared to SR group. Among the 75 patients in the SR group, 31 (41.3%) achieved pCR and 44 (58.7%) reached non-pCR. When compared with patients with pCR, those who achieved rCR in the W-W group showed comparable OS but inferior PFS rates. Moreover, patients who achieved rCR in the W-W group displayed both comparable OS and PFS rates to those with non-pCR. CONCLUSION: The W-W strategy offered comparable survival outcomes to SR in patients with initially uHCC who achieved rCR or cCR after conversion therapy. For these patients, the W-W strategy could be offered as an alternative treatment option.

No Genetic Causality between Tobacco Smoking and Venous Thromboembolism: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Given the current debate in clinical research about the relationship between tobacco smoking and the risk of venous thromboembolism (VTE), a Mendelian randomization (MR) study was conducted aimed at elucidating the causal associations of current and past tobacco smoking with the risk of VTE, from the perspective of genetics. METHODS: Two-sample univariate and multivariable MR analyses were designed, using summary-level data from large genome-wide association studies involving European individuals. Causality was primarily assessed using multiplicative fixed-effects or random-effects model and inverse variance weighting, supplemented by MR-Egger regression, MR-PRESSO, Cochran's Q test, and leave-one-out for sensitivity analysis to test the reliability of the results. RESULTS: In the univariate MR analysis, no significant causal effects were found between current tobacco smoking and the risk of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE). Similarly, no significant causal effects were found between past smoking and VTE, DVT, and PE. As for the multivariable MR analysis, results were consistent with univariate MR analysis, with no significant causal effect of either current or past tobacco smoking on the risk of VTE, DVT, and PE. CONCLUSION: Evidence from both univariate and multivariable MR analyses demonstrated no significant causal relationships between current and past tobacco smoking and VTE, DVT, and PE. This contradicts positive correlations reported in some previous observational studies, which may be explained by other confounding factors. This provided genetic evidence for the conclusion reported in other observational studies that smoking did not affect VTE risk.