Rapid Screening of New Psychoactive Substances Using pDART-QqQ-MS.

Drug abuse is a severe social problem worldwide. Particularly, the issue of new psychoactive substances (NPSs) have increasingly emerged. NPSs are structural or functional analogs of traditional illicit drugs, such as cocaine, cannabis, and amphetamine; these molecules provide the same or more severe neurological effects. Usually, immunoassays are utilized in the preliminary screening method. However, NPSs have poor detectability in commercially available immunoassay kits. Meanwhile, various chromatography combined with the mass spectrometry platform have been developed to quantify NPSs. Still, a significant amount of time and resources are required during these procedures. Therefore, we established a rapid analytical platform for NPSs employing paper-loaded direct analysis in real time triple quadrupole mass spectrometry (pDART-QqQ-MS). We implemented this platform for the semiquantitative analysis of forensic drug tests in urine. This platform significantly shrinks the analytical time of a single sample within 30 s and requires a low volume of the specimen. The platform can detect 21 NPSs in urine mixtures at a lower limit of qualification of concentration ranging from 20 to 75 nanograms per milliliter (ng mL-1) and is lower than the cutoff value of currently available immune-based devices for detecting multiple drugs (1000 ng mL-1). Urine samples from drug addicts have been collected to verify the platform's effectiveness. By combining efficiency and accuracy, our platform offers a promising solution for addressing the challenges posed by NPSs in drug abuse detection.

Pioneering Astaxanthin-Tumor Cell Membrane Nanoparticles for Innovative Targeted Drug Delivery on Melanoma.

Background: Recently, the use of the tumor or its secretions as drug carriers has gradually become popular, with the advantages of high biocompatibility and enhanced drug delivery to specific cells. Melanoma is the most malignant tumor of all skin cancers; it is the most metastatic and, therefore, the most difficult to treat. The main purpose of this study is to develop nanovesicles with tumor cell membrane secretion properties to encapsulate target substances to enhance the therapeutic effect of cancer. Methods: Astaxanthin was selected as an anticancer drug due to our previous research finding that astaxanthin has extremely high antioxidant, anti-ultraviolet damage, and anti-tumor properties. The manufacturing method of the astaxanthin nanovesicle carrier is to mix melanoma cells and astaxanthin in an appropriate ratio and then remove the genetic material and inflammatory factors of cancer cells by extrusion. Results: In terms of results, after the co-culture of astaxanthin nanovesicles and melanoma cancer cells, it was confirmed that the ability of astaxanthin nanovesicles to inhibit the growth and metastasis of melanoma cancer cells was significantly better than the same amount of astaxanthin alone, and it had no effect on normal Human cells are also effective. There was no apparent harm on normal cells, indicating the ability of the vesicles to be selectively transported. Conclusion: Our findings illustrated the potential of astaxanthin nanovesicles as an anticancer drug.

Brain gray matter morphometry relates to onset age of bilingualism and theory of mind in young and older adults.

Lifelong bilingualism may result in neural reserve against decline not only in the general cognitive domain, but also in social cognitive functioning. In this study, we show the brain structural correlates that are associated with second language age of acquisition (L2AoA) and theory of mind (the ability to reason about mental states) in normal aging. Participants were bilingual adults (46 young, 50 older) who completed a theory-of-mind task battery, a language background questionnaire, and an anatomical MRI scan to obtain cortical morphometric features (i.e., gray matter volume, thickness, and surface area). Findings indicated a theory-of-mind decline in older adults compared to young adults, controlling for education and general cognition. Importantly, earlier L2AoA and better theory-of-mind performance were associated with larger volume, higher thickness, and larger surface area in the bilateral temporal, medial temporal, superior parietal, and prefrontal brain regions. These regions are likely to be involved in mental representations, language, and cognitive control. The morphometric association with L2AoA in young and older adults were comparable, but its association with theory of mind was stronger in older adults than young adults. The results demonstrate that early bilingual acquisition may provide protective benefits to intact theory-of-mind abilities against normal age-related declines.

Impurities in over-the-counter pseudoephedrine leading to methcathinone detection in urine.

Methcathinone, a psychoactive substance with stimulant properties, has raised concerns in recent years due to its presence in urine screenings, even among individuals with no history of drug abuse. To prevent misjudgment, this work aims to explore the source of methcathinone in urine. A total of 58 urine samples tested positive for methcathinone in the National Taiwan University Hospital cohort, with 27 linked to illicit drug use and 31 from individuals with no drug use history. Co-occurrence analysis revealed a strong association between methcathinone and over-the-counter cold medications containing pseudoephedrine or ephedrine. In an in vivo experiment, participants who consumed pseudoephedrine-containing drugs showed the presence of methcathinone in their urine, suggesting a connection between these substances. Additionally, tests on pharmaceutical products containing pseudoephedrine detected small amounts of methcathinone as impurities. The findings suggest that the presence of methcathinone in nonillicit drug users may be attributed to impurities in over-the-counter pseudoephedrine-containing medications. This raises concerns about potential misinterpretations of drug screening results and underscores the need for more comprehensive criteria for assessing drug use. This study contributes to our understanding of the origin of methcathinone in urine, which has implications for legal justice and drug screening practices.

Estrogen, progesterone, cortisol, brain-derived neurotrophic factor, and vascular endothelial growth factor during the luteal phase of the menstrual cycle in women with premenstrual dysphoric disorder.

The interplay between ovarian hormones, stress, and inflammatory markers in developing premenstrual dysphoric disorder (PMDD) remains inadequately understood. This study investigated the associations of dynamic changes in the levels of estrogen, progesterone, cortisol, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) with PMDD during the luteal phase of the menstrual cycle. A total of 58 women with PMDD and 50 healthy women were recruited in this study. These women's estrogen, progesterone, cortisol, BDNF, and VEGF levels were evaluated during the preovulation (PO), mid-luteal (ML), and late-luteal (LL) phases. Furthermore, the severity of P MDD symptoms, depressive symptoms, perceived stress, inattention, craving for sweet foods, and fatigue was assessed. The findings revealed that women with PMDD with higher levels of progesterone during the ML or LL phase or a greater increase (ML-PO) or higher sum (ML + LL) of luteal progesterone level exhibited a greater increase in PMDD symptoms during the luteal phase than did the healthy controls. Furthermore, women with PMDD exhibited higher cortisol levels during the LL phase than did the controls. The BDNF level was negatively correlated with PMDD severity. Furthermore, BDNF and VEGF levels were negatively correlated with inattention and craving for sweet foods among women with PMDD. These results suggest an association between progesterone and the exacerbation of PMDD symptoms during the LL phase. Women with PMDD have relatively high cortisol levels during the LL phase. Future investigations with experimental designs or larger sample sizes are warranted to verify the roles of progesterone and cortisol in the development of PMDD.

Complete Suppression of Phase Segregation in Mixed-Halide Perovskite Nanocrystals under Periodic Heating.

Under continuous light illumination, it is known that localized domains with segregated halide compositions form in semiconducting mixed-halide perovskites, thus severely limiting their optoelectronic applications due to the negative changes in bandgap energies and charge-carrier characteristics. Here mixed-halide perovskite CsPbBr1.2 I1.8 nanocrystals are deposited onto an indium tin oxide substrate, whose temperature can be rapidly changed by ≈10 °C in a few seconds by applying or removing an external voltage. Such a sudden temperature change induces a temporary transition of CsPbBr1.2 I1.8 nanocrystals from the segregated phase to the mixed phase, the latter of which can be permanently maintained when the light illumination is coupled with periodic heating cycles. These findings mark the emergence of a practical solution to the detrimental phase-segregation problem, given that a small temperature modulation is readily available in various fundamental studies and practical devices of mixed-halide perovskites.

Draft genome of Castanopsis chinensis, a dominant species safeguarding biodiversity in subtropical broadleaved evergreen forests.

OBJECTIVES: Castanopsis is the third largest genus in the Fagaceae family and is essentially tropical or subtropical in origin. The species in this genus are mainly canopy-dominant trees, and the key components of evergreen broadleaved forests play a crucial role in the maintenance of local biodiversity. Castanopsis chinensis, distributed from South China to Vietnam, is a representative species. It currently suffers from a high disturbance of human activity and climate change. Here, we present its assembled genome to facilitate its preliminary conservation and breeding on the genome level. DATA DESCRIPTION: The C. chinensis genome was assembled and annotated by Nanopore and MGI whole-genome sequencing and RNA-seq reads using leaf tissues. The assembly was 888,699,661 bp in length, consisting of 133 contigs and a contig N50 of 23,395,510 bp. A completeness assessment of the assembly with Benchmarking Universal Single-Copy Orthologs (BUSCO) indicated a score of 98.3%. Repetitive elements comprised 471,006,885 bp, accounting for 55.9% of the assembled sequences. A total of 51,406 genes that coded for 54,310 proteins were predicted. Multiple databases were used to functionally annotate the protein sequences.

Heterogeneity of gaming disorder: A clinically-based typology for developing personalized interventions.

Background: The eleventh revision of the International Classification of Diseases (ICD-11) defines the three key diagnostic criteria for gaming disorder (GD). These are loss of control over gaming, gaming as a priority over daily activities, and impaired functioning due to gaming. While this definition has implications for the prevention and treatment of GD, there is significant heterogeneity in the symptoms and etiology of GD among individuals, which results in different treatment needs. Cognitive control, emotional regulation, and reward sensitivity are three critical dimensions in the etiology model for GD. Aspects such as gender, comorbidity, motivation for gaming, stage or severity of GD, and risk factors all contribute to the heterogeneity of etiology among individuals with the disorder. Method: On the basis of clinical symptoms and comorbidity characteristics among approximately 400 patients with gaming disorder, the present paper proposes a clinical typology of patients with GD based on the authors' clinical experience in treating individuals with GD. Results: The findings indicated three common types of patients with GD: (i) impulsive male patients with attention deficit hyperactivity disorder (ADHD), (ii) dysphoria patients with dysfunctional coping skills, and (iii) isolated patients with social anxiety. The paper also discusses the presentation and treatment priority for these patients. Conclusion: Personalized treatments for patients with GD should be developed to fit their individual needs. Future studies should examine the heterogeneity of GD and confirm these types, as well as obtain evidence-based information that can help in the development of personalized treatment. Treatment resources should be developed, and professionals should be trained to provide integrated individualized treatment.

Genome assembly of Erythrophleum Fordii, a special "ironwood" tree in China.

OBJECTIVES: Erythrophleum is a genus in the Fabaceae family. The genus contains only about 10 species, and it is best known for its hardwood and medical properties worldwide. Erythrophleum fordii Oliv. is the only species of this genus distributed in China. It has superior wood and can be used in folk medicine, which leads to its overexploitation in the wild. For its effective conservation and elucidation of the distinctive genetic traits of wood formation and medical components, we present its first genome assembly. DATA DESCRIPTION: This work generated ~ 160.8 Gb raw Nanopore whole genome sequencing (WGS) long reads, ~ 126.0 Gb raw MGI WGS short reads and ~ 29.0 Gb raw RNA-seq reads using E. fordii leaf tissues. The de novo assembly contained 864,825,911 bp in the E. fordii genome, with 59 contigs and a contig N50 of 30,830,834 bp. Benchmarking Universal Single-Copy Orthologs (BUSCO) revealed 98.7% completeness of the assembly. The assembly contained 471,006,885 bp (54.4%) repetitive sequences and 28,761 genes that coded for 33,803 proteins. The protein sequences were functionally annotated against multiple databases, facilitating comparative genomic analysis.

A DNA barcode library for woody plants in tropical and subtropical China.

The application of DNA barcoding has been significantly limited by the scarcity of reliable specimens and inadequate coverage and replication across all species. The deficiency of DNA barcode reference coverage is particularly striking for highly biodiverse subtropical and tropical regions. In this study, we present a comprehensive barcode library for woody plants in tropical and subtropical China. Our dataset includes a standard barcode library comprising the four most widely used barcodes (rbcL, matK, ITS, and ITS2) for 2,520 species from 4,654 samples across 49 orders, 144 families, and 693 genera, along with 79 samples identified at the genus level. This dataset also provides a super-barcode library consisting of 1,239 samples from 1,139 species, 411 genera, 113 families, and 40 orders. This newly developed library will serve as a valuable resource for DNA barcoding research in tropical and subtropical China and bordering countries, enable more accurate species identification, and contribute to the conservation and management of tropical and subtropical forests.

Identification of A Novel Variant of Filamin A Destroying the Attraction Between Benzene Rings and Sulfhydryl in Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH), characterized by acetabular deformity that manifests from loose ligaments to complete dislocation of the hip, can cause notable pain and dysfunction and lead to hip dislocation, secondary fractures, scoliosis, and osteoarthritis of hip. Variants in FLNA may produce a spectrum of malformations in multiple organs, especially the skeleton. This study aimed to identify the genetic etiologies of DDH patients and provide genetic testing information for further diagnosis and treatment of DDH. We recruited a Chinese woman with DDH and her family members. Whole-exome sequencing was used to identify the patient's genetic etiologies. Protein models were used to analyze the pathogenic mechanism of the identified variants. A novel variant (c.3493T>G, p.C1165G) of FLNA was detected. The structural models of the mutant FLNA protein indicated that the variant would lose its sulfhydryl side chain and destroy the attraction between benzene rings and sulfhydryl. We reported a novel variant (c.3493T>G, p.C1165G) of FLNA in a Chinese woman with DDH. Our research outcome enriches the gene pool for hip dysplasia and emphasizes the pathogenicity of sulfhydryl side chain disruption in FLNA.

Five new Camillea (Xylariales) species described from French Guiana.

BACKGROUND: The genus Camillea was created in 1849 from collections made in French Guiana with eight species included. Numerous species assigned to Camillea were subsequently discovered, especially in the forests of the Amazon basin, but new discoveries have not been reported from French Guiana since 1849. Recent fieldwork in French Guiana has begun to fill this gap by identifying five new species, most of which were collected in the vicinity of Saül village. RESULTS: Based on macro- and micromorphological study of their stromata, including SEM images of ascospore wall ornamentation, five new species were recognized, including C. cribellum, C. heterostomoides, C. nitida, C. rogersii and C. saulensis. Cultures could be obtained for C. heterostomoides and C. rogersii, and ITS and LSU sequences were obtained for all of the five new species. Camillea heterostoma and its variety microspora were shown to be conspecific. Provisional molecular phylogenetic analyses support the possible reinstatement of Hypoxylon melanaspis, currently regarded as merely an applanate form of C. leprieurii. CONCLUSION: The current study is based on a relatively limited fieldwork in its duration and sampling area but was able to substantially increase the number of Camillea species known from French Guiana. This augurs an exceptional and still unknown diversity of the genus in this area and by extension in the adjacent neotropical forests.

Circadian typologies and insomnia in individuals with internet gaming disorder comorbid with attention deficit/hyperactivity disorder.

The alteration in circadian typology and insomnia were prevalent among both Individuals with IGD and those with attention deficit hyperactivity disorder (ADHD), the most comorbid psychiatric disorder of IGD. This study aimed to evaluate the relationships between circadian typologies, insomnia, and internet gaming disorder (IGD) and how ADHD affects this relationship. We recruited three groups of 69 young adults: an IGD group, a control group comprising age- and sex-matched nongamers, and a group of gamers without IGD through diagnostic interviews. The participants with IGD exhibited lower composite scale of morningness (CSM) scores and thus a higher eveningness preference In addition, the score of Pittsburgh insomnia rating scale-20-item version (PIRS_20) was significantly higher among those with IGD. The participants with IGD and ADHD exhibited lower CSM scores but higher PRIS_20 scores than the participants with IGD but without ADHD. The present findings indicate that participants with IGD exhibited a tendency of eveningness preference and experienced more severe insomnia. ADHD exacerbated the eveningness preference and insomnia of individuals with IGD. Close attention should be paid to sleep problems in individuals with IGD, particularly to those with ADHD.

Diversity and biogeography of plant phyllosphere bacteria are governed by latitude-dependent mechanisms.

Predicting and managing the structure and function of plant microbiomes requires quantitative understanding of community assembly and predictive models of spatial distributions at broad geographic scales. Here, we quantified the relative contribution of abiotic and biotic factors to the assembly of phyllosphere bacterial communities, and developed spatial distribution models for keystone bacterial taxa along a latitudinal gradient, by analyzing 16S rRNA gene sequences from 1453 leaf samples taken from 329 plant species in China. We demonstrated a latitudinal gradient in phyllosphere bacterial diversity and community composition, which was mostly explained by climate and host plant factors. We found that host-related factors were increasingly important in explaining bacterial assembly at higher latitudes while nonhost factors including abiotic environments, spatial proximity and plant neighbors were more important at lower latitudes. We further showed that local plant-bacteria associations were interconnected by hub bacteria taxa to form metacommunity-level networks, and the spatial distribution of these hub taxa was controlled by hosts and spatial factors with varying importance across latitudes. For the first time, we documented a latitude-dependent importance in the driving factors of phyllosphere bacteria assembly and distribution, serving as a baseline for predicting future changes in plant phyllosphere microbiomes under global change and human activities.

IoT-based wearable health monitoring device and its validation for potential critical and emergency applications.

The COVID-19 pandemic brought the world to a standstill, posing unprecedented challenges for healthcare systems worldwide. The overwhelming number of patients infected with the virus placed an enormous burden on healthcare providers, who struggled to cope with the sheer volume of cases. Furthermore, the lack of effective treatments or vaccines means that quarantining has become a necessary measure to slow the spread of the virus. However, quarantining places a significant burden on healthcare providers, who often lack the resources to monitor patients with mild symptoms or asymptomatic patients. In this study, we propose an Internet of Things (IoT)-based wearable health monitoring system that can remotely monitor the exact locations and physiological parameters of quarantined individuals in real time. The system utilizes a combination of highly miniaturized optoelectronic and electronic technologies, an anti-epidemic watch, a mini-computer, and a monitor terminal to provide real-time updates on physiological parameters. Body temperature, peripheral oxygen saturation (SpO2), and heart rate are recorded as the most important measurements for critical care. If these three physiological parameters are aberrant, then it could represent a life-endangering situation and/or a short period over which irreversible damage may occur. Therefore, these parameters are automatically uploaded to a cloud database for remote monitoring by healthcare providers. The monitor terminal can display real-time health data for multiple patients and provide early warning functions for medical staff. The system significantly reduces the burden on healthcare providers, as it eliminates the need for manual monitoring of patients in quarantine. Moreover, it can help healthcare providers manage the COVID-19 pandemic more effectively by identifying patients who require medical attention in real time. We have validated the system and demonstrated that it is well suited to practical application, making it a promising solution for managing future pandemics. In summary, our IoT-based wearable health monitoring system has the potential to revolutionize healthcare by providing a cost-effective, remote monitoring solution for patients in quarantine. By allowing healthcare providers to monitor patients remotely in real time, the burden on medical resources is reduced, and more efficient use of limited resources is achieved. Furthermore, the system can be easily scaled to manage future pandemics, making it an ideal solution for managing the health challenges of the future.

Development and usability of a Mobile Interactive Application (VCPW) for Vascular Crisis Prewarning after Skin Flap Transplantation.

Background: In microsurgical tissue transfer, skin flap transplantation is frequently used to heal the surface of a wound. Effective microcirculation surveillance of the skin flap is crucial. However, with traditional monitoring methods-that is, clinical observation-vascular crisis can still occur, thereby impairing postoperative recovery. A smartphone application is required to assist health care professionals in the standardized collection of flap perfusion parameters for flap management. Methods: The Vascular Crisis Prewarning Application was created using a design science research methodology that prioritizes users and problems. The system usability scale was used to assess the application's usability among medical practitioners. The application was used at the clinic from December 2020 to September 2022. The unplanned return to the operating room, time to diagnose vascular crisis, and flap survival rate were compared with and without the application. Results: The application consisted of 5 modules: patient addition and basic information entry, flap labeling, flap observation, crisis warning, and case archiving. The average rating for the application's usability among medical practitioners was 97.95 score (SD 2.36). With the application, the time to detect vascular crisis reduced from 26.71 to 16.26 h (P < 0.001), the unplanned return to the operation room increased from 8.18% to 10.24% (P = 0.587), and the flap survival rate went from 94.55% to 99.21% (P = 0.083). Conclusions: An easy-to-use flap perfusion monitoring and prewarning application for medical practitioners was produced using a user-centered development method. The application provided a more standardized and accurate platform for data collection in flap management and reduced the time to detect vascular crisis. Larger cohort studies are required in the future to better assess the full potential of the application.

Xylaria species associated with fallen leaves and petioles.

BACKGROUND: Xylaria species growing on fallen leaves and petioles have not been treated systematically. One source of confusion in this group of Xylaria species has stemmed from X. filiformis, which is an ancient name published in 1805 as Sphaeria filiformis and has commonly labeled on specimen packets that contain leaf- and petiole-inhabiting Xylaria species. Here we clarified the identity of X. filiformis and distinguish it from the species that are easily confused with it, notably X. simplicissima, to which most specimens labeled as X. filiformis are referred. Our research also led us to encounter many other leaf- and petiole-inhabiting Xylaria species, prompting a comprehensive study of this group of fungi. RESULTS: Forty-five foliicolous and caulicolous species of Xylaria were studied, including nine newly described species-X. allima, X. appendiculatoides, X. hispidipes, X. minuscula, X. neblinensis, X. spiculaticlavata, X. vermiformis, X. vittatipiliformis, and X. vittiformis; three unnamed species-X. sp. AR1741, X. sp. GS7461A, and X. sp. GS7461B; X. simplicissima, a name newly combined with Xylaria from Rhizomorpha simplicissima; and X. noduliformis and X. imminuta, which are two new replacement names, respectively, for X. maitlandii var. nuda and X. hypsipoda var. microspora. The 45 taxa can be classified into three groups by stromatal shape and conspicuousness of perithecial mounds on the stromatal surface: (i) the X. filiformis group contains 10 species, (ii) the X. phyllocharis group contains 19 species, and (iii) the X. heloidea group contains 16 species. One of the newly described or unnamed species belongs to the X. filiformis group-X. vermiformis; nine of them belong to the X. phyllocharis group-X. allima, X. appendiculatoides, Xylaria minuscula, X. neblinensis, X. sp. AR1741, X. sp. GS7461B, X. spiculaticlavata, X. vittatipiliformis, and X. vittiformis; and three of them belong to the X. heloidea group-X. hispidipes, X. imminuta, and X. sp. GS7461A. CONCLUSION: The 45 species of Xylaria associated with fallen leaves and petioles can be identified by using the dichotomous identification key that we provided herein. It is important to note that most of the studied species are represented by only one or several specimens and many have not been recollected and cultured.

Xylaria furcata reconsidered and nine resembling species.

BACKGROUND: Xylaria collections from termite nests with dichotomously branched stromata have been identified as X. furcata. However, Léveillé's original material is no longer available, and the modern interpretation of X. furcata is based on a 1908 collection made by von Höhnel from termite nests at Buitenzorg Botanical Garden in Java. A packet of this von Höhnel material at FH was designated as the neotype by Rogers et al. in 2005. RESULTS: We reexamined the neotype from FH and its duplicates from various herbaria and found that three different species were mixed in these specimens. Despite that all of them have dichotomously branched stromata and tiny ascospores, only one fits the 2005 neotypification of X. furcata, where exposed perithecial mounds on the stromatal surface were unambiguously indicated. This portion of material is redesignated as the neotype, while the other two species with immersed perithecia are described as new: X. hoehnelii and X. robustifurcata. The ITS sequence obtained from the neotype helped us designate a specimen with cultures obtained from it as the epitype. From specimens identifiable as X. furcata, we describe four new species: X. brevifurcata, X. furcatula, X. insignifurcata, and X. tenellifurcata. Additionally, we recognize X. furcata var. hirsuta at the species level as X. hirsuta and consider X. scoparia a distinct species rather than a synonym of X. furcata. Molecular phylogenetic analyses based on three protein-coding loci showed that X. furcata and resembling species were grouped into two clusters: the X. furcata cluster with half-exposed to fully exposed perithecial mounds and the X. hoehnelii cluster with largely immersed perithecial mounds. CONCLUSION: Ten species are recognized for X. furcata and resembling species, all of which could have been identified as X. furcata in the past. Its diversity has been overlooked primarily due to the small and similar stromata. Several additional species have been confirmed to be related to X. furcata by DNA sequences but are yet to be described due to the lack of mature stromata. While the species diversity of macrotermitine termites is equally high in Africa as in Asia, all of the species are primarily found in Asia, with X. hirsuta as the only exception. This suggests that there may be many more undiscovered species for this fungal group.

Proteomic Profiling of Chemotherapy Responses in FOLFOX-Resistant Colorectal Cancer Cells.

Chemoresistance mechanisms of colorectal cancer remain largely elusive. We aim to compare the difference of chemotherapy responses between FOLFOX-resistant and wild-type colorectal cancer cells by proteomic profiling to suggest novel treatment targets. FOLFOX-resistant colorectal cancer cells DLD1-R and HCT116-R were developed by chronic exposure to progressive FOLFOX doses. Proteomic profiling of FOLFOX-resistant and wild-type cells under FOLFOX exposure were conducted by mass-spectrometry-based protein-analysis technology. Verification of selected KEGG pathways was conducted by Western blot. DLD1-R had significantly higher FOLFOX-chemoresistance (10.81 times) than its wild-type counterpart. A total of 309 and 90 differentially expressed proteins were identified in DLD1-R and HCT116-R, respectively. In terms of gene ontology molecular function, RNA binding and cadherin binding ranked first for DLD1 and HCT116 groups, respectively. For gene set enrichment analysis, ribosome pathway and DNA replication were significantly up-regulated and down-regulated in DLD1-R, respectively. The most significantly up-regulated pathway in HCT116-R was regulation of the actin cytoskeleton. Up-regulations in the ribosome pathway (DLD1-R) and actin cytoskeleton (HCT116-R) were verified by Western blot. There were several significantly altered signaling pathways in FOLFOX-resistant colorectal cancer cells under FOLFOX with notable up-regulations in the ribosomal process and actin cytoskeleton.

Efficacy comparison of vascularized iliac crest bone flap and Ilizarov bone transport in the treatment of traumatic bone defects of the tibia combined with large soft tissue defects.

BACKGROUND: Traumatic tibial defect complicated with soft tissue defect is a difficult problem in clinic. Vascularized iliac crest bone flap (VIBF) and Ilizarov bone transport are effective methods to treat tibial defects with limited defect length, which most need to be explored accordingly. METHODS: In this study, a total of 68 patients with traumatic tibial defect (ranging from 4 to 10 cm) and large soft tissue defect were collected retrospectively. The soft tissue defects were repaired by latissimus dorsal musculocutaneous flap (LD), anterolateral thigh flap (ALTF) or both. Thirty-three cases were treated with vascularized iliac crest bone flap transplantation and 35 cases were treated with Ilizarov bone transport. Intraoperative and postoperative follow-up data (including operation time, blood loss, bone union time, external fixation time, external fixation index, complication rate, reoperation rate, and functional evaluation) were recorded, and comparative analysis was performed. RESULTS: The median follow-up time was 32 months. Compared with Ilizarov group, the VIBF group exhibited statistically faster bone union time (6.3 ± 1.0 vs. 18.2 ± 3.0 months). Moreover, the VIBF group showed shorter EFT (7.3 ± 1.0 vs. 19.2 ± 3.0 months) and a better EFI (34.8 ± 9.2 vs. 84.2 ± 23.7 days/cm). The excellent and good rate of lower limb appearance evaluation in VIBP group was significantly better than that in Ilizarov group. The complication rate and reoperation rate were significantly higher in Ilizarov group. CONCLUSION: In summary, compared with Ilizarov bone transport, VIBP has the advantages of faster healing, shorter external fixation time, lower complication and reoperation rate, and better appearance within the limited defect length. Ilizarov bone transport is still preferred when the defect length exceeds the maximum repair length of the iliac flap. The daily handling required by bone transport process is painful. LEVEL OF EVIDENCE: III, Case-control study.