Target Identification and Mechanistic Characterization of Indole Terpenoid Mimics: Proper Spindle Microtubule Assembly Is Essential for Cdh1-Mediated Proteolysis of CENP-A.

Centromere protein A (CENP-A), a histone H3 variant specific to centromeres, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure-activity relationship (SAR) study of the cell-cycle-arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis reveals that both molecules bind to the colchicine-binding site of ß-tubulin. Treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, results in CENP-A accumulation by destabilizing Cdh1, a co-activator of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.

Transcriptome-wide analysis of a superior xylan degrading isolate Penicillium oxalicum 5-18 revealed active lignocellulosic degrading genes.

Lignocellulose biomass raw materials have a high value in energy conversion. Recently, there has been growing interest in using microorganisms to secret a series of enzymes for converting low-cost biomass into high-value products such as biofuels. We previously isolated a strain of Penicillium oxalicun 5-18 with promising lignocellulose-degrading capability. However, the mechanisms of lignocellulosic degradation of this fungus on various substrates are still unclear. In this study, we performed transcriptome-wide profiling and comparative analysis of strain 5-18 cultivated in liquid media with glucose (Glu), xylan (Xyl) or wheat bran (WB) as sole carbon source. In comparison to Glu culture, the number of differentially expressed genes (DEGs) induced by WB and Xyl was 4134 and 1484, respectively, with 1176 and 868 genes upregulated. Identified DEGs were enriched in many of the same pathways in both comparison groups (WB vs. Glu and Xly vs. Glu). Specially, 118 and 82 CAZyme coding genes were highly upregulated in WB and Xyl cultures, respectively. Some specific pathways including (Hemi)cellulose metabolic processes were enriched in both comparison groups. The high upregulation of these genes also confirmed the ability of strain 5-18 to degrade lignocellulose. Co-expression and co-upregulated of genes encoding CE and AA CAZy families, as well as other (hemi)cellulase revealed a complex degradation strategy in this strain. Our findings provide new insights into critical genes, key pathways and enzyme arsenal involved in the biomass degradation of P. oxalicum 5-18.

Pathogenic mechanisms of cardiovascular damage in COVID-19.

BACKGROUND: COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. PURPOSE: This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. METHODS: An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. RESULTS: The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. CONCLUSIONS: Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.

Sporotrichosis Mimicking Rosacea Lesions: A Case Report.

Sporotrichosis is a subacute or chronic infectious disease caused by sporothrix. It is mainly caused by Sporothrix inoculation after accidental skin injury during human labor. The clinical manifestations of sporotrichosis are variable, ranging from nodules, plaques, ulcers, verrucous lesions, and subcutaneous masses. Some reports indicate that sporotrichosis can mimic psoriasis-like lesions. We herein report a case of sporotrichosis mimicking rosacea lesions. In addition, the patient had a history of nasal trauma, and we believe that the patient was inoculated with Sporothrix after the nasal skin was damaged during labor activities. The patient was given itraconazole 200 mg orally daily for 3 months, which effectively resolved the rash.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Study on Quality Characteristic of Chebulae Fructus and Its Adulterants and Degradation Pathway of Hydrolyzable Tannins.

Chebulae Fructus (CF) is known as one of the richest sources of hydrolyzable tannins (HTs). In this study, ultra-performance liquid chromatography coupled with a photodiode array detector method was established for simultaneous determination of the 12 common phenolcarboxylic and tannic constituents (PTCs). Using this method, quantitative analysis was accomplished in CF and other four adulterants, including Terminaliae Belliricae Fructus, Phyllanthi Fructus, Chebulae Fructus Immaturus, and Canarii Fructus. Based on a quantitative analysis of the focused compounds, discrimination of CF and other four adulterants was successfully accomplished by hierarchical cluster analysis and principal component analysis. Additionally, the total contents of the 12 compounds that we focused on in this study were unveiled as 148.86 mg/g, 96.14 mg/g, and 18.64 mg/g in exocarp, mesocarp, and endocarp and seed of CF, respectively, and PTCs were witnessed to be the most abundant in the exocarp of CF. Noticeably, the HTs (chebulagic acid, chebulanin acid, chebulinic acid, and punicalagin) were observed to be ultimately degraded to chebulic acid, gallic acid, and ellagic acid during sunlight-drying of the fresh fruits. As a result, our study indicated that CF and its adulterants could be distinguished by the observed 12 PTCs, which were mainly distributed in the exocarp of the fruits. The HTs were prone to degrade into the three simple phenolcarboxylic acids during drying or processing, allowing us to obtain a more comprehensive understanding of the PTCs, with great significance in the improved quality of CF and related products.

Higher dietary live microbe intake is associated with a lower risk of sarcopenia.

OBJECTIVE: This study aimed to investigate the potential association between dietary live microbe intake and sarcopenia. METHODS: Data from 5368 participants were gathered from the National Health and Nutrition Examination Survey (NHANES). Dietary information was assessed using a self-report questionnaire. The participants were categorized into low, medium, and high dietary live microbe groups. Sarcopenia was defined according to the National Institutes of Health (NIH) definition (appendicular skeletal muscle mass/body mass index <0.789 for men and <0.512 for women). Multivariate regression analysis and stratified analyses were performed. RESULTS: After adjusting for potential confounding factors, individuals in the high dietary live microbe group exhibited a lower prevalence of sarcopenia compared to those in the low dietary live microbe group. The adjusted odds ratio (with 95% confidence intervals) was 0.63 (0.44-0.89) (p for trend <0.05). Subgroup analyses indicated a potential difference in the impact of dietary live microbe intake on sarcopenia between individuals with and without diabetes (p for interaction = 0.094). CONCLUSION: Higher dietary live microbe intake was associated with a lower risk of sarcopenia.

Ursolic acid molecules dock MAPK1 to modulate gut microbiota diversity to reduce neuropathic pain.

To investigate the efficacy of Ursolic acid in alleviating neuropathic pain in rats with spinal nerve ligation (SNL), the SNL rat model was surgically induced. Different concentrations of Ursolic acid and manipulated target mitogen-activated protein kinase 1 (MAPK1) were administered to the SNL rats. Fecal samples were collected from each group of rats for 16S rDNA analysis to examine the impact of gut microbiota. Molecular docking experiments were conducted to assess the binding energy between Ursolic acid and MAPK1. In vivo studies were carried out to evaluate the expression of inflammatory factors and signaling pathways in spinal cord and colon tissues. Ursolic acid was found to have a beneficial effect on pain reduction in rats by increasing plantar withdrawal latency (PWL) and paw withdrawal threshold (PWT). Comparing the Ursolic acid group with the control group revealed notable differences in the distribution of Staphylococcus, Allobaculum, Clostridium, Blautia, Bifidobacterium, and Prevotella species. Network pharmacology analysis identified MAPK1 and intercellular adhesion molecule-1 (ICAM1) as common targets for Ursolic acid, SNL, and neuropathic pain. Binding sites between Ursolic acid and these targets were identified. Additionally, immunofluorescent staining showed a decrease in GFAP and IBA1 intensity in the spinal cord along with an increase in NeuN following Ursolic acid treatment. Overexpression of MAPK1 in SNL rats led to an increase in inflammatory factors and a decrease in PWL and PWT. Furthermore, MAPK1 counteracted the pain-relieving effects of Ursolic acid in SNL rats. Ursolic acid was found to alleviate neuropathic pain in SNL rats by targeting MAPK1 and influencing gut microbiota homeostasis.

Decellularized extracellular matrix enriched with GDNF enhances neurogenesis and remyelination for improved motor recovery after spinal cord injury.

Motor functional improvement represents a paramount treatment objective in the post-spinal cord injury (SCI) recovery process. However, neuronal cell death and axonal degeneration following SCI disrupt neural signaling, impeding the motor functional recovery. In this study, we developed a multifunctional decellularized spinal cord-derived extracellular matrix (dSECM), crosslinked with glial cell-derived neurotrophic factor (GDNF), to promote differentiation of stem cells into neural-like cells and facilitate axonogenesis and remyelination. After decellularization, the immunogenic cellular components were effectively removed in dSECM, while the crucial protein components were retained which supports stem cells proliferation and differentiation. Furthermore, sustained release of GDNF from the dSECM facilitated axonogenesis and remyelination by activating the PI3K/Akt and MEK/Erk pathways. Our findings demonstrate that the dSECM-GDNF platform promotes neurogenesis, axonogenesis, and remyelination to enhance neural signaling, thereby yielding promising therapeutic effects for motor functional improvement after SCI. STATEMENT OF SIGNIFICANCE: The dSECM promotes the proliferation and differentiation of MSCs or NSCs by retaining proteins associated with positive regulation of neurogenesis and neuronal differentiation, while eliminating proteins related to negative regulation of neurogenesis. After crosslinking, GDNF can be gradually released from the platform, thereby promoting neural differentiation, axonogenesis, and remyelination to enhance neural signaling through activation of the PI3K/Akt and MEK/Erk pathways. In vivo experiments demonstrated that dSECM-GDNF/MSC@GelMA hydrogel exhibited the ability to facilitate neuronal regeneration at 4 weeks post-surgery, while promoting axonogenesis and remyelination at 8 weeks post-surgery, ultimately leading to enhanced motor functional recovery. This study elucidates the ability of neural regeneration strategy to promote motor functional recovery and provides a promising approach for designing multifunctional tissue for SCI treatment.

Effectiveness of a Full Course Health Education in the Care of Patients with Chronic Kidney Disease Receiving Peritoneal Dialysis.

Background: Chronic kidney disease (CKD) patients undergoing peritoneal dialysis face numerous challenges that can impact their health behaviors, treatment adherence, and overall quality of life. A comprehensive health education program tailored for CKD patients on peritoneal dialysis is imperative to enhance the effectiveness of treatment and address these issues. Objective: The primary objective was to evaluate the impact of a full course health education program on health behaviors, treatment adherence, quality of life, and the occurrence of adverse events in CKD patients receiving peritoneal dialysis. Methods: A total of 98 CKD patients on peritoneal dialysis at our hospital between October 2019 and October 2022 were selected. The patients were randomly assigned to receive either routine care (n=52) or participate in a full-course health education program (n=46). The comparative assessments included health behavior scores, treatment adherence, Kidney Disease Targeted Area (KDTA) scores, monitoring adverse events, and tracking readmissions. Results: Patients in the observation group who underwent the full course health education program exhibited significant improvements in health behavior scores and treatment adherence (P < .05). Notably, the observation group demonstrated higher levels of medication compliance, timely reviews, and catheter maintenance. Moreover, full-course health education contributed to an enhanced quality of life, reflected in higher KATA scores, and led to a reduction in adverse events and readmission rates compared to routine care (P < .05). Conclusions: This study concludes that a full-course health education program is effective in improving health behaviors, treatment adherence, and quality of life while reducing adverse events among CKD patients undergoing peritoneal dialysis.

In Situ Polymer-Solution-Processed Graphene-PDMS Nanocomposites for Application in Intracranial Pressure Sensors.

Polydimethylsiloxane (PDMS) has emerged as a promising candidate for the dielectric layer in implantable sensors due to its exceptional biocompatibility, stability, and flexibility. This study introduces an innovative approach to produce graphene-reinforced PDMS (Gr-PDMS), where graphite powders are exfoliated into mono- and few-layer graphene sheets within the polymer solution, concurrently forming cross-linkages with PDMS. This method yields a uniformly distributed graphene within the polymer matrix with improved interfaces between graphene and PDMS, significantly reducing the percolation threshold of graphene dispersed in PDMS from 10% to 5%. As-synthesized Gr-PDMS exhibits improved mechanical and electrical properties, tested for potential use in capacitive pressure sensors. The results demonstrate an impressive pressure sensitivity up to 0.0273 kpa-1, 45 times higher than that of pristine PDMS and 2.5 times higher than the reported literature value. The Gr-PDMS showcases excellent pressure sensing ability and stability, fulfilling the requirements for implantable intracranial pressure (ICP) sensors.

Implications of carbon catabolite repression for Aspergillus-based cell factories: A review.

Carbon catabolite repression (CCR) is a global regulatory mechanism that allows organisms to preferentially utilize a preferred carbon source (usually glucose) by suppressing the expression of genes associated with the utilization of nonpreferred carbon sources. Aspergillus is a large genus of filamentous fungi, some species of which have been used as microbial cell factories for the production of organic acids, industrial enzymes, pharmaceuticals, and other fermented products due to their safety, substrate convenience, and well-established post-translational modifications. Many recent studies have verified that CCR-related genetic alterations can boost the yield of various carbohydrate-active enzymes (CAZymes), even under CCR conditions. Based on these findings, we emphasize that appropriate regulation of the CCR pathway, especially the expression of the key transcription factor CreA gene, has great potential for further expanding the application of Aspergillus cell factories to develop strains for industrial CAZymes production. Further, the genetically modified CCR strains (chassis hosts) can also be used for the production of other useful natural products and recombinant proteins, among others. We here review the regulatory mechanisms of CCR in Aspergillus and its direct application in enzyme production, as well as its potential application in organic acid and pharmaceutical production to illustrate the effects of CCR on Aspergillus cell factories.

Vitamin D3 improves iminodipropionitrile-induced tic-like behavior in rats through regulation of GDNF/c-Ret signaling activity.

Children with chronic tic disorders (CTD), including Tourette syndrome (TS), have significantly reduced serum 25-hydroxyvitamin D [25(OH)D]. While vitamin D3 supplementation (VDS) may reduce tic symptoms in these children, its mechanism is unclear. The study aim was to investigate the effects and mechanisms of vitamin D deficiency (VDD) and VDS on TS model behavior. Forty 5-week-old male Sprague-Dawley rats were randomly divided into (n = 10 each): control, TS model, TS model with VDD (TS + VDD), or TS model with VDS (TS + VDS; two intramuscular injections of 20,000 IU/200 g) groups. The VDD model was diet-induced (0 IU vitamin D/kg); the TS model was iminodipropionitrile (IDPN)-induced. All groups were tested for behavior, serum and striatal 25(OH)D and dopamine (DA), mRNA expressions of vitamin D receptor (VDR), glial cell line-derived neurotrophic factor (GDNF), protooncogene tyrosine-protein kinase receptor Ret (c-Ret), and DA D1 (DRD1) and D2 (DRD2) receptor genes in the striatum. TS + VDD had higher behavior activity scores throughout, and higher total behavior score at day 21 compared with TS model. In contrast, day 21 TS + VDS stereotyped behavior scores and total scores were lower than TS model. The serum 25(OH)D in TS + VDD was < 20 ng/mL, and lower than control. Striatal DA of TS was lower than control. Compared with TS model, striatal DA of TS + VDD was lower, while in TS + VDS it was higher than TS model. Furthermore, mRNA expression of VDR, GDNF, and c-Ret genes decreased in TS model, and GDNF expression decreased more in TS + VDD, while TS + VDS had higher GDNF and c-Ret expressions. VDD aggravates, and VDS ameliorates tic-like behavior in an IDPN-induced model. VDS may upregulate GDNF/c-Ret signaling activity through VDR, reversing the striatal DA decrease and alleviating tic-like behavior.

A modified adventitial inversion with graft insertion technique in acute Type A aortic dissection.

Acute type A aortic dissection may originate from a primary intimal tear located in the ascending aorta and often extends retrogradely into the aortic root. How to prevent bleeding in the aortic root and eliminate false lumen is very important in aortic dissection. We have developed a modified anastomotic technique that involves inverting adventitial and graft into aorta and reinforcing with a felt strip on the external border of the aortic wall. Since 2020, 45 consecutive patients with type A aortic coarctation have undergone this aortic root reconstruction procedure, to date, none have been reopened for bleeding or remnant dissection.

Comprehensive metabolome characterization and comparison between two sources of Dragon's blood by integrating liquid chromatography/mass spectrometry and chemometrics.

Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.

Management of biofilm by an innovative layer-structured membrane for membrane biofilm reactor (MBfR) to efficient methane oxidation coupled to denitrification (AME-D).

Aerobic methane oxidation coupled with denitrification (AME-D) has garnered significant attention as a promising technology for nitrogen removal from water. Effective biofilm management on the membrane surface is essential to enhance the efficiency of nitrate removal in AME-D systems. In this study, we introduce a novel and scalable layer-structured membrane (LSM) developed using a meticulously designed polyurethane sponge. The application of the LSM in advanced biofilm management for AME-D resulted in a substantial enhancement of denitrification performance. Our experimental results demonstrated remarkable improvements in nitrate-removal flux (92.8 mmol-N m-2 d-1) and methane-oxidation rate (325.6 mmol m-2 d-1) when using an LSM in a membrane biofilm reactor (L-MBfR) compared with a conventional membrane reactor (C-MBfR). The l-MBfR exhibited 12.4-, 6.8- and 3.4-fold increases in nitrate-removal rate, biomass-retention capacity, and methane-oxidation rate, respectively, relative to the control C-MBfR. Notably, the l-MBfR demonstrated a 3.5-fold higher abundance of denitrifying bacteria, including Xanthomonadaceae, Rhodocyclaceae, and Methylophilaceae. In addition, the denitrification-related enzyme activity was twice as high in the l-MBfR than in the C-MBfR. These findings underscore the LSM's ability to create anoxic/anaerobic microenvironments conducive to biofilm formation and denitrification. Furthermore, the LSM exhibited a unique advantage in shaping microbial community structures and facilitating cross-feeding interactions between denitrifying bacteria and aerobic methanotrophs. The results of this study hold great promise for advancing the application of MBfRs in achieving efficient and reliable nitrate removal through the AME-D pathway, facilitated by effective biofilm management.

Laser manufacturing of spatial resolution approaching quantum limit.

Atomic and close-to-atom scale manufacturing is a promising avenue toward single-photon emitters, single-electron transistors, single-atom memory, and quantum-bit devices for future communication, computation, and sensing applications. Laser manufacturing is outstanding to this end for ease of beam manipulation, batch production, and no requirement for photomasks. It is, however, suffering from optical diffraction limits. Herein, we report a spatial resolution improved to the quantum limit by exploiting a threshold tracing and lock-in method, whereby the two-order gap between atomic point defect complexes and optical diffraction limit is surpassed, and a feature size of <5 nm is realized. The underlying physics is that the uncertainty of local atom thermal motion dominates electron excitation, rather than the power density slope of the incident laser. We show that the colour centre yield in hexagonal boron nitride is transformed from stochastic to deterministic, and the emission from individual sites becomes polychromatic to monochromatic. As a result, single colour centres in the regular array are deterministically created with a unity yield and high positional accuracy, serving as a step forward for integrated quantum technological applications.

Experiences of cancer survivors returning to work decision-making: a meta-synthesis of qualitative studies.

PURPOSE: Return to work for cancer survivors (CSs) may be challenging, and there is a research gap in integrating the relevant experiences of the return-to-work decision-making process for CSs. Our aim was to synthesize existing qualitative research that integrates the dynamic experiences of CSs in the return-to-work decision-making process and highlights the factors influencing the return-to-work decisions of CSs. METHODS: We retrieved qualitative studies on a relevant theme published in the PubMed, EBSCO, Scopus, Web of Science, Cochrane Library, and CINAHL databases since construction to December 2023. Literature screening, quality evaluation, and data analysis followed the PRISMA, Joanna Briggs Institute Critical Appraisal Tool (2016), and thematic analysis methods to ensure study reliability. The study was registered on PROSPERO (registration number: CRD42023429623). RESULTS: Ten articles were included, and six key outcomes were identified based on Social Cognitive Career Theory (SCCT) integration: points of concern for individuals, sense of self-efficacy, outcome expectations, work perception and belonging, medical advice and guidance, and effects of the external reactions. CONCLUSION: The decision-making process for CSs to return to work is affected by various personal and external factors. Effectively addressing personal appearance, financial, and emotional issues can enhance self-efficacy of CSs. Improving external perceptions of cancer patients and enhancing social support in the workplace and medical settings can help CSs make informed decisions regarding their return to work. IMPLICATIONS FOR CANCER SURVIVORS: The decision of CSs to return to work is a result of integrating personal, job, and medical care considerations. These findings contribute to the development of future interventions for CSs' return-to-work decisions that target an array of potential factors.

Cross­talk between lymphangiogenesis and malignant melanoma cells: New opinions on tumour drainage and immunization (Review).

Malignant melanoma (MM) is a highly aggressive tumour that can easily metastasize through the lymphatic system at the early stages. Lymph node (LN) involvement and lymphatic vessel (LV) density (LVD) represent a harbinger of an adverse prognosis, indicating a strong link between the state of the lymphatic system and the advancement of MM. Permeable capillary lymphatic vessels are the optimal conduits for melanoma cell (MMC) invasion, and lymphatic endothelial cells (LECs) can also release a variety of chemokines that actively attract MMCs expressing chemokine ligands through a gradient orientation. Moreover, due to the lower oxidative stress environment in the lymph compared with the blood circulation, MMCs are more likely to survive and colonize. The number of LVs surrounding MM is associated with tumour-infiltrating lymphocytes (TILs), which is crucial for the effectiveness of immunotherapy. On the other hand, MMCs can release various endothelial growth factors such as VEGF-C/D-VEGFR3 to mediate LN education and promote lymphangiogenesis. Tumour-derived extracellular vesicles are also used to promote lymphangiogenesis and create a microenvironment that is more conducive to tumour progression. MM is surrounded by a large number of lymphocytes. However, both LECs and MMCs are highly plastic, playing multiple roles in evading immune surveillance. They achieve this by expressing inhibitory ligands or reducing antigen recognition. In recent years, tertiary lymphoid structures have been shown to be associated with response to anti-immune checkpoint therapy, which is often a positive prognostic feature in MM. The present review discusses the interaction between lymphangiogenesis and MM metastasis, and it was concluded that the relationship between LVD and TILs and patient prognosis is analogous to a dynamically tilted scale.

Severe Hypertensive Response to Atropine Therapy for Bradycardia Associated with Dexmedetomidine: Case Report and Literature Review.

Dexmedetomidine is a selective and potent α2-adrenoceptor agonist used for sedation, analgesia, and anxiolysis, with minimal respiratory depression; therefore, it is widely used in clinical practice. Transient hypertension has been reported to be an indication for the use of dexmedetomidine. The authors report three female patients who experienced hypertensive crisis when used atropine to treat bradycardia caused by dexmedetomidine. The transient hypertension is a relatively common side effect of dexmedetomidine, hypertensive crisis seen with coadministration of atropine is much less frequently reported. This is the first report to describe the use of atropine to treat bradycardia induced by dexmedetomidine, which may cause severe hypertension in female patients. They discuss the reason for and treatment of hypertension caused by administration of atropine and dexmedetomidine together and review the relevant literature.