A case series on safety and tolerability of human umbilical cord-derived mesenchymal stem cells on patients in Malaysia.

Umbilical cord-derived mesenchymal stem cells for regenerative therapy are a promising treatment option for chronic illnesses. Umbilical cord-derived mesenchymal stem cells offer several advantages over other sources, which makes them an attractive option in tissue repair and regeneration. This clinical study describes a 1-year follow-up on the safety and tolerance of umbilical cord-derived mesenchymal stem cell therapy on nine patients in Malaysia. Patients were assessed for adverse effects, and liver function tests were carried out on both pre- and post-treatments. Umbilical cord-derived mesenchymal stem cells' effectiveness and safety were assessed by follow-up evaluations. All nine patients responded positively towards umbilical cord-derived mesenchymal stem cell therapy, without any adverse effects. After umbilical cord-derived mesenchymal stem cell therapy, a significant improvement was observed in liver functioning test outcomes, as haematological parameters and tumour markers were stable. The present study concludes that umbilical cord-derived mesenchymal stem cell therapy is well tolerated by Malaysian patients; however, further clinical screening must be done over a large number of patients population.

Learning Curve for No-Touch Vein Harvesting Technique in Off-Pump Coronary Artery Bypass Grafting.

INTRODUCTION: This study aims to evaluate the learning curve associated with the no-touch vein harvesting technique in off-pump coronary artery bypass grafting (CABG), highlighting its impact on surgical proficiency. METHODS: We employed logarithmic curve fitting to analyze the learning curves of 160 patients undergoing no-touch CABG, with a detailed retrospective examination of 89 patients who received three grafts using Cumulative Sum (CUSUM) analysis. Patients were categorized into two phases: the initial learning phase and the subsequent mastery phase, based on the chronological order of surgeries. We then compared perioperative outcomes between these phases. RESULTS: The learning curve for the no-touch vein harvesting technique was quantitatively established at 51 cases via CUSUM analysis, with supporting evidence from logarithmic curve fitting indicating a significant proficiency milestone. In the mastery phase, median operative times, aorta-saphenous vein graft (SVG) anastomosis, and SVG inspection durations were notably reduced (230 vs. 250 minutes, P = 0.002; 11.5 vs. 13.0 minutes, P = 0.025; 9.0 vs. 11.0 minutes, P = 0.002, respectively), alongside decreased initial 48-hour chest tube drainage, shorter postoperative hospital stays, and fewer incidences of delayed leg incision healing compared to the learning phase [312.6 (140.7) ml vs. 401.0 (233.5) ml, P = 0.029; 11.0 d vs. 12.0 d, P = 0.026; 15.7% vs. 2.6%, P = 0.043)]. CONCLUSION: Cardiac surgeons adopting the full-incision SVG harvesting method for no-touch CABG undergo a discernible learning curve before achieving early proficiency. It is crucial, especially during the initial learning phase, to focus on aorta-SVG anastomosis, the meticulous inspection for bleeding, and the management of wound complications to optimize patient outcomes.

Survival outcomes in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy: a meta-analysis.

BACKGROUND: The survival outcomes in HER2-low versus HER2-zero breast cancer (BC) after neoadjuvant chemotherapy (NACT) remain unclear. The meta-analysis was conducted to summarize current evidence about the survival outcomes in HER2-low versus HER2-zero BC. METHODS: We conducted a systematic search in PubMed and EMBASE databases to identify relevant studies. RESULTS: A total of 14 studies with 53,714 patients were included. Overall, 34,037 patients (63.37%) were HER2-low, and 19,677 patients (36.63%) were HER2-zero. Patients with HER2-low tumors had a significantly lower pathological complete response (pCR) rate than patients with HER2-zero tumors, regardless of the hormone receptor status. Compared with HER2-zero breast cancer, the overall survival (OS) and disease-free survival (DFS) of HER2-low BC were longer in the overall cohort (HR = 0.72; 95% CI = 0.61-0.85; P < 0.0001; HR = 0.83; 95% CI = 0.75-0.92; P = 0.0002); however, no differences were observed in terms of OS and DFS between HER2-low and HER2-zero BC in the HR-negative group. In the HR-positive group, HER2-low status had no significant impact on OS, while significantly associated with increased DFS (HR = 0.85; 95% CI = 0.76-0.96; P = 0.007). CONCLUSION: These results suggest that although HER2-low BC has a poor response to NACT, it is correlated with favorable OS and DFS after NACT in the overall cohort as well as longer DFS in the HR-positive group.

Characterization of bacterial diversity and screening of cellulose-degrading bacteria in the gut system of Glenea cantor (Fabricius) larvae.

The intestinal bacteria of longhorn beetles would be ideal targets for pest control and lignocellulosic resources by destroying or exploiting their cellulose-degrading function. This article aims to investigate the diversity and community structure of intestinal bacteria the oligophagous longhorn beetle Glenea cantor. Additionally, it seeks to identify the presence of lignocellulose-degrading bacteria in the gut, and explore their role in consuming host kapok trees Bombax malabaricum. In this study, the bacterial community from G. cantor was examined by Illumina sequencing of 16S ribosomal RNA (rRNA) targeting the V3 and V4 regions. A total of 563,201 valid sequences and 814 OTUs were obtained. The dominant phyla were Proteobacteria, and the dominant genera were Acinetobacter and Lactococcus. The analysis of microbial diversity revealed a high bacterial diversity in the samples, with the gut bacteria playing a crucial role in the physiological activities of the host, particularly, 9 genera of intestinal bacteria with cellulose degradation function were found, highlighting their vital role in cellulose degradation. Five strains of cellulose-degrading bacteria, belonging to the genus Pseudomonas, were obtained from the intestinal tract of G. cantor larvae using traditional isolation and culture techniques as well as 16S rDNA sequencing. Among these strains, A4 exhibited a cellulase activity of 94.42 ± 0.42 U/mL, while A5 displayed the highest filter paper enzyme activity of 127.46 ± 3.54 U/mL. These results offered valuable insights into potential targets for pest control through internal attack digestion and cellulose-degrading bacteria in longhorn beetles.

Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

Abnormal occipital and frontal activity during voluntary convergence in intermittent exotropia: A task-fMRI study.

Intermittent exotropia (IXT) is characterized by intermittently outward deviation of the eye and involved with vergence dysfunction. This study aimed to investigate the brain areas related to voluntary convergence and cortical activation changes between IXT patients and normal subjects. A total of 21 subjects, including 11 IXT patients and 10 age- and sex-matched normal subjects, were recruited for this study. A voluntary convergence task was employed, with changes in brain function measured by functional magnetic resonance imaging (fMRI). Correlations between cortical activation and clinical measurements were conducted by Pearson's correlation analysis. fMRI results showed that during voluntary convergence, the medial frontal gyrus (MFG) and bilateral occipital cortex were activated in the normal group, whereas only activation of the occipital cortex in IXT patients. Compared with the normal, IXT patients showed hypo-activation of both the MFG and cuneus during the task. The activation of MFG was negatively correlated to the duration of IXT. This study demonstrates that both MFG and occipital cortex may participate in voluntary convergence in normal subjects, while IXT patients have an aberrant cortical function of the MFG and cuneus, and the duration of IXT likely influences the severity of MFG. These findings may provide valuable insights for understanding the relationship between convergence and IXT.

The characteristics of suicide attempters in Chinese patients: Comparison of adolescents, youths, middle-aged and elderly.

BACKGROUND: Potential risk factors for suicide differ by age group. Therefore, this study aims to investigate the characteristics of patients with suicide attempts according to age group and any the relevant risk factors. METHODS: This study retrospectively reviewed the medical records of attempted suicide patients who were admitted to the emergency departments (ED) of the First Affiliated Hospital of Wenzhou Medical University between January 1, 2017, and December 31, 2021. Demographic information and clinical characteristics were collected. The participants were divided into four age groups and the characteristics of each group were compared. RESULTS: A total of 834 participants were included in this study. Suicide attempts were more prevalent in females, and the gender difference decreased with age. Having religious belief and less educated suicide attempts were concentrated in the elderly groups. Adolescents suicide attempts were more likely to occur in the spring, autumn and during non-office hours. Mental disorders were the major motivation for suicide among adolescents, and interpersonal and social problems were more prevalent among youths. Psychiatric medication was the leading suicidal substances among adolescents, while pesticides and herbicides were more prevalent in adults. The history of psychiatric diagnosis was more common in adolescents, while the history of somatic disorder was more prevalent in the elderly. CONCLUSION: This study confirmed differences in the demographic and clinical characteristics of patients in different age groups. Therefore, it is necessary to construct individualized intervention strategies for each age group based on the characteristics of the patients in order to reduce suicide.

[Short-term Effect of Venetoclax Combined with Azacitidine and "7+3" Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia].

OBJECTIVE: To compare the short-term effect and adverse reaction of venetoclax (VEN) combined with azacitidine (AZA) versus "7+3" regimen in newly diagnosed elder patients with acute myeloid leukemia (AML). METHODS: From January 2021 to January 2022, the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed, including VEN+AZA group (41 cases) and "7+3" group (38 cases). The propensity score matching(PSM) method was used to balance confounding factors， then response， overall survival(OS), progressionfree survival(PFS) and adverse reactions between the two groups were compared. RESULTS: The ORR of VEN+AZA group and "7+3" group was 68% and 84%, respectively, and the CRc was 64% and 72%, respectively, the differents were not statistically significant (P >0.05). In the VEN+AZA group, there were 5 non-remission (NR) patients, 4 with chromosome 7 abnormality (7q-/-7), and 1 with ETV6 gene mutation. Median followed-up time between the two groups was 8 months and 12 months, respectively, and the 6-months OS was 84% vs 92% (P =0.389), while 6-months PFS was 84% vs 92% (P =0.258). The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳ myelosuppression, and the incidence rate was not statistically different(P >0.05). The median time of neutrophil recovery in two groups was 27(11-70) d, 25(14-61) d （P =0.161）, and platelet recovery was 27(11-75) d, 25(16-50) d （P =0.270）, respectively. The infection rate of VEN+AZA group was lower than that of "7+3" group (56% vs 88%, P =0.012）. The rate of lung infections of two groups was 36% and 64%, respectively, the difference was statistically significant (P =0.048). CONCLUSION: The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similar， but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormality（7q-/-7） may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

A human serum albumin-indocyanine green complex offers improved tumor identification in fluorescence-guided surgery.

Background: Complete tumor removal is critical for achieving a good prognosis in patients but remains challenging for surgeons. Near-infrared fluorescence-guided surgery (NIRFGS) enables surgeons to accurately localize tumors in real time and facilitates accurate resection. Indocyanine green (ICG) has been approved by the U.S. Food and Drug Administration and the National Medical Products Administration for many years. Although the application of ICG has progressed for a variety of surgeries, there are inherent limitations to ICG, including poor water solubility and photostability, short blood half-life, and aggregation in blood, resulting in poor imaging performance. We found that mixing ICG with human serum albumin (HSA) preoperatively and then injecting it can improve the imaging performance. Methods: We prepared fluorescent probes by combining ICG with HSA and identified their optimal ratio via in vitro absorption measurement and emission spectrum characterization of ICG-HSA complex with different mixing ratios and concentration gradients. Subsequently, under the optimal ratio and clinical simulated concentration, we conducted dynamic change analysis of the fluorescence spectral properties after mixing. We then compared the uptake of ICG-HSA in vitro for two different cell types and the imaging performance of different molar ratios of ICG and HSA in mouse models. Results: Through in vitro absorption and emission spectrum characterization of ICG-HSA mixtures with different mixing ratios and concentration gradients, the optimal ratio of the mixture was obtained (ICG:HSA =4:5). Using this ratio, clinical simulated concentration, and mixing, we completed the dynamic change analysis of the fluorescence spectrum properties. The results verified that HSA can improve the dispersion and stability of ICG in aqueous solution, reduce the proportion of free-state ICG, and thus improve the biodistribution. Moreover, the fluorescence performance of ICG was improved. ICG-HSA and ICG uptake in MDA-MB-231 cells and imaging in vivo showed that HSA increased the enrichment of ICG in tumor compared to ICG alone (ICG-HSAfluorescence intensity =237.3±10.7 vs. ICGfluorescence intensity =127.1±10.7). Compared with ICG alone, ICG-HSA provided a clearer tumor boundary and higher tumor-to-background ratio (TBR) (ICG-HSATBRmax 3.49±0.56 vs. ICGTBRmax 1.94±0.23). Conclusions: This study suggests that ICG-HSA can achieve higher tumor-to-background contrast with shorter time and can provide an overall superior imaging performance compared to ICG alone, thus exhibiting considerable potential for clinical application.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Obesity and acute type A aortic dissection: unraveling surgical outcomes through the lens of the upper hemisternotomy approach.

Background: Acute type A aortic dissection (ATAAD) is a pressing cardiovascular emergency necessitating prompt surgical intervention. Obesity, a pervasive health concern, has been identified as a significant risk factor for ATAAD, introducing unique surgical challenges that can influence postoperative outcomes. This study aimed to investigate the outcomes of ATAAD surgery across various body mass index (BMI) categories, focusing on the implications of the upper hemisternotomy (UHS) approach. Methods: Between April 2017 and October 2023, 229 patients diagnosed with ATAAD underwent aortic arch intervention via UHS at the General Hospital of Northern Theater Command. Based on BMI (WS/T 428-2013), patients were categorized into normal weight, overweight, and obese. The primary outcomes included perioperative parameters, intraoperative details, and postoperative complications, with specific emphasis on hypoxemia, defined by the Berlin criteria as a PaO2/FiO2 ratio of ≤300 mmHg. Results: The average age of the cohort was 50.1 ± 11.2 years with a male predominance (174 males). Preoperatively, 49.0% presented with hypoxemia, with the Obese group exhibiting a significantly elevated rate (77.9%, P < 0.001). Postoperatively, while the Normal group demonstrated a lower thoracic drainage volume 24 h post-surgery [180.0 (140.0) ml; P < 0.001], the Obese group indicated prolonged durations for mechanical ventilation and ICU stay, without statistical significance. Unlike the Normal and Overweight groups, the Obese group showed no notable changes in pre- and postoperative PaO2/FiO2 ratio. No significant difference was observed in severe postoperative complications among the groups. Further ROC curve analysis identifies a BMI cutoff of 25.5 for predicting postoperative hypoxemia, with 76.3% sensitivity and 84.4% specificity. And multivariate analysis reveals BMI and preoperative hypoxemia as independent predictors of postoperative hypoxemia. Conclusion: Obesity, although presenting unique challenges in ATAAD interventions, does not necessarily portend adverse outcomes when managed with meticulous surgical planning and postoperative care. The study emphasizes the significance of individualized patient assessment and tailoring surgical strategies, suggesting the potential of UHS in addressing the surgical intricacies posed by obesity in ATAAD patients. Further research is warranted to consolidate these findings.

Total arch replacement via single upper hemisternotomy approach for aortic aneurysm in syphilis: Case report.

RATIONALE: Syphilitic aortic aneurysm is a relatively rare type of cardiovascular syphilis. A small number of patients with syphilitic aortic aneurysms will be accompanied by aortic regurgitation and coronary stenosis. Apart from aortic rupture or dissection, syphilitic aortic aneurysm often causes associated vascular disorders, including left common carotid artery, innominate artery, and celiac artery stenosis or obstruction. PATIENT CONCERNS: In this case, we observed left common carotid artery occlusion based on both ultrasound and intraoperative exploration. For patients with syphilitic aortic aneurysm, the first choice is still sufficient antibiotic therapy. The surgical indications include symptom relief and prevention of aortic rupture or sudden death. DIAGNOSES: Aortic valve insufficiency, aortic aneurysm, and syphilis. INTERVENTIONS: Aortic valve replacement, aneurysmectomy and total arch replacement combined with frozen elephant trunk implantation via single upper hemisternotomy approach. OUTCOMES: The patient did not suffer reventilation and reoperation. No transient or permanent neurological dysfunction was observed in this patient. And no acute renal failure occurred. The patient was discharged on 43 days after the operation. LESSONS SUBSECTIONS: The upper hemisternotomy has the advantages of faster postoperative recovery, shorter ventilation time, shorter intensive care unit stay, less blood transfusion, and less incisional pain compared with the full sternotomy, which is one of the reasons why we chose this procedure for this patient.

Spatiotemporal development and the regulatory mechanisms of cardiac resident macrophages: Contribution in cardiac development and steady state.

Cardiac resident macrophages (CRMs) are integral components of the heart and play significant roles in cardiac development, steady-state, and injury. Advances in sequencing technology have revealed that CRMs are a highly heterogeneous population, with significant differences in phenotype and function at different developmental stages and locations within the heart. In addition to research focused on diseases, recent years have witnessed a heightened interest in elucidating the involvement of CRMs in heart development and the maintenance of cardiac function. In this review, we primarily concentrated on summarizing the developmental trajectories, both spatial and temporal, of CRMs and their impact on cardiac development and steady-state. Moreover, we discuss the possible factors by which the cardiac microenvironment regulates macrophages from the perspectives of migration, proliferation, and differentiation under physiological conditions. Gaining insight into the spatiotemporal heterogeneity and regulatory mechanisms of CRMs is of paramount importance in comprehending the involvement of macrophages in cardiac development, injury, and repair, and also provides new ideas and therapeutic methods for treating heart diseases.

Recent progress in engineering Clostridium autoethanogenum to synthesize the biochemicals and biocommodities.

Excessive mining and utilization fossil fuels has led to drastic environmental consequences, which will contribute to global warming and cause further climate change with severe consequences for the human population. The magnitude of these challenges requires several approaches to develop sustainable alternatives for chemicals and fuels production. In this context, biological processes, mainly microbial fermentation, have gained particular interest. For example, autotrophic gas-fermenting acetogenic bacteria are capable of converting CO, CO2 and H2 into biomass and multiple metabolites through Wood-Ljungdahl pathway, which can be exploited for large-scale fermentation processes to sustainably produce bulk biochemicals and biofuels (e.g. acetate and ethanol) from syngas. Clostridium autoethanogenum is one representative of these chemoautotrophic bacteria and considered as the model for the gas fermentation. Recently, the development of synthetic biology toolbox for this strain has enabled us to study and genetically improve their metabolic capability in gas fermentation. In this review, we will summarize the recent progress involved in the understanding of physiological mechanism and strain engineering for C. autoethanogenum, and provide our perspectives on the future development about the basic biology and engineering biology of this strain.

Metabolism Serves as a Bridge Between Cardiomyocytes and Immune Cells in Cardiovascular Diseases.

Metabolic disorders of cardiomyocytes play an important role in the progression of various cardiovascular diseases. Metabolic reprogramming can provide ATP to cardiomyocytes and protect them during diseases, but this transformation also leads to adverse consequences such as oxidative stress, mitochondrial dysfunction, and eventually aggravates myocardial injury. Moreover, abnormal accumulation of metabolites induced by metabolic reprogramming of cardiomyocytes alters the cardiac microenvironment and affects the metabolism of immune cells. Immunometabolism, as a research hotspot, is involved in regulating the phenotype and function of immune cells. After myocardial injury, both cardiac resident immune cells and heart-infiltrating immune cells significantly contribute to the inflammation, repair and remodeling of the heart. In addition, metabolites generated by the metabolic reprogramming of immune cells can further affect the microenvironment, thereby affecting the function of cardiomyocytes and other immune cells. Therefore, metabolic reprogramming and abnormal metabolite levels may serve as a bridge between cardiomyocytes and immune cells, leading to the development of cardiovascular diseases. Herein, we summarize the metabolic relationship between cardiomyocytes and immune cells in cardiovascular diseases, and the effect on cardiac injury, which could be therapeutic strategy for cardiovascular diseases, especially in drug research.

METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control.

BACKGROUND: RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined. METHODS: METTL1/WDR4 expression levels were quantified using qRT-PCR, western blot analysis on AML clinical samples, and bioinformatics analysis on publicly available AML datasets. CCK-8 assays and cell count assays were performed to determine cell proliferation. Flow cytometry assays were conducted to assess cell cycle and apoptosis rates. Multiple techniques were used for mechanism studies in vitro assays, such as northern blotting, liquid chromatography-coupled mass spectrometry (LC-MS/MS), tRNA stability analysis, transcriptome sequencing, small non-coding RNA sequencing, quantitative proteomics, and protein synthesis measurements. RESULTS: METTL1/WDR4 are significantly elevated in AML patients and associated with poor prognosis. METTL1 knockdown resulted in reduced cell proliferation and increased apoptosis in AML cells. Mechanically, METTL1 knockdown leads to significant decrease of m7G modification abundance on tRNA, which further destabilizes tRNAs and facilitates the biogenesis of tsRNAs in AML cells. In addition, profiling of nascent proteins revealed that METTL1 knockdown and transfection of total tRNAs that were isolated from METTL1 knockdown AML cells decreased global translation efficiency in AML cells. CONCLUSIONS: Taken together, our study demonstrates the important role of METTL1/WDR4 in AML leukaemogenesis, which provides a promising target candidate for AML therapy.

Perceptions of adult patients with cancer towards telemedicine: A qualitative meta-synthesis.

Objective: This study aims to systematically identify, evaluate, and synthesize published qualitative research on the views and attitudes of adult cancer patients toward telemedicine and, consequently to better inform the future development of telemedicine technology and interventions. Methods: A meta-synthesis review was conducted to identify qualitative studies that reported adult cancer patients' perceptions toward telemedicine applications using nine electronic databases, including PubMed, MEDLINE, Web of Science, the Cochrane Library, PsycINFO, CINAHL, Wan Fang, VIP, and CNKI, from inception to November 2022. Quality appraisal was guided by the Joanna Briggs Institute's (JBI) Critical Appraisal Checklist for Qualitative Research. Data were synthesized using "thematic synthesis" to identify themes and concepts. Results: A total of 3518 articles were retrieved, of which 23 met the inclusion and exclusion criteria. These studies identified three key meta-themes and 11 key sub-themes: (1) Benefits of telemedicine: obtaining information and social support, maintaining the continuity of treatment, receiving professional assistance, having greater flexibility, and promoting physical and mental health; (2) Limitations of telemedicine: interference with normal life, privacy and security issues, auxiliary function issues, and increased psychological burden; (3) Expectations for future telemedicine: more personalized intervention, more specific and diverse information. Conclusions: The study showed that the benefits and limitations coexisted in the process of telemedicine application among adult cancer patients. It is necessary to develop personalized applications that are better suited to the needs and characteristics of adult cancer patients. Future telemedicine interventions should focus on information diversification and provide patients with more diverse and effective information. Systematic review registration: PROSPERO, CRD42022324528.

Role of Histiocyte-Derived frHMGB1 as a Facilitator in Non-Canonical Pyroptosis of Monocytes/Macrophages in Lethal Sepsis.

In this study, we investigated the role of the non-canonical pyroptosis pathway in the progression of lethal sepsis. Our findings emphasize the significance of non-canonical pyroptosis in monocytes/macrophages for the survival of septic mice. We observed that inhibiting pyroptosis alone significantly improved the survival rate of septic mice, and the HMGB1 A box effectively suppressed this non-canonical pyroptosis, thereby enhancing the survival of septic mice. Additionally, our cell in vitro experiments further unveil that frHMGB1, originating from LPS-carrying histiocytes, enters macrophages via RAGE, resulting in the direct activation of caspase-11 and the induction of non-canonical pyroptosis. Notably, the A Box's competitive binding with LPS thereby impedes its entry into the cell cytosol. These findings reveal potential therapeutic strategies for slowing the progression of lethal sepsis by modulating the non-canonical pyroptosis pathway.

Development of a theory-based family resilience intervention program for parents of children with chronic diseases: A Delphi study.

BACKGROUND: Long-term illness exposes children with chronic diseases to a high risk of deterioration of physical and mental health. Developing an effective family resilience intervention program is a critical concern. OBJECTIVE: To develop a theory-based family resilience intervention program for parents of children with chronic diseases and provide a reference for clinical intervention. METHODS: A two-phased research design, guided by the Walsh family resilience process model, was employed to develop the intervention program. In phase 1, a scoping literature review was conducted to identify the possible elements of family resilience interventions. In phase 2, a three-round Delphi survey was conducted with experts (n = 14) using an online electronic survey to obtain their consensus on the intervention content. RESULTS: Three main components were identified: (1) strengthening family beliefs, (2) adjusting the family organization pattern, and (3) improving the family communication process. And 8 modules were developed: "introducing adversity and family resilience", "finding and strengthening positive family beliefs, and building confidence to live with the disease", "analyzing and adjusting family structure", "assisting families to increase and utilizing internal and external resources", "optimizing communication skills", "strengthening collaborative problem-solving capacity", "enhancing the family narrative ability", and "enhancing emotional expression". After 3-round Delphi, the findings indicated that the intervention program is applicable and feasible for parents of children with chronic diseases in China. CONCLUSION: The principal merit of this study lies in the development of a family resilience intervention program for parents of children with chronic diseases. The intervention's usability and efficacy should be investigated in future studies. IMPLICATIONS TO PRACTICE: Developing a family resilience intervention program is a critical first step toward providing effective care for parents of children with chronic diseases, and evaluating the program's feasibility and suitability in the target population is warranted.

Branched-chain amino acid catabolic defect in vascular smooth muscle cells drives thoracic aortic dissection via mTOR hyperactivation.

Metabolic reprogramming of vascular smooth muscle cell (VSMC) plays a critical role in the pathogenesis of thoracic aortic dissection (TAD). Previous researches have mainly focused on dysregulation of fatty acid or glucose metabolism, while the impact of amino acids catabolic disorder in VSMCs during the development of TAD remains elusive. Here, we identified branched-chain amino acid (BCAA) catabolic defect as a metabolic hallmark of TAD. The bioinformatics analysis and data from human aorta revealed impaired BCAA catabolism in TAD individuals. This was accompanied by upregulated branched-chain α-ketoacid dehydrogenase kinase (BCKDK) expression and BCKD E1 subunit alpha (BCKDHA) phosphorylation, enhanced vascular inflammation, and hyperactivation of mTOR signaling. Further in vivo experiments demonstrated that inhibition of BCKDK with BT2 (a BCKDK allosteric inhibitor) treatment dephosphorylated BCKDHA and re-activated BCAA catabolism, attenuated VSMCs phenotypic switching, alleviated aortic remodeling, mitochondrial reactive oxygen species (ROS) damage and vascular inflammation. Additionally, the beneficial actions of BT2 were validated in a TNF-α challenged murine VSMC cell line. Meanwhile, rapamycin conferred similar beneficial effects against VSMC phenotypic switching, cellular ROS damage as well as inflammatory response. However, co-treatment with MHY1485 (a classic mTOR activator) reversed the beneficial effects of BT2 by reactivating mTOR signaling. Taken together, the in vivo and in vitro evidence showed that impairment of BCAA catabolism resulted in aortic accumulation of BCAA and further caused VSMC phenotypic switching, mitochondrial ROS damage and inflammatory response via mTOR hyperactivation. BCKDK and mTOR signaling may serve as the potential drug targets for the prevention and treatment of TAD.