In-hospital outcomes of older patients with gastric cancer and their risk factors: large comprehensive institution-based study.

PURPOSE: Gastric cancer (GC) is mostly a disease of aging, and older patients with GC are generally frailer. This study aimed to describe the characteristics and in-hospital outcomes, both overall and stratified by gender and resection, and to explore factors associated with outcomes of first hospitalization, in older GC patients. METHODS: Data on GC patients ≥ 65 years hospitalized from January 2016 until December 2020 were retrieved from the electronic medical records of a large tertiary hospital. Patient and tumor characteristics, duration and fee of hospitalization, and in-hospital mortality were described for overall patients and compared by gender and resection. Factors associated with outcomes of first hospitalization were explored using multivariable-adjusted logistic regression. RESULTS: 3238 eligible patients were analyzed, with a mean age of 71 years and a male proportion of 74%. The median duration and fee of first hospitalization were 13 days and 40,000 RMB, respectively, with a median fee of 17,000 RMB not covered by insurance. 16 (< 1%) and 32 (1%) deaths occurred during first and any hospitalization, respectively, with only 4 (< 1%) perioperative deaths. Compared to male patients, female cases had more often signet-ring-cell carcinoma, reduced food intake, resection, and history of major abdominal surgery. Compared to unresected cases, resected patients had higher body-mass-index and Barthel index, less often reduced food intake, weight loss, and risk of malnutrition, and more often common diet, longer hospital stay, and higher fee. Through multivariable-adjusted analysis, longer first hospital-stay was associated with earlier year of diagnosis, older ages, emergency admission, signet-ring-cell carcinoma, resection, history of anticoagulant intake, larger body-mass-index, non-common diet, and non-low-salt and non-diabetes diets; higher fee of first hospitalization was associated with later year of diagnosis, male gender, older ages, emergency admission, signet-ring-cell carcinoma, and resection. CONCLUSIONS: In this large institution-based study, older GC patients had low in-hospital mortality rates; the insurance coverage needs to be improved. Several characteristics and in-hospital outcomes significantly differed by gender and resection status, and various factors associated with duration and fee of first hospitalization were identified, providing important hints for individualized and stratified geriatric GC care.

Long-term outcomes of Allium ureteral stent as a treatment for ureteral obstruction.

Ureteral obstruction is a prevalent urological condition associated with significant complications. The purpose of our study was to assess the safety and efficacy of a novel self-expanding, large caliber, biocompatible polymer-coated ureteral stent (Allium) for the treatment of ureteral obstructions. We conducted a retrospective analysis of data from patients who underwent Allium ureteral stent placement at our institute between November 2018 and May 2023. Demographic, clinical, and perioperative parameters were collected and analyzed. Logistic regression analyses were performed to identify preoperative factors predicting Allium stent migration. The study cohort comprised 30 patients who received a total of 40 successfully implanted Allium stents. No significant adverse events related to the insertion procedure were observed. During a median follow-up period of 29 months (range: 1-60 months), migration occurred in 11 (27.5%) stents while encrustation was noted in 8 (20%) stents. The median functional duration of the Allium stents was found to be 22 months (range:1-60 months), with an overall functioning rate at last follow-up being recorded as 59.5%. Multivariate analysis revealed that the glomerular filtration rate of the ipsilateral kidney was the sole risk factor predictive of Allium stent migration. With its minimal invasiveness and good tolerability, the Allium stent represents a safe and viable management option for treating ureteric obstructions; however, it should not be considered as definitive treatment but rather as an alternative option for patients unwilling or unsuitable for definitive treatment, particularly high-risk individuals or elderly patients exhibiting decreased ipsilateral glomerular filtration rates.

Low-dose Ultra-high-resolution Photon-Counting Detector CT for Visceral Artery CT Angiography: A Preliminary Study.

RATIONALE AND OBJECTIVES: To validate the image quality of low-dose ultra-high-resolution (UHR) scanning mode of photon-counting detector CT (PCD-CT) for visceral artery computed tomography angiography (CTA). MATERIAL AND METHODS: We prospectively enrolled 57 patients each in the full dose (FD) and low-dose (LD) protocols, respectively, to undergo abdominal CT scans using the UHR mode on a PCD-CT system (NAEOTOM Alpha), between April 2023 and September 2023. Both the FD data and LD data were then reconstructed into two series of images: (a) 0.2 mm slice thickness, reconstruction kernel Bv48, quantum iterative reconstruction (QIR) 4; (b)1 mm slice thickness, Bv40, QIR 3. The signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of seven arteries were objectively measured. The image noise, vessel sharpness, overall quality, and visibility of nine arteries were subjectively assessed by three radiologists. RESULTS: The SNRs and CNRs of 0.2 mm reconstruction set was inferior to that of 1 mm reconstruction set (p < 0.001 for all the arteries and noise), however, the image quality of 0.2 mm reconstruction set was higher than that of 1 mm reconstruction set in qualitative evaluation especially for tiny arteries in Volume-rendered (VR) image (p < 0.001). The SNRs and CNRs were not significantly higher for FD group than LD group on the same slice thickness except for SNRs of common hepatic artery, splenic artery and bilateral renal arteries in 0.2 mm reconstruction set. In the comparison on image quality between normal weight and overweight patients within the same reconstruction set, the results showed that low-dose scan did not significantly impact the image quality in overweight patients. The ratings of visibility of nine visceral arteries were not significantly different among FD and LD at the same thickness reconstruction set except for superior mesenteric artery (p = 0.002 and 0.007 for 0.2 mm and 1 mm reconstruction set in axial image; p = 0.002 and 0.007 for 0.2 mm and 1 mm reconstruction set in coronal image, respectively) and left gastric artery (p = 0.002 and p < 0.001 for 0.2 mm and 1 mm reconstruction set in VR image, respectively). CONCLUSION: The low-dose UHR scanning mode of PCD-CT has proven to be adequate for the clinical evaluation of visceral arteries. Utilizing a reconstruction with a slice thickness of 0.2 mm could enhance arterial depiction, particularly for small vessels.

Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study.

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 µm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Characterizing the skeletal muscle immune microenvironment for sarcopenia: insights from transcriptome analysis and histological validation.

Background: Sarcopenia is a condition characterized by the age-related loss of skeletal muscle mass and function. The pathogenesis of the disease is influenced by chronic low-grade inflammation. However, the specific changes in the immune landscape changes of sarcopenic muscle are not yet fully understood. Methods: To gain insights into the immune cell composition and interactions, we combined single-nucleus RNA sequencing data, bulk RNA sequencing dataset, and comprehensive bioinformatic analyses on the skeletal muscle samples from young, aged, and sarcopenic individuals. Histological staining was then performed on skeletal muscles to validate the distribution of immune cells in clinical samples. Results: We analyzed the transcriptomes of 101,862 single nuclei, revealing a total of 10 major cell types and 6 subclusters of immune cell types within the human skeletal muscle tissues. Notable variations were identified in the immune microenvironment between young and aged skeletal muscle. Among the immune cells from skeletal muscle microenvironment, macrophages constituted the largest fraction. A specific marker gene LYVE1 for skeletal muscle resident macrophages was further identified. Cellular subclasses included four distinct groups of resident macrophages, which play different roles in physiological or non-physiological conditions. Utilizing bulk RNA sequencing data, we observed a significant enrichment of macrophage-rich inflammation in sarcopenia. Conclusions: Our findings demonstrate age-related changes in the composition and cross-talk of immune cells in human skeletal muscle microenvironment, which contribute to chronic inflammation in aged or sarcopenia muscle. Furthermore, macrophages emerge as a potential therapeutic target, thus advancing our understanding of the pathogenesis of sarcopenia.

[Macroreplantation of the upper extremity: Inventory in 2024]. / Macro-réimplantation du membre supérieur : état des lieux en 2024.

Macro-amputations are extremely serious traumas and represent one of the rare extreme emergencies in hand and upper limb surgery. Their rarity, especially in our developed countries, makes their treatment relatively unknown by surgical and anesthetic teams. However, the action plan to use during a macro-reimplantation, the decisive elements of pre- and post-operative management, and the key stages of the surgery, must be perfectly known, because they determine the success of a major reimplantation, for the limb survival and the future functional result. After a brief historical overview, the literature review proposed here provides an opportunity for an update on these formidable injuries and propose a treatment algorithm to guide the medical team in the management of these complex patients.

CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation.

ABSTRACT: Excessively activated or dysregulated complement activation may contribute to the pathogenesis of a wide range of human diseases, thus leading to a surge in complement inhibitors. Herein, we developed a human-derived and antibody-like C3b-targeted fusion protein (CRIg-FH-Fc) x2, termed CG001, that could potently block all 3 complement pathways. Complement receptor of the immunoglobulin superfamily (CRIg) and factor H (FH) bind to distinct sites in C3b and synergistically inhibit complement activation. CRIg occupancy in C3b prevents the recruitment of C3 and C5 substrates, whereas FH occupancy in C3b accelerates the decay of C3/C5 convertases and promotes the factor I-mediated degradation and inactivation of C3b. CG001 also showed therapeutic effects in alternative pathways-induced hemolytic mouse and classical pathways-induced mesangial proliferative glomerulonephritis rat models. In the pharmacological/toxicological evaluation in rats and cynomolgus monkeys, CG001 displayed an antibody-like pharmacokinetic profile, a convincing complement inhibitory effect, and no observable toxic effects. Therefore, CG001 holds substantial potential for human clinical studies.

A functional variant rs10409772 in FUT6 promoter regulates colorectal cancer progression through PKA/CREB signaling.

Fucosyltransferase 6 (FUT6) is overexpressed in colorectal cancer tissue according to TCGA samples and immunohistochemistry results of a tissue microarray. FUT6 effects cell migration, tumor formation and proliferation of colorectal cancer cells in different essays. FUT6 promotes cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by upregulating PKA/CREB pathway activation. Moreover, FUT6 expression is regulated by rs10409772 shown in the luciferase essays, a single nucleotide polymorphism in the promoter of FUT6. Our study suggests that elevated expression of FUT6 promotes PKA/CREB signaling, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased FUT6 expression.

Needle-perc-assisted endoscopic surgery versus retrograde intrarenal surgery for the treatment of 1- to 2-cm lower-pole renal stones in patients with unfavorable infundibulopelvic anatomy: a matched-pair analysis.

PURPOSE: To compare the safety and efficacy of needle-perc-assisted endoscopic surgery (NAES) and retrograde intrarenal surgery (RIRS) for the treatment of 1- to 2-cm lower-pole stones (LPS) in patients with complex infundibulopelvic anatomy. METHODS: Between June 2020 and July 2022, 32 patients with 1- to 2-cm LPS and unfavorable lower-pole anatomy for flexible ureteroscopy were treated with NAES. The outcomes of these patients were compared with patients who underwent RIRS using matched-pair analysis (1:1 scenario). The matching parameters such as age, gender, body mass index, stone size, hardness, and pelvicalyceal anatomy characteristics including infundibular pelvic angle, infundibular length, and width were recorded. Data were analyzed using the Student's t-test, Mann-Whitney U test, and Fisher's exact test. RESULTS: The two groups had similar baseline characteristics and lower-pole anatomy. The stone burden was comparable between both groups. NASE achieved a significantly better initial stone-free rate (SFR) than RIRS (87.5% vs 62.5%, p = 0.04). The auxiliary rates for the NAES and RIRS groups were 12.5% and 31.3%, respectively (p = 0.13). Finally, the SFR after 1 month follow-up period was still higher for the NAES group than RIRS group (93.8% versus 81.3%), but the difference was not statistically significant (p = 0.26). Concerning the operation duration, overall complication rates, and postoperative hospital stay, there were no differences between two groups. CONCLUSION: Compared to RIRS for treating 1- to 2-cm LPS in patients with unfavorable infundibulopelvic anatomy for flexible ureteroscopy, NAES was safe and effective with higher SFR and similar complication rate.

Automatic grading evaluation of winter wheat lodging based on deep learning.

Lodging is a crucial factor that limits wheat yield and quality in wheat breeding. Therefore, accurate and timely determination of winter wheat lodging grading is of great practical importance for agricultural insurance companies to assess agricultural losses and good seed selection. However, using artificial fields to investigate the inclination angle and lodging area of winter wheat lodging in actual production is time-consuming, laborious, subjective, and unreliable in measuring results. This study addresses these issues by designing a classification-semantic segmentation multitasking neural network model MLP_U-Net, which can accurately estimate the inclination angle and lodging area of winter wheat lodging. This model can also comprehensively, qualitatively, and quantitatively evaluate the grading of winter wheat lodging. The model is based on U-Net architecture and improves the shift MLP module structure to achieve network refinement and segmentation for complex tasks. The model utilizes a common encoder to enhance its robustness, improve classification accuracy, and strengthen the segmentation network, considering the correlation between lodging degree and lodging area parameters. This study used 82 winter wheat varieties sourced from the regional experiment of national winter wheat in the Huang-Huai-Hai southern area of the water land group at the Henan Modern Agriculture Research and Development Base. The base is located in Xinxiang City, Henan Province. Winter wheat lodging images were collected using the unmanned aerial vehicle (UAV) remote sensing platform. Based on these images, winter wheat lodging datasets were created using different time sequences and different UAV flight heights. These datasets aid in segmenting and classifying winter wheat lodging degrees and areas. The results show that MLP_U-Net has demonstrated superior detection performance in a small sample dataset. The accuracies of winter wheat lodging degree and lodging area grading were 96.1% and 92.2%, respectively, when the UAV flight height was 30 m. For a UAV flight height of 50 m, the accuracies of winter wheat lodging degree and lodging area grading were 84.1% and 84.7%, respectively. These findings indicate that MLP_U-Net is highly robust and efficient in accurately completing the winter wheat lodging-grading task. This valuable insight provides technical references for UAV remote sensing of winter wheat disaster severity and the assessment of losses.

The effect of self-designed metabolic equivalent exercises on cancer-related fatigue in patients with gastric cancer: A randomized controlled trial.

AIMS: To investigate the effect of Self-designed Metabolic Equivalent Exercises (SMEE) on cancer-related fatigue in patients with gastric cancer. METHODS: 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ-C30 Quality of Life Scale were used to measure cancer-caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. RESULTS: After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow-up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ-C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p < 0.001) subscales; in the SMEE group, QLQ-C30 scores in somatic (2.00 ± 0.27 vs. 1.31 ± 0.26, p < 0.001), emotional (2.67 ± 0.58 vs. 2.07 ± 0.48, p < 0.001), and social (3.23 ± 0.58 vs. 1.64 ± 0.51, p < 0.001) functioning were significantly higher than those in the control group, with significant improvements in fatigue (p < 0.001), nausea/vomiting (p = 0.014), shortness of breath (p < 0.001), constipation (p < 0.001), and diarrhea (p = 0.001) dimensions. CONCLUSION: The self-programmed metabolic equivalent manipulation as an exercise intervention could effectively reduce the degree of cancer-caused fatigue and improve quality of life in patients with gastric cancer.

Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Dynamic video recognition for cell-encapsulating microfluidic droplets.

Droplet microfluidics is a highly sensitive and high-throughput technology extensively utilized in biomedical applications, such as single-cell sequencing and cell screening. However, its performance is highly influenced by the droplet size and single-cell encapsulation rate (following random distribution), thereby creating an urgent need for quality control. Machine learning has the potential to revolutionize droplet microfluidics, but it requires tedious pixel-level annotation for network training. This paper investigates the application software of the weakly supervised cell-counting network (WSCApp) for video recognition of microdroplets. We demonstrated its real-time performance in video processing of microfluidic droplets and further identified the locations of droplets and encapsulated cells. We verified our methods on droplets encapsulating six types of cells/beads, which were collected from various microfluidic structures. Quantitative experimental results showed that our approach can not only accurately distinguish droplet encapsulations (micro-F1 score > 0.94), but also locate each cell without any supervised location information. Furthermore, fine-tuning transfer learning on the pre-trained model also significantly reduced (>80%) annotation. This software provides a user-friendly and assistive annotation platform for the quantitative assessment of cell-encapsulating microfluidic droplets.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Cadaveric study of flexor digitorum profundus and superficialis and flexor pollicis longus innervation patterns for application in selective neurectomy.

PURPOSE: Spasticity management in finger flexors (flexor digitorum profundus and superficialis and flexor pollicis longus) is a challenge. Recent studies demonstrated the short- and long-term efficacy of selective and hyperselective neurectomy for the spastic upper limb. However, hyperselective neurectomy of flexor digitorum profundus and flexor digitorum superficialis branches was incomplete, without impairing their muscular body and function. This cadaveric study describes a novel medial approach in the forearm, to reach all the muscular branches: flexor digitorum superficialis and profundus and flexor pollicis longus. MATERIAL AND METHODS: Fourteen cadaveric fresh frozen upper limbs were used. The feasibility of the medial surgical approach was studied, as well as the number, length and point of emergence of the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis. RESULTS: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, in all cases. A Martin Gruber communicating branch was found in 7 cases out of 14. CONCLUSION: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerve to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, without extensive transmuscular dissection of the pronator teres or flexor digitorum superficialis muscles. This approach opens the way for selective neurectomy of the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis muscles. LEVEL OF EVIDENCE: IV.

Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

Transcription factor 12-mediated self-feedback regulatory mechanism is required in DUX4 fusion leukaemia.

BACKGROUND: IGH::DUX4 is frequently observed in 4% B-cell acute lymphoblastic leukaemia patients. Regarding the IGH::DUX4-driven transactivation and alternative splicing, which are the main reasons behind this acute leukaemia outbreak, it remains unclear how transcriptional cofactors contribute to this oncogenic process. Further investigation is required to elucidate their specific role in leukaemogenesis. METHODS: In order to investigate the cofactors of IGH::DUX4, integrated mining of Chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing of leukaemia cells and patient samples were conducted. Furthermore, to elucidate the synergistic interaction between transcription factor 12 (TCF12) and IGH::DUX4, knockdown and knockout experiment, mammalian two-hybridisation assay, co-immunoprecipitation and in situ proximity ligation assays were carried out. Additionally, to further investigate the direct interaction between TCF12 and IGH::DUX4, AI-based structural simulations were utilised. Finally, to validate the synergistic role of TCF12 in promoting IGH::DUX4 leukaemia, cell proliferation, apoptosis and drug sensitivity experiments were performed. RESULTS: In this study, we observed that the IGH::DUX4 target gene TCF12 might be an important cofactor/helper for this oncogenic driver. The co-expression of IGH::DUX4 and TCF12 resulted in enhanced DUX4-driven transactivation. Supportively, knockdown and knockout of TCF12 significantly reduced expression of IGH::DUX4-driven target genes in leukaemia REH (a precursor B-cell leukaemia cell line) and NALM-6 cells (a precursor B-cell leukaemia cell line). Consistently, in TCF12 knockout cells, the expression of structure-based TCF12 mutant, but not wild-type TCF12, failed to restore the TCF12-IGH::DUX4 crosstalk and the synergistic transactivation. More importantly, the breakdown in TCF12-IGH::DUX4 cooperation impaired IGH::DUX4-driven leukaemia cell survival, caused sensitivity to the chemotherapy. CONCLUSIONS: Altogether, these results helped to define a previously unrecognised TCF12-mediated positive self-feedback regulatory mechanism in IGH::DUX4 leukaemia, which holds the potential to function as a pivotal drug target for the management of this particular form of leukaemia. HIGHLIGHTS: Transcription factor 12 (TCF12) is a new novel cofactor in IGH::DUX4 transcriptional complexes/machinery. TCF12 mediates a positive self-feedback regulatory mechanism in IGH::DUX4-driven oncogenic transaction. IGH::DUX4-TCF12 structure/cooperation might represent a potent target/direction in future drug design against B-cell acute lymphoblastic leukaemia.

Transfer of the palmaris brevis motor branch to the thenar motor branch: A cadaveric preliminary study.

OBJECTIVE: High median nerve injuries can lead to poor distal recovery, especially poor functioning of median innervated thenar muscles involved in thumb opposition and palmar abduction. The palmaris brevis (PB) is a small subcutaneous muscle innervated by ulnar nerve. Innervation of the PB is in most of cases provided by the ulnar digital nerve to the little finger. The purpose of this study is to assess the feasibility of transferring the PB motor branch (PBMB) to the median nerve thenar motor branch (TMB), in order to allow for early restoration of thumb palmar abduction and opposition, through a preliminary cadaveric study. METHODS: Twenty-five cadaver upper limbs were dissected under magnification. The length of the PBMB and TMB, and their origin were recorded. Nerve transfer from PBMB to TMB was conducted, and evaluated on 2 parameters: surgical feasibility, and distance from the coaptation site to the recipient nerve muscle entry point. The PBMB and TMB were harvested, fixated in formalin, then embedded in paraffin. They were sectioned transversely, and stained with a combination of hematoxylin-eosin and Luxol fast blue. Myelinated axons were counted in each specimen and the donor-to-recipient axon ratio was recorded. RESULTS: The PBMB was constant and originated from the ulnar digital nerve of the little finger in all cases. The transfer from PBMB to TMB was feasible in all cases. Mean myelinated axon counts of PBMB and TMB were 253±142 and 356±198, respectively (p=0.06). The donor-to-recipient axon ratio was 1:1.41. The mean distance from coaptation of the PBMB to the recipient thenar muscles was 23.1±3.0mm. CONCLUSIONS: Based on our results, PBMB to TMB transfer is feasible. The PBMB has the advantage over other distal nerve transfer donors to be constant and superficial, allowing for an easier harvest. Moreover, this procedure does not sacrifice any intrinsic function of the hand, and the proximity of the PBMB with the carpal tunnel allows for a single incision procedure. Therefore, early restoration of the median innervated thenar muscles may be feasible by the PBMB to TMB transfer in cases of high median nerve lesions. LEVEL OF EVIDENCE: IV.

Needle-perc-assisted endoscopic surgery (NAES) for patients with complicated solitary kidney stones: a prospective randomized study from a single center.

PURPOSE: The goal of this study is to compare traditional percutaneous nephrolithotomy (PCNL) and needle-perc-assisted endoscopic surgery (NAES) in the treatment of complicated solitary kidney stones via a single-center randomized controlled prospective study. METHODS: A total of patients with complex (Guy's score II-IV) solitary kidney stones between July 2019 to June 2022 were enrolled in the study. Participants were stratified into two groups: needle-perc-assisted endoscopic surgery group (group A) and traditional PCNL group (group B). All procedures were finished by X-ray free technique. The clinical characteristics and outcomes were analyzed. RESULTS: A total of 90 (44 in Group A and 46 in Group B) patients were finally included in our study. There were no statistically differences in terms of gender, age, body mass index (BMI), stone burden between two groups. The mean operative duration of Group A was significant higher than group B (95.1 ± 21.4 min vs 72.5 ± 29.5 min, p=0.02). The 1-month stone-free rate (SFR) was significant higher in Group A than B (90.9% vs 73.9%, p=0.03). A less hemoglobin drop (p=0.01), shorter postoperative in-hospital day (p=0.04), and lower severe complication (Clavien-Dindo III and above) rates (p=0.03) were observed in Group A. CONCLUSION: For patients with solitary kidney stones, NAES technique provides a higher one-session SFR, a better renal function recovery and compared with traditional PCNL.