Comparison of proximal gastrectomy and total gastrectomy in proximal gastric cancer: a meta-analysis of postoperative health condition using the PGSAS-45.

PURPOSE: Proximal gastrectomy (PG) offers advantages over total gastrectomy (TG) in enhancing the postoperative nutritional status of patients with proximal gastric cancer (PGC), yet its effect on long-term quality of life is still debated. This study aims to thoroughly compare postoperative health condition outcomes between PG and TG. METHODS: We conducted a systematic search of English-language articles from the PubMed, Web of Science, and Cochrane Library databases, covering studies published up to February 2023. Key evaluation endpoints included surgical outcomes and postoperative health condition, assessed using the Post-Gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). RESULTS: Six retrospective cohort studies were included in the analysis. The PG group demonstrated no significant negative impact on surgical outcomes compared to the TG group. Notably, patients who underwent PG experienced a superior postoperative health condition, characterized by fewer gastroesophageal reflux symptoms (WMD = -0.106, 95% CI -0.183 to -0.029, P < 0.01), less weight loss (WMD = 4.440, 95% CI 3.900 to 4.979, P < 0.01), and reduced dietary dissatisfaction (WMD = -0.205, 95% CI -0.385 to -0.025, P = 0.03). CONCLUSION: This study provides compelling evidence that PG is superior to TG in enhancing postoperative health condition for patients with proximal gastric cancer, without compromising surgical outcomes. However, further rigorous randomized controlled trials are necessary to inform surgical decision-making more effectively.

[Comparison of Blood Oxygen Saturation Detection Methods in Patients with Hyperleukocytic Acute Leukemia].

OBJECTIVE: To investigate which indicator is more advantageous when using arterial oxygen saturation (SaO2) and fingertip pulse oxygen saturation (SpO2) for blood oxygen detection in patients with hyperleukocytic acute leukemia (HAL). METHODS: In this prospective research, the difference between SaO2 and SpO2 of 18 HAL patients (observation group) and 14 patients (control group), as well as the relationship between the difference and white blood cell (WBC) counts were analyzed. RESULTS: SaO2 was lower than SpO2 in the observation group (P <0.05), and SpO2-SaO2 difference was positively correlated with WBC counts (r =0.47). However, there was no statistical difference between SaO2 and SpO2 in the control group. SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group, but there was no statistical difference. There was no downward trend of SaO2 and PO2 in the control group. CONCLUSION: HAL patients have a phenomenon where SaO2 is lower than SpO2, that is pseudohypoxemia, and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro SpO2 can be monitored bedside in real time and is non-invasive, it is a better way to detect the blood oxygen status of HAL patients.

When IGF-1 Meets Metabolic Inflammation and Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with insulin resistance (IR) and hyperandrogenaemia (HA). Metabolic inflammation (MI), characterized by a chronic low-grade inflammatory state, is intimately linked with chronic metabolic diseases such as IR and diabetes and is also considered an essential factor in the development of PCOS. Insulin-like growth factor 1 (IGF-1) plays an essential role in PCOS pathogenesis through its multiple functions in regulating cell proliferation metabolic processes and reducing inflammatory responses. This review summarizes the molecular mechanisms by which IGF-1, via MI, participates in the onset and progression of PCOS, aiming to provide insights for studies and clinical treatment of PCOS.

Combining avidin with CD63 improves basophil activation test accuracy in classifying peanut allergy.

BACKGROUND: Conventional basophil activation tests (BATs) measure basophil activation by the increased expression of CD63. Previously, fluorophore-labeled avidin, a positively-charged molecule, was found to bind to activated basophils, which tend to expose negatively charged granule constituents during degranulation. This study further compares avidin versus CD63 as basophil activation biomarkers in classifying peanut allergy. METHODS: Seventy subjects with either a peanut allergy (N = 47), a food allergy other than peanut (N = 6), or no food allergy (N = 17) were evaluated. We conducted BATs in response to seven peanut extract (PE) concentrations (0.01-10,000 ng/mL) and four control conditions (no stimulant, anti-IgE, fMLP (N-formylmethionine-leucyl-phenylalanine), and anti-FcεRI). We measured avidin binding and CD63 expression on basophils with flow cytometry. We evaluated logistic regression and XGBoost models for peanut allergy classification and feature identification. RESULTS: Avidin binding was correlated with CD63 expression. Both markers discriminated between subjects with and without a peanut allergy. Although small by percentage, an avidin+ /CD63- cell subset was found in all allergic subjects tested, indicating that the combination of avidin and CD63 could allow a more comprehensive identification of activated basophils. Indeed, we obtained the best classification accuracy (97.8% sensitivity, 96.7% specificity) by combining avidin and CD63 across seven PE doses. Similar accuracy was obtained by combining PE dose of 10,000 ng/mL for avidin and PE doses of 10 and 100 ng/mL for CD63. CONCLUSIONS: Avidin and CD63 are reliable BAT activation markers associated with degranulation. Their combination enhances the identification of activated basophils and improves the classification accuracy of peanut allergy.

[Inhibitory Effect of Resveratrol on the Proliferation of Multiple Myeloma Cells and the Underlying Mechanism].

OBJECTIVE: To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism. METHODS: MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot. RESULTS: RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G1 phase was increased, and that in G2/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV. CONCLUSION: RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.

Modified ulnar lengthening for correction of the Masada type 2 forearm deformity in hereditary multiple exostosis.

Few articles have reported on the treatment of Masada type 2 forearm deformities in hereditary multiple exostosis, possibly because of the high redislocation rate and other complications. This study precisely declares the use of modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities. 20 children with Masada type 2 forearm deformities were admitted for surgical treatment at our hospital from February 2014 to February 2021. There were 13 girls and 7 boys, ranging in age from 3.5 to 15 years (mean: 9 years) at the time of operation. We removed the prominent osteochondromas of the distal ulna and the proximal radius, positioned a classic Ilizarov external fixator on the forearm and then performed ulnar transverse one-third proximal diaphyseal subperiosteal osteotomy. We adopted modified ulnar lengthening postoperatively. The effects of surgical correction of deformity and functional improvement of the limb were assessed via regular follow-up and X-ray. The patients were followed up for 36 months, and the ulna was lengthened 26.99 mm on average; all radial heads remained relocated. The radiographic evaluations, including relative ulnar shortening, radial articular angle, and carpal slip, were improved. The functions of the elbow and forearm were all improved after surgery. Modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities in hereditary multiple exostoses has been proven to be an effective and reliable technique in the early stage.

MicroRNA, mRNA, and Proteomics Biomarkers and Therapeutic Targets for Improving Lung Cancer Treatment Outcomes.

The majority of lung cancer patients are diagnosed with metastatic disease. This study identified a set of 73 microRNAs (miRNAs) that classified lung cancer tumors from normal lung tissues with an overall accuracy of 96.3% in the training patient cohort (n = 109) and 91.7% in unsupervised classification and 92.3% in supervised classification in the validation set (n = 375). Based on association with patient survival (n = 1016), 10 miRNAs were identified as potential tumor suppressors (hsa-miR-144, hsa-miR-195, hsa-miR-223, hsa-miR-30a, hsa-miR-30b, hsa-miR-30d, hsa-miR-335, hsa-miR-363, hsa-miR-451, and hsa-miR-99a), and 4 were identified as potential oncogenes (hsa-miR-21, hsa-miR-31, hsa-miR-411, and hsa-miR-494) in lung cancer. Experimentally confirmed target genes were identified for the 73 diagnostic miRNAs, from which proliferation genes were selected from CRISPR-Cas9/RNA interference (RNAi) screening assays. Pansensitive and panresistant genes to 21 NCCN-recommended drugs with concordant mRNA and protein expression were identified. DGKE and WDR47 were found with significant associations with responses to both systemic therapies and radiotherapy in lung cancer. Based on our identified miRNA-regulated molecular machinery, an inhibitor of PDK1/Akt BX-912, an anthracycline antibiotic daunorubicin, and a multi-targeted protein kinase inhibitor midostaurin were discovered as potential repositioning drugs for treating lung cancer. These findings have implications for improving lung cancer diagnosis, optimizing treatment selection, and discovering new drug options for better patient outcomes.

Strategies of Targeting CK2 in Drug Discovery: Challenges, Opportunities, and Emerging Prospects.

CK2 (casein kinase 2) is a serine/threonine protein kinase that is ubiquitous in eukaryotic cells and plays important roles in a variety of cellular functions, including cell growth, apoptosis, circadian rhythms, DNA damage repair, transcription, and translation. CK2 is involved in cancer pathogenesis and the occurrence of many diseases. Therefore, targeting CK2 is a promising therapeutic strategy. Although many CK2-specific small-molecule inhibitors have been developed, only CX-4945 has progressed to clinical trials. In recent years, novel CK2 inhibitors have gradually become a research hotspot, which is expected to overcome the limitations of traditional inhibitors. Herein, we summarize the structure, biological functions, and disease relevance of CK2 and emphatically analyze the structure-activity relationship (SAR) and binding modes of small-molecule CK2 inhibitors. We also discuss the latest progress of novel strategies, providing insights into new drugs targeting CK2 for clinical practice.

Effect of chemotherapy (with and without radiotherapy) on the intelligence of children and adolescents treated for acute lymphoblastic leukemia; a meta-analysis.

OBJECTIVE: This meta-analysis assesses cognitive functioning in children with acute lymphoblastic leukemia post-treatment who were treated with either chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). METHODS: The databases Pubmed and PsychInfo were searched between 1-1-2000 and 31-12-2021. Data were analyzed using Comprehensive Meta-Analysis (version 2). RESULTS: Mean weighted intelligence after treatment was 100.2 (number of studies n = 51, 95% CI: 98.8-101.5). For CT-only, it was 100.8 (95% CI: 99.5-102.2) and for CTRT 97.8 (95% CI: 95.9-100.2). Compared to recruited healthy controls, treated children had on average lower IQ scores (n = 23, mean difference -7.8, 95% CI: -10.7 to -5.0, p < 0.001). When looking only at studies using controls recruited from the patient's family, results remained significant (n = 5, mean difference -6.0, 95% CI: -8.6 to -3.5, p = 0.001). Meta-regressions aimed at identifying predictors of IQ after treatment failed to find an effect for sex or age. We could demonstrate an effect of time between diagnosis and IQ measurement for the CTRT treated patient (B = -0.26, 95% CI: -0.40 to -0.1, p = 0.002). CONCLUSIONS: IQ scores of patients treated with CT-only or CTRT treatment regimens did not differ from the normative population. However, compared to recruited control groups, patients showed lower mean IQ scores. The Flynn effect and/or selection effects may play a role in this discrepancy. Considering time since diagnosis may have a significant impact on IQ, at least in CTRT treated patients, long-term clinical follow-up of neurocognitive development may be prudent to detect possible (late) neurocognitive effects.

Hydrogen sulfide treatment improves quality attributes via regulating the antioxidant system in goji berry (Lycium barbarum L.).

Hydrogen sulfide (H2S) has been identified as a critical gaseous signaling chemical. Herein, the effects of H2S treatment on the postharvest goji berries and antioxidant enzyme activities were determined. H2S application delayed the decay index, loss of firmness, color, flavor, and total sugars and loss of total protein, betaine and ascorbic acid in goji berries during postharvest storage. Meanwhile, H2S noticeably reduced the MDA, H2O2, and O2- accumulation. Additionally, it was shown that H2S increased the activity of catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), glutathione reductase (GR) and superoxide dismutase (SOD) while decreased the quantity of lipoxygenase (LOX). The mRNA expression of LDC, DCD, CAT, APX, POD, GR and SOD was up-regulated but LOX, RBOH-b and RBOH-e was down-regulated in goji berries after H2S treatment. Altogether, H2S could efficiently delay the senescence, improves postharvest quality, increase the bioactive compounds accumulation, and boost the antioxidant capacity of goji berries through modulating antioxidant enzyme system.

An Effective Technique for Managing the Calcaneus Osteomyelitis Combined with Soft-Tissue Defect.

The treatment of the Cierny-Mader (C-M) type III-IV calcaneus osteomyelitis combining with the soft-tissue defect is sophisticated and difficult. The aim of this study is to introduce the application and availability of the modified distally based sural flap with an adipofascial extension to reconstruct these defects. We retrospectively reviewed the data of 37 patients with C-M type III-IV calcaneus osteomyelitis accompanied with soft-tissue defect between December 2004 and December 2019. A modified distally based sural flap with an adipofascial extension was conducted to reconstruct the defect. The patient's demographics, duration of the diseases, etiology, reconstruction outcomes, infection control rate, recurrence rate, amputation rate, and follow-up data were collected to evaluate the effectiveness and reliability of the modification. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot scale was applied to assess the function of the ankle and hindfoot. Thirty-four flaps survived uneventfully, 1 flap displayed marginal necrosis and 2 flaps (5.41%) developed partial necrosis. Using this modified flap alone or combining with some simple salvage methods reconstructed all of the defects successfully. The calcaneus osteomyelitis was cured successfully, and no recurrences were observed during the follow-up period. The AOFAS ankle and hindfoot scores were excellent in 27 patients and good in 8 patients. The distally based sural flap with an adipofacial extension is a simple and effective technique to reconstruct the calcaneus osteomyelitis combined with soft-tissue defect in 1 stage. Applications of the adipofacial extension to obliterate the dead space and the well-vascularized skin island to cover the defect are the guarantee of achieving good ankle and foot functions. However, this technique is not appropriate for the patients with calcaneum less than half weight-bearing area.

Insights into pralsetinib resistance to the non-gatekeeper RET kinase G810C mutation through molecular dynamics simulations.

OBJECTIVE: RET (rearranged during transfection) kinase, as a transmembrane receptor tyrosine kinase, is a therapeutic target for several human cancer such as non-small cell lung cancer (NSCLC) and thyroid cancer. Pralsetinib is a recently approved drug for the treatment of RET-driven NSCLC and thyroid cancers. A single point mutation G810C at the C-lobe of the RET kinase causes pralsetinib resistance to this non-gatekeeper variant. However, the detailed mechanism remains poorly understood. METHODS: Here, multiple microsecond molecular dynamics (MD) simulations, molecular mechanics/generalized born surface area (MM/GBSA) binding free energy calculations, and community network analysis were performed to reveal the mechanism of pralsetinib resistance to the RET G810C mutant. RESULTS: The simulations showed that the G810C mutation had a minor effect on the overall conformational dynamics of the RET kinase domain. Energetic analysis suggested that the G810C mutation reduced the binding affinity of pralsetinib to the mutant. Per-residue energy contribution and structural analyses revealed that the hydrogen bonding interactions between pralsetinib and the hinge residues Glu805 and Ala807 were disrupted in the G810C mutant, which were responsible for the decreased binding affinity of pralsetinib to the mutant. CONCLUSIONS: The obtained results may provide understanding of the mechanism of pralsetinib resistance to the non-gatekeeper RET G810C mutant.

[MiR-21 Regulates the Proliferation of Multiple Myeloma Cells by Inhibiting the Expression of KLF5].

OBJECTIVE: To study the expression of miR-21 in multiple myeloma (MM) cell lines and plasma cells of patients, and explore the mechanism of miR-21 in MM. METHODS: Bone marrow samples from 30 patients with MM and 18 healthy controls were collected. The plasma cells were separated by magnetic beads. MM cell lines (MM1.S cells, RPMI-8226 cells and U266 cells) were cultured. The expression level of miR-21 was detected by real-time fluorescent quantitative PCR (qRT-PCR). After transfection with hsa-miR-21 mimics and hsa-miR-21 inhibitor, the proliferation of MM cells was detected by CCK-8 and cell cloning assay. The target genes regulated by miR-21 were predicted by bioinformatics website. The binding sites of miR-21 and KLF5 were detected by luciferase reporter gene assay. The expression of KLF5 were detected by Western blot and qRT-PCR after hsa-miR-21 mimics and hsa-miR-21 inhibitor were transfected into RPMI-8226 cells. KLF5 plasmid with 3'UTR knockout was synthesized and cotransfected into RPMI-8226 cells with hsa-miR-21 mimics, and the proliferation of MM cells was detected by CCK-8 and cell cloning assay. RESULTS: Compared with healthy donors, the expression level of miR-21 in plasma cells of patients with MM was significantly increased (P<0.001); the expression of miR-21 in MM cell lines MM1.S, RPMI-8226 and U266 was significantly higher than that in control group (P<0.05). After hsa-miR-21 mimics transfection, the proliferation and the number of colony formation of MM cells was significantly increased, while the proliferation and the number of colony formation of MM cells was decreased after hsa-miR-21 inhibitor transfection (P<0.01). The results of luciferase reporter gene assay showed that miR-21 could bind to 3'UTR of KLF5, and the expression level of KLF5 protein was significantly decreased after hsa-miR-21 mimics transfection. After 3'UTR-knockout KLF5 plasmid and hsa-miR-21 mimics were cotransfected into RPMI-8226 cells, the proliferation of the cells was significantly decreased. CONCLUSION: MiR-21 may be involved in regulating the proliferation of MM cells by inhibiting the expression of KLF5.

The value of NSE to predict ICU mortality in patients with septic shock: A prospective observational study.

To investigate the predictive value of neuron-specific enolase (NSE) on intensive care unit (ICU) mortality in patients with septic shock. Seventy-five patients with septic shock hospitalized in the emergency intensive care unit (EICU) of Hebei General Hospital from March 2020 to September 2021 were included, and the patients' baseline characteristics and laboratory findings were collected. NSE levels on the first and fourth days after admission were retrieved. NSE% [(NSEday1 - NSEday4)/NSEday1 × 100%] and δNSE (NSEday1 - NSEday4) were calculated. The outcome indicator was ICU mortality. The patients were divided into the survivors group (n = 57) and the nonsurvivors group (n = 18). Multivariate analysis was performed to assess the relationship between NSE and ICU mortality. The predictive value of NSE was evaluated using receiver operating characteristic (ROC) curve. There were no significant differences in age, gender, systolic blood pressure (SBP), heart rate (HR), acute physiology and chronic health evaluation II score (APACHE II score), source of infection, and comorbidities between the 2 groups (all P > .05). Interleukin-6 (IL-6), NSE (day1), and NSE (day4) were significantly higher in patients in the nonsurvivors group (all P < .05), and there were no statistical differences in other laboratory tests between the 2 groups (all P > .05). APACHE II score, IL-6, lactate (Lac), total bilirubin (TBil), NSE (day1), and NSE (day4) showed a weak positive correlation with ICU mortality in patients with septic shock (all P < .05). Multivariate logistic regression analysis demonstrated that APACHE II score (odds ratio [OR] = 1.166, 95% confidence interval [95% confidence interval [CI]] 1.005-1.352, P = .042), IL-6 (OR = 1.001, 95% CI 1.000-1.001, P = .003) and NSE (day4) (OR = 1.099, 95% CI 1.027-1.176, P = .006) were independently associated with the ICU mortality of sepsis shock patients. The area under the curve (AUCs) of APACHE II score, IL-6, NSE (day1), and NSE (day4) for predicting prognosis were 0.650, 0.694, 0.758 and 0.770, respectively (all P < .05). NSE(day4) displayed good sensitivity and specificity (Sn = 61.11%, Sp = 91.23%) for predicting ICU mortality with a cutoff value of 25.94 ug/L. High-level NSE (day4) is an independent predictor of ICU mortality in sepsis shock patients, which may become a good alternate option for evaluating sepsis severity. More extensive studies are needed in the future to demonstrate the prognosis value of NSE.

Comparison of mid-term clinical results between lag screw fixation and Kirschner wire fixation after close reduction in adolescent triplane distal tibia epiphyseal fracture.

OBJECTIVE: To compare the mid-term clinical results of lag screw and Kirschner wire fixation(KWF) for close reduction in triplane distal tibia epiphyseal fracture. METHODS: A retrospective analysis of 25 cases of triplane fractures of the distal tibia treated in our department from Jan 2017 to Dec 2019 was performed, Lag screw fixation(LSF) was used in 14 cases and Kirschner wire fixation in 11 cases, the clinical results were evaluated by premature epiphyseal closure(PPC) rate, the American Orthopaedic Foot and Ankle Score (AOFAS) Ankle-hindfoot foot scoring system, the lateral distal tibial angle (LDTA) from X-ray. RESULTS: All the 25 children were followed up for a mean of 34(ranging 26-52) months. AOFAS scores improved from a mean of 33(ranging 29-43) pre-op, to 82(ranging 77-88) at three month follow up, to 92 (ranging 88-98) at last follow-up in all 25 cases. Till last follow up there was no cases premature physeal closure in LSF group but 4 cases in KWF group, LDTA in both groups at last follow up shows no ankle varus or valgus deformity, and the ankle joint function was not limited in all cases. CONCLUSION: Lag screw and Kirschner wire fixation methods can both achieve good clinical effects for triplane distal tibia epiphyseal fracture. Lag screw fixation provide lower PPC rate but Kirschner wire fixation save one anesthesia and surgery.

P. edulis Extract Protects Against Amyloid-ß Toxicity in Alzheimer's Disease Models Through Maintenance of Mitochondrial Homeostasis via the FOXO3/DAF-16 Pathway.

Alzheimer's disease (AD) is a common and devastating disease characterized by pathological aggregations of beta-amyloid (Aß) plaques extracellularly, and Tau tangles intracellularly. While our understandings of the aetiologies of AD have greatly expanded over the decades, there is no drug available to stop disease progression. Here, we demonstrate the potential of Passiflora edulis (P. edulis) pericarp extract in protecting against Aß-mediated neurotoxicity in mammalian cells and Caenorhabditis elegans (C. elegans) models of AD. We show P. edulis pericarp protects against memory deficit and neuronal loss, and promotes longevity in the Aß model of AD via stimulation of mitophagy, a selective cellular clearance of damaged and dysfunctional mitochondria. P. edulis pericarp also restores memory and increases neuronal resilience in a C. elegans Tau model of AD. While defective mitophagy-induced accumulation of damaged mitochondria contributes to AD progression, P. edulis pericarp improves mitochondrial quality and homeostasis through BNIP3/DCT1-dependent mitophagy and SOD-3-dependent mitochondrial resilience, both via increased nuclear translocation of the upstream transcriptional regulator FOXO3/DAF-16. Further studies to identify active molecules in P. edulis pericarp that could maintain neuronal mitochondrial homeostasis may enable the development of potential drug candidates for AD.

Modified lateral gastrocnemius myocutaneous flap with extended anterior and/or inferior boundary.

There is little information regarding the boundaries of the lateral gastrocnemius myocutaneous (LGM) flap. The aim of this study was to introduce the modified technique of the LGM flap with extended anterior and/or inferior boundaries and its anatomical basis. Five fresh lower limb specimens were perfused and radiographed. Between December 2003 and August 2018, 27 modified LGM flaps with extended anterior and/or inferior boundaries were raised in 27 patients to reconstruct the soft tissue defects over the middle and upper leg, knee, and lower thigh. Both the lateral popliteal cutaneous artery and musculocutaneous perforators from the lateral sural artery had rich linked arteries communicating with the chain-linked arterial network around both the posterolateral intermuscular septum and the sural nerve, and they also had rich transverse communicating arteries connecting with the perifascial arterial network overlying the anterior compartment in the upper and middle calf. Continuous fascial arterial networks were extended up to the level at the intermalleolar line. Twenty-three flaps survived uneventfully, 2 flaps displayed distal de-epithelialization, and 2 flaps (7.41%) developed partial necrosis. Osteomyelitis was cured successfully in all patients, and no relapse of infection was encountered during the follow-up period. Multiple feeder arteries are the arterial anatomic basis of the modified LGM flap. The modified LGM flap with extended anterior and/or inferior boundaries is feasible, and the modified flap with extended anterior boundaries is safe and reliable.

Outcomes Following Intolerance to Tacrolimus/Sirolimus Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation.

Although tacrolimus and sirolimus (TAC/SIR) is an accepted graft-versus-host disease (GVHD) prophylaxis regimen following allogeneic hematopoietic cell transplantation (HCT), toxicity from this regimen can lead to premature discontinuation of immunosuppression. There are limited studies reporting outcomes and subsequent treatment of patients with TAC/SIR intolerance. This study was conducted to assess the outcomes of patients with TAC/SIR intolerance and guide their subsequent management. We retrospectively analyzed transplantation outcomes of consecutive adult patients at Moffitt Cancer Center who underwent allogeneic HCT with TAC/SIR as GVHD prophylaxis between 2009 and 2018. TAC/SIR intolerance was defined as discontinuation of either TAC or SIR due to toxicity before post-transplantation day +100. A total of 777 patients met the inclusion criteria. The median duration of follow-up was 22 months (range, 0.2 to 125 months). Intolerance occurred in 13% (n = 104) of the patients at a median of 30 days (range, 5 to 90 days). The most common causes of intolerance were acute kidney injury (n = 53; 51%), thrombotic microangiopathy (n = 31; 28%), and veno-occlusive disease (n = 23; 22%). The cumulative incidence of grade II-IV acute GVHD at 100 days was 50% (95% CI, 39% to 64%) in the TAC/SIR-intolerant patients and 25% (95% CI, 22% to 29%) in patients tolerant to this regimen (P < .0001). In multivariate analyses, the incidence of grade II-IV 4 acute GVHD was significantly higher in the TAC/SIR-intolerant patients (hazard ratio [HR], 2.40; 95% CI, 1.59 to 3.61; P < .0001). Similarly, in multivariate analyses, the TAC/SIR-intolerant patients had a higher incidence of chronic GVHD (HR, 1.48; 95% CI, 1.03 to 2.12; P = .03). The nonrelapse mortality (NRM) at 1 year was 47% (95% CI, 38% to 59%) in the TAC/SIR-intolerant patients and 12% (95% CI, 10% to 15%) in those tolerant to the regimen (P < .0001). The 2-year relapse-free survival was 35% (95% CI, 25% to 44%) in the TAC/SIR-intolerant patients and 60% (95% CI, 57% to 65%) in the TAC/SIR-tolerant patients (HR, 2.30; 95% CI, 1.61 to 3.28; P < .0001). Intolerance stratified by early (≤30 days) versus late (31 to 100 days) significantly affected the cumulative incidence of acute GVHD at 75% (early; 95% CI, 59% to 94%) versus 33% (late; 95% CI, 21% to 50%) (P = .001), as well as the cumulative incidence of NRM at 61% (early; 95% CI, 48% to 77%) versus 35% (late; 95% CI, 24% to 51%) (P = .006). Most patients who developed TAC/SIR intolerance were switched to an alternative 2-drug regimen (71 of 104; 68%), most commonly mycophenolate mofetil in addition to continuing TAC or SIR (68 of 71; 96%). Overall, TAC/SIR intolerance was associated with poorer outcomes. Early intolerance contributed to a higher risk of acute GVHD, increased NRM, and inferior survival. Patients with early intolerance were often switched to an alternative agent, and patients with late intolerance tended to be continued on single-drug therapy without substitution. The use of single-drug versus 2-drug regimens after intolerance did not appear to affect outcomes. Management strategies to mitigate the risks of intolerance are warranted.

DUBR suppresses migration and invasion of human lung adenocarcinoma cells via ZBTB11-mediated inhibition of oxidative phosphorylation.

Long noncoding RNAs (lncRNAs) are involved in a variety of cancers, but the role of LncRNA DUBR in lung adenocarcinoma (LUAD), the most prevalent form of lung cancer, remains unclear. In this study we investigated the expression of DUBR in LUAD to ascertain its association with the clinical pathology and prognosis of LUAD. Analysis of mRNA expression in The Cancer Genome Atlas (TCGA) LUAD database and in-house LUAD cohort (n = 94) showed that DUBR was significantly downregulated in LUAD, and was associated with poor prognosis. In LUAD cell lines (H1975, A549), overexpression of DUBR significantly suppressed the migration and invasion of the LUAD cells. We demonstrated that c-Myc could bind to the promoter of DUBR, and transcriptionally suppressed its expression. Knockdown of c-Myc almost completely blocked the invasion and migration of LUAD cells, whereas knockdown of DUBR partially rescued c-Myc-knockdown suppressed cell migration and invasion. Furthermore, DUBR overexpression significantly increased the expression of a downstream protein of DUBR, zinc finger, and BTB domain containing 11 (ZBTB11), in H1975 and A549 cells; knockdown of ZBTB11 partially rescued the DUBR-overexpression suppressed cell migration and invasion; knockdown of c-Myc significantly upregulated the expression of ZBTB11 in LUAD cells. Finally, we revealed that DUBR/ZBTB11 axis suppressed oxidative phosphorylation in LUAD cells. In short, we demonstrate that c-Myc/DUBR/ZBTB11 axis suppresses migration and invasion of LUAD by attenuating cell oxidative phosphorylation, which provides new insights into the regulatory mechanism of DUBR.

Revisit of flap factors relating to partial necrosis of distally based sural flaps: an analysis of 435 cases in a single center.

BACKGROUND: Partial necrosis is an ongoing topic in regard to flap complications of the distally based sural (DBS) flap However, the factors influencing partial necrosis of the flap remain in debate. The aim of the present study is to further illuminate the flap-related risk factors and the effects of several technical improvements. METHODS: We retrospectively reviewed the data of 429 patients who underwent 435 DBS flaps between April 2001 and December 2019. The reconstruction outcomes, flap viability-related complications, and potential risk factors were compared between the survival group and partial necrosis group, as well as between group A (the procedures performed from April 2001 to March 2010) and group B (those from April 2010 to December 2019). RESULTS: Among the 435 flaps, 39 flaps (8.97%) exhibited partial necrosis. With the increase of the top edge of the flap, the partial necrosis rate increased significantly (P < 0.05). When the length-to-width ratio [LWR] of the flap was more than 5:1 or the total length of the flap (the length of the skin island plus the length of the adipofascial pedicle) was more than 20 cm, the partial necrosis rate increased significantly (P < 0.05). The partial necrosis rate in group B (5.86%, 15/256) was significantly lower than that in group A (13.41%, 24/179) (P = 0.007). CONCLUSIONS: The top edge of the flap is an essential indicator for predicting the prognosis of the DBS flap. When the total length of the flap is more than 20 cm or the LWR of the flap more than 5:1, the partial necrosis rate will increase significantly. Various technical modifications can lower the top edge of the flap and reduce the LWR of the flap and width of the skin island, and thus improve the flap survival effectively.