Sequential bowel necrosis and large gastric ulcer in a patient with a ruptured femoral artery: A case report.

BACKGROUND: Severe bleeding as a result of a major vascular injury is a potentially fatal event commonly observed in the emergency department. Bowel necrosis and gastric ulcers secondary to ischemia are rare due to their rich blood supply. In this case, we present the case of a patient who was treated successfully following rupture of his femoral artery resulting in bowel necrosis and an unusually large gastric ulcer. CASE SUMMARY: A 28-year-old male patient sustained a knife stab wound to the right thigh, causing rupture of his femoral artery and leading to massive bleeding. He underwent cardiopulmonary resuscitation and received a large blood transfusion. Abdominal surgeries confirmed bowel necrosis, and jejunostomy was performed. The necrotic intestine was removed, the remaining intestine was anastomosed, and the right thigh was amputated. After three surgeries, the patient's overall condition gradually improved, and the patient was discharged from the hospital. However, one day after discharge, the patient was admitted again due to dizziness and melena, and a gastroduodenoscopy revealed a giant banded ulcer. After 2 weeks of treatment, the ulcer had decreased in size without bleeding. Six months after the last surgery, enterostomy and reintroduction surgery were completed. The patient was fitted with a right lower limb prosthesis one year after surgery. After 3 years of follow-up, the patient did not complain of discomfort. CONCLUSION: Trauma department physicians need to be aware of the possible serious complications involving the abdomen of trauma patients with massive bleeding.

A Theoretical Study on the Influence of Five- and Six-Membered N-Heterocyclic Ring Side Chains of the N-Donor Extractants on Am(III)/Eu(III) Extraction and Separation.

According to the green development requirements of carbon neutrality and carbon peaking, the effective separation of lanthanides and actinides is one of the key factors for nuclear energy to become a sustainable energy source. In recent years, o-phenanthroline-based ligands have been proven to be effective in the separation of lanthanides and actinides. In this work, based on 5,9b-dihydro-4aH-cyclopenta[1,2-b:5,4-b']dipyridines, we designed six N-heterocyclic ring ligands and theoretically studied their extraction capacity and separation selectivity for the Am(III) and Eu(III) ions. Various theoretical methods were used to analyze the properties of the ligands and study the bonding nature of the ligands with the metal ions. Thermodynamic parameters were calculated to measure the extraction ability of the ligands to the metal ions and to explore the separation capacity of the ligand for the Am(III) and Eu(III) ions. The calculated results show that the five- and six-membered N-heterocyclic ring side chains of the ligands and the distribution of the N atoms on the side chain rings have obvious effects on the bonding of the ligands to metal ions and on the extraction and separation properties of the ligands for the metal ions. It was found that the extractants with six-membered ring side chains possess an extraction ability slightly better than that of the ligands with five-membered ring side chains and that the ligands with a pair of adjacent N atoms on the side chains have a stronger separation selectivity for the Am(III)/Eu(III) ions. The theoretical research in this work will help to understand the details of binding and extraction properties of similar ligands and provide insights for the future design of five- and six-membered heterocyclic ligands.

High-Electrochemical-Activity Composite Cathode Enabled by Fast Segmental Relaxation for Solid-State Lithium-Sulfur Batteries.

Solid-state lithium-sulfur batteries (SSLSBs) have attracted a great deal of attention because of their high theoretical energy density and intrinsic safety. However, their practical applications are severely impeded by slow redox kinetics and poor cycling stability. Herein, we revealed the detrimental effect of aggregation of lithium polysulfides (LiPSs) on the redox kinetics and reversibility of SSLSBs. As a paradigm, we introduced a multifunctional hyperbranched ionic conducting (HIC) polymer serving as a solid polymer electrolyte (SPE) and cathode binder for constructing SSLSBs featuring high electrochemical activity and high cycling stability. It is demonstrated that the unique structure of the HIC polymer with numerous flexible ether oxygen dangling chains and fast segmental relaxation enables the dissociation of LiPS clusters, facilitates the conversion kinetics of LiPSs, and improves the battery's performance. A Li|HIC SPE|HIC-S battery, in which the HIC polymer acts as an SPE and cathode binder, exhibits an initial capacity of 910.1 mA h gS-1 at 0.1C and 40 °C, a capacity retention of 73.7% at the end of 200 cycles, and an average Coulombic efficiency of approximately 99.0%, demonstrating high potential for application in SSLSBs. This work provides insights into the electrochemistry performance of SSLSBs and provides a guideline for SPE design for SSLSBs with high specific energy and high safety.

Ectopic enhancer-enhancer interactions as causal forces driving RNA-directed DNA methylation in gene regulatory regions.

Cis-regulatory elements (CREs) are integral to the spatiotemporal and quantitative expression dynamics of target genes, thus directly influencing phenotypic variation and evolution. However, many of these CREs become highly susceptible to transcriptional silencing when in a transgenic state, particularly when organised as tandem repeats. We investigated the mechanism of this phenomenon and found that three of the six selected flower-specific CREs were prone to transcriptional silencing when in a transgenic context. We determined that this silencing was caused by the ectopic expression of non-coding RNAs (ncRNAs), which were processed into 24-nt small interfering RNAs (siRNAs) that drove RNA-directed DNA methylation (RdDM). Detailed analyses revealed that aberrant ncRNA transcription within the AGAMOUS enhancer (AGe) in a transgenic context was significantly enhanced by an adjacent CaMV35S enhancer (35Se). This particular enhancer is known to mis-activate the regulatory activities of various CREs, including the AGe. Furthermore, an insertion of 35Se approximately 3.5 kb upstream of the AGe in its genomic locus also resulted in the ectopic induction of ncRNA/siRNA production and de novo methylation specifically in the AGe, but not other regions, as well as the production of mutant flowers. This confirmed that interactions between the 35Se and AGe can induce RdDM activity in both genomic and transgenic states. These findings highlight a novel epigenetic role for CRE-CRE interactions in plants, shedding light on the underlying forces driving hypermethylation in transgenes, duplicate genes/enhancers, and repetitive transposons, in which interactions between CREs are inevitable.

The Role of Grifola frondosa Polysaccharide in Preventing Skeletal Muscle Atrophy in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a burgeoning public health challenge worldwide. Individuals with T2DM are at increased risk for skeletal muscle atrophy, a serious complication that significantly compromises quality of life and for which effective prevention measures are currently inadequate. Emerging evidence indicates that systemic and local inflammation stemming from the compromised intestinal barrier is one of the crucial mechanisms contributing to skeletal muscle atrophy in T2DM patients. Notably, natural plant polysaccharides were found to be capable of enhancing intestinal barrier function and mitigating secondary inflammation in some diseases. Herein, we hypothesized that Grifola frondosa polysaccharide (GFP), one of the major plant polysaccharides, could prevent skeletal muscle atrophy in T2DM via regulating intestinal barrier function and inhibiting systemic and local inflammation. Using a well-established T2DM rat model, we demonstrated that GFP was able to not only prevent hyperglycemia and insulin resistance but also repair intestinal mucosal barrier damage and subsequent inflammation, thereby alleviating the skeletal muscle atrophy in the T2DM rat model. Additionally, the binding free energy analysis and molecular docking of monosaccharides constituting GFP were further expanded for related targets to uncover more potential mechanisms. These results provide a novel preventative and therapeutic strategy for T2DM patients.

Time-Resolved Evaluation of L-Dopa Metabolism in Bacteria-Host Symbiotic System and the Effect on Parkinson's Molecular Pathology.

The gut microbiome influences drug metabolism and therapeutic efficacy. Still, the lack of a general label-free approach for monitoring bacterial or host metabolic contribution hampers deeper insights. Here, a 2D nuclear magnetic resonance (NMR) approach is introduced that enables real-time monitoring of the metabolism of Levodopa (L-dopa), an anti-Parkinson drug, in both live bacteria and bacteria-host (Caenorhabditis elegans) symbiotic systems. The quantitative method reveals that discrete Enterococcus faecalis substrains produce different amounts of dopamine in live hosts, even though they are a single species and all have the Tyrosine decarboxylase (TyrDC) gene involved in L-dopa metabolism. The differential bacterial metabolic activity correlates with differing Parkinson's molecular pathology concerning alpha-synuclein aggregation as well as behavioral phenotypes. The gene's existence or expression is not an indicator of metabolic activity is also shown, underscoring the significance of quantitative metabolic estimation in vivo. This simple approach is widely adaptable to any chemical drug to elucidate pharmacomicrobiomic relationships and may help rapidly screen bacterial metabolic effects in drug development.

A Mendelian randomization study on the causal effects of cigarette smoking on liver fibrosis and cirrhosis.

Background: Liver fibrosis significantly impacts public health globally. Untreated liver fibrosis eventually results in cirrhosis. Cigarette smoking is the main etiologic factor for various diseases. However, the causal effects of cigarette smoking on liver fibrosis and cirrhosis have yet to be fully elucidated. Methods: In this study, Mendelian randomization (MR) analysis was performed to assess the association between cigarette smoking, liver fibrosis, and cirrhosis. Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables from a genome-wide association study (GWAS) of European ancestry. Patients were divided into six exposure categories as follows: "ever smoked," "pack years of smoking," "age of smoking initiation," "smoking status: never," "smoking status: current," and "smoking status: previous." The outcomes of this study included liver fibrosis and cirrhosis. MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode were selected as the analysis methods. Cochran's Q and the MR-PRESSO tests were conducted to measure heterogeneity. The MR-Egger method was performed to evaluate horizontal pleiotropy, while the "leave-one-out" analysis was performed for sensitivity testing. Results: The results of this study showed that having a smoking history increases the risk of liver fibrosis and cirrhosis ["ever smoked": odds ratio (OR) = 5.704, 95% CI: 1.166-27.910, p = 0.032; "smoking status: previous": OR = 99.783, 95% CI: 2.969-3.353e+03, p = 0.010]. A negative correlation was observed between patients who never smoked and liver fibrosis and cirrhosis ("smoking status: never": OR = 0.171, 95% CI: 0.041-0.719, p = 0.016). However, there were no significant associations between "smoking status: current," "pack years of smoking," and "age of smoking initiation" and liver fibrosis and cirrhosis. Cigarette smoking did not have a significant horizontal pleiotropic effect on liver fibrosis and cirrhosis. The "Leave-one-out" sensitivity analysis indicated that the results were stable. Conclusion: The study confirmed the causal effects of cigarette smoking on liver fibrosis and cirrhosis.

Postural change, gait, and physical function in older adults.

In a more clinical setting, abrupt posture change may be used to determine the presence of orthostatic hypotension, a hemodynamic response with relationships to physical function. Certain gait features and physical function performance are also associated with risk of falling in older adults. However, the extent to which posture change is associated with subsequent gait and physical function has received little attention in the literature. This study aims to determine the effects of posture change on spatiotemporal parameters of gait and Timed Up-and-Go (TUG) performance. METHODS: Forty-two volunteers (age 73.21 ± 6.22 years) participated in the study. A custom Tekscan Strideway (Tekscan, Boston, MA.) gait system was used to measure gait velocity (VEL), cadence (CAD), stride length (SL), and percent of time spent in active propulsion (AP). Dependent t-tests were used to compare TUG time, VEL, CAD, SL and AP after at least 10 mins of seated rest and supine rest. RESULTS: Time to complete the TUG was significantly slower after supine rest compared to seated (11.47 ± 0.51 and 10.01 ± 0.33 s, respectively, p<0.001); VEL was significantly slower after supine rest compared to seated (0.888 ± 0.042 and 1.049 ± 0.033 m/s, respectively, p=0.003); CAD was significantly slower after supine rest compared to seated (111.21 ± 2.87 and 120.97 ± 2.56spm, respectively, p=0.001); and AP was significantly lower after supine rest compared to seated (56.87 ± 4.76 and 70.79 ± 4.05 %, respectively, p<0.001). No significant differences were detected in stride length between conditions. CONCLUSIONS: Among this sample of older adults, standing from a supine posture is associated with spatiotemporal gait parameters consistent with a risk for falling and aging. Additionally, TUG performance worsens significantly after supine rest. Future studies could explore the sensitivity and specificity of falls risk screening after supine rest.

Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity.

BACKGROUND: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation. METHODS: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study. RESULTS: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING. CONCLUSIONS: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin.

Clinical presentation and treatment of four children with pulmonary mucoepidermoid carcinoma.

Primary lung cancer in childhood is extremely rare, with an incidence rate of less than 2/100,0000, and pulmonary mucoepidermoid carcinoma (PMEC), is even rarer. Their symptoms are usually not specific, and there are no guidelines for their management, which makes their clinical management a challenge for pediatricians. The purpose of this report is to discuss the clinical presentation, positive signs, examinations, pathological characteristics, surgical modalities, chemotherapy regimens, and prognosis in children. The clinical data of four patients diagnosed with PMEC at the Children's Hospital of Chongqing Medical University from June 2021 to November 2022 were retrospectively analyzed, and their clinical features, treatment, and prognosis were summarized. Among them, two were male and two were female; their ages ranged from 3 years and 10 months to 10 years and 11 months, and all were staged according to tumor node metastasis classification (TNM). Immunohistochemical tests were performed in all children, among which four cases were positive for cytokeratin (CK), two cases were positive for CK7, four cases were positive for p63, about 5-10% of tumor cells were positive for Ki67. Among the four children, three had surgery alone and one had surgery + chemotherapy. All four children are presently living, with no evidence of tumor recurrence or metastasis. PMEC in children is very rare, and its age of onset and symptoms are not specific, and there is no obvious correlation with gender. Its diagnosis mainly relies on pathomorphological diagnosis, and immunohistochemical detection has no specific performance. The prognosis of children with PMEC is related to the clinical stage and whether surgery is performed. Whether further chemotherapy or radiotherapy is needed for patients who cannot undergo surgical resection and for those who have a combination of distant metastases requires further clinical studies.

Clinical presentation and treatment of 4 children with pulmonary mucoepidermoid carcinomaLung cancer in childhood is extremely rare, occurring at a rate of less than 2/1000000, and a type of lung cancer called pulmonary mucoepidermoid carcinoma (PMEC), is even rarer. The symptoms are usually not specific, and there are no guidelines for its management, which is a challenge for doctors. The purpose of this report is to discuss the signs and symptoms medical examinations, disease characteristics, surgical procedures, chemotherapy regimens and prognosis in children with pulmonary mucoepidermoid carcinoma. The clinical data of four patients diagnosed with pulmonary mucoepidermoid carcinoma at the Children's Hospital of Chongqing Medical University from June 2021 to November 2022 were analyzed, and their clinical features, treatment and prognosis were summarized. All four children are currently alive, and there is no recurrence or spread of the tumor after treatment. We have discussed various aspects of the disease, such as the rate of occurrence, causes, signs and symptoms, the way in which it might be diagnosed and treated, and the survival rate after operation, hoping to provide some insights for future work.