Case report: heart failure related to intravitreal injection of anti-VEGF.

BACKGROUND: Intravitreal injection of anti-vascular endothelial growth factor is considered the first-line treatment for polypoidal choroidal vasculopathy. It has potential risks for circulatory system, which should be particularly carefully evaluated in older patients. In this case study, we aim to discuss the potential impact of this treatment regimen on cardiac health. CASE PRESENTATION: This case report describes an elderly patient with no prior history of heart disease who exhibited unexpected heart enlargement and dysfunction. Throughout the patient's hospital stay, various potential causes were investigated, leading to the hypothesis that a 10-year history of intravitreal injections of anti-vascular endothelial growth factor could be related to the observed clinical manifestations. The patient was advised to discontinue this treatment, and after a 2-month follow-up period, there was a gradual improvement in the patient's cardiac structure and function. CONCLUSION: This manuscript highlights the importance of conducting cardiac examinations before and after anti-vascular endothelial growth factor treatment, especially for individuals at risk of heart diseases like the elderly. It emphasizes the need to carefully weigh the benefits and risks of treatment regimens to ensure optimal therapeutic outcomes.

Deep learning based method for predicting DNA N6-methyladenosine sites.

DNA N6 methyladenine (6mA) plays an important role in many biological processes, and accurately identifying its sites helps one to understand its biological effects more comprehensively. Previous traditional experimental methods are very labor-intensive and traditional machine learning methods also seem to be somewhat insufficient as the database of 6mA methylation groups becomes progressively larger, so we propose a deep learning-based method called multi-scale convolutional model based on global response normalization (CG6mA) to solve the prediction problem of 6mA site. This method is tested with other methods on three different kinds of benchmark datasets, and the results show that our model can get more excellent prediction results.

Cobalt-Catalyzed Enantioselective Reductive Arylation, Heteroarylation, and Alkenylation of Michael Acceptors via an Elementary Mechanism of 1,4-Addition.

Cobalt complexes with chiral quinox ligands effectively promote the enantioselective conjugate addition of enones using aryl, heteroaryl, and alkenyl halides and sulfonates. Additionally, a cobalt complex with a strongly donating diphosphine, BenzP*, successfully catalyzes the asymmetric reductive arylation and alkenylation of α,ß-unsaturated amides. Both catalytic systems show broad scopes and tolerance of sensitive functional groups. Both reactions can be scaled up with low loadings of cobalt catalysts. Experimental results and density functional theory (DFT) calculations suggest a new mechanism of elementary 1,4-addition of aryl cobalt(I) complexes.

Oxidative Nickel-Catalyzed ortho-C-H Amination of (Iso)quinolines with Alicyclic Amines Directed by a Sacrificial N-Oxide Group.

Transition metal (TM)-catalyzed direct amination of C-H bonds on free or fused pyridine (Py) rings with free amines still remains scarce because amines and the Py ring tend to adopt a nonproductive N-bound coordination with many TMs, leading to a significant decrease of catalytic reactivity. We herein disclose a nickel-catalyzed and a sacrificial N-oxide group directed oxidative coupling of (iso)quinolyl C-H bonds and alicyclic amines, which furnishes bioimportant amino(iso)quinolines efficiently and selectively in a single step. Noteworthy, this protocol avoids the use of aggressive reactants and very strong bases usually required when aminating on nonoxidized Py rings.

Long-Term Efficacy and Safety of Low-Dose Rituximab in Patients with Refractory Myasthenia Gravis.

INTRODUCTION: Rituximab is a monoclonal chimeric antibody against CD20+ B cells. We aimed to assess the long-term efficacy and safety of CD20+ B cell-guided treatment with low-dose rituximab in refractory myasthenia gravis patients. METHODS: Patients with refractory myasthenia gravis treated with rituximab for more than 2 years were included. Rituximab was administered when CD20+ B cells were greater than 1%. We analysed the efficacy of rituximab, treatment interval, side effects, prognosis, and treatment course. RESULTS: A total of 22 patients were included. All patients received 2-12 doses of rituximab, and the median follow-up time was 48.5 months. The scores of the Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Composite were significantly lower than those at baseline (p < 0.05). MGFA-PIS was significantly improved in 21 (95.45%) patients and 14 (63.64%) patients have reached MGFA-PIS minimal manifestations. The average daily dose of prednisone and pyridostigmine bromide and the proportion of immunosuppressants were significantly lower (p < 0.05). Seven patients suffered from 14 worsenings. Eight patients terminated rituximab due to good efficacy. Most patients tolerated rituximab well, although 1 patient had opportunistic infection and hypogammaglobulinemia, 1 patient had an intracranial mass. CONCLUSION: Long-term CD20+ B-cell-guided low-dose rituximab showed good efficacy and tolerance in patients with refractory myasthenia gravis.

Sarmentosin Induces Autophagy-dependent Apoptosis via Activation of Nrf2 in Hepatocellular Carcinoma.

Background and Aims: Hepatocellular carcinoma (HCC) is a common and deadly cancer. Accumulating evidence supports modulation of autophagy as a novel approach for determining cancer cell fate. The aim of this study to evaluate the effectiveness of sarmentosin, a natural compound, on HCC in vitro and in vivo and elucidated the underlying mechanisms. Methods: Cell functions and signaling pathways were analyzed in HepG2 cells using western blotting, real-time PCR, siRNA, transmission electron microscopy and flow cytometry. BALB/c nude mice were injected with HepG2 cells to produce a xenograft tumour nude mouse model for in vivo assessments and their tumors, hearts, lungs and kidneys were isolated. Results: We found that autophagy was induced by sarmentosin in a concentration- and time-dependent manner in human HCC HepG2 cells by western blot assays and scanning electron microscopy. Sarmentosin-induced autophagy was abolished by the autophagy inhibitors 3-methyladenine, chloroquine, and bafilomycin A1. Sarmentosin activated Nrf2 in HepG2 cells, as shown by increased nuclear translocation and upregulated expression of Nrf2 target genes. Phosphorylation of mTOR was also inhibited by sarmentosin. Sarmentosin stimulated caspase-dependent apoptosis in HepG2 cells, which was impaired by silencing Nrf2 or chloroquine or knocking down ATG7. Finally, sarmentosin effectively repressed HCC growth in xenograft nude mice and activated autophagy and apoptosis in HCC tissues. Conclusions: This study showed sarmentosin stimulated autophagic and caspase-dependent apoptosis in HCC, which required activation of Nrf2 and inhibition of mTOR. Our research supports Nrf2 as a therapeutic target for HCC and sarmentosin as a promising candidate for HCC chemotherapy.

Multimorbidity and polypharmacy in hospitalized older patients: a cross-sectional study.

BACKGROUND: The growing trend of ageing population has become a worldwide concern. In comparison with the youth, older people are more likely to suffer from multimorbidity and polypharmacy, both of which are associated with adverse outcomes and increased healthcare costs. This study aimed to investigate the status of multimorbidity and polypharmacy in a large sample of hospitalized older patients aged 60 years and over. METHODS: A retrospective cross-sectional study was conducted among 46,799 eligible patients aged 60 years and over, who were hospitalized from January 1, 2021 to December 31, 2021. Multimorbidity was defined as the presence of 2 or more morbidities in one patient during the stay in hospital, and polypharmacy as prescription of 5 or more different oral medications. Spearman rank correlation analysis was used to assess the relationship of factors with the number of morbidities or oral medications. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated from logistic regression models to determine the predictors for polypharmacy and all-cause death. RESULTS: The prevalence of multimorbidity was 91.07% and increased with age. The prevalence of polypharmacy was 56.32%. Older age, polypharmacy, prolonged length of stay (LOS), higher cost on medications were significantly associated with an increased number of morbidities (all P < 0.01). The number of morbidities (OR = 1.29, 95% CI: 1.208-1.229) and LOS (OR = 1.171, 95% CI: 1.166-1.177) were potential risk factors for polypharmacy. As for all-cause death, age (OR = 1.107, 95% CI: 1.092-1.122), number of morbidities (OR = 1.495, 95% CI: 1.435-1.558) and LOS (OR = 1.020, 95% CI: 1.013-1.027) were the potential risk factors, but the number of medications (OR = 0.930, 95% CI: 0.907-0.952) and polypharmacy (OR = 0.764, 95% CI: 0.608-0.960) were associated with a reduction of mortality. CONCLUSION: Morbidities and LOS might be predictors for polypharmacy and all-cause death. The number of oral medications was inversely associated with the risk of all-cause mortality. Appropriate polypharmacy was beneficial for the clinical outcomes of older patients during hospitalization.

Case report: Concurrent pylephlebitis and subarachnoid hemorrhage in an octogenarian patient with Escherichia coli sepsis.

Background: Pylephlebitis refers to an infective suppurative thrombosis that occurs in the portal vein and its branches. Concurrent pylephlebitis and subarachnoid hemorrhage (SAH) are rare but fatal for patients with sepsis. This scenario drives the clinicians into a dilemma of how to deal with coagulation and bleeding simultaneously. Case summary: An 86-year-old man was admitted to hospital for chills and fever. After admission, he developed headache and abdominal distension. Neck stiffness, Kernig's and Brudzinski's sign were present. Laboratory tests discovered decreased platelet count, elevated inflammatory parameters, aggravated transaminitis, and acute kidney injury. Escherichia coli (E. coli) were identified in blood culture. Computed tomography (CT) revealed thrombosis in the superior mesenteric vein and portal veins. Lumbar puncture and Brain CT indicated SAH. The patient had eaten cooked oysters prior to illness. It was speculated that the debris from oyster shell might have injured his intestinal mucosa and resulted in bacterial embolus and secondary thrombosis in portal veins. The patient was treated with effective antibiotics, fluid resuscitation, and anticoagulation. The dose titration of low molecular weight heparin (LMWH) under close monitoring attributed to diminution of the thrombosis and absorption of SAH. He recovered and was discharged after 33-day treatment. One-year follow-up indicated that the post-discharge course was uneventful. Conclusion: This report describes a case of an octogenarian with E. coli septicemia who survived from concurrent pylephlebitis and SAH along with multiple organ dysfunction syndrome. For such patients with life-threatening complications, even in the acute stage of SAH, decisive employment of LMWH is essential to resolve thrombosis and confers a favorable prognosis.

Case report: Persistent hypogammaglobulinemia in thymoma-associated myasthenia gravis: the impact of rituximab or Good's syndrome?

Introduction: Rituximab (RTX) showed good efficacy and safety for patients with myasthenia gravis. However, the percentage of peripheral CD20+ B cell may be absent for years after low dose of RTX treatment. Persistent hypogammaglobulinemia and opportunistic infection may occur in patients under treatment of RTX with thymoma relapse. Case representation: We report a case of refractory myasthenia gravis. After two doses of 100 mg rituximab, the patient developed transient neutropenia. The peripheral blood CD20+ B cell percentage was 0 more than 3 years. Eighteen months later, the patient's symptoms relapsed with thymoma recurred. She had persistent hypogammaglobulinemia and multiple opportunistic infections. Conclusion: In MG patient under B cell depletion therapy had thymoma relapse, Good's syndrome may induce prolonged B cell depletion, hypogammaglobulinemia and opportunistic infections.

Prediction of drug-target interactions via neural tangent kernel extraction feature matrix factorization model.

Drug discovery is a complex and lengthy process that often requires years of research and development. Therefore, drug research and development require a lot of investment and resource support, as well as professional knowledge, technology, skills, and other elements. Predicting of drug-target interactions (DTIs) is an important part of drug development. If machine learning is used to predict DTIs, the cost and time of drug development can be significantly reduced. Currently, machine learning methods are widely used to predict DTIs. In this study neighborhood regularized logistic matrix factorization method based on extracted features from a neural tangent kernel (NTK) to predict DTIs. First, the potential feature matrix of drugs and targets is extracted from the NTK model, then the corresponding Laplacian matrix is constructed according to the feature matrix. Next, the Laplacian matrix of the drugs and targets is used as the condition for matrix factorization to obtain two low-dimensional matrices. Finally, the matrix of the predicted DTIs was obtained by multiplying these two low-dimensional matrices. For the four gold standard datasets, the present method is significantly better than the other methods that is compared to, indicating that the automatic feature extraction method using the deep learning model is competitive compared with the manual feature selection method.

Clostridium perfringens gas gangrene caused by closed abdominal injury: A case report and review of the literature.

BACKGROUND: Abdominal Clostridium perfringens (C. perfringens) gas gangrene is a rare infection that has been described in the literature as most frequently occurring in postoperative patients with open trauma. Intra-abdominal gas gangrene caused by C. perfringens infection after closed abdominal injury is extremely rare, difficult to diagnose, and progresses rapidly with high mortality risk. Here, we report a case of C. perfringens infection caused by closed abdominal injury. CASE SUMMARY: A 54-year-old male suffered multiple intestinal tears and necrosis after sustaining an injury caused by falling from a high height. These injuries and the subsequent necrosis resulted in intra-abdominal C. perfringens infection. In the first operation, we removed the necrotic intestinal segment, kept the abdomen open and covered the intestine with a Bogota bag. A vacuum sealing drainage system was used to cover the outer layer of the Bogota bag, and the drainage was flushed under negative pressure. The patient was transferred to the intensive care unit for supportive care and empirical antibiotic treatment. The antibiotics were not changed until the results of bacterial culture and drug susceptibility testing were obtained. Two consecutive operations were then performed due to secondary intestinal necrosis. After three definitive operations, the patient successfully survived the perioperative period. Unfortunately, he died of complications related to Guillain-Barre syndrome 75 d after the first surgery. This paper presents this case of intra-abdominal gas gangrene infection and analyzes the diagnosis and treatment based on a review of current literature. CONCLUSION: When the intestines rupture leading to contamination of the abdominal cavity by intestinal contents, C. perfringens bacteria normally present in the intestinal tract may proliferate in large numbers and lead to intra-abdominal infection. Prompt surgical intervention, adequate drainage, appropriate antibiotic therapy, and intensive supportive care comprise the most effective treatment strategy. If the abdominal cavity is heavily contaminated, an open abdominal approach may be a beneficial treatment.

A review of methods for predicting DNA N6-methyladenine sites.

Deoxyribonucleic acid(DNA) N6-methyladenine plays a vital role in various biological processes, and the accurate identification of its site can provide a more comprehensive understanding of its biological effects. There are several methods for 6mA site prediction. With the continuous development of technology, traditional techniques with the high costs and low efficiencies are gradually being replaced by computer methods. Computer methods that are widely used can be divided into two categories: traditional machine learning and deep learning methods. We first list some existing experimental methods for predicting the 6mA site, then analyze the general process from sequence input to results in computer methods and review existing model architectures. Finally, the results were summarized and compared to facilitate subsequent researchers in choosing the most suitable method for their work.

Evaluation of potentially inappropriate medications for the elderly according to beers, STOPP, START, and Chinese criteria.

Objective: Polypharmacy prevalence is increasing worldwide, and it is becoming more popular among the elderly. This study aimed to compare the prevalence of potentially inappropriate medications (PIMs) using the Beers criteria (2019 edition), criteria for potentially inappropriate medications for older adults in China (Chinese criteria), Screening Tool of Older Persons' Prescriptions (STOPP), and Screening Tool to Alert to Right Treatment (START) criteria and to identify risk factors associated with PIM use. Methods: This was a cross-sectional study with a sample of 276 inpatients aged ≥65 years old from January 2020 to June 2020. A cross-sectional study was conducted to analyze PIMs based on the Beers (2019 edition), Chinese, STOPP, and START criteria. PIMs use was analysed based on four different criteria and logistic regression analysis was used to investigate independent factors associated with PIM use. Results: The mean number of medications used by the elderly population was nine (range, 0-28). A total of 252 patients (accounting for 91.30%) took five or more medications and 120 patients (accounting for 43.48%) took 10 or more medications. The prevalence rates of PIMs were 66.30% (183/276), 55.07% (152/276), 26.45% (73/276), and 64.13% (177/276) determined by the Beers, Chinese, STOPP, and START criteria, respectively. The top PIMs screened using the Beers, Chinese, and STOPP criteria were proton pump inhibitors, clopidogrel, and benzodiazepines, respectively. Missed use of ACEI in patients with systolic heart failure and/or coronary artery disease was found to be the most common potential prescription omission (PPOs) analyzed using the START criteria. Logistic regression analysis showed that the strongest predictor of PIMs, as determined by all four criteria, was an increased number of medications (p < 0.001). Age was another risk factor for PIMs based on the STOPP criteria in our study (p < 0.05). Conclusion: Polypharmacy and PIMs were common in our study, and the risk of PIMs correlated with polypharmacy. Application of the Beers, Chinese, STOPP, and START criteria is a useful tool for detecting PIM use.

Study on inversion method of wall erosion information of on-orbit Hall thruster based on low-frequency oscillation signals and neural networks.

Hall thrusters function as power plants on spacecraft, and its development is crucial for the aerospace industry. The wall erosion of the on-orbit Hall thruster cannot be measured by the control center through ground measurement, but can obtain the discharge current low-frequency oscillation data. Therefore, this study proposes an inversion method to obtain the wall erosion information based on low-frequency oscillation signals and neural networks. Firstly, we use an improved one-dimensional quasi-neutral dynamic fluid mathematical model to build a low-frequency oscillation simulation platform which obtains the corresponding data by varying the cross-sectional area. Secondly, a nonlinear neural network model is established based on the obtained low-frequency oscillation data to invert the wall erosion information. The training function, transfer function, number of hidden layer nodes, and other parameters affecting the results are analyzed and the best model parameters are obtained. The Elman neural network is established and compared with the BP neural network and RBF neural network. The training results of the Elman neural network algorithm present small and stable errors, and the results of multiple predictions remain consistent. The root means square error, average absolute error, and average absolute percentage are 0.0084, 0.0637, and 0.045%, respectively.

Integrated analysis of the genomic and transcriptional profile of gliomas with isocitrate dehydrogenase-1 and tumor protein 53 mutations.

Background: The gene mutation of isocitrate dehydrogenase-1 (IDH1) is commonly found in LGG and some GBM patients and usually carries tumor protein 53 (TP53) mutations. However, the underlying mechanisms on both mutations of glioma patients in IDH1 and TP53 are still unclear. Aim: To find the potential target markers in GBM and LGG patients with IDH1 and TP53 mutation.Method: A total of 1122 glioma patients from The Cancer Genome Atlas were enrolled and divided as wild-type (without IDH1 and TP53 mutations) or both mutant (both IDH1 and TP53 mutations). The data of clinicopathological characteristics, mRNA, mutations, and copy number alteration were analyzed. Results: IDH1 and TP53 mutations, not gene expression, affect the survival probability of GBM and LGG patients, which might be related to neuron function, immune function, tumor invasion, and metastasis. The effects of the selected gene (EMILIN3, SAA1, VSTM2A, HAMP, IFT80, and CHIC2) on glioma patients could be regulated by IDH1 and TP53 mutations and had a higher survival possibility in these patients. Conclusions: The selected genes in GBM and LGG patients with IDH1 and TP53 mutations could be a potential prognosis marker in the future.

An integrated learning algorithm for early prediction of melon harvest.

Different modeling techniques must be applied to manage production and statistical estimation to predict the expected harvest. By calculating advanced production methods and the rational valuation of different factors, we can accurately capture the variety of growth characteristics and the expected yield. This paper obtained 32 feature variables related to melons, including phenological features, shape features, and color features. The Gradient Boosted Decision Tree (GBDT) network and the Grid Search (GS) hyperparameter seeking method was applied to calculate the degree of importance of all melon fruits' characteristics and construct prediction models for three expected harvest indexes of melon yield, sugar content, and endocarp hardness. To facilitate growers to carry out prediction and estimation in the field without destroying the melon fruits. The reduced feature variables were selected as inputs. The GBDT model was used to provide a significant advantage in prediction compared to both Random Forest (RF) and Support Vector Regression (SVR) methods. In addition, to verify the feasibility of using only reduced feature variables as input for the evaluation work, this study also compares the predictive effects of the model when all feature variables and only reduced feature variables are used. The GBDT prediction model proposed in this paper predicted melon yield, sugar content, and hardness using reduced features as input, and the model R2 could reach more than 90%. Therefore, this method can effectively help growers carry out early non-destructive inspection and growth prediction of melons in the field.

Asymmetric Jetting during the Impact of Liquid Drops on Superhydrophobic Concave Surfaces.

The impact of liquid drops on superhydrophobic solid surfaces is ubiquitous and of practical importance in many industrial processes. Here, we study the impingement of droplets on superhydrophobic surfaces with a macroscopic dimple structure, during which the droplet exhibits asymmetric jetting. Systematic experimental investigations and numerical simulations provide insight into the dynamics and underlying mechanisms of the observed phenomenon. The observation is a result of the interaction between the spreading droplet and the dimple. An upward internal flow is induced by the dimple, which is then superimposed on the horizontal flow inside the spreading droplet. As such, an inclined jet is issued asymmetrically into the air. This work would be conducive to the development of an open-space microfluidic platform for droplet manipulation and generation.