ObjectiveTo predict the in-hospital mortality risk among patients with ischemic stroke combined by dysphagia using interpretable machine learning methods, so as to provide more evidence-based support for the prognosis prediction of patients with ischemic stroke combined by dysphagia. MethodsMedical record of 308 patients diagnosed with ischemic stroke combined by dysphagia in the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) (2.0) in the United States were retrospectively analyzed. Features of the research data were screened based on the least absolute shrinkage and selection operator, and which were randomly divided into a training set and a test set at a ratio of 7∶3. Then ten models, including logistic regression, random forest, K-nearest neighbor, linear discriminant analysis, naive bayes (NB), neural network, quadratic discriminant analysis, recursive partitioning tree, extreme gradient boosting tree, and support vector machine, etc. were constructed. The predictive effect was measured by calculating the area under the curve (AUC) of receiver operating characteristics. In addition, the calibration curve and Brier score were used to evaluate the calibration degree of the model, and the decision curve was drawn to reflect the clinical net benefit. The Shapley additive explanation method was used to analyze the interpretability of the black box model and explore the important decision-making factors. ResultsThe NB model in the test set showed better predictive ability compared with other models (AUC=0.85, 95%CI: 0.83‒0.88). After interpretability analysis, it was found that blood urea nitrogen (BUN), age, sequential organ failure assessment, bicarbonate, chloride, and hypertension were important risk factors for in-hospital mortality in patients with ischemic stroke combined by dysphagia. ConclusionThe comprehensive performance of the NB model is better than that of the other nine models in predicting the risk of in-hospital mortality in patients with ischemic stroke combined by dysphagia. The interpretability of the model can help clinicians better understand the reasons behind the results and take further reasonable intervention measures for risk factors to improve the survival probability of patients.

Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.
Male ; Humans ; Autophagy/physiology* ; Apoptosis/physiology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Penis/pathology* ; Animals ; Endothelial Cells/pathology* ; Myocytes, Smooth Muscle/pathology*

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective To investigate the role and mechanism of acyl-CoA syntbetase long chain family member 4(ACSL4)in Sevoflurane(Sev)induced neuronal cell damage.Methods Human neuroblastoma SH-SY5Y cells were used as the research object,and control group(dimethyl sulfoxide,10 μmol/L),Sev group and Sev+iron death inhibitor Ferrostatin-1(Fer-1,10 μmol/L)group were set up.CCK-8 method was used to detect cell activity in each group.4.1%Sev exposed postoperative cognitive dysfunction model was constructed in vitro and divided into Ctrol group,Sev group,Sev+si-NC group,Sev+si-ACSL4 group,and Sev+si-ACSL4+compound C group according to the transfection category.The contents of Malonaldehyde(MDA),4-hydroxynonenal(4-HNE),Glutathione(GSH)and Fe2+in each group were detected by colorimetry.The level of reactive oxygen species was detected using a 2',7'-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe.Real time fluorescence quantitative PCR(qRT-PCR)was used to detect the mRNA expression of ACSL4,glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11).Protein immunoblotting was used to detect the expression of ACSL4,GPX4,adenosine 5'-monophosphate activated protein kinase(AMPK),phosphorylated(p)-AMPK,mammalian target of rapamycin(mTOR)and p-mTOR proteins.Results CCK-8 results showed that the cell viability of Sev group(0.41±0.11)was significantly lower than that of control group(0.98±0.07),and the cell viability of Sev+Fer-1 group(0.83±0.09)was significantly higher than that of Sev group(0.41±0.11),and the differences were statistically significant(t=7.572,5.118,all P<0.01).The levels of Fe2+,MDA,4-HNE,ROS and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev group cells,were higher than those in the Ctrol group(t=5.900,7.421,4.795,13.517,10.825,9.945,11.334),the GSH conten,p-mTOR/mTOR ratio,and mRNA and protein expression of SLC7A11 and GPX4 were lower than those in the Ctrol group(t=20.438,3.551,11.460,12.211,6.845,8.287),and the differences were statistically significant(all P<0.05)repectively.The levels of Fe2+,MDA,4-HNE,ROS,and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev+si-ACSL4 group,were lower than those in the Sev+si-NC group(t=3.818,3.164,3.054,4.465,13.088,7.918,9.737),the cell viability,GSH content,p-mTOR/mTOR ratio,and protein expression of SLC7A11 and GPX4 were higher than those in the Sev+si-NC group(t=2.912,7.248,7.574,20.092,5.915),and the differences were statistically significant(all P<0.05),respectively.The cell viability,GSH content,SLC7A11,and GPX4 protein expression in the Sev+si-ACSL4+compound C group were lower than those in the Sev+si-ACSL4 group(t=4.435,8.521,4.522,8.767),while the levels of Fe2+,MDA,4-HNE,and ROS were higher than those in the Sev+si-ACSL4 group(t=10.046,4.004,2.957,3.752),and the differences were statistically significant(all P<0.05).Conclusion Inhibiting ACSL4 expression attenuates Sev-induced iron death in SH-SY5Y cells by activating the AMPK/mTOR signaling pathway.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Objective:To investigate the etiology of hand, foot and mouth disease (HFMD) in Mianyang city in 2022, and to analyze the genetic characteristics of coxsackievirus A6.Methods:Pharyngeal swabs were collected from patients with HFMD in Mianyang city in 2022. Real-time fluorescence quantitative PCR was used to detect enteroviruses in the samples. Part of the VP1 gene in enterovirus-positive samples was amplified by nested PCR using enterovirus typing primers to further identify the viral types. The VP1 coding region of all CVA6-positive samples and the whole genome of some samples were amplified and sequenced by PCR. The endemic strain in Mianyang city was analyzed for phylogeny, gene homology, amino acid variation and genetic recombination.Results:A total of 151 pharyngeal swabs were collected, and 104 enterovirus-positive samples were detected by real-time fluorescence quantitative PCR, with an overall detection rate of 68.88% (104/151). The typing results showed that there were 77 cases of CVA6 infection, with a positive rate of 50.99% (77/151). The full-length VP1 genes of 77 CVA6 strains were amplified, sequenced, and successfully spliced, and phylogenetic analysis showed that all 77 strains were of the D3 genotype. There were multiple amino acid variant sites in the prevalent strains in Mianyang city compared with the reference strain. Twenty whole genome sequences were amplified, sequenced, and successfully spliced, and homology analysis showed that the nucleotide homology between the 20 positive sequences ranged from 97.0% to 99.9%. Phylogenetic tree and recombination analysis showed that no recombination occurred in the coding regions of the epidemic strains in this study.Conclusions:The predominant pathogen causing HFMD in Mianyang city in 2022 is CVA6 D3 subtype, which is consistent with the national epidemic in 2022.

Objective To explore the value of deep learning(DL)models semi-automatic training system for automatic optimization of clinical image quality control of transthoracic echocardiography(TTE).Methods Totally 1 250 TTE videos from 402 patients were retrospectively collected,including 490 apical four chamber(A4C),310 parasternal long axis view of left ventricle(PLAX)and 450 parasternal short axis view of great vessel(PSAXGv).The videos were divided into development set(245 A4C,155 PLAX,225 PSAXGV),semi-automated training set(98 A4C,62 PLAX,90 PSAXGV)and test set(147 A4C,93 PLAX,135 PSAXGV)at the ratio of 5:2:3.Based on development set and semi-automatic training set,DL model of quality control was semi-automatically iteratively optimized,and a semi-automatic training system was constructed,then the efficacy of DL models for recognizing TTE views and assessing imaging quality of TTE were verified in test set.Results After optimization,the overall accuracy,precision,recall,and F1 score of DL models for recognizing TTE views in test set improved from 97.33％,97.26％,97.26％and 97.26％to 99.73％,99.65％,99.77％and 99.71％,respectively,while the overall accuracy for assessing A4C,PLAX and PSAXGV TTE as standard views in test set improved from 89.12％,83.87％and 90.37％to 93.20％,90.32％and 93.33％,respectively.Conclusion The developed DL models semi-automatic training system could improve the efficiency of clinical imaging quality control of TTE and increase iteration speed.