Therapeutic effect of nicotinamide mononucleotide on Alzheimer's disease through activating autophagy and anti-oxidative stress.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of ß-amyloid (Aß) plaques and neurofibrillary tangles composed of tau protein in the brain. These neuropathological hallmarks contribute to cognitive impairment by inducing neuronal loss in the cerebral cortex and hippocampus. Unfortunately, current therapeutic approaches only target symptomatic relief and do not impede disease progression. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), has emerged as a promising candidate for the treatment of age-related neurodegenerative disorders. NMN supplementation could restore NAD+ levels, thereby alleviating neuronal damage and slowing the progression of AD and other aging-associated diseases. AD is closely associated with autophagic impairment and oxidative stress. Our in vivo experiments demonstrated that NMN could ameliorate pathological and behavioral impairments in AD mice. Specifically, NMN enhanced autophagy and promoted p-tau clearance. Meanwhile, NMN could activate the Nrf2/Keap1/NQO1 pathway, thereby reducing the oxidative stress. Immunofluorescence results demonstrated that NMN could alleviate neuronal damage in AD mice. Furthermore, in vitro results showed that the p-tau clearance and antioxidant stress effects of NMN were suppressed by autophagy inhibitor, chloroquine (CQ) or bafilomycin A1 (BafA1), in Aß-induced PC12 cells. Lastly, when Nrf2 was knocked down, the antioxidant stress, autophagy enhancement, and p-tau clearance effects of NMN were all inhibited. In conclusion, our research indicates that NMN exerts therapeutic effect against AD by activating autophagy and the Nrf2/Keap1/NQO1 pathway through a mutual regulating mechanism of autophagy and antioxidative stress. These findings highlight the promising potential of NMN for the treatment of AD.

[Research on the classification model of chronic sinusitis based on VGG].

Objective:To build a VGG-based computer-aided diagnostic model for chronic sinusitis and evaluate its efficacy. Methods:①A total of 5 000 frames of diagnosed sinus CT images were collected. The normal group consisted of 1 000 frames（250 frames each of maxillary sinus, frontal sinus, septal sinus, and pterygoid sinus）, while the abnormal group consisted of 4 000 frames（1 000 frames each of maxillary sinusitis, frontal sinusitis, septal sinusitis, and pterygoid sinusitis）. ②The models were trained and simulated to obtain five classification models for the normal group, the pteroid sinusitis group, the frontal sinusitis group, the septal sinusitis group and the maxillary sinusitis group, respectively. The classification efficacy of the models was evaluated objectively in six dimensions: accuracy, precision, sensitivity, specificity, interpretation time and area under the ROC curve（AUC）. ③Two hundred randomly selected images were read by the model with three groups of physicians（low, middle and high seniority） to constitute a comparative experiment. The efficacy of the model was objectively evaluated using the aforementioned evaluation indexes in conjunction with clinical analysis. Results:①Simulation experiment: The overall recognition accuracy of the model is 83.94%, with a precision of 89.52%, sensitivity of 83.94%, specificity of 95.99%, and the average interpretation time of each frame is 0.2 s. The AUC for sphenoid sinusitis was 0.865（95%CI 0.849-0.881）, for frontal sinusitis was 0.924（0.991-0.936）, for ethmoidoid sinusitis was 0.895（0.880-0.909）, and for maxillary sinusitis was 0.974（0.967-0.982）. ②Comparison experiment: In terms of recognition accuracy, the model was 84.52%, while the low-seniority physicians group was 78.50%, the middle-seniority physicians group was 80.50%, and the seniority physicians group was 83.50%; In terms of recognition accuracy, the model was 85.67%, the low seniority physicians group was 79.72%, the middle seniority physicians group was 82.67%, and the high seniority physicians group was 83.66%. In terms of recognition sensitivity, the model was 84.52%, the low seniority group was 78.50%, the middle seniority group was 80.50%, and the high seniority group was 83.50%. In terms of recognition specificity, the model was 96.58%, the low-seniority physicians group was 94.63%, the middle-seniority physicians group was 95.13%, and the seniority physicians group was 95.88%. In terms of time consumption, the average image per frame of the model is 0.20 s, the average image per frame of the low-seniority physicians group is 2.35 s, the average image per frame of the middle-seniority physicians group is 1.98 s, and the average image per frame of the senior physicians group is 2.19 s. Conclusion:This study demonstrates the potential of a deep learning-based artificial intelligence diagnostic model for chronic sinusitis to classify and diagnose chronic sinusitis; the deep learning-based artificial intelligence diagnosis model for chronic sinusitis has good classification performance and high diagnostic efficacy.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

CircRNA hsa_circ_0069,399 as a potential clinical prognostic marker in laryngeal squamous cell carcinoma.

Objective: Circular RNAs (circRNAs) significantly influence the invasion, metastasis, gene expression, proliferation, and apoptosis of tumor cells. However, the roles of circRNAs in laryngeal squamous cell carcinoma (LSCC) remain largely unexplored. This study aims to examine circRNA expression patterns in LSCC and adjacent non-tumorous tissues, with the goal of uncovering potential biomarkers for LSCC. Methods: Tissue samples were collected from both the tumor and adjacent normal tissues of ten patients who had undergone surgical resection. The profiling of circRNAs was conducted through transcriptomic sequencing and analytical bioinformatics approaches. A ternary regulatory network based on the competitive endogenous RNA (ceRNA) hypothesis was established, linking target circRNAs to clinical immunohistochemical parameters for comparison. Verification of target circRNAs in LSCC tissues was performed using quantitative real-time PCR (RT-qPCR), whereas target mRNAs were analyzed through immunohistochemistry. Results: A total of 126 significantly different circRNAs were identified, including 40 up-regulated genes and 86 down-regulated genes. Furthermore, 92 circRNA-miRNA-mRNA regulatory relationship axes related to clinical immunohistochemical indicators were found based on 5 candidate circRNAs. Interestingly, all axes related to the target genes MKI67 and TP53 were found to compete with the same circRNA: hsa_circ_0069,399. Further verification confirmed that the hsa_circ_0069,399 expression was overtly upregulated in tumor tissues from LSCC patients, which was consistent with the sequencing results. Conclusion: hsa_circ_0069,399 could be a potential prognostic marker for LSCC.

Development of a tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with antibacterial effects as a wound dressing.

Traditional dressings exhibit several disadvantages, as they frequently lead to bacterial infections, cause severe tissue adhesion and perform a relatively single function. Therefore, in this study, a composite sponge dressing with antibacterial properties and excellent physicochemical properties was developed. Six groups of tobramycin-loaded calcium alginate microspheres were prepared by changing the amount of tobramycin added, and the optimal group was selected. Then, seven groups of tobramycin-loaded calcium alginate microsphere/chitosan composite sponges were fabricated via a solvent blending process and a freeze-drying method. The surface morphology, physicochemical properties,in vitrodegradation properties,in vitrodrug release properties, antibacterial properties and cytotoxicity of the composite sponges were examined. Group 3.0 contained the best microspheres with the largest drug loading capacity, good swelling performance and cumulative drug release rate, obvious and sustained antibacterial activity, and good cytocompatibility. The tobramycin-loaded calcium alginate microsphere/chitosan composite sponges exhibited three-dimensional porous structures, and their porosity, swelling rate, water absorption and water retention rates and water vapor transmission rate met the standards needed for an ideal dressing. The comprehensive performance of the sponge was best when 20 mg of drug-loaded microspheres was added (i.e. group 20). The cumulative drug release rate of the sponge was 29.67 ± 4.14% at 7 d, the diameters of the inhibition zones against the three bacteria were greater than 15 mm, and L929 cell proliferation was promoted. These results demonstrated that the tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with 20 mg of tobramycin-loaded microspheres shows promise as a dressing for infected wounds.

NRSN2 promotes the malignant behavior of HPV-transfected laryngeal carcinoma cells through AMPK/ULK1 pathway mediated autophagy activation.

Neurensin-2 (NRSN2) performs a pro-carcinogenic function in multiple cancers. However, the function of NRSN2 in HPV-infected laryngeal carcinoma (LC) remains unclear. HPV transfection was performed in LC cells. The mRNA and protein levels were monitored using RT-qPCR, immunoblotting, and IF. Cell viability and proliferation were found using the CCK-8 assay and Edu staining. Cell invasion, migration, and apoptosis were probed using the Transwell, wound healing, and flow cytometry, respectively. The autophagosome was observed using TEM. NRSN2 was overexpressed in HPV-transfected LC cells. Inhibition of NRSN2 restrained the autophagy and malignant behavior of HPV-transfected LC cells. Meanwhile, the inhibition of AMPK/ULK1 pathway limited the increased autophagy of HPV-transfected LC cells caused by NRSN2 overexpression. Furthermore, NRSN2 knockdown inhibits autophagy by suppressing AMPK/ULK1 pathway, thereby restraining the malignant behavior of HPV-transfected LC cells. Our research confirmed that HPV transfection increased the autophagy and malignant behavior of LC cells by regulating the NRSN2-mediated activation of the AMPK/ULK1 pathway, offering a new target for cure of LC.

Sacubitril/valsartan ameliorates tubulointerstitial fibrosis by restoring mitochondrial homeostasis in diabetic kidney disease.

BACKGROUND: Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear. METHODS: Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro. RESULTS: We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor. CONCLUSIONS: Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.

Hepatic Pecoma versus Hepatocellular Carcinoma In The Noncirrhotic Liver on Gd-EOB-DTPA-Enhanced MRI: A Diagnostic Challenge.

AIM: Hepatic perivascular epithelioid cell tumors (PEComa) often mimic hepatocellular carcinoma (HCC) in patients without cirrhosis. This study aimed to develop a nomogram using imaging characteristics on Gd-EOB-DTPA-enhanced MRI and to distinguish PEComa from HCC in a noncirrhotic liver. METHODS: Forty patients with non-cirrhotic Gd-EOB-DTPA-enhanced magnetic resonance imaging(MRI) were included in our study. A multivariate logistic regression model was used to select significant variables to distinguish PEComa from HCC. A nomogram was developed based on the regression model. The performance of the nomogram was assessed with respect to the ROC curve and calibration curve. Decision curve analysis (DCA) was performed to evaluate the clinical usefulness of the nomogram. RESULTS: Two significant predictors were identified: the appearance of an early draining vein and the T1D value of tumors. The ROC curve showed that the area under the curve (AUC) of the model to predict the risk of PEComa was 0.91 (95% CI: 0.80~1) and showed that the model had high specificity (92.3%) and sensitivity (88.9%). The nomogram incorporating these two predictors showed favorable calibration, which was validated using 1000 resampling procedures, and the corrected C-index of this model was 0.90. Furthermore, DCA analysis showed that the model had clinical practicability. CONCLUSION: In conclusion, the nomogram model showed favorable predictive accuracy for distinguishing PEComa from HCC in non-cirrhotic patients and may aid in clinical decision-making.

Tubular TMEM16A promotes tubulointerstitial fibrosis by suppressing PGC-1α-mediated mitochondrial homeostasis in diabetic kidney disease.

Tubulointerstitial fibrosis (TIF) plays a crucial role in the progression of diabetic kidney disease (DKD). However, the underlying molecular mechanisms remain obscure. The present study aimed to examine whether transmembrane member 16A (TMEM16A), a Ca2+-activated chloride channel, contributes to the development of TIF in DKD. Interestingly, we found that TMEM16A expression was significantly up-regulated in tubule of murine model of DKD, which was associated with development of TIF. In vivo inhibition of TMEM16A channel activity with specific inhibitors Ani9 effectively protects against TIF. Then, we found that TMEM16A activation induces tubular mitochondrial dysfunction in in vivo and in vitro models, with the evidence of the TMEM16A inhibition with specific inhibitor. Mechanically, TMEM16A mediated tubular mitochondrial dysfunction through inhibiting PGC-1α, whereas overexpression of PGC-1α could rescue the changes. In addition, TMEM16A-induced fibrogenesis was dependent on increased intracellular Cl-, and reducing intracellular Cl- significantly blunted high glucose-induced PGC-1α and profibrotic factors expression. Taken together, our studies demonstrated that tubular TMEM16A promotes TIF by suppressing PGC-1α-mediated mitochondrial homeostasis in DKD. Blockade of TMEM16A may serve as a novel therapeutic approach to ameliorate TIF.

Preoperative assessment of peripheral vascular invasion of pancreatic ductal adenocarcinoma based on high-resolution MRI.

OBJECTIVES: Preoperative imaging of vascular invasion is important for surgical resection of pancreatic ductal adenocarcinoma (PDAC). However, whether MRI and CT share the same evaluation criteria remains unclear. This study aimed to compare the diagnostic accuracy of high-resolution MRI (HR-MRI), conventional MRI (non-HR-MRI) and CT for PDAC vascular invasion. METHODS: Pathologically proven PDAC with preoperative HR-MRI (79 cases, 58 with CT) and non-HR-MRI (77 cases, 59 with CT) were retrospectively collected. Vascular invasion was confirmed surgically or pathologically. The degree of tumour-vascular contact, vessel narrowing and contour irregularity were reviewed respectively. Diagnostic criteria 1 (C1) was the presence of all three characteristics, and criteria 2 (C2) was the presence of any one of them. The diagnostic efficacies of different examination methods and criteria were evaluated and compared. RESULTS: HR-MRI showed satisfactory performance in assessing vascular invasion (AUC: 0.87-0.92), especially better sensitivity (0.79-0.86 vs. 0.40-0.79) than that with non-HR-MRI and CT. HR-MRI was superior to non-HR-MRI. C2 was superior to C1 on CT evaluation (0.85 vs. 0.79, P = 0.03). C1 was superior to C2 in the venous assessment using HR-MRI (0.90 vs. 0.87, P = 0.04) and in the arterial assessment using non-HR-MRI (0.69 vs. 0.68, P = 0.04). The combination of C1-assessed HR-MRI and C2-assessed CT was significantly better than that of CT alone (0.96 vs. 0.86, P = 0.04). CONCLUSIONS: HR-MRI more accurately assessed PDAC vascular invasion than conventional MRI and may contribute to operative decision-making. C1 was more applicable to MRI scans, and C2 to CT scans. The combination of C1-assessed HR-MRI and C2-assessed CT outperformed CT alone and showed the best efficacy in preoperative examination of PDAC.

[Analysis of medium and long term efficacy of ossicle chain bypass technique in treatment of tympanosclerosis].

Objective:For tympanosclerosis patients with ossicular chain fixation, we use ossicular chain bypass technique and evaluate its long-term effects. Methods:From June 2017 to June 2019, 147 patients with tympanosclerosis who underwent middle ear surgery with otoscopy in Yinchuan First People's Hospital were reviewed. The subjects were divided into three groups according to the implemented operation plan, 51 cases in the ossicular chain mobilization group（OCM）, 56 cases in the ossicular chain bypass reconstruction group（OCB）, and 40 cases in the malleus-incus complex resection reconstruction group（MICR）. Through a three-year follow-up, the medium and long-term effects of different operation plans were compared and analyzed. Results:There was no significant difference among the three groups in the incidence of tympanic membrane perforation, delayed facial nerve palsy, and the dispatch and displacement of PORP. The incidence of tympanic membrane retraction pocket or cholesteatoma after operation in OCB group（0） was significantly lower than that in OCM group（11.76%） and MICR group（7.5%）（P<0.05）. At 12 months after operation, ΔABG of OCB group and MICR group were better than that in the OCM group（P<0.05）. At 36 months after operation, ΔABG of OCB group was better than that in the OCM group（P<0.05）, and there was no significant difference between OCB group and MICR group. The audiological performance of patients with epitympanic sclerosis（ETS） at 12, 24 and 36 months after operation was better than that of patients with posterior tympanosclerosis（PTS） and total tympanosclerosis（TTS）（P<0.05）. Conclusion:Compared with patients undergoing ossicular chain mobilization and malleus-incus complex resection for ossicular chain reconstruction, patients with tympanosclerosis undergoing bypass technique have better and stable hearing prognosis in medium and long term. This technique can effectively prevent the formation of retracted pocket and cholesteatoma in patients with tympanosclerosis after operation.

Development and validation of a prognostic nomogram for the renal relapse of lupus nephritis / Desarrollo y validación de un nomograma pronóstico para la recaída renal de la nefritis lúpica

Objectives This study aims to assess the risk of relapse after complete remission (CR) and partial remission (PR), and to develop a prognostic nomogram predicting the probability in lupus nephritis (LN) patients. Methods Data from patients with LN who had been in remission were collected as a training cohort. The prognostic factors were analyzed using the univariable and multivariable Cox model for the training group. A nomogram was then developed using significant predictors in multivariable analysis. Both discrimination and calibration were assessed by bootstrapping with 100 resamples. Results A total of 247 participants were enrolled, including 108 in the relapse group and 139 in the no relapse group. In multivariate Cox analysis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), erythrocyte sedimentation rate (ESR), complement 1q (C1q), and antiphospholipid (aPL), anti-Sm antibody were found to be significant for predicting relapse rates. The prognostic nomogram including the aforementioned factors effectively predicted 1- and 3-year probability of flare-free. Moreover, a favorable consistency between the predicted and actual survival probabilities was demonstrated using calibration curves. Conclusions High SLEDAI, ESR, and positive aPL, anti-Sm antibody are potential risk factors for LN flare, while high C1q can reduce its recurrence. The visualized model we established can help predict the relapse risk of LN and aid clinical decision-making for individual patients (AU)

Objetivos Este estudio pretende evaluar el riesgo de recaída tras la remisión completa y la remisión parcial, y desarrollar un nomograma pronóstico que prediga la probabilidad en pacientes con nefritis lúpica (NL). Métodos Se recogieron datos de pacientes con NL que habían estado en remisión como cohorte de entrenamiento. Se analizaron los factores pronósticos utilizando el modelo COX univariable y multivariable para el grupo de entrenamiento. A continuación se desarrolló un nomograma utilizando los predictores significativos en el análisis multivariable. Tanto la discriminación como la calibración se evaluaron mediante bootstrapping con 100 remuestreos. Resultados Se inscribió a un total de 247 participantes, incluidos 108 en el grupo de recaída y 139 en el grupo sin recaída. En el análisis multivariante de Cox, el índice de actividad de la enfermedad lúpica eritematosa sistémica (SLEDAI), la velocidad de sedimentación globular (VSG), el complemento 1q (C1q) y los anticuerpos antifosfolípidos (aPL) y anti-Sm resultaron significativos para predecir las tasas de recaída. El nomograma pronóstico que incluía los factores mencionados predijo eficazmente la probabilidad a 1 y a 3 años de estar libre de reagudizaciones. Además, se demostró una coherencia favorable entre las probabilidades de supervivencia previstas y las reales mediante curvas de calibración. Conclusiones SLEDAI alto, VSG y aPL positivo, anticuerpos anti-Sm son factores de riesgo potenciales de reagudización de la NL, mientras que C1q alto puede reducir su recurrencia. El modelo visualizado que establecimos puede ayudar a predecir el riesgo de recidiva de la NL y ayudar a la toma de decisiones clínicas para pacientes individuales (AU)

Review of PINK1-Parkin-mediated mitochondrial autophagy in Alzheimer's disease.

Mitochondrial autophagy plays an important role in maintaining the complexity of mitochondrial functions and removing damaged mitochondria, of which the PINK1-Parkin signal pathway is one of the most classical pathways. Thus, a comprehensive and in-depth interpretation of the PINK1-Parkin signal pathway might deepen our understanding on the impacts of mitochondrial autophagy. Alzheimer's disease (AD) is a classical example of neurodegenerative disease. Research on the pathogenesis and treatments of AD has been a focus of scientific research because of its complexity and the limitations of current drug therapies. It was reported that the pathogenesis of AD might be related to mitochondrial autophagy due to excessive deposition of Aß protein and aggravation of the phosphorylation of Tau protein. Two key proteins in the PINK1-Parkin signaling pathway, PINK1 and Parkin, have important roles in the folding and accumulation of Aß protein and the phosphorylation of Tau protein. In addition, the intermediate signal molecules in the PINK1-Parkin signal pathway also have certain effects on AD. In this paper, we first described the role of PINK1-Parkin signal pathway on mitochondrial autophagy, then discussed and analyzed the effect of the PINK1-Parkin signal pathway in AD and other metabolic diseases. Our aim was to provide a theoretical direction to further elucidate the pathogenesis of AD and highlight the key molecules related to AD that could be important targets used for AD drug development.

Clinical Interpretability of Deep Learning for Predicting Microvascular Invasion in Hepatocellular Carcinoma by Using Attention Mechanism.

Preoperative prediction of microvascular invasion (MVI) is essential for management decision in hepatocellular carcinoma (HCC). Deep learning-based prediction models of MVI are numerous but lack clinical interpretation due to their "black-box" nature. Consequently, we aimed to use an attention-guided feature fusion network, including intra- and inter-attention modules, to solve this problem. This retrospective study recruited 210 HCC patients who underwent gadoxetate-enhanced MRI examination before surgery. The MRIs on pre-contrast, arterial, portal, and hepatobiliary phases (hepatobiliary phase: HBP) were used to develop single-phase and multi-phase models. Attention weights provided by attention modules were used to obtain visual explanations of predictive decisions. The four-phase fusion model achieved the highest area under the curve (AUC) of 0.92 (95% CI: 0.84-1.00), and the other models proposed AUCs of 0.75-0.91. Attention heatmaps of collaborative-attention layers revealed that tumor margins in all phases and peritumoral areas in the arterial phase and HBP were salient regions for MVI prediction. Heatmaps of weights in fully connected layers showed that the HBP contributed the most to MVI prediction. Our study firstly implemented self-attention and collaborative-attention to reveal the relationship between deep features and MVI, improving the clinical interpretation of prediction models. The clinical interpretability offers radiologists and clinicians more confidence to apply deep learning models in clinical practice, helping HCC patients formulate personalized therapies.

[Distribution characteristics and results of allergens in patients with allergic rhinitis in Ningxia area].

Objective:To investigate the distribution of allergens in patients with allergic rhinitis （AR） in Ningxia, and provide theoretical data for the prevention and treatment of AR in this region. Methods:A total of 1664 patients diagnosed with AR in the Otorhinolaryngology Head and Neck Surgery Department of Yinchuan First People's Hospital Outpatient Clinic from January 2018 to December 2021 were retrospectively collected. Use the allergen sIgE antibody detection kit （immunoblotting method） to detect inhalation and ingestion allergens in patients.Results: ①Among all AR patients, 1 158 cases were detected positive, resulting in the detection rate was 69.59%; ②The detection rate of inhalation allergen was 65.87%, and the detection rate of ingestion allergen was 19.83%; ③Mugwort was the most sensitive allergen, and 76.32% of the patients having a positive grade ≥3; ④Out of the patients, 294 cases （25.39%） were allergic to only one allergen, 244 cases （21.07%） were allergic to two allergens, and 620 cases （53.54%） were allergic to three or more allergens; ⑤During different seasons, the highest number of positive allergens detected was in the summer, with 968 cases （83.59%）. Mugwort was the main allergen during this season （69.01%）. After the COVID-19 epidemic, the total positive rate of sIgE tests in AR patients decreased compared to before, and the difference was statistically significant （P<0.001）; ⑥Mugwort, dog epithelium, mold combination, egg, peanut, soybean, Marine fish combination and fruit combination all showed statistically significant differences between different gender groups （P<0.05）; ⑦Common ragweed, mugwort, dust mite combination, cockroach, egg, milk, Marine fish combination, shrimp, fruit combination and nut combination all showed statistically significant differences among different age groups （P<0.05）; ⑧There were statistically significant differences in hay dust among different ethnic groups （P<0.05）. Conclusion:Artemisia argyi is the main allergen in Ningxia, and the distribution characteristics of different allergens are influenced by treatment season, the COVID-19 epidemic, gender, age, ethnicity, and other factors, showing certain distribution patterns and rules.

Development and validation of a prognostic nomogram for the renal relapse of lupus nephritis.

OBJECTIVES: This study aims to assess the risk of relapse after complete remission (CR) and partial remission (PR), and to develop a prognostic nomogram predicting the probability in lupus nephritis (LN) patients. METHODS: Data from patients with LN who had been in remission were collected as a training cohort. The prognostic factors were analyzed using the univariable and multivariable Cox model for the training group. A nomogram was then developed using significant predictors in multivariable analysis. Both discrimination and calibration were assessed by bootstrapping with 100 resamples. RESULTS: A total of 247 participants were enrolled, including 108 in the relapse group and 139 in the no relapse group. In multivariate Cox analysis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), erythrocyte sedimentation rate (ESR), complement 1q (C1q), and antiphospholipid (aPL), anti-Sm antibody were found to be significant for predicting relapse rates. The prognostic nomogram including the aforementioned factors effectively predicted 1- and 3-year probability of flare-free. Moreover, a favorable consistency between the predicted and actual survival probabilities was demonstrated using calibration curves. CONCLUSIONS: High SLEDAI, ESR, and positive aPL, anti-Sm antibody are potential risk factors for LN flare, while high C1q can reduce its recurrence. The visualized model we established can help predict the relapse risk of LN and aid clinical decision-making for individual patients.

(2E)-1-(2,4,6-Trimethoxyphenyl)-3-(4-chlorophenyl)prop-2-en-1-one, a Chalcone Derivative, Promotes Apoptosis by Suppressing RAS-ERK and AKT/FOXO3a Pathways in Hepatocellular Carcinoma Cells.

BACKGROUND: Liver cancer is an extremely common cancer with the highest mortality rate and poor prognosis. Owing to their low systemic toxicity and few side effects, natural compounds may provide better therapeutic effects for patients. (2E)-1-(2,4,6-trimethoxyphenyl)-3-(4-chlorophenyl)prop-2-en-1-one (TMOCC), a chalcone derivative, exhibits cytotoxicity towards many tumor cells. However, the anticancer mechanism of TMOCC has not been elucidated in human hepatocellular carcinoma (HCC). METHODS: Cell Counting Kit-8 and colony formation assays were used to evaluate the effects of TMOCC on viability and proliferation. Mitochondrial transmembrane potential and flow cytometry assays were used to detect apoptosis. The expression levels of proteins related to apoptosis, the RAS-ERK and AKT/FOXO3a signaling pathways were assessed using western blot. Potential targets of TMOCC were detected using molecular docking analysis. RESULTS: TMOCC inhibited viability and proliferation, and induced the loss of mitochondrial transmembrane potential, apoptosis and DNA double-strand breaks in both HCC cells. The RAS-ERK and AKT/FOXO3a signaling pathways were suppressed by TMOCC. Finally, ERK1, PARP-1, and BAX were identified as potential targets of TMOCC. CONCLUSION: Taken together, our results show that TMOCC promotes apoptosis by suppressing the RAS-ERK and AKT/FOXO3a signaling pathways. TMOCC may be a potential multi-target compound that is effective against liver cancer.

Gut Microbiota is an Impact Factor based on the Brain-Gut Axis to Alzheimer's Disease: A Systematic Review.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic, ß-amyloid toxicity, tau protein hyperphosphorylation, and oxidative stress theories. However, an effective treatment method has not been developed. In recent years, with the discovery of the brain-gut axis (BGA) and breakthroughs made in Parkinson's disease, depression, autism, and other diseases, BGA has become a hotspot in AD research. Several studies have shown that gut microbiota can affect the brain and behavior of patients with AD, especially their cognitive function. Animal models, fecal microbiota transplantation, and probiotic intervention also provide evidence regarding the correlation between gut microbiota and AD. This article discusses the relationship and related mechanisms between gut microbiota and AD based on BGA to provide possible strategies for preventing or alleviating AD symptoms by regulating gut microbiota.

Activation of HIF-1α C-terminal transactivation domain protects against hypoxia-induced kidney injury through hexokinase 2-mediated mitophagy.

The transcription factor hypoxia-inducible factor-1α (HIF-1α), as a master regulator of adaptive responses to hypoxia, possesses two transcriptional activation domains [TAD, N-terminal (NTAD), and C-terminal (CTAD)]. Although the roles of HIF-1α NTAD in kidney diseases have been recognized, the exact effects of HIF-1α CTAD in kidney diseases are poorly understood. Here, two independent mouse models of hypoxia-induced kidney injury were established using HIF-1α CTAD knockout (HIF-1α CTAD-/-) mice. Furthermore, hexokinase 2 (HK2) and mitophagy pathway are modulated using genetic and pharmacological methods, respectively. We demonstrated that HIF-1α CTAD-/- aggravated kidney injury in two independent mouse models of hypoxia-induced kidney injury, including ischemia/reperfusion-induced kidney injury and unilateral ureteral obstruction-induced nephropathy. Mechanistically, we found that HIF-1α CTAD could transcriptionally regulate HK2 and subsequently ameliorate hypoxia-induced tubule injury. Furthermore, it was found that HK2 deficiency contributed to severe renal injury through mitophagy inhibition, while mitophagy activation using urolithin A could significantly protect against hypoxia-induced kidney injury in HIF-1α C-TAD-/- mice. Our findings suggested that the HIF-1α CTAD-HK2 pathway represents a novel mechanism of kidney response to hypoxia, which provides a promising therapeutic strategy for hypoxia-induced kidney injury.