Conditional Survival of Patients with Limited-Stage Small Cell Lung Cancer After Surgery: A National Real-World Cohort Study.

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.

Circuit-based neuromodulation enhances delayed recall in amnestic mild cognitive impairment.

BACKGROUND: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI). METHODS: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits. RESULTS: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017). CONCLUSIONS: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus. TRIAL REGISTRATION NUMBER: ChiCTR2100053315; Chinese Clinical Trial Registry.

Prokaryotic virus host prediction with graph contrastive augmentaion.

Prokaryotic viruses, also known as bacteriophages, play crucial roles in regulating microbial communities and have the potential for phage therapy applications. Accurate prediction of phage-host interactions is essential for understanding the dynamics of these viruses and their impacts on bacterial populations. Numerous computational methods have been developed to tackle this challenging task. However, most existing prediction models can be constrained due to the substantial number of unknown interactions in comparison to the constrained diversity of available training data. To solve the problem, we introduce a model for prokaryotic virus host prediction with graph contrastive augmentation (PHPGCA). Specifically, we construct a comprehensive heterogeneous graph by integrating virus-virus protein similarity and virus-host DNA sequence similarity information. As the backbone encoder for learning node representations in the virus-prokaryote graph, we employ LGCN, a state-of-the-art graph embedding technique. Additionally, we apply graph contrastive learning to augment the node representations without the need for additional labels. We further conducted two case studies aimed at predicting the host range of multi-species phages, helping to understand the phage ecology and evolution.

Construction and validation of a risk-scoring model to predict lymph node metastasis in T1b-T2 esophageal cancer.

BACKGROUND: Lymph node status is an important factor in determining preoperative treatment strategies for stage T1b-T2 esophageal cancer (EC). Thus, the aim of this study was to investigate the risk factors for lymph node metastasis (LNM) in T1b-T2 EC and to establish and validate a risk-scoring model to guide the selection of optimal treatment options. METHODS: Patients who underwent upfront surgery for pT1b-T2 EC between January 2016 and December 2022 were analyzed. On the basis of the independent risk factors determined by multivariate logistic regression analysis, a risk-scoring model for the prediction of LNM was constructed and then validated. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminant ability of the model. RESULTS: The incidence of LNM was 33.5% (214/638) in our cohort, 33.4% (169/506) in the primary cohort and 34.1% (45/132) in the validation cohort. Multivariate analysis confirmed that primary site, tumor grade, tumor size, depth, and lymphovascular invasion were independent risk factors for LNM (all P < 0.05), and patients were grouped based on these factors. A 7-point risk-scoring model based on these variables had good predictive accuracy in both the primary cohort (AUC, 0.749; 95% confidence interval 0.709-0.786) and the validation cohort (AUC, 0.738; 95% confidence interval 0.655-0.811). CONCLUSION: A novel risk-scoring model for lymph node metastasis was established to guide the optimal treatment of patients with T1b-T2 EC.

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study.

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares.

Analysis of the efficacy of separation surgery for severe neurological compression in multiple myeloma: a retrospective analysis of 35 cases.

PURPOSE: To investigate the effectiveness and safety of separation surgery for Epidural Spinal Cord Compression (ESCC) graded ≥ 2 in patients with Multiple Myeloma (MM), analyze factors influencing surgical outcomes, and develop a preliminary treatment decision framework for these patients. METHODS: A retrospective analysis was conducted on clinical data from 35 MM patients who underwent separation surgery for ESCC graded ≥ 2 between 2013 and 2018. Patient data, including baseline information, surgical details, complications, and pre-operative as well as one-month post-operative efficacy evaluation indicators were recorded. Statistical analysis was performed on pre-operative and post-operative efficacy indicators to determine if there were significant improvements (p < 0.05). Ordered logistic regression was utilized to assess factors associated with an unfavorable post-operative quality of life outcome. RESULTS: Compared to pre-operative values, at one-month post-surgery, patients showed significant improvements in Frankel Score Classification (4 vs 5, p < 0.05), Karnofsky Performance Score (30 vs 70, p < 0.05), and Visual Analogue Scale (8 vs 3, p < 0.05). Complications occurred in 7 cases (20%). The number of segments with ESCC (OR = 0.171, p < 0.05) and pre-operative chemotherapy (OR = 5.202, p = 0.05) were identified as independent factors influencing patient outcomes. Patients with more than two vertebral segments with ESCC exhibited significantly worse post-operative conditions. CONCLUSIONS: Separation surgery effectively alleviates pain, improves neurological function, and enhances the quality of life in patients with ESCC graded ≥ 2 due to MM.

Which factors are associated with adverse prognosis in multiple myeloma patients after surgery? - preliminary establishment and validation of the nomogram.

BACKGROUND: To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram. METHODS: Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients' pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated. RESULTS: Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%. CONCLUSION: This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.

Reduced microbial stability in the active layer is associated with carbon loss under alpine permafrost degradation.

Permafrost degradation may induce soil carbon (C) loss, critical for global C cycling, and be mediated by microbes. Despite larger C stored within the active layer of permafrost regions, which are more affected by warming, and the critical roles of Qinghai-Tibet Plateau in C cycling, most previous studies focused on the permafrost layer and in high-latitude areas. We demonstrate in situ that permafrost degradation alters the diversity and potentially decreases the stability of active layer microbial communities. These changes are associated with soil C loss and potentially a positive C feedback. This study provides insights into microbial-mediated mechanisms responsible for C loss within the active layer in degraded permafrost, aiding in the modeling of C emission under future scenarios.

Nomogram to Predict Recurrence and Guide a Pragmatic Surveillance Strategy After Resection of Hepatoid Adenocarcinoma of the Stomach: A Retrospective Multicenter Study.

BACKGROUND: An accurate recurrence risk assessment system and surveillance strategy for hepatoid adenocarcinoma of the stomach (HAS) remain poorly defined. This study aimed to develop a nomogram to predict postoperative recurrence of HAS and guide individually tailored surveillance strategies. METHODS: The study enrolled all patients with primary HAS who had undergone curative-intent resection at 14 institutions from 2004 to 2019. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram to build a recurrence predictive model. RESULTS: The nomogram of recurrence-free survival (RFS) based on independent prognostic factors, including age, preoperative carcinoembryonic antigen, number of examined lymph nodes, perineural invasion, and lymph node ratio, achieved a C-index of 0.723 (95% confidence interval [CI], 0.674-0.772) in the whole cohort, which was significantly higher than those of the eighth American Joint Committed on Cancer (AJCC) staging system (C-index, 0.629; 95% CI, 0.573-0.685; P < 0.001). The nomogram accurately stratified patients into low-, middle-, and high-risk groups of postoperative recurrence. The postoperative recurrence risk rates for patients in the middle- and high-risk groups were respectively 3 and 10 times higher than for the low-risk group. The patients in the middle- and high-risk groups showed more recurrence and metastasis, particularly multiple site metastasis, within 36 months after the operation than those in the low-risk group (low, 2.2%; middle, 8.6%; high, 24.0%; P = 0.003). CONCLUSIONS: The nomogram achieved good prediction of postoperative recurrence for the patients with HAS after radical resection. For the middle- and high-risk patients, more active surveillance and targeted examination methods should be adopted within 36 months after the operation, particularly for liver and multiple metastases.

Study on the transmission characteristics and band structure of 2D and 3D plasma photonic crystals.

In this paper, 2D and 3D plasma photonic crystals (PPCs) were constructed using argon-mercury glow discharge tubes. Firstly, the collisional radiative model (CRM) was established for the glow discharge process, the average electron density of plasma in the discharge tube was calculated, and the average electron density was experimentally diagnosed by microwave diagnosis. By comparing the calculated and experimental results, the variation range of the average electron density in the tube was given. Secondly, according to the analysis results of the average electron density, a layered model of the discharge tube was established, and the transmission characteristics of the 2D and 3D PPC were calculated and measured. Finally, to analyze the cause of the photonic bandgap (PBG) in the transmission spectra, the band structures of 2D and 3D PPC were calculated using the plane wave expansion (PWE) method and the symplectic finite difference time domain (SFDTD) method. The results show that: the layered model is a valid discharge tube model; for 2D PPC, the formation of Localized Surface Plasmons (LSPs) under TE polarization is the main cause of PBG generation, and the number of LSP bandgap increases as the electron density rises; The existence of cutoff bandgap under TM polarization is due to the cutoff effect of plasma on electromagnetic waves. For 3D PPC, both cutoff bandgap and LSP bandgap exist in the transmission spectra, and the cutoff bandgap is shifted to lower frequencies due to the presence of Fano mode. The results of the study can be used as a reference for communication, microwave device fabrication, and military target stealth.

Polymorphism at codon 31 of CDKN1A (p21) as a predictive factor for bevacizumab therapy in glioblastoma multiforme.

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR-RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.

Burden and Trends of IBD in 5 Asian Countries From 1990 to 2019: A Comparison With the United States and the United Kingdom.

BACKGROUND: IBD is becoming a global health challenge, with substantial variations in incidence and death rates between Eastern and Western countries. OBJECTIVE: This study aimed to investigate the burden and trends of IBD in 5 Asian countries, the United States, and the United Kingdom. DESIGN: This was a cross-sectional study. SETTING: Data were obtained from Global Burden of Disease 2019 Study. PATIENTS: Patients with IBD were included. MAIN OUTCOME MEASURES: Incidence, death, and age-standardized rates of IBD were measured. RESULTS: The age-standardized incidence and rates of death from IBD gradually decreased worldwide from 1990 to 2019. The age-standardized incidence rate in the United States decreased from 1990 to 2000 and then increased gradually from 2000 to 2019; the age-standardized incidence rates in the United Kingdom, Mongolia, and China increased gradually from 1990 to 2019, whereas in the Democratic People's Republic of Korea, it decreased from 1990 to 1995 and increased gradually from 1995 to 2019. The age-standardized death rate in the Republic of Korea exhibited a rising trend until 1995, fell significantly up to 2015, and then stabilized from 2015 to 2019. The age-standardized death rate in the United States showed a rising trend until 2007, and then decreased gradually from 2007 to 2019, whereas the rate in the United Kingdom showed a rising trend until 2010 and decreased from 2010 to 2019. The age-standardized death rates in China, Mongolia, the Democratic People's Republic of Korea, and Japan decreased gradually from 1990 to 2019. The age-standardized incidence and death rates in the United States and United Kingdom in recent decades were higher than those in the 5 Asian countries. The peak age-standardized incidence rates in the 7 countries were among people of 20 to 60 years of age. The age-standardized death rates in all 7 countries exhibited rising trends with increasing age, with older individuals, particularly those aged ≥70 years, accounting for the most deaths. LIMITATIONS: Limitations of this study include data from different countries with different quality and accuracy. CONCLUSIONS: There have been large variations in the burdens and trends of IBD between 5 Asian countries, the United States, and the United Kingdom during the past 3 decades. These findings may help policymakers to make better public decisions and allocate appropriate resources. See Video Abstract at http://links.lww.com/DCR/B996 . CARGA Y TENDENCIAS DE LA ENFERMEDAD INFLAMATORIA INTESTINAL EN CINCO PASES ASITICOS DESDE HASTA UNA COMPARACIN CON LOS ESTADOS UNIDOS Y EL REINO UNIDO: ANTECEDENTES:La enfermedad inflamatoria intestinal se está convirtiendo en un desafío en la salud mundial, con variaciones sustanciales en las tasas de incidencia y mortalidad entre los países orientales y occidentales.OBJETIVO:Investigar la carga y las tendencias de la enfermedad inflamatoria intestinal en cinco países asiáticos, EE. UU. y el Reino Unido.DISEÑO:Estudio transversal.ESCENARIO:Estudio de carga global de morbilidad 2019.PACIENTES:Enfermedad inflamatoria intestinal.PRINCIPALES MEDIDAS DE RESULTADO:Incidencia, muerte y tasas estandarizadas por edad de enfermedad inflamatoria intestinal.RESULTADOS:Las tasas de incidencia y muerte estandarizadas por edad de la enfermedad inflamatoria intestinal disminuyeron gradualmente en todo el mundo desde 1990 hasta 2019. La tasa de incidencia estandarizada por edad en los EE. UU. disminuyó de 1990 a 2000 y luego aumentó gradualmente de 2000 a 2019, las tasas en el Reino Unido, Mongolia y China aumentaron gradualmente de 1990 a 2019, mientras que la tasa en la República Popular Democrática de Corea disminuyó de 1990 a 1995 y aumentó gradualmente de 1990 a 2019. La tasa de mortalidad estandarizada por edad en la República de Corea exhibió un tendencia ascendente hasta 1995, cayó significativamente hasta 2015 y luego se estabilizó de 2015 a 2019. La tasa de mortalidad estandarizada por edad en los EE. UU. mostró una tendencia ascendente hasta 2007 y luego disminuyó gradualmente de 2007 a 2019, mientras que la tasa en el Reino Unido mostró una tendencia ascendente hasta 2010 y disminuyó de 2010 a 2019. Las tasas de mortalidad estandarizadas por edad en China, Mongolia, la República Popular Democrática de Corea y Japón disminuyeron gradualmente de 1990 a 2019. La tasa de incidencia estandarizada por edad y mortalidad en los EE. UU. y el Reino Unido en la última década fueron más altas que las de los cinco países asiáticos. Las tasas máximas de incidencia estandarizadas por edad en los siete países se dieron entre personas de 20 a 60 años. Las tasas de mortalidad estandarizadas por edad en los siete países exhibieron tendencias crecientes con el aumento de la edad, y las personas mayores, en particular las de ≥70 años, representaron la mayoría de las muertes.LIMITACIONES:Datos de diferentes países con diferente calidad y precisión.CONCLUSIONES:Ha habido grandes variaciones en las cargas y tendencias de la enfermedad inflamatoria intestinal entre cinco países asiáticos, EE. UU. y el Reino Unido durante las últimas tres décadas. Estos hallazgos pueden ayudar a los formuladores de políticas a tomar mejores decisiones públicas y asignar los recursos apropiados. Consulte Video Resumen en http://links.lww.com/DCR/B996 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Effects of cortico-cortical paired associative stimulation based on multisensory integration to brain network connectivity in stroke patients: study protocol for a randomized doubled blind clinical trial.

INTRODUCTION: Brain has a spontaneous recovery after stroke, reflecting the plasticity of the brain. Currently, TMS is used for studies of single-target brain region modulation, which lacks consideration of brain networks and functional connectivity. Cortico-cortical paired associative stimulation (ccPAS) promotes recovery of motor function. Multisensory effects in primary visual cortex(V1) directly influence behavior and perception, which facilitate motor functional recovery in stroke patients. Therefore, in this study, dual-targeted precise stimulation of V1 and primary motor cortex(M1) on the affected hemisphere of stroke patients will be used for cortical visuomotor multisensory integration to improve motor function. METHOD: This study is a randomized, double-blind controlled clinical trial over a 14-week period. 69 stroke subjects will be enrolled and divided into sham stimulation group, ccPAS low frequency group, and ccPAS high frequency group. All groups will receive conventional rehabilitation. The intervention lasted for two weeks, five times a week. Assessments will be performed before the intervention, at the end of the intervention, and followed up at 6 and 14 weeks. The primary assessment indicator is the 'Fugl-Meyer Assessment of the Upper Extremity ', secondary outcomes were 'The line bisection test', 'Modified Taylor Complex Figure', 'NIHSS' and neuroimaging assessments. All adverse events will be recorded. DISCUSSION: Currently, ccPAS is used for the modulation of neural circuits. Based on spike-timing dependent plasticity theory, we can precisely intervene in the connections between different cortices to promote the recovery of functional connectivity on damaged brain networks after stroke. We hope to achieve the modulation of cortical visuomotor interaction by combining ccPAS with the concept of multisensory integration. We will further analyze the correlation between analyzing visual and motor circuits and explore the alteration of neuroplasticity by the interactions between different brain networks. This study will provide us with a new clinical treatment strategy to achieve precise rehabilitation for patient with motor dysfunction after stroke. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry with code ChiCTR2300067422 and was approved on January 16, 2023.

Focal ischemic stroke modifies microglia-derived exosomal miRNAs: potential role of mir-212-5p in neuronal protection and functional recovery.

BACKGROUND: Ischemic stroke is a severe type of stroke with high disability and mortality rates. In recent years, microglial exosome-derived miRNAs have been shown to be promising candidates for the treatment of ischemic brain injury and exert neuroprotective effects. Mechanisms underlying miRNA dysregulation in ischemic stroke are still being explored. Here, we aimed to verify whether miRNAs derived from exosomes exert effects on functional recovery. METHODS: MiR-212-5p agomir was employed to upregulate miR-212-5p expression in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Western blot analysis, qRT-PCR and immunofluorescence staining and other methods were applied to explore the underlying mechanisms of action of miR-212-5p. RESULTS: The results of our study found that intervention with miR-212-5p agomir effectively decreased infarct volume and restored motor function in MCAO/R rats. Mechanistically, miR-212-5p agomir significantly reduced the expression of PlexinA2 (PLXNA2). Additionally, the results obtained in vitro were similar to those achieved in vivo. CONCLUSION: In conclusion, the present study indicated that PLXNA2 may be a target gene of miR-212-5p, and miR-212-5p has great potential as a target for the treatment and diagnosis of ischemic stroke.

Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3-5: a randomized controlled trial.

BACKGROUND: Although combining a low-protein diet (LPD) with oral nutritional supplements increases treatment adherence and nutritional status in patients with chronic kidney disease (CKD), the effect of this combination approach in older adults remains unclear. This study examined the impact of a 6% low-protein formula (6% LPF) with diet counseling in older adults with stage 3-5 CKD. METHODS: In this three-month randomized controlled study, 66 patients (eGFR < 60 mL/min/1.73 m2, non-dialysis, over 65 years of age) were randomly assigned to an intervention group (LPD plus a 6% LPF) or control group (LPD alone). The 6% LPF comprised 400 kcal, 6 g of protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and various micronutrients. All data were collected at baseline and after three months, including physical performance based on hand grip strength (HGS) and gait speed, nutritional status using Mini Nutritional Assessment-Short Form (MNA-SF) scores, body composition through bioelectrical impedance analysis, and dietary intake from 24-h dietary records. RESULTS: This study incorporated 47 participants (median age, 73; median eGFR, 36 ml/min/1.73 m2; intervention group: 24; control group: 23). The intervention group exhibited significant differences in HGS and gait speed, and micronutrient analysis revealed significantly higher monounsaturated fatty acids (MUFA), EPA, DHA, calcium, iron, zinc, copper, thiamine, riboflavin, niacin, B6, B12, and folic acid intake than the control group. MNA-SF scores, macronutrient intake, and body composition did not differ significantly between the two groups. CONCLUSIONS: Compared to LPD counseling alone, an LPD prescription with 6% LPF in older adults with CKD stages 3-5 helped relieve physical deterioration and increased micronutrient intake after three months. TRIAL REGISTRATION: ClinicalTrials.gov NCT05318014 (retrospectively registered on 08/04/2022).

[Panax notoginseng saponins improve monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting ADAM10/Notch3 signaling pathway].

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.

Radiographical Evaluation of Tumor Immunosuppressive Microenvironment and Treatment Outcomes in Gastric Cancer: A Retrospective, Multicohort Study.

BACKGROUND: The tumor immunosuppressive microenvironment can influence treatment response and outcomes. A previously validated immunosuppression scoring system (ISS) assesses multiple immune checkpoints in gastric cancer (GC) using tissue-based assays. We aimed to develop a radiological signature for non-invasive assessment of ISS and treatment outcomes. METHODS: A total of 642 patients with resectable GC from three centers were divided into four cohorts. Radiomic features were extracted from portal venous-phase CT images of GC. A radiomic signature for predicting ISS (RISS) was constructed using the least absolute shrinkage and selection operator (LASSO) regression method. Moreover, we investigated the value of the RISS in predicting survival and chemotherapy response. RESULTS: The RISS, which consisted of 10 selected features, showed good discrimination of immunosuppressive status in three independent cohorts (area under the curve = 0.840, 0.809, and 0.843, respectively). Multivariate analysis revealed that the RISS was an independent prognostic factor for both disease-free survival (DFS) and overall survival (OS) in all cohorts (all p < 0.05). Further analysis revealed that stage II and III GC patients with low RISS exhibited a favorable response to adjuvant chemotherapy (OS: hazard ratio [HR] 0.407, 95% confidence interval [CI] 0.284-0.584); DFS: HR 0.395, 95% CI 0.275-0.568). Furthermore, the RISS could predict prognosis and select stage II and III GC patients who could benefit from adjuvant chemotherapy independent of microsatellite instability status and Epstein-Barr virus status. CONCLUSION: The new, non-invasive radiomic signature could effectively predict the immunosuppressive status and prognosis of GC. Moreover, the RISS could help identify stage II and III GC patients most likely to benefit from adjuvant chemotherapy and avoid overtreatment.

The novel role and function of LINC01235 in metastasis of gastric cancer cells by inducing epithelial-mesenchymal transition.

LncRNAs play a vital role in the tumorigenesis of gastric cancer (GC). This study determined that LINC01235 expression has greater fold changes by analyzing TCGA RNA-Seq data. The qRT-PCR assay confirmed that LINC01235 is significantly over-expressed in GC cells and tissues. Additionally, the overall survival analysis showed that patients with a higher LINC01235 expression had a poorer prognosis than those with a lower LINC01235 expression. Univariate Cox regression analysis indicated that high LINC01235 expression is positively correlated with poor prognosis. Moreover, LINC01235 was an independent poor prognostic marker for GC in multivariate Cox analysis. Invitro assays suggested that LINC01235 knockdown suppresses GC cell migration and invasion. GSEA revealed that high LINC01235 expression is strongly enriched in the EMT pathway. Western blotting results revealed that LINC01235 silencing decreases the expression of EMT-induced proteins. In conclusion, LINC01235 can promote GC cell metastasis via EMT and function as a prognostic biomarker.

High flow nasal oxygen versus conventional oxygen therapy in gastrointestinal endoscopy with conscious sedation: Systematic review and meta-analysis with trial sequential analysis.

OBJECTIVES: Although conventional oxygen therapy (COT) is widely used, hypoxemia frequently occurs in gastrointestinal endoscopy with conscious sedation and can lead to life-threatening consequences. High flow nasal oxygen (HFNO) has been applied to improve oxygenation in clinical entities. However, its efficacy to prevent hypoxemia in gastrointestinal endoscopy with conscious sedation has not been evaluated. METHODS: We searched databases to identify randomized controlled trials that compared the efficacy of HFNO with COT in gastrointestinal endoscopy with conscious sedation. The primary outcome was hypoxemia. Meta-analyses with trial sequential analysis were performed using a random-effects model. RESULTS: Eight trials with 3212 patients were included. Compared with COT, HFNO significantly reduced the risk of hypoxemia (eight trials; 3212 patients; risk ratio 0.30; 95% confidence interval [CI] 0.13-0.70). Trial sequential analysis showed that the cumulative Z curve did not cross the monitoring or futility boundaries, nor reach the required information size line, indicating that more trials are needed to reach a definitive conclusion. Subgroup analyses indicated the superiority of HFNO over COT with respect to hypoxemia in patients at low risk and high risk. HFNO further improved the lowest oxygen saturation (four trials; 459 patients; mean difference 2.30, 95% CI 0.84-3.77). CONCLUSIONS: Compared with COT, HFNO can reduce the risk of hypoxemia and improve the lowest oxygen saturation in gastrointestinal endoscopy with conscious sedation. However, the results should be interpreted with caution due to substantial heterogeneity and limited evidence. Further studies are needed to verify the preliminary findings.

[Three-Dimensional Nonlinear Finite Element Modeling and Analysis of Concomitant Atlanto-Occipital Fusion and Atlantoaxial Joint Dislocation].

OBJECTIVE: To establish, with finite element technology, a three-dimensional nonlinear finite element model of the normal occipital bone, atlas and axis and a three-dimensional nonlinear finite element model of concomitant atlanto-occipital fusion and atlantoaxial dislocation, providing a biomechanical method for clinical research on the upper cervical spine. METHODS: Finite element analysis was conducted with the CT data of a 27-year-old male volunteer, and a three-dimensional nonlinear finite element model, i.e., the normal model, of the normal occipital bone, atlas and axis was established accordingly. Finite element analysis was conducted with the CT data of a 35-year-old male patient with concomitant atlanto-occipital fusion and atlantoaxial dislocation. Then, the ideal state of a simple ligament rupture under high load was generated by computer simulation, and a three-dimensional nonlinear finite element model of concomitant atlanto-occipital fusion and atlantoaxial dislocation was established, i.e., the atlanto-occipital fusion with atlantoaxial dislocation model. For both models, a vertical upward torque of 1.5 N·m was applied on the upper surface of the occipital bone. Through comparative analysis of the two models under stress, the data of the range of motion (ROM) for flexion, extension, lateral bending, and rotation were examined. In addition, stress and deformation analysis with 1.5 N·m torque load was conducted to validate the effectiveness of the two three-dimensional nonlinear finite element models established in the study. RESULTS: When the normal model established in the study was under 1.5 N·m torque load, it exhibited a maximum ROM for each unit of flexion, extension, and the ROM approximated the experimental measurement results of human mechanics, confirming the validity of the simulation. The stress and deformation results of the model were consistent with the basic principles of mechanics. The moment-angular displacement of the model showed obvious nonlinear characteristics. Compared with the normal model, the atlanto-occipital fusion with atlantoaxial dislocation model showed reduced ROM of the atlanto-occipital joint under a torque of 1.5 N·m, while the ROM of the C1-C2 joint for the four conditions of flexion, posterior extention, lateral bending, and rotation under load, with the exception of rotating motion, was greatly increased compared with that of the normal model, which was in line with the actual clinical performance of the patient. CONCLUSION: The atlanto-occipital fusion with atlantoaxial dislocation model and the three-dimensional nonlinear finite element model of the normal occipital bone, atlas and axis were successfully established by finite element technology. The models had valid simulation and reliable kinematic characteristics, and could be used as a reliable tool to simulate clinical diseases.