Effects of cyclical short-term food deprivation and refeeding on compensatory growth and gene expression of SOD, GPX and HSP70 in Schizothorax wangchiachii.

The present study evaluated the effects of cyclical short-term food deprivation and refeeding on growth performance, body composition, and gene expression of SOD, GPX and HSP70 in Schizothorax wangchiachii.The experimental design included four feeding protocols for eight weeks: feeding every day of the week (control), starvation for one day and refeeding for six days per week (S1F6 treatment), starvation for two days and refeeding for five days per week (S2F5 treatment), and starvation for three days and refeeding for four days per week (S3F4 treatment). The results showed that no significant difference in final body weight, specific growth rate and feed conversion efficiency were observed among the treatments (P > 0.05).The feeding rate significantly increased with the duration of food deprivation per week compared to the control (P < 0.05). The expression levels of HSP70 showed no significant differences in the gill, liver and spleen of S.wangchiachii subjected to different feed restriction regimes(P > 0.05), but in the kidney, the expression levels of HSP70 were significantly downregulated in S1F6 and S2F5 compared to the control(P < 0.05). The expression levels of SOD and GPX in the examined tissues were not affected by the different feed restriction regimes(P > 0.05). In conclusion, full compensatory growth was observed in S.wangchiachii under eight cycles of food deprivation and refeeding. Hyperphagia was the main mechanism of compensatory growth of S.wangchiachii.

Bifunctional Thiourea-Ammonium Salt Catalysts Derived from Cinchona Alkaloids: Cooperative Phase-Transfer Catalysts in the Enantioselective Aza-Henry Reaction of Ketimines.

An efficient enantioselective aza-Henry reaction of aryl α-ketoester-derived ketimines has been realized by using bifunctional thiourea-ammonium salt phase-transfer catalysts, which were derived from quinine. A variety of aryl α-ketoester-derived N-Ts ketimines were investigated, and the corresponding products were obtained in high to excellent yields (up to 99%) with good to high enantioselectivities (up to >99% ee).

Typicality effects in picture-word interference paradigm: An evaluation of the response exclusion hypothesis.

The response exclusion hypothesis suggests that the polarity of semantic effects in the picture-word interference paradigm is determined by the response-relevant criteria. Semantic interference effects would be observed when semantically related distractor words satisfy the response-relevant criteria; otherwise, semantic facilitation effects should be found. The purpose of this study was to further evaluate the response exclusion hypothesis by exploring the typicality effects in pictures naming. In two experiments, pictures of objects were named either in the context of verb distractor words with different typicality of passive functions or in the context of adjective distractor words with different typicality of characteristics. Facilitation effects were observed in context of typical verbs and adjectives, while interference effects were observed in the context of atypical verbs and adjectives. Given that neither typical nor atypical distractor words satisfy the response-relevant criteria to produce noun, these findings are problematic for the response exclusion hypothesis. Role of syntagmatic relationships in lexical retrieval was invoked to explain present findings.

Elevated hydrogen sulfide levels in vitreous body and plasma in patients with proliferative diabetic retinopathy.

PURPOSE: Hydrogen sulfide (H2S), a colorless gas, has been confirmed to be a gaseous messenger molecule and an endogenous stimulus for angiogenesis recently. This study was performed to investigate the role of H2S in diabetic retinopathy. METHODS: Blood samples were collected from normal controls and patients with diabetes. Vitreous samples were collected from patients with proliferative diabetic retinopathy (PDR) and patients with rhegmatogenous retinal detachment. Patients were grouped into diabetic patients without diabetic retinopathy (non-DR), with nonproliferative DR, and with PDR. Concentrations of H2S and vascular endothelial growth factor in the plasma and vitreous body were detected using a spectrophotometer. RESULTS: A decreased H2S level in the plasma was observed in non-DR group (41.89 ± 8.52 µM, P < 0.05), and an increased H2S level in the plasma was observed in PDR group (60.49 ± 11.14 µM, P < 0.001), when compared with that in normal controls (49.67 ± 9.72 µM). There was no difference in plasma H2S level between patients with nonproliferative DR (54.13 ± 8.61 µM) and normal controls. In the vitreous body, H2S levels in PDR group were significantly higher (76.80 ± 24.08 µM, P < 0.001) than that in rhegmatogenous retinal detachment group (24.37 ± 11.25 µM). Levels of vascular endothelial growth factor in plasma from patients with diabetes were significantly lower (P < 0.001) than that in normal controls. Vascular endothelial growth factor levels in the vitreous body from diabetic patients with PDR were significantly higher (885.61 ± 190.41 pg/mL, P < 0.001) than that from patients with rhegmatogenous retinal detachment (89.98 ± 19.56 pg/mL). Seven days after an intravitreal injection of ranibizumab, a significantly decreased H2S level (55.58 ± 7.20 µM, P < 0.05) was observed in the vitreous body in patients with PDR when compared with that (75.07 ± 12.95 µM) in the vitreous body collected just before intravitreal injection. CONCLUSION: These results indicated that anti-vascular endothelial growth factor may downregulate the H2S level in the vitreous body, and H2S may play a role in the development of DR. Hydrogen sulfide may be a novel target for the therapy of DR.

SIPA1 promotes angiogenesis by regulating VEGF secretion in Müller cells through STAT3 activation.

Diabetic retinopathy (DR) is a prevalent complication of diabetes that can lead to vision loss. The chronic hyperglycemia associated with DR results in damage to the retinal microvasculature. Müller cells, as a kind of macroglia, play a crucial role in regulating the retinal vascular microenvironment. The objective of this study was to investigate the role of signal-induced proliferation-associated protein 1 (SIPA1) in regulating angiogenesis in Müller cells. Through proteomics, database analysis, endothelial cell function tests, and Western blot detection, we observed an up-regulation of SIPA1 expression in Müller cells upon high glucose stimulation. SIPA1 expression contributed to VEGF secretion in Müller cells and regulated the mobility of retinal vascular endothelial cells. Further investigation of the dependence of SIPA1 on VEGF secretion revealed that SIPA1 activated the phosphorylation STAT3, leading to its translocation into the nucleus. Overexpression of SIPA1 combined with the STAT3 inhibitor STATTIC demonstrated the regulation of SIPA1 in VEGF expression, dependent on STAT3 activation. These findings suggest that SIPA1 promotes the secretion of pro-angiogenic factors in Müller cells by activating the STAT3 signaling pathway, thereby highlighting SIPA1 as a potential therapeutic target for DR.

On implications of somatostatin in diabetic retinopathy.

Somatostatin, a naturally produced neuroprotective peptide, depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina. In this review, we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases. Insufficient neuroprotection, which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy, triggers retinal neurovascular unit impairment and microvascular damage. Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy. Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated. In one such trial (EUROCONDOR), topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction, but had no impact on the onset of diabetic retinopathy. Overall, we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy. In order to achieve early prevention of diabetic retinopathy initiation, and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy, several issues need to be addressed. These include the needs to: a) update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration, b) identify patient subgroups who would benefit from somatostatin analog supplementation, c) elucidate the interactions of somatostatin, particularly exogenously-delivered somatostatin analogs, with other retinal peptides in the context of hyperglycemia, and d) design safe, feasible, low cost, and effective administration routes.

Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the UCHL-1/NF-κB signaling pathway.

Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.

5-Bromo-3,4-dihydroxybenzaldehyde stabilizes diabetic retinal neurovascular units by inhibiting the inflammatory microenvironment.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness characterized by damage to the retinal neurovascular unit, which is caused by hyperglycemia-induced metabolic and inflammatory responses. 5-Bromo-3,4-dihydroxybenzaldehyde (BDB) is a compound derived from marine red algae and known for its anti-inflammatory effects. METHODS: This study aimed to investigate the potential protective effects of BDB on DR using primary human retinal vascular endothelial cells and retinal tissue explants. The analysis involved assessing vascular integrity, expression of tight junction protein, hyperglycemia-induced permeability, and retinal ganglion cell (RGC) apoptosis. The protective effect of BDB in maintaining the diabetic retinal neurovascular units was verified using type 1 diabetic mouse models. Additionally, the inhibitory effect of BDB on the levels of inflammatory cytokines TNF-α, IL-1ß, and IL-6 were examined. RESULTS: In vitro experiments revealed that BDB promoted vascular integrity, inhibited the transcription of pro-inflammatory factors, and alleviated hyperglycemia-induced permeability. BDB also protected RGC from hyperglycemia-induced apoptosis. In diabetic mice models, BDB treatment maintained the integrity of diabetic retinal neurovascular units and inhibited the secretion of TNF-α, IL-1ß, and IL-6. CONCLUSION: BDB demonstrated a protective effect on DR by inhibiting the secretion of inflammatory factors, suggesting its potential as a therapeutic agent for the treatment of DR. Further research is warranted to validate its safety and efficacy for clinical application.

Early-stage predictors of deterioration among 3145 nonsevere SARS-CoV-2-infected people community-isolated in Wuhan, China: A combination of machine learning algorithms and competing risk survival analyses.

OBJECTIVE: To determine which early-stage variables best predicted the deterioration of coronavirus disease 2019 (COVID-19) among community-isolated people infected with severe acute respiratory syndrome coronavirus 2 and to test the performance of prediction using only inexpensive-to-measure variables. METHODS: Medical records of 3145 people isolated in two Fangcang shelter hospitals (large-scale community isolation centers) from February to March 2020 were accessed. Two complementary methods-machine learning algorithms and competing risk survival analyses-were used to test potential predictors, including age, gender, severity upon admission, symptoms (general symptoms, respiratory symptoms, and gastrointestinal symptoms), computed tomography (CT) signs, and comorbid chronic diseases. All variables were measured upon (or shortly after) admission. The outcome was deterioration versus recovery of COVID-19. RESULTS: More than a quarter of the 3145 people did not present any symptoms, while one-third ended isolation due to deterioration. Machine learning models identified moderate severity upon admission, old age, and CT ground-glass opacity as the most important predictors of deterioration. Removing CT signs did not degrade the performance of models. Competing risk models identified age ≥ 35 years, male gender, moderate severity upon admission, cough, expectoration, CT patchy opacity, CT consolidation, comorbid diabetes, and comorbid cardiovascular or cerebrovascular diseases as significant predictors of deterioration, while a stuffy or runny nose as a predictor of recovery. CONCLUSIONS: Early-stage prediction of COVID-19 deterioration can be made with inexpensive-to-measure variables, such as demographic characteristics, severity upon admission, observable symptoms, and self-reported comorbid diseases, among asymptomatic people and mildly to moderately symptomatic patients.

Visual impairment and blindness caused by retinal diseases: A nationwide register-based study.

Background: Retinal disorders cause substantial visual burden globally. Accurate estimates of the vision loss due to retinal diseases are pivotal to inform optimal eye health care planning and allocation of medical resources. The purpose of this study is to describe the proportion of visual impairment and blindness caused by major retinal diseases in China. Methods: A nationwide register-based study of vitreoretinal disease covering all 31 provinces (51 treating centres) of mainland China. A total of 28 320 adults diagnosed with retinal diseases were included. Participants underwent standardised ocular examinations, which included best-corrected visual acuity (BCVA), dilated-fundus assessments, and optical coherence tomography. Visual impairment and blindness are defined using BCVA according to the World Health Organization (WHO) (visual impairment: <20/63-≥20/400; blindness: <20/400) and the United States (visual impairment: <20/40-≥20/200; blindness: <20/200) definitions. The risk factors of vision loss were explored by logistic regression analyses. Results: Based on the WHO definitions, the proportions for unilateral visual impairment and blindness were 46% and 18%, respectively, whereas those for bilateral visual impairment and blindness were 31% and 3.3%, respectively. Diabetic retinopathy (DR) accounts for the largest proportion of patients with visual impairment (unilateral visual impairment: 32%, bilateral visual impairment: 60%) and blindness (unilateral blindness: 35%; bilateral blindness: 64%). Other retinal diseases that contributed significantly to vision loss included age-related macular degeneration, myopic maculopathy, retinal vein occlusion, and rhegmatogenous retinal detachment and other macular diseases. Women (bilateral vision loss: P = 0.011), aged patients (unilateral vision loss: 45-64 years: P < 0.001, ≥65 years: P < 0.001; bilateral vision loss: 45-64 years: P = 0.003, ≥65 years: P < 0.001 (reference: 18-44 years)) and those from Midwest China (unilateral and bilateral vision loss: both P < 0.001) were more likely to suffer from vision loss. Conclusions: Retinal disorders cause substantial visual burden among patients with retinal diseases in China. DR, the predominant retinal disease, is accountable for the most prevalent visual disabilities. Better control of diabetes and scaled-up screenings are warranted to prevent DR. Specific attention should be paid to women, aged patients, and less developed regions.

[The protective effects on the function and structure of retinae in diabetic rats by intravitreal injection of cyclosporin A].

OBJECTIVE: To investigate the electrophysiological and morphological changes of retinae after intravitreal injection of cyclosporin A (CsA) in experimental diabetic rats. METHODS: Experimental study. SD diabetic mellitus (DM) rat models were induced with intraperitoneal injection of streptozotocin. The rats were divided into four groups, with 9 rats in each group:the normal control (group CON), the diabetic rats with or without CsA intravitreal injection respectively (group DM + CsA and group DM), and the diabetic rats with dimethyl sulfoxide (DMSO) intravitreal injection (group DM + DMSO). The intravitreal injection of CsA or contrast solution was performed 4 weeks after the modeling. The retinal function of rats was examined by electroretinogram (ERG) 48 hours after the intravitreal injection. All rats were sacrificed and the structural changes of retina were observed by optical and transmission electron microscope. The datas of ERG including amplitudes and latencies of a-wave and b-wave were analyzed by One-way ANOVA and Bonferroni post hoc test. RESULTS: There was difference in ERG b-wave among the 4 groups under different stimuli light intensity (F = 14.760 - 28.890, all P value < 0.01). And there was difference in ERG a-wave among the 4 groups when the stimuli light intensity ≥ -0.35 log cd×s×m(-2) (F = 12.510, 15.500, both P value < 0.01). Comparing to the group CON (ERG a-wave: 82.43 ± 26.68, ERG b-wave: 208.40 ± 51.20), the ERG a-wave and b-wave amplitudes of group DM (ERG a-wave: 39.71 ± 7.61, ERG b-wave: 92.20 ± 24.42) and group DM + DMSO (ERG a-wave: 37.63 ± 17.25, ERG b-wave: 93.11 ± 22.50)(t = 5.448 - 7.872, all P value < 0.05), and the ERG b-wave of group DM + CsA (160.10 ± 43.39) (t = 3.299, P < 0.05) were declined in dark adaptation, while the ERG a-wave (63.91 ± 20.32) of group DM ± CsA had no difference (P > 0.05). The a-wave and b-wave amplitudes of group DM + CsA were significantly increased compared to the other two groups in dark adaptation (t = 3.203 - 4.759, both P < 0.05). Under optical microscope, group DM, DM + DMSO and DM + CsA had outer nuclear layer (ONL) disorder. Under transmission electron microscope, there were ultrastructure changes of the three groups. Furthermore, the ONL disorder and ultrastructure changes of group DM + CsA were less severe than the other two groups. CONCLUSIONS: Functional and morphological changes are evident in the early stages in DM rats. Intravitreal injection with CsA shows protective effects on the nerve function in DM retina.

5-Bromo-3,4-dihydroxybenzaldehyde attenuates endothelial cells injury from high glucose-induced damage.

Hyperglycemia triggers metabolic and inflammatory responses, which lead to vascular inflammation and consequently induce microvascular and/or macrovascular diabetic complications. 5-bromo-3,4-dihydroxybenzaldehyde (BDB), a marine red algae-derived bromophenol compound, is found to have diverse bioactivities, including the effect of anti-inflammation and anti-diabetes, though the mechanism of which is still unclear. To evaluate the anti-vasculopathy of BDB and explore the possible mechanism involved. Firstly, MTT assay was used to optimize the treatment concentration of glucose and BDB with HUVECs. Subsequently, we adopted two concentrations of BDB (50 µM and 100 µM) to verify the protective effect of BDB on vascular model, which was established by HUVECs from high glucose (30 mM)-induced damage. The cell migration and tube formation were used to evaluate the function of HUVECS. Moreover, the related mechanisms were analyzed by assays for flow cytometry, ELISA, qPCR, intracellular ROS and western blot. The present study demonstrated that BDB could protect endothelial cells from apoptosis caused by high glucose treatment. BDB also significantly reduced the secretion of inflammatory cytokines, such as TNF-α, IL-1ß and IL-6, induced by high glucose, which was also in agreement to the decrease of p65 protein expression and activities of NF-ĸB regulated by BDB. The reactive oxygen species (ROS) production and phosphorylation of 38 protein expression were also down-regulated by BDB compared to high glucose alone treatment. Furthermore, BDB reserved the endothelial cells functions of migration and tube formation under high glucose condition, which suggested that BDB could be a potential candidate in treating vascular inflammation induced by hyperglycemia.

Association between immunity and viral shedding duration in non-severe SARS-CoV-2 Omicron variant-infected patients.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory-related disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than 200 countries worldwide are affected by this disease. The Omicron variant of SARS-CoV-2 is the major epidemic variant worldwide and is characterized by higher infectivity. However, the immunity and risk factors for prolonged viral elimination in patients with non-severe SARS-CoV-2 Omicron variant infections are unclear. Therefore, this study aimed to examine the relationship between immunity and duration of viral elimination in non-severe SARS-CoV-2 Omicron variant-infected patients in Shanghai. Methods: In total, 108 non-severe SARS-CoV-2 Omicron variant-infected patients from Shanghai New International Expo Center Fangcang Shelter Hospital were recruited in this study. They were further allocated to the early elimination (EE) and prolonged elimination (PE) groups according to SARS-CoV-2 nucleic acid positivity duration. Results: Compared to patients with EE, those with PE had increased serum concentrations of interleukin (IL)-5, IL-6, and IL-8; higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR); lower lymphocyte, eosinophil, and red blood cell counts; and lower concentrations of hemoglobin and albumin (ALB). In lymphocyte subpopulation analysis, lower numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, and NK cells and a higher CD4/CD8 ratio were observed in patients with PE. In addition, correlation analysis results revealed that cycle threshold values of SARS-CoV-2 Omicron variant ORF1ab and N were negatively correlated with IL-6 and IL-8 levels and positively correlated with eosinophil count in patients with COVID-19. Finally, multivariate regression analysis showed that ALB, CD4/CD8 ratio, NLR, and eosinophil count were predictors of the SARS-CoV-2 Omicron variant elimination. Conclusion: In this study, we identified that the ALB, CD4/CD8 ratio, NLR, and eosinophil count were risk factors for prolonged viral elimination in non-severe SARS-CoV-2 Omicron variant-infected patients. These factors might be efficient indicators in the diagnosis, evaluation, and prognosis monitoring of the disease.

The Effect of Graphene Nanofiller on the Surface Structure and Performance of Epoxy Resin-Polyhedral Oligomeric Silsesquioxane (EP-POSS).

Epoxy resin-polyhedral oligomeric silsesquioxane (EP-POSS) has excellent mechanical properties and hydrophobic properties. In order to adapt for application in sensor and photovoltaic fields, graphene, nano-SiO2 and nano-ZnO were used to modify EP-POSS. FTIR was used to characterize changes on the surface structure after introducing nanoparticles. The change of hydrophobicity was measured using a contact angle test. TEM test results showed that nanoparticles were successfully inserted between the graphene sheets. However, the content of Si on the surface was low, as the cage structure of POSS in the molecular chain was coated by epoxy groups. XRD tests indicated that nanoparticles facilitated the dispersion of graphene in EP-POSS. XPS characterized the chemical state and content of the elements, confirming that the addition of graphene can induce the enrichment of Si on the surface of EP-POSS, which had a shielding effect on the main chain and improved the hydrophobicity. Wear resistance and adhesion tests showed that, after the introduction of nanoparticles, the EP-POSS coating film met the requirements of graphene materials.

Hydrophobic Epoxy Caged Silsesquioxane Film (EP-POSS): Synthesis and Performance Characterization.

Hydrophobic films are widely used in aerospace, military weapons, high-rise building exterior glass, and non-destructive pipeline transportation due to their antifouling and self-cleaning properties. This paper details the successful preparation of hydrophobic epoxy caged sesquioxane (EP-POSS) via two steps of simple organic synthesis, along with studies on the effects of viscosity and reaction time on the reaction. Interestingly, the EP-POSS presented a large contact angle of 125°, indicating its excellent hydrophobicity. The surface micromorphology was observed via FE-SEM (field emission scanning electron microscopy), transmission electron microscopy (TEM), and atomic force microscopy (AFM), and the structural composition and elemental contents were analyzed via X-ray photoelectron spectroscopy (XPS) and energy-dispersive spectrometry (EDS). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) tests showed that EP-POSS had excellent thermal properties, and the first degradation reaction occurred at 354 °C. The mechanical performance and abrasion resistance results demonstrated that EP-POSS could be used in solar panels.

Application Value of Magnetic Resonance Radiomics and Clinical Nomograms in Evaluating the Sensitivity of Neoadjuvant Chemotherapy for Nasopharyngeal Carcinoma.

OBJECTIVE: To predict the sensitivity of nasopharyngeal carcinoma (NPC) to neoadjuvant chemotherapy (NACT) based on magnetic resonance (MR) radiomics and clinical nomograms prior to NACT. MATERIALS AND METHODS: From January 2014 to July 2015, 284 consecutive patients with pathologically confirmed NPC underwent 3.0 T MR imaging (MRI) before initiating NACT. The patients' data were randomly assigned to a training set (n = 200) or a test set (n = 84) at a ratio of 7:3. The clinical data included sex, tumor (T) stage, lymph node (N) stage, American Joint Committee on Cancer (AJCC) stage, and the plasma concentration of Epstein-Barr virus (EBV) DNA. The regions of interest (ROI) were manually segmented on the axial T2-weighted imaging (T2WI) and enhanced T1-weighted imaging (T1WI) sequences using ITK-SNAP software. The radiomics data were post-processed using AK software. Moreover, the Maximum Relevance Minimum Redundancy (mRMR) algorithm and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for dimensionality reduction to screen for the features that best predicted the treatment efficacy, and clinical risk factors were used in combination with radiomics scores (Rad-scores) to construct the clinical radiomics-based nomogram. DeLong's test was utilized to compare the area under the curve (AUC) values of the clinical radiomics-based nomogram, radiomics model, and clinical nomogram. Decision curve analysis (DCA) was employed to evaluate each model's net benefit. RESULTS: The clinical nomogram was constructed based on data from patients who were randomly assigned according to T2WI and enhanced T1WI sequences. In the training set, the T2WI sequence-based clinical radiomics nomogram and the radiomics model outperformed the clinical nomogram in predicting the NACT efficacy (AUC, 0.81 vs. 0.60, p = 0.001279 and 0.76 vs. 0.60, p = 0.03026). These findings were well-verified in the test set. The enhanced T1WI sequence-based clinical radiomics nomogram exhibited better performance in predicting treatment efficacy than the clinical nomogram (AUC, 0.79 vs. 0.62, respectively; p = 0.0000834). The DCA revealed that the T2WI and clinical radiomics-based nomograms resulted in a net benefit in predicting the NACT efficacy. CONCLUSION: The clinical radiomics-based nomogram improved the prediction of NACT efficacy, with the T2WI sequence-based clinical radiomics achieving the best effect.

Co-infusion of high-dose haploidentical donor cells and CD19-targeted CART cells achieves complete remission, successful donor engraftment and significant CART amplification in advanced ALL.

Autologous CD19-targeted chimeric antigen receptor-modified T cells (CD19-CART) remarkably improved the outcome of patients with advanced B-cell acute lymphoblastic leukemia (B-ALL). However, the application and outcomes of allogeneic CART cells is still uncertain. Two patients with advanced B-ALL were enrolled to receive a co-infusion of high-dose human leukocyte antigen-haploidentical donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cells (GPBMCs; 21.01-25.34 × 108/kg) and the same donor-derived CD19-targeted CART cells (8.44-22.19 × 106/kg) without additional in vitro gene-editing following a reinduction chemotherapy as precondition. They achieved complete remission and full donor chimerism (FDC) with ongoing 20- and 4-month leukemia-free survival. A significant amplification of donor CART cells was detected in peripheral blood and/or cerebrospinal fluid and was associated with the formation of FDC. The highest amount of copies of the donor CART cells reached 4962 per µg of genomic DNA (gDNA) and 2449 per µg of gDNA, and the longest persistence was 20 months associated with B cell aplasia. Two patients experienced Grade II or III cytokine release syndromes and developed controllable Grade II intestinal acute graft-versus-host disease (GVHD) or limited chronic oral GVHD. High-dose donor GPBMC infusion may enhance amplification and persistence of haploidentical CD19-targeted CART cells, suggesting an alternative therapy for advanced B-ALL patients.

Prognostic value of radiologic extranodal extension and its potential role in future N classification for nasopharyngeal carcinoma.

PURPOSE: We evaluated the prognostic value of various grades of radiologic extranodal extension (rENE) and their potential roles in N-classification refinement for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All NPC patients treated with IMRT in our institution between 2005 and 2011 were included. Pre-treatment MR of cN+ cases were reviewed and rENE was recorded asG0: lymph nodes (LNs) without rENE; G1: tumor infiltrating beyond individual nodal capsule(s) into the surrounding fat plane; G2: coalescent nodal mass with unequivocal evidence of rENE; G3: tumor infiltrating beyond nodal capsule into adjacent structures. Multivariable analysis (MVA) assessed prognostic value of rENE for distant metastasis (DM) and death adjusted for age, gender, LDH, T-classification, N-classification, and chemotherapy cycles. RESULTS: A total of 1390 of 1616 (86%) NPC were cN+, and rENE was detected in 826/1390 (59%) patients: 256 (18.4%) G1-rENE, 487 (35%) G2-rENE, and 83 (6%) G3-rENE. MVA confirmed that G2-/G3-rENE had increased risk of DM (HR: 2.05/3.18, both p < 0.001) and death (HR: 1.62/2.39, p = 0.002/p < 0.001), while G1-rENE was non-prognostic (DM: p = 0.172; death: p = 0.320). We propose a refined N: New-N1: N1/N2 without G2-/G3-rENE; New-N2: N1_G2-rENE; New-N3: N2_G2-rENE, N1/N2_G3-rENE, or N3. The New-N classification had a lower AIC and higher c-index for DM (AIC: 3809.6 vs 3830.9; c-index: 0.700 vs. 0.677) and death (AIC: 3693.8 vs. 3705.9; c-index: 0.735 vs. 0.725) versus TNM-8 N. CONCLUSIONS: G2- and G3-rENE are independently prognostic for DM and death in NPC. Compared to the TNM8 N-classification, a refined N-classification incorporating G2- and G3-rENE improves prognostication of DM and mortality risk.

High-grade radiologic extra-nodal extension predicts distant metastasis in stage II nasopharyngeal carcinoma.

BACKGROUND: To investigate the prognostic value of radiologic extra-nodal extension (rENE) in stage II nasopharyngeal carcinoma (NPC). METHODS: Stage II NPC patients with N1 category (n = 365) were enrolled and divided into three groups according to the situation of rENE: without rENE, suspected rENE, and confirmed rENE (grades: A, infiltration into surrounding fat; B, matted nodes; C, infiltration into adjacent structures). RESULTS: Only high-grade rENE (including matted nodes and infiltration into adjacent structures) could significantly influence the survival outcomes, patients with high-grade rENE had significantly poorer survival than those without, with the 7-year distant metastasis-free survival and overall survival demonstrated to be 78.5% vs 93.0% (P < .001) and 81.9% vs 89.9% (P = .05), respectively. High-grade rENE, as defined in our study, is a stable criterion, with high intra-rater and inter-rater consistency. CONCLUSION: High-grade rENE was an evaluable predictor that could help with the selection of stage II patients with high risk of distant metastasis.