A water transfer printing method for contact lenses surface 2D MXene modification to resist bacterial infection and inflammation.

Contact lenses (CLs) are prone to adhesion and invasion by pollutants and pathogenic bacteria, leading to infection and inflammatory diseases. However, the functionalization of CL (biological functions such as anti-fouling, antibacterial, and anti-inflammatory) and maintaining its transparency still face great challenges. In this work, as a member of the MXenes family, vanadium carbide (V2C) is modified onto CL via a water transfer printing method after the formation of a tightly arranged uniform film at the water surface under the action of the Marangoni effect. The coating interface is stable owing to the electrostatic forces. The V2C-modified CL (V2C@CL) maintains optical clarity while providing good biocompatibility, strong antioxidant properties, and anti-inflammatory activities. In vitro antibacterial experiments indicate that V2C@CL shows excellent performance in bacterial anti-adhesion, sterilization, and anti-biofilm formation. Last, V2C@CL displays notable advantages of bacteria elimination and inflammation removal in infectious keratitis treatment.

Burkitt's lymphoma in a young boy progressing to systemic lupus erythematosus during follow-up: a case report and literature review.

Introduction: Patients with systemic lupus erythematosus (SLE) are at a higher risk of developing cancer, particularly hematological malignancies such as lymphoma and leukemia. However, existing studies on this topic that assess cancer incidence following SLE diagnosis are limited. In addition, SLE can be diagnosed after cancer, although such cases in children have been rarely reported. Case report: We present the case of a 2.6-year-old boy who presented to our institute with fever and abdominal pain. His physical examination revealed a periumbilical mass, which was pathologically diagnosed as Burkitt's lymphoma. Autologous stem cell transplantation was performed to consolidate the effect of chemotherapy and reduce the risk of cancer relapse. He was diagnosed with SLE 5 years later, following the presentation of a fever with rash, positive autoantibodies, decreased complement, and kidney involvement. At the final follow-up, the patient was still alive and showed no recurrence of Burkitt's lymphoma or disease activity of SLE. Conclusion: Despite the low frequency of SLE in children with lymphoma, cancer and SLE may be induced by a common mechanism involving B-cell cloning and proliferation. Therefore, hematologists and rheumatologists should be aware of the occurrence of these two conditions during patient follow-up.

Paeonol interferes with lupus nephritis by regulating M1/M2 polarization of macrophages.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology. It is marked by the production of pathogenic autoantibodies and the deposition of immune complexes. Lupus nephritis (LN) is a prevalent and challenging clinical complications of SLE. Cortex Moutan contains paeonol as its main effective component. In this study, using the animal model of SLE induced by R848, it was found that paeonol could alleviate the lupus-like symptoms of lupus mouse model induced by R848 activating TLR7, reduce the mortality and ameliorate the renal damage of mice. In order to explore the mechanism of paeonol on lupus nephritis, we studied the effect of paeonol on the polarization of Raw264.7 macrophages in vitro. The experimental results show that paeonol can inhibit the polarization of macrophages to M1 and promote their polarization to M2, which may be related to the inhibition of MAPK and NF-κB signaling pathways. Our research provides a new insight into paeonol in the treatment of lupus nephritis, which is of great importance for the treatment of systemic lupus erythematosus and its complications.

Female frogs communicate with males through blinking.

Blinking is a behavior unique to animal taxa with motile eyelids, such as most amphibians and reptiles as well as all birds and mammals1. Eyelid movement has physiological functions, such as lubricating the cornea and washing away dust, but its potential signaling functions are not well understood1,2. The use of eyeblinks as a social signal is currently thought to be restricted to some primates, especially humans and their companion animals, but has not been verified in other taxa1,3,4. Here, through field observation and experiments, we demonstrate that female concave-eared torrent frogs (Odorrana tormota), which inhabit noisy streams, use eyeblinks to communicate with males to urge them to initiate amplexus for mating. Our findings reveal that eyeblinks may serve as a social signal in non-primate species.

Suppression of ZNF205-AS1/EGR4 positive feedback loop attenuates cisplatin resistance of non-small cell lung cancer cells via targeting miR-138-5p/OCT4 pathway.

Background: Long non-coding RNAs (lncRNAs) are frequently reported to involve in the onset and development of non-small cell lung cancer (NSCLC). Cisplatin (DDP) resistance continues to pose a daunting challenge for improving the prognosis of NSCLC patients. The current study intends to elucidate the molecular mechanisms underlying the function of lncRNA ZNF205 AS1/early growth response 4 (EGR4) positive feedback loop in DDP resistance of NSCLC. Methods: A series of assays, including real-time polymerase chain reaction (PCR), western blotting, flow cytometry, and dual-luciferase reporter, were performed to evaluate the effect of ZNF205-AS1/EGR4 loop in the established DDP-resistant A549 cell line and its progenitor A549 cell line. Immunohistochemistry (IHC) technique was conducted to investigate the expression pattern of EGR4 and octamer-binding protein 4 (OCT4) in NSCLC tissues. RNA pull-down assay was carried out to evaluate the interaction between miR-138-5p and EGR4 and OCT4. Transwell assay and wound healing assay was used to evaluate the invasive and migratory potential of cells subject to various treatment. The protein levels of Bcl2, Bax, Cl-caspase 3, Cl-PARP and OCT4 were measured in western blotting assay. Results: The levels of ZNF205-AS1, EGR4 and OCT4 were notably upregulated in post-chemotherapy DDP-resistant lung specimens, as opposed to those pre-chemotherapy, and in A549/DDP cells than the progenitor DDP-sensitive A549 cells. In contrast, the level of miR-138-5p was significantly reduced in A549/DDP cells (P<0.05). Luciferase reporter assay confirmed the interaction between ZNF205-AS1 and miRNA-138-5p. Protein-RNA interaction was validated between miR-138-5p, EGR4 and OCT4. The higher chemosensitivity of DDP-resistant cells induced by the loss-of-function of ZNF205-AS1 could be diminished by a miR-138-5p inhibitor. Conclusions: Our data demonstrated that miR-138-5p/OCT4 functions as a downstream effector of the ZNF205-AS1/EGR4 positive feedback loop and mediates resistance of NSCLC cells to DDP. Our work sheds light on the therapeutic strategies for NSCLC with DDP chemoresistance.

Multilayer factors associated with excess all-cause mortality during the omicron and non-omicron waves of the COVID-19 pandemic: time series analysis in 29 countries.

BACKGROUND: The COVID-19 pandemic has resulted in significant excess mortality globally. However, the differences in excess mortality between the Omicron and non-Omicron waves, as well as the contribution of local epidemiological characteristics, population immunity, and social factors to excess mortality, remain poorly understood. This study aims to solve the above problems. METHODS: Weekly all-cause death data and covariates from 29 countries for the period 2015-2022 were collected and used. The Bayesian Structured Time Series Model predicted expected weekly deaths, stratified by gender and age groups for the period 2020-2022. The quantile-based g-computation approach accounted for the effects of factors on the excess all-cause mortality rate. Sensitivity analyses were conducted using alternative Omicron proportion thresholds. RESULTS: From the first week of 2021 to the 30th week of 2022, the estimated cumulative number of excess deaths due to COVID-19 globally was nearly 1.39 million. The estimated weekly excess all-cause mortality rate in the 29 countries was approximately 2.17 per 100,000 (95% CI: 1.47 to 2.86). Weekly all-cause excess mortality rates were significantly higher in both male and female groups and all age groups during the non-Omicron wave, except for those younger than 15 years (P < 0.001). Sensitivity analysis confirmed the stability of the results. Positive associations with all-cause excess mortality were found for the constituent ratio of non-Omicron in all variants, new cases per million, positive rate, cardiovascular death rate, people fully vaccinated per hundred, extreme poverty, hospital patients per million humans, people vaccinated per hundred, and stringency index. Conversely, other factors demonstrated negative associations with all-cause excess mortality from the first week of 2021 to the 30th week of 2022. CONCLUSION: Our findings indicate that the COVID-19 Omicron wave was associated with lower excess mortality compared to the non-Omicron wave. This study's analysis of the factors influencing excess deaths suggests that effective strategies to mitigate all-cause mortality include improving economic conditions, promoting widespread vaccination, and enhancing overall population health. Implementing these measures could significantly reduce the burden of COVID-19, facilitate coexistence with the virus, and potentially contribute to its elimination.

Libman-Sacks endocarditis in a child with systemic lupus erythematosus: a case report and literature review.

Libman-Sacks endocarditis (LSE) is a cardiac condition characterized by the growth of verrucous vegetation. Although relatively rare in children, LSE is nevertheless a known cardiac manifestation of autoimmune diseases, including systemic lupus erythematosus (SLE). The mitral valve is the most commonly affected region, followed by the aortic valve, while the tricuspid and pulmonary valves are rarely affected. The management of established Libman-Sacks vegetation poses significant challenges, often necessitating surgical interventions, although surgery is not the primary treatment modality. Herein, we present the case of a 14-year-old Chinese female patient whose initial lupus manifestation included LSE, among other symptoms and signs that provided insights into the final diagnosis of SLE. After early comprehensive pharmacological treatment, tricuspid regurgitation and vegetation disappeared within 28 days without necessitating cardiac surgery, indicating that the resolution of LSE vegetation in this patient was achieved through a combination of immunosuppressive and anticoagulant therapy. These findings suggest the potential of this treatment approach as a viable model for the management of LSE in young patients.

Computationally Designed Molecules Modulate ALS-Related Amyloidogenic TDP-43307-319 Aggregation.

Abnormal cytosolic aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is observed in multiple diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and Alzheimer's disease. Previous studies have shown that TDP-43307-319 located at the C-terminal of TDP-43 can form higher-order oligomers and fibrils. Of particular interest are the hexamers that adopt a cylindrin structure that has been strongly correlated to neurotoxicity. In this study, we use the joint pharmacophore space (JPS) model to identify and generate potential TDP-43 inhibitors. Five JPS-designed molecules are evaluated using both experimental and computational methods: ion mobility mass spectrometry, thioflavin T fluorescence assay, circular dichroism spectroscopy, atomic force microscopy, and molecular dynamics simulations. We found that all five molecules can prevent the amyloid fibril formation of TDP-43307-319, but their efficacy varies significantly. Furthermore, among the five molecules, [AC0101] is the most efficient in preventing the formation of higher-order oligomers and dissociating preformed higher-order oligomers. Molecular dynamics simulations show that [AC0101] both is the most flexible and forms the most hydrogen bonds with the TDP-43307-319 monomer. The JPS-designed molecules can insert themselves between the ß-strands in the hexameric cylindrin structure of TDP-43307-319 and can open its structure. Possible mechanisms for JPS-designed molecules to inhibit and dissociate TDP-43307-319 oligomers on an atomistic scale are proposed.

Tau P301L mutation promotes core 4R tauopathy fibril fold through near-surface water structuring and conformational rearrangement.

Tau forms toxic fibrillar aggregates in a family of neurodegenerative diseases known as tauopathies. The faithful replication of tauopathy-specific fibril structures is a critical gap for developing diagnostic and therapeutic tools. This study debuts a strategy of identifying a critical segment of tau that forms a folding motif that is characteristic of a family of tauopathies and isolating it as a standalone peptide that form seeding-competent fibrils. The 19-residue jR2R3 peptide (295-313) spanning the R2/R3 splice junction of tau, in the presence of P301L, forms seeding-competent amyloid fibrils. This tau fragment contains the hydrophobic VQIVYK hexapeptide that is part of the core of every pathological tau fibril structure solved to-date and an intramolecular counter-strand that stabilizes the strand-loop-strand (SLS) motif observed in 4R tauopathy fibrils. This study shows that P301L exhibits a duality of effects: it lowers the barrier for the peptide to adopt aggregation-prone conformations and enhances the local structuring of water around the mutation site that facilitates site-specific dewetting and in-register stacking of tau to form cross ß-sheets. We solve a 3 Å cryo-EM structure of jR2R3-P301L fibrils with a pseudo 2 1 screw symmetry in which each half of the fibril's cross-section contains two jR2R3-P301L peptides. One chain adopts a SLS fold found in 4R tauopathies that is stabilized by a second chain wrapping around the SLS fold, reminiscent of the 3-fold and 4-fold structures observed in 4R tauopathies. These jR2R3-P301L fibrils are able to template full length tau in a prion-like fashion. Significance Statement: This study presents a first step towards designing a tauopathy specific aggregation pathway by engineering a minimal tau prion building block, jR2R3, that can template and propagate distinct disease folds. We present the discovery that P301L-among the widest used mutations in cell and animal models of Alzheimer's Disease-destabilizes an aggregation-prohibiting internal hairpin and enhances the local surface water structure that serves as an entropic hotspot to exert a hyper-localized effect in jR2R3. Our study suggests that P301L may be a more suitable mutation to include in modeling 4R tauopathies than for modelling Alzheimer's Disease, and that mutations are powerful tools for the purpose of designing of tau prion models as therapeutic tools.

Synthesis, structures and properties of two donor-acceptor acridone-based compounds.

Two donor-acceptor acridone-based compounds, namely, 2-{10-[4-(diphenylamino)phenyl]acridin-9-ylidene}malononitrile (TPA-AD-DCN), C34H22N4, and 2-{10-[4-(9H-carbazol-9-yl)phenyl]acridin-9-ylidene}malononitrile (CzPh-AD-DCN), C34H20N4, have been synthesized in high yield and their structures determined. TPA-AD-DCN and CzPh-AD-DCN crystallized in the centrosymmetric space groups P-1 and P21/c, respectively. Both molecules adopt a `butterfly-like' configuration of the common part of the structure and differences occur within the substituents on the acridine N atom. A Hirshfeld surface analysis showed that the H...H and C...H/H...C contacts constitute a high percentage of the intermolecular interactions. The optical and electrochemical properties, as well as theoretical calculations, of TPA-AD-DCN and CzPh-AD-DCN support the structural characterization of these materials. As crystallization-induced emission materials, TPA-AD-DCN and CzPh-AD-DCN are anticipated to be of potential use in the construction of promising optoelectronic materials.

Expression of concern: Bacterial self-defense antibiotics release from organic-inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties.

Expression of concern for 'Bacterial self-defense antibiotics release from organic-inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties' by Qingwen Xu, Nanoscale, 2017, 9, 19245-19254, https://doi.org/10.1039/C7NR07106J.

Expression of concern: Bacterial infection microenvironment-responsive enzymatically degradable multilayer films for multifunctional antibacterial properties.

Expression of concern for 'Bacterial infection microenvironment-responsive enzymatically degradable multilayer films for multifunctional antibacterial properties' by Qingqing Yao et al., J. Mater. Chem. B, 2017, 5, 8532-8541, https://doi.org/10.1039/C7TB02114C.

Computationally Designed Small Molecules Disassemble Both Soluble Oligomers and Protofibrils of Amyloid ß-Protein Responsible for Alzheimer's Disease.

Alzheimer's disease (AD) is one of the world's most pressing health crises. AD is an incurable disease affecting more than 6.5 million Americans, predominantly the elderly, and in its later stages, leads to memory loss, dementia, and death. Amyloid ß (Aß) protein aggregates have been one of the pathological hallmarks of AD since its initial characterization. The early stages of Aß accumulation and aggregation involve the formation of oligomers, which are considered neurotoxic and play a key role in further aggregation into fibrils that eventually appear in the brain as amyloid plaques. We have recently shown by combining ion mobility mass spectrometry (IM-MS) and atomic force microscopy (AFM) that Aß42 rapidly forms dodecamers (12-mers) as the terminal oligomeric state, and these dodecamers seed the early formation of Aß42 protofibrils. The link between soluble oligomers and fibril formation is one of the essential aspects for understanding the root cause of the disease state and is critical to developing therapeutic interventions. Utilizing a joint pharmacophore space (JPS) method, potential drugs have been designed specifically for amyloid-related diseases. These small molecules were generated based on crucial chemical features necessary for target selectivity. In this paper, we utilize our combined IM-MS and AFM methods to investigate the impact of three second-generation JPS small-molecule inhibitors, AC0201, AC0202, and AC0203, on dodecamer as well as fibril formation in Aß42. Our results indicate that AC0201 works well as an inhibitor and remodeler of both dodecamers and fibril formation, AC0203 behaves less efficiently, and AC0202 is ineffective.

Willingness to practice medicine and related influential factors among medical undergraduates during COVID-19: a cross-sectional study.

BACKGROUND: As the medical undergraduates constitute the future workforce in China, their career preferences hold a significant bearing on the quality of healthcare services, particularly in light of the ongoing COVID-19 pandemic. We aim to understand the current state of the willingness to practice medicine among medical undergraduates and to analyze the related influential factors. METHODS: During the COVID-19 epidemic, we conducted a cross-sectional survey via an online platform from February 15, 2022, to May 31, 2022, to collect participants' demographic information, psychology, and factors influencing their career choices. The general self-efficacy scale (GSES) was used to evaluate medical students' perceptions of their self-efficacy. Futhermore, we conducted multivariate logistic regression analyses to explore the influencing factors of medical undergraduates' willingness to pursure a caree in medicine. RESULTS: A total of 2348 valid questionnaires were included, and 1573 (66.99%) were willing to practice medicine for medical undergraduates after graduation. The mean GESE scores in the willingness group (2.87 ± 0.54) were significantly higher than those of the unwillingness group (2.73 ± 0.49). The multiple logistic regression showed that several factors were positively associated with willingness to practice medicine as a career, including students' GSES score (OR = 1.87), current major, household income, personal ideals (OR = 1.97), family support (OR = 1.44), high income (OR = 1.77), and social respect (OR = 2.19). Compared with those who were very afraid of COVID-19, students who did not express any fear towards the COVID-19 pandemic had a higher preference for choosing the medical profession as a career. Conversely, students thinking of high tension in the doctor-patient relationship, heavy workload, and long training were less likely to choose medical work after graduation. CONCLUSIONS: The study highlights a noteworthy prevalence of medical undergraduates who expressed their willingness to pursue medicine as a career post-graduation. Several factors, including but not limited to current major, household income, psychological factors, personal preferences, and career needs or preferences, were significantly associated with this willingness. Moreover, the impact of the COVID-19 pandemic on medical students' career choices cannot be overlooked.

The plasma levels of Dickkopf-1 elevated in patients with Juvenile Idiopathic Arthritis.

BACKGROUND: To explore the role of two major inhibitors of Wnt signal pathway, Dickkopf-1(DKK-1) and Sclerostin (SOST), in the pathogenesis of juvenile idiopathic arthritis (JIA). METHODS: 88 patients with JIA, which including 49 patients with enthesitis-related arthritis (ERA), 21 oligoarthritis (oJIA) and 18 polyarthritis (pJIA), and 36 age-and sex-matched children as healthy controls (HC) were enrolled in this study. The plasma levels of DKK-1 and SOST, measured using commercially available ELISA kits, were analyzed the correlation between the levels of DKK-1/SOST and JIA, and were analyzed in 14 patients with JIA during before and after treatment. RESULTS: Plasma levels of DKK-1 were significantly higher in the patients with JIA than that in HC, the elevation of DKK-1 level was positively correlated with HLA-B27 positive JIA. DKK-1 levels dropped significantly in patient with JIA after treatment (P < 0.05). There was no significant change in SOST levels among different subtypes of JIA, patients with JIA during before and after treatment, and HC. CONCLUSION: It was suggested that the DKK-1 may have a certain correlation with the pathogenesis of JIA, and DKK-1 levels are more closely related to the HLA-B27 positive-ERA. IMPACT: The abnormally elevated levels of Dickkopf-1 (DKK-1) may be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). DKK-1 levels were more closely related to the HLA-B27 positive-enthesitis-related arthritis (ERA). DKK-1 is an inhibitor of Wnt signaling pathway that promotes osteoblastic new bone formation; it is very rare for pediatric patients with HLA-B27 positive-ERA to manifest typical spondylitis, while sacroiliac arthritis is relatively common, which may be related to the high levels of DKK-1, which is consistent with the early stage of ankylosing spondylitis (AS).

Major Infections of Newly Diagnosed Childhood-Onset Systemic Lupus Erythematosus.

Objective: To evaluate the risk of major infections in children with newly diagnosed childhood-onset systemic lupus erythematosus (cSLE). Methods: Predictors of major infections were identified by the multivariable logistic regression. Major infection free was defined as no major infection events within 6 months after the diagnosis of cSLE. The Kaplan-Meier survival plot was performed. A prediction model for major infection events was established and examined by receiver operating characteristic (ROC) curve analysis. Results: A total of 98 eligible patients were recorded in the medical charts. Sixty-three documented events of major infections were found in 60 (61.2%) cSLE patients. Furthermore, 90.5% (57/63) of infection events occurred within the first 6 months after the diagnosis of cSLE. The high SLEDAI (SLEDAI >10), lupus nephritis and lymphocyte count <0.8×109/L were predictors for major infections. The CALL score (Children with high disease activity [SLEDAI >10], lymphopenia, and LN) was defined by the number of predictors. Patients were then categorized into two groups: low-risk (score 0-1) and high-risk (score 2-3). Patients in the high-risk group had higher rates of the major infection occurrence than those in the low-risk group during the 6 months after the diagnosis of the cSLE (P<0.001) (HR:14.10, 95% CI 8.43 to 23.59). The ROC curve analysis indicated that the CALL score was effective both in the whole cSLE cohort [area under the curve (AUC) = 0.89, 95% CI: 0.81-0.97] and in the subgroup of lung infections (n = 35) (AUC = 0.79, 95% CI: 0.57-0.99). Conclusion: High disease activity, LN and lymphopenia were predictors for major infections in newly diagnosed cSLE patients. Specific predictors help identify the cSLE patients with the high risk of major infections. The CALL score could be a useful tool to stratify cSLE patients in practice.

High-power continuous-wave optical waveguiding in a silica micro/nanofibre.

As miniature fibre-optic platforms, micro/nanofibres (MNFs) taper-drawn from silica fibres have been widely studied for applications from optical sensing, nonlinear optics to optomechanics and atom optics. While continuous-wave (CW) optical waveguiding is frequently adopted, so far almost all MNFs are operated in low-power region (e.g., <0.1 W). Here, we demonstrate high-power low-loss CW optical waveguiding in MNFs around 1550-nm wavelength. We show that a pristine MNF, even with a diameter down to 410 nm, can waveguide an optical power higher than 10 W, which is about 30 times higher than demonstrated previously. Also, we predict an optical damage threshold of 70 W. In high-power CW waveguiding MNFs, we demonstrate high-speed optomechanical driving of microparticles in air, and second harmonic generation efficiency higher than those pumped by short pulses. Our results may pave a way towards high-power MNF optics, for both scientific research and technological applications.

Autoantibody-based subgroups and longitudinal seroconversion in juvenile-onset systemic lupus erythematosus.

OBJECTIVE: To explore the clinical value of autoantibody-based subgroup framework and the trend of autoantibody fluctuation in juvenile-onset SLE (JSLE). METHODS: Eighty-seven patients with JSLE were retrospectively collected and divided into subgroups via a two-step cluster based on the status of nine autoantibodies (double-stranded-DNA (dsDNA), nucleosome, histone, ribosomal P protein, Smith (Sm), u1-ribonucleoprotein (RNP), Sjögren's syndrome antigen A (SSA)/Ro52, SSA/Ro60, Sjögren's syndrome antigen B (SSB)/La). The final model selected in this study was based on adequate goodness of fit of the Silhouette coefficient and clinical interpretability. Clinical manifestations, organ involvements and disease activity were compared among the subgroups. Fluctuation in autoantibody status was also collected and analysed. Flare-free survival rates of the patients with positive/negative seroconversion and patients without seroconversion were studied by the Kaplan-Meier method and compared using a log-rank test. RESULTS: Two clusters were identified: subgroup 1 (positive anti-Sm/RNP group) and subgroup 2 (negative anti-Sm/RNP group). There were more lupus nephritis (LN) and neuropsychiatric SLE (NPSLE) cases in subgroup 1 than in subgroup 2. Patients in subgroup 1 exhibited higher SLE Disease Activity Index scores compared with those in subgroup 2. Furthermore, anti-ribosomal P protein (61.1%), anti-nucleosome (58.3%) and anti-dsDNA (54%) were most commonly positive autoantibodies. A progressive decrease in the frequency of patients with positive results was demonstrated during the follow-up years. The decrease was notable for anti-dsDNA, anti-nucleosome and anti-ribosomal P protein (remaining 27.27%, 38.89% and 45.00% positive in the fifth year, respectively). While for those negative at baseline diagnosis, the decrease in the frequency of negative results was progressive but modest. Kaplan-Meier curve showed that the flare-free survival of patients with positive seroconversion was significantly lower than those without seroconversion and those with negative seroconversion (p<0.001). CONCLUSIONS: In children with SLE, subgroups based on autoantibody profile can be applied to differentiate phenotypes and disease activity. Two important organ involvements, LN and NPSLE, are more common in patients with positive anti-Sm/RNP autoantibodies. Positive seroconversion may provide a valuable perspective for assessing flare, and it is worthwhile to retest the array of autoantibodies during follow-up.

Intensity modulated radiation therapy for elderly patients with esophageal cancer: Our experience.

The aim of this study was to discuss the treatment mode of radical radiotherapy for elderly patients with esophageal cancer. The clinical data of 136 elderly patients (≥60 years old) with esophageal cancer (EC) who received radical intensity-modulated radiotherapy in the Second Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019 were retrospectively analyzed. Cox risk model was used for multivariate prognostic analysis, and Kaplan Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Cox regression analysis showed that ECOG score, basic diseases, T stage, radiation dose, radiation injury and chemotherapy were the prognostic factors of elderly patients. The median OS of the radiotherapy group, concurrent chemoradiotherapy group and sequential chemoradiotherapy group were 17, 41 and 10 months (p=0.009), respectively. The 3-year OS and PFS of concurrent intravenous chemotherapy and oral chemotherapy were 50%, 42.9% and 34.1%, 28.6% (p=0.641, p=0.702), respectively. The median OS of IFI and ENI were 23 and 24 months (p=0.219) and the local recurrence rate were 59.8% and 43.2% (p=0.069), respectively, but the incidence and mortality of radiation pneumonia and esophagitis in ENI were higher. The 3-year OS and PFS the low-dose group (≤60Gy) and high-dose group (>60Gy) were 19.1%, 40.4% and 14.9%, 29.2% (p=0.012, p=0.049), respectively. In conclusion, for elderly patients with inoperable EC, radical chemoradiotherapy should be considered a preferable selection. Among them, oral drugs and high-dose involved field irradiation exhibited better curative effects and safety.

A Novel "Inside-Out" Intraocular Nanomedicine Delivery Mode for Nanomaterials' Biological Effect Enhanced Choroidal Neovascularization Occlusion and Microenvironment Regulation.

Photodynamic therapy (PDT) is commonly used in choroidal neovascularization (CNV) treatment due to the superior light transmittance of the eye. However, PDT often leads to surrounding tissue damage and further microenvironmental deterioration, including exacerbated hypoxia, inflammation, and secondary neovascularization. In this work, Pt nanoparticles (NPs) and Au NPs decorated zeolitic imidazolate framework-8 nanoplatform is developed to load indocyanine green for precise PDT and microenvironment amelioration, which can penetrate the internal limiting membrane through Müller cells endocytosis and target to CNV by surface-grafted cyclo(Arg-Gly-Asp-d-Phe-Lys) after intravitreal injection. The excessive H2 O2 in the CNV microenvironment is catalyzed by catalase-like Pt NPs for hypoxia relief and enhanced PDT occlusion of neovascular. Meanwhile, Au NPs show significant anti-inflammatory and anti-angiogenesis properties in regulating macrophages and blocking vascular endothelial growth factor (VEGF). Compared with verteporfin treatment, the mRNA expressions of hypoxia-inducible factor-1α and VEGF in the nanoplatform group are downregulated by 90.2% and 81.7%, respectively. Therefore, the nanoplatform realizes a comprehensive CNV treatment effect based on the high drug loading capacity and biosafety. The CNV treatment mode developed in this work provides a valuable reference for treating other diseases with similar physiological barriers that limit drug delivery and similar microenvironment.