[Risk factors for recurrence of childhood acute lymphoblastic leukemia after treatment with the Chinese Children's Cancer Group ALL-2015 protocol]. / CCCG-ALL-2015æ–¹æ¡ˆæ²»ç–—å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— å¤å‘çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence. METHODS: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed. RESULTS: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol. CONCLUSIONS: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

miR-124-3p regulates the proliferation and differentiation of retinal progenitor cells through SEPT10.

Retinal degenerative diseases such as glaucoma, retinitis pigmentosa, and age-related macular degeneration pose serious threats to human visual health due to lack of effective therapeutic approaches. In recent years, the transplantation of retinal progenitor cells (RPCs) has shown increasing promise in the treatment of these diseases; however, the application of RPC transplantation is limited by both their poor proliferation and their differentiation capabilities. Previous studies have shown that microRNAs (miRNA) act as essential mediators in the fate determination of stem/progenitor cells. In this study, we hypothesized that miR-124-3p plays a regulatory role in the fate of RPC determination by targeting Septin10 (SEPT10) in vitro. We observed that the overexpression of miR124-3p downregulates SEPT10 expression in RPCs, leading to reduced RPC proliferation and increased differentiation, specifically towards both neurons and ganglion cells. Conversely, antisense knockdown of miR-124-3p was shown to boost SEPT10 expression, enhance RPC proliferation, and attenuate differentiation. Moreover, overexpression of SEPT10 rescued miR-124-3p-caused proliferation deficiency while weakening the enhancement of miR-124-3p-induced-RPC differentiation. Results from this study show that miR-124-3p regulates RPC proliferation and differentiation by targeting SEPT10. Furthermore, our findings enable a more comprehensive understanding into the mechanisms of proliferation and differentiation of RPC fate determination. Ultimately, this study may be useful for helping researchers and clinicians to develop more promising and effective approaches to optimize the use of RPCs in treating retinal degeneration diseases.

Design of Fourier ptychographic illuminator for single full-FOV reconstruction.

Fourier ptychographic microscopy (FPM) is a spatial-temporal-modulation high-throughput imaging technique via a sequential angle-varied LED illumination. Therefore, the illuminator is one of the key components and the design of this illuminator is significant. However, because of the property of spherical wave, partial coherence, and aperture-induced vignetting, the acquired images must be processed in blocks first, and rely on parallel reconstruction via a graphics processing unit (GPU). The high cost makes it unappealing compared with commercial whole slide imaging system via a low-cost central processing unit (CPU). Especially, the vignetting severely destroys the space-invariant model and induces obvious artifacts in FPM, which is the most difficult problem. The conventional method is to divide the field of view (FOV) into many tiles and omit those imperfect images, which is crude and may discards low frequency information. In this paper, we reevaluated the conditions of vignetting in FPM. Through our analysis, the maximum side length of FOV is 0.759 mm for a single full-FOV reconstruction via a 4×/0.1 NA objective and a 4 mm spacing LED array in theory, while almost 1.0 mm can be achieved in practice due to the tolerance of algorithm. We found that FPM system can treat the vignetting coefficient Vf below 0.1 as brightfield images and Vf lager than 0.9 as darkfield images, respectively. We reported an optimized distribution for designing an illuminator without vignetting effect according to the off-the-shelf commercial products, which can reconstruct full FOV in one time via a CPU. By adjusting the distribution of LED units, the system could retrieve the object with the side length of FOV up to 3.8 mm for a single full-FOV reconstruction, which achieves the largest FOV that a typical 4×/0.1 NA objective with the field number of 22 mm can afford.

Redundant information model for Fourier ptychographic microscopy.

Fourier ptychographic microscopy (FPM) is a computational optical imaging technique that overcomes the traditional trade-off between resolution and field of view (FOV) by exploiting abundant redundant information in both spatial and frequency domains for high-quality image reconstruction. However, the redundant information in FPM remains ambiguous or abstract, which presents challenges to further enhance imaging capabilities and deepen our understanding of the FPM technique. Inspired by Shannon's information theory and extensive experimental experience in FPM, we defined the specimen complexity and reconstruction algorithm utilization rate and reported a model of redundant information for FPM to predict reconstruction results and guide the optimization of imaging parameters. The model has been validated through extensive simulations and experiments. In addition, it provides a useful tool to evaluate different algorithms, revealing a utilization rate of 24%±1% for the Gauss-Newton algorithm, LED Multiplexing, Wavelength Multiplexing, EPRY-FPM, and GS. In contrast, mPIE exhibits a lower utilization rate of 19%±1%.

Effects of blue light-exposed retinal pigment epithelial cells on the process of ametropia.

Ametropia is one of the most common ocular disorders worldwide, to which almost half of visual impairments are attributed. Growing evidence has linked the development of ametropia with ambient light, including blue light, which is ubiquitous in our surroundings and has the highest photonic energy among the visible spectrum. However, the underlying mechanism of blue light-mediated ametropia remains controversial and unclear. In the present study, our data demonstrated that exposure of the retinal pigment epithelium (RPE) to blue light elevated the levels of the vital ametropia-related factor type Ⅰ collagen (COL1) via ß-catenin inhibition in scleral fibroblasts, leading to axial ametropia (hyperopic shift). Herein, our study provides evidence for the vital role of blue light-induced RPE dysfunction in the process of blue light-mediated ametropia, providing intriguing insights into ametropic aetiology and pathology by proposing a link among blue light, RPE dysfunction and ametropia.

Regular arrangement of collecting venules under endoscopy for predicting a Helicobacter pylori-negative stomach: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The regular arrangement of collecting venules (RAC) refers to the appearance of multiple regular tiny veins in the body of the stomach and is considered to be very effective for identifying gastric mucosa with non-Helicobacter pylori infection. This meta-analysis was conducted to systematically evaluate the value of the sign in predicting a Helicobacter pylori-negative stomach and the relevant factors that may affect the performance of this prediction. METHODS: Two biomedical databases (PubMed and EMBASE) were systematically searched through April 20, 2020. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the SROC curve (AUC) were calculated. RESULTS: Fourteen articles with 4070 patients were included. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for the RAC in predicting non-Hp infection were 0.80 (0.67-0.89), 0.97 (0.93-0.98), 24.8 (12.2-50.8), 0.21 (0.12-0.36), 120 (47-301) and 0.97 (0.19-1.00), respectively. CONCLUSIONS: The RAC is a valuable endoscopic feature for the prediction of patients without Hp infection.

[Effect of swertiamarin, gentiopicrin and sweroside on cell apoptosis and expression of Bcl-2 in rheumatoid arthritis fibroblast-like synoviocytes].

The aim of this paper was to discuss the effect of swertiamarin, gentiopicrin and sweroside on rheumatoid arthritis fibroblast-like synoviocytes(RA-FLSs) and B-cell lymphoma-2(Bcl-2) and their mechanisms. ZINC database and RCSB PDB database were retrieved for 3 D chemical structures of swertiamarin, gentiopicrin and sweroside and 3 D target protein structures. AutoDock Mgltools 1.5.6, AutoDockVina 1.1.2 and pyMOL 2.2.0 were applied for molecular docking to analyze the relationship between Bcl-2(1 GJH) target protein and important ingredients. The cell apoptosis of RA-FLSs was tested by Annexin V-FITC. The Bcl-2 protein expression of RA-FLSs treated with different ingredients was tested by Western blot. The Bcl-2 mRNA expression of RA-FLSs treated with different ingredients was tested by RT-PCR. Swertiamarin, gentiopicrin and sweroside were docked well with Bcl-2(1 GJH). The binding energy of swertiamarin was-6.9 kcal·mol~(-1), the binding energy of gentiopicrin was-6.7 kcal·mol~(-1) and the binding energy of sweroside was-6.4 kcal·mol~(-1). Compared with the blank group, the Bcl-2 protein expression of each group were reduced, while that of the gentiopicrin group was the highest(P<0.01). Compared with the blank group, the Bcl-2 mRNA expression of each groups were reduced. Gentiopicrin can reduce the Bcl-2 protein expression and the Bcl-2 mRNA expression, so as to promote the RA-FLSs apoptosis.

Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria. / ä¸åŒè¯Šæ–­æ ‡å‡†ä¸‹å„¿ç«¥æ€¥æ€§ä¸æ˜Žè°±ç³»ç™½è¡€ç— çš„ä¸´åºŠç‰¹ç‚¹å’Œé¢„åŽåˆ†æž.

OBJECTIVES: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria. METHODS: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group (n=28) and myeloid expression group (n=11). The clinical features, treatment, and prognosis were compared between the two groups. RESULTS: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% (P<0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P<0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1, positive MLL-r, and hyperleukocytosis (white blood cell count ≥50×109/L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P>0.05). CONCLUSIONS: ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.

miR-17 regulates the proliferation and differentiation of retinal progenitor cells by targeting CHMP1A.

MicroRNAs have a vital effect on the differentiation of many types of progenitor cells. Recent studies have suggested that miR-17 plays an important role in the differentiation process of brain neural progenitor cells (NPC). Nevertheless, its detailed functions in regulating retinal progenitor cells (RPC) remain unclear. In our study, overexpression and knockdown of miR-17 were performed by transfecting RPC with mimics and inhibitors, respectively. Next, we investigated the role of miR-17 in RPC proliferation and differentiation by the following experiments: qPCR, CCK8, Edu staining, immunostaining and Western blot. The results revealed that miR-17 inhibited RPC proliferation but enhanced differentiation. Furthermore, according to a web-based database analysis, we identified charged multivesicular body protein 1A (CHMP1A) as a target gene. A dual luciferase reporter system showed that miR-17 specifically binds to the CHMP1A 3' untranslated region (UTR). Next, our data showed upregulation of miR-17 decreased CHMP1A protein level, causing reduced proliferation and enhanced differentiation of RPC. Downregulation of miR-17 led to enhanced CHMP1A protein expression, increased RPC proliferation and decreased differentiation. Taken together, our data provide a proven pathway by which miR-17 regulates RPC proliferation and differentiation by targeting CHMP1A.

Diagnostic value of X-ray, endoscopy, and high-resolution manometry for hiatal hernia: A systematic review and meta-analysis.

BACKGROUND AND AIM: Hiatal hernia (HH) has been found in a large number of people, but there has been no unified way to diagnose it. The aim of this study was to compare the diagnostic efficiency of X-ray, endoscopy, and high-resolution manometry (HRM) in the diagnosis of HH using surgical diagnosis of HH as the gold standard. METHODS: Two biomedical databases (PubMed and EMBASE) were systematically searched through January 26, 2019. The pooled sensitivity, specificity, and area under the SROC curve (AUC) were calculated, and the AUC statistical significance was compared by Tukey's multiple comparisons test. RESULTS: A total of 5337 patients in seven articles were included. The pooled sensitivity, specificity, and AUC for X-ray were 0.63 (0.46-0.77), 0.85 (0.69-0.94), and 0.80 (0.77-0.84), respectively, for diagnosing HH. The pooled estimates for endoscopy in diagnosing HH were as follows: sensitivity, 0.72 (0.39-0.91); specificity, 0.80 (0.70-0.87); and AUC, 0.82 (0.78-0.85). Similarly, the corresponding values for HRM were 0.77 (0.70-0.83); 0.92 (0.85-0.96), and 0.9527. Tukey's multiple comparisons tests were used to compare the AUCs of the three diagnostic methods: No significant differences were found between X-ray and endoscopy (P = 0.7293), and HRM was superior to X-ray (P = 0.0127) and endoscopy (P = 0.0442). CONCLUSIONS: High-resolution manometry may exhibit a better diagnostic performance for hiatal hernia. In contrast, X-ray and endoscopy may not be the best methods, and there was no significant difference in diagnostic efficiency between the X-ray and endoscopy.

Serum C-Reactive Protein and Max Polyp Diameter Are Useful Markers of Complications of Small-Intestinal Polypectomy.

BACKGROUND This study aimed to identify the risk factors of complications after small-intestinal polypectomy by single-balloon enteroscopy (SBE), and to assess the value of serum C-reactive protein (CRP) and the max polyp diameter (Dmax) in predicting postoperative complications of small-intestinal polypectomy. MATERIAL AND METHODS Between April 2017 and April 2018, clinical data from 37 patients who underwent small-intestinal polypectomy were retrospectively analyzed. RESULTS Thirty-seven small-intestinal polypectomy procedures (18 oral and 19 anal) were carried out in 37 patients (M: F 20: 17; age 35.6±13.0 years). A total of 1081 small-intestine polyps were removed. Three patients (8.1%) had bleeding and 3 patients (8.1%) had perforation after small-intestinal polypectomy. Based on multivariate logistic analysis, CRP [1.104 (95% CI 1.022-1.191)] was the only risk factor for complications among the patients. According to the area under the receiver operating characteristic (AUROC) curve, CRP (27.5 mg/L), Dmax (3.5 cm), and the combination of CRP + Dmax appear to be predictive factors for complications after small-intestinal polypectomy. CONCLUSIONS SBE is an effective endoscopic tool for patients with small-intestinal polyps. CRP, Dmax, and the combination of CRP+Dmax may be potential predictors of complications from small-intestinal polypectomy.

Usnic Acid Induces Cycle Arrest, Apoptosis, and Autophagy in Gastric Cancer Cells In Vitro and In Vivo.

BACKGROUND Usnic acid (UA), a secondary metabolite, is mainly derived from certain lichen species. Growing evidence suggests that UA has antitumor, anti-oxidative, anti-inflammatory, and other activities in a variety of cancer cells. However, the antitumor effect of UA in gastric cancer cells (GC) is unclear. The aim of this investigation was to assess the antitumor effect of UA in GC cells in vitro and in vivo, and to explore the underlying mechanisms. MATERIAL AND METHODS Cell proliferation was measured by CCK8 assay, the arrest of cell cycle was assessed by flow cytometry, and cellular apoptosis was observed via Hoechst 33258 staining assay. Expression levels of apoptosis-related proteins (activated caspase-3 and PARP, Bax, Bcl2) and autophagy-associated proteins (LC3-II and p62) were verified through Western blot analysis. H&E staining and immunohistochemistry were carried out in the subcutaneously implanted BGC823 tumor model in a nude mouse experiment. RESULTS In vitro, we demonstrated that UA was significantly effective in inducing morphological changes, inhibiting the cell proliferation dose- and time-dependently, arresting the cell cycle phase, promoting cancer cellular apoptosis, and inducing autophagy activity. In vivo, compared to mice treated with 5-FU alone, UA treatment was significantly more effective in suppressing the tumor growth without affecting body weight, and in regulating the amount of Bax and Bcl2 in tumor tissues. CONCLUSIONS UA induces cell cycle arrest and autophagy and exerts anti-proliferative and apoptotic effects by modulating expression of apoptosis-related proteins in stomach neoplasm cells, and has a better antitumor effect compared to 5-Fu in the xenograft model.

[Research progress on pharmacological action and clinical application of Stephania Tetrandrae Radix].

Stephania Tetrandrae Radix is one of the common traditional Chinese medicines, which has bitter and pungent taste as well as cold properties. It can subside edema, get rid of rheumatism and relieve pain. Therefore, it is mainly used for the treatment of rheumatism arthralgia, edema, dysuria, athlete's foot, swollen wet sores and other diseases in traditional Chinese medicine(TCM). Stephania Tetrandrae Radix is mainly composed of dual-benzyl isoquinoline alkaloids, including tetrandrine, fangchinoline and so on. Modern pharmacology research shows that Stephania Tetrandrae Radix and its main components have a wide range of pharmacological activities in the anti-inflammatory, anti-pathogenic microorganisms, anti-tumor, anti-hypertensive, anti-arrhythmic, anti-myocardial ischemia, anti-fibrosis, anti-silicosis, inhibiting scar and other aspects, with broad application prospect. Stephania Tetrandrae Radix is often applied with compatibility of other Chinese medicines in clinically, and has achieved obvious effects in the treatment of rheumatoid arthritis, cardiovascular disease, cancer, hypertension, liver ascites and other diseases. There are some representative prescriptions, such as Fangji Fuling decoction, Fangji huangqi decoction, Jijiao Lizhuang pill, Xuanbi decoction, and compound Hanfangji granule. In this paper, the pharmacological effects and clinical applications of Stephania Tetrandrae Radix in the past ten years were reviewed, providing reference for its further development and application.

Novel therapeutic perspectives for wet age-related macular degeneration: RGD-modified liposomes loaded with 2-deoxy-D-glucose as a promising nanomedicine.

Choroidal neovascularization (CNV), characterized as a prominent feature of wet age-related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide-modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2-DG interfered with N-glycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.

An immunotherapeutic artificial vitreous body hydrogel to control choroidal melanoma and preserve vision after vitrectomy.

Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.

Thermodynamic 2D Silicene for Sequential and Multistage Bone Regeneration.

Bone healing is a multistage process involving the recruitment of cells, revascularization, and osteogenic differentiation, all of which are modulated in the temporal sequence to maximize cascade bone regeneration. However, insufficient osteoblast cells, poor blood supply, and limited bone induction at the site of critical-sized bone defect broadly impede bone repair. 2D SiO2 -silicene@2,2'-,azobis(2-[2-imidazolin-2-yl] propane) (SNSs@AIPH) with inherent thermodynamic property and osteoinductive activity is therefore designed and engineered for sequentially efficient bone repair. By means of controllable NIR-II irradiation, the integrated SNSs@AIPH stimulates the generation of appropriate intracellular reactive oxygen species, which accelerates early bone marrow mesenchymal stem cells (BMSCs) proliferation and angiogenesis remarkably. Importantly, as silicon-based 2D nanoparticles, the engineered SNSs@AIPH with high biocompatibility features distinct bioactivity to significantly promote BMSCs osteogenesis differentiation by activating TGFß and BMP pathways. In a rat cranial defect model, SNSs@AIPH-NIR-II leads to a comparable increase of BMSCs proliferation and local vascularization at an early stage, followed by significant osteogenic differentiation, synergically resulting in a highly effective bone repair. Collectively, the fascinating characteristics and exceptional bone repair efficiency of NIR-II-mediated SNSs@AIPH allow it to be a promising bionic-oriented strategy for bone regeneration, broadening a new perspective in the application of cell-instructive biomaterials in bone tissue engineering.

Injectable Anti-Inflammatory Supramolecular Nanofiber Hydrogel to Promote Anti-VEGF Therapy in Age-Related Macular Degeneration Treatment.

Age-related macular degeneration (AMD) is a major cause of visual impairment and severe vision loss worldwide, while the currently available treatments are often unsatisfactory. Previous studies have demonstrated both inflammation and oxidative-stress-induced damage to the retinal pigment epithelium are involved in the pathogenesis of aberrant development of blood vessels in wet AMD (wet-AMD). Although antivascular endothelial growth factor (VEGF) therapy (e.g., Ranibizumab) can impair the growth of new blood vessels, side effects are still found with repeated monthly intravitreal injections. Here, an injectable antibody-loaded supramolecular nanofiber hydrogel is fabricated by simply mixing betamethasone phosphate (BetP), a clinic anti-inflammatory drug, anti-VEGF, the gold-standard anti-VEGF drug for AMD treatment, with CaCl2 . Upon intravitreal injection, such BetP-based hydrogel (BetP-Gel), while enabling long-term sustained release of anti-VEGF to inhibit vascular proliferation in the retina and attenuate choroidal neovascularization, can also scavenge reactive oxygen species to reduce local inflammation. Remarkably, such BetP-Gel can dramatically prolong the effective treatment time of conventional anti-VEGF therapy. Notably, anti-VEGF-loaded supramolecular hydrogel based on all clinically approved agents may be readily translated into clinical use for AMD treatment, with the potential to replace the current anti-VEGF therapy.

Bifunctional MXene-Augmented Retinal Progenitor Cell Transplantation for Retinal Degeneration.

Retinal degeneration, characterized by the progressive loss of retinal neurons, is the leading cause of incurable visual impairment. Retinal progenitor cells (RPCs)-based transplantation can facilitate sight restoration, but the clinical efficacy of this process is compromised by the imprecise neurogenic differentiation of RPCs and undermining function of transplanted cells surrounded by severely oxidative retinal lesions. Here, it is shown that ultrathin niobium carbide (Nb2 C) MXene enables performance enhancement of RPCs for retinal regeneration. Nb2 C MXene with moderate photothermal effect markedly improves retinal neuronal differentiation of RPCs by activating intracellular signaling, in addition to the highly effective RPC protection by scavenging free radicals concurrently, which has been solidly evidenced by the comprehensive biomedical assessments and theoretical calculations. A dramatically increased neuronal differentiation is observed upon subretinal transplantation of MXene-assisted RPCs into the typical retinal degeneration 10 (rd10) mice, thereby contributing to the efficient restoration of retinal architecture and visual function. The dual-intrinsic function of MXene synergistically aids RPC transplantation, which represents an intriguing paradigm in vision-restoration research filed, and will broaden the multifunctionality horizon of nanomedicine.

Eyedrop-based macromolecular ophthalmic drug delivery for ocular fundus disease treatment.

Therapeutic antibodies are extensively used to treat fundus diseases by intravitreal injection, as eyedrop formulation has been rather challenging due to the presence of ocular barriers. Here, an innovative penetrating carrier was developed for antibody delivery in eyedrop formulations. We found that fluorocarbon-modified chitosan (FCS) would self-assemble with proteins to form nanocomplexes, which could effectively pass across the complicated ocular structure to reach the posterior eye segments in both mice and rabbits. In a choroidal melanoma-bearing mouse model, eyedrops containing FCS/anti-PDL1 could induce stronger antitumor immune responses than those triggered by intravenous injection of anti-PDL1. Moreover, in choroidal neovascularization-bearing mouse and rabbit models, FCS/anti-VEGFA eyedrops effectively inhibited vascular proliferation, achieving comparable therapeutic responses to those observed with intravitreal injection of anti-VEGFA. Our work presents an effective delivery carrier to treat fundus diseases using eyedrop of therapeutic proteins, which may enable at-home treatment of many eye diseases with great patient compliance.

Use of proton pump inhibitors for the risk of gastric cancer.

BACKGROUND: This study aimed to systematically analyze the association between long-term use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). METHODS: We performed a systematic search of articles on the relationship between long-term use of PPIs and the risk of GC from PubMed and EMBASE. We calculated the pooled odds ratio of GC in PPI users compared to non-PPI users using random-effects models. RESULTS: This meta-analysis included 18 studies from 20 different databases with 4348,905 patients enrolled. In the random effects model, we found that an increased risk of GC among PPI users (OR = 1.94; 95% CI [1.43, 2.64]). The long-term use of PPIs compared with histamine-2 receptor antagonist users did not increase the risk of GC (OR = 1.65; 95% CI [0.92, 2.97]). Stratified analysis showed that PPI users had a significantly increased risk of noncardia GC (OR = 2.53; 95% CI [2.03, 3.15]), but had a relatively small relationship with the risk of gastric cardia cancer. (OR = 1.79; 95% CI [1.06, 3.03]). With the extension of PPI use time, the estimated risk value decreases (<1 year: OR = 6.33, 95% CI [3.76, 10.65]; 1-3 years: OR = 1.82, 95% CI [1.30, 2.55]; >3 years: OR = 1.25, 95% CI [1.00, 1.56]). Despite Helicobacter pylori eradication, the long-term use of PPIs did not alter the increased risk of GC (OR = 2.29; 95% CI [1.57, 3.33]). CONCLUSION: Our meta-analysis found that PPI use may be associated with an increased risk of GC. Further research on the causal relationship between these factors is necessary.