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Abstract Delay-bandwidth product (DBP) is a key metric in slow light waveguides, requiring a balance between a large group index and broad bandwidth—two parameters that often involve a trade-off. Here, we propose and demonstrate a slow light waveguide with large DBP using a pseudospin-polarized transverse electromagnetic mode. This waveguide features a folded edge configuration that supports a 200% relative bandwidth from quasistatic limit (zero frequency) and an arbitrarily large group index. Owing to the pseudospin-polarized design, the dense folding would not introduce backscattering and the associated group velocity dispersion (GVD). The resulting gapless linear dispersion and pulse transmission behavior in folded edge waveguide are observed in microwave experiments. Our scheme provides a way to overcome the trade-off between group index and working bandwidth in slow light waveguide, which has potential applications in broadband optical buffering, light-matter interaction enhancement, terahertz radiation source and time domain processing.

Abstract 3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

AIM: To explore the effect of epidermal growth factor receptor (EGFR) inhibition by erlotinib and EGFR siRNA on epidermal growth factor (EGF)-induced activation of retinal pigment epithelium (RPE) cells. METHODS: Human RPE cell line (ARPE-19 cells) was activated by 100 ng/mL EGF. Erlotinib and EGFR siRNA were used to intervene EGF treatment. Cellular viability, proliferation, and migration were detected by methyl thiazolyl tetrazolium (MTT) assay, bromodeoxyuridine (BrdU) staining assay and wound healing assay, respectively. EGFR/protein kinase B (AKT) pathway proteins and N-cadherin, α-smooth muscle actin (α-SMA), and vimentin were tested by Western blot assay. EGFR was also determined by immunofluorescence staining. RESULTS: EGF treatment for 24h induced a significant increase of ARPE-19 cells' viability, proliferation and migration, phosphorylation of EGFR/AKT proteins, and decreased total EGFR expression. Erlotinib suppressed ARPE-19 cells' viability, proliferation and migration through down regulating total EGFR and AKT protein expressions. Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin, α-SMA, and vimentin proteins. Similarly, EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation, viability, and migration, phosphorylation of EGFR/AKT proteins, and up-regulation of N-cadherin, α-SMA, and vimentin proteins. CONCLUSION: Erlotinib and EGFR-knockdown suppress EGF-induced cell viability, proliferation, and migration via EGFR/AKT pathway in RPE cells. EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy (PVR).

BackgroundRecently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer.MethodsThis is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution.DiscussionThis is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma.Clinical trial registrationClinicalTrials.Gov, identifier NCT06266871.

Background: As prostaglandin medications, crucial in glaucoma treatment, become more widely used, their local adverse events are increasingly observed. Objectives: To evaluate the common adverse events of four clinically commonly used prostaglandin F (FP) receptor agonists in the treatment of glaucoma in the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Design: We screened and analyzed the generic and brand names of latanoprost, bimatoprost, travoprost, and tafluprost in the FAERS database and summarized and cleaned the baseline information of subjects receiving the above-mentioned drugs. Methods: Perform descriptive statistical analysis on the baseline information of subjects using the drugs. Conduct disproportionality analysis of drug-related adverse events. The criteria for positive signals of adverse events are established by simultaneously meeting the thresholds set by four methods: the ratio of reported odds, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. Additionally, assess the cumulative risk curves for drug-induced time of the aforementioned drugs and use one-way ANOVA to compare differences in drug-induced time across different groups. Results: The study included 1567 latanoprost, 1517 bimatoprost, 696 travoprost, and 82 tafluprost subjects. Adverse events mainly affected eye disorders, with significant issues in iris hyperpigmentation, ocular pemphigoid, corneal endothelial cell loss, periorbital fat atrophy, corneal irritation, eyelash growth, and ocular hyperemia. The time to onset varied among drugs, with latanoprost showing the longest (mean days = 344.37) and bimatoprost the shortest duration (mean days = 155.65; p

AIM: To explore the effects of hepatocyte growth factor (HGF) on retinal pigment epithelium (RPE) cell behaviors. METHODS: The human adult retinal pigment epithelial cell line-19 (ARPE-19) were treated by HGF or mesenchymal-epithelial transition factor (MET) inhibitor SU11274 in vitro. Cell viability was detected by a Cell Counting Kit-8 assay. Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay, respectively. The expression levels of MET, phosphorylated MET, protein kinase B (AKT), and phosphorylated AKT proteins were determined by Western blot assay. The MET and phosphorylated MET proteins were also determined by immunofluorescence assay. RESULTS: HGF increased ARPE-19 cells' viability, proliferation and migration, and induced an increase of phosphorylated MET and phosphorylated AKT proteins. SU11274 significantly reduced cell viability, proliferation, and migration and decreased the expression of MET and AKT proteins. SU11274 suppressed HGF-induced increase of viability, proliferation, and migration in ARPE-19 cells. Additionally, SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins. CONCLUSION: HGF enhances cellular viability, proliferation, and migration in RPE cells through the MET/AKT signaling pathway, whereas this enhancement is suppressed by the MET inhibitor SU11274. HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

Abstract Background Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. Methods The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a −/− and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. Results We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. Conclusions We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Topological boundary modes, which are localized at the edge of topological materials, have received significant attention for their various applications in robust waveguides, optical cavities, and topological lasers. To envision their further applications in tunable devices, we propose and demonstrate a scheme to dynamically manipulate topological boundary modes by exploiting the two translation parameters of photonic crystals. We find that the translation not only transports the Wannier state similar to conventional Thouless pumping but also induces a nonzero Chern number in the two-dimensional synthetic space while preserving the time-reversal symmetry in the real space. Through changing the translation, gapless and tunable topological boundary modes are demonstrated. As a specific application, we show a dynamic bandpass filter with real-time tuning over 100% bandgap, a capability that cannot be achieved with only one translation parameter. Our design opens a venue for the development of tunable topological devices based on synthetic parameter dimension and can be generalized to other bosonic systems.

Abstract The prevalence of infertility caused by endometrial defects is steadily increasing, posing a significant challenge to women's reproductive health. In this study, injectable “homing‐like” bioactive decellularized extracellular matrix short‐fibers (DEFs) of porcine skin origin are innovatively designed for endometrial and fertility restoration. The DEFs can effectively bind to endometrial cells through noncovalent dipole interactions and release bioactive growth factors in situ. In vitro, the DEFs effectively attracted endometrial cells through the “homing‐like” effect, enabling cell adhesion, spreading, and proliferation on their surface. Furthermore, the DEFs effectively facilitated the proliferation and angiogenesis of human primary endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs), and inhibited fibrosis of pretreated HESCs. In vivo, the DEFs significantly accelerated endometrial restoration, angiogenesis, and receptivity. Notably, the deposition of endometrial collagen decreased from 41.19 ± 2.16% to 14.15 ± 1.70% with DEFs treatment. Most importantly, in endometrium‐injured rats, the use of DEFs increased the live birth rate from 30% to an impressive 90%, and the number and development of live births close to normal rats. The injectable “homing‐like” bioactive DEFs system can achieve efficient live births and intrauterine injection of DEFs provides a new promising clinical strategy for endometrial factor infertility.

Abstract M7G modification, known as one of the common post-transcriptional modifications of RNA, is present in many different types of RNAs. With the accurate identification of m7G modifications within RNAs, their functional roles in the regulation of gene expression and different physiological functions have been revealed. In addition, there is growing evidence that m7G modifications are crucial in the emergence of cancer. Here, we review the most recent findings regarding the detection techniques, distribution, biological functions and Regulators of m7G. We also summarize the connections between m7G modifications and cancer development, drug resistance, and tumor microenvironment as well as we discuss the research’s future directions and trends.

AIM: To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PLGF) levels after intravitreal injections for the neovascular age-related macular degeneration (AMD). METHODS: Thirty-five patients (35 eyes) with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were detected before the intravitreal injection and at 1, 3, and 12mo after conbercept treatment. The levels of serum VEGF-A, VEGF-B, and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments. RESULTS: At baseline, the mean BCVA score was 39.89±14.64 letters. The mean BCVA scores were 51.03±15.78, 56.71±14.38, and 52.49±10.16 letters at 1, 3, and 12mo after conbercept treatment, and the BCVA improvements were all significant, respectively (P0.05). CONCLUSION: Conbercept intravitreal injection leads to BCVA and CRT improvement, however, it does not significantly affect systemic serum VEGF-A, VEGF-B, and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.

Amniotic membrane is the innermost membrane in human placenta. It supports epithelialization and has the characteristics of anti-fibrosis, anti-inflammation and anti-angiogenesis. It is gradually widely used in ophthalmic surgery and other surgical operations. In recently years, the amniotic membrane has been used more frequently in ophthalmic clinic and has achieved better curative effect. This article reviews the application of amniotic membrane transplantation in ocular diseases such as ocular burn, conjunctival disease, corneal disease, pterygium, glaucoma and macular hole. It is expected that amniotic membrane transplantation will bring new ideas for the treatment of ocular diseases.

Carotenoids are an important component of the human diet, and fruit is a primary source of carotenoids. The synthesis and regulation of carotenoids in fruit are important contributors to the formation of fruit quality. In China, strawberry is one of the main seasonal fruits grown in the winter. Previous studies have shown that light has a significant effect on the metabolism of anthocyanins, sugars, and polyphenols in strawberry. However, the understanding of the role of light in regulating the metabolism of carotenoids in strawberry remains limited. This study investigated the effects of blue, red, yellow-green, and white light on carotenoid metabolism in strawberry. Blue light treatment promoted the synthesis of multiple carotenoids, including lutein, compared with the other three treatment groups. The RNA sequencing data revealed that blue light treatment promoted the expression of lycopene ε-cyclase (LCYE), and the transient overexpression of LCYE in strawberry fruit promoted lutein accumulation in strawberry. Overall, the results suggest that blue light can promote the synthesis of lutein in strawberry by inducing the expression of LCYE.

Since 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)posed a great threat to human health and social economy, which has brought out hundreds of millions infection and caused millions of deaths worldwide. With the increasing research on SARS-CoV-2, angiotensin-converting enzyme 2(ACE2)has been regarded as a significant functional receptor for SARS-CoV-2 invasion. ACE2 is distributed in many tissues of human body, not only expressed in lung, cardiovascular, kidney tissues, but also in conjunctiva, cornea, uvea, retina and optic nerve tissue. More and more cases of SARS-CoV-2 infection through ocular tissues have been found; however, whether ocular ACE2 plays a role in SARS-CoV-2 infection is not completely clear. Therefore, study on expression and distribution of ACE2 in the ocular tissues can not only provide an in-depth understanding of the mechanism of SARS-CoV-2 infection, but also supply a comprehensive acquaintance with the mechanism of ACE2 action in the ocular tissues. In this paper, we review recent research progress about the expression and distribution of ACE2 in ocular tissues and hope to better understand the mechanism of ACE2 in the pathophysiological processes of ocular tissues.

Abstract Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the “immuno-privileged” status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient’s immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.

Abstract Besides chiral edge states, the hallmark of quantum Hall insulators, antichiral edge states can exhibit unidirectional transport behavior but in topological semimetals. Although such edge states provide more flexibility for molding the flow of light, their realization usually suffers from time-reversal breaking. In this study, we propose the realization of antichiral surface states in a time-reversal-invariant manner and demonstrate our idea with a three-dimensional (3D) photonic metacrystal. Our system is a photonic semimetal possessing two asymmetrically dispersed Dirac nodal lines. Via dimension reduction, the nodal lines are rendered a pair of offset Dirac points. By introducing synthetic gauge flux, each two-dimensional (2D) subsystem with nonzero k z is analogous to a modified Haldane model, yielding a k z -dependent antichiral surface transport. Through microwave experiments, the bulk dispersion with asymmetric nodal lines and associated twisted ribbon surface states are demonstrated in our 3D time-reversal-invariant system. Although our idea is demonstrated in a photonic system, we propose a general approach to realize antichiral edge states in time-reversal-invariant systems. This approach can be easily extended to systems beyond photonics and may pave the way for further applications of antichiral transport.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin–eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.

Plain English summary Limited data was available on the general quality of life (QoL) in pregnant women with atrial septal defect (ASD), even though the condition could produce anxiety over health of the pregnancy and fetus. The percutaneous closure procedure was available for ASD during pregnancy; however, pregnant women were often concerned that the required X-rays would harm the fetus. A safe and effective procedure, percutaneous closure of ASD guided by transthoracic echocardiography, was widely used for this condition. This study used the 36-Item Short Form Survey (SF-36) to assess QoL in pregnant women with ASD pre- and post-procedure and compared the results to those of healthy pregnant women at a similar stage of pregnancy. Post-procedure QoL in pregnant women with ASD was improved; however, the younger women and those on their first pregnancy performed more poorly in some dimensions (social functioning and role emotional). Our results suggested that these groups should receive more proactive intervention.

Acne scars are caused by inflammatory reactions, infections, and improper handling of acne lesions. Such scars have a high incidence and are difficult to treat. There are many methods currently used to treat acne scars, including medications, photoelectric technology, surgery, filling, chemical peeling, traditional Chinese medicine, biotherapy, and microneedle therapy, and many new methods are constantly emerging. However, there are still many issues, such as the lack of high-quality clinical studies, non-uniform treatment methods, and unsatisfactory therapeutic effects. The selection of appropriate methods for the comprehensive treatment of different types of acne scars at different stages in clinical practice remains challenging and is a research topic of great interest. From the perspective of evidence-based medicine, this consensus aims to provide a reference for the treatment of acne scars in clinical practice.

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy of the skin, and its incidence is increasing annually. Once cSCC becomes metastatic, its associated mortality rate is much higher than that of cSCC in situ. However, the current treatments for progressive cSCC have several limitations. The aim of this study was to suggest a potential compound for future research that may benefit patients with cSCC. Methods: In this study, we screened the following differentially expressed genes from the Gene Expression Omnibus database: GSE42677, GSE45164, GSE66359, and GSE98767. Using strategies such as protein-protein interaction network analysis and the CYTOSCAPE plugin MCODE, key modules were identified and then verified by Western blotting. Subsequently, related signalling pathways were constituted in the SIGNOR database. Finally, molecular docking analyses and cell viability assay were used to identify a potential candidate drug and verify its growth inhibition ability to A431 cell line. Results: Fifty-one common differentially expressed genes were screened and two key modules were identified. Among them, three core genes were extracted, constituting two signalling pathways, both of which belong to the module associated with mitotic spindles and cell division. A pathway involving CDK1, the TPX2-KIF11 complex, and spindle organization was validated in a series of analyses, including analyses for overall survival, genetic alteration, and molecular structure. Molecular docking analyses identified the pyridine 2-carbaldehyde thiosemicarbazone (NSC689534), which interacts with TPX2 and KIF11, as a potential candidate for the treatment of cSCC. Conclusions: NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC.

Conbercept is a novel anti-vascular endothelial growth factor drug independently developed by China. Since it was approved for clinical application by the State Food and Drug Administration of China in 2013, conbercept has shown reliable safety and efficacy in the treatment of ocular neovascular diseases such as wet age-related macular degeneration, choroidal neovascularization and macular edema. For different diseases, the treatment strategies of conbercept are different. This article mainly reviews the application progress of conbercept in ocular neovascularization related diseases including wet age-related macular degeneration, diabetic macular edema, pathologic myopia choroidal neovascularization, neovascular glaucoma, retinopathy of prematurity and corneal neovascularization, and summarizes and explores the indications, administration scheme and therapeutic effect of conbercept. It is expected that the indications of conbercept will be wider and the administration scheme will be more given, and the usage of conbercept will bring new ideas for the treatment of ocular neovascular diseases.

Abstract Background Current treatments for salivary gland (SG) hypofunction are palliative and do not address the underlying cause or progression of the disease. SG-derived stem cells have the potential to treat SG hypofunction, but their isolation is challenging, especially when the tissue has been damaged by disease or irradiation for head and neck cancer. In the current study, we test the hypothesis that multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model are capable of trans-differentiating to the SG epithelial cell lineage when induced by a native SG-specific extracellular matrix (SG-ECM) and thus may be a viable substitute for repairing damaged SGs. Methods Rat BM-MSCs were treated with homogenates of decellularized rat SG-ECM for one hour in cell suspension and then cultured in tissue culture plates for 7 days in growth media. By day 7, the cultures contained cell aggregates and a cell monolayer. The cell aggregates were hand-selected under a dissecting microscope, transferred to a new tissue culture dish, and cultured for an additional 7 days in epithelial cell differentiation media. Cell aggregates and cells isolated from the monolayer were evaluated for expression of SG progenitor and epithelial cell specific markers, cell morphology and ultrastructure, and ability to form SG-like organoids in vivo. Results The results showed that this approach was very effective and guided the trans-differentiation of a subpopulation of CD133-positive BM-MSCs to the SG epithelial cell lineage. These cells expressed amylase, tight junction proteins (Cldn 3 and 10), and markers for SG acinar (Aqp5 and Mist 1) and ductal (Krt 14) cells at both the transcript and protein levels, produced intracellular secretory granules which were morphologically identical to those found in submandibular gland, and formed SG-like organoids when implanted in the renal capsule in vivo. Conclusions The results of this study suggest the feasibility of using autologous BM-MSCs as an abundant source of stem cells for treating SG hypofunction and restoring the production of saliva in these patients.

Abstract Background Peritoneal metastasis often occurs in patients with colorectal cancer peritoneal metastasis, and the prognosis is poor. A large body of evidence highlights the beneficial effects of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is little consensus on the optimal treatment strategy for patients with colorectal cancer peritoneal metastasis. The purpose of this study is to evaluate the impact of CRS + HIPEC on survival and provide reference for the treatment of patients with colorectal cancer peritoneal metastasis. Methods This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed, Embase, Cochrane, Web of Knowledge, and ClinicalTrials.gov databases were screened from inception of the review to March 11, 2022. Ten studies were included in qualitative and quantitative analysis. Results A total of 3200 patients were enrolled in the study, including 788 patients in the CRS and HIPEC groups and 2412 patients in the control group, of which 3 were randomized controlled trials and 7 were cohort studies. The 3 randomized controlled studies were of high quality, and the quality scores of the 7 cohort studies were all 7 or above, indicating high quality. The results showed that the OS of CRS + HIPEC group was higher than that of control group (HR: 0.53, 95% CI: 0.38–0.73; P < 0.00001, I 2 = 82.9%); the heterogeneity of the studies was large. The subgroup analysis showed that the OS of CRS and HIPEC group was higher than that of PC group (HR: 0.37, 95% CI: 0.30–0.47; P = 0.215, I 2 = 31%) and higher than that in CRS group (HR: 0.73, 95% CI: 0.49–1.07; P = 0.163, I 2 = 44.8%); the heterogeneity of the studies was low. In the OPEN group, the OS of THE CRS and HIPEC groups was higher than that in the control group (HR: 0.51, 95% CI: 0.38–0.70; P = 0.353, I 2 = 3.9%); OPEN group showed lower heterogeneity. The OS of 60–100-min group was higher than that in the control group (HR: 0.65, 95% CI: 0.49–0.88; P = 0.172, I 2 = 37.4%); the heterogeneity of the studies was low. Sensitivity analysis showed that there was no significant difference in the results of the combined analysis after each study was deleted. The results of publication bias showed that the P-value of Egger and Begg tests was 0.078 > 0.05, indicating that there is no publication bias. Conclusions CRS + HIPEC can improve the survival rate of patients with colorectal cancer peritoneal metastasis

Abstract Three-dimensional (3D) artificial metacrystals host rich topological phases, such as Weyl points, nodal rings, and 3D photonic topological insulators. These topological states enable a wide range of applications, including 3D robust waveguides, one-way fiber, and negative refraction of the surface wave. However, these carefully designed metacrystals are usually very complex, hindering their extension to nanoscale photonic systems. Here, we theoretically proposed and experimentally realized an ideal nodal ring in the visible region using a simple 1D photonic crystal. The π-Berry phase around the ring is manifested by a 2π reflection phase’s winding and the resultant drumhead surface states. By breaking the inversion symmetry, the nodal ring can be gapped and the π-Berry phase would diffuse into a toroidal-shaped Berry flux, resulting in photonic ridge states (the 3D extension of quantum valley Hall states). Our results provide a simple and feasible platform for exploring 3D topological physics and its potential applications in nanophotonics.

HOXA transcript at the distal tip (HOTTIP), a newly identified long noncoding RNA, has been shown to exhibit anti-inflammatory effects and inhibit oxygen-glucose deprivation-induced neuronal apoptosis. However, its role in Parkinson’s disease (PD) remains unclear. 1-Methyl-4-phenylpyridium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used to establish PD models in SH-SY5Y and BV2 cells and in C57BL/6 male mice, respectively. In vitro, after HOTTIP knockdown by sh-HOTTIP transfection, HOTTIP and FOXO1 overexpression promoted SH-SY5Y apoptosis, BV2 microglial activation, proinflammatory cytokine expression, and nuclear factor kappa-B and NACHT, LRR and PYD domains-containing protein 3 inflammasome activation. Overexpression of miR-615-3p inhibited MPP+-induced neuronal apoptosis and microglial inflammation and ameliorated HOTTIP- and FOXO1-mediated nerve injury and inflammation. In vivo, HOTTIP knockdown alleviated motor dysfunction in PD mice and reduced neuronal apoptosis and microglial activation in the substantia nigra. These findings suggest that inhibition of HOTTIP mitigates neuronal apoptosis and microglial activation in PD models by modulating miR-615-3p/FOXO1. This study was approved by the Ethics Review Committee of the Affiliated Hospital of Qingdao University, China (approval No. UDX-2018-042) in June 2018.

Purpose Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an increased risk of 30-day readmission in gastric cancer. Methods We performed a retrospective study of patients who underwent radical gastrectomy for gastric cancer at our institution between July 2014 and May 2018. Balanced cohorts were created by propensity score matching (PSM) with a 1:1 ratio to generate the elevated LDH (ELDH) group (n = 151) and the low LDH group (Control) (n = 302). To determine the incidence, causes, and risk factors of 30-day readmission, subgroup analyzes were performed and used to develop an efficient prediction model. Results A total of 788 patients met the criteria to be included in the study. The cutoff value for serum LDH was 215.5. After PSM, a total of 302 patients were matched in pairs (ELDH group, n = 151, Control group, n = 151). ELDH levels had a higher risk of readmission (p = 0.005, Odds ratio 3.768, 95% confidence interval 1.493–9.510). The pre-match 30-day readmission rate was 7.2 percent, and common causes of post-match readmission included infection-related symptoms, gastrointestinal symptoms, and gastrointestinal bleeding. Conclusions Patients with preoperative ELDH levels, postoperative complications, and high preoperative American Society of Anesthesiologists Scores had a higher risk of readmission 30 days after surgery.

Abstract Background The current research is allocated to appraise the association between the parameters of body composition and findings in type A aortic dissection (TAAD) cases in diverse age groups. Methods Data from consecutive TAAD patients undergoing implantation of modified triple-branched stent-graft from January 2017 and December 2019 were prospectively collected and analyzed. A regression model of Cox proportional hazard was employed to assess correlations among body composition-related variables (body mass index [BMI], lean body mass [LBM], body surface area [BSA], and LBM index) as well as cumulative mortality. Results Overall, 258 patients (53.9 ± 11.1 years old; 72.9% male) were separated into young (n = 110) and elderly (n = 148) age groups based upon whether they were younger or older than 50 years of age. Of these patients, 247 survivors were included in subsequent analyses over an average 26.8 ± 11.6 month follow-up duration. Multivariate analyses in the elderly group instead of young group indicated that increased BMI (p = 0.042), BMI ≤ 18.5 kg/m2 (p = 0.025), and lower LBM index values (p = 0.019) were significant predictors of increased total all-cause cumulative mortality. BMI was considerably positively correlated with estimated all-cause cumulative mortality in elderly but not young TAAD cases. Conclusion Briefly, these results suggest that BMI and LBM indices are only significant predictors of TAAD patient all-cause mortality in elderly patient cohorts, whereas they do not offer significant prognostic value for younger patients. As such, these age differences must be taken into consideration when conducting stratified risk assessments based upon TAAD patient body composition characteristics.

The m7G modification has been proven to play an important role in RNA post-transcriptional modification and protein translation. However, the potential role of m7G modification patterns in assessing the prognosis of Skin cutaneous melanoma (SKCM) and tumor microenvironment (TME) has not been well studied. In this study, we investigated and finally identified 21 available m7G-related genes. We used hierarchical clustering (K-means) to classify 743 SKCM patients into three m7G-modified subtypes named m7G/gene cluster-A, B, C. We found that both m7G cluster B and gene cluster B exhibited higher prognosis and higher immune cell infiltration in TME compared to other subtypes. EIF4E3 and IFIT5, two m7G related genes, were both markedly elevated in Cluster B. Then, we constructed an m7G score system utilizing principal component analysis (PCA) in order to evaluate the patients' prognosis. High m7G score subtype was associated with better survival prognosis and active immune response. Overall, this article revealed that m7G modification patterns were involved in the development of the tumor microenvironment. Evaluating patients' m7G modification patterns will enhance our understanding of TME characteristics and help to guide personal treatment in clinics in the future.

Sugar is an important material basis in fruit development, and strawberry fruit flavour and sweetness largely depend on the sugar content and variety. Invertases (INVs) play an important role in the regulation of sugar accumulation because they irreversibly catalyse the hydrolysis of sucrose into the corresponding nucleoside diphosphate-glucose, glucose or fructose in fruit. In this work, we provided a comprehensive analysis of the INV gene family in octoploid strawberry (Fragaria×ananassa), including the gene structure, chromosomal locations, conserved domains, and gene evolution and expression profiles during strawberry fruit development. Our study revealed that polyploid events resulted in the abundant amplification (almost three- or four-fold) of the INV gene in the F.×ananassa genome, and these amplified INV genes showed dominant expression in strawberry fruit. More than half of the FaINVs transcripts with low expression had incomplete coding sequences by alternative splicing. Previous studies have shown that cell wall invertases (CWINV) are involved in the regulation of phloem unloading and sink strength establishment. The expression of FaCWINV1 was markedly upregulated during fruit development and strongly expressed in ripe fruit. Moreover, a significant correlation was observed between the total sugar content and the FaCWINV1 expression level. These findings suggest that FaCWINV1 may be involved in sugar accumulation in strawberry fruit. Taken together, the results of our study will be beneficial for further research into the functions of INVs in the regulation of fruit ripening.

AIM: To investigate the effect of conbercept intravitreal injection combined with glaucoma drainage device implantation and panretinal photocoagulation for neovascular glaucoma(NVG)with and without vitreous hemorrhage.METHODS: In this retrospective study, 39 eyes in 37 patients who were diagnosed with NVG with and without vitreous hemorrhage(where iridotrabecular contact is more than 180°)in the ophthalmology department of Xi'an No.1 Hospital between January 2016 and December 2017 were enrolled in this study. Patients were divided into two groups, based on whether they had vitreous hemorrhage. All patients received 0.5 mg(0.05 mL)conbercept intravitreal injection. Twenty-one eyes in 20 patiants(Group 1)without vitreous hemorrhage received EX-PRESS(P50)glaucoma drainage device implantation on 4d after conbercept intravitreal injection and then received panretinal photocoagulation 2wk after implantation. Eighteen eyes in 17 patients(Group 2)with vitreous hemorrhage received vitrectomy combined with the EX-PRESS(P50)glaucoma drainage device implantation and panretinal photocoagulation on 4d after conbercept intravitreal injection. Air or silicone oil was selectively filled according to the situation during the operation. All patients were followed up for 6mo after operation.RESULTS: No statistical difference was found between preoperative best corrected visual acuity(BCVA)and postoperative(6mo)BCVA in Group 1(P>0.05). There was statistical difference between preoperative BCVA and postoperative(6mo)BCVA in Group 2(P

Recently, mesenchymal stem cell (MSC) therapies have been questioned as MSCs are capable of both promoting and inhibiting tumorigenesis. Both MSCs and tumor cells replicate to increase their population size; however, MSCs, but not tumor cells, stop dividing when they reach confluence due to cell–cell contact inhibition and then differentiate. We hypothesized that contact inhibition results in the production of effector molecules by confluent MSCs and these effectors are capable of suppressing tumor cell growth. To test this hypothesis, we co-cultured breast cancer cells (MDA-MB-231) with either confluent or sub-confluent bone-marrow-derived MSCs (BM-MSCs); in addition, we treated various tumor cells with conditioned media (CM) obtained from either confluent or sub-confluent BM-MSCs. The results showed that the growth of tumor cells co-cultured with confluent BM-MSCs or treated with CM obtained from confluent BM-MSCs was inhibited, and this effect was significantly stronger than that seen with tumor cells co-cultured with sub-confluent BM-MSCs or CM obtained from sub-confluent BM-MSCs. Subcutaneous tumor formation was completely prevented by the inoculation of tumor cells mixed with CM. In the future, soluble anti-tumor effectors, produced by confluent MSCs, may be used as cell-free therapeutics; this approach provides a solution to current concerns associated with cell-based therapies.

BackgroundPreoperative sarcopenia is a prognostic risk factor for gastric cancer (GC). This study aimed to determine whether radiomic sarcopenia features on computed tomography (CT) could be used to diagnose sarcopenia preoperatively, and whether they could be used to accurately predict the postoperative survival and complication prognosis of patients with GC.MethodsWe retrospectively analyzed data of 550 patients with GC who underwent radical gastrectomy. The patients were divided into training (2014–2016) and validation (2017–2019) cohorts. We established a radiomics-based diagnosis tool for sarcopenia. Thereafter, univariate and multivariate analyses of diagnostic factors were carried out. Receiver operator characteristic (ROC) curves and area under the curve (AUC) were used to compare different diagnostic models. The Kaplan–Meier method was used to estimate the survival curve.ResultsRadiomic sarcopenia correlated with complications and long-term survival. Skeletal muscle index, grip strength, and walking speed were correlated with postoperative complications in both cohorts (AUCs: 0.632, 0.577, and 0.614, respectively in the training cohort; 0.570, 0.605, 0.546, respectively, in the validation cohort), and original sarcopenia was more accurate than any of these indicators. However, radiomic sarcopenia has a higher AUC in predicting short-term complications than original sarcopenia in both groups (AUCs: 0.646 vs. 0.635 in the training cohort; 0.641 vs. 0.625 in the validation cohort). In the training cohort, the overall survival time of patients with original sarcopenia was shorter than normal patients (hazard ratio, HR = 1.741; 95% confidence interval [CI], 1.044–2.903; p = 0.031). While radiomic sarcopenia had a greater prognostic significance, the overall survival time of patients with radiomic sarcopenia was significantly worse than normal patients (HR, 1.880; 95% CI, 1.225–2.885, p = 0.003).ConclusionExtracted sarcopenia features based on CT can predict long-term survival and short-term complications of GC patients after surgery, and its accuracy has been verified by training and validation groups. Compared with original sarcopenia, radiomic sarcopenia can effectively improve the accuracy of survival and complication prediction and also shorten the time and steps of traditional screening, thereby reducing the subjectivity effects of sarcopenia assessment.

AIM: To investigate YM155's effect on retinal pigment epithelium (RPE) cells' viability and the potential regulatory mechanisms. METHODS: Human immortalized RPE cell lines (ARPE-19 cell line) were processed with YM155 and epidermal growth factor (EGF). ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay, and apoptosis was tested by flow cytometry assay. ARPE-19 cell proliferation was assessed with bromodeoxyuridine tagged incorporation assay, and migration ability was evaluated via a wound-healing assay. Epidermal growth factor receptor (EGFR)/MAPK pathway proteins were tested via immunoblotting. EGFR localization was examined by immunofluorescence assay. RESULTS: YM155 suppressed ARPE-19 cells' viability in a time and concentration-dependent manner. A high dose of YM155 caused a small amount of ARPE-19 cell death. YM155 significantly diminished the ARPE-19 cells' proliferative and migrative capacity. YM155 down-regulated total EGFR and phosphorylated external signal-regulated protein kinase (ERK), and it up-regulated the phosphorylation of P38MAPK and c-Jun N-terminal kinase (JNK). YM155 induced endocytosis of EGFR in ARPE-19 cell. YM155 also attenuated EGF-induced ARPE-19 cells' proliferative and migrative capacity. Moreover, YM155 significantly decreased the expression of phosphorylated EGFR and ERK after treated by EGF. CONCLUSION: YM155 inhibits RPE cell survival, the cell proliferative and migrative capacity, and it effectuates a small amount of cell death through the EGFR/MAPK signaling pathway. YM155 might, therefore, be an agent to prevent and treat abnormal RPE cell survival in proliferative vitreoretinopathy.

ObjectiveMalnutrition is recognized as a risk factor for poor outcome in patients with gastric cancer (GC). In 2018, the Global Leadership Initiative on Malnutrition (GLIM) published standardized criteria for the diagnosis of malnutrition. Our aim was to investigate whether any of the components of the GLIM diagnostic criteria were related to worse clinical outcomes in patients with GC.MethodsThis study analyzed patients with GC who underwent radical gastrectomy in our hospital between 2014 and 2019. A preoperative nutritional assessment was performed for each patient. Matching was based on the presence of three GLIM components: high weight loss (WL), low body mass index (BMI), and low skeletal muscle index (SMI).ResultsThe analysis included 1,188 patients, including 241 (20.3%) with high WL, 156 (13.1%) with low BMI, and 355 (29.9%) with low SMI. Before matching, patients who met the GLIM component criteria were mostly associated with older age, low nutritional reserves, and late tumor progression. After matching, the clinical characteristics of the three cohorts were balanced. In the matched queue, the survival prognosis of the high WL group was worse than that of the non-WL group, and the postoperative complication rate was higher in the low SMI group than in the normal SMI group (P 0.05).ConclusionOf the GLIM criteria, high WL and low SMI may be associated with poor clinical outcomes in patients with GC, while a low BMI may not be associated with outcome.

Extracellular vesicles (EVs) are small membranous particles that contribute to intercellular communications. Separating EVs from tissue is still a technical challenge. Here, we present a rigorous method for extracting EVs from intestinal tissue in a mouse intestinal ischemia/reperfusion (I/R) model, and for analyzing their miRNA content. The isolated EVs show a typical cup shape with a size peak of 120–130 nm in diameter, confirmed by TEM and NTA. They also express EV markers such as CD9, CD63, CD81, Tsg101 and Alix. Real-time qPCR confirmed that these pellets contain miRNAs related to I/R injury. Our study presents a practical way to isolate EVs from intestinal tissue which is suitable for downstream applications such as miRNA analysis, and provides a novel method for investigating the mechanism of intestinal I/R injury.

Ilexonin A is a compound isolated from the root of Ilex pubescens, a traditional Chinese medicine. Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the peri-infarct area after ischemia. However, the effects of ilexonin A on astrocytes and microglia in the infarct-free region of the hippocampal CA1 region remain unclear. Focal cerebral ischemia models were established by 2-hour occlusion of the middle cerebral artery in rats. Ilexonin A (20, 40 or 80 mg/kg) was administered immediately after ischemia/reperfusion. The astrocyte marker glial fibrillary acidic protein, microglia marker Iba-1, neural stem cell marker nestin and inflammation markers were detected by immunohistochemistry and western blot assay. Expression levels of tumor necrosis factor-α and interleukin 1β were determined by enzyme linked immunosorbent assay in the hippocampal CA1 tissue. Astrocytes were activated immediately in progressively increasing numbers from 1, 3, to 7 days post-ischemia/reperfusion. The number of activated astrocytes further increased in the hippocampal CA1 region after treatment with ilexonin A. Microglial cells remained quiescent after ischemia/reperfusion, but became activated after treatment with ilexonin A. Ilexonin A enhanced nestin expression and reduced the expression of tumor necrosis factor-α and interleukin 1β in the hippocampus post-ischemia/reperfusion. The results of the present study suggest that ilexonin A has a neuroprotective effect in the hippocampus after ischemia/reperfusion, probably through regulating astrocytes and microglia activation, promoting neuronal stem cell proliferation and reducing the levels of pro-inflammatory factors. This study was approved by the Animal Ethics Committee of the Fujian Medical University Union Hospital, China.

Objective To investigate the imaging features differences of perivascular spaces(PVS) between cerebral small vessel disease(cSVD) and multiple sclerosis(MS). Methods The clinical data of 27 patients diagnosed with cSVD and 32 patients diagnosed with MS were collected retrospectively from January 2015 to December 2017. The grade of PVS in the centrum semiovale and basal ganglia were recorded and the sum of scores in the two regions were calculated in both diseases. Results The score of PVS in the area of basal ganglia and the total score in cSVD group were 1 (1,2) and 3 (2,4),which were both higher than 1 (1,1) and 1 (1,2) score in MS group respectively(Z=7.960, P=0.012; Z=14.033, P= 0.001). The score of PVS in centrum semiovale were similar in cSVD group and MS group[1(1,2)score vs. 0 (0, 1) score; Z =4.872, P =0.057]. Conclusions In the areas of basal ganglia, PVS are more common in cSVD patients than MS patients.

Backscattering is one of the major factors that limit the performance of integrated nanophotonics. Here, He et al. realize topologically protected, robust and unidirectional coupling as well as optical transport on a silicon-on-insulator platform by exploiting the valley degree of freedom.

Topological photonics is an emerging field that attracts enormous interest for its novel ways to engineer the flow of light. With the help of topological protection, the surface modes of topological photonic systems have intriguing properties, such as the unidirectional propagation, robust transmission against defects and disorders, which meet the rapidly growing demands for information processing. Valley photonic crystals, as one kind of topological photonic systems, not only support protected surface modes, but also are friendly to micro-nano fabrication. These advantages show that it has broad prospects in constructing high-performance photonic devices or even photonic integrated circuits. Here, we review the properties and development of valley photonic crystals. Firstly, the theory and structure are briefly introduced and then the discussion of robust transmission will be followed. Furthermore, prototypes of on-chip devices based on valley photonic crystals are reviewed. As a perspective in photonics, valley photonic crystal is expected to become a good platform to study nanophotonics and realize advancing integrated photonics devices.

We demonstrate a kind of grating coupler that generates a high quality flat-top beam with a small beamwidth from photonic integrated circuits into free-space. The grating coupler is designed on a silicon-on-insulator wafer with a 220-nm-thick silicon layer and consists of a dual-etch grating (DG) and a distributed Bragg reflector (DBR). By adjusting the structural parameters of DG and DBR, a pixel-level (6.6 µm) flat-top beam with a vertical radiation of −0.5 dB and a mode match of 97% at 1550 nm is realized. Furthermore, a series of high-efficiency grating couplers are designed to create a flat-top beam with different scales.

Mesenchymal stem cells (MSCs) are highly responsive to cues in the microenvironment (niche) that must be recapitulated ex vivo to study their authentic behavior. In this study, we hypothesized that native bone marrow (BM)- and adipose (AD)-derived extracellular matrices (ECM) were unique in their ability to control MSC behavior. To test this, we compared proliferation and differentiation of bone marrow (BM)-derived MSCs when maintained on native decellularized ECM produced by BM versus AD stromal cells (i.e. BM- versus AD-ECM).We found that both ECMs contained similar types of collagens but differed in the relative abundance of each. Type VI collagen was the most abundant (≈60% of the total collagen present), while type I was the next most abundant at ≈30%. These two types of collagen were found in nearly equal proportions in both ECMs. In contrast, type XII collagen was almost exclusively found in AD-ECM, while types IV and V were only found in BM-ECM. Physically and mechanically, BM-ECM was rougher and stiffer, but less adhesive, than AD-ECM.During 14 days in culture, both ECMs supported BM-MSC proliferation better than tissue culture plastic (TCP), although MSC-related surface marker expression remained relatively high on all three culture surfaces. BM-MSCs cultured in osteogenic (OS) differentiation media on BM-ECM displayed a significant increase in calcium deposition in the matrix, indicative of osteogenesis, while BM-MSCs cultured on AD-ECM in the presence of adipogenic (AP) differentiation media showed a significant increase in Oil Red O staining, indicative of adipogenesis. Further, culture on BM-ECM significantly increased BM-MSC-responsiveness to rhBMP-2 (an osteogenic inducer), while culture on AD-ECM enhanced responsiveness to rosiglitazone (an adipogenic inducer).These findings support our hypothesis and indicate that BM- and AD-ECMs retain unique elements, characteristic of their tissue-specific microenvironment (niche), which promote retention of MSC differentiation state (i.e. “stemness”) during expansion and direct cell response to lineage-specific inducers. This study provides a new paradigm for precisely controlling MSC fate to a desired cell lineage for tissue-specific cell-based therapies.

Abstract Introduction Limb‐shaking transient ischemic attack (LS‐TIA) is a clinical disease with severe carotid stenosis, which is characterized by unilateral rhythmic dance or tremor like involuntary movements of arms and/or legs, but facial muscles are usually unaffected. Methods Today, we report a 42‐year‐old man with transient ischemic attack who suffered from right limb shaking and right facial muscle twitching due to the obvious stenosis of left internal carotid artery (ICA). Written informed consent was obtained from participants according to the Declaration of Helsinki, and a local ethic committee approved the study. ICA angioplasty and stent implantation were performed as treatment attempts. A brain protection device was navigated through the lesion and placed at the distal end of the stenosis. Result The patient successfully completed the recanalization through stent placement, and the involuntary shaking of limbs and face was improved. During the 3‐month follow‐up, the patient's symptoms disappeared completely and did not attack again. Conclusion This case report highlights the importance of accurate diagnosis and treatment, because treatment‐related carotid artery occlusion can not only eliminate the attack, but also reduce the risk of future stroke.

Cyanobacterial blooms have become more frequent and serious in recent years. Not only do massive blooms cause environmental pollution and nutrient eutrophication, but they also produce microcystins (MCs), a group of toxic cycloheptapeptides, which threaten aquatic ecosystem and human health. As such, clarifying the allelopathic interactions between cyanobacteria and other algae is critical to better understand the driving factors of blooms. To date, however, such studies remain largely insufficient. Here, we treated model alga Chlamydomonas reinhardtii with microcystin-LR (MC-LR) to determine its allelopathic effects. Results showed that MC-LR markedly suppressed C. reinhardtii cell viability. Comparative proteomic and physiological analyses revealed that MC-LR significantly up-regulated protein abundance of antioxidants ascorbate peroxidase (APX) and catalase (CAT) at the beginning stage of exposure. This was accompanied by an over-accumulation of hydrogen peroxide (H2O2), suggesting that MC-LR suppresses cell viability via oxidative damage. Furthermore, we found that MCs induced desulfhydrase (DES) activity for hydrogen sulfide (H2S) generation at the beginning stage. Additional H2S donors reactivated antioxidant enzyme activity, which reduced H2O2 accumulation and ultimately enhanced C. reinhardtii tolerance to MC-LR damage. This effect could be reserved by inhibiting H2S biosynthesis. Simultaneously, we found that H2S also suppressed MC-LR-induced cell autophagy, and thus attenuated the toxic effects of MC-LR. Our findings suggest that oxidative bursts may be the main reason for the allelopathic effects of MC-LR on C. reinhardtii viability and that H2S signaling may enhance C. reinhardtii tolerance to MC-LR through the activation of antioxidant enzyme activity and suppression of cell autophagy.

Objectives: The present study aimed to explore the association between spleen density and post-operative outcomes of patients after curative gastrectomy.Methods: From June 2014 to December 2015, we conducted a retrospective study to analyze pertinent clinical data from gastric cancer patients who underwent gastrectomy at the First and the Second Affiliated Hospital of Wenzhou Medical University. Spleen density was determined via computed tomography scans. Univariate and multivariate analyses were performed to determine the risk factors associated with post-operative outcomes after gastric cancer surgery.Results: Three hundred and ninety five patients were included, of whom 98 (24.8%) were defined as having a diffuse reduction of spleen density based on diagnostic cutoff values (spleen density ≤43.89 HU). Multivariate analysis revealed diffuse reduction of spleen density as an independent risk factor for post-operative complications and long-term overall survival.Conclusions: Spleen density can predict severe postoperative complications and long-term overall survival in gastric cancer patients. As an imaging evaluation method, spleen density is a novel tool can be used in clinical as a prognostic predictor for patients with gastric cancer.

AIM:To investigate the effect of epidermal growth factor(EGF)on proliferation and migration of retinal pigment epithelial(RPE)cells. METHODS: Human RPE cell lines(ARPE-19 cell)were treated with different doses of EGF. The methyl thiazolyl tetrazolium(MTT)assay was used to detect cell viability. The 5-bromodeoxyuridine(BrdU)incorporation assay was used to detect cell proliferation and the “scratch-wound assay” was used to detect cell migration ability. The epidermal growth factor receptor(EGFR)and protein kinase B(AKT)proteins were detected by Western blot. RESULTS:The MTT assay results showed that treatment with 50 and 100ng/mL EGF for 12h increased ARPE-19 cell viability. The BrdU incorporation assay and the “scratch-wound assay” showed that treatment with 100ng/mL EGF for 24h increased ARPE-19 cell proliferation and migration. The Western blot results showed that treatment with 10-100ng/mL EGF for 12h or 100ng/mL EGF for 15-180min increased phosphorylation levels of EGFR and decreased total levels of EGFR. Similarly, treatment with 10-100ng/mL EGF for 12h or 100ng/mL EGF for 15-180min increased phosphorylation levels of AKT, but not affected total levels of AKT. CONCLUSION: EGF affects ARPE-19 cell viability, proliferation and migration through inducing phosphorylation of the EGFR/AKT signaling pathway. The EGFR/AKT signaling pathway might play an important role in abnormal proliferation and migration of RPE cells in proliferative vitreoretinopathy.

Abstract Background Degenerative diseases are a major public health concern for the aging population and mesenchymal stem cells (MSCs) have great potential for treating many of these diseases. However, the quantity and quality of MSCs declines with aging, limiting the potential efficacy of autologous MSCs for treating the elderly population. Methods Human bone marrow (BM)-derived MSCs from young and elderly donors were obtained and characterized using standard cell surface marker criteria (CD73, CD90, CD105) as recommended by the International Society for Cellular Therapy (ISCT). The elderly MSC population was isolated into four subpopulations based on size and stage-specific embryonic antigen-4 (SSEA-4) expression using fluorescence-activated cell sorting (FACS), and subpopulations were compared to the unfractionated young and elderly MSCs using assays that evaluate MSC proliferation, quality, morphology, intracellular reactive oxygen species, β-galactosidase expression, and adenosine triphosphate (ATP) content. Results The ISCT-recommended cell surface markers failed to detect any differences between young and elderly MSCs. Here, we report that elderly MSCs were larger in size and displayed substantially higher concentrations of intracellular reactive oxygen species and β-galactosidase expression and lower amounts of ATP and SSEA-4 expression. Based on these findings, cell size and SSEA-4 expression were used to separate the elderly MSCs into four subpopulations by FACS. The original populations (young and elderly MSCs), as well as the four subpopulations, were then characterized before and after culture on tissue culture plastic and BM-derived extracellular matrix (BM-ECM). The small SSEA-4-positive subpopulation representing ~ 8% of the original elderly MSC population exhibited a “youthful” phenotype that was similar to that of young MSCs. The biological activity of this elderly subpopulation was inhibited by senescence-associated factors produced by the unfractionated parent population. After these “youthful” cells were isolated and expanded (three passages) on a “young microenvironment” (i.e., BM-ECM produced by BM cells from young donors), the number of cells increased ≈ 17,000-fold to 3 × 109 cells and retained their “youthful” phenotype. Conclusions These results suggest that it is feasible to obtain large numbers of high-quality autologous MSCs from the elderly population and establish personal stem cell banks that will allow serial infusions of “rejuvenated” MSCs for treating age-related diseases.

Osteoarthritis (OA) is a common and dynamic disease of the joints, including the articular cartilage, underlying bones and synovium. In particular, OA is considered as the degeneration of the cartilage. Tectorigenin (Tec) is known to affect many biological processes; however, its effects on articular chondrocytes remain unclear. This study aimed to assess the effects of Tec on articular cartilage. In vitro, Tec inhibited the expression levels of type X collagen, cyclooxigenase-2, matrix metalloproteinase (MMP)-3 and MMP-13, but enhanced the expression of Runx1, type II collagen and aggrecan in the presence of IL-1β. Meanwhile, Tec inhibited apoptosis through the Bax/Bcl-2/caspase-3 pathway, upregulating p-Bad, downregulating the Bax/Bcl-2 ratio, and activating caspase-3 compared with IL-1β treatment only. Moreover, this process was partially regulated by NF-κB P65. In vivo, the chondroprotective effects of Tec were assessed by establishing a model of surgically induced OA. Tec-treated joints exhibited fewer osteoarthritic changes than saline-treated joints. Meanwhile, 1.5 μg/kg Tec treatment produced a greater protective effect than 0.75 μg/kg Tec. The Osteoarthritis Research Society International (OARSI) scoring system, employed to assess histopathological grading of the models, as well immunohistochemistry for Aggrecan Neoepitope and MMP-3, further confirmed the results. In conclusion, this study showed that Tec plays a chondroprotective role in the OA process by preventing articular cartilage degeneration and chondrocyte apoptosis via the NF-κB P65 pathway.

AIM: To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor (EGFR)/AKT signaling pathway in retinal pigment epithelial (RPE) cells. METHODS: Human RPE cell lines (ARPE-19 cell) were treated with different doses of epidermal growth factor (EGF) and hydrogen peroxide (H2O2). Cell viability was determined by a methyl thiazolyl tetrazolium assay. Cell proliferation was examined by a bromodeoxyuridine (BrdU) incorporation assay. EGFR/AKT signaling was detected by Western blot. EGFR localization was also detected by immunofluorescence. In addition, EGFR/AKT signaling was intervened upon by EGFR inhibitor (erlotinib), PI3K inhibitor (A66) and AKT inhibitor (MK-2206), respectively. H2O2-induced oxidative stress was blocked by antioxidant N-acetylcysteine (NAC). RESULTS: EGF treatment increased ARPE-19 cell viability and proliferation through inducing phosphorylation of EGFR and AKT. H2O2 inhibited ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated increase of RPE cell viability and proliferation by affecting the EGFR/AKT signaling pathway. EGFR inhibitor erlotinib blocked EGF-induced phosphorylation of EGFR and AKT, while A66 and MK-2206 only blocked EGF-induced phosphorylation of AKT. EGF-induced phosphorylation and endocytosis of EGFR were also affected by H2O2 treatment. In addition, antioxidant NAC attenuated H2O2-induced inhibition of ARPE-19 cell viability through alleviating reduction of EGFR, and phosphorylated and total AKT proteins. CONCLUSION: Oxidative stress affects RPE cell viability and proliferation through interfering with the EGFR/AKT signaling pathway. The EGFR/AKT signaling pathway may be an important target in oxidative stress-induced RPE cell dysfunction.

Background: To evaluate the clinical characteristic, microsurgical treatment and outcomes of patients with multi-segment intramedullary cervical spinal cord tumors (MSICCT). Materials and methods: Prospective single center cohort study. 63 patients underwent microsurgery for MSICCT. Pre and postoperative function were assessed using the modified McCormick's grade, IJOA scoring system, and analyzed using the appropriate statistical tests. Results: 41 males, 22 females, three spinal segments were involved in 22(35%) cases, four or more in 41(65%) of cases. Majority of the tumors were ependymoma (54%), followed by astrocytoma (low grade 25%, high grade 8%). McCormick's grade: I&II in 40 patients (64%). There was no statistical difference between preoperative and three-month postoperative IJOA scores (P = 0.76), indicating no significant neurological deterioration after surgery. The extent of surgical resection was highly correlated to histological tumor type of MSICCT (χ2 = 34.82, P = 0.0001) and three-month postoperative IJOA scores (F = 2.62, P = 0.006). There is a high proportion of total resection in ependymomas, haemangioblastomas, cavernomas and schwannoma, whereas, we only achieved partial resection in most gliomas. With a mean follow up of 5.5 years (3 months–more than 12 years), clinical outcome improved or stabilized in 91% of cases (80% improved, 11% stabilized, 9% deteriorated). Conclusion: This series of MSICCT showed that high extent of surgical resection could be achieved in most ependymomas with good long-term outcome. Astrocytomas, in contrary remained challenging with 25% achieved gross total resection. Overall, compared to previous surgical series, we showed encouraging improvement in the clinical outcome of these patients managed surgically.