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Purpose: The objective of the study was to investigate efficacy and mechanisms of mouse adipose-derived mesenchymal stem cell-derived exosomes (mADSC-Exos) in the benzalkonium chloride (BAC)-induced mouse dry eye model. Methods: Exosomes in the mADSC culture supernatant were isolated by ultracentrifugation. Western blotting, nanoparticle tracking analysis, and transmission electron microscopy were used to characterize mADSC-Exos. An experimental mouse model of dry eye was established by instillation of 0.2% BAC. mADSC-Exos were administered following BAC treatment. The positive control group was treated with commercial eye drops (0.1% pranoprofen). Corneal fluorescein staining, tear secretion, and tear film break-up time (BUT) were evaluated, and histologic analysis of the cornea and conjunctiva was performed by hematoxylin and eosin and periodic acid-Schiff staining. Apoptosis in the corneal epithelium was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and by Western blotting. Levels of pro-inflammatory cytokines in the cornea and conjunctiva were evaluated by flow cytometry, and mRNA and protein levels of NLR family pyrin domain-containing 3 (NLRP3) pathway components were assessed by quantitative real-time PCR and Western blotting, respectively. Results: mADSC-Exos were characterized as vesicles with a bilayer membrane. The particle size distribution peak was at 134 nm. mADSC-Exos specifically expressed cluster of differentiation (CD)9, CD63, and CD81. mADSC-Exos treatment repaired ocular surface damage. Additionally, mADSC-Exos inhibited cell apoptosis, decreased the levels of interleukin (IL)-1β, IL-6, IL-1α, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, and increased levels of the anti-inflammatory cytokine IL-10. Meanwhile, NLRP3 inflammasome activation and upregulation of caspase-1, IL-1β, and IL-18 were reversed by mADSC-Exos. Conclusions: mADSC-Exos alleviate ocular surface inflammation, suggesting that it is a promising treatment for dry eye.

We study construction and dynamics of two-dimensional (2D) anisotropic vortex-bright (VB) soliton in spinor dipolar Bose-Einstein condensates confined in a 2D optical lattice (OL), with two localized components linearly mixed by the spin-orbit coupling and long-range dipole-dipole interaction (DDI). It is found that the OL and DDI can support stable anisotropic VB soliton in the present setting for arbitrarily small value of norm N. We then present a new method via examining the mean square error of norm share of bright component to implement stability analysis. It is revealed that one can control the stability of anisotropic VB soliton only by adjusting OL depth for a fixed DDI. In addition, the dynamics of the anisotropic VB soliton was studied by applying the kick to them. The mobility of the single kicked VB solition is Rabbi-like oscillation. However, for the collision dynamics of two kicked anisotropic VB solitons, their properties mainly depend on their initial distance and OL, and they can realize the transition from the bright component to the vortex component. Our work may provides a convenient way to prepare and manipulate anisotropic VB soliton in high dimensional space.

A predictor–corrector compact finite difference scheme is proposed for a nonlinear partial integro-differential equation. In our method, the time direction is approximated by backward Euler scheme and the Riemann–Liouville (R–L) fractional integral term is treated by means of first order convolution quadrature suggested by Lubich. Meanwhile, a two-step predictor–corrector (P–C) algorithm called MacCormack method is used. A fully discrete scheme is constructed with space discretization by compact finite difference method. Numerical experiment presents the scheme is in good agreement with the theoretical analysis.

Many patients with type 2 diabetes treated with premixed insulin gradually have inadequate glycemic control and switch to a basal-bolus regimen, which raises some concerns for weight gain and increased hypoglycemic risk. Switching to combination use of glp-1 agonist and basal insulin may be an alternative option.After a 12-week premixed human insulin 70/30 dosage optimization period, 200 patients with HbA1c of 7.0% to 10.0% were randomized into 24-week treatment groups with exenatide twice a day plus glargine or with aspart 70/30 twice a day.After 24 weeks, the patients receiving exenatide plus glargine (n = 90) had improved HbA1c control compared with those receiving aspart 70/30 (n = 90) (least squares mean change: ‒0.59 vs ‒0.13%; difference [95% CI]: ‒0.45 [‒0.74 to ‒0.17]) in the full analysis set population. Weight decreased 3.5 kg with exenatide and decreased 0.4 kg with aspart 70/30 (P.001). The insulin dose was reduced 10.7 units/day (95% CI, ‒12.2 to ‒9.2 units; P.001) with exenatide, and increased 9.7 units/day (95% CI, 8.2 to 11.2 units; P.001) with aspart 70/30. The most common adverse events were gastrointestinal adverse effects in the exenatide group (nausea [21%], vomiting [16%], diarrhea [13%]). The incidence of hypoglycemia was similar in 2 groups (27% for exenatide and 38% for aspart 70/30; P = .1).In premixed human insulin‒treated patients with type 2 diabetes with inadequate glycemic control, switching to exenatide twice a day plus glargine was superior to aspart 70/30 twice a day for glycemic and weight control.

Astragaloside IV (ASV), which has several pharmacological abilities, shows potential therapeutic effects on certain cancers by regulating the expression of long noncoding RNA (lncRNA). However, the anticancer role that ASV plays by regulating lncRNAs in breast cancer remains unknown. In this study, we first demonstrated that the lncRNA of TRHDE antisense RNA 1 (TRHDE-AS1) was downregulated in breast cancer tissues and cells. Low TRHDE-AS1 expression is associated with poor outcomes in patients with breast cancer and potentially contributes to the aggressive tumor biology of breast cancer. Furthermore, ASV significantly increased TRHDE-AS1 expression in a dose- and time-dependent manner in breast cancer cells. By upregulating TRHDE-AS1, ASV repressed breast cancer cell growth and metastasis both in vitro and in vivo. Taken together, our data indicated that TRHDE-AS1 participates in the anticancer role of ASV in breast cancer, which provides evidence for the application of ASV for breast cancer therapy.

Neobavaisoflavone (Neo), as a traditional Chinese medicine, is the active ingredient in the herb Psoralea corylifolial and has antitumor activity. Myeloid-derived suppressor cells (MDSCs), which are a heterogeneous population of haematopoietic cells of the myeloid lineage, have been reported to be closely related to the pathogenesis of tumour progression, but whether Neo can regulate MDSC expansion and function remains unclear. Here, we found that Neo could inhibit the expansion and suppressive function of MDSCs by targeting STAT3. Importantly, Neo inhibited the growth of 4T1 and LLC tumours in vivo, as well as lung metastasis of 4T1 tumours in vivo. Furthermore, we identified MDSCs as the direct targets by which Neo attenuated tumour progression. In addition, Neo notably enhanced anti-PD-1 efficacy in anti-PD-1-insensitive 4T1 tumours. Therefore, our study sheds light on the development of Neobased therapeutic strategies against cancer.

Purpose: The removal of the giant breast fibroadenoma (GFA) with esthetic repair of the severe deformed breast is a surgical challenge. Materials and Methods: This was a retrospective study of data...

A backward Euler difference scheme is formulated and analyzed for the integro-differential equations with the multi-term kernels. The convolution quadrature is used to deal with the Riemann-Liouvil...

Neobavaisoflavone (Neo), is the active constituent of the herb Psoralea corylifolial, used in the traditional Chinese medicine, and has anti-inflammatory activity, but whether Neo could regulate colitis remains unclear. T helper 9 (T

In this study, we discuss the superconvergence of the space-time discontinuous Galerkin method for the first-order linear nonhomogeneous hyperbolic equation. By using the local differential projection method to construct comparison function, we prove that the numerical solution is $$(2n+1)$$ -th order superconvergent at the downwind-biased Radau points in the discrete $$L^2$$ -norm. As a by-product, we obtain a point-wise superconvergence with order $$2n+\frac{1}{2}$$ in vertices. We also find that, in order to obtain these superconvergence results, the source integral term has to be approximated by $$(n+1)$$ -point Radau-quadrature rule. Numerical results are presented to verify our theoretical findings.

Objective: Breast cancer remains the most threatening triggers of cancer death in women. Drug resistance inevitably leads to the weakness of treatment for breast cancer. Macrophages, as one of the most abundant immune cells in tumor immune-infiltrating microenvironment, involves in cell survival, migration, and invasion of breast cancer. Methods: In this study, we compared the proportions of macrophages in patients with breast cancer with and without paclitaxel treatment, and investigated the targeted genes associated with macrophages for paclitaxel response. To explore the relationship between drug-related genes and breast cancer prognosis, survival analysis based on the drug-related genes were performed by website of Kaplan-Meier plotter with the threshold of significant P value < .05. Results: Compared to the normal samples, we revealed that paclitaxel significantly enhanced the ratio of macrophages in the tumor microenvironment. Furthermore, the expression of 3 drug-related genes (IFT46, PEX11A, and TMEM223) were significantly negatively associated with the proportions of macrophages. And it is worth to notice that PEX11A and TMEM223 were associated with better progression-free survival outcomes of patients with breast cancer. Moreover, PEX11A was associated with longer overall survival time of breast cancer. Conclusion: Taken all together, all the findings support to gain a better understanding to the development of more effective therapies targeted with paclitaxel.

BackgroundSince the pandemic outbreak of coronavirus disease 2019 (COVID-19), the health system capacity in highly endemic areas has been overwhelmed. Approaches to efficient management are urgently needed. We aimed to develop and validate a score for early prediction of clinical deterioration of COVID-19 patients.MethodsIn this retrospective multicenter cohort study, we included 1138 mild to moderate COVID-19 patients admitted to 33 hospitals in Guangdong Province from December 27, 2019 to March 4, 2020 (N =818; training cohort), as well as two hospitals in Hubei Province from January 21 to February 22, 2020 (N =320; validation cohort) in the analysis.ResultsThe 14-day cumulative incidences of clinical deterioration were 7.9% and 12.1% in the training and validation cohorts, respectively. An Early WArning Score (EWAS) (ranging from 0 to 4.5), comprising of age, underlying chronic disease, neutrophil to lymphocyte ratio, C-reactive protein, and D-dimer levels, was developed (AUROC: 0.857). By applying the EWAS, patients were categorized into low-, medium-, and high risk groups (cut-off values: two and three). The 14-day cumulative incidence of clinical deterioration in the low-risk group was 1.8%, which was significantly lower than the incidence rates in the medium-(14.4%) and high-risk (40.9%) groups (P ConclusionThe EWAS, which is based on five common parameters, can predict COVID-19-related clinical deterioration and may be a useful tool for a rapid triage and establishing a COVID-19 hierarchical management system that will greatly focus clinical management and medical resources to reduce mortality in highly endemic areas.

BackgroundSince the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) outbreaks in Wuhan, China, healthcare systems capacities in highly endemic areas have been overwhelmed. Approaches to efficient management are urgently needed and key to a quicker control of the outbreaks and casualties. We aimed to characterize the clinical features of hospitalized patients with confirmed or suspected COVID-19, and develop a mortality risk index for COVID-19 patients.MethodsIn this retrospective one-centre cohort study, we included all the confirmed or suspected COVID-19 patients hospitalized in a COVID-19-designated hospital from January 21 to February 5, 2020. Demographic, clinical, laboratory, radiological and clinical outcome data were collected from the hospital information system, nursing records and laboratory reports.ResultsOf 577 patients with at least one post-admission evaluation, the median age was 55 years (interquartile range [IQR], 39 - 66); 254 (44.0%) were men; 22.8% (100/438) were severe pneumonia on admission, and 37.7% (75/199) patients were SARS-CoV-2 positive. The clinical, laboratory and radiological data were comparable between positive and negative SARS-CoV-2 patients. During a median follow-up of 8.4 days (IQR, 5.8 - 12.0), 39 patients died with a 12-day cumulative mortality of 8.7% (95% CI, 5.9% to 11.5%). A simple mortality risk index (called ACP index), composed of Age and C-reactive Protein, was developed. By applying the ACP index, patients were categorized into three grades. The 12-day cumulative mortality in grade three (age ≥ 60 years and CRP ≥ 34 mg/L) was 33.2% (95% CI, 19.8% to 44.3%), which was significantly higher than those of grade two (age ≥ 60 years and CRP < 34 mg/L; age < 60 years and CRP ≥ 34 mg/L; 5.6% [95% CI, 0 to 11.3%]) and grade one (age < 60 years and CRP < 34 mg/L, 0%) (P ConclusionThe ACP index can predict COVID-19 related short-term mortality, which may be a useful and convenient tool for quickly establishing a COVID-19 hierarchical management system that can greatly reduce the medical burden and therefore mortality in highly endemic areas.

Background: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) outbreaks in Wuhan, China, healthcare systems capacities in highly endemic areas have been overwhelmed. Approaches to efficient management are urgently needed and key to a quicker control of the outbreaks and casualties. We aimed to characterize the clinical features of hospitalized patients with confirmed or suspected COVID-19, and develop a mortality risk index for COVID-19 patients. Methods: In this retrospective one-centre cohort study, we included all the confirmed or suspected COVID-19 patients hospitalized in a COVID-19-designated hospital from January 21 to February 5, 2020. Demographic, clinical, laboratory, radiological and clinical outcome data were collected from the hospital information system, nursing records and laboratory reports. Findings: Of 577 patients with at least one post-admission evaluation, the median age was 55 years (interquartile range [IQR], 39 - 66); 254 (44·0%) were men; 22·8% (100/438) were severe pneumonia on admission, and 37·7% (75/199) patients were SARS-CoV-2 positive. The clinical, laboratory and radiological data were comparable between positive and negative SARS-CoV-2 patients. During a median follow-up of 8·4 days (IQR, 5·8 - 12·0), 39 patients died with a 12-day cumulative mortality of 8·7% (95% CI, 5·9% to 11·5%). A simple mortality risk index (called ACP index), composed of Age and C-reactive Protein, was developed. By applying the ACP index, patients were categorized into three grades. The 12-day cumulative mortality in grade three (age ≥ 60 years and CRP ≥ 34 mg/L) was 33·2% (95% CI, 19·8% to 44·3%), which was significantly higher than those of grade two (age ≥ 60 years and CRP < 34 mg/L; age < 60 years and CRP ≥ 34 mg/L; 5·6% [95% CI, 0 to 11·3%]) and grade one (age < 60 years and CRP < 34 mg/L, 0%) (P

Neobavaisoflavone (Neo), is the active constituent of the herb Psoralea corylifolial, used in the traditional Chinese medicine, and has anti-inflammatory activity, but whether Neo could regulate colitis remains unclear. T helper 9 (TH9) cells, a subset of CD4+ T helper cells characterized by secretion of IL-9, have been reported to be involved in the pathogenesis of many autoimmune and inflammatory diseases, but whether Neo could control TH9 cell differentiation also remains unclear. Here, we found that Neo could decrease IL-9 production of CD4+ T cells by targeting PU.1 in vitro. Importantly, Neo had therapeutic effects on DSS-induced colitis. Furthermore, we identified TH9 cells as the direct target of Neo for attenuating bowel inflammation. Therefore, Neo could serve as a lead for developing new therapeutics against inflammatory bowel disease.

Schisandrin B (Sch B) is the major active constituent of the traditional Chinese medicine Schisandra chinensis and has anti-inflammatory activity, but the target of Sch B remains unclear. T helper 17 (TH17) cells have been involved in the pathogenesis of many autoimmune and inflammatory diseases. Here, we showed that Sch B could decrease IL-17A production of CD4+ T cells by targeting STAT3 in vitro. Importantly, Sch B has therapeutic effects on DSS-induced acute and chronic colitis, CD4+CD45RBhigh T cell-induced colitis. Furthermore, we identified TH17 cells as the direct target of Sch B for mediating its anti-inflammatory activity. Sch B could serve as a lead for developing new therapeutics against TH17 cells or IL-17A cytokine-driven diseases.

Though it has been reported that Artemisinin (ART), a traditional Chinese herb extract medicine, might inhibit the transferrin receptor of tumor cells to transfer iron and induce cell apoptosis, it remains controversial about the mechanism of ART-induced cell apoptosis. In this study, the single-cell Raman spectral data during ART-induced Raji cells apoptosis were acquired by Micro-Raman spectroscopy. Correspondingly, Raman spectral data during Dexamethasone (DEX)-induced Raji cells apoptosis were also presented. The obtained result revealed that peaks at 1303 and 1655 cm−1 assigned to proteins and the peak at 785 cm−1 assigned to the symmetric stretching vibration mode of O P O of DNA were changed in intensity in ART-treated cells relative to untreated cells. One possible reason was that ART played a role to inhibit the receptors generation of Raji cells during apoptosis. Moreover, by combining Raman spectral differences and principal component analysis (PCA), it was presented that the main biochemical changes of ART-induced cell apoptosis were come from the content and structure changes of proteins and nucleic acids, which were different from DEX-induced DNA changes, indicating that the mechanism of ART-induced cell apoptosis might be different with DEX-induced DNA damaging cell apoptosis. Importantly, these results also showed that PCA based Raman spectral analysis should be a better approach to exhibit the drugs-induced cell apoptosis. Moreover, this method will provide a useful tool to construct a biological model of cell apoptosis in vitro for the clinical treatment and anticancer drug research.

A microspherical mesostructured zeolite (MMZ-5) with MFI-topological frameworks is employed. In-situ FT-IR spectra of pyridine and 2, 6-di-tert-butylpyridine have indicated that almost all of the acid sites are located on the zeolitic external surface, which are favorable for access of reactive large molecules. This key effect, along with the reduced diffusion and steric limitation, has been proposed to be main the reason for the enhanced catalytic activity, selectivity and stability exhibited in benzylation of aromatics with benzyl chloride. The need for optimized characterization of the mesoporous surface acidity for different aromatics is highlighted.

This paper is concerned with the finite element method for nonlinear Hamiltonian systems from three aspects: conservation of energy, symplicity, and the global error. To study the symplecticity of the finite element methods, we use an analytical method rather than the commonly used algebraic method. We prove optimal order of convergence at the nodes tn for mid-long time and demonstrate the symplecticity of high accuracy. The proofs depend strongly on superconvergence analysis. Numerical experiments show that the proposed method can preserve the energy very well and also can make the global trajectory error small for long time.

PURPOSE The objective of this study was to evaluate the feasibility and safety of vitrectomy combined with magnetic intraorbital foreign body (IOrFB) removal in the patients with perforating eye injury and retained magnetic IOrFBs. METHODS A consecutive series of 7 patients with perforating eye injury and retained magnetic IOrFBs were included to perform secondary combination surgery (vitrectomy combined with IOrFB removal) after primary repair. Clinical data such as age, sex, hours and cause of injury, site and size of penetrating wound and IOrFB, involved intraocular tissues, surgical intervention, interval between surgeries, length of follow-up, anatomic recovery, visual outcome, and so on were recorded. RESULTS Except for an unsuccessful IOrFB removal in case 6 in which IOrFB was finally extracted after 3 months, the remaining 6 cases had been operated on successfully both in vitrectomy and IOrFB removal. All the cases resulted in not only anatomic recovery but also good visual outcomes. No complications occurred. Seven cases revealed flat retina after silicone oil removal at a 3- to 12-month follow-up. Final best correct visual acuity equal to or better than 0.05 and 0.2 were 6 (85.7%) and 4 (57%) cases, respectively, and only 1 case was without improvement because of macular involvement. CONCLUSIONS A combination surgery of vitrectomy with IOrFB removal is a highly efficient and safe procedure for the management of perforating eye injury with magnetic IOrFB. Prompt and proper management, such as preoperative exact localization of IOrFB, thoroughly cleaning of vitreous hemorrhage, complete sealing of retinal hole, and so on, is crucial for the successful achievement.

We report two posttraumatic fungal endophthalmitis cases with anterior and entire segment involvement caused, respectively, by Candida albicans and Aspergillus fumigatus. The anterior endophthalmitis induced by C. albicans presented multifocal lesions with hyphael structures in anterior chamber, but without involvement of posterior vitreous. The pan-endophthalmitis caused by A. fumigatus displayed significant hypopyon and vitritis. Treatment strategies are anterior chamber cleaning for anterior endophthalmitis and vitrectomy for pan-endophthalmitis, excepting systemic and topical antifungal drug applications including intravitreal injection for both types of endophthalmitis. There is a much better outcome in the case with anterior segment involvement than that with entire segment involvement. This case report provides evidence that the different types of posttraumatic fungal endophthalmitis related to different fungal infections indeed existed and should be managed with different strategies.