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• It is the first clinical report of Nectria haematococca infection in humans. • N. haematococca keratitis is severe and likely to recur after keratoplasty. • The recurrence occurred primarily in the second week after keratoplasty. • The effect of local use of fluconazole and voriconazole is not ideal. • The next-generation sequencing is useful in the diagnosis of rare fungal infections. Fungal keratitis (FK) is a kind of serious corneal infection and penetrating keratoplasty (PKP) is needed when medical therapy fails. Although Nectria haematococca is found as endophytes in the roots of some plant species, there has been no report of N. haematococca infection in human. We reviewed 46 patients who underwent PKP due to FK in our hospital from July 2021 to December 2021, and there were three patients who had relapsed. The next-generation sequencing revealed that all three corneas were infected with N. haematococca. Based on the ocular manifestation and treatment course of three cases, we summarize the characteristics of N. haematococca FK: the scope of corneal infection was widespread with severe hypopyon. The effect of local use of fluconazole and voriconazole was not ideal, and PKP was the main treatment. Even after a large-scale corneal lesion resection, the lesion may recur. The recurrence occurred primarily in the second week after PKP. This is the first clinical report of N. haematococca infection in humans. Compared with the other currently known FK caused by the Fusarium solani species complex, N. haematococca keratitis is more severe and more likely to recur. [ABSTRACT FROM AUTHOR]

• We systematically analyzed several distinct and unique parasite characteristics on ocular surface, especially latency and crypsis • We proposed specific examination techniques and methods as well as prevention and treatment strategies from these specific perspectives • Our suggestions provide help with prompt timely diagnoses and early interventions for these diseases by health care workers and improve the public's awareness of parasitic infections. Parasitic infections of the eye are a major cause of ocular-surface diseases globally. While most infections are treatable, parasites can cause varying levels of damage mostly due to late diagnosis or misdiagnosis as a result of doctors' unfamiliarity with their characteristics of latency and crypsis, as well as lack of awareness by the patients. In this study, we present three cases of phthiriasis palpebrarum, thelaziasis, and ophthalmomyiasis, respectively. Two of the cases were treated at the clinic and did not recur. One patient refused treatment and was lost to follow-up. By evaluating the natural histories, morphology, symptoms, clinical findings, and treatment of these parasitic diseases, we systematically analyzed several distinct and unique parasite characteristics, especially latency and crypsis. Furthermore, we have proposed specific examination techniques and methods as well as prevention and treatment strategies from these specific perspectives, aiming to prompt timely diagnoses and early interventions for these diseases by health care workers and improve the public's awareness of parasitic infections. Parasitosis on the ocular surface is a global infectious disease, and prevention strategies include maintaining personal and environmental hygiene and limiting contact with animals. We recommend that health care workers should enhance their ability to detect and diagnose these diseases while promoting the public's awareness of them in the context of our new perspectives. [ABSTRACT FROM AUTHOR]

Anaerobic bacteria and facultative anaerobe are usually used as delivery carriers of antitumor drugs because of their tumor hypoxia targeting and antitumor immune activation abilities, but suffer from dose-dependent systemic side effects. Here, engineered probiotics Nissle 1917 (EcN-T) were constructed for in-situ synthesis of melanin in tumor region for enhanced photothermal therapy (PTT) combining with immunotherapy. By means of genetic engineering, EcN-T that could highly express tyrosinase under near-infrared (NIR) light irradiation were constructed. Due to their intrinsic tumor hypoxia targeting, EcN-T could accumulate and rapidly proliferate in tumor region after intravenous injection. Tyrosinase expression for the following melanin biosynthesis within tumor could be initiated upon NIR exposure. Hyperbaric oxygen treatment facilitated the oxidation of tyrosine to promote the generation of melanin in situ, giving robust photothermal performance to induce immunogenic tumor cell death. Assited by immunostimulatory responses of EcN, maturation of dendritic cells and priming of cytotoxic T cells were largely promoted in tumor tissue, resulting in significant inhibition of tumor growth and recurrence. This bacteria-mediated combined therapeutic strategy showed high efficacy and good safety. By means of genetic engineering and synthetic biology, engineered probiotics Nissle 1917 (EcN-T) which show excellent tumor targeting and proliferation abilities are constructed for in-situ synthesis of melanin in tumor region induced by NIR light irradiation and HBO treating. Upon light exposure, considerable heat can be generated to induce immunogenic tumor cell death. Assited by immunostimulatory responses of EcN, maturation of dendritic cells and priming of cytotoxic T cells are largely promoted in tumor tissue, giving significant inhibition of tumor growth and recurrence. [Display omitted] • Engineered probiotics Nissle 1917 can intracellularly produce melanin with excellent photothermal performance. • Engineered probiotics Nissle 1917 can rapidly proliferate and homogenously distribute in tumor region. • Melanin biosynthesis within tumor can be initiated upon external NIR exposure. • Hyperbaric oxygen can promote the generation of melanin within tumor. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the performance of combined T2 mapping and T2 iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) in orbital tissues to predict the therapeutic efficacy of intravenous glucocorticoids (IVGCs) for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO).Method: Sixty-three active and moderate-to-severe TAO patients (responsive group, n = 35; unresponsive group, n = 28) who underwent orbital MRI before receiving IVGCs were retrospectively enrolled. Baseline clinical characteristics and imaging parameters were analyzed and compared between the two groups of different therapeutic efficacy. Binary logistic regression analysis was conducted to determine the independent predictors, the predictive performance of which was evaluated using receiver operating characteristic curve analysis.Results: The mean T2 relaxation time of extraocular muscle (EOM-T2RTmean) (P = 0.001), maximum T2RT of EOM (EOM-T2RTmax) (P = 0.001), mean water fraction of EOM (EOM-WFmean) (P < 0.001), maximum WF of EOM (EOM-WFmax) (P < 0.001) and exophthalmos (P = 0.007) were significantly higher in the responsive group than in the unresponsive group. EOM-T2RTmean (P < 0.001) and EOM-WFmax (P < 0.001) were determined as independent predictors for responsive patients with TAO in the multivariable analysis. Combining EOM-T2RTmean ≥ 77.1 and EOM-WFmax ≥ 91.52 demonstrated optimal efficiency for prediction (area under the curve = 0.844) and optimal predictive sensitivity (77.1%). Setting EOM-WFmax ≥ 91.52 achieved the optimal predictive specificity (89.3%).Conclusions: Pretherapeutic quantitative measurements, based on combining T2 mapping and T2 IDEAL in orbital tissues, are valuable for predicting IVGC treatment response in active and moderate-to-severe TAO. EOM-T2RTmean and EOM-WFmax may become promising IVGC treatment response predictors. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether unilateral primary acquired nasolacrimal duct obstruction (PANDO) changes the volume and water fraction of both lacrimal glands, using three-dimensional fast spin echo (3D-FSE)-Cube-Flex images, and to identify whether the lacrimal gland is a target organ in this disease.Methods: 3D-FSE-Cube-Flex images of both lacrimal glands in 25 healthy volunteers and 31 patients with unilateral PANDO were retrospectively reviewed. The differences in volume and water content in the lacrimal glands between the controls, non-PANDO side, and PANDO side groups were examined. Moreover, the associations between magnetic resonance imaging (MRI) parameters and disease duration were assessed with correlation analysis.Results: The lacrimal gland volumes were not significantly different between the PANDO and non-PANDO side groups, compared to the control group (P = 0.484). However, the gland volumes tended to be increased bilaterally in patients with PANDO. In contrast, the gland water fractions in the PANDO and non-PANDO side groups were significantly higher than those in the control group (P = 0.009 and P = 0.014, respectively), and similar between the non-PANDO and PANDO side groups (P = 0.897). No correlation was found between the disease duration and the gland MRI parameters (volume and water fraction).Conclusions: Both lacrimal glands are affected by unilateral PANDO. A change in the water fraction of these glands appears to precede the change in volume and may be a sensitive early indicator. [ABSTRACT FROM AUTHOR]

We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1) 1 1 IGF1, insulin-like growth factor I. protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R) 2 2 OGD/R, oxygen and glucose deprivation and simulated reperfusion. , and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT 3 3 p-AKT, phospho-AKT. and p-GSK-3β 4 4 AKT, protein kinase B. , thus activating the AKT 5 5 p-GSK-3β, phospho-GSK-3β. signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1 6 6 Mcl-1, myeloid cell leukemia-1. and Bcl-2 7 7 Bcl-2, B-cell lymphoma-2. , and decreased the expression level of the pro-apoptotic protein Bax 8 8 Bax, Bcl-2 associated X protein. , thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP) 9 9 PPP, picropodophyllin. , the inhibitor of insulin-like growth factor I receptors (IGF1R) 10 10 IGF1R, insulin-like growth factor I receptors. . Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment. [ABSTRACT FROM AUTHOR]