The effect of airborne particulate matter 2.5 (PM2.5) on meibomian gland.

Exposure to particulate matters in air pollution of 2.5 µm or less (PM2.5) was associated with loss of meibomian glands. The aim of this study was to verify that PM2.5 could directly impact meibomian gland epithelial cells and damage their function. To investigate the impact of PM2.5 on meibomian gland, immortalized human meibomian gland epithelial cells were treated with various concentrations of PM2.5in vitro. Meibomian gland cell microstructure, cell viability, expression of proliferating cell nuclear antigen and IL-1ß, and intracellular accumulation of acidic vesicles were measured by transmission electron microscopy, cell counting, Western blot and LysoTracker staining, respectively. To further study the effect of PM2.5in vivo, male C57BL/6J mice were treated with 5 mg/ml PM2.5 or vehicle for 3 months. Corneal fluorescein staining and ocular examinations were done before and after the treatment. Eyelids tissues were processed for morphological studies, immunostaining and Oil Red O staining. Our data suggest that exposure to PM2.5 caused significant meibomian gland dropout, clogged gland orifice and increased corneal fluorescein staining that were consistent with the clinical presentations of meibomian gland dysfunction. Prominent changes in the morphology and ultrastructure of meibomian glands was observed with PM2.5 treatment. PM2.5 promoted ductal keratinization, inhibited cell proliferation, induced cell apoptosis and increased Interleukin-1ß production in meibomian gland epithelial cells. This study may explain the association between PM2.5 exposure and meibomian gland dropout observed in clinic. PM2.5 resuspension instillation could be used to induce a meibomian gland dysfunction animal model.

Do not stumble over the same "stone" twice: a case series of endogenous endophthalmitis secondary to severe systemic diseases.

BACKGROUND: Endogenous endophthalmitis (EE) is a rare but highly destructive eye emergency secondary to systemic infection. Acute endophthalmitis can lead to irreversible vision impairment or even loss of the whole eye, unless being diagnosed and treated promptly. CASE PRESENTATION: This study reports three typical EE cases of endogenous endophthalmitis secondary to different severe systemic diseases. Patients were recruited from the Department of ophthalmology at Zhongnan hospital of Wuhan University and the Department of ophthalmology at the Second Affiliated Hospital of Fujian Medical University. Patients were followed up for up to 60 days. Among these cases, the eye symptoms is the initial manifestations while secondary to original different special systemic conditions. Patients have been treated under dynamically prompt response undergoing systemic treatment and eye treatment at the same time. Best corrected visual acuity were 20/40, 20/60 and light perception during follow-up evaluation. CONCLUSIONS: Our observation suggest that prompt identification and treatment could save patients' vision from EE.

Eyes on the Lid: The Impact of Fibroblast Growth Factor Receptor Targeting Drug on Human Meibomian Gland.

OBJECTIVE: To determine whether fibroblast growth factor receptor (FGFR)-targeting drug could impact human meibomian gland. METHODS: We followed up with three patients who were using pemigatinib for 4 to 10 weeks. The patients were evaluated for their ocular surface disease index, best-corrected visual acuity, Schirmer test, cornea staining, meibum expressibility score, tear meniscus height, noninvasive tear film breakup time, and meibomian gland area. The distribution of the FGFR family, FGF7, and FGF10 were evaluated by immunofluorescence staining and Western blot in fresh tarsal tissues from deidentified patients who underwent lid plastic surgeries. RESULTS: All patients developed apparent meibomian gland atrophy, shortening and narrowing of ducts, and significantly increased meibum expressibility and decreased noninvasive tear film breakup time within 5 to 8 weeks. Laboratory evaluations confirmed that human meibomian gland expresses abundant fibroblast growth factor receptors. CONCLUSIONS: These findings indicate that meibomian gland is a target tissue of FGFR inhibitors, and patients who use these drugs may develop meibomian gland dysfunction.

Immunohistochemistry combined with NGS to assist the differential diagnosis of multiple primary lung cancer with lymph node metastasis: a case report.

In recent years, the incidence of synchronous multiple primary lung cancers (MPLCs) has gradually increased. Surgery is the preferred treatment for these patients. There are great differences in the driving genes between individual tumors in patients with MPLC, and tumors with targeted mutations do not represent other tumors, which challenges the selection of targeted therapies for patients with MPLC. Driving mutations in each lesion after surgery are crucial for establishing accurate pathological staging and subsequent treatment strategies. There are some mutated genes in the lymph nodes of postoperative metastatic MPLCs, and the tumor cell count/DNA concentration is low, which limits the next-generation sequencing (NGS) detection effect. A combination with immunohistochemistry to determine the source of metastasis may be a better choice. This study reports a rare case of lung cancer with double primary adenocarcinomas of the lung combined with 10 groups of lymph node metastases. The source of metastasis was identified using immunohistochemistry combined with NGS to guide postoperative adjuvant treatment. We hope that this case report can provide new ideas for the identification of MPLCs and assist in their diagnosis and individualized treatment. In addition, the combination specific immunohistochemistry and NGS seems to be an effective identification method. This approach can provide clinical benefits; however, this still requires further exploration through studies with large sample sizes.

Response to Pralsetinib in Multi-Drug-Resistant Breast Cancer With CCDC6-RET Mutation.

Triple-negative breast cancers (TNBC) represent a pathological subtype of breast cancer, which are characterized by strong invasiveness, high metastasis rate, low survival rate, and poor prognosis, especially in patients who have developed resistance to multiline treatments. Here, we present a female patient with advanced TNBC who progressed despite multiple lines of treatments; next-generation sequencing (NGS) was used to find drug mutation targets, which revealed a coiled-coil domain-containing protein 6 (CCDC6)-rearranged during transfection (RET) gene fusion mutation. The patient was then given pralsetinib, and after one treatment cycle, a CT scan revealed partial remission and adequate tolerance to therapy. Pralsetinib (BLU-667) is a RET-selective protein tyrosine kinase inhibitor that can inhibit the phosphorylation of RET and downstream molecules as well as the proliferation of cells expressing RET gene mutations. This is the first case in the literature of metastatic TNBC with CCDC6-RET fusion treated with pralsetinib, an RET-specific antagonist. This case demonstrates the potential efficacy of pralsetinib in cases of TNBC with RET fusion mutations and suggests that NGS may reveal new opportunities and bring new therapeutic interventions to patients with refractory TNBC.

Feasibility study and material selection for powder-bed fusion process in printing of denture clasps.

BACKGROUND AND OBJECTIVE: The retention of selective laser melting (SLM)-built denture clasps is inferior to that of cast cobalt-chromium (Co-Cr) clasps engaging 0.01-in undercuts, which are commonly used in clinical practice. Either the clasps engage in excessively deep undercuts or inappropriate printing process parameters are applied. With appropriate undercut engagement and levels of process parameters, the retention of SLM-built clasps (including Co-Cr, commercially pure titanium [CP Ti], and Ti alloy [Ti-6Al-4V] ones) may be comparable to that of cast Co-Cr clasps. Therefore, this feasibility study aimed to evaluate their retention to guide dentists during material selection for the powder-bed fusion process during the printing of denture clasps. METHODS: We engaged the clasp arm at an appropriate undercut depth (0.01 or 0.02 in), built clasps at the orientation of their longitudinal axes approximately parallel to the build platform, generated square prism support structures at a critical overhang angle of 30°, applied optimized laser parameters (laser power, scan speed, and hatch space), and adopted annealing treatment for Co-Cr, CP Ti, and Ti-6Al-4V clasps. After postprocessing and accuracy measurement, an insertion/removal test of the clasps for 15,000 cycles was performed to simulate 10 years of clinical use, and the retentive force was recorded every 1500 cycles. Permanent deformation of the retentive arms of the clasps was measured. Cast Co-Cr clasps engaging 0.01-in undercuts were designated the control group. RESULTS: The initial retentive forces of the SLM-built Co-Cr clasps engaging 0.01-in undercuts and CP Ti and Ti-6Al-4V clasps engaging 0.02-in undercuts were comparable to those of the control group. SLM-built Co-Cr clasps engaging 0.01-in undercuts and Ti-6Al-4V clasps engaging 0.02-in undercuts had similar final retentive force and less permanent deformation compared with those of the control group; SLM-built CP Ti clasps engaging 0.02-in undercuts had lower final retentive force and greater permanent deformation. CONCLUSIONS: Considering the long-term retention and permanent deformation of the retentive arms, Co-Cr and Ti-6Al-4V alloys, except CP Ti, are recommended for printing denture clasps. SLM-built Co-Cr clasps should engage 0.01-in undercuts, and Ti-6Al-4V clasps should engage 0.02-in undercuts.

Cancer stem-like cells contribute to paclitaxel resistance in esophageal squamous cell carcinoma.

OBJECTIVE: To examine the role of esophageal squamous cell carcinoma (ESCC) stem cells in paclitaxel resistance through the molecular characterization of ESCC stem cells. METHODS: A resistant cell line (RR-ECl09) of cells were established using intermittent induction and time increments of high-dose paclitaxel in a human esophageal squamous cell carcinoma line (EC109). The multidrug resistance of RR-ECl09 cells to anticancer agents was evaluated by MTT assay. The RR-EC109 and EC109 cells were used for sphere formation assays, clonogenicity assays, stem cell gene expression, and the expression of epithelial-mesenchymal transition markers. RESULTS: The RR-EC109 cells were established over 7 months. RR-ECl09 cells had 67.258 fold resistance to paclitaxel. The percentage of sphere formation and clone proliferation ability of RR-EC109 cells was higher than that of EC109 cells (P < 0.05). The amount of side population cells in RR-EC109 cells was higher than that of EC109 cells (P < 0.05). RR-EC109 cells produced more mRNA for Bmi1, Nanog, Oct4, Sox2, ABCG2, Nestin, and Ki-67 than EC109 cells (P < 0.05). E-cadherin expression was lower in RR-EC109 cells than in EC109 cells, while N-cadherin, Snail, and Twist expressions were higher in RR-EC109 cells than in EC109 cells (P < 0.05). CONCLUSIONS: Cancer stem cell (CSC)-like cells exist among paclitaxel-resistant cells in ESCC and may play a role in ESCC drug resistance.

Case Report: Response to Immunotherapy and Anti-Androgen Therapy in Male Occult Triple-Negative Breast Cancer.

Male occult triple-negative breast cancer (TNBC) is an exceedingly rare form of breast cancer, and prospective information regarding its management is therefore lacking. Current treatment strategies are largely extrapolated from clinical trials of female breast cancer, leading to substantial knowledge gaps concerning the optimal management of male breast cancer. Here, we present a male patient with occult TNBC who responded to immunotherapy, with an obvious reduction in his tumor burden following antiandrogen therapy, after heavy treatment with several lines of chemotherapy. This case highlights the potential efficacy of immunotherapy in cases of male TNBC and suggests a role for antiandrogen therapy in managing patients with luminal androgen receptor-positive TNBC.

Degradation of streptomycin in aquatic environment: kinetics, pathway, and antibacterial activity analysis.

Streptomycin used in human and veterinary medicine is released into the environment mainly through excretions. As such, its elimination in water should be investigated to control pollution. In this study, the degradation of streptomycin in water was studied, and the influence of variables, including light exposure, solution pH, temperature, ionic strength, dissolved organic matter (DOM), and coexisting surfactants, on degradation was investigated. Streptomycin degradation was consistent with the first-order model in aquatic environments. Its degradation rate under light exposure was 2.6-fold faster than that in the dark. Streptomycin was stable under neutral conditions, but it was easily decomposed in acidic and basic environments. Streptomycin degradation was enhanced by high temperature, and its half-life decreased from 103.4 days at 15 °C to 30.9 days at 40 °C. This process was also accelerated by the presence of Ca2+ and slightly improved by the addition of HA. Streptomycin degradation was suppressed by high levels of the cationic surfactant cetyltri- methylammonium bromide (CTAB), but was promoted by the anionic surfactant sodium dodecyl benzene sulfonate (SDBS). The main degradation intermediates/products were identified through liquid chromatography-mass spectrometry, and the possible degradation pathway was proposed. The antibacterial activity of streptomycin solution was also determined during degradation. Results showed that STR degradation generated intermediates/products with weaker antibacterial activity than the parent compound.