[Research Progress of Regulatory T Cells in the Pathogenesis of Multiple Myeloma --Review].

The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.

Atypical stromal herpes simplex keratitis: clinical features and diagnosis.

PURPOSE: To report atypical clinical features and diagnosis of stromal herpes simplex keratitis (HSK) and to evaluate the diagnostic efficiency of tear HSV-sIgA in atypical HSK. STUDY DESIGN: Prospective observational study. METHODS: Records of keratitis' patients with tear herpes simplex virus (HSV)-sIgA test results acquired between May 2019 and November 2021 were evaluated retrospectively. Positive tear HSV-sIgA test was used to identify herpes simplex virus (HSV) infection. Patients with typical presentations and histories of HSV keratitis (HSK) were excluded. RESULTS: Eleven eyes of 11 patients initially diagnosed as keratitis caused by other etiology were confirmed as having HSV infection by positive results of tear HSV-sIgA. Clinical features of atypical stromal HSK were variable. Antiviral treatment was effective in all patients. CONCLUSION: The appearance of an atypical stromal HSK represents a diagnostic challenge. Tear HSV-sIgA test could help provide a quick diagnosis.

Comprehensive Analysis of circRNA-Associated-ceRNA Networks in Human Corneal Endothelial Dysfunction.

PURPOSE: Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that regulate gene expression through the competitive endogenous RNA (ceRNA) mechanism. CircRNA-associated-ceRNA networks are closely related to oxidative stress-related diseases. Oxidative stress-induced dysfunction of the corneal endothelium (CE) is a major pathological feature in many corneal diseases. This study was aimed to analyze circRNA-associated-ceRNA networks in oxidative stress-induced CE dysfunction. METHODS: A CE dysfunction model was established using human corneal endothelial cells (HCECs) treated with H 2 O 2 at a concentration of 250 µM for 4 hours at 37°C. High-throughput sequencing was conducted to determine the expression profiles of circRNA, miRNA, and mRNA. Bioinformatic analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes analysis, were conducted to identify the potential biological modules and pathologic pathways of dysregulated circRNAs. CircRNA-associated-ceRNA networks were established based on the data of sequencing and bioinformatic analyses. RESULTS: We obtained 108 differentially expressed circRNAs, including 77 upregulated and 31 downregulated circRNAs. GO analysis suggested that dysregulated circRNAs were mainly targeted to protein quality control for misfolded or incompletely synthesized proteins (biologic process), nuclear chromatin (cellular component), and ubiquitin protein ligase binding (molecular function). GO terms related to CE functions responding to oxidative stress were also identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that dysregulated circRNAs were mostly enriched in the adherens junction pathway. Network analysis identified several potential therapeutic targets for CE dysfunction. CONCLUSIONS: CircRNAs are significantly dysregulated in HCECs under oxidative stress. The circRNA-associated-ceRNA networks are closely related to HCEC functions. Targeting these networks might provide novel therapies for CE dysfunction.

Recycling of spent mushroom substrate: Utilization as feed material for the larvae of the yellow mealworm Tenebrio molitor (Coleoptera: Tenebrionidae).

Spent mushroom substrate is made from the waste remaining after the harvest of mushrooms. Here, we evaluated the potential of five spent edible fungi (Auricularia cornea, Lentinus edodes, Pleurotus eryngii, P. citrinopileatus and P. ostreatus) substrates as feed sources for Tenebrio molitor larvae. Young larvae did not survive on any substrate except the spent L. edodes substrate (36.7%). The survival rates in young larvae were similar among the different diets in which wheat bran or rice bran was replaced with 0, 20, 30, 40, 50, or 60% spent L. edodes substrate. The weights of the surviving larvae were decreased only when 70% of wheat bran and > 40% of rice bran was replaced with spent L. edodes substrate. In addition, the middle-aged larvae fed wheat bran only were significantly larger than those fed diets with 30~60% spent L. edodes substrate in dry feed, but the larvae of all treatments failed to pupate. Whereas the green feed was added in dry feed, there were no significant differences in pupal weight, pupation rate, pupal duration, adult emergence, or deformed adults among the three treatments in middle-aged larvae that were fed on diets containing 0, 30, or 40% spent L. edodes substrate. Collectively, these results suggest that spent L. edodes substrate has considerable potential to be used as a partial replacement (< 40%) of conventional feed for T. molitor, and spent mushroom substrate waste may be recycled as feed material for resource insects.

Optimized pupal age of Tenebrio molitor L. (Coleoptera: Tenebrionidae) enhanced mass rearing efficiency of Chouioia cunea Yang (Hymenoptera: Eulophidae).

Chouioia cunea Yang (Hymenoptera: Eulophidae) has been widely used for biological control of the fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), in China. The yellow mealworm, Tenebrio molitor L. (Coleoptera: Tenebrionidae), an important resource insect species distributed worldwide, is considered to be a potential alternative host for mass rearing of C. cunea to the Chinese oak silkworm, Antheraea pernyi (Guerin-Meneville) (Lepidoptera: Saturniidae), which is currently used. In this study, we investigated the effects of host age on C. cunea mass rearing by measuring parasitism, development and adult fertility of C. cunea on T. molitor pupae of different ages. The results showed no significant differences in the percentage of parasitized hosts and developmental time of C. cunea in pupae of different ages. However, the number of C. cunea adults (137.2-154.7 adults per host) that emerged from 0, 1, and 2-day-old pupae was significantly higher than that from 4-day-old pupae. The lowest percentages of unemerged adults were found in 2-day-old (1.2%) and 3-day-old (1.4%) pupae, which were significantly lower than that of 4-day-old pupae (10.3%). The emergence of adult females from 0 to 2-day-old pupae (120.2-142.3 per pupa) was significantly higher than that from 4-day-old hosts (64.6). Adult females emerging from 2-day-old pupae carried significantly more eggs (258.2 eggs/female) than those from 0 and 1-day-old pupae (178.4-178.9 eggs/female). Our findings indicated that 2-day-old pupae of T. molitor were most suitable to rear C. cunea. Overall, this research provided valuable information to optimize pupae for the mass rearing of C. cunea on host T. molitor.

Tear HSV-specific secretory IgA as a potential indicator for recurrent stromal herpes simplex keratitis: a preliminary study.

PURPOSE: To assess the herpes simplex virus-specific tear secretory IgA (sIgA) and its correlation with specific serum antibodies and to evaluate the possible value of specific tear sIgA for prediction of herpes simplex keratitis (HSK) recurrence. METHODS: Tear sIgA and paired serum IgG/IgM/IgA from 41 stromal HSK patients and 15 controls were analyzed by enzyme-linked immunosorbent assay. Subsequent follow-up for monitoring recurrence was performed from the time of first cure on all patients for 4 months to 1 year. RESULTS: Serum IgG was positive in all participants. The concentration of serum IgA increased with the levels of tear sIgA (P = 0.017). The tear sIgA-positive rate was 36.59% in stromal keratitis, whereas none of the controls were found as sIgA positive. Positivity of sIgA was the only potential factor for predicting the risk of herpes keratitis recurrence (hazard ratio = 9.04; 95% confidence interval, 1.06-77.44; P = 0.045), with a sensitivity of 83.3% and a specificity of 71.4% (P = 0.034; 95% confidence interval, 0.58-0.97). Tear sIgA-positive patients had significantly shorter relapse-free survival compared with tear sIgA-negative patients (P = 0.015). CONCLUSIONS: This is the first preliminary study suggesting that the levels of tear sIgA could be a potential prognostic parameter for the recurrence of HSK.

[The effects of hyperosmotic stress on rabbit ocular surface and mucin 5AC expression].

OBJECTIVE: To investigate the effects of hyperosmotic stress on rabbit ocular surface and mucin 5AC (MUC5AC) expression. METHODS: Experimental study. Eighteen New Zealand white rabbits were randomly divided into three groups with equal number as hyperosmolar saline solution (HOSS, 500 mmol/L) group, normal saline (NS, 308 mmol/L) group and blank control group respectively. In HOSS and NS groups, the HOSS and NS eye drops were instilled on bilateral eyes six times every day for 14 days. On day 0, 7 and 14, Schirmer I test and tear break-up time (BUT) were measured and conjunctival impression cytology specimens were collected. On day 7 and 14, cornea and conjunctiva were harvested for Hematoxylin and Eosin (HE) staining, scanning and transmission electron microscopy observation and conjunctival TUNEL examination. On day 14, the conjunctiva were also harvested for immunology histological staining and western blot to evaluate the expression of MUC5AC. RESULTS: In HOSS group, the BUT on day 7 and 14 was (7.6 ± 2.5) and (7.0 ± 2.3) s respectively which was significantly shorter than the (10.3 ± 2.5) s on day 0(t = 5.800, 4.950; P < 0.01), and also significantly shorter than the BUT in NS and control groups (F = 8.030, P < 0.01). But the Schirmer I test value did not change obviously in and between all those three groups. The mean conjunctival goblet cell (GC) density in HOSS group on day 7 and 14 was (19.5 ± 16.6) and (32.3 ± 18.2) cells/mm(2) respectively which was also significantly lower than the (75.7 ± 43.4) cells/mm(2) on day 0 (t = 5.319, 2.970; P < 0.05). However the GC density did not change obviously in other two groups with time. After instillation of HOSS for 14 days, subepithelial inflammatory cell infiltration was showed on conjunctival tissue specimens and decreased epithelial layers and evident desquamation were found in the cornea specimens by the HE staining. Under the electron microscope, decreased microvilli and loosened intercellular junction in the superficial epithelium and increased autophagic vesicles in basal epithelium were observed in the cornea in HOSS group; and decreased microvilli and mucous granules were found in the conjunctiva in HOSS group. Obvious TUNEL positive staining was showed in the conjunctiva in the HOSS group. Also the MUC5AC immunology histological staining and western blot indicated decreased MUC5AC protein expression in HOSS group. CONCLUSION: Hyperosmotic stress destroyed the structure of ocular surface epithelium, induced the decrease of conjunctival goblet cell density and MUC5AC expression, and led to the decreased tear film stability.

[Comparative study on deep lamellar keratoplasty and penetrating keratoplasty for keratoconus].

OBJECTIVE: To investigate the therapeutic outcomes of deep lamellar keratoplasty (DLKP) and penetrating keratoplasty (PKP) for keratoconus. METHODS: Retrospective review of 29 eyes of 29 keratoconus patients, who underwent surgery in Eye & ENT Hospital of Fudan University from April in 2003 to April in 2006. Eleven eyes underwent DLKP and the rest had PKP. Pre- and post-operative visual acuity, astigmatism, complications and post-operative graft status were assessed. RESULTS: 82% of patients (9 eyes) in DLKP group gained BCVA better than 0.5, while in PKP group the proportion was just 78% (14 eyes). Postoperative astigmatism of two groups had no statistical significant difference with the value (-4.03 +/- 1.87) D and (-3.43 +/- 2.31) D respectively (DS: t = 2.135, P = 0.460, DC: t = -0.643, P = 0.528). The confocal image of epithelial cell, basal epithelium and Bowman's membrane was similar to that of normal cornea. The stromal cell was a little bit smaller and disordered. The endothelium in DLKP-treated eyes had normal cellular size and shape. There was no statistical significance between the density of operated eyes and contralateral unoperated eyes (2311.72 +/- 439.73) cells/mm2 and (2477.81 +/- 535.92) cells/mm2 respectively (t = 1.060, P = 0.780). However, the endothelial cells in PKP-treated eyes were highly pleomorphic with a decreased cellular density of (1642.17 +/- 583.41) cells/mm2, whereas the contralateral unoperated eyes had endothelium density of (2739.05 +/- 401.77) cells/mm2. The difference was statistical significance (Z = 7.32, P = 0.006). Complication rates were similar for DLKP and PKP, although the classification of the complications varied, being less severe in the DLKP group. CONCLUSIONS: DLKP seems to be a safe alternative for patients with keratoconus because of its equivalent effect to PKP. DLKP is more technically challenging but allows the risk of endothelial rejection to be avoided and may reduce the risk of late endothelial failure.

[Histopathological study of corneal wound healing in guinea pigs after deep lamellar endothelial keratoplasty with small incision].

OBJECTIVE: To study the histopathological characteristics of corneal wound healing after deep lamellar endothelial keratoplasty (DLEK) with small incision. METHODS: Forty-five guinea pigs were divided into the donor and recipient groups, which consisted of 15 and 30 guinea pigs respectively. DLEK was performed in the right eye, and the left eye was used as histopathological control. Two guinea pigs with clear right corneas under biomicroscopy examination were killed at 1 week, 2 weeks, 1 month, 2 months, 3 months and 4 months postoperatively, separately. Bilateral corneal buttons were harvested for the evaluation of endothelial cells (alizarin red stain) and for the light microscopy study (HE or PAS staining). RESULTS: Clear cornea could be obtained in 22 recipient eyes postoperatively. In these corneas, the endothelial cells either in the donor disc or recipient's bed were normal in shape and size. However, there was a band area between the donor disc and recipient's bed, where the endothelial cells were abnormal. In the early postoperative period, histopathological study disclosed increase of number of cells in the corneal stroma along the pathway of lamellar separation. The tissue connecting the gap between the donor and recipient lacked lamellar structure. The new descemet's membrane appeared beneath the endothelium 1 month postoperatively. Three to four months after the operation, the continuity of the descemet's membrane and the posterior lamella was rehabilitated. CONCLUSIONS: The corneal wound healing process after the DLEK with small incision is related with the type of trauma. Collagen is arranged well at the surface of the lamellar. Fibrotic repair is seen in the marginal area connecting the donor disc and recipient's bed.