Ocular biometric characteristics of Han ethnicity in Tianjin and Uyghur ethnicity in Xinjiang undergoing cataract surgery.

AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.

Disease-associated immune cell endotypes in anti-MDA5-positive dermatomyositis using unbiased hierarchical clustering.

Objective: Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen. Methods: This inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes. Results: Three disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4+ T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8+ T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8+ T cells and multiple cytokines than Endotype1. Conclusion: Clustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.

Immune profile alterations of systemic lupus erythematosus patients with infections.

This study aimed to elucidate the immune status of systemic lupus erythematosus (SLE) patients with infections. We enrolled 253 SLE patients including 77 patients with infections. Clinical features and immunological parameters were analyzed, with particular reference to neutrophil CD64 (nCD64) expression, myeloid-derived suppressor cells (MDSCs), activated T cells and multiple cytokines. Among the 77 SLE patients with infections, 32 patients (41.56%) developed fever and 20 patients (25.97%) developed serositis, which were higher compared to the non-infection group. A considerably higher level of nCD64 was found in the infection group (4.65 vs 1.01, P < 0.001). In addition, the infection group exhibited higher percentages of total MDSCs (6.99 vs 4.30%, P = 0.003), polymorphonuclear MDSCs (PMN-MDSCs) (P = 0.032) and monocytic MDSCs (M-MDSCs) (P = 0.015). T cells were more activated during infections, with an elevated level of IL-2R (P < 0.001). Specifically, higher percentages of CD4+CD38+ T cells (55.73 vs 50.17%, P = 0.036), CD8+HLA-DR+ T cells (59.82 vs 47.99%, P < 0.001) and CD8+CD38+ T cells (68.59 vs 63.90%, P = 0.044) were identified in the infection group. Furthermore, the serum levels of IL-6, IL-8 and IL-10 were elevated in the infection group (all P < 0.001). Higher proportions of neutrophils, CD4+ and CD8+ T cells, and MDSCs were activated during infections in SLE patients. Additionally, the serum cytokines altered during infections, with noticeably elevated levels of IL-6, IL-8 and IL-10. Infections may lead to the amplification of immune alterations in SLE.

Bilateral Diffuse Uveal Melanocytic Proliferation Initially Presented as Glaucoma.

PURPOSE: To report a bilateral diffuse uveal melanocytic proliferation (BDUMP) patient whose initial presentation was glaucoma. METHODS: Clinical review of a BDUMP case. RESULTS: A 65-year-old woman presented with ocular pain of the left eye for 1 day and vision loss of the right eye for 1 week. An ophthalmological examination revealed increased intraocularr pressure in the left eye and shallow anterior chamber in both eyes. BDUMP was diagnosed following a series of auxiliary examinations. After 1.5 years of follow-up, progressive cataracts appeared, and the patient accepted cataract surgery in both eyes. Visual acuity improved from light perception to 20/100 in both eyes 1.5 years after cataract surgery, but declined to light perception again at the last follow-up. CONCLUSION: BDUMP can be initially presented as glaucoma, and cataract surgery can be considered in BDUMP patients in order to improve the patients' quality of life, even if exudative retinal detachment exists.

Snowflakes in the Eye - An Uncommon Presentation of Iris Metastasis of Esophageal Carcinoma and Review of Literature.

PURPOSE: To alert clinicians to an uncommon presentation of iris metastasis of esophageal carcinoma. We reported a 67-year-old man complained of blurred vision and ocular pain of his right eye for 1 month. He was diagnosed iridocyclitis of the right eye 2 weeks ago and he had a history of esophageal squamous cell carcinoma for 5 years with no regular treatment. Under slit-lamp microscopy, accumulating snowflakes-like deposits were found in the anterior chamber of the right eye. Ocular metastasis was then confirmed by atypical cells in the aqueous humor and positron emission tomography (PET-CT). METHODS: Retrospective review of a case note and review of literature. CONCLUSION: We presented a rare case of iris metastasis of esophageal carcinoma and highlighted the importance of maintaining suspicion for metastasis in any elderly patients with uveitis, since the diseases masquerading as uveitis are not only vision threatening but may be potentially fatal.

The Role of RIPK1/3 in Adult Onset Still's Disease Patients With Liver Damage: A Preliminary Study.

Objective: This study aimed to investigate the distributions of lymphocytes in adult onset Still's disease (AOSD) with liver dysfunction, and further prospectively explore whether receptor interacting serine/threonine kinases (RIPKs) in lymphocytes play a role in the pathogenesis of AOSD especially liver involvement. Methods: Seventy-two AOSD patients and 19 cases of healthy controls (HCs) were retrospectively reviewed, the AOSD group was then divided into liver damage (LD) group and non-liver damage (NLD) group, and the distributions of lymphocytes in peripheral blood were analyzed. Another independent 24 AOSD patients and 20 HCs were recruited for prospective study of RIPKs; the RIPKs in peripheral blood lymphocytes were detected by flow cytometry. Liver biopsy specimens were obtained from two AOSD patients and underwent immunochemistry analysis with RIPK1 and RIPK3 antibody. Results: In the retrospective study, AOSD showed significantly abnormal lymphocytes distributions, and disease activity was positively correlated with percentage of CD3+ T cells. LD patients were younger in age and showed higher disease activity score than NLD patients; they had higher frequencies of CD3+ T cells, especially higher CD8+ T cells (all p<0.05). In the prospective study, RIPKs in lymphocytes were significantly higher in AOSD patients than that of HCs, and LD patients also showed higher RIPKs expression than NLD patients. In addition, RIPKs were positively correlated with erythrocyte sedimentation rate (ESR) and disease activity in AOSD patients and LD and NLD subgroups (all p<0.05). Further, RIPKs expression was confirmed in two AOSD patients' liver. ROC curve analysis indicated that RIPKs in lymphocytes (%) could be potential biomarkers in the diagnosis of AOSD and liver damage. Conclusions: Abnormal lymphocytes distributions and RIPKs expression were detected in AOSD. Aberrant expression of RIPKs in lymphocytes might be involved in the pathogenesis of AOSD. RIPKs could be candidate markers for AOSD and liver damage.

Identification and functional analysis of a novel missense mutation in GJA8, p.Ala69Thr.

BACKGROUND: To explore the molecular genetic cause of a four-generation autosomal dominant congenital cataract family in China. METHODS: Targeted region sequencing was performed to screen for the potential mutation, and Sanger sequencing was used to confirm the mutation. The homology model was constructed to identify the protein structural change, PolyPhen-2 and Provean were used to predict the mutation impact. Functional and cellular analysis of the wild and mutant GJA8 were performed in DF-1 cells by western blotting, dye uptake assay, immunofluorescence, Annexin V-FITC staining. RESULTS: A novel heterozygous mutation (c.205G > A; p.Ala69Thr) was identified within GJA8, which cosegregated with congenital cataract phenotype in this family. Bioinformatics analysis showed the mutation was located in a highly conserved region, and the mutation was predicted to be pathogenic. Function analysis indicated that the mutation inhibited GJA8 hemichannel activity, reduced cell tolerance to oxidative stress, changed the protein distribution pattern and inhibited the cell growth. CONCLUSIONS: We have identified a novel missense mutation in GJA8 (c.205G > A, p.Ala69Thr) in a four-generation Chinese family and our results will further broaden the gene mutation spectrum of GJA8.

Transscleral cyclophotocoagulation followed by cataract surgery: a novel protocol to treat refractory acute primary angle closure.

BACKGROUND: To introduce a novel protocol to treat refractory acute primary angle closure (APAC): transscleral cyclophotocoagulation (TCP) followed by cataract surgery. METHODS: Thirteen APAC eyes (13 patients) were enrolled in this prospective case series as study group. All patients underwent emergency TCP (20 pulses of 2000 mW during 2000 ms applied to the inferior quadrant) followed by scheduled cataract surgery. They were compared to 13 age- and gender-matched patients treated with emergency phacotrabeculectomy. We recorded intraocular pressure (IOP), best corrected visual acuity (BCVA), and complications, and several ultrasound biomicroscopy (UBM) parameters before and after TCP. RESULTS: In the study group, IOP decreased from 51.5 ± 7.0 mmHg (mean ± standard deviation) before TCP to 16.4 ± 5.4 mmHg 1 day after TCP (P < 0.001). At 6 months, there was no significant difference in IOP between the study group (14.0 ± 3.4 mmHg) and control group (16.7 ± 4.3 mmHg; P = 0.090); IOP lowering medications were used by 0/13 in the study group and 2/13 patients in the control group (P = 0.48). At 6 months, there was no significant difference in BCVA between the study group and the control group (20/25 (20/200 to 20/25) and 20/30 (20/50 to 20/25), respectively; P = 1.0). The UBM parameters anterior chamber depth (P = 0.016), angle-opening distance at 500 µm (P = 0.011), and maximum ciliary body thickness (P < 0.001) increased significantly while the iris-ciliary process distance decreased significantly (P = 0.020) after TCP. CONCLUSIONS: TCP effectively lowers IOP and modifies the anterior chamber morphology in APAC; TCP followed by cataract surgery can be considered an alternative to treat refractory APAC but needs further evaluation. TRIAL REGISTRATION: This project was registered in Chinese Clinical Trial Registry (ChiCTR1800017475) at July, 31, 2018 (http://www.chictr.org.cn/edit.aspx?pid=29629&htm=4).

MiRNA Regulation of MIF in SLE and Attenuation of Murine Lupus Nephritis With miR-654.

Objective: Macrophage Migration Inhibitory Factor (MIF) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). MicroRNAs (miRNAs) play important roles in LN but whether specific miRNAs regulate the expression of MIF in LN is unknown. We explore specific miRNAs that can regulate MIF expression, and investigate miR-654 for the treatment of experimentally-induced murine lupus nephritis. Methods: Sera samples from 24 SLE patients and 24 controls were collected to measure the MIF concentration and its correlation with disease activity. A luciferase reporter assay was used to explore the target of miR-654. ELISA was used to detect the downstream cytokines regulated by miR-654 and MIF. Western blot was applied to measure the impact of miR-654 inhibition on downstream MIF signaling. The therapeutic efficacy of miR-654 was tested in the pristine-induced lupus mouse model. We further measured miR-654 expression and analyzed its relationship with MIF expression in SLE patients. Results: The serum MIF level was increased in SLE patients (p < 0.001) and positively correlated with the SLEDAI score (r = 0.5473; p = 0.0056). MiR-654 inhibited MIF and downstream inflammatory cytokine production by selectively inhibiting the phosphorylation of ERK and AKT. Activation of miR-654 reduced IL-1ß, IL-6, IL-8, and TNF-α production, reduced gomerulonephritis, and decreased MIF, IgG, and C3 expression in murine lupus glomeruli. Furthermore, MIF was negatively correlated with miR-654 expression (r = -0.4644; p = 0.0222) in SLE patients. Conclusion: MiR-654 negatively correlated with MIF and disease activity in patients with SLE. MiR-654 inhibits MIF expression via binding to MIF 3'UTR, selectively suppresses the phosphorylation of ERK and AKT, and reduces downstream inflammatory cytokine production. In vivo miR-654 treatment decreases MIF and downstream cytokine production and ameliorates murine lupus nephritis.

Galactomannan detection in bronchoalveolar lavage fluid corrected by urea dilution for the diagnosis of invasive pulmonary aspergillosis among nonneutropenic patients.

BACKGROUND: To investigate the diagnostic performance of galactomannan (GM) detection in bronchoalveolar lavage fluid (BALF) corrected by urea dilution and modification of the AspICU clinical algorithm. METHODS: GM detection in serum and BALF samples was performed in nonneutropenic patients on the day of clinically suspected invasive pulmonary aspergillosis (IPA) between January 2016 and June 2018, and urea was measured in the plasma and BALF. The BALF GM concentration was corrected by urea dilution, and receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value. RESULTS: A total of 184 patients who were suspected of IPA, were enrolled in this prospective study together with 30 patients with lung cancer as a control group. Seventy-eight patients were diagnosed with IPA, including 37 who were verified by pathology. The urea plasma-to-urea BALF ratio in the IPA group [4.18 (IQR, 3.52-4.91)] was greater than that in the non-IPA group [3.42 (IQR, 3.12-3.76), P<0.001]. The ROC curve showed that defining the cut-off value as 2.94 optical density index (ODI) for the corrected BALF GM resulted in a sensitivity and specificity of 85.91% and 94.07%, respectively, and was more accurate than the use of the uncorrected values (P<0.05). CONCLUSIONS: The corrected BALF GM was valuable for diagnosing IPA in nonneutropenic patients. The modified AspICU clinical algorithm based on this measurement represents a reliable diagnostic instrument in clinical settings.

miR-152 Attenuates the Severity of Lupus Nephritis Through the Downregulation of Macrophage Migration Inhibitory Factor (MIF)-Induced Expression of COL1A1.

Background: The role of miR-152 in lupus nephritis has not been elucidated. The aim of this study was to investigate the role of miR-152 in the pathogenesis of lupus nephritis (LN). Methods: miR-152 expression was detected using RT-PCR in LN tissue and normal controls. The miR-152 expression was compared with clinical parameters such as 24 h urine protein excretion level, serum creatinine, and serum complement level and SLEDAI score. The function of miR-152 was examined using human renal proximal tubular epithelial cells (HRPTE). miR-152 mimics and inhibitors were transfected to HRPTEs to ascertain the effects of miR-152. Results: miR-152 expression was downregulated in LN tissue. There was an inverse correlation between miR-152 expression in LN tissue and clinical parameters like 24 h urine protein excretion levels and serum creatinine, but not serum complement levels or SLEDAI. Further analysis showed that macrophage migration inhibitory factor (MIF) was a direct target of miR-152. Downregulation of MIF through complementary binding of miR-152 inhibited the renal expression of COL1A1. Conclusion: miR-152 expression was tapered in LN tissue and miR-152 expression was inversely correlated with chronicity index (CI), serum creatinine and severity of proteinuria. miR-152 may attenuate the severity of LN through the downregulation of MIF-induced expression of COL1A1. These findings suggest that miR-152 may be a potential target for the treatment of LN.

Signal Transducer and Activator of Transcription 3 Hyperactivation Associates With Follicular Helper T Cell Differentiation and Disease Activity in Rheumatoid Arthritis.

Follicular helper T (Tfh) cells are the specialized CD4+ T cell subset that supports B cells to produce high-affinity antibodies and generate humoral memory. Not only is the function of Tfh cells instrumental to mount protect antibodies but also to support autoantibody production and promote systemic inflammation in autoimmune diseases. However, it remains unclear how the activation of Tfh cells is driven in autoimmune diseases. Here, we report that in patients with rheumatoid arthritis (RA), excessive generation of CXCR5+PD-1+ memory Tfh cells was observed and the frequency of memory Tfh cells correlated with disease activity score calculator for RA (DAS28). The differentiation of Tfh cells is dependent on signal transducer and activator of transcription 3 (STAT3), the key transcription factor downstream of cytokine signal pathways. A drastic increase of phosphorylated STAT3 (pSTAT3) in CD4+ T cells were detected in RA patients who also produced larger amounts of STAT3-stimulating cytokines, including IL-6, IL-21, IL-10, and leptin than those of healthy controls. Importantly, the phosphorylation status of STAT3 in CD4+ T cells positively correlated with the plasma concentration of IL-6 and the frequency of memory Tfh cells. This study reveals an IL-6-pSTAT3-Tfh immunoregulatory axis in the pathogenesis of RA and reinforces its candidature as biomarkers and targets for diagnosis and therapy.