A Modular Cataract Surgery Training Model Incorporating Human Factors and a Pedagogical Theory.

Synopsis: High volume cataract lists are cost-effective, reduce waiting times, and facilitate surgical teaching. We propose a stepwise training model that incorporates human factor principles and a reflective pedagogical approach, which has not been documented previously. Background/Aims: Surgical training in ophthalmology is effective when a modular approach is utilised. High volume lists further enhance training by increasing exposure to a newer way of learning and working. We evaluated the efficiency and safety of trainee-assisted cataract surgery across a single NHS eye unit and an independent sector (IS) provider. Methods: We examined results from audits of surgical efficiency and safety in trainee-assisted high-volume lists, including a single-centre comparative evaluation of consultant-only and trainee lists. The quantitative and qualitative information gained from these projects helped us to implement a modular, structured training programme that utilises a reflective cycle of pedagogy, suitable for any grade of trainee. Results: Our projects included an audit following cataract surgery performed by a surgical trainee over a 5-month period, which showed excellent post-op refractive results and no cases of intra-operative and post-operative complications. A single-centre observational study demonstrated comparable surgical throughput and safety results for trainee and solo consultant high volume lists. Systemic and ocular complication rates were reported to be similar for low and medium risk cataract surgery among trainee supervised IS and NHS lists. Conclusion: Cataract surgery outcomes and patient feedback support the effectiveness of the surgical training model. Combining Gibbs' reflective cycle of critical reflection with the International Council of Ophthalmology's principles helped us to develop the QM Model of modular teaching for cataract surgery, which we believe is suitable for utilisation in all surgical centres in the NHS and IS settings, for both low volume and high-volume surgical lists regardless of trainee experience.

What Is Already Known on This Topic High volume lists are increasingly popular for cataract surgery; however, trainee exposure to high flow cataract surgery lists is limited. What This Study Adds A modular approach to training via high volume training lists is possible.Origination and implementation of a stepwise cataract surgery training model that incorporates human factors and a pedagogical learning approach within high volume lists in the independent sector and NHS setting. How This Study Might Affect Research, Practice, or Policy Promote the widespread adoption of the QM model which integrates modular-based experiential learning approaches for surgical training in both NHS and independent sector settings, applicable to low and high volume surgical lists, irrespective of trainee experience.

Migrasomes from adipose derived stem cells enrich CXCL12 to recruit stem cells via CXCR4/RhoA for a positive feedback loop mediating soft tissue regeneration.

BACKGROUND: Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration. METHODS: Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system. RESULTS: Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration. CONCLUSIONS: Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.

New Insights and Advanced Strategies for In Vitro Construction of Vascularized Tissue Engineering.

Inadequate vascularization is a significant barrier to clinical application of large-volume tissue engineered grafts. In contrast to in vivo vascularization, in vitro prevascularization shortens the time required for host vessels to grow into the graft core and minimizes necrosis in the core region of the graft. However, the challenge of prevascularization is to construct hierarchical perfusable vascular networks, increase graft volume, and form a vascular tip that can anastomose with host vessels. Understanding advances in in vitro prevascularization techniques and new insights into angiogenesis could overcome these obstacles. In the present review, we discuss new perspectives on angiogenesis, the differences between in vivo and in vitro tissue vascularization, the four elements of prevascularized constructs, recent advances in perfusion-based in vitro prevascularized tissue fabrication, and prospects for large-volume prevascularized tissue engineering.

Parkin increases the risk of colitis by downregulation of VDR via autophagy-lysosome degradation.

Parkin, an E3 ubiquitin ligase, plays an essential role in mitophagy. Emerging evidence indicates that mitophagy is involved in various processes closely related to immune diseases, including inflammatory bowel diseases (IBD). Here, the authors show that Parkin increases the occurrence of colitis and severe inflammation. Deletion of Parkin resulted in marked reductions in colonic inflammation and exhibited high resistance to DSS-induced colitis. Mechanism investigation indicated that Parkin interacts with Vitamin D receptors (VDR), a critical inhibitory regulator in IBD. Parkin promotes VDR degradation via the p62-related autophagy-lysosome pathway. Comparison of colitis in Parkin-/- and Parkin-/-Vdr-/- mice showed that the protective effect of Parkin deletion against colitis was abolished by VDR deletion. The result suggests that the regulatory effect of Parkin in colitis is a VDR-dependent pathway. Our research provides a new role of Parkin in colitis by downregulating VDR, which provides a potential strategy for treating IBD.

Endogenous Bone Marrow-Derived Stem Cell Mobilization and Homing for In Situ Tissue Regeneration.

In mammals, post-injury repair and regenerative events rely predominantly on stem cell function. Stem cell transplantation has achieved considerable success in animals but remains unfavorable for humans because of the unavoidable drawbacks. Nevertheless, substantial evidence suggests the regenerative potential of endogenous stem cells can be improved for functional and structural recovery of tissue damage or in disease conditions. Endogenous stem cells are mostly quiescent under steady-state conditions and reside in their niche. Once faced with tissue injury, physiological and molecular changes within the niche or from distant tissues activate the migration, proliferation, and differentiation of stem cells, contributing to tissue repair. Tissue regeneration is augmented by artificially amplifying the factors that promote stem cell mobilization or enhance the homing of endogenous stem cells. This cell-free strategy, known as "in situ tissue regeneration," represents a safer and more efficient means to conduct tissue regeneration. Bone marrow (BM) is considered the central niche and main reservoir of many types of stem cells. These stem cells hold great therapeutic potential for the regeneration of multiple injured tissues. Herein, we review recent strategies for promoting in situ tissue regeneration through BM-derived stem cell mobilization or homing in animal models as well as in human trials. With the advancement in biomaterial engineering, chemoattractant signals combined with functionalized bioscaffolds have accomplished sustained activation of endogenous BM-derived stem cells that can be used as an attractive strategy for efficient in situ tissue regeneration.

Fascia Promotes Adipose Tissue Regeneration by Improving Early Macrophage Infiltration after Fat Grafting in a Mouse Model.

BACKGROUND: Low early macrophage fat graft infiltration (within a week of surgery) hinders tissue regeneration, suggesting that macrophages play a vital role in early angiogenesis and adipogenesis. However, the source of macrophages during this period is unclear. METHOD: C57BL/6 mice were split into fascial removal (FR) group and control groups (CG). Mice had a piece of back fascia removed in the FR group, which was immediately replaced in the CG, and inguinal fat injected into the transplantation site of both groups. Separately, fascia was harvested from green fluorescent protein-expressing mice and transplanted into C57BL/6 mice for tracing macrophage infiltration after fat grafting. RESULTS: The number of capillaries in the FR group was lower than that in the CG at days 3 ( P < 0.01) and 7 ( P < 0.05). Moreover, the number of small adipocytes in the FR group was lower than in the CG on days 3, 7, and 14 (all P < 0.05), and the relative expression of several adipogenic proteins was significantly lower in the FR group than in the CG on days 14 and 30. The timeline of macrophage infiltration was consistent with angiogenesis and adipogenesis. The number of macrophages in the FR group was significantly lower than in the CG at days 3 and 7 ( P < 0.05), and there were more fascia-derived macrophages than circulation-derived macrophages infiltrated into fat grafts within 7 days. Finally, the graft retention was lower in the FR group than the CG at day 90 ( P < 0.05). CONCLUSION: In the early stage after fat grafting, fascial macrophage infiltration initiates tissue regeneration, thereby improving graft retention by promoting angiogenesis and adipogenesis. CLINICAL RELEVANCE STATEMENT: In the clinic, injecting fat close to the fascia may increase fat retention. Fascia is widespread and self-regenerating, which may be a promising alternative source of local macrophages, with implications for tissue-engineering therapies such as correction of soft-tissue defects and breast reconstruction.

Early Angiogenesis-Dependent CXCL12 Attracts Adipose-Derived Stem Cells to Promote the Repair of Fat Grafting in a Mouse Model.

BACKGROUND: The unpredictable and unstable tissue retention rate of autologous fat grafting remains an obstacle faced by plastic surgeons. The authors' previous study using a fat grafting mouse model with donor sites showed that adipose-derived stem cell (ASC) infiltration in the recipient site was delayed, leading to poor regeneration and lower retention. Thus, the mechanism behind the differential infiltration of ASCs needed to be explored. METHODS: First, the authors locally injected C-X-C chemokine ligand 12 (CXCL12) or C-X-C motif chemokine receptor 4 (CXCR4) inhibitor AMD3100 in the recipient or donor site, respectively (CXCL12 + AMD3100 - , CXCL12 - AMD3100 + , and CXCL12 + AMD3100 + groups). The authors compared the migration of ASCs, adipose regeneration, and long-term retention. Next, the authors explored the role of angiogenesis using a normal/ischemic mice model in which the authors test the expression of CXCL12/CXCR4, migration of ASCs, and adipose regeneration. RESULTS: Blocking CXCL12 in the donor site using AMD3100 (CXCL12 - AMD3100 + and CXCL12+AMD3100+ groups) could accelerate ASC infiltration and promote adipose regeneration and long-term retention ( P < 0.05) compared with the other groups. CXCL12 and its receptor CXCR4 were more highly expressed in normal than in ischemic adipose tissue; consistently, there were more ASCs infiltrating normal than ischemic adipose tissue early after surgery ( P < 0.05). CONCLUSION: Early angiogenesis is essential for CXCL12 in promoting ASC infiltration, improving adipose tissue repair in the recipient site, and potentiating the long-term fat retention rate. CLINICAL RELEVANCE STATEMENT: The authors provide a proof-of-concept way to improve the outcomes of fat grafting by locally injecting AMD3100, also known as plerixafor, to the donor site.

The Danger of Laser Pointer-Induced Retinal Damage in Children: A Large United Kingdom Case Series and Survey of Public Awareness.

PURPOSE: To explore the clinical features of laser pointer-related retinal injuries among children and gain insight into the general public awareness around laser pointer use. METHODS: This was a retrospective case series of 9 children (12 eyes) with laser pointer-related retinal injury from a United Kingdom tertiary ophthalmology unit and a prospective survey of laser pointer use and awareness among children and parents presenting to the hospital eye service for other eye conditions. RESULTS: Within the case series, 67% of patients were asymptomatic on presentation. A mean follow-up of 25.6 months showed that structural changes persisted in all cases, and in one case, there was progression in the macular lesion size. One case presented with secondary choroidal neovascular membrane, requiring intravitreal anti-vascular endothelial growth factor injections. A survey showed that 9% of children admitted to having played with laser pointers and 13% of parents were aware of their children playing with laser pointers. Only one-third of children and parents were aware of laws regulating laser pointers. Most parents (96%) agreed that there needs to be increased awareness regarding laser pointers' effect on vision. CONCLUSIONS: This study has highlighted that although children may be asymptomatic at presentation, there is usually permanent structural damage to the macula, and complications such as secondary choroidal neovascular membrane can develop years later. The survey found a relatively high incidence of laser pointer use with little awareness of the regulation laws. There is an urgent need to establish more robust measures to improve public awareness and regulations around laser pointers. [J Pediatr Ophthalmol Strabismus. 2023;60(1):52-59.].

Adipose-derived stem cells regulate CD4+ T-cell-mediated macrophage polarization and fibrosis in fat grafting in a mouse model.

Autologous fat grafting is becoming increasingly common worldly. However, the long-term retention of fat grafting is still unpredictable due to the inevitable fibrosis arising during tissue repair. Fibrosis may be regulated by T-cell immune responses that are influenced by adipose-derived stem cells (ASCs). Therefore, we hypothesized that overly abundant ASCs might promote fibrosis by promoting T-cell immune responses to adipose tissue. We performed 0.3 ml fat grafts with 104/ml, 106/ml and 108/ml ASCs and control group in C57 BL/6 mice in vivo. We observed retention, fibrosis, T-cell immunity, and macrophage infiltration over 12 weeks. Besides, CD4+ T-helper 1 (Th1) cells and T-helper 2 (Th2) cells were co-cultured with ASCs or ASCs conditioned media (ASCs-CM) in vitro. We detected the ratio of Th2%/Th1%. Results showed that the retention rate was higher in 104 group, while even lower in 108 group with significantly increased inflammation and fibrosis than control group at week 12 in vivo. There was no significance between control group and 106 group. Also, 108 group increased the infiltration of M2 macrophages, CD4+ T-cells and Th2/Th1 ratio. In vitro, the ratio of Th2%/Th1% induced by ASCs-transwell group was higher than ASCs-CM group and showed concentration-dependent. Accordingly, high concentrations of ASCs in adipose tissue can promote Th1-Th2 shifting, and excessive Th2 cells might promote the persistence of M2 macrophages and increase the level of fibrosis which lead to a decrease in the long-term retention of fat grafts. Also, we found ASCs promoted Th1-Th2 shifting in vitro.

Three-Dimensional Culture Promotes Secretion of Extracellular Matrix Structure Fat Flap with Lipoaspirates in Vitro.

Adipose tissue engineering represents a possible solution for large-volume soft-tissue reconstruction. Although there have been several reports on the construction of tissue-engineered fat (TEF) flaps in vivo and in vitro, each condition has various limitations. Thus, we developed a novel approach for engineering fat tissue using a three-dimensional culture system. We used different volumes of lipoaspirates to fill the same tissue engineering chamber (30%, 50%, 80%, and 100% volume/space ratio) for different periods (3, 5, 7, and 14 days) to determine whether lipoaspirates can form structural fat tissue in vitro. We then studied the histological structure and extracellular matrix (ECM) of the tissue formed in vitro. We selected engineering tissue-like fat of the 80% volume/space ratio group cultured for 7 days to be subcutaneously implanted into mice for up to 3 months, and lipoaspirates without structure in vitro were used as a control. The lipoaspirates from the 80% volume/space ratio group cultured in vitro formed TEF-like tissue, which increased in small adipocytes and ECM with time until becoming stable on day 7. The live/dead test showed that the tissue cultured in vitro remained viable until day 7. Immunofluorescence staining results revealed that the collagen I and IV content increased over time. Moreover, after grafting, "self-assembly" fat had higher volume retention, better vascularization, fewer oil droplets, and less fibrosis than the lipoaspirates without structure in vitro. Therefore, our results demonstrate that lipoaspirates filled in tissue engineering chamber can be cultured in vitro and can "self-assemble" into TEF-like tissue. Furthermore, the "self-assembly" fat tissue produced better grafting results than those of lipoaspirates without structure in vitro.

Vitamin D receptor enhances NLRC4 inflammasome activation by promoting NAIPs-NLRC4 association.

Inflammasomes are cytosolic multiprotein complexes that initiate host defense against bacterial pathogens. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family caspase-associated recruitment domain-containing protein 4 (NLRC4) inflammasomes plays a critical role in the inflammatory response against intracellular bacterial infection. The NLR family apoptosis inhibitory proteins (NAIPs) detect Flagellin or type III secretion system (T3SS) microbial components to activate NLRC4 inflammasome. However, the underlying mechanism of NLRC4 inflammasome activation is not completely understood. Here, we show that the vitamin D receptor (VDR) is an essential immunological regulator of the NLRC4 inflammasome. Conditional VDR knockout mice (VDRflox/flox lyz2-Cre) exhibited impaired clearance of pathogens after acute Salmonella Typhimurium infection leading to poor survival. In macrophages, VDR deficiency reduced caspase-1 activation and IL-1ß secretion upon S. Typhimurium infection. For NAIPs act as upstream sensors for NLRC4 inflammasome assembly, the further study demonstrated that VDR promoted the NAIP-NLRC4 association and triggered NAIP-NLRC4 inflammasome activation, not NLRP3 activation. Moreover, Lys123 residue of VDR is identified as the critical amino acid for VDR-NLRC4 interaction, and the mutant VDR (K123A) effectively attenuates the NLRC4 inflammasome activation. Together, our findings suggest that VDR is a critical regulator of NAIPs-NLRC4 inflammasome activation, mediating innate immunity against bacterial infection.

Density-Based High-Quality Fat: Characterization and Correlation with Different Body Fat Ratio.

BACKGROUND: Lipoaspirate can be divided into high-quality fat and low-quality fat using Coleman's centrifugation by adding 0.935 g/ml marker float; the ratio obtained by different individuals is different. OBJECTIVES: This study aimed to examine the HQF obtained from different individuals and establish the relationship between individual body data and HQF. METHODS: We used Coleman's centrifugation method (1200 g, 3 min) with 0.935 g/ml density float to process lipoaspirate and collect HQF from different individuals for the analysis of fat characteristics and in vivo grafting. RESULTS: The HQF obtained from different individuals had similar stromal vascular fraction cell numbers and extracellular matrix content. In animal experiments at different time points (especially 12 weeks), the appearance, retention rate, hematoxylin and eosin staining, and immunohistochemistry results of HQF grafts were similar, while being different from those of Coleman fat. The HQF obtained from individuals with higher body fat ratio was less than those with lower body fat ratio. Following the establishment of the relationship between high-quality fat percentage and the body fat ratio of the donors, we proposed an innovative calculation formula model for the required lipoaspirate. CONCLUSIONS: HQF obtained from different individuals has similar fat characteristics, transplantation process, and outcome. The HQF percentage obtained from different individuals is negatively correlated with the body fat ratio. The amount of liposuction can be predicted using the proposed formula and improve the predictability of fat transplantation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Alternatively activated macrophages at the recipient site improve fat graft retention by promoting angiogenesis and adipogenesis.

The inflammatory response mediated by macrophages plays a role in tissue repair. Macrophages preferentially infiltrate the donor site and subsequently, infiltrate the recipient site after fat grafting. This study aimed to trace host-derived macrophages and to evaluate the effects of macrophage infiltration at the recipient site during the early stage on long-term fat graft retention. In our novel mouse model, all mice underwent simulated liposuction and were divided into 2 groups. The fat procurement plus grafting (Pro-Grafting) group was engrafted with prepared fat (0.3 ml). The pro-Grafting+M2 group was engrafted with prepared fat (0.3 ml) mixed with 1.0 × 106 GFP+M0 macrophages, and then, 2 ng IL-4 was injected into the grafts on Day 3. In addition, 1.0 × 106 GFP+M0 macrophages were injected into the tail vein for tracing in the Pro-Grafting group. As a result, GFP+macrophages first infiltrated the donor site and subsequently infiltrated the recipient site in the Pro-Grafting group. The long-term retention rate was higher in the Pro-Grafting+M2 group (52% ± 6.5%) than in the Pro-Grafting group (40% ± 3.5%). CD34+ and CD31+ areas were observed earlier, and expression of the adipogenic proteins PPAR-γ, C/EBP and AP2 was higher in the Pro-Grafting+M2 group than in the Pro-Grafting group. The host macrophages preferentially infiltrate the donor site, and then, infiltrate the recipient site after fat grafting. At the early stage, an increase in macrophages at the recipient site may promote vascularization and regeneration, and thereby improve the fat graft retention rate.

1,25-Dihydroxyvitamin D Inhibits Osteoarthritis by Modulating Interaction Between Vitamin D Receptor and NLRP3 in Macrophages.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disease globally. Loss of extracellular matrix (ECM) by chondrocytes is a classic feature of OA. Inflammatory cytokines, such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), secreted mainly by macrophages, promote expression of matrix degrading proteins and further aggravate progression of OA. 1,25-dihydroxyvitamin D (1,25VD) modulates inflammation thus exerting protective effects on cartilage tissue. However, the underlying mechanisms of 1,25VD activity have not been fully elucidated. METHODS: The destabilization of the medial meniscus (DMM)-induced mice model of OA was established to investigate the protective effects of 1,25VD by micro-CT and Safranin-O and Fast Green staining. And the co-culture system between THP-1 cells and primary chondrocytes was constructed to explore the effects of vitamin D receptor (VDR) and 1,25VD on chondrogenic proliferation, apoptosis, and migration. The immunofluorescence staining and Western blot analysis were used to detect the expressions of ECM proteins and matrix degradation-associated proteases. Enzyme-linked immunosorbent assay (ELISA) was used to examine the expression levels of inflammatory cytokines. RESULTS: The findings of the study showed that 1,25VD prevented cartilage degeneration and osteophyte formation by inhibiting secretion of inflammatory cytokines in OA mice model. These protective effects were exerted through the vitamin D receptor (VDR). Further studies showed that 1,25VD increased ubiquitination level of NLRP3 by binding to VDR, resulting in decrease in IL-1ß and IL-18 secretion. These findings indicate that 1,25VD binds to VDR thus preventing chondrogenic ECM degradation by modulating macrophage NLRP3 activation and secretion of inflammatory cytokines, thus alleviating OA progression. CONCLUSION: Here, our study suggests that 1,25VD, targeting to VDR, prevents chondrogenic ECM degradation through regulating macrophage NLRP3 activation and inflammatory cytokines secretion, thereby alleviating OA. These findings provide information on a novel molecular mechanism for application of 1,25VD as OA therapy.

Tumor protein D52 promotes breast cancer proliferation and migration via the long non-coding RNA NEAT1/microRNA-218-5p axis.

BACKGROUND: Breast cancer is an aggressive disease with high morbidity and mortality rates among women globally. Tumor protein D52 (TPD52) is an oncogene in breast cancer; however, its physiological function remains elusive. This study set out to obtain a deeper understanding of the functions of TPD52 in the pathophysiology of breast cancer by exploring its effects on breast cancer cell proliferation and migration. METHODS: Bioinformatics analysis was performed to predict the bonding of TPD52 and nuclear paraspeckle assembly transcript 1 (NEAT1) with miR-218-5p. The bonding of TPD52 and NEAT1 with miR-218-5p were verified by luciferase reporter assays. The mRNA expression of TPD52, miR-218-5p or NEAT1 were tested by Rt-qPCR and the protein expression of TPD52 was tested by western blot. Colony formation and EdU assays were carried out to evaluate cell proliferation. Wound healing and Transwell assays were used to evaluate migration. RESULTS: In this study, TPD52 was upregulated in breast cancer cells, and silencing of TPD52 repressed the proliferation and migration of breast cancer cells in vitro and in vivo. Further, microRNA (miR)-218-5p reduced the expression level of TPD52, while overexpression of TPD52 attenuated the effects of miR-218-5p mimics on breast cancer cell proliferation and migration. Also, NEAT1 acted as a competitive endogenous sponge of miR-218-5p to downregulate free miR-218-5p levels. It was further observed that TPD52 overexpression recovered the inhibition of breast cancer cell growth and migration caused by NEAT1 downregulation. These results confirmed the functions of NEAT1 in breast cancer and supported the mechanism of the NEAT1/miR-218-5p/TPD52 axis. CONCLUSIONS: Our findings highlight the important role of the NEAT1/miR-218-5p/TPD52 axis in breast cancer cell proliferation and migration. This axis may be a potential therapeutic target for breast cancer.

Clinical evaluation of vitamin D status and its relationship with disease activity and changes of intestinal immune function in patients with Crohn's disease in the Chinese population.

BACKGROUND: High prevalence of vitamin D deficiency has been found among Crohn's disease (CD) patients. Vitamin D probably participates in the pathogenesis of CD, but this idea remains controversial. This study was to investigate the levels of vitamin D in CD patients and analyze the relationship between vitamin D and intestinal inflammation. METHODS: Vitamin D levels were measured by chemiluminescence immunoassay in 198 CD patients (96 in active, 102 in remission) and 100 healthy controls. The correlation between vitamin D levels and clinical parameters was analysed. The expression of intestinal tight junction (TJ) proteins in CD patients was measured by immunofluorescence staining. Treg and Th17 percentages in the peripheral blood were determined by flow cytometry. RESULTS: CD patients exhibited significantly lower 25(OH)D levels than healthy controls, especially in active CD patients. Serum 25(OH)D levels in CD patients were negatively correlated with the CD activity index (CDAI), the simple endoscopic score for CD (SES-CD), and inflammatory markers, including erythrocyte sedimentation rate (ESR), platelet (PLT) count and faecal calprotectin (FC) levels. Moreover, in patients with vitamin D deficiency, the expression of TJ proteins (Occludin, claudin-1, ZO-1 and JAM-1) in the intestinal mucosa was reduced, and Treg cells in the peripheral blood were decreased, while Th17 cells were increased compared to those with vitamin D sufficiency and controls. CONCLUSIONS: Vitamin D deficiency in CD patients is common. Vitamin D is associated with disease activity and intestinal inflammation, which may affect the Treg/Th17 balance and the expression of gut TJ proteins.

Effects of whole globe enucleation versus in situ corneoscleral excision on donor cornea tissue quality: a systematic review protocol.

OBJECTIVE: The objective of this review is to systemically compare the effects of whole globe enucleation versus in situ corneoscleral excision on donor cornea tissue quality. INTRODUCTION: Corneal transplantation serves as a sight-restoring surgery for corneal diseases, but the treatment is limited by the persistent shortage of donor corneas globally. Whole globe enucleation and in situ corneoscleral excision are the two methods for eye retrieval. Although studies have reported a higher acceptance rate for corneal donation among donors' relatives with in situ corneoscleral excision than whole globe enucleation, there are concerns regarding the impact on donor cornea tissue quality with in situ corneoscleral excision. Currently, there is limited high-quality evidence comparing the two methods. INCLUSION CRITERIA: We will consider prospective and retrospective comparative studies that examine the effects of whole globe enucleation and in situ corneoscleral excision on donor cornea tissue quality. There will be no restrictions on the recipients' characteristics, including age, sex, ocular comorbidities, or potential visual acuity after corneal transplantation. METHODS: Electronic databases, including (but not limited to) MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials,gov, and ISRCTN registry will be searched, with no restriction to the language used or date of publication. Retrieval of full-text studies, assessment of methodological quality, and data extraction will be performed independently by two reviewers. A meta-analysis, using fixed or random effects, will be performed for the included randomized controlled trials when there are sufficient similarities in the reporting of outcome measures. If meta-analysis is not possible, the pre-specified outcomes will be narratively synthesized. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42020210575).

The Association between Foveal Floor Measurements and Macular Hole Size.

PURPOSE: Determining which factors influence idiopathic macular hole (MH) size is important because it is a major prognostic indicator of treatment success. Foveal pit morphologic features are highly symmetrical within individuals and may influence idiopathic MH size. Using a series of patients with unilateral idiopathic MHs, we examined the foveal floor size of the fellow eye to evaluate its relationship with idiopathic MH size and postoperative outcomes. DESIGN: Retrospective observational study. PARTICIPANTS: Two hundred forty-one participants with a unilateral idiopathic MH treated with surgery and a fellow eye with no ocular pathologic features. METHODS: Both eyes underwent spectral-domain (SD) OCT imaging at the time of surgery. Minimum linear diameter (MLD) and base diameter (BD) defined idiopathic MH size. Foveal floor width (FFW) and minimal foveal thickness defined foveal pit morphologic features of the fellow eye. MAIN OUTCOME MEASURES: Baseline characteristics, SD OCT measurements, and preoperative variables were compared to determine their relationship with idiopathic MH size and postoperative visual acuity (VA) in logarithm of the minimum angle of resolution units. RESULTS: Foveal floor width was correlated with MLD (r = 0.36; P ≤ 0.001) and BD (r = 0.30; P ≤ 0.001), but not postoperative VA. Minimum linear diameter correlated with preoperative VA (r = 0.49; P ≤ 0.0001) and postoperative VA (r = 0.54; P ≤ 0.0001). A 2-stage regression model was developed to predict postoperative VA (r2 = 0.28): preoperative VA (ß = 0.36; P = 0.002) explained 13% of variability and MLD (ß = 0.29; P = 0.002), and idiopathic MH duration (ß = 0.23; P = 0.004) explained a further 16%. CONCLUSIONS: Foveal floor width of the fellow eye in patients with a unilateral idiopathic MH was correlated significantly with idiopathic MH size and may explain some of the variability in idiopathic MH size observed between individuals. However, FFW could not predict postoperative vision.