Endocrine diseases are a big health problem worldwide, due to their complex pathophysiology, the diversity of clinical phenotypes and the necessity of sensitive, stable, and real‑time monitoring of hormonal and metabolic biomarkers. Conventional endocrine assays are plagued by the need for the presence of large amounts of biomarker, the time needed for the response, poor enzyme stability, matrix effects and lack of continuous or point of care suitability. To overcome these limitations, technical approaches are based on nanostructured enzyme-immobilized platforms that provide high surface to volume ratio for high enzyme loading, tunable surface chemistry for control of immobilization, enhanced electron-transfer pathways for electrochemical signal amplification, porous architecture to confine and stabilize enzyme, and plasmonic effects (eg, localized surface plasmon resonance) for optical signal enhancement. In this review, an updated overview of the design principles, mechanisms and biomedical relevance of enzyme immobilization on nanostructured platforms for the diagnosis and treatment-related management of endocrine diseases is provided. The carbon-based materials, metallic and metal-oxide nanoparticles, polymeric systems, metal-organic frameworks, covalent organic frameworks, and hybrid nanocomposites are discussed in the context of their role in tuning the loading of enzymes, catalytic activity, operational stability, signal transduction and biocompatibility. Particular emphasis is placed on applications in diabetes mellitus, thyroid, adrenal disorders and lipid metabolic imbalance, as well as emerging applications in targeted therapy, enzyme guided drug delivery, oxidative-stress regulation and nanotheranostics. The current problems of reproducibility, long-term stability, scalability, biocompatibility and clinical translation are critically discussed. Potential future trends, such as AI-powered biosensors, next-generation nanozymes, multiplexed platforms, and personalized nanomedicine strategies, are suggested.

We highlighted the importance of KIF2C in the development of resistance to tamoxifen and its role in promoting lung metastasis in breast cancer, as well as the mechanisms that underpin these processes. KIF2C overexpression and knockdown lentiviruses were transfected into MCF-7 and MCF-7/TAM cells. A nude mouse model of MCF-7/TAM tumors and lung metastasis was established. The PLK1 inhibitor BI2536 was used to explore the underlying mechanism. KIF2C is elevated in tamoxifen-resistant breast cancer. KIF2C knockdown MCF7/TAM cells show increased sensitivity to tamoxifen, indicated by fewer cell clones, invasive cells, migration area, and lumen count, as well as a higher rate of cell apoptosis. KIF2C is linked to the PLK1/c-Myc signaling pathway, and BI2536 inhibits its enhancement of tamoxifen resistance. Results from an in situ experiment on breast cancer in mice are consistent with in vitro findings. KIF2C upregulation is linked to greater tamoxifen resistance in breast cancer, facilitating progression and lung metastasis in resistant cases. KIF2C's potential mechanism of action is linked to the PLK1/c-Myc signaling pathway.

PURPOSE:To introduce a modified, effective, and versatile inverted internal limiting membrane flap technique, providing a novel option for the treatment of macular holes, with or without retinal detachment. METHODS:We conducted a retrospective analysis of 20 patients (20 eyes) with macular holes who underwent pars plana vitrectomy using the pear flower petal-shaped inverted internal limiting membrane flap technique. Best-corrected visual acuity, optical coherence tomography, and morphological assessments were performed at baseline and during each postoperative follow-up visit. RESULTS:Postoperative macular holes closure and retinal reattachment rates were both 100%. The baseline best-corrected visual acuity was logMAR 1.892 ± 0.495, which significantly improved to logMAR 0.968 ± 0.348 at the final follow-up ( P < 0.001). Optical coherence tomography imaging demonstrated favorable postoperative retinal microstructural recovery, with a healing process highly similar to that observed in spontaneous closures. CONCLUSION:This novel technique promotes anatomical and functional recovery in patients with macular holes, with or without retinal detachment, resembling the natural healing process. It serves as a remedial measure in case of intraoperative complications, offering a simple and flexible approach, ensuring that there is always a suitable flap for each situation.

The number of people suffering from type 2 diabetes (DM2) is increasing and over 30 percent of DM2 patients will develop diabetic retinopathy (DR). Available therapeutic approaches for DR have their limitations. It is of great significance to search for other effective alternate therapeutic approaches. The present study aimed to explore the beneficial effects of photobiomodulation (PBM) on the diabetic retinopathy and underlying mechanisms. Streptozotocin was administered to male mice to establish diabetic model. The mice in the diabetic group (DM) received no treatment, and the mice in DM + PBM group received LED illumination (wavelength 670 nm) once a day for 20 consecutive weeks. Retinal vessel degenerate changes, the expression levels of E-Cadherin, NCadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-alpha in retina, the levels of SDF-1 alpha and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 were determined. PBM could significantly inhibit the degenerative change of diabetic retinal vessels, decrease the expression levels of ECadherin and N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-alpha and increase VEGF mRNA levels in retina. PBM could also increase the levels of SDF-1 alpha and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 in diabetic mice. PBM at 4 min/day for 20 consecutive weeks significantly inhibit the degenerative change of diabetic retinal vessels, and PBM is likely to produce its beneficial effects on the retina through promoting the migration of bone marrow stem cells to circulation and diabetic retinal tissue. The present study provides a new therapeutic direction and experimental foundation for the treatment of diabetic retinopathy.

Diabetes mellitus is a metabolic disease that is marked by persistent hyperglycemia due to inadequate insulin secretion or insulin resistance. Its prevalence is increasing yearly. Diabetes mellitus can lead to serious health complications that are the primary cause of mortality and disability among diabetic patients, including diabetic retinopathy, diabetic foot ulcers, diabetic peripheral neuropathy, and diabetic periodontitis, and so on. Traditional treatments for diabetes and its complications still suffer from limited clinical efficacy and high therapeutic side effects. Photobiomodulation (PBM), which utilizes low levels of red or near-infrared laser to irradiate cells and tissues, has been shown to be efficacious for a wide range of organ damage. In this study, we focus on the application of PBM in diabetes and its complications and mechanisms, as well as the advantages, disadvantages with the aim of developing new ideas for the application of PBM.

High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It's essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV.

报道2例在吉林大学白求恩第二医院内分泌科就诊的2型糖尿病（T2DM）患者，由基础胰岛素联合口服降糖药物治疗调整为德谷胰岛素利拉鲁肽注射液取得了良好的效果。2例患者均为应用基础胰岛素联合口服降糖药血糖控制不佳（糖化血红蛋白分别为8.9%、9.5%）的成人T2DM患者，病程均约10年，胰岛功能欠佳，合并高脂血症、超重或腹型肥胖。结合患者个人意愿，转换为德谷胰岛素利拉鲁肽注射液联合口服药物降糖治疗后，血糖短期内改善并持续达标（<7 mmol/L），体重及腰围有不同程度下降，无胃肠道不良反应及低血糖事件，耐受程度及安全性良好。

BACKGROUND:In diabetic retinopathy, increasing evidence points to a link between the pathogenesis of retinal microangiopathy and the endothelial cell-specific factor roundabout4 (ROBO4). According to earlier research, specificity protein 1 (SP1) enhances the binding to the ROBO4 promoter, increasing Robo4 expression and hastening the progression of diabetic retinopathy. To determine if this is related to aberrant epigenetic modifications of ROBO4, we examined the methylation level of the ROBO4 promoter and the corresponding regulatory mechanism during the course of diabetic retinopathy and explored the effect of this mechanism on retinal vascular leakage and neovascularization.METHODS:The methylation level of CpG sites in the ROBO4 promoter was detected in human retinal endothelial cells (HRECs) cultured under hyperglycemic conditions and retinas from streptozotocin-induced diabetic mice. The effects of hyperglycemia on DNA methyltransferase 1, Tet methylcytosine dioxygenase 2 (TET2), 5-methylcytosine, 5-hydroxymethylcytosine, and the binding of TET2 and SP1 to the ROBO4 promoter, as well as the expression of ROBO4, zonula occludens 1 (ZO-1) and occludin were examined. Short hairpin RNA was used to suppress the expression of TET2 or ROBO4 and the structural and functional changes in the retinal microvascular system were assessed.RESULTS:In HRECs cultured under hyperglycemic conditions, the ROBO4 promoter methylation level decreased. Hyperglycemia-induced TET2 overexpression caused active demethylation of ROBO4 by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, which enhanced the binding of SP1 to ROBO4, increased the expression of ROBO4, and decreased the expression of ZO-1 and occludin, leading to the abnormalities in monolayer permeability, migratory ability and angiogenesis of HRECs. The above pathway was also demonstrated in the retinas of diabetic mice, which caused leakage from retinal capillaries and neovascularization. Inhibition of TET2 or ROBO4 expression significantly ameliorated the dysfunction of HRECs and retinal vascular abnormalities.CONCLUSIONS:In diabetes, TET2 can regulate the expression of ROBO4 and its downstream proteins by mediating active demethylation of the ROBO4 promoter, which accelerates the development of retinal vasculopathy. These findings suggest that TET2-induced ROBO4 hypomethylation is a potential therapeutic target, and anti- TET2/ROBO4 therapy is anticipated to emerge as a novel strategy for early intervention and delayed progression of diabetic retinopathy.

Diabetes mellitus is a metabolic disease, characterized by chronic hyperglycemia caused by an abnormality in insulin secretion or action. Millions of people across the world are affected by diabetes mellitus which has serious implications for their health. Over the past few decades, diabetes has become a major cause of mortality and morbidity across the world due to its rapid prevalence. Treatment for diabetes that focuses on insulin secretion and sensitization can lead to unwanted side effects and/or poor compliance, as well as treatment failure. A promising way to treat diabetes is through gene-editing technologies such as clustered regularly interspaced short palindromic repeats (CRISPR/Cas9). However, issues such as efficiency and off-target effects have hindered the use of these technologies. In this review, we summarize what we know today about CRISPR/Cas9 technology's therapeutic potential for treating diabetes. We discuss how different strategies are employed, including cellbased therapies (such as stem cells and brown adipocytes), targeting critical genes involved in diabetes pathogenesis, and discussing the challenges and limitations associated with this technology. A novel and powerful treatment approach to diabetes and other diseases can be found with CRISPR/Cas9 technology, and further research should be carried out in this field.

Abstract Purpose: To investigate aqueous cytokine levels associated with proliferative diabetic retinopathy (PDR) prognosis after intravitreal conbercept injection (IVC). Methods: The Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) measured aqueous humour cytokine and chemokine levels. In this retrospective study, control samples were collected from 10 patients undergoing pars plana vitrectomy (PPV), and test samples were collected from 15 patients undergoing PPV and IVC. Intraoperative complications and postoperative outcome parameters were compared. Cytokine concentration association with PDR prognosis after IVC combined with PPV was assessed by correlation analysis. Results: Baseline cytokine levels did not significantly differ between the control and IVC groups. IVC affected IL-8, VEGF and FGF levels, significantly increasing interleukin 8 (IL-8) levels and (P=0.05) decreasing VEGF and FGF levels (P<0.05). Intraoperative bleeding risk was lower in the IVC group versus the control group (P=0.022). Endodiathermy use was reduced in the IVC group versus the control group (P=0.006). The vitrectomy time in the IVC group was significantly shorter than in the control group (P=0.035). IL-8, VEGF, and FGF levels significantly positively correlated with vitrectomy time and intraoperative bleeding risk, intraoperative bleeding risk and endodiathermy use, and endodiathermy use, respectively. Conclusions: Conbercept may shorten the vitrectomy time, reduce intraoperative bleeding and affect IL-8, VEGF and FGF levels in PDR patient aqueous humour.

Retinal vein occlusion (RVO) is the second most prevalent retinal disease. Despite this, the pathogenic mechanisms and risk factors are not entirely clear. In this article, we review recent publications on the classification, pathogenesis, risk factors, ischemic changes, cytokines, and vital complications of RVO. Risk factors and cytokines are important for exploring the mechanisms and new treatment targets. Furthermore, risk factors are interrelated, making RVO mechanisms more complex. Cytokines act as powerful mediators of pathological conditions, such as inflammation, neovascularization, and macular edema. This review aims to summarize the updated knowledge on risk factors, cytokines of RVO and signaling in order to provide valuable insight on managing the disease.

Objective: Expression of circular RNAs (circRNAs) in the peripheral blood of individuals with latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM) were quantified to identify dysregulated circRNAs compared with control individuals.Methods: circRNAs were obtained from the peripheral blood serum of 12 healthy adults and 12 individuals with LADA and 12 type 2 diabetics. The circRNA expression profiles were analyzed by high-throughput RNA sequencing. The most highly dysregulated circular RNAs were validated by quantitative real-time polymerase chain reaction. A circular RNA-microRNA (miRNA) network diagram predicted the interactions of circular RNAs, miRNAs, and coding genes.Results: A total of 2334 differentially expressed circRNAs were detected among the three groups, with 277 circRNAs in the Group DM versus Group NG; 992 circRNAs in the Group LADA versus Group NG and 1065 circRNAs in the Group DM versus Group LADA. Six circRNAs were identified as the most distinctive differentially expressed targets (p < 0.05). The proposed molecular functions of these differentially expressed circRNAS included the tumor necrosis factor signaling pathway, the FoxO signaling pathway, cellular senescence, and long-term potentiation (all false discovery rate p < 0.05) which may contribute to T2DM and LADA.Conclusion: circRNAs are aberrantly expressed in the peripheral blood of patients with T2DM and LADA and may interact with miRNA and circRNA-derived peptides in the development of diabetes. Further investigations may illustrate the partial pathogenesis of diabetes mellitus.Clinical Trial Registration number: ChiCTR1900020644.

Introduction: Terson's syndrome with inner limiting membrane (ILM) peeled off spontaneously is rarely seen, and the mechanism of it is not clear. Here we report a case of Terson Syndrome with a rare finding: the ILM peeled off spontaneously associated with macular hole (MH). Patient concerns: A 36-year-old female patient was admitted to our hospital with decreased visual acuity in the right eye lasting for 1 month. She just had surgery for subarachnoid hemorrhage that occurred 1 month before due to the rupture of the intracranial aneurysm. Diagnosis: Terson syndrome was diagnosed according to her medical history and examination. A partial posterior vitreous detachment (PVD) and dense vitreous hemorrhage (VH) was confirmed in the right eye by performing ophthalmic B-scan ultrasonography examination. Head computed tomography showed the subarachnoid hemorrhage after aneurysmal rupture. Interventions: The patient underwent pars plana vitrectomy in her right eye to remove the VH. After removal of the VH, a full-thickness macular hole was noted with the ILM peeled off spontaneously. So we conducted gas tamponade, and face-down positioning after pas plana vitrectomy. Outcomes: At two weeks follow-up, her best corrected visual acuity was 0.15 in the right eye. Spectral domain optical coherence tomography showed that the MH was closed completely, while the thickness of the nasal retina of the foveal was thicker than that on the temporal side. Lessons: ILM peeled off spontaneously associated with MH is a rarely seen complication of Terson Syndrome. Due to the large-scale of the ILM peeling off, final visual acuity may be poor in patients, even though successful macular hole closure after the operation.

An 82-year-old female patient received monotherapy with nivolumab (240 mg by an IV infusion on the firsr day, 14 days as a cycle) because of multiple metastases of central adenocarcinoma in the right upper lobe of the lung. After 8 cycles of immunotherapy (about 4 months), the patient developed severe nausea and vomiting. Laboratory tests showed random blood glucose 43.2 mmol/L and β-hydroxybutyric acid 5.3 mmol/L. Blood gas analysis showed pH 7.01, bicarbonate root 4.0 mmol/L, alkali residual -22.4 mmol/L, serum potassium 6.1 mmol/L, and lactic acid 2.9 mmol/L. The patient had no previous history of diabetes mellitus. Fulminant type 1 diabetes mellitus due to nivolimab was considered. Nivolumab was stopped and rehydration, hypoglycemia, acidosis correction, and other symptomatic treatments were given. Two days later, her symptoms were improved obviously. Laboratory tests showed fasting plasma glucose 15.8 mmol/L and β-hydroxybutyric acid 0.2 mmol/L. Blood gas analysis showed pH 7.39, bicarbonate root 21.2 mmol/L, alkali residual -3.8 mmol/L, serum potassium 4.3 mmol/L, and lactic acid 1.0 mmol/L.

糖尿病大疱病是一种少见的糖尿病并发症,发病率为0.16％-0.5％[1-2],发病时皮肤水疱突然形成,可自行消退,一般在2-5周愈合,不遗留疤痕或萎缩,常有反复发作病史,多合并有糖尿病周围神经病变[3-4]、大血管病变[5]、微血管病和血糖控制不佳[6],以及钙,镁代谢紊乱等.目前糖尿病酮症酸中毒合并心衰是否能够诱发糖尿病大疱病,或是该状态下快速补液能否诱发糖尿病大疱病尚不明确.本文报道1例糖尿病酮症酸中毒(DKA)合并心衰及糖尿病大疱病的患者,探讨该状态下诱发糖尿病大疱病的可能因素.

Abstract Rationale: Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis. Necrotizing retinitis is a rare manifestation of ocular syphilis and mimics ARN. Patient concerns: We report a male patient who presented with bilateral dense vitritis obscuring fundus details similar to ARN, as a rare reported manifestation of syphilis, who was initially given intravitreal ganciclovir. Diagnosis: After the results for herpes viral PCR disclosed negative, the diagnosis of syphilitic necrotizing retinitis was made based on positive RPR. Intervention and Outcomes: With the clinical diagnosis of ocular syphilis, treatment with intravenous penicillin was promptly initiated. His visual acuity improved to 20/100 in the right eye and still light perception in the left. Pars plana vitrectomy with silicon oil tamponade was performed in his left eye. Lessons: Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis. However, whenever ARN is clinically suspected, empiric treatment against herpetic viruses should be promptly administered while awaiting further infectious disease study results. Recognition of syphilitic retinitis and prompt initiation of intravenous penicillin is of critical important for clinicians.

RATIONALE:Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis. Necrotizing retinitis is a rare manifestation of ocular syphilis and mimics ARN.PATIENT CONCERNS:We report a male patient who presented with bilateral dense vitritis obscuring fundus details similar to ARN, as a rare reported manifestation of syphilis, who was initially given intravitreal ganciclovir.DIAGNOSIS:After the results for herpes viral PCR disclosed negative, the diagnosis of syphilitic necrotizing retinitis was made based on positive RPR.INTERVENTION AND OUTCOMES:With the clinical diagnosis of ocular syphilis, treatment with intravenous penicillin was promptly initiated. His visual acuity improved to 20/100 in the right eye and still light perception in the left. Pars plana vitrectomy with silicon oil tamponade was performed in his left eye.LESSONS:Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis. However, whenever ARN is clinically suspected, empiric treatment against herpetic viruses should be promptly administered while awaiting further infectious disease study results. Recognition of syphilitic retinitis and prompt initiation of intravenous penicillin is of critical important for clinicians.

Background: Stickler syndrome is a group of connective tissue disorders that can affect eye (myopia, cataract, and retinal detachment), skeleton (spondyloepiphyseal dysplasia and precocious arthritis), craniofacies (midfacial under development and cleft palate), and inner ear (conductive and sensorineural); with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, and COL9A3 procollagen genes cause Stickler syndrome. Case presentation: A 16-year-old Mongolian girl approached our clinics with retinal detachment. The proband had vitreous degeneration in both eyes, rhegmatogenous retinal detachment in her right eye, a large area of retina degeneration in her left eye, and coupled with severe myopia. No obvious hearing disorder was found, no abnormalities in bones and joints, and her communication and learning capability were also normal. Further clinical examination showed that the patient's other five family members across three generations had vitreous and retina degenerations. Exome sequencing showed a heterozygous splicing variant in COL2A1 in all patients. Conclusions: In this case report, a pathogenic splicing variant in the COL2A1 gene was identified in a Mongolian family affected with Stickler syndrome type I by exome sequencing. This heterozygous splicing variant in COL2A1 (NM_001844.4:C.2518-1G>A) that may impair splicing, which was suggested by in silico prediction. Next-generation sequencing is helpful for the differential diagnosis of this clinically variable and genetically heterogeneous disorder.

目的 探讨长链非编码RNA(LncRNA)在LADA和T2DM中的表达,并预测LncRNA作用的靶向基因,为LADA和T2DM的诊断及鉴别诊断提供基因表达谱.方法 选取2017年7月至2018年6月于吉林大学第二医院内分泌科就诊的DM患者或正常糖耐量(NGT)人群,分为T2DM组、LADA组及NGT组,每组各4例.采用高通量测序检测,挑选表达差异有统计学意义的LncRNA构建基因表达谱.结果 与NGT组比较,T2DM组LncRNA 68763个表达上调,28523个表达下调;LADA组LncRNA 68748个表达上调,28538个表达下调.各组LncRNA表达差异显著.在有统计学意义的数据中选取2个差异倍数最高的LncRNA(LncRNA ENST00000602845-NCBP2、LncRNA ENST00000364558-HECTD4)进一步分析,并通过GO、KEGG通路分析预测LncRNA的靶基因功能.结论 LADA、T2DM患者LncRNA表达谱与NGT人群存在明显差异,可能通过多种机制参与发病.

Lili Ning Jilin Univeristy Second Hospital Yan Yan Jilin University Second Hospital Xiying Fu Jilin University Second Hospital Yan Cheng Jilin University Second Hospital Mo Li Jilin University Second Hospital Xiujuan Zhang Jilin University Second Hospital Hong Shen Jilin University Second Hospital Maoguang Yang Jilin University Second Hospital Lijuan Wang Jilin University Second Hospital Hanqing Cai (  caihanqing16@163.com ) Jilin University Second Hospital https://orcid.org/0000-0002-9386-5286