Microstructure of the cornea in high myopia with confocal microscope through focusing in vivo.

We prospectively investigated the changes of microstructure of the cornea in 54 high myopias with confocal microscopy via focusing in vivo. The microstructure of high myopic cornea is different from that of low and moderate myopia, however, whether corneal function would be involved is not clear.

Effect and significance of secretogranin Ⅲ in diabetic retinal neovascularization / 中华实验眼科杂志

Secretogranin Ⅲ (SCG3) is a kind of secretory granule widely distributed in tissues and cells with endocrine functions in the human body.As a member of the granin family, it is generally considered to be involved in endocrine and neuroendocrine regulatory activities, and also as a highly disease-selective angiogenic factor that reduces vascular leakage and neovascularization in animal models of diabetic retinopathy and retinopathy of prematurity.In addition, SCG3 also co-expresses with inflammatory factors, anti-brain-derived neurotrophic factors in nerve cells.This article reviewed the current understanding of SCG3 as a secretory granular protein and its granulocyte family, analyzed the distribution of SCG3 in vivo, discussed its role in angiogenesis, and considered the correlation between SCG3 and neovascularization.It focused on the possible role and significance of SCG3 in diabetic retinopathy, especially in relation to microangiopathy, inflammatory factors and retinal neurodegeneration.By comparing the differences between SCG3 and vascular endothelial growth factor (VEGF) in the binding of signaling pathways and related receptors, the effects and advantages of anti-SCG3 drugs in the treatment of DR were prospected.

Expert consensus on community screening of diabetic retinopathy / 中华眼底病杂志

Diabetic retinopathy is one of the microvascular complications of diabetes and a major cause of blindness in adults. Early screening is an effective way to reduce blindness caused by diabetic retinopathy. The diabetic retinopathy is one of the chronic retinal diseases highlighted in the "14th Five-Year" National Eye Health Plan (2021-2025). The establishment of effective and practical community screening model is a powerful guarantee to complete early screening. It is of great significance to standardize screening methods, screening personnel duties, equipment allocation, referral conditions and screening sustainability. Chinese fundus disease and related field experts developed the consensus through a serious, comprehensive, and complete discussion, to provide more reference for establishing a suitable community screening model of diabetic retinopathy and increasing the screening rate of diabetic retinopathy.

Interpretation of Expert consensus on community screening of diabetic retinopathy / 中华眼底病杂志

Diabetes retinopathy (DR) is listed as one of the chronic diseases that should be focused on in the "14th Five-Year" National Eye Health Plan (2021-2025). Early screening is one of the effective measures to reduce blindness caused by DR. Establishing an efficient and practical community screening model is a powerful guarantee for completing early screening. The Ocular Fundus Diseases Group of the Ophthalmology Branch of the Chinese Medical Association has led the development of Expert consensus on community screening of diabetic retinopathy among DR community screening experts that is suitable for the current national situation, in order to guide and promote the further improvement of DR community screening work in China. This Expert Consensus provides detailed specifications on the current domestic trend of DR, the necessity of screening, the role of artificial intelligence grading, screening process, and quality control. This interpretation further emphasizes the importance of DR community screening, while emphasizing the responsibilities of different departments in the screening process. Finally, recommendations are provided for the sustainability of DR community screening. It is hoped that the screening rate of DR in China can be improved and blindness can be reduced by DR through Expert consensus on community screening of diabetic retinopathy and interpretation of the content.

Effect of α-Klotho on macrophage-vascular endothelial cell crosstalk in diabetic oxidative stress environment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effects of overexpressing α-Klotho(KL)in RAW264.7 cells stimulated by oxidative stress on the proliferation, migration, tube-formation and tight junction of human umbilical vein endothelial cells(HUVECs).METHODS:RAW264.7 cells were categorized into control, 4-hydroxynonenal(4HNE), and 4HNE+KL groups, with F4/80 expression assessed via immunofluorescence staining. Three groups of conditional media were prepared for HUVECs and culture divided into Mø-NC, Mø-4HNE, and Mø-4HNE+KL groups. Cell proliferation was evaluated using CCK8 assay, while scratch test and Transwell assays were employed to measure cell migration. Additionally, tube-formation assay was conducted to assess cell tubule formation, and Western blot assay was utilized to detect the protein expression levels of Claudin 5, Occludin and ZO 1.RESULTS:The results of immunofluorescence staining showed that the fluorescence intensity of F4/80 of RAW264.7 cells in the 4HNE group was significantly enhanced compared with the control group, while that of F4/80 in the 4HNE+KL group was significantly decreased compared with the 4HNE group(all P<0.05). The CCK8 assay results revealed a significant increase in the proliferation of HUVECs in the Mø-4HNE group compared with the Mø-NC group. Conversely, the proliferation of the Mø-4HNE+KL group exhibited a significant decrease compared with that in the Mø-4HNE group(all P<0.01). The results of scratch test and Transwell assays demonstrated a significant increase in the migration of HUVECs in the Mø-4HNE group compared with the Mø-NC group, while the migration of the Mø-4HNE+KL group exhibited a significant decrease compared with the Mø-4HNE group(all P<0.01). In the tube-formation assay, it was observed that the number of tubes formed by HUVECs in the Mø-4HNE group was significantly increased compared with the Mø-NC group, while that of tubes formed in the Mø-4HNE+KL group was significantly decreased compared with the Mø-4HNE group(all P<0.01). Additionally, the Western blot results revealed a significant decrease in the relative expression levels of Claudin 5, Occludin, and ZO 1 in the Mø-4HNE group compared with the Mø-NC group. Conversely, in the Mø-4HNE+KL group, there was a significant increase in the relative expression levels of Claudin 5, Occludin, and ZO 1 compared to the Mø-4HNE group(all P<0.01).CONCLUSIONS: KL inhibits the proliferation, migration, and tube-formation of HUVECs while enhancing the tight junction by changing the activation state of macrophages in the diabetic oxidative stress environment.

The molecular mechanism of Liuwei Dihuang Pill in the treatment of premature ovarian insufficiency in a mouse model / 中国组织工程研究

BACKGROUND:Most of the formulas for the clinical treatment of premature ovarian insufficiency have evolved from the basic formula of Liuwei Dihuang Pills,and have achieved good therapeutic efficacy.Currently,most of the experimental studies on Liuwei Dihuang Pills focus on morphological observations and physiological and biochemical detection of in vivo animal models,while fewer studies on molecular mechanisms have been reported. OBJECTIVE:To explore the molecular mechanism of Liuwei Dihuang Pills in the treatment of premature ovarian insufficiency based on the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species pathway. METHODS:Premature ovarian insufficiency model was established in mice by intraperitoneal injection of cyclophosphamide 120 mg/kg combined with busulfan 12 mg/kg,and then Liuwei Dihuang Pill suspension was used to intervene in premature ovarian insufficiency mice.After 12 weeks of intervention,the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,anti-Mullerian hormone,8-hydroxydeoxyguanosine,total antioxidant capacity and reactive oxygen species in serum of mice were detected by ELISA method.The morphological changes in mouse ovaries were observed by hematoxylin-eosin staining.The ultrastructure of mouse follicular granulosa cells and the apoptosis of granulosa cell mitochondria were observed by transmission electron microscopy.The expression levels of receptor gamma coactivator-1 alpha and mitochondrial transcription factor A in mouse ovarian granulosa cells were detected by immunohistochemistry. RESULTS AND CONCLUSION:Compared with the model group,serum levels of follicle-stimulating hormone,luteinizing hormone,reactive oxygen species,and 8-hydroxydeoxyguanosine were decreased in the experimental group(P＜0.05),and the levels of estradiol,anti-Mullerian hormone,and total antioxidant capacity were increased(P＜0.05).Hematoxylin-eosin staining showed that in the model group,there were more atretic follicles and corpus luteum forms,some secondary follicles,and interstitial fibrosis and hyperplasia;in the experimental group,a large number of atretic follicles,few corpus luteum forms,primordial follicles were observed at the edges but there were few secondary follicles and no mature follicles.Transmission electron microscopy showed that the organelles in ovarian granulosa cells of mice in the experimental groups were relatively intact.Immunohistochemical results showed that compared with the model group,the expression level of receptor gamma coactivator-1 alpha in the ovarian tissue of mice increased slightly in the experimental group at the 4th week,and there was no significant change at the 8th and 12th weeks.The expression level of mitochondrial transcription factor A in the ovarian tissues of mice in the experimental group was transiently increased at the 4th week,and then slightly decreased,which were all significantly different from those of the model group.To conclude,Liuwei Dihuang Pills inhibit ovarian granulosa cell apoptosis in mice with premature ovarian insufficiency to a certain extent through the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species signaling pathway,thereby improving the endocrine function of the ovary,enhancing the antioxidant capacity,and attenuating the degree of oxidative stress damage.

The relationship between blood cell-related inflammatory markers and diabetic retinopathy: a study from Beichen Eye Study / 中华眼底病杂志

Objective:To observe the correlation between blood cell-related inflammatory markers and diabetic retinopathy (DR).Methods:A cross-sectional study. From June 2020 to February 2022, the phase Ⅰ data of Beichen Eye Study in Tianjin Medical University Eye Hospital were included in the study. The research contents included questionnaires, routine systemic and ocular examinations, and laboratory blood cell-related indicators including mean platelet volume (MPV), platelet distribution width (PDW), neutrophils, and lymphocytes were performed. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were calculated. The diagnosis and classification of DR referred to the international clinical classification standard of DR. Monocular or binocular DR was defined as DR patients. Participants were categorized into different groups based on whether they had diabetes and whether they had DR. The groups included the no-diabetes group, the diabetes without DR group, and the DR group. The Kruskal-Wallis H test was used for the comparison of quantitative data among multiple groups. Wilcoxon test was used for comparison between the two groups. The χ2 test was used to compare the categorical variables between groups. The variables was adjusted step by step, an unadjusted univariate model was built and the different parameters of the model Ⅰ, Ⅱ, Ⅲ were adjusted. The correlation between MPV, PDW, NLR, PLR, and DR in different models was analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different NLR models for DR. Results:A total of 3 328 subjects were recruited. Among them, 1 121 (33.68 %, 1 121/3 328) were males and 2 207 (66.32 %, 2 207/3 328) were females. The median age of the included participants was 61.84 (6.05) years. The no-diabetes group, the diabetes without DR group, and the DR group were 2 679, 476, and 173, respectively. There was no significant difference in MPV and PLR among the three groups ( H=5.98, 1.94; P=0.051, 0.379). However, compared with no-diabetes group and the diabetes without DR group, PDW and NLR in the DR group showed an upward trend. In model Ⅲ with completely adjusted related factors, NLR was an independent risk factor for DR in no-diabetes group and DR group [odds ratio ( OR)=1.440, 95% confidence interval ( CI) 1.087-1.920, P=0.041], diabetes without DR group and DR group [ OR=1.990, 95% CI 1.440-2.749, P<0.001]. The results of ROC curve analysis showed that the diagnostic efficiency of NLR model Ⅲ was the highest, the area under the curve was 0.751 (95% CI 0.706-0.796, P<0.001), the optimal cutoff value was 0.390, and the sensitivity and specificity were 74.3% and 64.8%, respectively. Conclusions:The NLR of the DR group is significantly higher than that of the no-diabetes group and diabetes without DR group. NLR is an independent risk factor for DR.

Underexpression of deleted in liver cancer 2 (DLC2) is associated with overexpression of RhoA and poor prognosis in hepatocellular carcinoma.

BACKGROUND: DLC2, a unique RhoGAP, has been recently identified as a tumor suppressor gene in hepatocellular carcinoma (HCC). However, the expression of DLC2 protein, and its relationship with RhoA in clinical hepatocellular carcinoma have not been studied. The aim of this study was to investigate the DLC2 protein expression and its correlation with expression of RhoA, as well as to evaluate the prognostic value of DLC2 for HCC patients. METHODS: Western blot and immunohistochemical staining were employed to detect DLC2 protein expression in 128 HCC specimens. The correlation between DLC2 protein expression and clinicopathologic outcome, and prognostic value of DLC2 for HCC patients were analyzed. RESULTS: HCC tissues revealed significantly lower level of DLC2 protein than pericarcinomatous liver tissues (PCLT). There was significant correlation between underexpression of DLC2 protein and cell differentiation. Meanwhile, underexpression of DLC2 protein was correlated with overexression of RhoA. Furthermore, HCC Patients with DLC2-negative expression showed a significantly poorer prognosis than those with DLC2-positve expression. CONCLUSION: Our data strongly suggested that decreased DLC2 expression in HCC correlates with cell differentiation of HCC and overexpression of RhoA, underexpression of DLC2 is associated with poor prognosis in HCC patients.

Paying attention to importance to the innovation in retinal surgery / 中华眼底病杂志

With the continuous advancement of technology, the field of retinal surgery is poised to witness an increasing array of innovations and breakthroughs. The innovation in retinal surgery plays a pivotal role in enhancing the success rate of operations, reducing the risk of complications, and improving patient prognosis and quality of life. This encompasses innovations in vitrectomy systems, the novel application of vitrectomy in treating other ocular diseases, advancements in retinal surgical techniques, technological and conceptual innovations, as well as multidisciplinary collaboration, all of which contribute to the ongoing development in the treatment of retinal diseases. Therefore, innovations in retinal surgery should receive significant attention from ophthalmologists specializing in retinal diseases with the best service to patients.

Research progress on the correlation between metabolic memory and mito-chondrial function in diabetic retinopathy / 眼科新进展

Diabetic retinopathy(DR)is a severe blinding eye disease caused by diabetes.A number of studies have shown that there is a phenomenon of"metabolic memory"in diabetic patients,but its mechanism is still unclear.In the oc-currence and progression of DR,oxidative stress in a high-glucose environment causes abnormal mutations of mitochondrial DNA(mtDNA)copy number in retinal cells,and its repair system is destroyed at the same time and forms a vicious circle,resulting in excessive production of reactive oxygen,destruction of redox homeostasis and apoptosis.The mtDNA can be independently replicated and passed on to the next generation,and epigenetic modification can also affect the regulation of genes related to the pathogenesis of DR.In the occurrence and development of DR,it is of great significance to clarify the mechanism of mitochondrial damage and"metabolic memory"for the prevention and treatment of DR.The emergence of mitochondrial transfer technology is expected to break the"metabolic memory"phenomenon and open up new avenues for treating such diseases.This article gives a review of the related research and development.

Research progress of ferroptosis involved in the pathogenesis of diabetic retinopathy / 中华眼底病杂志

Diabetic retinopathy (DR) constitutes a major retinal vascular disorder leading to blindness in adults. Current therapeutic approaches for DR exhibit certain degrees of efficacy but are constrained by a spectrum of limitations. Hence, there is a pressing need to deeply investigate the underlying pathogenesis of DR and explore novel therapeutic targets. Ferroptosis, a distinctive form of programmed cell death, has emerged as a pertinent phenomenon in recent years. Notably, ferroptosis has been implicated in the progression of DR through mechanisms involving the induction of retinal oxidative stress, provocation of anomalous retinal vascular alterations, exacerbation of retinal neural damage, and elicitation of immune dysregulation. Thus, elucidating the mechanistic role of ferroptosis in DR holds the potential to establish a robust foundational rationale. This could potentially facilitate the clinical translation of ferroptosis inhibitors as promising agents for the prevention and treatment of DR, thereby forging novel avenues in the landscape of DR management.

One-stop intravitreal injection model: expert consensus on establishment and management / 中华眼底病杂志

Intravitreal drug injection is a treatment for common chronic fundus diseases such as age-related macular degeneration and diabetic retinopathy. The "14th Five-Year" National Eye Health Plan (2021-2025) recommends focusing on fundus diseases and improve the management mode of patients with chronic eye diseases. Therefore, it is imperative to explore how to further optimize the service process of intravitreal injection under the premise of guaranteeing patients' medical safety, to promote medical service efficiency and standardized management level and improve the medical experience of patients. Based on the quality control standard of vitreous cavity injection for retinopathy in China, Chinese fundus disease and related field experts developed the present expert consensus on the establishment of a one-stop intravitreal injection model and the management of its organization after a serious, comprehensive, and complete discussion, focusing on a standardized operation process, quality control, and safety management, providing more references for establishing a suitable intravitreal injection management model for ophthalmology and promoting the development of diagnostic and treatment models for fundus disease in China.

Progress on the function and mechanism of pigment epithelium derived factor receptors in the occurrence and development of diabetic retinopathy / 中华眼底病杂志

Endogenous pigment epithelium derived factor (PEDF) shows great potential as a drug target for the treatment of diabetes retinopathy (DR) due to its anti-angiogenesis, anti-inflammatory, neuroprotective and neurotrophic effects. PEDF plays a biological role by combining with receptor proteins on cell membrane surface and regulating a variety of signaling pathways. Low density lipoprotein receptor related protein 6 plays a role in inhibiting oxidative stress reaction, inflammatory reaction, and neovascularization of DR. Adipose triglyceride lipase, laminin receptor, plexin domain containing 1 (PLXDC) 1, PLXDC2 and F 1-adenosine triphosphate synthase have the effect of promoting endothelial cell apoptosis, among which PLXDC1 also has neuroprotective effect. By clarifying the receptor that PEDF acts on, exploring the affinity between the receptor and PEDF, the difference in the expression level of each receptor in the process of disease, and the specific function that PEDF plays after binding with specific receptors, we can develop fusion protein drugs for the active domain of high affinity of receptors, have a clearer understanding of the pathogenesis of DR, and take PEDF or PEDF receptor as the target to consolidate the theoretical basis for the development of new therapeutic drugs and strategies for DR.

Risk factors of postoperative vitreous hemorrhage after pars plana vitrectomy for vitreous hemorrhage secondary to retinal vein occlusion / 中华眼底病杂志

Objective:To analyze the risk factors of postoperative vitreous hemorrhage (PVH) after pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) secondary to retinal vein occlusion (RVO).Methods:A retrospective case-control study. A total of 195 RVO patients (195 eyes) with VH were first treated with PPV from November 2015 to December 2021 were included in this study. There were 102 males (102 eyes) and 93 females (93 eyes), with an age of (62.93±9.78) years. The patients were divided into PVH group (17 patients, 8.72%) and non-PVH group (178 patients, 91.28%) according to the occurrence of PVH. The time of occurrence of PVH was (140.33±130.85) days after PPV. All eyes were performed 23G or 25G systematic PPV by the same doctor. During the operation, different types of intraocular tamponade and intravitreal injection of anti-vascular endothelial growth factor or triamcinolone acetonide after operation were selected according to the severity of retinopathy. The follow-up time was (9.45±6.68) months. The baseline systemic parameters, ocular parameters and intraoperative parameters affecting the occurrence of PVH were analyzed. Baseline systemic parameters included sex, age, diabetes mellitus and hypertension; ocular parameters included RVO type, lens status, VH course, preoperative best corrected visual acuity and intraocular pressure; intraoperative parameters included cataract phacoemulsification, removal of internal limiting membrane, type of intraocular tamponade, type of intravitreal injection drug at the end of operation, etc. Kaplan-Meier survival analysis, and Cox univariate and multivariate regression analysis were performed to analyze the risk factors of PVH after PPV in RVO with VH patients.Results:In PVH group, the number of patients with diabetes was more than that in the non-PVH group, and the course of diabetes was longer, and differences were statistically significant. There were significant differences in RVO type, lens status and type of intraocular tamponade. Univariate Cox regression analysis showed that the combination with diabetes [odds ratio ( OR)=2.724, 95% confidence interval ( CI) 1.006-7.374, P=0.049], duration of diabetes ( OR=1.071, 95% CI 1.013-1.134, P=0.016), central retinal vein occlusion ( OR=4.387, 95% CI 1.421-13.546, P=0.010), intraocular lens ( OR=3.493, 95% CI 1.229-9.925, P=0.019), and intraocular gas tamponade ( OR=3.640, 95% CI 1.365-9.702, P=0.010) were associated with PVH. Multivariate Cox regression analysis showed that intraocular gas tamponade was independent risk factor for PVH. Conclusion:Intraocular gas tamponade can increase the risk of PVH after PPV in patients with VH secondary to RVO.

Research progress on the combination therapy of diabetic macular edema / 中华眼底病杂志

Diabetic macular edema (DME) is the most threatening complication of diabetic retinopathy that affects visual function, which is characterized by intractability and recurrent attacks. Currently, the clinical routine treatments for DME mainly include intravitreal injection, grid laser photocoagulation in the macular area, subthreshold micropulse laser, periocular corticosteroid injection, and vitrectomy. Although conventional treatments are effective for some patients, persistent, refractory, and recurrent DME remains a clinical challenge that needs to be urgently addressed. In recent years, clinical studies have found that certain combination therapies are superior to monotherapy, which can not only restore the anatomical structure of the macular area and effectively reduce macular edema but also improve visual function to some extent while reducing the number of treatments and the overall cost. This makes up for the shortcomings of single treatment modalities and is highly anticipated in the clinical setting. However, the application of combination therapy in clinical practice is relatively short, and its safety and long-term effectiveness need further exploration. Currently, new drugs, new formulations, and new therapeutic targets are still under research and development to address different mechanisms of DME occurrence and development, such as anti-vascular endothelial growth factor agents designed to anchor repetitive sequence proteins with stronger inhibition of vascular leakage, multiple growth factor inhibitors, anti-inflammatory agents, and stem cell therapy. With the continuous improvement of the combination application of existing drugs and treatments and the development of new drugs and treatment technologies, personalized treatment for DME will become possible.

Progress in controlled ocular anti-VEGF drug release delivery system / 中华实验眼科杂志

Neovascularization is the hallmark of many fundus diseases, including diabetic retinopathy, retinal vein occlusion and neovascular age-related macular degeneration.More and more evidence suggests that vascular endothelial growth factor (VEGF) plays a critical role in neovascularization.Anti-VEGF drugs are the first-line treatment for neovascular fundus diseases and have achieved significant results.However, there are drawbacks such as short drug half-lives and the need for long-term administration to maintain effective concentrations, which increases the economic burden and medical risk for patients and reduces compliance.Therefore, finding a new method for intraocular drug delivery is of great clinical importance.Based on the principle that diabetes patients use insulin pumps to gradually release drugs, the ocular anti-VEGF drug delivery system can continuously release anti-VEGF drugs over a period of time, significantly reducing the injection frequency and improving patient compliance.At present, the research on ocular anti-VEGF drug delivery systems is still immature, and various systems are in different stages of clinical trials.According to different design principles, they can be divided into three categories with their characteristics, micropump (extraocular storage delivery systems), biodegradable implants, and non-biodegradable implants.This article summarized and analyzed the controlled ocular anti-VEGF drug release delivery systems currently in clinical trials.

Paying close attention to the therapeutic effect of brolucizumab on polypoidal choroidal vasculopathy and its clinical application / 中华实验眼科杂志

Polypoidal choroidal vasculopathy (PCV) occurs in the middle-aged and elderly population and is characterized by abnormal intrachoroidal vascular patterns such as branching choroidal vascular networks and polypoidal dilatation of vessel terminals, subretinal orange nodular lesions and hemorrhagic or plasma retinal pigment epithelial detachment (PED), which can cause retinal hemorrhage or vitreous hematopoiesis and is one of the major blinding fundus lesions.Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is currently the main method of PCV treatment, and has certain advantages in eliminating abnormal vascular networks and removing polypoidal lesions, reducing vascular exudation and promoting exudate absorption, and improving visual prognosis.However, frequent intravitreal drug injections increase the risk of infection and the treatment burden for patients.In addition, the high recurrence rate after treatment poses a significant challenge to clinical practice, so the search for new therapeutic agents that are durable and less costly is a focus of clinical research in PCV.The literature from abroad suggests that brolucizumab is a novel small-molecule anti-VEGF humanized monoclonal antibody with the advantages of high tissue penetration, high local drug concentration and bioavailability, small injectable dose, long-lasting efficacy and long injection interval, which brings new hope for the clinical treatment of PCV and improving the prognosis of affected eyes.Although the efficacy and safety of brolucizumab in the treatment of PCV have been well documented, the literature is mainly from Japan, India and Korea, and clinical practice data from China are still lacking.With the approval of the drug in several countries, it is believed that more PCV patients could benefit from this treatment in the near future.Ophthalmologists and researchers in China should closely follow the progress of brolucizumab in the treatment of PCV.

Analysis of early predictors of severe and critical SARS-CoV-2 infection / 实用医学杂志

Objective To explore the early predictors of the development of the novel coronavirus infection(COVID-19)into severe and critical forms.Methods COVID-19 patients hospitalized in the Department of Intensive Care Medicine,Infection ward,Respiratory and Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University from December 2022 to March 2023 were selected as the study objects,and were divided into mild/medium group,severe group,and critical group according to the severity of illness during hospitalization.General clinical data and early laboratory results of the three groups were collected and compared.Results A total of 242 patients with novel coronavirus infection were included,including 117 mild/medium patients,55 severe patients,and 70 critically severe patients.There were 165 males and 77 females with a median age of 70(59,80)years.The age,sex,diabetes,heart disease,stroke,combined pneumonia,combined bloodstream infection,APACHE Ⅱ score,respiratory rate on admission,systolic blood pressure,and early white blood cell count(WBC),lymphocyte count(LYM),urea,creatinine,albumin,C-reactive protein,D-dimer,interleukin-6(IL-6),and calcium reduction of patients in the three groups had significant(all P<0.05).Ordered logistic regression shows,previous heart disease,stroke,combined bloodstream infection,WBC,high IL-6 level,and low LYM level were independent risk factors for severe and critical COVID-19 infection[odds ratio(OR)and 95%confidence interval(95%CI)were 3.253(1.694～6.246),5.251(2.378～11.592),respectively.6.920(2.499～19.189),1.111(1.041～1.186),1.003(1.001～1.006),0.571(0.353～0.926)].ROC curve analysis showed that WBC,LYM,IL-6 and their combined detection had certain predictive value for the severity of COVID-19(all P<0.05),and the combined detection of WBC,LYM and IL-6 had better predictive value than a single indicator(P<0.05).Conclusion Previous heart disease,cerebrovascular disease,early combination of bloodstream infection,high levels of IL-6,white blood cell count,and low lymphocyte levels at admission were independent risk factors that helped to predict the severity of COVID-19 infection early.The combined detection of WBC,LYM and IL-6 has certain predictive value for the development of severe and critical COVID-19.

Circ_0075960 targets the miR-202-5p/CTNND1 axis to promote the growth and migration of endometrial carcinoma cells via regulating Wnt/β-catenin signaling activity / 부인종양

Background@#Endometrial carcinoma (EC) is one of the most common malignant tumors of the female reproductive tract, involving multiple molecular alterations. Circular RNA (circRNA) dysregulation is frequently observed in EC tissues, suggesting the involvement of circRNA in EC development. We aimed to investigate the role of circ_0075960 in EC. @*Methods@#Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays were applied for expression analysis. CCK-8, EdU, colony formation, flow cytometry and wound healing assays were employed for functional analysis. The predicted binding relationship between miR-202-5p and circ_0075960 or CTNND1 was validated by dual-luciferase reporter experiment. In vivo animal models were constructed in nude mice to verify the role of circ_0075960 in tumor growth. @*Results@#Circ_0075960 and CTNND1 were upregulated, while miR-202-5p was downregulated in EC. Knockdown of circ_0075960 induced EC cell apoptosis, suppressed cell proliferation and migration, and repressed tumor growth in animal models. MiR-202-5p was targeted by circ_0075960 and it directly bound to CTNND1 3’UTR. The inhibition of circ_0075960 knockdown or miR-202-5p enrichment on EC cell proliferation and migration was reversed by miR-202-5p depletion or CTNND1 overexpression, respectively. Circ_0075960 targeted miR-202-5p to positively regulate CTNND1 expression. Moreover, circ_0075960 knockdown weakened the activity of Wnt/β-catenin signaling via targeting the miR-202-5p/CTNND1 axis. @*Conclusion@#Circ_0075960 targets the miR-202-5p/CTNND1 axis to modulate Wnt/β-catenin signaling activity, thus contributing to the malignant development of EC.

Therapeutic effect of small extracellular vesicles derived from mesenchymal stem cells on retinal light injury and its mechanism / 中华实验眼科杂志

Objective:To investigate the effect of small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) in mouse model of retinal light injury and the possible mechanism.Methods:Human umbilical cord derived MSCs were identified by flow cytometry.Supernatants of passage 3-5 MSCs were collected.sEVs were harvested by ultracentrifugation and were identified by transmission electron microscopy.Sixty-five healthy female SPF-grade BALB/c mice aged 8-10 weeks were randomly divided into normal group (17 mice), phosphate buffered saline (PBS) group (24 mice) and sEVs group (24 mice). Mice in PBS and sEVs groups were intravitreally injected with 2 μl of PBS and sEVs, respectively, and were exposed to 930 lx blue light for 6 hours.No intervention was administered to the normal group.Three days after lighting, mice retinal structure was observed by hematoxylin-eosin staining.Apoptotic retinal cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Retinal function was tested by electroretinogram.Differentially expressed mRNAs between PBS group and sEVs group were assayed by mRNA transcriptome sequencing and were analyzed through KEGG cluster analysis.The differential mRNAs were verified via real-time quantitative PCR.The study protocol was approved by the Animal Ethics Committee of Tianjin Medical University Eye Hospital (No.TJYY20201221035).Results:MSCs were positive for CD90 and CD105, negative for CD34 and CD45.The extracted MSC-sEVs showed a bilayer membrane vesicle with a diameter of 80-140 nm.Hematoxylin-eosin staining showed the arrangement of photoreceptor nuclei was disordered in outer nuclear layer in PBS group.The disorder of photoreceptor nuclei arrangement of sEVs group was slighter than that of PBS group.The apoptotic cell number of sEVs group was (14.60±4.04)/visual field, which was lower than (24.00±8.52)/visual field of PBS group, with a statistically significant difference ( t=2.37, P<0.05). The a-wave amplitude of sEVs group was (64.38±16.70)μV, which was higher than (16.78±6.37) μV of PBS group, showing a statistically significant difference ( P<0.05). The b-wave amplitudes of PBS and sEVs groups were (132.40±39.41) μV and (154.86±34.08) μV, respectively, which were lower than (338.38±27.41) μV of normal group, and the differences were statistically significant (both at P<0.05). A total of 110 differentially expressed mRNAs were detected.There were 109 downregulated mRNAs in sEVs group.Differentially expressed mRNAs were mainly inflammation- and immune-related pathways.PCR showed that the expression level of C-C motif chemokine ligand 2, C-C motif chemokine receptor 2, leukotriene B4, leukocyte Ig-like receptor A6 and interleukin-1β in sEVs group were significantly decreased in comparison with PBS group (all at P<0.05). Conclusions:MSC-sEVs can ameliorate blue light-induced retinal structural and functional damage.The protective effect may be achieved through inhibiting inflammatory response.