Research progress of retinal neurovascular unit injury in glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Glaucoma is one of the leading causes of vision loss worldwide. More and more studies have suggested that glaucoma is a complicated retinal neurovascular disease. The homeostasis imbalance of retinal neurovascular unit(RNVU)composed of neurons, glial cells and microvascular cells not only induces changes in microvascular structure and glial cells, but also affects the nerve tissue of the retina, resulting in vision loss, which there is no effective treatment to reverse, currently. Exploring the cellular composition and molecular structure of RNVU and investigating the destruction mechanism of normal cellular environment and intercellular connections in glaucoma are of great significance in exploring the pathogenesis and the treatment of glaucoma. The research progress on structural changes and dysfunction of RNVU in glaucoma are reviewed, hoping to provide new ideas for the treatment of glaucoma.

Retrospective investigation on the normal range of serum alanine aminotransferase levels in healthy adults in Ningbo area / 中华传染病杂志

Objective:To reevaluate the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) by retrospectively analyzing the ALT levels in healthy people in Ningbo area.Methods:A total of 56 140 people who underwent health examination and detection of liver biochemical indexes in the Affiliated Hospital of Medical School of Ningbo University and Yinzhou Huamao Hospital of Ningbo from 2018 to 2020 were enrolled. After excluding relevant factors that may lead to liver injury, 11 411 people were included to compare the difference of serum ALT levels among different genders and age groups (20 to 29 years, 30 to 39 years, 40 to 49 years and 50 to 59 years) to determine the ALT ULN in different gender groups. Statistical methods were performed using two independent samples t test and analysis of variance. Results:The serum ALT of males was (19.20±7.90) U/L, which was higher than that of females ((13.75±6.17) U/L), with statistical significance ( t=41.16, P<0.001). The serum ALT ULN in males and in females were 35 U/L and 26 U/L, respectively. The serum ALT levels of 20 to 29, 30 to 39, 40 to 49 and 50 to 59 years old groups were (15.48±7.61) U/L, (16.21±7.40) U/L, (17.36±7.52) U/L and (18.77±7.57) U/L, respectively.The difference was statistically significant ( F=71.51, P<0.001). Serum ALT level in 50 to 59 years old group was higher than that in 20 to 29 years old group, and the difference was statistically significant ( t=13.11, P<0.01). In males, the ALT ULN of 20 to 29 years old was the lowest of 34.43 U/L, and highest of 35.29 U/L in 40 to 49 years old. In females, the ALT ULN in the 20 to 29 years old group was the lowest of 23.01 U/L, and the ALT ULN in the 50 to 59 years old group was the highest of 30.79 U/L. ALT ULN increased with age in females. The serum ALT of males was higher than that of females in all age groups ( t=29.55, 26.91, 13.43 and 4.62, respectively, all P<0.05). Conclusions:The serum ALT level is significantly correlated to gender and age. The serum ALT ULNs of healthy adult are 35 U/L in males and 26 U/L in females in Ningbo area.

Path of constructing a "seven-in-one" medical postgraduate education quality assurance system in military medical universities / 中华医学教育探索杂志

This paper analyzes the current situation of constructing postgraduate education quality assurance systems worldwide, and explores the specific path of constructing a "seven-in-one" medical postgraduate education quality assurance system. The system should be constructed according to the education practice in military medical universities and consider the following aspects: first-class students, first-class teaching, first-class tutors, first-class disciplines, first-class management, first-class culture, and first-class achievements. The system should be constructed by enrollment reform and innovation, teaching method reform, tutor team construction, discipline construction, cultural atmosphere creation, and emphasis on cultivating achievements.

Comparison between white light endoscopy and narrow-band imaging endoscopy in predicting histological healing of ulcerative colitis in remission / 中华消化内镜杂志

Objective:To investigate the predictive value of mucosal vascular pattern (MVP) under narrow-band imaging (NBI) enteroscopy in patients with ulcerative colitis (UC) in clinical remission for histological healing and clinical recurrence.Methods:A total of 142 patients with UC in clinical remission who visited the First Affiliated Hospital of Weifang Medical University from January 2018 to January 2021 were included in the study and underwent colonoscopy. The white light and NBI endoscopic images were collected and biopsies were obtained. The Mayo endoscopic score (MES) was calculated based on white light images, and MVP staging was evaluated based on mucosal vascular patterns under NBI. Nancy index (NI) was used to evaluate histological healing and patients were followed up for 1 year. The Spearman correlation coefficients of MES and MVP with histological healing and recurrence were calculated. The receiver operator characteristic (ROC) curve was plotted and the area under curve (AUC) was applied to evaluate the accuracy of white light and NBI endoscopy for predicting histological healing of UC in clinical remission.Results:According to the MVP criteria, 47 were defined as clear, 63 blurred, and 32 invisible. Spearman correlation analysis showed a significant correlation between MVP under NBI and histological healing ( r=0.549, P<0.001) and a moderate correlation between MES under white light and histological healing ( r=0.462, P<0.001). Spearman correlation analysis showed a moderate correlation between MVP under NBI and clinical recurrence ( r=0.451, P<0.001) and a moderate correlation between MES under white light and clinical recurrence ( r=0.352, P<0.001). AUC of NBI for diagnosing histological healing of UC in clinical remission was 0.809 (95% CI: 0.738-0.879), with a sensitivity of 84.6% (77/91) and specificity of 64.7% (33/51), superior to the white light endoscopy, of which AUC, sensitivity and specificity were 0.763 (95% CI: 0.678-0.848), 81.3% (74/91) and 66.7% (34/51). Conclusion:MVP staging under NBI could predict histological healing of UC patients in clinical remission and is superior to white light endoscopy.

Lymph node dissection for patients with intrahepatic cholangiocarcinoma in China: a meta-analysis / 中华肝胆外科杂志

Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.

Risk factors and risk model construction of coronary heart disease in patients with type 2 diabetes mellitus in Suining area / 公共卫生与预防医学

Objective To analyze the risk factors of coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2M) in Suining area, and build a risk prediction model to provide theoretical basis for the prevention and treatment of CHD in PATIENTS with T2M. Methods A total of 476 T2M patients treated in our hospital from January 2021 to December 2021 were selected and divided into experimental group (n=79) and control group (n=397) according to whether they had coronary heart disease. The angiographic characteristics of coronary artery lesions in patients with T2M combined with coronary heart disease were observed. Age, sex, body mass index (BMI), smoking, alcohol consumption , T2M course, FBG, FINS, HOMA, TC, LDL-C, SBP, DBP and UA levels of all patients were analyzed. Univariate analysis and Logistic regression were used to analyze the influencing factors of coronary heart disease and establish a risk prediction model. ROC curve was used to predict the efficiency of the model. Results A total of 79 cases (16.60%) of patients with T2M complicated with coronary heart disease, including 64 cases (81.01%) of patients with T2M complicated with coronary artery disease. Mild stenosis in 5 cases (6.33%), moderate stenosis in 20 cases (25.32%) and severe stenosis in 54 cases (68.35%); The mean age, smoking proportion, BMI, T2M course and the levels of FBG, FINS, HOMA-IR, TC, LDL-C, SBP, DBP and UA in experimental group were significantly higher than those in control group (P-(-0.513+0.919×(old age)+1.129×(increased SBP)+ 1.724×(increased FBG)+ 1.529×(increased LDL-C)]. ROC curve was used to analyze the predictive performance of the regression model. The results showed that the AUC of the risk prediction model for coronary heart disease in T2M patients was 0.728, 95% CI (0.651-0.829). Conclusions T2M patients in Suining have a high risk of coronary heart disease. For elderly patients with elevated SBP, LDL-C and FBG, the risk of coronary heart disease can be assessed by predictive model and targeted intervention measures can reduce the risk of coronary heart disease in T2M patients.

A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8+ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

Progress in Development of Dose Verification System Software KylinRay-Dose4D / 中国医疗器械杂志

Advanced radiotherapy technology enables the dose to more accurately conform to the tumor target area of the patient, providing accurate treatment for the patient, but the gradient of the patient's radiation dose at the tumor edge is getting larger, which putting forward higher requirements for radiotherapy dose verification. The dose verification system software KylinRay-Dose4D can verify the patient's pre-treatment plan and the in vivo/on-line dose during the patient's treatment, providing important reference for the physicist to modify the radiotherapy plan and ensuring that the patient receives accurate treatment. This study introduces the overall design and key technologies of KylinRay-Dose4D, and tests the pre-treatment plan dose checking calculation and 2D/3D dose verification through clinical cases. The test results showed that the 2D/3D gamma pass rate (3 mm/3%) of KylinRay-Dose4D reconstructed dose compared with TPS plan dose and measured dose is larger than 95%, which indicating that the reconstructed dose of KylinRay-Dose4D meets the requirement of clinical application.

Total Glucosides of Paeony Improve Renal Injury in Mice with Systemic Lupus Erythematosus by Regulating TLR9/MyD88/NF-κB Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of total glucosides of paeony （TGP） on the renal injury of MRL/lpr mice based on the Toll-like receptor 9 （TLR9）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway and explore the immunological mechanism of TGP in preventing and treating systemic lupus erythematosus （SLE）. MethodMRL/lpr female mice of SPF grade were randomly divided into a model group， a dexamethasone group （0.15 g·kg-1）， and high- （0.078 g·kg-1） and low-dose （0.039 g·kg-1） TGP groups， and female C57BL/6J mice were assigned to a blank group， with 7 mice in each group. Mice in each group were treated with corresponding drugs or normal saline by gavage at the same time every day. After 4 weeks， samples were collected. The kidney and spleen were weighed， and the organ index was calculated. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels in each group were detected by biochemical assay. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the kidney. The degree of renal fibrosis was evaluated by Masson staining. The serum levels of interleukin （IL）-2， interferon （IFN）-α， IL-4， and anti-nuclear antibody （ANA） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of TLR9， MyD88， and NF-κB p65 in renal tissues was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of TLR9 and NF-κB p65 in renal tissues was detected by immunofluorescence. The protein expression of TLR9， MyD88， and NF-κB p65 in renal and spleen tissues was tested by Western blot. ResultCompared with the blank group， the model group showed increased SCr， BUN， spleen index， and kidney index （P<0.05）， deteriorated pathological injury and fibrosis in renal tissues， elevated serum levels of IFN-α， IL-4， and ANA， decreased level of IL-2 （P<0.05）， and up-regulated TLR9， MyD88， and NF-κB p65 mRNA and protein levels in the kidney and spleen （P<0.05）. Compared with the model group， the TGP groups displayed reduced SCr， BUN， spleen index， and kidney index （P<0.05）， relieved pathological damage and fibrosis in renal tissues， decreased serum levels of IFN-α， IL-4， and ANA （P<0.05）， increased level of IL-2， and declining mRNA and protein expression levels of TLR9， MyD88， and NF-κB p65 in the kidney and spleen （P<0.05）. ConclusionTGP may inhibit the expression of downstream inflammatory factors to regulate immunity and resist SLE-induced renal injury by regulating the TLR9/MyD88/NF-κB signaling pathway.

Common problems analysis and improvements of medical records writing in the standardized residency training of ophthalmology / 中华医学教育探索杂志

Objectives:To investigate common problems analysis and improvements of medical records writing in the standardized residency training of ophthalmology.Methods:A total of 100 defective medical records of Renmin Hospital of Wuhan University from September 2019 to January 2020 were collected and analyzed for the problems and the reasons, as well as the improvements.Results:A total of 286 defects were found in these 100 medical records. Of which, content-related defects were detected in 89 medical records (31.12%), while quality-related problems were found in 151 records (52.80%). In addition, other defects were found in 46 records (16.08%). Major reasons included personal attitude, insufficient ophthalmic knowledge, heavy workload, lack of standardized guidance and insufficient communicational skills.Conclusion:By analyzing the major reasons of medical records writing, the following approaches, including standardized pre-job training, learning of medical dispute cases and online training, communicational skills training, in-time feedback and evaluation improvement, would be help to reduce the defects in the medical records written by ophthalmic residents.

Research progress of TGF-β in the formation of epiretinal membrane / 国际眼科杂志(Guoji Yanke Zazhi)

Epiretinal membrane(ERM)is a retinal disease characterized by a fibrocell membranes that can develop on the inner surface of the retina. The existing clinical guidelines and literature have reached a consensus on the diagnosis and treatment of ERM, but the explanation of their mechanism is still controversial. Transforming growth factor-β(TGF-β)is a highly pleiotropic cytokine that plays an important role in wound healing, angiogenesis, immune regulation, cancer, inflammation and fibrosis diseases. Studies have increasingly shown that ERM is a kind of pathological changes in fibrosis that caused by the posterior vitreous detachment(PVD)and lead to the retinal inflammatory damage and epithelial to mesenchymal transition(EMT)of retinal pigment epithelial cells. A variety of cytokines regulate TGF-β-mediated EMT process by participating in the non-classical TGF-β-Snail pathway and the classical TGF-β-Smad pathway. At present, some drugs targeting cytokines related to the above pathway have entered the development stage, which is of great significance to provide new ideas for clinical treatment and prevention of ERM. This review reviews the progress of TGF-β related cytokines in ERM formation.

Research progress of β-adrenergic receptor antagonists in the treatment of ocular neovascular diseases / 中华眼底病杂志

Ocular neovascularization is a pathological change in various ocular diseases such as diabetic retinopathy, retinopathy of prematurity, central retinal vein occlusion and age-related macular degeneration, which seriously affects patient's vision. β receptors are expressed in conjunctiva, corneal epithelial cells, corneal endothelial cells, extraocular muscles, trabecular meshwork, ciliary muscle, lens and retina. β adrenergic receptor antagonists bind to β receptors to exert anti-angiogenic effects by inhibiting the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1, interleukin-6 and other angiogenic cytokines; reducing macrophage-related inflammatory response; increasing the expression of anti-angiogenic factors. In the treatment of corneal neovascularization, choroidal neovascularization, and retinopathy of prematurity, it can significantly reduce the area of neovascularization and delay disease progression. Co-administration of anti-VEGF drugs can reduce the frequency of administration of anti-VEGF drugs. At effective therapeutic concentrations, β-adrenergic receptor antagonists are well tolerated; they have broader targets than anti-VEGF drugs, which offers new treatment strategies for ocular neovascularization such as corneal, choroidal and retinal neovascularization.

Reform in cultivation of medical graduate innovation ability / 中华医学教育探索杂志

This article elaborates how to facilitate the cultivation reform of medical graduate innovation ability from four perspectives: graduates, colleges or universities, supervisors and the society. Graduates should focus on studying high-quality academic papers, participate in various academic competitions, and actively apply for research projects; universities should innovate education philosophy, optimize curriculum system, create innovation-stimulating cultural atmosphere, establish quality supervision mechanism; supervisors should set a good example for their students, maintain a harmonious relationship with students, take the responsibility of fostering virtue though education and organize excellent supervisor team; and the society should support universities to realize "industry-education collaboration".

Significance of serum hepcidin in assessment of liver inflammation activity among patients with chronic hepatitis B / 预防医学

Objective@#To investigate the value of serum hepcidin in assessment of liver inflammation activity among patients with chronic hepatitis B ( CHB ), so as to provide insights into the assessment of liver inflammation activity among CHB patients.@*Methods@#A total of 79 CHB patients who were admitted to the Affiliated Hospital of Hangzhou Normal University were selected as the experimental group, while 40 healthy volunteers were randomly sampled as controls. Subjects'demographic data, liver function tests and iron metabolism parameters were collected from medical records, and serum hepcidin was measured using enzyme-linked immunosorbent assay ( ELISA ). In addition, ultrasound-guided liver biopsy was performed in CHB patients, and mild and moderate-to-severe CHB were classified according to liver inflammation activity and degree of liver fibrosis. Serum hepcidin levels were compared between the experimental and control groups and between patients with mild and moderate-to-severe CHB. The value of serum hepcidin in assessment of liver inflammation activity was examined among CHB patients using the receiver operating characteristic ( ROC ) curve analysis.@*Results@#Subjects in the experimental group included 54 men ( 68.35% ) and had a mean age of ( 39.06±10.67 ) years, while the controls included 24 men (60.00%) and had a mean age of ( 42.43±11.44 ) years. Lower hepcidin levels were measured in the experimental group than in the control group [( 11.70±5.64 ) vs. ( 17.82±3.63 ) μg/L; P<0.05 ]. There were 54 patients with mild CHB ( 68.35% ) and 25 cases with moderate-to-severe CHB ( 31.65% ), and lower hepcidin levels were detected in patients with moderate-to-severe CHB than in those with mild CHB [ ( 6.92±2.21 ) vs. ( 13.95±5.36 ) μg/L; P<0.05 ]. The area under the ROC curve, optimal cut-off, sensitivity and specificity of serum hepcidin were 0.903 ( P<0.05 ), 10.365 μg/L, 100.0% and 72.2% for assessment of moderate-to-severe CHB, respectively.@*Conclusion@#Serum hepcidin is feasible to evaluate the liver inflammatory activity among patients with CHB.

Research progress of Müller cell and macular hole / 中华眼底病杂志

Müller cells are glial cells of the retina, whose major processes cross the internal and external limiting membranes of the retina, maintaining the function and metabolism of retinal photoreceptors and neurons. Their structure and function are closely related to the development of macular hole (MH). Müller cells are involved in the formation and recovery of MH from the aspect of traction and protein, and their morphology and biological function also influence the regression of MH. The current treatment modality for MH is vitrectomy combined with internal limiting membrane (ILM) peeling, in which Müller cells play a dual role after ILM peeling in different stages of MH. And its potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons making it a current research hot topic, which can be a reference and inspiration for clinical treatment.

Analysis of changes in serum metabolites of uremia patients based on ultra-high performance liquid chromatography-mass spectrometry / 中华肾脏病杂志

Objective:To analyze the changes in serum metabolites of patients with uremia using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), and provide a theoretical basis for the prevention and treatment of uremia.Methods:Uremia patients from the Department of Nephrology, the Affiliated Hospital of Southwest Medical University, and the volunteers from the Health Examination Center were enrolled in this study. According to the inclusion and exclusion criteria, 20 uremia patients (experimental group) and 20 volunteers (control group) were screened out. UHPLC-MS was used to detect the metabolites in the serum of subjects from the two groups, and difference analysis was made to screen the different metabolites, followed by correlation analysis and pathway enrichment study.Results:A total of 412 metabolites were identified by UHPLC-MS. Principal components analysis (PCA) proved that these metabolites could distinguish the control group and the experimental group well. The criteria [variable importance for the projection (VIP)>1, fold changes (FC)>1.25 or FC<0.8 and P value<0.05] was set to screen those significantly different metabolites. Finally, 28 significantly different metabolites were screened out, of which 18 metabolites increased significantly, the other 10 different metabolites decreased significantly. Correlation analysis results proved a certain correlation among 28 different metabolites and the experimental group and control group samples, and between the 28 differential metabolites themselves. Enrichment analysis found that 28 different metabolites might enrich the catecholamine biosynthetic pathway, and pathway analysis suggested that 28 different metabolites might affect glutamate, aspartame acid and glutamate metabolic pathways. Conclusion:Based on metabonomic analysis, some metabolites in the serum of patients with uremia have changed, which can affect some metabolic pathways, thus affecting the pathophysiological process of patients with uremia.

Predictive value of low-density lipoprotein cholesterol in cardiovascular events in elderly diabetic patients / 公共卫生与预防医学

Objective To analyze the predictive value of low-density lipoprotein cholesterol (LDL-c) on cardiovascular events in elderly patients with diabetes, and to provide theoretical guidance for the prevention of cardiovascular disease in elderly patients with diabetes. Methods A total of 180 elderly patients with diabetes treated at the Department of Cardiovascular Medicine, Hubei Jianghan Oilfield General Hospital from June 2019 to June 2020 were selected. According to the LDL-c level, they were divided into low-risk group (LDL-c 0.05). The serum TG, TC, and LDL-c levels, and Gensini scores in the high-risk group were significantly higher than those in the low-risk group, and the serum LDL-c level in the high-risk group was significantly lower than that in the low-risk group (P2=7.500, P<0.05). Spearman correlation analysis showed that LDL-C was positively correlated with the incidence of MACE (r=0.781, P<0.05). Multivariate logistic regression analysis showed that LDL-c≥2.6mmol/L was an independent risk factor for cardiovascular disease in elderly diabetic patients (P<0.05). The area under ROC curve for LDL-c to predict cardiovascular events in DM patients was 0.814 (95%CI:0.767~0.912), and the sensitivity and specificity were 78.40% and 84.80%, respectively. Conclusion LDL-c level is significantly increased in elderly patients with diabetes, and LDL-c≥2.6 mmol/L is of certain value in predicting cardiovascular events in patients with diabetes.

Effects of DJ-1 protein on retinal ganglion cells and visual function in mice after optic nerve crush injury / 中华眼底病杂志

Objective:To investigate the effect of DJ-1 encoded by Park7 gene on retinal ganglion cells(RGC) and visual function after optic nerve crush injury (ONC) in mice.Methods:Thirty-seven and 116 healthy male C57BL/6J mice were randomly divided into group normal, group ONC 2d, group ONC 5d, group ONC 7d and group control, group Park7, group Park7-ONC, group ONC and group green fluorescent protein (GFP)-ONC. Group ONC 2d, group ONC 5d and group ONC 7d were sacrificed on the 2nd, 5th and 7th day after the establishment of ONC model, and the follow-up experiments were carried out. The mice in group Park7 and group Park7-ONC were injected 1 μ recombinant adeno-associated virus (rAAV) with knocking down Park7 gene into vitreous cavity, and 1 μl rAAV with only GFP was injected into vitreous cavity of mice in group GFP-ONC, and virus transfection was observed 4 weeks after injection. The injury of ONC was perfomed at 23 days after vitreous injection in group ONC, group Park7-ONC and group GFP-ONC, and the samples were taken for follow-up experiment 5 days after modeling. The average density of RGC was observed by immunofluorescence staining, the latencies and amplitudes of a-wave, b-wave and photopic negative response (phNR) and the amplitude of oscillatory potential (OPs)were detected by full-field flash electroretinogram,and the visual acuity of mice was measured by optomotor response (OMR). The relative expression levels of DJ-1, Bax and B lymphoblastoma / leukemia-2 (Bcl-2) protein in the retina of mice in each group were detected by Western blot. One-way ANOVA was used to compare the data between groups, and t-test was used for pairwise comparison between groups.Results:Compared with the normal group, the relative expression of DJ-1 protein in the retina of the ONC 2 d group and ONC 5 d group increased significantly, and the difference was statistically significant ( t=16.610, 5.628, P<0.01,<0.05). Four weeks after virus transfection, strong GFP expression was seen in the RGC layer and inner plexiform layer of the retina of mice in the Park7 group. Compared with the control group, the RGC density of the retina in the ONC group decreased significantly, and the difference was statistically significant ( t=16.520, P<0.000); compared with the ONC group, the RGC density of the retina in the Park7- ONC group decreased significantly, and the difference was statistically significant ( t=6.074, P<0.01). With the increase of stimulus light intensity, the dark adaptation a wave and b wave latency of the mice in the control group gradually shortened, and the amplitude gradually increased. The stimulus light intensity was 3 cd·s/m 2. There was no statistically significant difference in the dark adaptation a wave and b wave latency and amplitude of the control group, Park7 group, Park7-ONC group, ONC group, and GFP-ONC group (Incubation period: F=0.503, 2.592; P=0.734, 0.068. Amplitude: F=0.439, 1.451; P=0.779, 0.247). Compared with the control group, the Ops and PhNR amplitudes of the ONC group mice were significantly decreased ( t=15.07, 12.80; P<0.000,<0.001). Compared with the ONC group, the Ops and PhNR amplitudes of the mice in the Park7- ONC group were significantly decreased ( t=4.042, 5.062; P<0.05,<0.01); there was no statistically significant difference in the PhNR latency of the mice in each group ( F=1.327, P=0.287). Compared with the control group, the visual acuity of the mice in the ONC group was significantly decreased, and the difference was statistically significant ( t=23.020, P<0.000); compared with the ONC group, the visual acuity of the mice in the Park7-ONC group was significantly decreased, and the difference was statistically significant ( t=3.669, P<0.05). Compared with the control group, Park7-ONC group and ONC group, the relative expression of DJ-1 protein in the mouse retina was significantly down-regulated, and the difference was statistically significant ( t=47.140, 26.920; P<0.000,<0.000). There was no significant difference between ONC group and GFP-ONC group ( t=0.739, P=0.983). Compared with the ONC group, the relative expression of Bax protein in the mouse retina of the Park7-ONC group was significantly increased, and the relative expression of Bcl-2 protein was significantly reduced. The differences were statistically significant ( t=5.960, 9.710; P<0.05,<0.05); the relative expression ratio of Bcl-2/Bax in the Park7-ONC group was significantly lower than that in the ONC group, and the difference was statistically significant ( t=13.620, P<0.01). Conclusion:The expression of DJ-1 encoded by Park7 gene is down-regulated after Park7 gene was knocked down, which aggravates the RGC damage and the decrease of retinal electrophysiological response and visual function in ONC injury mice.

Downregulation of heat shock protein B8 protects retinal ganglion cell after optic nerve injury in mice / 中华眼底病杂志

Objective:To investigate the effect of heat shock protein B8 (HspB8) downregulation on retinal ganglion cell (RGC) and retinal function in the mice model of optic nerve injury (ONC).Methods:Adeno-Associated Virus (AAV) 2 AAV2-shHspB8-GFP was constructed to knockdown HspB8. 66 adult male C57/BL6 mice were randomly divided into the control group, the ONC group, the AAV2-shHspB8 group, the ONC+AAV2-shHspB8 group, and the ONC+AAV2-GFP group. There were 10, 20, 16, 10 and 10 mice respectively, and both eyes were used as experimental eyes. Western blot was used to evaluate the expression of HspB8 on day 3 and 7 after ONC. By GFP immunofluorescence staining, the efficacy of AAV2-shHspB8-GFP transfer was accessed. Moreover, it was possible to identify functional and RGC survival differences between groups by optomotor response (OMR), dark adapted full-field flash electroretinogram (ff-ERG), oscillatory potentials (OPs), photopic negative response (PhNR) and retinal flat-mount RGC counting 5 days after ONC. Comparisons between two groups were made using Mann-Whitney U test, unpaired t-test, unpaired t-test with Welch’s correction, one-way ANOVA, and Bonferroni t test. Results:Compared with the control group, the expression of HSPB8 protein in the retina of mice in ONC3 group was significantly increased, and the difference was statistically significant ( F=43.63, P<0.01). Compared with the control group, the ONC group showed obviously lower visual acuity ( P<0.01), lower a-wave, b-wave, OPs, PhNR amplitude, longer b-wave latency ( P<0.05), and the survival rates of RGC in ONC3 group, ONC5 group and ONC7 group decreased in a time-dependent manner( F=384.90, P<0.01). Transfection of AAV2 efficiency was highest on 4 weeks after IVT. Besides, there was no significant differences between the control group and the AAV2-shHspB8 group on visual acuity, ff-ERG, OPs, PhNR and RGC survival ( P>0.05). In comparison of the control group, we found that RGC survival of the ONC5+AAV2-shHspB8 group was significantly elevated ( F=10.62, P<0.01). Conclusions:Expression of HspB8 on the retina can be induced by ONC. The investigation of RGC counting, visual acuity, and ff-ERG revealed that optic nerve injury destructed functionality of mice retina and resulted to RGC death ultimately. The Most crucial finding of this research is that HspB8 knockdown had a neuroprotective effect in RGC after ONC.

Experimental study of biomimetic nanoparticle probe containing hematoporphyrin monomethyl ether and its imaging and sonodynamic therapy for breast cancer / 中华超声影像学杂志

Objective:To develop a biomimetic nanoparticle probe of hematoporphyrin monomethyl ether (HMME) coated with breast cancer cell membrane, to observe its ability to target homologous breast cancer cells in vitro, and to investigate its effect of enhanced photoacoustic imaging and sonodynamic therapy (SDT) for breast cancer in vitro.Methods:The cell membrane of breast cancer 4T1 was extracted by chemical cleavage and repeated freezing and thawing. Then the HMME-coated polylactic acid-glycolic acid copolymer biomimetic nanoparticle was prepared by double emulsification and extrusion. The basic characteristics of nanoparticles were detected. The target ability of nanoparticles to homologous breast cancer cells and the enhancement of photoacoustic imaging were observed in vitro. Singlet oxygen sensor green (SOSG) was used to verify the reactive oxygen species (ROS) production of nanoparticles, and its SDT effect on breast cancer cells was evaluated by CCK8 cytotoxicity assay.Results:The size of the prepared CHP-NPs was uniform, the morphology was spherical "core-shell structure" , the particle size was (275.23±8.25)nm, and the surface potential was (-18.43±0.45)mV. It was observed that CHP-NPs could target homologous 4T1 cells under laser confocal microscopy. In vitro photoacoustic imaging experiments show that the photoacoustic signal of nanoparticles increases with the increase of its concentration. According to SOSG probe detection, CHP-NPs could produce ROS under ultrasonic irradiation.When CHP-NPs was incubated with 4T1 cells alone and no ultrasonic irradiation was used, the cell survival rate was not significantly affected. When the concentration was 0.6 mg/ml, the cell survival rate was still 95%. After ultrasonic irradiation, CCK8 experiment showed that the CHP-NPs had a significant SDT effect on breast cancer cells.Conclusions:The biomimetic nanomolecular probe of breast cancer cell membrane is successfully prepared. The probe has good ability to target homologous tumor, and can significantly enhance tumor photoacoustic imaging and SDT effect.