Protective Effect and Autophagy Mechanism of Lycium barbarum Polysaccharides on Retinal Pigment Epithelial Cells Under High-Glucose Conditions

Objective:To study the effects of Lycium barbarum polysaccharide(LBP)on the proliferation,apoptosis,and autophagy of retinal pigment epithelial(RPE)cells cultured under high-glucose conditions.Methods:The ARPE-19 cell line was randomly divided into a control group(normally cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12[DMEM/F-12]medium),a high-glucose group(HG;50 mmol/L glucose added to DMEM/F-12 medium),and a HG+LBP group(incubated in DMEM/F-12 medium containing 1 mg/mL LBP for 24 h,and then treated with 50 mmol/L glucose for 24 h).Following Ad-mCherry-GFP-LC3B infection,cell proliferation,apoptosis,mammalian target of rapamy-cin(mTOR)expression,and autophagic flux were determined by Cell Counting Kit-8(CCK-8),AnnexinV-APC/7-AAD Apoptosis Detection Kit,Western blot,and laser confocal microscopy,respectively.Results:The proliferation rate of ARPE-19 cells in the HG group was significantly lower than that in the control group(P<0.05),while the proliferation rate of ARPE-19 cells in the HG+LBP group was significantly higher than that in the HG group(P<0.05).The apoptosis rate of ARPE-19 cells in the HG group was significantly higher than that in the control group(P<0.05),while the apoptosis rate of ARPE-19 cells in the HG+LBP group was significantly lower than that in the HG group(P<0.05).The relative expression of phosphorylated mTOR(p-mTOR)of ARPE-19 cells in the HG group was significantly lower than that in the control group(P<0.05),with enhanced autophagic flux;when compared with the HG group,the HG+LBP group had significantly higher expression of p-mTOR(P<0.05),with diminished autophagic flux.Conclusion:LBP has a protective effect on RPE cells with high glucose-induced injury,and its mechanism may be related to LBP inhibition of high glucose-induced abnormal autophagy.

Autophagy dysregulation mediates the damage of high glucose to retinal pigment epithelium cells

AIM:To observe the role and mechanism of autophagy in retinal pigment epithelial cell(RPE)damaged by high glucose,so as to offer a new idea for the treatment of diabetic retinopathy(DR).METHODS:ARPE-19,a human RPE cell line cultured in vitro was divided into the normal control(NC),autophagy inhibitor 3-methyladenine(3-MA),high-glucose(HG),and HG+3-MA groups.Cell viability was detected by CCK-8 assay and the apoptosis rate was measured by flow cytometry.The protein expressions of apoptosis markers,including Bax,Bcl-2,and Caspase-3,as well as autophagy marker including microtubule-related protein 1 light chain 3(LC3),p62,and mechanistic target of rapamycin(m TOR)were detected by Western blotting.Autophagic flux was detected by transfection with Ad-m Cherry-GFP-LC3 B.RESULTS:Under high glucose conditions,the viability of ARPE-19 was decreased,and the apoptosis rate increased,the protein expressions of Bax,Caspase-3,and LC3-II/LC3-I were all increased and the expressions of Bcl-2,p62 and p-m TOR decreased,and autophagic flux was increased compared with that of the controls.Treatment with 3-MA reversed all these changes caused by high glucose.CONCLUSION:The current study demonstrates the mechanisms of cell damage of ARPE-19 through high glucose/m TOR/autophagy/apoptosis pathway,and new strategies for DR may be developed based on autophagy regulation to manage cell death of RPE cells.

Teaching Effect of Online Live Broadcasting with Screen Sharing and PowerPoint Recording and Broadcasting on Medical Students'Learning of Obstetrics and Gynecology

Objective:During the prevention and control of the outbreak of the new coronavirus,an upsurge of online teaching was set off in various teaching institutions.There is a relatively new online teaching method that has stood out,namely the screen sharing method.The purpose of this study was to compare the effectiveness of live broadcasting and PowerPoint recorded lectures in terms of medical students' mastery of knowledge.Methods:The study was carried out among medical students of class 1806 from the First Affiliated Hospital of Xi'an Medical University who were in their clinical years.The students were randomly divided into two groups,in which 15 students were enrolled in the live broadcast lecture group,while 13 were in the PowerPoint recorded lecture group.Each group underwent two weeks of teaching in obstetrics and gynecology.After the second week of the course,a knowledge post-test and satisfaction survey were carried out,and the same test paper was used again 14 days after the previous test.The knowledge post-test and satisfaction survey were carried out using the Dingding intelligent form.Results:With regard to the post-test knowledge,the scores of the students under the two teaching methods were high,indicating that the learning effects from the two methods are similar(p>0.05).In terms of satisfaction,students showed more acceptance to screen sharing lectures(p<0.01).Conclusion:In small-scale online teaching,live lecture with screen sharing is a better and more effective teaching method,and students are more likely to accept this teaching method.

Experimental Research on Intratumoral Injection of Sal Ammoniac Extract in the Treatment of Mouse Liver Cancer

Objective:To study the effect of sal ammoniac extract on the treatment of liver cancer and analyze its possibility of replacing absolute ethanol.Methods:Sixty Kunming mice(5-6 weeks old,18-22g in weight,male and female in half)were selected and inoculated with 0.1 ml of 1:4 ascitic diluent from mouse liver cancer H22 under the axilla of the right limb.After tumor formation,they were randomly divided into 3 groups with 20 mice in each group.Normal saline(NS),sal ammoniac extract(N),and absolute ethanol(E)were injected into the tumor once a day for four times.The death,tumor weight,tumor inhibition rate,lactate dehydrogenase(LDH),and succinate dehydrogenase(SDH)expression of the mice in each group were analyzed.Results:In the course of treatment,3 mice died in the normal saline group,2 mice died in the sal ammoniac treatment group,and 7 mice died in the absolute ethanol group.The tumor weight of the normal saline group,sal ammoniac treatment group,and absolute ethanol group were 1.880.26,1.41±0.49,and 1.51±0.46,respectively.The tumor inhibition rates were 0%,31.0%,and 21.6%,respectively.Comparing the sal ammoniac treatment group and the normal saline group,t=3.5133,p=0.0013;comparing the absolute ethanol group and the normal saline group,t=2.7926,p=0.0093.The expression of LDH was 81±10,51±11,and 32±9 in the normal saline group,sal ammoniac treatment group,and absolute ethanol group,respectively,while the expression of SDH was 80±10,5110,and 51±12 in the normal saline group,sal ammoniac treatment group,and absolute ethanol group,respectively.Comparing the LDH of the sal ammoniac treatment group with that of the saline group,t=8.4264,ρ=0.0000;comparing the absolute ethanol group and normal saline group,t=13.8763,p=0.0000.Comparing the SDH of the sal ammoniac treatment group with that of the normal saline group,t=8.1455,ρ=0.0000;comparing the absolute ethanol group with the normal saline group,t=7.2197,ρ=0.0000.Conclusion:The traditional Chinese antitumor medicine,sal ammoniac and its main effective components have good antitumor effect,which can be further popularized and applied in clinical practice.

Experimental Research on the Inhibitory Effect of IFN-Lambda 3 Combined with Sorafenib on the Growth of Liver Cancer Transplanted into Nude Mice

Objective:To investigate the effect of sorafenib combined with interferon-lambda 3 on the growth of liver cancer transplanted into nude mice.Methods:Female nude mice of 4-5 weeks of age that passed quarantine were selected and fed for 1-2 weeks before experimental operation.The cell suspension of human hepatoma cell line SMMC-7721 was inoculated into the right cervical axillary fossa with a syringe.The tumor-bearing mice were randomly divided into a control group and an experimental group.The control group received normal saline whereas the experimental group was further divided into three other groups:IFN-lambda 3 treatment group,sorafenib treatment group,and IFN-lambda 3 combined with sorafenib treatment group.The situation of nude mice was analyzed.At the end of the experiment,the volume of allogeneic transplanted tumor was measured,and the morphology of tumor cells,the expression of proliferating protein Ki-67,as well as the number of apoptotic cells were observed by hematoxylin and eosin(H&E)staining,immunohistochemistry(IHC),and TUNEL staining.Results:The tumor cell volume of the IFN-lambda 3 treatment group,sorafenib treatment group,and IFN-lambda 3 combined with sorafenib treatment group decreased,which was statistically significant compared with the control group(p<0.05).The increment rate of proliferating protein Ki-67 in the transplanted tumor tissue of the three drug groups was significantly lower than that of the control group(p<0.05).IFN-lambda 3 combined with sorafenib had the greatest effect on the expression level of Ki-67 protein.Compared with the control group,the expression rate was significantly lower(p<0.05).In terms of cell apoptosis,IFN-lambda 3 and/or sorafenib,as well as the combination of the two,showed statistically significant differences compared with the control group(p<0.05).The rate of cell apoptosis was the highest in the IFN-lambda 3 combined with sorafenib group.Conclusion:IFN-lambda 3 combined with sorafenib can inhibit the growth and proliferation of human hepatocellular carcinoma cells in nude mice and promote the apoptosis of hepatocellular carcinoma cells,which proves that IFN-lambda 3 combined with sorafenib can treat hepatocellular carcinoma in vivo.

Managing diabetes mellitus in underserved subjects of Western China using a telemedicine system— A clinical trial

Objective:To evaluate the effectiveness of Internet and telephone-based telemedicine system managing on patients’glycemic index,blood pressure,and lipid level control in underserved subjects with type 2 diabetes in Western China.Research designs and methods:In a 3 years,randomized,controlled,single-blind,parallel-group treat-to-target study,412 subjects with type 2 diabetes were randomized to telemedicine(Tel;n=208)group and usual care(control;n=204)group.We evaluated the effects of the intervention on blood sugar,blood pressure,and lipid levels at 1,2,3 years point,and investigated the cause of the loss during follow-up by phone call.Results:Intra-group comparison:in the Tel group,the FBS,2HPG,HbA1c,and SBP at 1,2,3 years and DBP,TC,TG,BMI at 2,3 years were significantly decreased compared with baseline level(P<0.05).Moreover,the Tel group had an obvious better control of their HbA1c at 2 and 3 years and 2HPG at 3 years of follow-up respectively compared with the outcomes at 1 year(P<0.05).Inter-group comparison:the FBS,2HPG,and HbA1c of Tel group decreased significantly from the baseline to the 1 year more than those of control group(P<0.05 or P<0.01).In this analysis,all clinical measures of Tel group had a significant downward compared with the outcomes of Control group at 2 years,the FBS,HbA1c and BMI(P<0.001),the 2HPG and SBP(P<0.01)and DBP,TC,and TG(P<0.05)were statistically significant respectively.Logistic regression analysis showed that the subject loss during follow-up was associated with worse diabetes management(OR=3.842),low income(OR=3.201),low education level(OR=0.923),and greater distance to the hospital(OR=0.921).Conclusions:The study results indicated that the telemedicine may be a useful tool for managing diabetes mellitus.

Inhibition of RNaseH2A Induces Fas-Regulated Programmed Cell Death in Hepatoma Cells

Objective:To screen clinically significant potential drug targets in liver cancer and to study the function and potential molecular mechanisms of this target protein in the development of liver cancer.Methods:By using the clinical database GEPIAto find genes that are differentially expressed in liver cancer compared to normal tissues,we further screened the genes that are highly expressed in hepatocellular carcinoma and have clinical prognostic relevance.Heat maps were used to sort these genes according to their clinical prognostic relevance,so as to screen for the target gene of interest.The characteristics of target gene expression and clinical prognosis in hepatocellular carcinoma were studied.The target gene was knocked down through siRNA,and cell proliferation experiments and apoptosis experiments were used to verify the importance of the target gene in the occurrence and development of liver cancer.Finally,we elucidated the potential molecular mechanism of the target gene's function in liver cancer based on the mutual regulatory relationship between the target gene and key apoptosis genes.Results:1482 genes were significantly underexpressed in liver cancer,and 725 genes were significantly overexpressed in liver cancer,of which RNaseH2A was significantly overexpressed in liver cancer and had a significant clinical prognosis.Knockdown of RNaseH2A inhibited the proliferation of hepatocellular carcinoma cells and induced apoptosis.Knockdown of RNaseH2A induced the high expression of Fas,a key gene for apoptosis,and liver cancer usually features low expression of Fas.After hepatocellular carcinoma cells that were knocked down of RNaseH2A continued were subject to Fas knockdown,hepatocellular carcinoma cell proliferation and apoptosis returned to normal levels.Conclusion:The high expression of RNaseH2A regulates the low expression of Fas,a key gene for apoptosis,thereby inhibiting apoptosis,promoting cell proliferation,and participating in the development of liver cancer.

Frosted Branch Angiitis: A Case of Bilateral Frosted Branch Angiitis After Fever

Frosted branch angiitis(FBA)is a rare retinal vascular disease that usually affects healthy,young adolescents and tends to be bilateral.Cxirrently,there are limited reports on FBA worldwide.In this paper,we will present a case of FBA after fever.

Can Fundus Fluorescein Angiography be Performed for Diabetic Patients on Oral Metformin

Metformin 是一种 biguanide 广泛地与糖尿病 mellitus 在病人被使用了的血糖过低的代理人。在临床的实践， metformin 是否应该在宫底荧光黄 angiography (船边交货) 前被停止，仍然保持大部分不清楚。一些内分泌学家在船边交货前建议站 metformin。然而，眼科医师总是不在他们的实践采用这条意见。这种状况可以导致医生和病人之间的争论。这篇文章分析了导致对比的 nephropathy (CIN ) 和相关对比代理人，以及荧光黄 angiography 的不利反应。它指出差异可以被在船边交货使用的对比代理人的误解引起。为用碘对比代理人的 angiography，，因为 CIN 的增加的可能性， metformin 必须为使用荧光黄钠的船边交货被停止，没有 CIN 还被报导了。因此，作者相信船边交货为有口头的 metformin 的糖尿病的病人是安全的，在考试前停止 metformin 是不必要的。

Glycemic control predicts the risk of hepatic fibrosis in biopsy-proven NAFLD:a possible mediating role for leukemia inhibitory factor?

Background:Despite the clear link between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus,little is understood about how glycemic control impacts histological severity.We aimed to investigate the deeper association between hemoglobin A1c(HbA1c)and the histologic severity of liver fibrosis.Methods:A total of 568 adults with biopsy-proven NAFLD from the PERSONS cohort in Wenzhou were enrolled.The association between mean HbA1c and hepatic histological features was investigated with ordinal logistic regression.Generalized additive models were used to identify the non-linear relationship between HbA1c and increased fibrosis stage(stage F
3).Causal mediation analysis was performed to calculate the indirect effect of the relationship between HbA1c and hepatic fibrosis mediated by cytokines.Results:Every 1%increase in mean HbA1c was associated with 16%higher odds of increased fibrosis stage(odds ratio 1.16,95%CI 1.04–1.30),even after adjustment for confounding factors.There was a non-linear association between HbA1c and increased fibrosis stage(stage F
3),and the HbA1c inflection point was 9.2%.In particular,the ORs on the left and right sides of this inflection point were 2.1(95%CI 1.4–3.3)and 0.1(95%CI 0–4.8),respectively.7%of the association(OR 1.07,95%CI 1.01–1.12)between HbA1c and liver fibrosis was mediated by leukemia inhibitory factor.Conclusions:Glycemic control predicts severity of hepatic fibrosis and leukemia inhibitory factor plays an intermediary role between them,and thus optimizing glycemic control may be a means of modifying the risk of fibrosis progression in NAFLD.

Research Progress on Serum Porphyrin and Chronic Liver Disease

Liver cirrhosis is an important cause of chronic liver cancer.At present,a breakthrough has been achieved in the development of chronic hepatitis C treatment,but there is no effective measure to completely cure chronic hepatitis B.Porphyrins are a class of macromolecular heterocyclic compounds formed by interconnecting the a-carbon atoms of four pyrrole-like substituents through hypomethyl bonds.Porphyrins and their derivatives widely exist in organelles related to energy transfer in organisms.They are mainly involved in the synthesis of heme in human body.Heme is an iron-containing porphyrin compound,15-20% of which is synthesized and utilized in the liver.Studies have found that porphyrin metabolism disorder can occur in patients with chronic liver disease.The early stage of viral hepatitis is accompanied by increased production of porphyrins and their compounds,increased levels of peripheral circulating porphyrins,porphyrin cholestasis,and biochemical changes of free porphyrins which precede the histological changes.The accumulation of serum and liver protoporphyrins and the oxidative stress can cause liver and extrahepatic damage.On the one hand,porphyrin metabolism disorder can aggravate chronic liver disease,and even progress to liver cirrhosis and liver cancer.On the other hand,chronic liver disease can also aggravate porphyrin metabolism disorder,recurrent attacks,and damage to liver and extrahepatic tissues and organs.

Buried penis:a histological and histochemical study of dartos fascia

This study aimed to determine whether the abnormal deep layer of dartos fascia plays an important role in buried penis.Forty-nine patients with buried penis were treated with anatomical resection of the deep layer of dartos fascia under a microscope.Penile length was measured before and after completely resecting the deep layer to investigate the role of this layer in penile retraction.The superficial and deep layers of dartos fascia were collected from 49 patients with buried penis,the normal superficial layers were collected from 25 children/adults who underwent circumcision for nonmedical reasons,and the normal deep layers were collected from 20 adult cadavers.The penile fascia samples were stained with hematoxylin-eosin,Masson’s trichrome,Sirius red,and Verhoeff’s Van Gieson,and subjected to immunohistochemical examination and scanning electron microscopy.The penile shaft(mean±standard deviation)was found to be significantly elongated after resecting the deep layer compared with that before resection(6.8±1.9 cm vs 6.0±1.6 cm,P<0.001).An abnormal deep layer of dartos fascia characterized by disordered and fragmented elastic fibers was observed in 87.8%(43/49)of buried penis samples,whereas no abnormal deep layer was observed in normal penises from cadavers(0/20,P<0.001).Thus,the abnormal deep layer of dartos fascia plays an important role in the buried penis.Its resection is helpful for avoiding recurrence.

Symptoms of long-term exposure to moxa smoke in acupuncturists： a correlation analysis

OBJECTIVE: To investigate the effects of long-term exposure to moxa smoke on acupuncturists and to consider the association between physical symptoms and gender, age, secondhand smoke(SHS) exposure, and the duration of exposure.METHODS: A self-report, web-based questionnaire was used to evaluate the effects of moxa smoke onacupuncturists. Logistic regression was used to analyze the relationship between physical symptoms and possible correlative factors.RESULTS: A total of 858 questionnaires were analyzed. The data showed that 42.42% of acupuncturists had been exposed to moxa smoke for 5-10 years. The most frequent symptom was tearing(32.98%) and the least frequent symptom was asthma(5.24%). Logistic regression analysis showed that female acupuncturists were slightly more susceptible to cough and tearing than males(cough:OR: 1.583, 95% CI: 1.079, 2.321, P = 0.019; tearing:OR: 1.519, 95% CI: 1.094, 2.108, P = 0.013). Acupuncturists aged over 25 years reported a slightly lower incidence of eye itchiness than those aged under25 years(26-40 years: OR: 0.604, 95% CI: 0.379,0.965, P = 0.035; over 40 years: OR: 0.330, 95% CI:0.114, 0.958, P = 0.042). Ophthalmodynia occurred less in acupuncturists aged 26-40 years(OR: 0.591,95% CI: 0.359, 0.970, P = 0.038) than in those younger than 25 years. The only association between prevalence of symptoms and tobacco use and SHS exposure was that smokers had a lower occurrence of phlegm in the throat(OR: 0.579, 95% CI: 0.392,0.856, P = 0.006). Shortness of breath was less frequent in participants exposed to moxa smoke for more than 5 years(5-10 years: OR: 0.400, 95% CI:0.204, 0.785, P = 0.008; 11-20 years: OR: 0.392, 95%CI: 0.178, 0.864, P = 0.02), but a slightly higher incidence of eye itchiness was found in those with over20 years of moxa exposure(OR: 4.200, 95% CI:1.344, 3.128, P = 0.014).CONCLUSION: The most frequent symptom of moxa smoke exposure in acupuncturists was tear-ing. The association of symptoms with age and duration of exposure to moxa smoke were rather complicated; hence, care should be taken in drawing conclusions about the safety of moxa smoke based solely on its potentially harmful ingredients.