Objective To investigate the role of autophagy involving the protein kinase B/sterol regulatory element binding protein 1(Akt/SREBP-1)signaling pathway in diabetic retinopathy(DR).Methods DR rat models were estab-lished via the intraperitoneal injection of streptozotocin.Rats were randomized into control(normal rats)and DM-DR groups(DR rats).The expression of autophagy-related proteins(autophagy markers LC3-Ⅱ and LC3-Ⅰ,autophagy specific substrate p62,and autophagy-related protein Beclin1)in rat retinas was compared between the two groups.Rats were di-vided into control B(normal rats injected with 1 μL saline),DR(DR rats injected with 1 μL saline),DR+si-NC(DR rats injected with 1 μL of the negative control siRNA),and DR+si-SREBP-1 groups(DR rats injected with 1 μL of the SREBP-1 siRNA).All interventions were given 1 day before modeling and 8 weeks after modeling.Akt/SREBP-1 expression and retinal ganglion cell(RGC)survival were compared among groups.R28 rat retinal precursor cells were classified into con-trol C(normal glucose,24 h),HG(high glucose,24 h),HG+si-NC(si-NC transfection+high glucose,24 h),and HG+si-SREBP-1 groups(si-SREBP-1 transfection+high glucose,24 h).The expression of autophagy-related proteins and au-tophagosome-lysosome fusion were compared among groups.Western blot and immunofluorescence were used to examine the expression of Akt,SREBP-1 and autophagy-related proteins.Results The relative expression of Beclin1 and p62 pro-teins and the LC3-Ⅱ/Ⅰ ratio in the DM-DR group were significantly higher than those in the control group 1 and 8 weeks after modeling(all P＜0.001).Compared with the control B group,the DR group exhibited elevated SREBP-1 and reduced Akt protein levels 1 and 8 weeks after modeling(all P＜0.01).RGC counts in the DR and DR+si-NC groups were significantly lower than those in the control B group(P＜0.001).The RGC count in the DR+si-SREBP-1 group was significantly higher than that in the DR+si-NC group(P＜0.001).Compared with those in the control C group,the Beclin1 and p62 protein levels and the LC3-Ⅱ/Ⅰ ratio were increased in the HG and HG+si-NC groups(all P＜0.01).Compared with those in the HG+si-NC group,the Beclin1 and p62 protein levels and the LC3-Ⅱ/Ⅰ ratio were reduced in the HG+si-SREBP-1 group(all P＜0.05).The HG and HG+si-NC groups showed significantly more LC3B/LAMP1 dual-positive puncta than the control C group(P＜0.001).The HG+si-SREBP-1 group showed significantly less LC3B/LAMP1 dual-positive puncta than the HG+si-NC group(P＜0.001).Conclusion SREBP-1 knockdown enhances autophagic flux in early DR to attenuate RGC loss.Thus,the Akt/SREBP-1 axis represents a promising therapeutic target for DR.

Objective To investigate the role of autophagy involving the protein kinase B/sterol regulatory element binding protein 1(Akt/SREBP-1)signaling pathway in diabetic retinopathy(DR).Methods DR rat models were estab-lished via the intraperitoneal injection of streptozotocin.Rats were randomized into control(normal rats)and DM-DR groups(DR rats).The expression of autophagy-related proteins(autophagy markers LC3-Ⅱ and LC3-Ⅰ,autophagy specific substrate p62,and autophagy-related protein Beclin1)in rat retinas was compared between the two groups.Rats were di-vided into control B(normal rats injected with 1 μL saline),DR(DR rats injected with 1 μL saline),DR+si-NC(DR rats injected with 1 μL of the negative control siRNA),and DR+si-SREBP-1 groups(DR rats injected with 1 μL of the SREBP-1 siRNA).All interventions were given 1 day before modeling and 8 weeks after modeling.Akt/SREBP-1 expression and retinal ganglion cell(RGC)survival were compared among groups.R28 rat retinal precursor cells were classified into con-trol C(normal glucose,24 h),HG(high glucose,24 h),HG+si-NC(si-NC transfection+high glucose,24 h),and HG+si-SREBP-1 groups(si-SREBP-1 transfection+high glucose,24 h).The expression of autophagy-related proteins and au-tophagosome-lysosome fusion were compared among groups.Western blot and immunofluorescence were used to examine the expression of Akt,SREBP-1 and autophagy-related proteins.Results The relative expression of Beclin1 and p62 pro-teins and the LC3-Ⅱ/Ⅰ ratio in the DM-DR group were significantly higher than those in the control group 1 and 8 weeks after modeling(all P＜0.001).Compared with the control B group,the DR group exhibited elevated SREBP-1 and reduced Akt protein levels 1 and 8 weeks after modeling(all P＜0.01).RGC counts in the DR and DR+si-NC groups were significantly lower than those in the control B group(P＜0.001).The RGC count in the DR+si-SREBP-1 group was significantly higher than that in the DR+si-NC group(P＜0.001).Compared with those in the control C group,the Beclin1 and p62 protein levels and the LC3-Ⅱ/Ⅰ ratio were increased in the HG and HG+si-NC groups(all P＜0.01).Compared with those in the HG+si-NC group,the Beclin1 and p62 protein levels and the LC3-Ⅱ/Ⅰ ratio were reduced in the HG+si-SREBP-1 group(all P＜0.05).The HG and HG+si-NC groups showed significantly more LC3B/LAMP1 dual-positive puncta than the control C group(P＜0.001).The HG+si-SREBP-1 group showed significantly less LC3B/LAMP1 dual-positive puncta than the HG+si-NC group(P＜0.001).Conclusion SREBP-1 knockdown enhances autophagic flux in early DR to attenuate RGC loss.Thus,the Akt/SREBP-1 axis represents a promising therapeutic target for DR.

ObjectiveTo observe the effect of modified Tianwang Buxindan （MTBD） on the skin of sleep-deprived （SD） mice and investigate its mechanism. MethodSixty 2-month-old female Kunming mice were randomly divided into a blank group， a model group， a vitamin C （VC， 0.08 g·kg^-1）， and MTBD low-， medium-， and high-dose groups （6.5， 12.5， 25 g·kg^-1）. Except for the blank group， the other groups were subjected to SD mouse model induction （using multiple platform water environment method for 18 hours of sleep deprivation daily from 15：00 to next day 9：00）， continuously for 14 days， and caffeine （CAF， 7.5 mg·kg^-1） was injected intraperitoneally from the 2nd week onwards， continuously for 7 days. While modeling， the blank group and the model group were administered with normal saline （0.01 mL·g^-1）， and the other groups received corresponding drugs for treatment. On the day of the experiment， general observations were recorded （such as body weight， spirit， fur， and skin）. After sampling， skin tissue pathological changes were observed under an optical microscope using hematoxylin-eosin （HE） and Masson staining methods. Skin thickness and skin moisture content were measured. Biochemical assay kits were used to detect skin hydroxyproline （HYP） content， skin and serum superoxide dismutase （SOD） activity， and malondialdehyde （MDA） content. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum interleukin （IL）-6， tumor necrosis factor （TNF）-α， and IL-1β levels in mice. Western blot was used to detect skin tissue type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated （p）-PI3K， protein kinase B （Akt）， p-Akt， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase （HO）-1， and nuclear factor （NF）-κB protein expression. ResultCompared with the blank group， the model group showed varying degrees of changes. In general， signs of aging such as reduced body weight （P<0.01）， listlessness， dull fur color， and formation of wrinkles on the skin appeared. Tissue specimen testing revealed skin thinning， flattening of the dermoepidermal junction （DEJ）， and reduced collagen fibers under the optical microscope. Skin thickness and moisture content decreased， skin tissue HYP content significantly decreased （P<0.01）， skin and serum SOD activity significantly decreased （P<0.01）， and MDA content significantly increased （P<0.01）. Serum IL-6， TNF-α， and IL-1β levels significantly increased （P<0.01）. Skin ColⅠ， ColⅢ， p-PI3K/PI3K， p-Akt/Akt， Nrf2， and HO-1 protein expression significantly decreased （P<0.05， P<0.01）， and NF-κB expression increased （P<0.01）. Compared with the model group， the VC group and the MTBD low-dose group showed increased skin moisture content， HYP content， SOD activity， and ColⅠ， ColⅢ， p-PI3K/PI3K protein expression （P<0.05， P<0.01）， and decreased serum MDA content （P<0.05）. In addition， a decrease in serum IL-6 and IL-1β levels was detected in the MTBD low-dose group （P<0.05）， while the above indicators in the MTBD medium- and high-dose groups improved （P<0.05， P<0.01）. ConclusionSleep deprivation accelerates the aging process of the skin in SD model mice. MTBD can improve this phenomenon， exerting anti-inflammatory and antioxidant effects， and its mechanism of action may be related to the activation of the PI3K/Akt/Nrf2 signaling pathway.

Objective To investigate the role of growth arrest-specific 6(Gas6)/Mer tyrosine kinase(MerTK)signaling pathway in ferroptosis in diabetes retinopathy(DR).Methods Human retinal pigment epithelial cells(ARPE-19)were divided into control group,HG group,HG+sh-Gas6 group,and HG+Gas6 group.Cells were exposed to 25 mmol/L D-glucose for simulating an in vitro hyperglycemic(HG)environment.The control group was exposed to a 20 mmol/L mannitol+5.5 mmol/L glucose environment.Rats were randomly divided into normal control group,DR group,and DR+Gas6 group,with 20 rats in each group.A DR model was established by intra-peritoneal injection of STZ solution.Cell proliferation was evaluated using the cell count kit 8(CCK-8)assay.Lip-id reactive oxygen species(ROS)levels were measured by flow cytometry,and levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)were measured by biochemical assays to eval-uate iron death.The expression of Gas6 and MerTK proteins was analyzed by Western blot.Results Compared with HG group,the cell viability,SOD,GSH-Px levels in HG+Gas6 group increased significantly(P＜0.05),while the levels of lipid-ROS and MDA decreased significantly(P＜0.05).In HG+sh-Gas6 group,the cell via-bility,SOD and GSH-Px levels decreased significantly(P＜0.05),while the levels of lipid-ROS and MDA in-creased significantly(P＜0.05).In addition,the expression of GPX4 protein in HG+Gas6 group was significant-ly higher than that in HG group(P＜0.05),and the expression of GPX4 protein in HG+sh-Gas6 group was sig-nificantly lower than that in HG group(P＜0.05).Compared with the control group,the average thickness of reti-nal nerve fiber layer in DR group significantly decreased(P＜0.05),while that in DR+Gas6 group increased sig-nificantly(P＜0.05).In addition,the levels of MDA and iron in retinal pigment epithelium(RPE)tissues of DR+Gas6 group decreased significantly(P＜0.05),while the levels of GSH and the expressions of Gas6,MerTK and GPX4 proteins increased significantly(P＜0.05).Conclusion HG treatment accelerates the clearance of GPX4 by inhibiting the Gas6/MerTK signaling pathway,inducing ferroptosis and cell growth inhibition in ARPE-19 cells.In addition,up-regulating the expression of Gas6/MerTK signal in DR rat retina can alleviate ferroptosis and oxidative stress in RPE tissue,and help to restore the average retinal nerve fiber layer thickness.

ObjectiveTo compare the differences between residents who did and who did not participate in a community colorectal cancer screening based on the results of their colorectal colonoscopy and explore the reasons. MethodsThe residents who underwent a colonoscopy in a central hospital in Shanghai from 2017 to 2020 were divided into two groups according to whether they had been screened in the community， and t test and χ² test were used to compare the results of the colonoscopy （detection of lesions） of the examinees with different ages， genders， whether they had a history of colorectal cancer， and whether they had been screened in the community. The correlation between whether they had participated in the community screening and the detection of lesions was analyzed by the logistic regression model. ResultsFrom 2017 to 2020， the hospital had performed a colonoscopy for 6 389 people， and 3 623 lesions were detected， with a detection rate of 56.71%. There were 413 residents who had been screened in the community， accounting for 6.46% of the total number of those receiving a colonoscopy. 243 patients were found with pathological changes， with a detection rate of 58.84%. Compared with the residents who did not participate in the community screening， the proportion of adenoma and polyp was higher in those who had participated in the screening （χ²=50.44， P<0.001）. Among the residents without a history of colorectal cancer， the proportion of adenoma and polyp was higher in those who had participated in the community primary screening （χ²=51.86， P<0.001）. Among the residents who had not participated in the community screening， the proportion of residents with colorectal cancer history was higher （χ²=74.33， P<0.001）. Multivariate regression analysis showed that there was no correlation between participation in community screening and detection of any lesions by colonoscopy （OR=0.905， 95%CI： 0.734‒1.117） or detection of colorectal cancer related lesions （OR=1.113， 95%CI： 0.901‒1.375）. ConclusionThe proportion of residents who have participated in community screening among patients undergoing colonoscopy is low， but the asymptomatic population initially screened by the community and the symptomatic population not initially screened by the community are homogeneous， and the detection rate of precancerous lesions such as adenomas and polyps is high. It is suggested that local measures should be taken to improve residents' colonoscopy response rate， so as to obtain better screening benefits.

Objective:To explore the feasibility of deep learning-based restoration of obscured thyroid ultrasound images.Methods:A total of 358 images of thyroid nodules were retropectively collected from January 2020 to October 2021 at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and the images were randomly masked and restored using DeepFillv2. The difference in grey values between the images before and after restoration was compared, and 6 sonographers (2 chief physicians, 2 attending physicians, 2 residents) were invited to compare the rate of correctness of judgement and detection of image discrepancies. The ultrasound features of thyroid nodules (solid composition, microcalcifications, markedly hypoechoic, ill-defined or irregular margins, or extrathyroidal extensions, vertical orientation and comet-tail artifact) were extracted according to the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). The consistency of ultrasound features of thyroid nodules before and after restoration were compared.Results:The mean squared error of the images before and after restoration ranged from 0.274 to 0.522, and there were significant differences in the rate of correctness of judgement and detection of image discrepancies between physicians of different groups(all P<0.001). The overall accuracy rate was 51.95%, the overall detection rate was 1.79%, there were significant differences also within the chief physicians and resident groups (all P<0.001). The agreement rate of all ultrasound features of the nodules before and after image restoration was higher than 70%, over 90% agreement rate for features such as solid composition and comet-tail artifact. Conclusions:The algorithm can effectively repair obscured thyroid ultrasound images while preserving image features, which is expected to expand the deep learning image database, and promote the development of deep learning in the field of ultrasound images.

Objective:To investigate the types of cervical epithelial cells and the Human Papillomavirus (HPV) infection subtypes of 7 646 women specimens in Anhui province, and provide evidence for cervical cancer prevention.Methods:Thinprep cytologic test (TCT) and flow fluorescence hybridization technique were used to detect cervical epithelial lesions and HPV subtypes.Results:The total positive rate for TCT was 20.25%, and the positive rate was the highest in ≥ 60 age group (28.41%), followed by 10 to ≤ 19 age group (26.32%). The atypical squamous cells-undetermined significance (ASC-US), cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and HSIL positive rates were the highest in the ≥60 age group, and the low-grade squamous intraepithelial lesions (LSIL) positive rate was highest in the 10-19 age group. The proportion of patients with 40-49 age group was the highest, and that of ≥60 age group was the highest. The single infection rate of different cervical epithelial cell lesions was higher than that of multiple infection rates. As the deepening degree of the lesion, the high-risk single infection rate of HPV showed a increasing trend from ASCUS, LSIL, ASC-H to high-grade squamous intraepithelial lesions (HSIL); The common subtypes of HPV infection in negative for intraepithelial lesion or malignancy (NILM) are 52, 16, 58, 53 and 6. The common subtypes of ASCUS are 52, 16, 53, 58 and 51. The common subtypes of ASC-H are 18, 58 and16. LSIL common subtypes are 16, 52, 56, 58, 53 and 66, HSIL common subtypes are16, 58, 33, 52 and 59 type.Conclusions:The high risk and single genotypes of infection were dominant in different cervical epithelial cell lesions in Anhui. Women who aged ≥60 should pay attention and regularly undergo HPV testing and cervical cancer screening. The HPV infection subtypes of different cervical epithelial cell lesions are different, and the common subtypes are HPV52, 16, 58, 53, among which types 16, 58 and 33 are common infection subtypes detected in different lesions.

Objective To investigate the relationship between (serum neutrophil gelatinase-associated lipocalin,sNGAL) and cardiovascular events in patients with chronic kidney disease(CKD).Methods 300 patients with CKD were divided into two groups according to the level of sNGAL:high sNGAL group (n=158) and low sNGAL group (n=142).The incidence of cardiovascular events and cumulative survival rate were analyzed by ROC curve,and the correlation between sNGAL and cardiovascular risk factors,cardiovascular events in patients with chronic renal disease was analyzed.Influencing factors of cardiovascular events in CKD patients was analyzed.Results There were significant differences in the data about BMI,diabetes proportion,CKD staging,eGFR,hsCRP,24h proteinuria,HDL,iPTH,phosphate and blood calcium between the two groups (P＜0.05).The 3-year cumulative survival rate of high sNGAL group(77.2％) was significantly lower than that of low sNGAL group(96.5％),and the 3-year incidence of cardiovascular events (37.9％) was significantly higher than that of low sNGAL group (9.8％) (P＜ 0.05).AUC in diagnosing cardiovascular events in high sNGAL group (0.746) was significantly higher than that in eGFR(0.636),age (0.504),serum calcium (0.545),HDL(0.594) and LDL (0.508,all P＜0.05).There was a significant correlation between sNGAL and eGFR,HDL,BMI,hs-CRP,iPTH and phosphate (P＜ 0.05).Both univariate and multivariate fact ors COX showed that sNGAL was a risk factor of cardiovascular events in patients with CKD (P＜0.05),((HR=1.976 and 1.588,95％ CI=1.443-2.724 and 1.144-2.143,respectively,P=0.O00 and 0.000)).Conclusions The incidence of cardiovascular events in patients with CKD with high sNGAL is significantly increased.sNGAL is an independent factor of cardiovascular events in patients with chronic renal disease.

Objective To study the change and clinical significance of serum sex hormone levels in patients with Alzheimer's disease(AD).Methods The 1:1 case-control study,male AD group in 25 cases,control group in 25 cases,female AD group in 25 cases,25 cases in the control group.The serum sex hormone levels were measured by chemiluminescence immtmoassay in the two groups,and the data were analyzed.Results There was statistically significant difference in estradiol level between female patients and the control group[(40.820 ± 23.249) pmol/L vs.(153.700 ±113.900) pmol/L,t =4.85,P ＜ 0.001].There were statistically significant differences between male patients and the control group,in estradiol[(99.243 ± 34.657) pmol/L vs.(124.t00 ± 38.432) pmool/L],testosterone [(7.904 ±3.944) nmol/L vs.(19.142 ±7.882) nmol/L] levels (t =2.40,6.37,all P ＜0.05).No significant difference was observed in testosterone level in the female groups (P ＞ 0.05).The promoting follicle stimulating hormone and luteinizing hormone,progesterone,prolactin levels between the male group and female group had no statistically significant differences (all P ＞ 0.05).In patients with simple intelligent screening scale (Mini-Mental State Examination,MMSE),the score was significantly correlated with the level of estradiol (r =-0.281,P ＜ 0.05).Conclusion The level of women's estrogen decline is related to factor in the pathogenesis of AD,estradiol,testosterone levels of male decline is related to factor in the pathogenesis of AD.Estradiol level is low,the severity of the disease moreand more heavy.

Aim To observe the effects of icariin on depressive-like behavior in prenatally stressed offsprings and explore its mechanism.Methods The model of depression was established by prenatal restraint stress on late pregnant mother, then male offspring rats were randomly divided into five groups of eight: Control, PS model, Saline group(NS), ICA(80 mg·kg-1), ICA(40 mg·kg-1).The effects of icariin on PS-induced depressive-like behaviors in male offsprings were examined by forced swimming test(FST) and open-field test(OFT).Furthermore, the protein expressions of group I metabotropic glutamate receptors(I mGluRs) and excitatory amino acid transporter 2(EAAT2) in prefrontal cortex were detected by Western blot.Results PS group exhibited depressive-like behaviors with decreased struggling time(P<0.01) and center crossing numbers(P<0.05) compared to CON, with increased protein expressions of group I mGluRs(P<0.01,P<0.05) and decreased EAAT2(P<0.05) in prefrontal cortex compared to CON.Treatment with icariin(80 mg·kg-1, 40 mg·kg-1)significantly increased struggling time(P<0.05,P<0.01) and center crossing numbers(P<0.05) in PS-exposed male offspring rats.Treatment with icariin markedly modulated the protein levels of mGluR1, mGluR5 and EAAT2 in prefrontal cortex.Conclusion Icariin has significant antidepressant effects in prenatally stressed rats, and the mechanism might be associated with the modulation of Ⅰ mGluRs.