Objective:To observe and analyze the correlations between aqueous humor cytokine concentrations and disorganization of retinal inner layers (DRIL), as well as postoperative visual acuity, in patients with idiopathic epiretinal membrane (iERM).Methods:A prospective clinical study. From November 2022 to October 2024, 40 eyes of 40 patients diagnosed with iERM at Ophthalmology Center of Zhejiang Provincial People's Hospital (Affiliated People's Hospital) underwent cataract surgery alone or combined with pars plana vitrectomy (iERM group) were enrolled; 19 eyes of 19 patients undergoing cataract surgery alone during the same period served as the control group. All eyes underwent best-corrected visual acuity (BCVA) testing and swept-source optical coherence tomography (SS-OCT). BCVA was assessed using a logarithmic visual acuity chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Central macular thickness (CMT) was measured using SS-OCT. The iERM group was further subdivided into DRIL-positive and DRIL-negative subgroups (21 eyes and 19 eyes, respectively), based on the presence or absence of DRIL. Aqueous humor samples were collected preoperatively from eyes in both the iERM and control groups. Concentrations of transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor, fibroblast growth factor, vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), glial cell line-derived neurotrophic factor (GDNF), intercellular adhesion molecule-1 (ICAM-1), angiopoietin (Ang)-1, Ang-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Follow-up examinations using the same equipment and methods were performed at 1 month postoperatively. Aqueous cytokine levels were compared between the iERM group, control group, DRIL-positive subgroup, and DRIL-negative subgroup. Correlations between aqueous cytokine levels in the iERM group and BCVA or CMT were also analyzed. Intergroup comparisons utilized the Mann-Whitney U test; correlations between variables were assessed using Spearman's rank correlation analysis. Results:Compared to the control group, the iERM group exhibited significantly higher aqueous concentrations of TGF-β1, TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, and TNF-α ( P<0.05). Compared to the DRIL-negative subgroup, the DRIL-positive subgroup showed significantly elevated aqueous concentrations of TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, Ang-2, TNF-α, and IL-6 ( P<0.05). Significant differences were observed in logMAR BCVA ( P=0.028) and CMT ( P<0.001) within the iERM group between preoperative and 1-month postoperative measurements. LogMAR BCVA differed significantly between the DRIL-positive and DRIL-negative subgroups ( P=0.048). Correlation analysis revealed that baseline aqueous levels of VEGF-A and IL-6 in eyes with DRIL were positively correlated with postoperative BCVA ( r=0.324, 0.452; P=0.042, 0.003). No significant correlation was found between CMT and any cytokine ( P>0.05). Conclusions:Aqueous humor cytokines are closely associated with DRIL in iERM patients. IL-6 and VEGF-A may serve as potential predictive biomarkers for early postoperative visual recovery.

Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

Objective:To observe and analyze the correlations between aqueous humor cytokine concentrations and disorganization of retinal inner layers (DRIL), as well as postoperative visual acuity, in patients with idiopathic epiretinal membrane (iERM).Methods:A prospective clinical study. From November 2022 to October 2024, 40 eyes of 40 patients diagnosed with iERM at Ophthalmology Center of Zhejiang Provincial People's Hospital (Affiliated People's Hospital) underwent cataract surgery alone or combined with pars plana vitrectomy (iERM group) were enrolled; 19 eyes of 19 patients undergoing cataract surgery alone during the same period served as the control group. All eyes underwent best-corrected visual acuity (BCVA) testing and swept-source optical coherence tomography (SS-OCT). BCVA was assessed using a logarithmic visual acuity chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Central macular thickness (CMT) was measured using SS-OCT. The iERM group was further subdivided into DRIL-positive and DRIL-negative subgroups (21 eyes and 19 eyes, respectively), based on the presence or absence of DRIL. Aqueous humor samples were collected preoperatively from eyes in both the iERM and control groups. Concentrations of transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor, fibroblast growth factor, vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), glial cell line-derived neurotrophic factor (GDNF), intercellular adhesion molecule-1 (ICAM-1), angiopoietin (Ang)-1, Ang-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Follow-up examinations using the same equipment and methods were performed at 1 month postoperatively. Aqueous cytokine levels were compared between the iERM group, control group, DRIL-positive subgroup, and DRIL-negative subgroup. Correlations between aqueous cytokine levels in the iERM group and BCVA or CMT were also analyzed. Intergroup comparisons utilized the Mann-Whitney U test; correlations between variables were assessed using Spearman's rank correlation analysis. Results:Compared to the control group, the iERM group exhibited significantly higher aqueous concentrations of TGF-β1, TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, and TNF-α ( P<0.05). Compared to the DRIL-negative subgroup, the DRIL-positive subgroup showed significantly elevated aqueous concentrations of TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, Ang-2, TNF-α, and IL-6 ( P<0.05). Significant differences were observed in logMAR BCVA ( P=0.028) and CMT ( P<0.001) within the iERM group between preoperative and 1-month postoperative measurements. LogMAR BCVA differed significantly between the DRIL-positive and DRIL-negative subgroups ( P=0.048). Correlation analysis revealed that baseline aqueous levels of VEGF-A and IL-6 in eyes with DRIL were positively correlated with postoperative BCVA ( r=0.324, 0.452; P=0.042, 0.003). No significant correlation was found between CMT and any cytokine ( P>0.05). Conclusions:Aqueous humor cytokines are closely associated with DRIL in iERM patients. IL-6 and VEGF-A may serve as potential predictive biomarkers for early postoperative visual recovery.

Objective:To understand the molecular characteristics of the mutant strain of polymerase basic protein 2 (PB2) gene of influenza A (H1N1pdm) in Guangdong province, and to explore its specific molecular sites, so as to provide scientific basis for the prevention and control of influenza virus.Methods:Throat swab samples were collected from 2 cases infected with PB2 gene variant strains for virus isolation, and 23 influenza virus strains were selected from Guangdong province for sequencing analysis. The reference sequences and vaccine strain sequences provided by GISAID were used to perform evolutionary analysis on hemagglutinin (HA) and PB2 genes. Virus strain antigen analysis and neuraminidase (NA) inhibition test were carried out. PB2 protein model was constructed and polymerase activity was analyzed.Results:H399N amino acid mutation occurred in the HA gene of PB2-D701N and PB2-A271S variant strains, both of which belonged to the branch of 6B.1A.5a.2a. They belonged to the same big branch and different small branches as the vaccine strain A/Victoria/4897/2022, and they are all vaccine-like strains. In the three-dimensional structure, the mutations of PB2-D701N and PB2-A271S change charge and hydrophobicity.Conclusions:PB2-D701 and A271 were highly conserved, and PB2 mutant strains were not the dominant strains. The PB2 mutant had high antigenicity with the vaccine. The PB2 mutant strain is sensitive to NA inhibitors. The three-dimensional model predicted that PB2-D701N mutation could enhance virulence and affect transmissibility of influenza virus, while PB2-A271S mutation could affect polymerase activity and polymerase complex synthesis of influenza virus.

Objective:To analyze and reveal the genetic evolution and variation of influenza viruses in cases of co-infection in Guangdong Province.Methods:Throat swab samples were collected from four cases of H1N1pdm and H3N2 co-infection for viral isolation. The isolated strains were subjected to antigen analysis and neuraminidase inhibitor susceptibility test. High-throughput sequencing was used to detect the sequences of strains in three throat swab samples and one virus strain, and then genetic variations were analyzed.Results:Four influenza viruses were isolated with one strain of H1N1pdm and three of H3N2 subtype, and all of them were genetically similar to the vaccine strain in 2022-2023. The HA genes of H1N1pdm and H3N2 strains belonged to clade 6B.1A.5a.2a and 2a.3a.1, respectively. The isolated strains belonged to the same clade as the strains prevalent in Guangdong during the same period. No drug-resistant variations were detected in N1 or N2 gene, and the isolated strains were sensitive to oseltamivir and zanamivir.Conclusions:H1pdm subtype had stronger replication ability than H3 subtype in the influenza viruses isolated from co-infected cases. H1N1pdm and H3N2 subtype influenza viruses were genetically similar to the strains circulating in Guangdong at the same time. The isolated H1N1pdm and H3N2 strains were sensitive to both oseltamivir and zanamivir, indicating that they could continue to be used in the treatment of influenza virus infections caused by one or two genotypes.

Objective　To analyze the composition, population density, seasonal trends, and insecticide resistance monitoring results of vector mosquitoes in Liaocheng City from 2020 to 2022, providing a reference basis for further mosquito control measures. Methods　According to the "Implementation Plan for National Vector Biomonitoring", adult mosquito monitoring was carried out using mosquito traps and double-layer stacked nets at two national level monitoring points in Dong’e and Chiping. The Bretu Index method was used for monitoring throughout the city, and the immersion method was used for monitoring mosquito insecticide resistance. The monitoring period for adult mosquitoes was from March to November, and for juvenile mosquitoes was from May to October. Results　From 2020 to 2022, a total of 816 mosquito traps were deployed, capturing 4 717 adult mosquitoes with an average density of 5.78 mosquitoes per trap-night. Among them, 4 232 were Culex pipiens pallens, accounting for 89.72% of the total mosquito population, followed by 15 were Anopheles sinensis, accounting for 0.32%; 10 Aedes albopictus, accounting for 0.21%; 460 other mosquito species, accounting for 9.75%. Mosquito density was higher in rural areas compared to urban areas, with the highest density found in livestock sheds, followed by parks, hospitals, farms, and residential areas. Adult mosquito was first observed in May, with the peak activity occurring from June to August. The double-layer net method captures only Aedes albopictus, with an average net trapping index of 2.99 mosquitoes/(net·h), and their activity was concentrated from June to September. The average Brayton Index (BI) from May to October was 15.95, with a peak occurring in July and gradually decreasing after August. Insecticide resistance monitoring found that Culex pipiens pallens in Liaocheng City exhibited low resistance to permethrin, deltamethrin, dithion, and beta cypermethrin, with beta cypermethrin having the highest resistance. Conclusion　The dominant mosquito species in Liaocheng City is Culex pipiens pallens, followed by Aedes albopictus. The peak activity of adult and juvenile mosquitoes is concentrated between July and September, showing a distinct seasonal trend of growth and decline, posing a risk of dengue fever outbreaks. Culex pipiens pallens exhibits resistance to some insecticides, and timely measures should be taken to prevent the outbreak of mosquito-borne infectious diseases.

Objective:To evaluate the application of intraoperative optical coherence tomography (iOCT) in vitreoretinal surgery.Methods:An observational case series study was conducted.A total of 316 patients (316 eyes) who received vitreoretinal surgery and iOCT from January 2015 to December 2017 in Hangzhou Branch of Eye Hospital, Wenzhou Medical University were enrolled.The iOCT scanning time and result, the consistency between iOCT result and observation under the operating microscope as well as the influence of iOCT on surgical strategy were recorded.The postoperative adverse reactions and complications were observed.The study protocol was approved by an Ethics Committee of Eye Hospital, Wenzhou Medical University(No.2019-168-K-160). Written informed consent was obtained from all patients prior to any medical examination.Results:There were 85.8% (271/316) of patients who successfully completed iOCT scanning, with an average scanning time of (3.54±2.30)minutes.Among the 271 successful eyes, there were 51 with idiopathic macular hole (IMH), 95 with epiretinal membrane, 50 with dense vitreous hemorrhage (VH), 30 with macular lamellar hole, 12 with vitreous macular traction syndrome, 33 with myopic maculopathy.There were 45 eyes, accounting for 16.6%, the iOCT results of which were inconsistent with the observation of operator under the operating microscope.There were 27 eyes, accounting for 10.0%, the surgical strategy of which was changed.The iOCT results of IMH showed that intra-retinal bridge connection appeared in 2 eyes after ILM peeling, then air tamponade was used.High-reflection strips on the edge of the MH after ILM peeling, called the Hole-door phenomenon, were found in 15 eyes, accounting for 32.6%.In MH with a diameter >400 μm, the postoperative best corrected visual acuity and continuity of outer limiting membrane were better in eyes with Hole-door phenomenon than eyes without Hole-door phenomenon.There were 8 eyes, accounting for 8.4%, showing residual membrane, 3 eyes of which received extra ERM peeling.There were 56 eyes, accounting for 58.9%, showing the secondary changes after membrane peeling.For 50 eyes with dense VH, there were 17 eyes showing the normal macular structure, accounting for 34%, and 33 eyes showing the abnormal macular structure, accounting for 66.0%.In addition, the macular structures of 14 eyes, accounting for 28.0%, observed in iOCT image were inconsistent with the intraocular microscope finding, and 11 of them received extra ERM peeling.Conclusions:The application of iOCT in vitreoretinal surgery can guide the selection of reasonable surgical methods during operation, predict postoperative recovery as well as improve postoperative outcomes.

Plant biology is a basic course for students majoring in biological science. Under the guidance of developmental biology, we have constructed a comprehensive, systematic and dynamic new curriculum system for plant biology. There are still some problems existing in the current curriculum teaching mode, e.g. the students do not listen carefully to the lecture due to single classroom teaching mode, the mismatch between theoretical and experimental courses in terms of content and timing, the incomplete understanding on plants and the difficulty of integrating learning and practicing due to insufficient field practices. In view of these problems, a series of new teaching strategies for bioscience major of Harbin Institute of Technology were proposed and implemented. The combination of lectures and high quality massive open online courses (MOOC) were used for theoretical study, to which the flipped classroom was added. In addition, the theoretical study and the experiment work were combined. Moreover, the plant cognitive practices were carried out in the campus and the botanical garden in early spring, late spring and summer, respectively. Satisfactory results were achieved after two rounds of teaching practice, which fulfilled the education requirements and laid foundations for students to continue follow-up basic and professional courses.
Biological Science Disciplines ; Biology ; Curriculum ; Humans ; Learning ; Students

Objective:To deliver understanding of the latest research progress on clinical trials and approval of dermatological drugs in China in 2020.Methods:A registration and information disclosure platform for drug clinical studies and a query system for domestic and imported drugs in the National Medical Products Administration of China were searched for registered clinical trials and approved dermatological drugs, respectively. The number and stages of clinical trials, indications and classification of involved products, and listed dermatological drugs in 2020 were summarized and depicted.Results:There were 157 dermatological drug trials registered in China in 2020, accounting for 6.16% of all the 2 548 clinical drug trials, including 127 (80.9%) initiated by Chinese pharmaceutical enterprises and 25 (15.9%) international multicenter trials. Among the 127 drug trials initiated by Chinese pharmaceutical enterprises, bioequivalence trials were mostly common, accounting for 55.9% (71/127) . Compared with global pharmaceutical enterprises, domestic pharmaceutical companies initiated significantly decreased proportions of international multicenter trials (1.9% [3/157] vs. 14.0% [22/157], P < 0.001) , but significantly increased proportions of phaseⅠclinical trials and bioequivalence trials (24.4% [31/127] vs. 10.0% [3/30], 55.9% [71/127] vs. 0, respectively, both P < 0.001) . Totally, 90 kinds of dermatological drug were involved in all the trials, psoriasis, atopic dermatitis and melanoma were the most common indications, and innovative drugs accounted for 53.3% (48/90) ; the proportion of innovative drugs was significantly lower in domestic pharmaceutical companies than in global pharmaceutical companies (43.2% [32/74] vs. 16/16, P < 0.001) . In addition, 28 dermatological drugs developed by 22 pharmaceutical companies were approved in China in 2020, of which 21 drugs were developed by domestic pharmaceutical companies. Conclusion:Clinical drug trials carried out by domestic pharmaceutical companies mostly focus on generic drugs, and it is still necessary for domestic pharmaceutical companies to further improve the innovation ability.

Objective:To observe the expression of vascular endothelial growth factor (VEGF) and aquaporin 4 (AQP4) in the inner limiting membrane (ILM) of diabetic retinopathy (DR) with macular edema, and analyze the correlation between VEGF and AQP4 expression.Methods:A cross-sectional study. From September 2019 to September 2020, 38 eyes of 38 patients with DR and idiopathic macular hole (iMH) who underwent vitrectomy (PPV) combined with ILM stripping at the Hangzhou campus of The Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. Among them, there were 25 males and 13 females who aged 37-76 years old, average age was 59±10 years old; All eye included 15 right eyes and 23 left eyes. iMH and DR included 9 eyes in 9 cases and 29 eyes in 29 cases, respectively, and they were divided into iMH group and DR group. The DR group was divided into DME group and no DME group according to whether it was accompanied by diabetic macular edema (DME), with 14 eyes and 15 eyes respectively. After the stripped ILM tissue was fixed, immunofluorescence analysis was performed to obtain a picture of the fluorescence mode of AQP4 and VEGF, and the fluorescence intensity value of VEGF and AQP4 was measured by Image J software. The differences of VEGF and AQP4 immunofluorescence values in the specimens between groups were compared by one-way analysis of variance. The correlation between the fluorescence intensity of AQP4 and the fluorescence intensity of VEGF was analyzed by Pearson correlation analysis.Results:The average fluorescence intensity valuesof VEGF and AQP4 in ILM specimens of DME group, no DME group and iMH group were 38.96±7.53, 28.25±3.12, 30.07±4.84 and 49.07±8.73, 37.96±6.45, 38.08±5.04, respectively. The average fluorescence intensity of VEGF and AQP4 in the ILM specimens of the DME group was significantly higher than that of the no DME group and iMH group, and the difference was statistically significant ( F=13.977, 9.454; P<0.05). The average fluorescence intensity values of VEGF and AQP4 on IML specimens in the DR group were 33.80±7.91, 43.76±9.44, respectively. The results of Pearson correlation analysis showed that the fluorescence intensity of VEGF and AQP4 in the ILM specimens of the DR group was significantly positively correlated ( r=0.597, P=0.003). Conclusions:The expressions of VEGF and AQP4 in ILM of eyes with DR and DME are significantly increased compared with those without DME. The expression of VEGF and AQP4 in ILM of eyes with DR is positively correlated.