1.Optical coherence tomography angiography in diabetic retinopathy: focusing on microvascular changes
Xiongyi YANG ; Guoguo YI ; Yanxia CHEN ; Siyu YANG ; Shibei AI ; Cong ZHENG ; Mingzhe CAO ; Min FU
International Eye Science 2025;25(2):179-190
AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR), and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS: A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital, Sun Yat-sen University from 2022 to 2023 were included, including 95 first-diagnosed DR patients and 105 patients without DR, and all patients underwent OCTA examination and a collection of demographics and renal function parameters. After a quality check, automated measurements of the foveal avascular zone area, vessel density(VD), and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS: Using random forest and multivariate Logistic regression methods, we developed a diagnostic model for DR based on 12 variables(age, FBG, SBP, DBP, HbA1c, ALT, ALP, urea/Scr, DM duration, HUA, DN, and CMT). Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window, AUC=0.837 vs 0.819, P=0.03). In the study of DN patients, the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD; outer VD; full VD; outer PD; full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model. Meanwhile, compared with the 3 mm×3 mm window, the microvascular parameters in the 6 mm× 6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.
2.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies
Zheng ZHU ; Zheng-Shan CHEN ; Guan-Ying ZHANG ; Ting FANG ; Pu FAN ; Lei BI ; Yue CUI ; Ze-Ya LI ; Chun-Yi SU ; Xiang-Yang CHI ; Chang-Ming YU
Progress in Biochemistry and Biophysics 2025;52(4):957-969
ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.
3.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
4.Subchronic exposure to benzoapyrene results in lung tissue cell damage caused by ferroptosis in mice
Chaoli ZHOU ; Shihan DING ; Hui HE ; Zhirui MA ; Jie CHEN ; Xingdi GUO ; Yi LYU ; Jinping ZHENG
Journal of Environmental and Occupational Medicine 2025;42(8):971-977
Background Exposure to benzo[a]pyrene (BaP) may impair lung function through various mechanisms; however, it remains uncertain whether BaP induces ferroptosis in lung tissue cells, resulting in lung function impairment. Objective To investigate the ferroptosis of lung tissue cells triggered by subchronic BaP exposure in mice and its correlation with lung injury, and to explore the function of ferroptosis in BaP-induced lung tissue damage. Method Seventy-two healthy 3-weeks-old male C57BL/6J mice were acclimatized for 1 week and then randomly divided into six groups: control group (corn oil 10 mL·kg−1), low-dose BaP group (2.5 mg·kg−1), medium-dose BaP group (5 mg·kg−1), high-dose BaP group (10 mg·kg−1), BaP+ferrostatin-1 (Fer-1) group (10 mg·kg−1+1 mg·kg−1), and Fer-1 group (1 mg·kg−1), with 12 mice each group. Corn oil and BaP were administered via gavage every other day, followed by an intraperitoneal injection of Fer-1 the subsequent day, throughout a period of 90 d. Whole-body plethysmography was applied to detect lung function; hematoxylin-eosin staining (HE) and Masson staining were used to observe lung tissue injury and fibrosis; microscopy of alveolar epithelial cells was conducted to reveal mitochondrial morphology; biochemical assays were used to measure the content of tissue iron, malondialdehyde (MDA), and glutathione (GSH), as well as the activity of glutathione peroxidase (GSH-Px); Western blotting and real-time quantitative PCR (RT-qPCR) analyses were performed to reveal the protein and mRNA expression of ferroptosis markers. Results Compared to the control group, the high-dose BaP group showed a significant increase in expiration time (Te) (P<0.01), and a significant decrease in ratio rate of achieving peak expiratory flow (Rpef), tidal volume (TVb), peak inspiratory flow (PIF), minute volume (MVb), and peak expiratory flow (PEF) (P<0.05 or 0.01). Based on the results of HE and Masson staining, partial destruction of alveolar structures, thickening of alveolar walls, infiltration of inflammatory cells, significant thickening of tracheal walls and a large deposition of collagen fibers in lung tissue were observed in the medium- and high-dose BaP groups. By microscopy, the alveolar epithelial cells exposed to low-dose BaP showed condensed chromatin, and the mitochondria exposed to medium and high-dose BaP showed wrinkles, increased mitochondrial membrane density, and diminished mitochondrial cristae. Compared to the control group, in the medium- and high-dose BaP groups, the lung tissue iron content and the expression levels of ACSL4 protein and mRNA significantly elevated (P<0.01 or 0.05), while the mRNA expression level of SLC7A11 significantly decreased (P<0.05); in the high-dose BaP group, the MDA content, COX2 protein, and PTGS2 mRNA expression levels significantly increased (P<0.05 or 0.01), GSH content and GSH-Px activity, GPX4 protein and mRNA expression levels, and the expression level of SLC7A11 protein significantly decreased (P<0.01 or 0.05). The ferroptosis inhibitor Fer-1 markedly reversed respiratory function, morphology, mitochondrial alterations, and the aforementioned ferroptosis-related biochemical indicators. Conclusion Subchronic exposure to BaP can induce ferroptosis in mice lung tissue cells, resulting in compromised lung function.
5.Rehmanniae Radix Praeparata Improves Neurological Function of Ischemic Stroke Rats by Inhibiting Autophagy and Ferroptosis
Saifei LI ; Peipei YUAN ; Yaxin WEI ; Liyuan GAO ; Panying LI ; Yuan RUAN ; Yi CHEN ; Yang FU ; Xiaoke ZHENG ; Weisheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):26-33
ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation, model, low- and high -dose (3.5 g·kg-1 and 7 g·kg-1) Rehmannia Radix Praeparata, and nimodipine (0.01 g·kg-1) groups. The rat model of middle cerebral artery occlusion (MCAO) was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile, the serum levels of lactate dehydrogenase (LDH), oxidative stress-related indicators superoxide dismutase (SOD), glutathione peroxidase 4 (GPX4), and malondialdehyde (MDA), and the iron (Fe) content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats, Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector (beclin-1), microtubule-associated protein light chain 3 (LC3B), and ubiquitin-binding protein p62 (p62). The ferroptosis-associated proteins included transferrin (TF), transferrin receptor 1 (TFR1), ferritin heavy chain 1 (FTH1), and ferropotin (FPN1). The neurological function injury-associated proteins included brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). ResultCompared with the sham operation group, the model group showed increased neurological function score, cerebral infarction volume, and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition, the model group presented elevated levels of LDH, MDA, and Fe (P<0.01) and lowered levels of SOD and GPX4 (P<0.01). Compared with the model group, Rehmanniae Radix Praeparata decreased the content of LDH, MDA, and Fe (P<0.05, P<0.01) and elevated the levels of SOD and GPX4 (P<0.05, P<0.01). Compared with the sham operation group, the modeling promoted the expression of beclin-1,LC3B Ⅱ/Ⅰ, TF, and TFR1 and inhibited the expression of p62, FTH1, FPN1, BDNF, and TrkB (P<0.01). The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.
6. Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis
Zheng-Yang SUN ; Nan-Nan LIU ; Xue-Fei FAN ; Su-Huan CHEN ; Xiao-Yu CHEN ; Zheng-Yang SUN ; Wu-Qi CHEN ; Guang-Yi CHEN ; Yu-Bao SHAO ; Xiao-Yu CHEN
Chinese Pharmacological Bulletin 2024;40(2):292-298
Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L
7.Interpretation of the updates of the NCCN esophageal and esophagogastric junction cancers clinical practice guidelines in oncology (version 3. 2023)
Yi, WANG ; Chen ZHENG ; Qihui LI ; Jun WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):11-16
Esophageal cancer is the seventh most common cancer worldwide. On August 29, 2023, National Comprehensive Cancer Network (NCCN) released the NCCN esophageal and esophagogastric junction cancers clinical practice guidelines in oncology (version 3. 2023). This article aims to highlight the key updates in treatment and follow-up recommendations between the version 3 and the version 2 in 2023, providing the latest guidance for the management of esophageal cancer in our country.
8.Clinical value of serum TgAb and TPOAb in diagnosis and treatment of papillary thyroid microcarcinoma
Wenzhen DENG ; Cheng CHEN ; Bing LING ; Li ZHAO ; Li ZHENG ; Xianqun ZHOU ; Qian LIANG ; Jixiu YI
Chongqing Medicine 2024;53(5):727-732,737
Objective To investigate the clinical value of thyroid globulin antibody(TgAb)and thyroid peroxidase antibody(TPOAb)in the diagnosis and treatment of papillary thyroid microcarcinoma(PTMC).Methods A total of 346 patients with thyroid nodules who underwent surgical treatment in the hospital from August 2012 to October 2021 were selected as the research objects.According to the postoperative pathologi-cal results,the patients were divided into the benign nodule group,PTMC group and non-micro papillary thy-roid carcinoma(PTC)group.The general data of the patients and thyroid function indexes[free triiodothyro-nine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH),TgAb and TPOAb]before and after operation were collected,the tumor recurrence or lymph node metastasis after operation were ob-served,and the relationship between serum TgAb and TPOAb and the risk and prognosis of PTMC was ana-lyzed.Results The positivity rate of TgAb in the PTMC and non-micro PTC groups was significantly higher than that in the benign nodule group(P<0.05).The TPOAb positivity rate was not significantly different among the three groups(P>0.05).Only the TSH level in the PTMC group was higher than that in the non-micro PTC group(P<0.05).Multivariate logistic analysis showed that younger age,higher TSH and positive TgAb were independent risk factors for PTMC and non-micro PTC(P<0.05).However,the risk of PTC didn't increase with increasing TgAb titres.The positivity rate of TgAb in the PTMC and non-micro PTC groups didn't change significantly within one month after operation,but decreased in one year after operation(P<0.05).The TPOAb positivity rate decreased after operation,but the difference was not statistically sig-nificant(P>0.05).In the PTMC group,four cases had tumor recurrence or lymph node metastasis,and the TgAb level increased by 88.4%,49.5%,5.7%and 84.0%respectively when the tumor recurred or metasta-sized.Among them,the TPOAb level increased by 51.6%,30.0%and 2.9%respectively in three cases and decreased by 53.9%in one case.In the PTMC group,there were 11 patients with cervical lymph node enlarge-ment,and there was no statistical difference in TgAb and TPOAb levels when the condition changed(P>0.05).Conclusion TgAb is a risk factor for PTMC,and can be followed up regularly during the diagnosis and treatment of PTMC.The specificity of TPOAb is not as good as that of TgAb,and appropriate follow-up can be chosen during the course of the disease.
9.Development,reliability and validity of nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia
Yi LIU ; Liqun ZHU ; Sheng SUI ; Ruo ZHUANG ; Yiyi NI ; Yuanyuan MI ; Lei BAO ; Li LI ; Lanping ZHENG ; Mengmeng CHEN
Chongqing Medicine 2024;53(5):738-744
Objective To develop nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia,and test its reliability and validity.Methods Based on the evidence-based summary of the best evidence of medication management for patients with dysphagia,guided by the the-ory of knowledge,attitude and practice,the basic dimensions and item pool of the questionnaire were deter-mined through group discussion,Delphi expert consultation and pre-investigation.In order to revise the ques-tionnaire,437 nurses from 10 tertiary hospitals in Jiangsu Province were conveniently selected for investigation,and the reliability and validity of the questionnaire were tested according to the survey results.Results The nurses'knowl-edge,attitude and practice questionnaire on medication management for patients with dysphagia included 43 items in three dimensions.The three dimensions were analyzed by exploratory factors,and six common factors with characteristic roots>1 were extracted.Two factors were extracted from the knowledge dimension,and the cumulative variance contribution rate was 74.958%,One factor was extracted from the attitude dimen-sion,and the cumulative variance contribution rate was 77.655%.Three factors were extracted from the prac-tice dimension,and the cumulative variance contribution rate was 72.274%.The factor load of each item was 0.618-0.902,Cronbach's α coefficient of the total questionnaire was 0.949,and the test-retest reliability was 0.909.The overall content validity coefficient of the questionnaire was 0.922,and the content validity coeffi-cient for each item was 0.800-1.000.Conclusion The nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia developed in this study has good reliability and validi-ty,and could be used as an effective tool to evaluate the status quo of nurses'medication management for pa-tients with dysphagia.
10.Clinical study on the construction of risk prediction model for postoperative recurrence of advanced epithelial ovarian cancer based on serum HE4,PLR,RLX and KPNA2
Chen SHEN ; Yi WANG ; Cui ZHENG ; Jun YANG
International Journal of Laboratory Medicine 2024;45(3):295-300
Objective To study the construction of risk prediction model for postoperative recurrence of ad-vanced epithelial ovarian cancer based on serum human epididymis protein 4(HE4),platelet count/lymphocyte count ratio(PLR),relaxin(RLX),karyopherin α2(KPNA2).Methods 124 patients with advanced epithelial o-varian cancer diagnosed and treated in Suzhou Municipal Hospital(East District)from January 2016 to January 2019 were selected as the study objects,patients with advanced epithelial ovarian cancer were divided into re-currence group and the non-recurrence group based on whether they had recurred or not.The level of HE4 was detected by electrochemical luminescence immunoassay,PLR was calculated according to the blood routine re-sults,and RLX and KPNA2 levels were detected by enzyme-related immunosorbent assay.Multivariate Logis-tic regression analysis was used to analyze the influencing factors of postoperative recurrence in patients with advanced epithelial ovarian cancer,and establish a risk prediction model for postoperative recurrence of ad-vanced epithelial ovarian cancer.Receiver operating characteristic(ROC)curve was used to evaluate the pre-dictive efficacy of the model for postoperative recurrence of advanced epithelial ovarian cancer,and Hosmer-Lemeshow test was used to analyze the fitting of recurrence risk prediction model for patients with advanced epithelial ovarian cancer.Results There was a statistically significant difference in International Federation of Gynecology and Obstetrics(FIGO)staging and serum levels of carbohydrate antigen 125,HE4,PLR,RLX and KPNA2 between the recurrence group and the non-recurrence group(P<0.05).FIGO staging Ⅳ of cancer and elevated serum HE4,PLR,RLX and KPNA2 were risk factors for postoperative recurrence in patients with advanced epithelial ovarian cancer(P<0.05).ROC curve analysis showed that,the area under the curve of the recurrence risk prediction model for postoperative recurrence risk of advanced epithelial ovarian cancer was 0.859,which was significantly higher than that single indicator detected by HE4,PLR,RLX and KP-NA2.Hosmer-Lemeshow test showed that the recurrence risk prediction model of advanced epithelial ovarian cancer had a good fitting(x2=7.869,P=0.437).Conclusion The risk prediction model for postoperative re-currence of advanced epithelial ovarian cancer based on serum HE4,PLR,RLX,KPNA2 and FIGO staging of cancer has high predictive value for evaluating postoperative recurrence of advanced epithelial ovarian cancer,and deserves clinical attention.

Result Analysis
Print
Save
E-mail