Objective:To detect the expression of microRNA (miR)-211-5p, erythropoietin hepatocyte kinase receptor B2 (EphB2) and erythropoietin hepatocyte kinase ligand B2 (ephrin B2) in spinal cord tissues as well as nerve cells after spinal cord injury (SCI), and to explore their mechanisms and effects on neurological recovery in SCI rats.Methods:The study was conducted from May 2020 to June 2021 using Sprague Dawley (SD) rats and PC12 cells. SD rats were divided into sham-operated group and SCI group of 30 rats each, and Basso-Beattie-Bresnahan (BBB) score were performed at different postoperative time points (1, 3, 7, 14, 21 and 28 d), and the relative expression of miR-211-5p and Eph/ephrin B2 mRNA was measured by quantitative real-time polymerase chain reaction (qPCR); the SCI rats were divided into recombinant lentiviral vector LV-miR-211-5p group (group A), empty lentiviral vector LV-eGFP (group B) and saline group (group C), with 15 rats in each group, respectively. The recombinant lentiviral vector, empty lentiviral vector and saline were injected on the cephalic and caudal sides of the spinal cord injury, and the relative expression of miR-211-5p and Eph/ephrin B2 mRNA in the spinal cord tissue was measured at 1, 7 and 14 d after surgery. In addition, a PC12 injury cell line model was established with 150 μmol/L hydrogen peroxide (H 2O 2), and the apoptosis rate and apoptosis-related proteins and contents of different cell lines were detected by flow cytometry and Western blot, respectively. MiR-211-5p was verified to target EphB2 by dual luciferase reporter gene. Results:The results of the animal experiments showed that at different postoperative time points, the miR-211-5p levels in the SCI group were lower than those in the SHAM group: 0.70 ± 0.03 vs. 1.00 ± 0.10, 0.60 ± 0.04 vs. 1.00 ± 0.05, 0.45 ± 0.10 vs. 1.00 ± 0.12, 0.30 ± 0.06 vs. 1.00 ± 0.15, 0.20 ± 0.05 vs. 1.00 ± 0.13, 0.10 ± 0.02 vs. 1.00 ± 0.07. In contrast, levels of Eph/ephrin B2 were higher in the SCI group compared to the SHAM group: 1.10 ± 0.05 vs. 1.00 ± 0.01, 1.80 ± 0.01 vs. 1.00 ± 0.08, 2.30 ± 0.01 vs. 1.00 ± 0.10, 2.60 ± 0.01 vs. 1.00 ± 0.05, 2.80 ± 0.01 vs. 1.00 ± 0.06, 3.00 ± 0.01 vs. 1.00 ± 0.07 and 1.20 ± 0.05 vs. 1.00 ± 0.02, 1.60 ± 0.01 vs. 1.00 ± 0.03, 2.10 ± 0.10 vs. 1.00 ± 0.01, 2.40 ± 0.11 vs. 1.00 ± 0.09, 2.70 ± 0.13 vs. 1.00 ± 0.05, 2.90 ± 0.12 vs. 1.00 ± 0.03 ( P<0.05). At 14 d after surgery, Group A exhibited higher BBB scores than Groups B and C: (14.0 ± 1.1) points vs. (8.0 ± 1.1) and (8.2 ± 1.2) points, while miR-211-5p levels were higher than those in Groups B and C: 1.90 ± 0.10 vs. 0.40 ± 0.01 and 0.50 ± 0.02, and Eph/ephrin B2 levels were lower than those in Groups B and C: 0.70 ± 0.10 vs. 1.80 ± 0.04 and 1.90 ± 0.06, 0.60 ± 0.03 vs. 2.00 ± 0.04 and 2.10 ± 0.05 ( P<0.05). Immunofluorescence staining showed that the levels of GAP-43 and synaptophysin in group A were higher than those in groups B and C at 14 d after surgery ( P<0.05). Cellular assays showed that overexpression of miR-211-5p inhibited the apoptosis rate of H 2O 2-induced PC12 cells and the expression of the apoptosis-related gene Cleaved-caspase3 ( P<0.05). Knockdown of miR-211-5p increased the apoptosis rate of H 2O 2-induced PC12 cells and the expression of the apoptosis-related gene Cleaved-caspase3 ( P<0.05). Dual luciferase reporter gene assay confirmed that EphB2 was a target gene of miR-211-5p and overexpression of EphB2 antagonized the inhibitory apoptosis effect of miR-211-5p on H 2O 2-induced PC12 cells. Conclusions:This study showed that miR-211-5p could promote neurological repair in SCI by inhibiting the expression of Eph/ephrin B2 signaling pathway, suggesting that using miR-211-5p as a target to inhibit Eph/ephrin B2 signaling pathway may have a protective effect on SCI.

Objective To explore the protective effect of modified Taoren Chengqi Decoction on ventilator-induced lung injury(VILI)in rats based on the nuclear factor-erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)-ferroptosis pathway.Methods Rats were randomly separated into the control group,the model group,the modified Taoren Chengqi Decoction group,the ML385(Nrf2 inhibitor)group,and the modified Taoren Chengqi Decoction+ML385 group,with 12 rats in each group.The rats in control group underwent tracheal intubation and kept spontaneous breathing.The rats of other groups were subjected to mechanical ventilation for 4 hours.Seven days before mechanical ventilation,medication treatment was carried out once a day for seven days.After mechanical ventilation,ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin 6(IL-6)in bronchoalveolar lavage fluid(BALF).Lung wet/dry weight ratio and lung tissue pathology of rat were detected.The reagent kit was applied to detect the content of glutathione(GSH),malonaldehyde(MDA),and Fe2+in rat lung tissue.The relative fluorescence intensity of reactive oxygen species(ROS)and 4-hydroxynonenal(4-HNE)in lung tissue was detected by immunofluorescence staining.The mRNA and protein expressions of solute carrier family 7 member 11(SLC7A11),Nrf2,GPX4 were detected.Results Compared with the control group,the lung tissue of rats in model group was severely damaged,the levels of TNF-α and IL-6 in BALF increased,lung wet/dry weight ratio,content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE increased,but the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 decreased(P＜0.01).Compared with the model group,the pathological damage of lung tissue in the modified Taoren Chengqi Decoction group was improved,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,content of MDA and Fe2+,the relative fluorescence intensity of ROS and 4-HNE decreased,the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 increased(P＜0.01).However,an opposite trend for corresponding indicators in the ML385 group was found(P＜0.01).The pathological injury of lung tissue was alleviated,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE decreased,GSH content,the mRNA expression of Nrf2,SLC7A11 and GPX4,as well as the protein expression of Nrf2 and GPX4 increased in modified Taoren Chengqi Decoction+ML385 group(P＜0.01,P＜0.05).Compared with ML385 group,the pathological injury of lung tissue was alleviated,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,the content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE decreased,GSH content,the mRNA and protein expression of Nrf2,SLC7A11 and GPX4 increased in modified Taoren Chengqi Decoction+ML385 group(P＜0.01).Compared with the modified Taoren Chengqi Decoction group,the pathological damage in lung tissue of rats was intensified,the levels of TNF-α and IL-6 in BALF increased,lung wet/dry weight ratio,the content of MDA and Fe2+,the relative fluorescence intensity of ROS and 4-HNE increased,the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 decreased(P＜0.01)in modified Taoren Chengqi Decoction+ML385 group.Conclusion Modified Taoren Chengqi Decoction may improve rat VILI by activating the Nrf2/GPX4 pathway to inhibit ferroptosis.

Objective:To investigate the correlation between thyroid hormone resistance and hyperuricemia in euthyroid population.Methods:It was a cross-sectional study. A total of 548 euthyroid subjects who were hospitalized or underwent physical examination in the Heart Center and Health Management Center of the First Affiliated Hospital of Tsinghua University from January 2021 to December 2022 were selected. Thyroid function, uric acid, blood lipid and other indicators were collected in the subjects, and thyroid function parameters were calculated: thyroid-stimulating hormone index (TSHI), thyrotropin T4 resistance index (TT4RI), parametric thyroid feedback quantile-based index (PTFQI), free triiodothyronine/free thyroxine (FT3/FT4), the sum activity of peripheral deiodinases (SPINA-GD) and the secretory capacity of the thyroid gland (SPINA-GT). According to uric acid level, the subjects were divided into high uric acid group and normal group, the clinical characteristics and thyroid function parameters of the two groups were compared, the correlation between thyroid hormone resistance and hyperuricemia was further explored.Results:Compared with the normal group, male proportion (94.4% and 52.5%), smoking rate (5.2% and 21.3%), body mass index [(27.10±3.96) and (24.26±3.42) kg/m 2], waist-to-hip ratio [0.90(0.86, 0.94) and 0.86(0.80, 0.91)], serum creatinine [(85.50±12.27) and (73.77±28.79) μmol/L], total cholesterol [(5.08±0.99) and (4.72±0.86) mmol/L], triglyceride [2.10(4.40, 5.59) and 1.14(0.79, 1.67)mmol/L], low-density lipoprotein [(3.19±0.97) and (2.85±0.84) mmol/L] and homocystine [(15.07±9.13) and (12.50±10.85) μmol/L] were all higher in the high uric acid group, and the level of high-density lipoprotein [1.15(1.43, 2.88) and 1.39(1.16, 1.64) mmol/L] was lower (all P<0.05). In the aspect of thyroid hormone and thyroid function parameters, the FT4[16.90(5.40,17.95) and 16.00(14.30,17.80) pmol/L], FT3[5.56(5.25, 5.94) and 5.22(4.81, 5.63) pmol/L], FT3/FT4 [0.34(0.31, 0.37) and 0.32(0.29, 0.36)], TSHI (2.70±0.50 and 2.58±0.60), PTFQI (0.406±0.332 and 0.335±0.353) and SPINA-GD [3.72(3.41, 4.05) and 3.52(3.18, 4.00) ]were all higher in high uric acid group than those in normal group(all P<0.05). Spearman correlation analysis showed that blood uric acid level was positively correlated with FT4 ( r=0.185), FT3 ( r=0.422), FT3/FT4 ( r=0.16), TSHI ( r=0.134), TT4RI ( r=0.09), PTFQI ( r=0.121) and SPINA-GD ( r=0.157) (all P<0.05). Conclusion:In people with euthyroid function, central resistance to thyroid hormone is correlated with hyperuricemia.

Objective:To observe and analyze the clinical characteristics of children with autosomal dominant hereditary microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability syndrome (MCLMR).Methods:A retrospective clinical study. In September 2023, the first patient and three family members (parents, brother) of MCLMR who were diagnosed through ophthalmic examination and genetic testing at Department of Ophthalmology of Henan Children's Hospital were included in the study. Clinical data were collected, inquired about medical history and family history in detail, and performed best corrected visual acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography (FFA), flash visual evoked potential (F-VEP), full field electroretinogram (ERG), cranial magnetic resonance imaging (MRI), and systemic examination. 3 ml of peripheral venous blood were collected from the proband, her parents and younger brother, and extracted whole genome DNA. Second generation sequencing technology was used for gene sequencing. For suspected pathogenic sites, Sanger sequencing was used for validation, and bioinformatics analysis was performed to determine the pathogenicity of the genetic variant sites. The relevant literature of PubMed of the National Library of Medicine and Wan Fang Med Online by computer were searched. The genetic characteristics and conducted literature review were summarized.Results:The proband (Ⅱ-1) was an 8-year-old and 5-month-old female. Her head was relatively small, the lower jaw was small, the ears protrude, the nose was wide, the eyelid was tilted upwards, philtrum was long. Mild intellectual disability, no history of lymphedema. The BCVA values for the right and left eyes were 0.08 and 0.1, respectively. Bilateral nystagmus. Atrophic lesioned in the macular area and below choroid retina of both eyes. FFA examination showed mottled fluorescent staining in the macular area and the below retina, with no obvious fluorescein leakage in the late stage. OCT examination revealed shallow macular fovea morphology, absence of ellipsoidal bands, unclear layers, thinning of the entire retina, and significant atrophy of the choroid and retina beneath the macula. F-VEP examination, no waveform was detected in both eyes. Full field ERG examination showed severe reduction in amplitude of a wave and b wave in both eyes. Head magnetic resonance imaging showed widening of the subarachnoid space in the left temporal region, with no significant abnormal signals observed in the brain parenchyma. Her father (Ⅰ-1) had mild nystagmus and strabismus. The phenotypes of the eyes of the mother (Ⅰ-2) and brother (Ⅱ-2) were not significantly abnormal. The genetic testing results showed that the proband (Ⅱ-1) had a heterozygous missense mutation c.895A>G (p.Ile299Val) in exon 8 of the KIF11 gene, which was a known mutation. Her parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) were both wild-type. The bioinformatics analysis results indicated that this mutation is a potentially pathogenic variant. A total of 109 cases were retrieved from 20 relevant literatures. Among them, 55 were male, 54 were females. There were 61 cases with family history and 48 cases without family history, respectively. Among the 109 cases, 98 cases (89.9%, 98/109) had microcephaly, 2 cases had premature closure of cranial sutures, and 11 patients underwent cranial MRI, which showed 11 cases of small head with simplified development of the cerebral gyrus. 50 cases (45.9%, 50/109) of lymphedema. 83 cases (76.1%, 83/109) of intellectual developmental disorders. 92 cases (84.4%, 92/109) had ocular abnormalities, 69 cases (63.3%, 69/109) had chorioretinopathy, 20 cases (18.3%, 20/109) had retinal folds, 10 cases (9.2%, 10/109) had nystagmus, and 17 cases (15.6%, 17/109) had retinal detachment. Conclusions:The main clinical manifestations of MCLMR are microcephaly, chorioretinopathy, with or without lymphedema, and intellectual disability. The main manifestations of eye diseases are low vision, nystagmus, and chorioretinopathy. The heterozygous missense mutation c.895A>G (p.Ile299Val) in exon 8 of KIF11 gene is the pathogenic variant of this family.

Objective:To observe the clinical features of eyes in children with methylmalonic acidemia (MMA).Methods:A retrospective clinical case study. From June 2019 to June 2022, 13 children with MMA visited on the Department of Ophthalmology of Henan Children's Hospital were included in the study. The anterior segment and fundus were examined under surface or general anesthesia. Best corrected visual acuity (BCVA) and refraction were performed in 9 cases; fluorescein fundus angiography (FFA) was performed in 3 cases; flash electroretinogram (FERG) was performed in 6 cases; flash visual evoked potential (FVEP) was detected in 6 cases; optical coherence tomography (OCT) was performed in 3 cases.Results:Among the 13 pediatric patients with methylmalonic acidemia, 6 cases were male and 7 cases were female. The average age at first visit was 45 months. All cases suffered from hyperhomocysteinemia; 9 cases were with epilepsy; 2 cases were with infantile spasms; 11 cases were with stunting, 13 cases were with repeated pulmonary infection during growth period; 4 cases were with hydrocephalus; 1 cases was with hypertension and renal insufficiency. Genetic dectection results of 8 cases were recorded, MMACHC:c.609G>A:p.W203* mutation site was found in all cases. One case was accompanied by corneal ulcer. There were 10 cases with nystagmus, 4 cases with macular degeneration, 3 cases with hyperopic refractive error and esotropia. Nine cases underwent BCVA examination, BCVA was light perception-0.6. In OCT, 2 cases of 3 cases showed retinal thinning and photoreceptor cell layer atrophy in the macular area. In FFA, 2 cases of 3 cases showed circular transparent fluorescence in the macular area. Five cases of 6 cases who with FVEP had different degrees of P100 peak time delay and decreased amplitude, and 4 cases of 6 cases with FERG had decrease of a and b wave in light and dark adaptation. Conclusions:The clinical phenotypes of eyes in children with MMA are various and the severity was different; most of them are accompanied by nystagmus, and the fundus lesions are common in the characteristic bovine eye like macular region. Those with macular disease have severe visual impairment.

Objective To explore the impact of Jiawei Taoren Chengqi Decoction on autophagy in rats with mechanical ventilation-induced lung injury(VILI)through adenylate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Sixty SPF male rats were randomly grouped into the sham operation group,the model group,the low-dose Jiawei Taoren Chengqi Decoction group(TCM-L group,2.85 g/kg),the high-dose Jiawei Taoren Chengqi Decoction group(TCM-H group,8.55 g/kg)and the high-dose Jiawei Taoren Chengqi Decoction + AMPK inhibitor Compound C group(TCM-H+CC group,Jiawei Taoren Chengqi Decoction 8.55 g/kg+ Compound C 250μg/kg),12 in each group.Oxygenation index(OI)was measured immediately after intubation and at 1 h,2 h and 4 h after mechanical ventilation.Bronchoalveolar lavage fluid(BALF)was collected after mechanical ventilation,levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-18 in BALF were detected by enzyme-linked immunosorbent assay(ELISA).Rats were sacrificed,and lung tissue was taken to measure the wet/dry weight(W/D)ratio.HE staining was used to observe pathological changes of lung tissue in each group of rats.Lung injury scores were carried out.Morphology of alveolar epithelial cells was observed by transmission electron microscopy.RT-qPCR was applied to detect mRNA expression levels of AMPK and mTORC1 in rat lung tissue.Western blot assay was applied to detect expression levels of AMPK,p-AMPK,mTORC1,p-mTORC1 and autophagy-related proteins in rat lung tissue.Results Compared with the sham group,the pathological damage of lung tissue was serious,lung W/D,levels of TNF-α,IL-1β and IL-18 in BALF,lung injury score,mTORC1 mRNA expression level,and p-mTORC1 protein expression were increased in the model group(P＜0.05).OI values at 2 h and 4 h of mechanical ventilation,AMPK mRNA expression level,p-AMPK,LC3-II/LC3-I and Beclin-1 protein expression in lung tissue were decreased(P＜0.05).Compared with the model group,the pathological damage of lung tissue was alleviated in the Chinese medicine-H group,and the trend of changes in related indexes was opposite to the above(P＜0.05).Autophagosomes in alveolar epithelial cells were increased.Compound C attenuated the protective effect of Jiawei Taoren Chengqi Decoction on VILI rats(P＜0.05).Conclusion Jiawei Taoren Chengqi Decoction may promote autophagy and reduce VILI in rats by activating AMPK/mTOR signaling pathway.

Objectives:To verify the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of its clinical application.Methods:A convenience sampling method was used to collect 129 geriatric patients who underwent inguinal hernia surgery from January 2018 to January 2023 in nine hospitals in Liaoning Province. There were 120 males and 9 females, of whom 89 patients were 60 to <75 years old, 33 patients were 75 to <85 years old and 7 patients were ≥85 years old. The 129 patients included 11 elderly patients with inguinal hernia who had recovered from preoperative infection with COVID-19. Statistical methods such as Cronbach′s coefficient, Kaiser-Meyer-Olkin test, Bartlett′s test, Pearson′s correlation analysis, etc. were calculated to verify the reliability indexes such as feasibility, content validity, structural validity, criterion-related validity, internal consistency reliability, and re-test reliability. Taking the 5-item modified frailty index (5-mFI) as the gold standard, the area under the curve was used to analyze the ability of the two scales to predict the occurrence of postoperative acute urinary retention, postoperative delirium, poor incision healing, operative hematoma seroma, and postoperative complications.Results:The frailty assessment scale for elderly patients with inguinal hernia showed good reliability and validity (valid completion rate of 99.2%; item content validity index of 1.000, and the scale content validity index of 1.000; exploratory factor analysis extracted a total of 1 principal component, and factor loadings of each item of 0.565 to 0.873; the AUC for frailty diagnosis using 5-mFI as the gold standard of 0.795 ( P<0.01) Cronbach′s coefficient of 0.916, retest reliability coefficient of 0.926), it could effectively predict postoperative acute urinary retention, delirium, hematoma seroma in the operative area and total complications (AUC of 0.746, 0.870, 0.806, and 0.738, respectively; all P<0.05), and prediction efficiency was higher than that of 5-mFI (AUC of 0.694, 0.838, 0.626 and 0.641, P<0.05 for delirium only), but both scales were inaccurate in predicting poor incision healing (AUC of 0.519, P=0.913 for the frailty assessment scale and 0.455, P=0.791 for the 5-mFI). Conclusions:The frailty assessment scale for elderly patients with inguinal hernia is reliable and significantly predicts the occurrence of postoperative adverse events in elderly inguinal hernia patients. The scale can also be used for preoperative frailty assessment in elderly patients with inguinal hernia after rehabilitation from COVID-19 infection.

Objectives:To verify the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of its clinical application.Methods:A convenience sampling method was used to collect 129 geriatric patients who underwent inguinal hernia surgery from January 2018 to January 2023 in nine hospitals in Liaoning Province. There were 120 males and 9 females, of whom 89 patients were 60 to <75 years old, 33 patients were 75 to <85 years old and 7 patients were ≥85 years old. The 129 patients included 11 elderly patients with inguinal hernia who had recovered from preoperative infection with COVID-19. Statistical methods such as Cronbach′s coefficient, Kaiser-Meyer-Olkin test, Bartlett′s test, Pearson′s correlation analysis, etc. were calculated to verify the reliability indexes such as feasibility, content validity, structural validity, criterion-related validity, internal consistency reliability, and re-test reliability. Taking the 5-item modified frailty index (5-mFI) as the gold standard, the area under the curve was used to analyze the ability of the two scales to predict the occurrence of postoperative acute urinary retention, postoperative delirium, poor incision healing, operative hematoma seroma, and postoperative complications.Results:The frailty assessment scale for elderly patients with inguinal hernia showed good reliability and validity (valid completion rate of 99.2%; item content validity index of 1.000, and the scale content validity index of 1.000; exploratory factor analysis extracted a total of 1 principal component, and factor loadings of each item of 0.565 to 0.873; the AUC for frailty diagnosis using 5-mFI as the gold standard of 0.795 ( P<0.01) Cronbach′s coefficient of 0.916, retest reliability coefficient of 0.926), it could effectively predict postoperative acute urinary retention, delirium, hematoma seroma in the operative area and total complications (AUC of 0.746, 0.870, 0.806, and 0.738, respectively; all P<0.05), and prediction efficiency was higher than that of 5-mFI (AUC of 0.694, 0.838, 0.626 and 0.641, P<0.05 for delirium only), but both scales were inaccurate in predicting poor incision healing (AUC of 0.519, P=0.913 for the frailty assessment scale and 0.455, P=0.791 for the 5-mFI). Conclusions:The frailty assessment scale for elderly patients with inguinal hernia is reliable and significantly predicts the occurrence of postoperative adverse events in elderly inguinal hernia patients. The scale can also be used for preoperative frailty assessment in elderly patients with inguinal hernia after rehabilitation from COVID-19 infection.

Platinum anti-tumor drugs are currently the most widely used first-line chemotherapeutic drugs in clinical practice, and their curative effects are remarkable. However, the problems of platinum drug resistance in non-small cell lung cancer, breast cancer, ovarian cancer and others seriously limit effectiveness and clinical application of platinum drugs. The occurrence of platinum drug resistance is caused by many factors. At present, the resistance mechanism of platinum drugs mainly includes the following aspects: decreasing the accumulation of platinum in cells, increasing the inactivation of platinum in cells, repairing DNA damage and tumor cell apoptosis inactivation. This article reviews the drug resistance mechanism and coping strategy of platinum anti-tumor drugs, providing ideas for the development of platinum anti-tumor drugs and references for overcoming clinical platinum drug resistance.

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence