Objective:To investigate interleukin-37 (IL-37) expression in patients with diabetic kidney disease (DKD), and to assess the regulation of exogenous IL-37 on CD8 + T cell function in DKD patients. Methods:A cross-section study was carried out. Twenty healthy controls, thirty-six patients with diabetes mellitus type 2 (T2DM), and forty-seven DKD patients were enrolled in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble IL-1 receptor 8 (IL-1R8) levels in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-18 receptor α chain (IL-18Rα), IL-1R8 and immune checkpoint molecules levels in CD8 + T cells were measured by flow cytometry. CD8 + T cells were purified, and were stimulated with recombinant IL-37. CD8 + T cells were co-cultured with HEK293 cells in either direct contact or indirect contact manner. Levels of perforin, granzyme B, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The proportion of target cell death was assessed by measuring lactate dehydrogenase level. Results:Plasma IL-37 levels in DKD patients [(63.42±23.30) ng/L] were significant lower than those in healthy controls [(143.02±50.67) ng/L] and T2DM patients [(87.88±40.62) ng/L] ( t=8.848, P<0.001; t=3.456, P<0.001). Plasma IL-37 level had good predictive values for T2DM in health individuals and for DKD in T2DM patients [the area under the curve was 0.797 (95% CI 0.676-0.917, P<0.001) and 0.691 (95% CI 0.576-0.807, P=0.003), respectively]. Plasma IL-37 level was negatively correlated with urea nitrogen ( r=-0.313, P=0.032) and creatinine ( r=-0.477, P<0.001), and positively correlated with estimated glomerular filtration rate (eGFR) ( r s=0.478, P<0.001) in DKD patients. IL-1R8 + CD8 + cell proportion in DKD patients (33.60%±9.47%) was significantly higher compared to healthy controls (16.29%±5.97%) and T2DM patients (17.13%±4.85%) ( t=7.545, 9.516, both P<0.001), but did not correlate with fast blood glucose, urea nitrogen, creatinine, or eGFR (all P>0.05). There were no statistical differences of IL-18Rα + CD8 + cell proportion, soluble IL-1R8 level, or immune checkpoint molecule proportion in CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). Perforin and granzyme B secretions by CD8 + T cells were significantly elevated in DKD patients compared with healthy controls [(108.78±12.42) ng/L vs. (94.60±10.07) ng/L, t=3.096, P=0.005; (261.34±48.79) ng/L vs. (166.28±30.80) ng/L, t=3.387, P=0.002] and T2DM patients [(108.78±12.42) ng/L vs. (92.58±14.71) ng/L, t=3.263, P=0.003; (261.34±48.79) ng/L vs. (170.66±39.24) ng/L, t=2.627, P=0.014]. There were no significant differences of either IFN-γ or TNF-α secretions by CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). In direct contact co-culture manner, CD8 + T cell-induced HEK293 cell death was down- regulated (13.03%±4.97% vs. 17.88%±5.19%, t=2.235, P=0.037). The levels of perforin [(222.02±25.79) ng/L vs. (294.30±25.58) ng/L, t=6.603, P<0.001], granzyme B [(416.27±90.24) ng/L vs. (524.71±115.53) ng/L, t=2.454, P=0.023], IFN-γ [(23.66±4.20) ng/L vs. (35.18±8.51) ng/L, t=4.026, P<0.001] and TNF-α [(1.62±0.29) μg/L vs. (2.09±0.57) μg/L, t=2.302, P=0.034] were also reduced as well. In indirect contact co-culture manner, there were no significant differences of CD8 + T cell-induced HEK293 cell death, perforin, or granzyme B levels between no stimulation and IL-37 stimulation (all P>0.05). IFN-γ and TNF-α levels in the supernatants were reduced in response to IL-37 stimulation [(23.56±6.24) ng/L vs. (32.56±9.90) ng/L, t=2.550, P=0.019; (1.41±0.31) μg/L vs. (2.10±0.44) μg/L, t=4.011, P<0.001]. Conclusion:IL-37 level is reduced in DKD patients.Exogenous IL-37 suppresses the cytotoxicity of CD8 + T cells in DKD patients.

Goniotomy (GT) is a safe and effective type of minimally invasive glaucoma surgery (MIGS) extensively utilized in China.It is particularly suited for treating primary open-angle glaucoma and advanced primary angle-closure glaucoma.Although GT is generally safe, hyphema and postoperative intraocular pressure (IOP) spikes remain common complications after GT.Currently, there is no standardized protocol for managing these issues, which can impact clinicians' assessment of surgical outcomes and potentially affect the prognosis.Therefore, it is crucial to establish comprehensive and detailed management protocols for perioperative hyphema and IOP spike following GT.This will guide clinical practitioners in managing complications appropriately and systematically, thereby promoting the further development and refinement of MIGS.To address these concerns, several domestic glaucoma treatment experts along with members of the Glaucoma Society of Ophthalmology, Guangdong Medical Association reviewed existing literature and held recommendation meetings to develop a guideline for managing perioperative hyphema and IOP spikes following GT.It includes defining perioperative hyphema in GT, discussing its high-risk factors and outcomes, exploring methods for prevention prior to surgery and techniques to reduce bleeding during the procedure, and managing postoperative hemorrhage.Additionally, it covers defining IOP spikes after GT, investigates their causes and contributing factors, and outlines management strategies and anticipated outcomes to provide a valuable resource for clinicians.

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.

Objective:To investigate the injury effect of hyperoxali acid on human arterial endothelial cells (HAECs) and its mechanism.Methods:HAECs were divided into intervention group and control group according to whether oxalic acid was used for intervention. The cells in the intervention group were stimulated with 30, 100, 200 and 300 μmol/L oxalic for different time. The effect of oxalic acid on the proliferation of HAECs was detected by MTT colorimetry. The change of cell cycle was analyzed by flow cytometry. The content of intracellular calcium was detected by fluorescence detection technology. The protein and mRNA expressions of cell cycle and anion transporter-related proteins were detected by Western blotting and fluorescence quantitative PCR. Besides, JAK2/STAT3 signaling pathway-related proteins were measured by Western blotting.Results:MTT colorimetry results showed that the intervention groups with high concentration of oxalic acid (100, 200, 300 μmol/L) could significantly inhibit the proliferation of HAECs, which was significantly different from the control group (all P<0.05). Fluorescence detection showed that the contents of intracellular calcium of HAECs in the intervention groups with high concentration of oxalic acid (100, 200, 300 μmol/L) were significantly higher than those in the control group after 48 hours ( P<0.05, P<0.001, P<0.001, respectively). Flow cytometry showed that the proportion of S phase of cells in the 200 μmol/L oxalic acid intervention group was significantly higher than that in the control group ( P<0.05). The results of Western blotting and PCR showed that the relative protein and mRNA expressions of anion transporter-related proteins slc26a1, slc26a5, slc26a11 in the intervention groups were higher than those in the control group (all P<0.05). Western blotting showed that the expression of p-JAK2 and p-STAT3 in the intervention groups after 24 hours were significantly higher than those in control group (all P<0.05). Conclusions:Hyperoxalic acid may enter HAECs through transporters slc26a1, slc26a5 and slc26a11 to inhibit cell proliferation and increase the intracellular calcium concentration. The mechanism may be through the activation of JAK2/STAT3 signaling pathway. Therefore, oxalic acid may be one of the uremic toxins leading to atherosclerosis.

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.

Objective: To analyze the immune responses of bone-marrow derived macrophages and osteoclasts to lipopolysaccharide from Porphyromonas gingivalis (Pg-LPS) so as to provide reference for host immunomodulatory therapy of periodontitis. Methods: Bone marrow mononuclear cells from C57BL/6 mice were obtained and induced into bone marrow macrophages (BMM) and osteoclasts (OC) by conditioned medium. The BMMs and OCs were divided into blank control group and Pg-LPS treated experimental group. Pg-LPS (10 μg/ml) was used to stimulate BMM and OC. The mRNA and protein expression of TLR-2 and TLR-4 and secretion of inflammatory cytokines were detected, respectively. Furthermore, the effect of Pg-LPS on the differentiation of BMM into OC was evaluated. Results: Mouse bone marrow mononuclear cells were successfully induced into BMM and mature OC. In the presence of Pg-LPS, the gene level of TLR-2 in BMM was significantly up-regulated by (41.41±13.07) folds (P<0.01), while the level of TLR-4 mRNA was not significantly changed. TLR-2 mRNA and TLR-4 mRNA levels in OC increased by (2.24±0.23) times (P<0.05) and (4.83±1.07) times (P<0.01), respectively. Flow cytometry results showed that TLR-2 protein expression in BMM was robustly enhanced (P<0.01), as mean fluorescence intensities (MFI) were (39.85±5.27) in blank group and (221.57±13.13) in experimental group, respectively. The MFI of TLR-2 in OC also increased as (83.31±2.69) in blank group and (108.65±6.32) in experimental group, respectively (P<0.01). However, no significant TLR-4 expressions were observed in both BMM and OC (P>0.05). Moreover, the productions of tumor necrosis factor-α and interleukin-6 in response to LPS in BMM and OC remarkably increased (P<0.01). Lower cytokine expression was observed in OC than that in BMM (P<0.01). In addition, Pg-LPS obviously inhibited the number and size of OC formation, with a reduction in area percentage of approximately 47%. Conclusions Pg-LPS generated a robust immune inflammatory response to BMM, while OC had a relatively weaker immune response to the Pg-LPS. Pg-LPS might inhibite the differentiation of BMM into OC.

Objective To study the clinical value of whole －body magnetic resonance diffusion weighted imaging(WB－DWI) in evaluating the chemotherapy response for lung cancer,thus to provide evidence for optimizing clinical imaging examination. Methods From October 2017 to May 2018,60 patients with lung cancer confirmed by histopathology in Linfen Central Hospital were selected. The patients underwent DWI examinations before chemotherapy and after two cycles of chemotherapy. The change of tumor size,distant metastasis and apparent diffusion coefficient (ADC) value were compared before and after chemotherapy. The correlation between the change rate of ADC value and the shrinkage rate of tumor size in the effective group was analyzed. Results Of 60 cases,1 case had new cerebral metastases after chemotherapy. There were statistically significant differences in ADC value [(1. 12 ± 0.33) ×10 －3mm2/svs.(1.56±0.40) ×10 －3mm2/s]andtumorsize[(4.63±2.75)cmvs.(2.28±1.45)cm] between before and after chemotherapy in the effective group(t= －3. 954,4. 711,all P＜0. 01). There was correlation between the change of ADC value and tumor size(r=0. 34,P＜0. 05). Conclusion WB－DWI can not only detect the change of tumor size and distant metastasis quickly and effectively,but also can observe the microscopic changes of tumor cells by measuring ADC value. So it can predict the early therapeutic response of the tumor and make effective evaluation for the staging and chemotherapy response of lung cancer.

Objective: To compare the clinical efficacy and drug safety between oral apatinib combined with conventional chemotherapy and conventional chemotherapy alone for the treatment of osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis. Methods: Thirty-three osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis who were treated in the Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University from January 2015 to December 2017 were enrolled in this study. Patients with osteosarcoma received methotrexate, adriamycin (ADM), cisplatin (CDDP), ifosfamide (IFO) sequential regimen; patients with soft tissue sarcoma were treated with IFO and ADM regimen. Eighteen of these patients received an additional oral dose of apatinib. The patients were followed up regularly for changes in primary tumors and metastases, adverse reactions and prognosis. Results: Before treatment, the maximum diameter of pulmonary metastases in patients of apatinib group and routine treatment group were (4.46±1.70) cm and (4.53±2.00) cm, respectively, without significant difference (P=0.909). After treatment, the maximum diameter of pulmonary metastases in patients of apatinib group was (1.46±1.39) cm, significantly smaller than (3.02±1.20) cm of routine treatment group (P=0.002). After treatment, the maximum diameter of the primary lesions in the apatinib group and the conventional treatment group median decreased 0.31 cm and 0.12 cm, respectively, without significant difference (P=0.542). After treatment, the maximum diameter of the lung metastases in the apatinib group median decreased 0.59 cm, significantly more than 0.18 cm of the conventional treatment group (P=0.027). The median progression-free survival (PFS) was 9.4 months in the 33 patients. The median PFS was 9.6 months and 8.3 months in the apatinib group and the conventional treatment group, respectively, without significant difference (P=0.593). Specific adverse reactions both occurred in apatinib group and routine treatment group, mainly including oral mucosal reactions and digestive tract reactions (including nausea, vomiting and diarrhea). Conclusions Apatinib can effectively reduce the volume of primary and metastatic lesions in patients with bone and soft tissue sarcoma accompanied by lung metastasis without reducing the survival rate or causing uncontrollable adverse reactions. The safety and clinical efficacy of apatinib are significant.