Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

This paper analyzes the treatment process of a patient who developed severe acute respiratory distress syndrome (ARDS) following a chemical leak of dimethyl sulfate caused by factory operational error in February 2023, and explores the efficacy of extracorporeal membrane oxygenation (ECMO) in patient management. The patient developed severe respiratory symptoms five hours after chemical exposure and received sequential treatment with nasal high-flow oxygen therapy and invasive mechanical ventilation upon admission. When the oxygenation index dropped below 100 mmHg, veno-venous (VV) ECMO was initiated alongside 12-hour daily prone position ventilation to improve oxygenation and lung compliance. The patient recovered and was discharged following treatment. For patients with dimethyl sulfate poisoning complicated by severe ARDS, early implementation of VV-ECMO significantly improves treatment outcomes and prognosis.

Objective To establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics. Methods Allogeneic BALB/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed. Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment [(28.2±4.1) d vs. (7.0±0.7) d, P < 0.01]. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation and worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells. Conclusions Mouse allogeneic heart transplantation combined with CTLA4-Ig successfully establishes a CR model, which provides a basis for subsequent studies on the pathogenesis and intervention of CR.

Objective To analyze the clinical significance of subjective visual vertical (SVV) tests at different head deflection angles in assessing utricle function in patients with benign paroxysmal positional vertigo (BPPV). Methods A total of 61 BPPV patients who were treated at the Hearing Impairment and Vertigo Diagnosis and Treatment Center of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2022 to May 2023 were retrospectively included, and 29 healthy adults were selected as controls. SVV tests were performed on all research subjects at different head deflection angles: upright head (0°), left head 45° (L45°), right head 45° (R45°). The test results between the two groups were compared. Results SVV absolute value at R45° in BPPV group was lower than that in the control group (P＝0.003); there was no significant difference in SVV values at 0° and L45° between the two groups. There was no statistical difference in SVV values at different head deflection angles between the control group and the left BPPV group. SVV absolute value at R45° in right BPPV group was lower than that in the control group (P＜0.001); there was no statistical difference in SVV values at 0° and L45° between the two groups. Conclusions SVV test can provide subjective information about the utricle, and SVV tests at different head deflection angles can fine-tune evaluate the function of the utricle in BPPV patients.

Objective To establish a rat model of acute antibody-mediated rejection (AMR) in kidney transplantation and investigate the preventive effect of dihydroartemisinin (DHA) on acute AMR. Methods BN rats were used as donors and Lewis rats as recipients. Kidney transplantation was performed 2 weeks after skin transplantation for sensitization. After establishing the acute AMR model in rat kidney transplantation, the recipients of experimental groups included the syngeneic kidney transplantation group (6 rats), the allogeneic kidney transplantation group (6 rats), the syngeneic skin transplantation followed by kidney transplantation group (12 rats), and the allogeneic skin transplantation followed by kidney transplantation group (24 rats). The groups for investigating the preventive effect of DHA on acute AMR included the control group (allogeneic skin transplantation followed by kidney transplantation) and the DHA group (allogeneic skin transplantation followed by kidney transplantation + DHA), with 12 rats in each group. The survival time of recipient rats, serum donor-specific antibody (DSA) levels and graft pathological changes were used to identify the acute AMR model. On this basis, DSA levels, pathological changes in the transplant kidneys and peripheral blood B-cell levels were detected to assess the preventive effect of DHA on acute AMR. Results Compared with the allogeneic kidney transplantation group, skin transplantation sensitization significantly shortened the survival time of recipient rats (P<0.01). Compared with the syngeneic skin transplantation followed by kidney transplantation group, the allogeneic skin transplantation followed by kidney transplantation group showed significantly elevated serum DSA-IgG levels from 7 days after skin transplantation to 5 days after kidney transplantation (P<0.01), and significantly elevated DSA-IgM levels at 7 and 14 days after skin transplantation(all P<0.01). The transplant kidneys in the allogeneic skin transplantation followed by kidney transplantation group showed a small number of inflammatory cell infiltrations, tubular necrosis, capillaritis, and C4d deposition starting from 1 day after kidney transplantation, with these pathological changes worsening as the post-transplantation days increased. The kidney damage became significant starting from 3 days after transplantation. The above pathology manifestations were consistent with the characteristics of acute AMR. On the basis of establishing the acute AMR model, DHA treatment significantly prolonged the survival time of recipient rats (P<0.01) , and reduced serum DSA-IgG and DSA-IgM levels. DHA treatment significantly alleviated the pathological manifestations of acute AMR, including kidney damage, inflammatory cell infiltration, capillaritis and tubular necrosis, and also reduced C4d deposition in the transplant kidneys, inflammatory cell infiltration and peripheral blood CD19⁺ B-cell levels. Conclusions An acute AMR model is established by performing kidney transplantation 2 weeks after allogeneic skin transplantation in rats. It is discovered that DHA has immunosuppressive effects and may effectively prevent acute AMR, which provides a new strategy for the management of clinical AMR.

This study aims to inquire about the fluctuations of ubiquitin-specific protease 47 on neu-roblastoma cells(Neuro-2a,N2a)infected by rabies virus(RABV).USP47 expression levels were detected after RABV infection in N2a cells through RT-qPCR,protein immunoblotting,and virus titer determination.The levels of RABV nucleoprotein and phosphoprotein gene and protein,and RABV titers in supernatants were analyzed during overexpression and knockdown of USP47.The results showed that RABV infection increased USP47 gene level in N2a cells.When overexpression of USP47,the levels of RABV N and P were increased,and the virus titers were also improved.Mo-reover,the level of interleukin-6(IL-6)genes decreased.Knocking down USP47 expression reduced levels of RABV N and P genes and proteins,lowered the virus titer,and elevated the IL-6 gene lev-el.The results suggest that USP47 promotes RABV infection and suppresses IL-6 expression.This finding lays the foundation for further investigation into the molecular mechanisms by which USP47 regulates RABV infection.

The rabies virus(RABV)that causes rabies mainly attacks the peripheral and central nervous systems.In the later stages of infection,it is scattered in the salivary glands and transmit-ted to other susceptible animals through infectious saliva.To study dispersion of the RABV in the three pairs of salivary gland tissues,the street strain PB4 of the RABV was inoculated into 21-day-old female mice through the hind limb muscles.During the moribund stage of the mice,the sublin-gual gland,submandibular gland and parotid gland were collected,respectively.The TCID50 titer of RABV in the three kinds of glands of the mice and the copy number of the RABV N gene were de-tected,and RABV in different salivary glands was observed by immunofluorescence.The results showed that PB4 was dispersed in all three kinds of salivary glands of the mice,with the largest a-mounts in the parotid gland,followed by the submandibular gland,and the lowest amount in the sublingual gland.Three-month-old dogs were inoculated with PB4 through the cranial cavity,and saliva were collected every 12 h after inoculation.The saliva samples were detected by TCID50 and RT-qPCR.And during the moribund stage of the dogs when the disease occurred,the three pairs of salivary glands were collected.Through the determination of the TCID50 titer,RT-qPCR and immu-nofluorescence detection,it was demonstrated that among the three different salivary glands of the dogs,the largest amount of PB4 was found in the parotid gland and the lowest in the sublingual gland.Our results in mice and dogs clearly proved that the parotid gland was consistently found to exhibit the highest content of street RABV among the three major salivary glands,which could en-rich experimental data for analyzing the dispersion of RABV in the salivary glands and interpreta-tion of the intermittent secretion of saliva in clinically rabid dogs.

BACKGROUND:More and more scholars are investigating the mechanism of hypoxia-inducible factor-1α in regulating bone homeostasis and oral and maxillofacial diseases to provide new targets and strategies for the treatment of related disorders,but there is no relevant review.OBJECTIVE:To summarize the regulatory potential of hypoxia-inducible factor-1α in a variety of oral and maxillofacial diseases and bone homeostasis with the aim of providing a new research direction for oral and maxillofacial bone tissue engineering.METHODS:A literature review was conducted in databases such as PubMed,Web of Science and CNKI,for articles Published from 2003 to 2024.The keywords were"hypoxia inducible factor-1α,oral cavity,bone formation,osteoclast,angiogenesis,oxidative stress,tissue engineering,periodontitis,pulpitis,temporomandibular joint osteoarthritis"in Chinese and English.Finally,84 articles were included for review.RESULTS AND CONCLUSION:(1)Hypoxia-inducible factor-1α is essential in promoting bone tissue regeneration,facilitating osteogenic-angiogenic coupling,and mitigating damage from oxidative stress in bone tissue.(2)Increasing levels of hypoxia-inducible factor-1α in tissue cells reduces inflammation in periodontitis and promotes periodontal tissue remodeling,pulp regeneration,and involves in joint remodeling after temporomandibular joint osteoarthritis.(3)By stabilizing the level of hypoxia-inducible factor-1α in tissue cells,the micronutrient-carrying biomaterial promotes bone marrow mesenchymal stem cells to migrate and attach to the bone defect area,coupling angiogenesis and osteogenesis to achieve bone regeneration.(4)How to increase the level of hypoxia-inducible factor-1α in oral and maxillofacial tissues using bioactive materials to achieve bone regeneration at maxillofacial bone defects remains to be investigated.

Objective::To analyze fetal renal abnormality genetic features and the prenatal characteristics of the 17q12 microdeletion syndrome.Methods::This prospective cohort study examined prenatal ultrasound findings of renal abnormalities in pregnant women who underwent single nucleotide polymorphism (SNP) array or copy number variation sequencing (CNV-seq) testing on amniotic fluid or fetal tissue at Tianjin Central Obstetrics and Gynecology Hospital between January 2016 and August 2022. The study cohort comprised women with advanced maternal age, fetal ultrasound anomalies, high-risk non-invasive prenatal testing results, or suspected 17q12 microdeletion syndrome. Comprehensive clinical data, including maternal age, detailed ultrasound findings, and pregnancy outcomes, were systematically collected. SNP-array analysis was conducted using an Affymetrix CytoScan 750 K Array Chip to identify CNVs and loss of heterozygosity, while CNV-seq was performed on the Illumina HiSeq 2000 platform. Detected variants were classified according to the American College of Medical Genetics and Genomics guidelines. Statistical analyses were performed using SPSS version 27.0.Results::Abnormal renal development was identified in 141 patients, among whom 26 exhibited hyperechogenic kidneys (HCK). Of these, 12 cases were associated with 17q12 microdeletion syndrome, while the remaining 14 were linked to other chromosomal abnormalities. When excluding patients with HCK, those diagnosed with polycystic kidney disease demonstrated a higher prevalence of chromosomal abnormalities compared to those with multicystic dysplastic kidney and renal dysplasia. Although isolated conditions such as horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney typically presented with normal chromosomal findings, the incidence of chromosomal abnormalities increased when these conditions coexisted with other anomalies. A detailed analysis of the correlation between 17q12 microdeletion syndrome and HCK revealed that 12 out of the 14 patients diagnosed with 17q12 microdeletion syndrome exhibited HCK. Genetic testing confirmed the syndrome in seven patients, with five cases attributed to novel mutations and two cases resulting from inherited mutations.Conclusion::Fetal HCK was closely associated with the 17q12 microdeletion syndrome, and polycystic kidney disease showed a higher rate of chromosomal abnormalities. Chromosome test results were mostly normal in patients with other renal abnormalities, such as kidney dysplasia, horseshoe kidneys, hydronephrosis, kidney deficiency, and ectopic kidneys. Prenatal diagnosis is recommended, especially in cases of non-isolated fetal renal abnormalities. This study provides strong evidence supporting a link between fetal renal abnormalities and genetic syndromes.

Objective:To investigate the influences of paeonol(PAE)on balance of Th17/Treg in autoimmune thyroiditis(AIT)rats by regulating high-mobility group box 1(HMGB1)/receptor for advanced glycation end product(RAGE)signal axis.Methods:Eighty-four rats were randomly divided into control group(NC group),Model group,low-dose PAE group(PAE-L group,8 mg/kg),medium-dose PAE group(PAE-M group,16 mg/kg),high-dose PAE group(PAE-H group,32 mg/kg),selenious yeast group(SY group,36 μg/kg)and PAE-H+rHMGB1(HMGB1 activator)group(32 mg/kg+8 μg/kg),with 12 rats in each group.Except for NC group,AIT models were established in other groups,and after successful modeling,rats were administered once a day for 6 weeks.ELISA was applied to detect the levels of thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb),free triiodothyro-nine(FT3),free thyroxine(FT4),IL-17 and IL-10 in rat serum;flow cytometry was applied to detect ratios of Th17,Treg,Th17/Treg in peripheral blood of rats in each group;HE staining was applied to detect pathological changes of thyroid tissue in rats;qRT-PCR was applied to detect expression levels of retinoic acid-related orphan receptor γt(RORγt)and forkhead box protein P3(Foxp3)mRNA in rat thyroid tissue;Western blot was applied to detect expressions of HMGB1 and RAGE proteins in thyroid tissue of rats.Results:Compared with NC group,pathological damages of thyroid tissue in Model group were serious,TPOAb,TGAb,FT3,FT4,IL-17 levels,Th17 ratio,Th17/Treg,RORγt mRNA level,HMGB1 and RAGE protein expressions were increased,while IL-10 level,Treg ratio,and Foxp3 mRNA level were decreased(P<0.05);compared with Model group,pathological damages of thyroid tissue in PAE-L group,PAE-M group,PAE-H group and SY group were reduced,TPOAb,TGAb,FT3,FT4,IL-17 levels,Th17 ratio,Th17/Treg,RORγt mRNA level,HMGB1 and RAGE protein expressions were decreased,while IL-10 level,Treg ratio,and Foxp3 mRNA level were increased(P<0.05);rHMGB1 attenuated the promotion of high dose PAE on Th17/Treg balance in AIT rats.Conclusion:PAE may promote Th17/Treg balance in AIT rats by inhibiting HMGB1/RAGE pathway.