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.

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.

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 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.

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.

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 explore the predictive value of methylenetetrahydrofolate reductase(MTHFR)gene C677T polymorphism and serum homocysteine(Hcy)level for adverse pregnancy outcomes.Methods The clinical data of 698 pregnant women who received antenatal care and deliv-ered at Ji'an Central People's Hospital were retrospectively collected.According to the research pur-pose,the pregnant women were divided into internal study cohort(n=483)or external validation co-hort(n=215).Each cohort was further divided into adverse pregnancy group and normal pregnancy group based on whether adverse pregnancy outcomes occurred.The MTHFR gene C677T polymor-phism and serum Hcy level of all pregnant women were detected.Binary Logistic regression analysis was used to investigate the relationships of MTHFR gene C677T polymorphism,Hcy level,and other indicators with adverse pregnancy outcomes.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive efficacy of different indicators when used alone and their combina-tion.Results In the internal study cohort,compared with the normal pregnancy group,the detection frequency of the CC genotype at the MTHFR gene C677T locus was lower,while the detection frequencies of the CT and TT genotypes were higher in the adverse pregnancy group(P＜0.001).The proportion of pregnant women with high Hcy levels was higher in the adverse pregnancy group than that in the normal pregnancy group(P＜0.001).Binary Logistic regression analysis showed that age,folic acid level during pregnancy,MTHFR gene C677T polymorphism,and Hcy level were all independ-ent influencing factors for adverse pregnancy outcomes(P＜0.05).The ROC curve indicated that the area under the curve(AUC)of the combined prediction model was 0.938,which was greater than that of each indicator.In the external validation cohort,the AUC of the combined prediction model was 0.917,validating the stability and clinical applicability of the model.Conclusion The TT and CT genotypes at the MTHFR gene C677T locus and high Hcy level are all independent risk factors for adverse pregnancy outcomes.The prediction model constructed by combining these factors with age and folic acid level during pregnancy has a high predictive efficacy for adverse pregnancy outcomes.

Objective To investigate the effects of goal-directed fluid therapy(GDFT)based on pulse pressure variation(PPV)on postoperative cognitive function in patients undergoing Da Vinci robot-assisted radical resection of gynecological malignancies.Methods A total of 60 patients who underwent robot-assisted radical resection of gynecological malignancies were randomly divided into control group and observation group using a random number table method,with 30 patients in each group.The control group received conventional fluid replacement regimen,while the observation group received GDFT regimen based on PPV.The surgical conditions,hemodynamic indices[heart rate(HR),mean arterial pressure(MAP),PPV],cerebral oxygen saturation(rSO2),gastrointesti-nal function,renal function,cognitive function[Mini-Mental State Examination(MMSE)score],and postoperative conditions of the two groups were compared.Results The amount of crystalloid fluid and urine output in the observation group were less than those in the control group,while the amount of colloid fluid was more than that in the control group,with statistically significant differences(P＜0.05).Five minutes after anesthesia induction,the levels of MAP,HR and rSO2 in the observation group were higher than those in the control group,with statistically significant differences(P＜0.05).Five minutes after anesthesia induction,1 hour after the Trendelenburg position,and imme-diately after the end of surgery,the PPV levels in the observation group were lower than those in the control group,with statistically significant differences(P＜0.05).After surgery,the levels of lactic acid and urea nitrogen in both groupswere higher than those before surgery,but those in the observa-tion group were lower than those in the control group,with statistically significant differences(P＜0.05).After surgery,the creatinine levels in both groups were lower than those before surgery,but those in the observation group were higher than those in the control group,with statistically signifi-cant differences(P＜0.05).The time to first flatus in the observation group was earlier than that in the control group,with a statistically significant difference(P＜0.05).On days 3,7 and 30 after surgery,the MMSE scores in the observation group were higher than those in the control group,with statistically significant differences(P＜0.05).The drainage tube indwelling time and hospital stay in the observation group were shorter than those in the control group,with statistically significant differences(P＜0.05).There was no statistically significant difference in the overall incidence of postoperative complications between the two groups(P＞0.05).Conclusion GDFT based on PPV can stabilize the hemodynamic status and rSO2 in patients undergoing Da Vinci robot-assisted radical resection of gynecological malignancies and reduce postoperative cognitive impairment.