The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Systemic lupus erythematosus(SLE)is characterized by a large number of anti-autoantibodies produced by abnormally activated B cells,which form immune complexes with autoantigens to induce systemic inflammation,leading to the involvement of multiple systems and organs.Existing treatment strategies targeting B cells(such as belimumab,telitacicept,and rituximab)had limited efficacy.Recently,CD 19 targeting chimeric antigen receptor(CAR)-T cell has shown excellent efficacy in the treatment of SLE.However,autologous CAR-T cell therapy has potential risks such as cytokine release syndrome(CRS),T cell tumors,and infections,and it is expensive.CAR-natural killer(NK)cell therapy,on the other hand,is an off-the-shelf cellular therapy with high safety,no neurotoxicity or tumorigenic risk,and with low treatment costs.Currently,CAR-NK cell has achieved remarkable research results in treating hematological malignancies,and preliminary clinical studies of CAR-NK cell therapy for SLE have showed good efficacy,excellent safety,and predictable durability.This article focuses on the characteristics of the new generation of universal CAR-NK cell and the latest clinical research results for the treatment of relapsed and refractory SLE,offering insights into its promising future in the treatment of SLE and B-cell-related autoimmune diseases.

Objective Aiming at improving biomechanical strength of the anastomotic stoma as well as reducing tissue thermal damage, a novel radiofrequency (RF) tissue welding electrode was developed. Methods A novel electrode with a hollow structure on the surface ( the plum electrode) was designed and the ring electrode was used as control group to conduct the welding of intestinal tissues based on RF energy. Biomechanical properties of anastomotic stoma were studied by shear test and burst pressure test. The tissue thermal damage during welding was investigated by finite element electro-thermal-mechanical multi-field coupling simulation analysis and thermocouple probe, and the tissue microstructures were also studied. Results Under 120 W RF energy, 8 s welding duration and 20 kPa compression pressure, the anastomotic stoma had the optimal biomechanical properties. Compared with the ring electrode group, biomechanical strength of the anastomotic stoma in plum electrode group was higher, with the shear strength and burst pressure increasing from (9. 7±1. 47) N, (84. 0±5. 99) mmHg to (11. 1±1. 71) N, (89. 4±6. 60) mmHg, respectively. There was a significant reduction in tissue thermal damage, and intact and fully fused stomas could be formed in anastomotic area. Conclusions The proposed novel electrode could improve biomechanical strength of the anastomosis as well as reduce tissue hermal damage, thus achieve better fusion. The research result provide references for realizing the seamless connection of human lumen tissues

Objective:To compare the clinical features between chronic active Epstein-Barr virus infection(CAEBV) and infectious mononucleosis(IM)in adult patients.Methods:Clinical data from 56 adult IM patients and 14 adult CAEBV patients admitted in the First Affiliated Hospital of Nanjing Medical University during January 2011 to December 2019 were enrolled. Clinical manifestations, laboratory indicators, treatment and outcomes were compared between two groups. Chi-square test and Mann-whitney U test were used to analyze data. Results:The average age of CAEBV patients was higher than that of IM patients [36.0(23.8, 50.5)years vs. 19.0(17.3, 22.8) years; U=90.0, P<0.05]. The symptoms of sore throat, throat congestion, tonsilla enlargement and lymphadenopathy in IM group were more common than those in CAEBV group( χ2=14.088, 16.875, 31.855 and 10.938, all P<0.01). However, the incidence of pulmonary infection, sleepiness/dysphoria and splenomegaly in CAEBV group were significantly higher than those in IM group( χ2=17.217, 5.809 and 6.254, P<0.05 or <0.01). The white blood cell counts, hemoglobin levels, platelet counts, alanine aminotransferase(ALT) and albumin in CAEBV group were significantly lower than those in IM group( U=47.0, 49.5, 158.5, 173.0 and 263.5, all P<0.01). The levels of neutrophil ratio, C-reactive protein, serum ferritin and EBV DNA load in CAEBV group were significantly higher than those in IM group( U=145.0, 140.0, 128.5 and 115.0, P<0.05 or <0.01). The proportions of CD3 + T cell counts and CD8 + T cell counts in CAEBV group were significantly lower compared to those in IM group( U=42.0 and 24.5, P<0.01); the proportions of CD4 + T cell counts, the CD4 + T/CD8 + T cell counts ratio and B lymphocytes in CAEBV group were significantly higher compared to those in IM group( U=29.0, 23.5 and 34.5, P<0.01). Fifty-six IM patients were all cured and discharged from hospital. In CAEBV group, 8 cases died, 3 cases were improved and 3 cases lost follow-up. Conclusions:Patients with IM represent a favorable prognosis, while the prognosis of CAEBV is relatively poor and complication with HLH may occur. For older patients with EBV infection complicated with pulmonary infection, lethargy/irritability, attention should be paid to monitor blood routine, liver function, serum EBV DNA load and peripheral blood lymphocyte subsets.

Objective:To investigate the outcomes and influencing factors of newly diagnosed prediabetic subjects aged 40 years and above in Guiyang.Methods:A total of 10 015 residents aged 40 years and above were recruited from the Yunyan community, Guiyang, from May to August 2011. Physical examination, laboratory measurements, and questionnaires were conducted. The follow-up survey was conducted in July 2014. A total of 2 530 newly diagnosed prediabetic subjects at baseline were included in the analysis.Results:The 3-year cumulative morbidity of diabetes mellitus was 14.3%, and the risk of diabetes mellitus in combined impaired fasting glucose(IFG)and impaired glucose tolerance(IGT)groups was significantly higher than that in isolated IFG(i-IFG)or isolated IGT(i-IGT)group( P<0.01). High baseline fasting plasma glucose, 2 h plasma glucose, and HbA 1C levels were the independent risk factors for the development of diabetes( OR=1.836, 95% CI 1.374-2.454; OR=1.398, 95% CI 1.261-1.550; OR=2.526, 95% CI 1.804-3.538, all P<0.01)and the inhibitory factors for reversion to normal glucose tolerance( OR=0.511, 95% CI 0.409-0.638; OR=0.715, 95% CI 0.661-0.774; OR=0.638, 95% CI 0.500-0.816, all P<0.01). High level of high density lipoprotein-cholesterol(HDL-C)was an promoting factor for reversion to normal glucose tolerance( OR=1.306, 95% CI 1.017-1.678, P=0.036). Subjects in the highest tertile of baseline HbA 1C level and body mass index(BMI)change before and after follow-up(ΔBMI=follow-up BMI minus baseline BMI)had a higher risk of diabetes mellitus than those in the lowest tertile( OR=2.398, 95% CI 1.733-3.322; OR=2.402, 95% CI 1.859-3.105, both P<0.01). The risk of diabetes mellitus in the significant weight loss group was reduced by 40.4% compared with the non-significant weight loss group when the subjects were divided into two groups according to the cutoff of the lower tertile of ΔBMI( RR=0.596, 95% CI 0.463-0.766, P<0.01). Conclusion:The risk of diabetes mellitus in combined IFG/IGT group was significantly higher than that in i-IFG or i-IGT group. High baseline fasting plasma glucose, 2 h plasma glucose, and HbA 1C levels were the independent risk factors for the development of diabetes. High level of HDL-C was an promoting factor for reversion to normal glucose tolerance. Weight loss can significantly reduce the risk of progression to diabetes in individuals with prediabetes.

Objective    To investigate the effect of artificial colloid on coagulation function in pediatric patients weighing less than 5 kg with congenital heart disease during cardiopulmonary bypass in congenital heart disease surgery by using artificial colloid instead of human serum albumin. Methods    A total of 65 pediatric patients with weight less than 5 kg who underwent congenital heart disease surgery in our hospital from September 2016 to December 2017 were included in the study. They were randomly divided into two groups: an artificial colloid group (the experimental group, n=33) and a human serum albumin combined artificial colloid group (the control group, n=32). Perioperative hemoglobin concentration (Hb), blood products and hemostatic drugs used, postoperative coagulation function index and pleural fluid volume 24 hours after surgery were monitored. Results    There was no significant difference in perioperative Hb and chest tube drainage between the two groups. The platelet utilization rate in the experimental group was significantly lower than that in the control group (P<0.05). No significant difference was found in the dosage of other blood products and hemostatic drugs between the two groups during the perioperative period. There was no significant difference in coagulation parameters between the two groups before and after surgery (P>0.05). Conclusion    The use of artificial colloid as colloid priming solution during cardiopulmonary bypass has no adverse effect on coagulation function in pediatric patients weighting less than 5 kg with congenital heart disease.

Objective To investigate the change of prevalence of autoimmune thyroiditis in Guiyang city after adjustment of salt iodine content, and to study the link between the level of iodine intake and the development of autoimmune thyroiditis. Methods With cluster sampling method, a cross-sectional study was conducted among adults aged 20 years old or above in Guiyang in 2009 (before adjustment, n=1 509) and 2015 (after adjustment, n=1 368). After an overnight fasting, thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured. The serum FT4 and FT3 were determined for the subjects with abnormal TSH. Meanwhile, urine iodine levels of children aged 8-10 years old in the same community were measured after an overnight fasting in these two studies. Results In 2009, the median level of 8-10 years old children′s urinary iodine was 228.7 μg/L. The prevalence of positive TPOAb, positive TgAb, and thyroid autoantibodies (TAAs) were 14.38%, 13.59%, 18.89%, the standardized prevalence were 14.35%, 13.59%, 18.89% respectively. The prevalence of subclinical hypothyroidism, autoimmune thyroiditis were 14.12% and 4.44%, with the standardized prevalence were 14.12%, 4.42% respectively. In 2015, the median urinary iodine level of 8-10 years old children was 190.1 μg/L, the prevalence of positive TPOAb, positive TgAb, and TAAs were 8.77%, 7.82%, 11.77%, the standardized prevalence were 8.98%, 7.97%, 12.13% respectively; the prevalence of subclinical hypothyroidism, autoimmune thyroiditis were 22.89%, 2.92%, with the standardized prevalences of 23.19%, 3.02% respectively. Conclusion After adjustment of salt iodine content, the iodine nutrition in Guiyang is at the appropriate level, and the values of TPOAb, TgAb, TAA, and autoimmune thyroiditis in adults of Guiyang city were all decreased.

Objective To evaluate the diagnostic accuracy of dual source CT angiography (DSCTA) for coronary artery stenosis.Methods During the period from November 2012 to November 2013, a total of 210 patients with coronary artery disease underwent DSCTA and selective coronary arteriography (CAG). Taking CAG as the gold standard, the diagnostic accuracy of DSCTA for coronary artery stenosis was evaluated. Thirty patients receiving DSCTA and 30 patients receiving CAG were selected, and all of them underwent stent implantation in the anterior descending branch after imaging examination. The angiography positions, the used time of PCI and the used dosage of contrast agent were compared between the two groups. Results DSCTA was performed in 210 patients and a total of 2 630 segments of coronary stenosis or occlusion were detected. Compared with CAG, the diagnostic sensitivity, specificity, positive predictive value and negative predictive value of DSCTA were 95.4%, 96.2%, 91.3%and 100%respectively, which were not significantly different from those obtained by CAG (P=0.066). In performing DSCTA, 2-3 angiography positions were used (2-4 positions less than that of CAG), the used time of PCI was about 15 min (about 10 min less than that of CAG), and the mean used dosage of contrast agent was 48 ml (30-150 ml) (about half less than that of CAG). Conclusion DSCTA has higher accuracy in diagnosing coronary artery stenosis, quite similar to that of CAG. DSCTA is a safe, reliable and noninvasive examination method. Preoperative DSCTA can reduce exposure positions during angiography, can reduce the dosage of contrast agent, and can shorten the time of PCI as well, thus, iatrogenic radioactive radiation dose can be reduced.

OBJECTIVE: To evaluate the effect of the combined application of dissociate skin flap and vacuum sealing drainage (VSD) for the repairing for defect after surgical management of huge neck neoplasms. METHOD: Nineteen patients with huge neck malignant tumor involving the skin of the neck were given radical operation, making use of VSD covering the wound surface. After giving 6.65-7.98 mm Hg continuous negative pressure drainage for 72 h, the patients turned to be treated by intermittent negative pressure therapy with 2 min free interval after each treatment period for 5 min. After dismantling the VSD at 7th to 10th day postoperatively, the good wounds covered by granulation tissue were treated by the skin graft operation with dissociate skin flap from thighs; as for the wounds of which the granulation tissue didn't grow well and important cervical tissues was not fully covered by the granulation tissue, VSD was applied again for 1 week, followed by the skin graft operation. RESULT: Nineteen patients have received a total of 23 times of VSD wound treatment, one-stage operation time was significantly shortened. The granulation tissue grew faster on the wound after VSD treatment, and the important cervical tissues such as great vessels could be well covered. The infection and tumor recurrence were observed directly after dismantling the VSD. The skin graft transplantation would be performed after 1-3 weeks. CONCLUSION The treatment by vacuum sealing drainage combined with skin graft for surgical wounds of huge neck tumor postoperatively has the advantages of simple operation, little injury and promotion of the wound healing, which is an effective way for treatment of neck skin defect by surgical operation for the huge tumor.
Adult ; Aged ; Female ; Head and Neck Neoplasms ; surgery ; Humans ; Male ; Middle Aged ; Negative-Pressure Wound Therapy ; Skin Transplantation ; methods ; Soft Tissue Injuries ; etiology ; surgery ; Surgical Flaps

Objective To determine the safety and the therapeutic efficacy of autolagous nonmyeloablative hematopoietic stem cell transplantation (AHST) in newly-onset type 1 diabetes mellitus patients. Methods Fifteen patients with type 1 diabetes mellitus were enrolled. Hematopoietic stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were injected intravenously after conditioning with cyclophosphamide and rabbit antithymocyte globulin. Serum levels of HbA1c, C-peptide levels, and anti-glutamic acid decarboxylase antibody (GAD-Ab)titers were measured before and after AHST. Meanwhile, adverse event was recorded.Results The average age of 18 patients (6 males and 12 females)was ( 18.8±4.4 )years, the mean follow-up was ( 414± 150 ) days. 67 % ( 12/18 ) patients became insulin free, the earliest one happened at 2 weeks after AHST, and the latest one at 6 months. 4 cases resumed insulin use because of influenza and other reasons resulting in the rise of blood glucose level. Currently, 8 patients (44.4%) were completely free of insulin therapy, and the remaining cases reduced the insulin dosage by 67.3% ±22.4%. 18 cases had lowered GAD-Ab level, the negative rate was 33.3% (6/18 ). Fasting and postprandial 2 h C-peptide levels increased significantly after A HST. Area under the curve for C-peptide ( AUCC ) increased much more markedly, and it could be maintained for 1 year. Duringtransplantation,all patients had varying degrees of gastrointestinal reactions, hair loss, fever, bone marrow suppression, and other side effects. 5 patients received blood component transfusion. No damage or other severe adverse events of heart, liver, kidney, and other organs were observed. Most side effects gradually disappeared after 2-4 weeks. The recovery of neutropenia was the slowest. Conclusion Autologous hematopoietic stem cell transplantation for treatment of newly-onset type 1 diabetes with residual islet function showed a certain effect and high safety. The widened use of this new technique should be cautious until the therapeutic mechanism has been further studied.