A large congenital atrial septal defect in an adult with delayed therapy

Patients with a large congenital atrial septal defect (ASD) traditionally have the ASD repaired at the preschool age. Unfortunately, insufficient education of patients regarding medical science and clinical recommendations can lead to delayed therapy, resulting in complications during adulthood. We report a rare case of a large congenital ASD in a 20-year-old man. Echocardiography showed a 67-mm ostium secundum defect and moderate mitral and tricuspid regurgitation. The patient underwent transthoracic ASD repair along with mitral and tricuspid valvuloplasty. This report emphasizes the importance of educating patients about congenital malformations and potential interventions in developing countries, particularly in rural communities.     

Differential requirements of CD4+ T‐cell signals for effector cytotoxic T‐lymphocyte (CTL) priming and functional memory CTL development at higher CD8+ T‐cell precursor frequency

Increased CD8⁺ T‐cell precursor frequency (PF) precludes the requirement of CD4⁺ helper T (Th) cells for primary CD8⁺ cytotoxic T‐lymphocyte (CTL) responses. However, the key questions of whether unhelped CTLs generated at higher PF are functional effectors, and whether unhelped CTLs can differentiate into functional memory cells at higher PF are unclear. In this study, ovalbumin (OVA) ‐pulsed dendritic cells (DC_OVA) derived from C57BL/6, CD40 knockout (CD40^?/?) or CD40 ligand knockout (CD40L^?/?) mice were used to immunize C57BL/6, Ia^b?/?, CD40^?/? or CD40L^?/? mice, whose PF was previously increased with transfer of 1 × 10⁶ CD8⁺ T cells derived from OVA‐specific T‐cell receptor (TCR) transgenic OTI, OTI(CD40^?/?) or OTI(CD40L^?/?) mice. All the immunized mice were then assessed for effector and memory CTL responses. Following DC immunization, relatively comparable CTL priming occurred without CD4⁺ T‐cell help and Th‐provided CD40/CD40L signalling. In addition, the unhelped CTLs were functional effectors capable of inducing therapeutic immunity against established OVA‐expressing tumours. In contrast, the functional memory development of CTLs was severely impaired in the absence of CD4⁺ T‐cell help and CD40/CD40L signalling. Finally, unhelped memory CTLs failed to protect mice against lethal tumour challenge. Taken together, these results demonstrate that CD4⁺ T‐cell help at higher PF, is not required for effector CTL priming, but is required for functional memory CTL development against cancer. Our data may impact the development of novel preventive and therapeutic approaches in cancer patients with compromised CD4⁺ T‐cell functions.     

Effects of Matrine on JAK-STAT Signaling Transduction Pathways in Bleomycin-Induced Pulmonary Fibrosis

The current study aims to investigate the effects of matrine on the JAK-STAT signaling transduction pathways in bleomycin (BLM)-induced pulmonary fibrosis (PF) and to explore its action mechanism. A total of 72 male C57BL/6 mice were randomized into the control, model, and treatment groups. PF models were established by instilling BLM intratracheally. The treatment group was given daily matrine through gastric lavage. Six mice were sacrificed in each group at 3, 7, 14, and 28 days. The lung tissues were observed using hematoxylin-eosin staining. The expression of JAK, STAT1, and STAT3 was observed using immunohistochemistry and then determined using real-time polymerase chain reaction. Alveolitis and PF significantly improved in the treatment group compared with the model group (P < 0.05). The expression of JAK, STAT1, and STAT3 in the model group increased at day 7, peaked at day 14 and then decreased, but the expression was still higher than that in the control group at day 28 (P < 0.05). The three indices in the treatment group were significantly lower than those in the model group at any detection time point (P < 0.05). PF causes high expression of JAK, STAT1, and STAT3. Matrine exerts an anti-PF effect by inhibiting the JAK-STAT signaling transduction pathways.     

A risk prediction model of urinary tract infections for patients with neurogenic bladder

Abstract

Objectives: To develop a nomogram to evaluate the risk of urinary tract infections (UTI) in patients with neurogenic bladder (NGB)

Methods: A retrospective analysis was conducted on 337 patients with NGB admitted to three hospitals. Collected data included clinical symptoms, patients’ general characteristics, laboratory examinations and imaging findings. Multivariate logistic regression analysis was conducted to develop the risk prediction nomogram of UTIs for NGB patients. C index was used for the internal and external validation of that model.

Results: The occurrence of UTIs was 45.7% (154 of 337), 52.6% (102 of 194), and 36.4% (52 of 143) in the overall, training and validation data sets, respectively. The prediction nomogram was developed with 5 prognostic factors which included white blood cell (WBC) in blood, Leukocyte (LEU) in urine, Urinary pH, length of stay and urination mode. The nomogram presented good discrimination with a C-index value of 0.921 (95% confidence interval: 0.87396???0.96804) and good calibration. The C-index values of the interval validation and external validation were 0.8905541 and 0.817, respectively. The results of decision curve analysis (DCA) demonstrated that the model was clinically useful.

Conclusions: The prediction nomogram we developed is a simple and accurate tool for early prediction of UTIs in patients with NGB. This tool can assess risk of UTIs early, allowing for timely initiation of appropriate preventive measures.     

Third‐party Tolerogenic Dendritic Cells Reduce Allo‐reactivity In vitro and Ameliorate the Severity of Acute graft‐Versus‐host Disease in Allo‐bone Marrow Transplantation

Tolerogenic dendritic cells (tDCs) potently induce and maintain tolerance based on their distinct characteristics compared with conventional DCs. Recent reports show that donor or host tDCs promote allograft survival in mice. In this study, the efficacy of third‐party tDCs in the prevention of acute graft‐versus‐host disease (aGVHD) was evaluated. In vitro, tDCs derived from the bone marrow (BM) of D1 mice were induced by GM‐CSF, IL‐10 and TGF‐β1. The phenotypes, expression of cytokines and suppression of tDCs were analysed. In vivo, the effects of adoptive transfer of third‐party‐tDCs were evaluated in an MHC‐mismatched aGVHD mouse model. Survival, body weight, GVHD scoring, histopathological specimens and serum cytokines were analysed in tDC‐treated mice and untreated controls. Tolerogenic DCs had low expression of MHC and co‐stimulatory molecules, expressed high levels of ‘immunosuppressive’ cytokines and suppressed allo‐CD4⁺T cell proliferation. In the B6→D2 mouse model, all aGVHD mice died within 18 days. Fortunately, third‐party tDCs transferred at low doses (10⁴) effectively prolonged survival after allo‐BMT. Furthermore, in the mice treated with 10⁴ tDCs, serum levels of IL‐10/TGF‐β were significantly higher and the percentage of Foxp3⁺ cells continually increased compared with the mice treated with other doses of tDCs. Third‐party tDCs play a crucial role in reducing the severity of aGVHD by modulating the secretion of various cytokines and expanding Foxp3⁺ regulatory T cells, which suggests the possibility of using third‐party tDCs for therapeutic applications. Furthermore, special attention should be paid to the optimal range of tDCs for preventing allograft rejection.     

职业性有机溶剂中毒15例临床表现和影像学特征分析

目的 探讨职业性有机溶剂中毒的临床表现、神经影像学特征、治疗及预后。方法 回顾性分析15例职业性有机溶剂中毒患者的临床资料。结果 15例患者均急性或亚急性起病,有明确的有机溶剂职业接触史,主要临床表现包括头晕(73.3%)、认知功能下降(60%)、锥体束损害(53.3%)、颅内高压综合征(46.7%)、意识障碍(33.3%); 其中14例患者头颅磁共振成像(Magnetic resonance imaging,MRI)显示为弥漫性脑组织肿胀,以双侧大脑半球白质为主,呈“火焰状”,10例累及双侧基底节(苍白球),8例累及双侧小脑齿状核,呈“肾形”改变,5例累及双侧丘脑; 所有患者使用脱水剂、糖皮质激素及高压氧等综合治疗后,其中12例患者好转出院,无或仅遗留轻微后遗症,3例患者无明显改善,预后差。结论 职业性有机溶剂中毒以头晕、认知功能下降、锥体束损害、颅内高压综合征及意识障碍等中毒性脑病表现为主,典型头颅MRI为双侧大脑半球白质、苍白球及小脑齿状核对称性病变,结合患者职业接触史需考虑本病; 早期、长程、足量给予脱水剂、糖皮质激素及高压氧等综合治疗,大多数患者预后良好。     

黄芪多糖对阿尔茨海默病大鼠神经细胞活性、认知功能及Caspase-9表达水平的影响

目的 探讨黄芪多糖(Astragalus polysacharin,APS)对阿尔茨海默病(Alzheimer’s disease,AD)大鼠神经细胞活性、认知功能及天冬氨酸特异性半胱氨酸蛋白酶(Cysteinyl aspartate specific protease,Caspase)-9表达水平的影响。方法 36只无特定病原体(Specific pathogen free, SPF)级美国斯泼累格·多雷(Sprague Dawley)雌雄各半的大鼠,按照随机数字表分为6组,正常组、AD组、药物对照组、干预A组、干预B组及干预C组; 除正常组外,其余大鼠建立AD大鼠模型; 建模后药物对照组采用0.5 g/kg的吡拉西坦灌胃,干预A组、干预B组及干预C祖均采用0.2、0.4及0.8 g/kg的黄芪多糖(Astragalus polysacharin,APS)灌胃,正常组及AD组灌胃等剂量的生理盐水,均1次/d,灌胃时间连续60 d。采用Morris水迷宫实验观察认知功能; 苏木精-伊红(Hematoxy lin-Eosin,HE)染色观察海马组织病理学表现; 末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法[Terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling,TUNEL]法检测神经细胞凋亡率; 免疫印迹及实时定量聚合酶链反应(Quantitatie real time polymerase chain reaction,QRT-PCR)技术分别检测细胞色素C(Cytochrome c,Cyt-c),Caspase-3及Caspase-9蛋白及信使核糖核酸(Messenger RNA,mRNA)相对表达水平。结果 与正常组比较,AD组大鼠灌胃后第1～5 d的逃避潜伏期均延长(P<0.05); 与AD组比较, 干预A组、干预B组、干预C组逃避潜伏期均缩短(P<0.05),药物对照组逃避潜伏期与干预C组比较无明显差异(P>0.05)。与正常组比较,AD组大鼠游泳距离增加(P<0.05); 与AD组比较,干预A组、干预B组及干预C组大鼠游泳距离均减少(P<0.05),干预C组与药物对照组相似(P>0.05)。正常组海马结构完成,神经元排列紧密,细胞核清晰且无空泡; AD组大鼠海马组织结构紊乱,神经元数目减少,细胞核深染,细胞膜收缩及部分消失; APS干预组及药物对照组神经元排列较AD组整齐有序,肿胀程度减轻,细胞核较清晰。各组大鼠海马组织神经细胞凋亡率比较有明显差异(F=134.900,P<0.001); 与正常组比较,AD组神经细胞凋亡率升高(P<0.05); 与AD组比较,干预A组、干预B组及干预C组神经细胞凋亡率降低(P<0.05),药物对照组与干预C组神经细胞凋亡率相似(P>0.05)。与正常组比较,AD组海马组织Cyt-C,Caspase-3及Caspase-9蛋白及mRNA 相对表达水平上调(P<0.05); 与AD组比较,不同水平干预组海马组织Cyt-C,Caspase-3及Caspase-9蛋白及mRNA 相对表达水平下调(P<0.05),药物对照组与干预C组上述蛋白及mRNA相对表达水平相似(P>0.05)。结论 黄芪多糖能够改善AD大鼠认知功能,减轻海马组织病理损伤,抑制神经元凋亡且呈现水平依赖性,其机制可能与抑制Cyt-C及caspase-3/9信号通路有关。