全身亚低温联合人脐带血间充质干细胞移植改善新生大鼠缺氧缺血性脑损伤后认知障碍和能量衰竭的机制研究

目的探究全身亚低温联合人脐带血间充质干细胞(hCMNCs)移植改善新生大鼠缺氧缺血性脑损伤(HIBD)后认知障碍和能量衰竭的机制。方法7日龄新生SD乳鼠330只。随机分为11组,每组30只。空白对照组(A组)、HIBD常温组(B组)、HIBD亚低温持续72 h组(C组)、HIBD亚低温24 h干细胞移植组(D组)、HIBD亚低温48 h干细胞移植组(E组)、HIBD亚低温72 h移植组(F组)、HIBD亚低温24 h后持续3 d移植干细胞(G组)、HIBD 24 h干细胞移植组(H组)、HIBD 48 h干细胞移植组(I组)、HIBD 72 h干细胞移植组(J组)、HIBD 24 h、48 h、72 h干细胞移植组(K组)。乳鼠生长的第10天、第21天和第35天对其进行称重;通过Morris水迷宫实验检测乳鼠学习和记忆能力,超微电镜观察分析乳鼠脑组织神经元细胞及突触超微结构的变化,苏木精-伊红(HE)染色观察脑组织病理学变化,酶联免疫吸附试验检测乳鼠脑组织炎症因子和干细胞分化标记蛋白含量,免疫荧光染色检测脐带CD24和CD29阳性表达率,荧光显微镜测量线粒体膜电位。结果A、B、C、D、E、F、G、H、I、J、K组乳鼠生长第10天、第21天和第35天体重比较,采用重复测量设计的方差分析,结果:①不同时间点乳鼠体重有差异(F=13.285,P=0.000),各组乳鼠第21天与第35天体重比较,差异有统计学意义(P<0.05);②各组乳鼠体重有差异(F=20.097,P=0.000),B组乳鼠体重较A组降低(P<0.05),C~K组乳鼠体重较B组升高(P<0.05),G、I组乳鼠体重较B、C、D、E、F、H、J、K组均升高(P<0.05),且G组与I组乳鼠体重比较,差异无统计学意义(P>0.05);③各组乳鼠体重变化趋势有差异(F=28.712,P=0.000)。C~F组3种反射(悬崖调转反射、阴性趋地性、步态反射)时间较A组延长(P<0.05),但较B组缩短(P<0.05);C组3种反射时间较A、D~J组延长(P<0.05);G~K组3种反射时间与A组比较,差异无统计学意义(P>0.05);C~F组3种反射时间较G~K组延长(P<0.05)。HE染色结果显示,与A组比较,B~K组乳鼠HIBD模型复制成功后第3天,脑间质水肿,小血管间隙增宽,左侧大脑出现大片坏死,细胞溶解、破坏、消失;皮质海马神经元排列紊乱,核固缩、崩解,细胞浓染,并见小胶质细胞。第21天,B~K组与A组有差异,B~K组脑组织见不同程度的损伤,其中B组可见大的梗塞灶及液化空洞形成。C~K组表现为部分炎症细胞;B组与C~K组比较,脑损伤程度较大。其中G、J、K组脑损伤及炎症程度较C~F、H、I组小。B~K组逃避潜伏期较A组延长(P<0.05),G、J、K组逃避潜伏期较B~F、H组缩短(P<0.05)。B~K组神经元致密区长度较A组变短(P<0.05),厚度较A组变薄(P<0.05),而突触间隙宽度较A组变厚(P<0.05)。C~K组乳鼠神经元致密区长度较B组变长(P<0.05),厚度较B组变厚(P<0.05),突触间隙宽度较B组变薄(P<0.05)。G~J组乳鼠神经元致密区长度较D~F、K组变长(P<0.05),厚度较D~F、K组变厚(P<0.05),突触间隙宽度较D~F、K组变薄(P<0.05)。A、B、C、D、E、F、G、H、I、J、K组乳鼠HIBD模型复制成功后第3天、第8天、第12天的TNF-α、IL-6、Nestin、TUBB、MBP比较,采用重复测量设计的方差分析,结果:①不同时间点TNF-α、IL-6、Nestin、TUBB、MBP有差异(F=39.451、19.754、36.957、16.794和16.958,均P=0.000);②各组乳鼠TNF-α、IL-6、Nestin、TUBB、MBP有差异(F=10.719、10.159、43.271、5.947和11.217,P=0.000、0.000、0.000、0.012和0.000);B~K组TNF-α、IL-6在HIBD模型复制成功第3天、第8天和第12天较A组升高(P<0.05),C~K组TNF-α、IL-6较B组降低(P<0.05)。C~K组Nestin、TUBB和MBP较B组升高(P<0.05)。③各组乳鼠TNF-α、IL-6、Nestin、TUBB、MBP变化趋势有差异(F=22.678、25.483、6.597、20.159和20.154,P=0.000、0.000、0.003、0.000和0.000)。A~C组CD24和CD29阳性表达率较E~K组降低(P<0.05),G、I组较H、J、K组CD24和CD29阳性表达率升高(P<0.05)。B~K组线粒体膜电位较A组降低(P<0.05),C~K组线粒体膜电位较B组升高(P<0.05),G~J组线粒体膜电位较C~F组升高(P<0.05)。结论亚低温联合UCMSCs能改善HIBD乳鼠认知障碍和能量衰竭,对脑神经有保护作用。

Full recovery from chronic headache and hypopituitarism caused by lymphocytic hypophysitis:A case report

BACKGROUND Lymphocytic hypophysitis(LYH)is an important condition to consider in the differential diagnosis of patients with a pituitary mass.The main clinical manifestations of LYH include headache,symptoms related to sellar compression,hypopituitarism,diabetes insipidus and hyperprolactinemia.Headache,which is a frequent complaint of patients with LYH,is thought to be related to the occupying effect of the pituitary mass and is rapidly resolved with a good outcome after timely and adequate glucocorticoid treatment or surgery.CASE SUMMARY Here,we report a patient with LYH whose initial symptom was headache and whose pituitary function assessment showed the presence of secondary hypoadrenalism,central hypothyroidism and hypogonadotropic hypogonadism.Pituitary magnetic resonance imaging showed symmetrical enlargement of the pituitary gland with suprasellar extension in a dumbbell shape with significant homogeneous enhancement after gadolinium enhancement.The size of the gland was approximately 17.7 mm×14.3 mm×13.8 mm.The pituitary stalk was thickened without deviation,and there was an elevation of the optimal crossing.The lesion grew bilaterally toward the cavernous sinuses,and the parasternal dural caudal sign was visible.The patient presented with repeatedly worsening and prolonged headaches three times even though the hypopituitarism had fully resolved after glucocorticoid treatment during this course.CONCLUSION This rare headache regression suggests that patients with chronic headaches should also be alerted to the possibility of LYH.

Optimal Cut-off Point of Waist to Height Ratio in Beijing and Its Association with Clusters of Metabolic Risk Factors

A host of studies found waist-to-height ratio(WHtR)having higher diagnostic value than other abdominal obesity anthropometric indicators for metabolic disorders.But the cut-off points are still not consistent.This study was aimed to explore the optimal cut-off point of WHtR in Chinese population and identify the association between WHtR and cluster of metabolic risk factors.In total,13379 Han adults(7553 men and 5726 women)from over 40 institutions who took physical examination in Xuanwu Hospital of Capital Medical University between January 2014 and January 2015 were involved in this cross-sectional study.Subjects with two or more components of metabolic syndrome(MetS)were considered to have multiple risk factors.Optimal cut-off points of WHtR for cluster of metabolic risk factors were analyzed by receiver operating characteristic(ROC)curve analysis.The optimal cut-off points of WHtR were 0.51 for men and 0.49 for women.People with elevated WHtR had higher levels of metabolic risk factors.And the prevalence of individual and clusters of 5 risk factors were all higher among WHtR-defined abdominal obesity people than in normal subjects.The optimal cut-off points of WHtR were 0.51 for men and 0.49 for women.In conclusion,people with elevated WHtR.are susceptible to cluster of metabolic risk factors.

Current carrying states in the disordered quantum anomalous Hall effect

In a quantum Hall effect,flat Landau levels may be broadened by disorder.However,it has been found that in the thermodynamic limit,all extended(or current carrying)states shrink to one single energy value within each Landau level.On the other hand,a quantum anomalous Hall effect consists of dispersive bands with finite widths.We numerically investigate the picture of current carrying states in this case.With size scaling,the spectrum width of these states in each bulk band still shrinks to a single energy value in the thermodynamic limit,in a power law way.The magnitude of the scaling exponent at the intermediate disorder is close to that in the quantum Hall effects.The number of current carrying states obeys similar scaling rules,so that the density of states of current carrying states is finite.Other states in the bulk band are localized and may contribute to the formation of a topological Anderson insulator.

电针对急慢性痛转化大鼠背根神经节EP1-TRPV1通路的干预机制研究

Objective:To observe the law of changes in mechanical paw-withdrawal threshold(MPWT) and thermal paw-withdrawal latency(TPWL) on the modeled side of rats with pain transition(hyperalgesic priming[HP]),and the expression of prostaglandin E receptor 1(EP1) and transient receptor potential vanilloid type 1(TRPV1) in the dorsal root ganglion(DRG) of the affected side of rats.To observe the effects of electroacupuncture(EA) on the TPWL on the modeled side of rats with pain transition and regulation of EP1 and TRPV1 expression in DRG.Methods:Part 1:Eighteen SD rats were randomly divided into control,sham HP,and HP groups,with 6rats in each group.The modeling comprised two injections.The rats in the HP group were subcutaneously injected with 1% carrageenan(100 μL) into the left hind paw in the first injection(those in the control and sham HP groups were injected with saline).The second injection was administered 8 days later by injecting prostaglandin E2(PGE2)(100 ng/25 μL) into the dorsum of the paw(the rats in the control group were administered with saline and those in the sham HP group PGE2),thereby developing a pain transition model.TPWL and MPWT were measured before rat modeling,4 h,and 1,2,3,and 7 days after the first injection,and 1,4,24,and 48 h after the second injection(8 days after the first injection).The expression rates of EP1-and TRPV1-positive cells in the affected DRG were measured by immunofluorescence(IF).Part 2:Eighteen SD rats were randomly divided into sham HP(6 rats),and HP groups(12rats),then the rats in HP group were randomly divided into HP(6 rats) and HP+EP1 antagonist(6 rats)groups for the detection of TPWL.Rats in the EP1 antagonist group were injected with EP1 antagonist5 min before PGE2 injection.The expression rate of TRPV1-positive cells in the affected DRG 48 h after PGE2 injection was detected using the IF method.Part 3:Twenty-four SD rats were randomly divided into sham HP(6 rats),and HP groups(18 rats),then the rats in HP group were randomly divided into HP(6 rats),sham EA(6 rats) and EA(6 rats) groups for the detection of TPWL.Following the injection of carrageenan,rats in the EA group were intervened at "Zúsanlǐ(足三里 ST36)" and "Kūnlun(昆仑 BL60)"acupoints bilaterally,once a day.The expression rate of EP1-and TRPV1-positive cells in the affected DRG was detected by the IF method.Results:Part 1:1.Compared with the control and sham HP groups,the MPWT of the affected paw of the rats in the HP group was significantly reduced at 4,24,48,and 72 h after carrageenan injection,and at 4,24,and 48 h after PGE2 injection(all P <0.01).2.Compared with the control group,the TPWL of the affected paw was significantly decreased in the HP group at 4,24,48,and 72 h after carrageenan injection,and at 4,24,and 48 h after PGE2 injection(all P <0.01);compared with the MPWT of the HP rats,the TPWL of the HP rats increased and recovered 4 h after PGE2 injection,while there was no such trend in the MPWT.3.The expression of EP1-and TRPV1-positive cells in the affected DRG of rats in the HP group was increased compared with that of the control and sham HP rats(all P <0.01).Part2:1.TPWL was significantly increased in the EP1 antagonist group compared with the HP group at 1,4,24,and 48 h after PGE2 injection(1 h P <0.01,4 h P <0.05,24 h P <0.05,and 48 h P <0.05).2.Compared with the HP group,the expression rate of TRPV1-positive cells in the affected DRG of the rats in the EP1 antagonist group was significantly lower 48 h after PGE2 injection(P <0.01),while there was no statistical difference compared with the sham HP group.Part 3:1.EA significantly elevated the TPWL on the affected side at 24,48,and 72 h after the first injection,and at 4,24,and 48 h after the second injection,compared with the HP group(P <0.05,P <0.01),whereas there was no such change in the sham EA group.2.The expression rates of EP1-and TRPV1-positive cells in the affected DRG were increased in the HP group compared with the sham HP group(both P <0.01).Compared with the HP group,the expression rates of EP1-and TRPV1-positive cells in the affected DRG were decreased in the EA group(both P <0.01);however,there was no significant change in the sham EA group.Conclusion:1.HP induces decreased MPWT and TPWL and prolonged hyperalgesia in rats,resulting in the transition from acute to chronic pain;however,the changing pattern of TPWL differs from that of MPWT;2.EP1-TRPV1 signaling pathway in DRG is involved in HP and promotes the transition from acute to chronic pain;3.The analgesic effect of EA on HP thermal pain in rats may relate to the inhibition of the expression of the EP1-TRPV1 signaling pathway;thus,inhibiting the transition from acute to chronic pain.

Tumor-infiltrating B cells:their role and application in antitumor immunity in lung cancer

Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells,stromal fibroblasts,and immune cells.Tumor-infiltrating immune cells play a significant role in the promotion or inhibition of tumor growth.As an integral component of the tumor microenvironment,tumor-infiltrating B lymphocytes(TIBs)exist in all stages of cancer and play important roles in shaping tumor development.Here,we review recent clinical and preclinical studies that outline the role of TIBs in lung cancer development,assess their prognostic significance,and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment.