Cerebral small vessel disease （CSVD） is a spectrum of pathological conditions affecting intracranial small blood vessels and is associated with a variety of clinical manifestations， including cognitive impairment， gait abnormalities， and sleep disorders. In recent years， the association between CSVD and sleep disorders has attracted increasing attention. This article reviews the association of CSVD with various sleep disorders such as obstructive/central sleep apnea hypoventilation syndrome， restless legs syndrome， and insomnia， analyzes the mechanisms by which sleep disorders cause CSVD， and proposes potential directions for future research.

Objective To explore the clinical application value of emergency bedside echocardiography(EB-Echo)in the diagnosis and treatment of reverse-Takotsubo syndrome(r-TTS).Methods A retrospective study method was conducted,the EB-Echo imaging and clinical data of 10 patients already diagnosed with r-TTS and admitted to the department of critical care medicine of Zhengzhou People's Hospital from January 2014 to December 2021 were selected.The r-TTS group,while data from 33 concurrently admitted patients with classic Takotsubo syndrome(TTS)were selected as the classic TTS group.Comparisons were made in terms of EB-Echo detection rates,diagnosis times,cardiac function indicators[left ventricular ejection fraction(LVEF),left ventricular stroke volume(LVSV)],blood volume indicators[inferior vena cava diameter(IVCD),collapse degree of inferior vena cava(cIVC)],complications[acute left ventricular outflow tract obstruction(ALVOTO),acute mitral regurgitation(AMR),and pulmonary hypertension(PH)],and prognosis between the two groups.Results The detection rate of EB-Echo in the r-TTS group was significantly higher than that in the classic TTS group[100.0%(10/10)vs.66.7%(22/33),P<0.05],and the diagnosis time was significantly shorter(minutes:26.80±3.77 vs.41.18±6.61,P<0.05).In terms of cardiac function indicators,both LVEF and LVSV were significantly lower in the r-TTS group compared to the classic TTS group[LVEF:0.36±0.05 vs.0.41±0.04,LVSV(mL):36.43±4.30 vs.40.65±5.09,both P<0.05].However,there were no significant differences in blood volume indicators(IVCD and cIVC)between the r-TTS group and the classic TTS group[IVCD(mm):15.02±1.88 vs.14.94±1.75,cIVC:(0.43±0.06)%vs.(0.44±0.07)%,both P>0.05].Concerning complications,the incidence of ALVOTO was slightly lower in the r-TTS group compared to the classic TTS group[0%(0/10)vs.21.2%(7/33),P>0.05],while the incidences of AMR and PH were similar between the two groups[AMR incidence:40.0%(4/10)vs.24.2%(8/33),PH incidence:30.0%(3/10)vs.18.2%(6/33),both P>0.05].After a follow-up ranging from 6 months to 3 years,no deaths were reported in the r-TTS group,whereas there was one fatality in the classic TTS group.Nevertheless,the mortality difference between the groups was not statistically significant.Conclusion EB-Echo demonstrates significant clinical value in the early diagnosis,guiding therapy,and enhancing prognosis of r-TTS.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective:To detect the levels of cytokines in peripheral blood of patients with chronic immune thrombocytopenia (ITP) and analyze their significance in the clinical prognosis of children with chronic ITP.Methods:Thirty patients with chronic ITP who were treated in the Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical Univercity from October 2015 to October 2018 were followed and enrolled in the experimental group and 40 healthy children in the same hospital were enrolled in the healthy control group.The levels of interleukin-2(IL-2), interferon-γ(IFN-γ), tumor necrosis factor(TNF), interleukin-4(IL-4), interleukin-6(IL-6), interleukin-10(IL-10) and interleukin-17A(IL-17A) in the experimental group and the healthy control group were detected by flow cytometry (CBA). The relationship between cytokines and prognosis of children with chronic ITP were analyzed.Results:Thirty patients with ITP were enrolled. The expressions of IL-2 and IL-17A in the experimental group before treatment were (7.86±3.90) ng/L and (10.45±12.35) ng/L, while those of IL-2 and IL-17A in the healthy control group were (3.11±2.41) ng/L and (2.97±7.04) ng/L. The levels of IL-2 and IL-17A in the experimental group were significantly higher than those in the healthy control group, and the differences were statistically significant ( t=-7.123, -5.582, all P<0.01). The expressions of IL-4 and IL-10 in the experimental group before treatment were (0.38±0.25) ng/L and (1.80±1.25) ng/L, while those of IL-4 and IL-10 in the healthy control group were (3.08±0.26) ng/L and (4.55±3.44) ng/L. The levels of IL-4 and IL-10 in the experimental group were significantly lower than those in the healthy control group, and the differences were statistically significant ( t=8.400, 5.653, all P<0.01). The expressions of IL-6, TNF and IFN-γ in the experimental group before treatment were (7.30±9.16) ng/L, (4.85±7.60) ng/L and (7.68±20.41) ng/L, while those of IL-6, TNF and IFN-γ in the healthy control group were (5.44±4.18) ng/L, (1.97±0.37) ng/L, (4.81±17.71) ng/L. There was no significant difference between the two groups ( P>0.05), and no significant difference in the levels of cytokines between the patients with chronic ITP before and 12 months after treatment ( P>0.05). Conclusions:The changes of T lymphocyte related cytokines are closely related to the pathogenesis and development of chronic ITP in children. There may be persistent immune dysfunction in children with chronic ITP. Dynamic monitoring of cytokines IL-2, IL-4, IL-10, IL-17A, especially IL-17A, is helpful to judge the prognosis of ITP in children, and may be of guiding significance in evaluating clinical prognosis.

Objective To analyze the functional changes and the clinical significance of B cell specific mono-clonal murine leukemia virus integration site -1 (Bmi -1 )and Th1 /Th2 cells in children with newly diagnosed im-mune thrombocytopenia(ITP)by testing the mRNA expressions of Bmi -1,helper T cell -related cytokine interferon (IFN)-γand interleukin(IL)-4 in children with newly diagnosed ITP.Methods Thirty -six cases of patients with newly diagnosed ITP in the experimental group came from the inpatient and outpatient children admitted to the Depart-ment of Pediatrics of the First Affiliated Hospital of Xinxiang Medical University from April to December 201 3.In the control group,26 cases of children requiring selective operation were admitted to the Department of Pediatric Surgery during the same period.The mRNA expressions of Bmi -1,IFN -γand IL -4 in the peripheral blood lymphocytes were detected by means of the reverse transcription -polymerase chain reaction(RT -PCR)method,and were analyzed and compared by t test and linear correlation analysis.Results (1 )The mRNA expressions of Bmi -1,IFN -γand IL -4 in peripheral blood lymphocytes in the experimental group were 2.63 ±0.54,3.84 ±0.43 and 1 .44 ±0.39,respec-tively;while the mRNA expressions of Bmi -1,IFN -γand IL -4 in the peripheral blood lymphocytes in the control group were 3.91 ±0.92,2.88 ±0.57 and 1 .87 ±0.34,respectively.The levels of IFN -γof the experimental group were significantly higher than those of the control group (P <0.001 )and the levels of Bmi -1 and IL -4 in the experi-mental group were significantly lower than those in the control group (all P <0.001 ).(2)The mRNA expressions be-tween IFN -γand IL -4 in the peripheral blood lymphocytes in the experimental group were in negative correlation (r =-0.667,P <0.001 ).The mRNA expressions between IL -4 and Bmi -1 in the same group were in a positive correlation (r =0.776,P <0.001 ).There were no correlation in the mRNA expressions between IFN -γand Bmi -1 (r =-0.206,P >0.05).Conclusions Bmi -1 may be involved in the pathogenesis of ITP by regulating Th cell, and Th cell dysfunction may occur in the children with ITP,and the disproportion between Th1 and Th2 may be due to the advantages of Th1 .

Objective In the present study, we investigated the effects of advanced oxidation protein products(AOPP) on reactive oxygen species(ROS) production in murine osteoblastic MC3T3-E1 cells by NADPH oxidase enzymes pathway. Methods Experiments were divided into three groups, including control group, rats albumin(RSA) group, and AOPP group. Different concentrations of AOPP were added to the osteoblastic MC3T3-E1 cells culture medium. The production of ROS in MC3T3-E1 cells was measured by the fluorescence intensity of intracellular fluoroprobe ( DCFD ) . In order to verify the effect of enzyme of the production of ROS, the specific inhibitors of corresponding enzymes were added in the MC3T3-E1 cells which were cultured in the medium with AOPP. Finally, western blot and immunofluorescence were used to observe the changes of NADPH oxidase enzymes subunits. Results Different concentrations of AOPP (50,100,200μg/ml) induced MC3T3-E1 cells to produce different amount of ROS. The higher concentrations of AOPP were added, the more ROS were produced. Furthermore,200μg/ml AOPP induced the maximum amount of ROS production(P<0. 05). Meanwhile, AOPP induced MC3T3-E1 cells to produce different amount of ROS with a time-dependent manner. The peak amount of ROS production in MC3T3-E1 cells was observed in 3h when AOPP were added (P<0. 05). In addition, when specific inhibitors of corresponding enzymes were added in the MC3T3-E1 cells, the production of ROS were significantly suppressed by C-SOD, DPI, and apocynin(P<0. 05). On the other hand, AOPP can up-regulate the expression of Nox4 protein of the MC3T3-E1 cells, which is one of the subunits of NADPH oxidase enzymes. Meanwhile, AOPP can also induce the membrane migration of p47phox subunit. Conclusion AOPP induces osteoblastic MC3T3-E1 cells to produce ROS by NADPH oxidase enzymes pathway, and which may be one of the pathogenesis of AOPP involved in osteoporosis.

Objective To investigate the expression and clinical significance of Smac and HtrA2 in children with acute leukemia(AL).Methods Bone marrow samples were obtained from 77 children with AL (including 32 newly diagnosed children,33 complete remission children and 12 relapsed children)and the control group of 15 children without malignant blood disease.The expressions of Smac and HtrA2 protein were measured by streptavidin/peroxidase immunoperoxidase technique(SP) in all children.SPSS 13.0 software was applied to analyze the statistical data.Results Protein Smac was detected only in some samples,but HtrA2 was detected in all samples.The levels of Smac and HtrA2 protein in newly diagnosed AL children were both higher than those of the complete remission children (x2 =17.38,F =2.36,all P ＜ 0.05) and normal controls (x2 =12.89,F =5.26,all P ＜ 0.05),there was a statistical significance,but compared with those in the relapsed children,the difference had no statistical significance (x2 =1.18,F =1.57,all P ＞ 0.05).The levels of Smac and HtrA2 protein in complete remission children were both higher than those of the normal controls,and the difference had no statistical sigmficance(x2 =1.20,F =2.23,all P ＞ 0.05).In the newly diagnosed children,the levels of Smac and HtrA2 protein in children with acute lymphocytic leukemia(ALL) were higher than those of the acute myeloid leukemia(AML),but the differences had no statistical significance(x2 =0.113,t =1.024,all P ＞ 0.05).In newly diagnosed AL children,the complete remission(CR) rate of the negative expression of Smac(Smac-,90.9％) and the low expression of HtrA2(HtrA2low,84.6％) in the level of protein were higher than those of the positive expression of Smac(Smac +,47.6％) and the high expression of HtrA2 (HtrA2high,47.4％),and there was statistical significance respectively(x2 =5.772,4.596,all P ＜ 0.05).The CR rate of Smac-HtrA2low group (100％) was higher than that of Smac+ HtrA2high group(30.8％)in the children with AL,and the statistical data were of great significance(x =9.692,P ＜0.01).The protein level of Smac in newly diagnosed AL children was correlatedwith HtrA2 (r =0.979,P ＜ 0.001).Conclusions Pro-apoptotic protein Smac and HtrA2 may be involved in and af-fected each other in the pathogenesis and progression in AL,but levels of Smac and HtrA2 protein may be not correlatedwith the types of AL.In newly diagnosed AL children,the high expression of protein Smac and HtrA2 predicts poorprognosis.

Objective To understand the occurrence and the related risk factors of birth defects. Methods Descriptive analysis was conducted on birth detect surveillance in the infants during January 2008 to June 2014. Results A total of 777 cases of birth defect were detected in 73498 infants, and the incidence of birth defect was 1.06%. The 5 most common birth de-fects were congenital heart disease, multi ifnger (toe), hypospadias, cleft lip, and palate and deformity of external ear. Compared infants born with no birth defects, male, preterm, low birth weight, twin and multiple births and resident were statistically higher in infants with birth defects (P<0.05). The major risk factors of birth defects were the medication history, spontaneous abortion, gestational diabetes mellitus, and family history. Conclusions The incidence of birth defect can be reduced by providing good health care during pre-marriage and pregnant so as to decrease the occurrence of premature infants, twins and multiple births, and low birth weight as well as improving prenatal diagnosis and intensifying birth defects surveillance.

Objective To study the relationship between DNA methylation and pathogenesis of childhood immune thrombocytopenic purpura (ITP) by examining the expression of DNA methyltransferase 1(Dnmt1) and DNA methyltransferase 3a (Dnmt3a) mRNA in peripheral blood lymphocytes of the children with ITP. Methods Expression of Dnmt 1 and Dnmt3a mRNA in the peripheral blood lymphocytes in 36 children with newly diagnosed ITP and 26 healthy children were detected using RT-PCR. Results Dnmt1 mRNA expression in peripheral blood lymphocytes in children diagnosed with ITP was 3.02±0.49, significantly lower than 4.58±0.52 in the control group (t=11.95, P<0.001). Dnmt3a mRNA expression in peripheral blood lymphocytes in children diagnosed with ITP was 1.49±0.44, signiifcantly lower than 2.41±0.32 in the control group (t=9.12, P<0.001). Conclusions Children with newly diagnosed ITP have lower DNA methylation status in peripheral blood lymphocytes as compared to that in healthy children. The DNA methylation may play an important role in the etiology of acute ITP in children.

Objective To observe the effect of kallikrein and ozagrel on hemorheology in the treatment of patients with acute cerebral infarction,provide a theoretical basis for clinical treatment.Methods 100 patients with acute cerebral infarction met the inclusion criteria were randomly divided into 50 cases of observation group and 50 cases of control group,the control group were received conventional drug therapy,the observation group were given kallikrein and ozagrel on the basis of the control group,kallikrein 0.15PNA /times,ozagrel 80mg one time,bid,14d for a course of treatment.The symptoms improvement were observed,the NIHSS score and ADL score were calculated after treatment,then the blood were extraced for detecting high shear viscosity of whole blood,red blood cell aggrega-tion index,hematocrit,fibrinogen,erythrocyte sedimentation rate,and the clinical efficacy were judged.Results The total effective rate of the observation group were 96% (48 /50),which of the control group were 66% (33 /50),the total effective of the observation group was significantly higher than the control group (χ2 =16.105,P <0.01);The high shear viscosity of whole blood,red blood cell aggregation index,hematocrit,fibrinogen,erythrocyte sedimentation rate,NHISS of the observation group and the control group after treatment were lower than before treatment (t =6.589 and 3.762,6.204 and 3.661,8.112 and 5.774,5.542 and 3.529,9.429 and 3.962,9.621 and 6.586,all P <0.05),the ADL score was significantly higher than before treatment(t =7.673 and 5.446,all P <0.05),the high shear viscosity of whole blood,red blood cell aggregation index,hematocrit,fibrinogen,erythrocyte sedimentation rate, NHISS of the observation group after treatment were lower than those of the control group (t =3.387,3.545,3.525, 3.288,3.302,4.988,all P <0.05),the ADL score was significantly higher than the control group (t =3.446,P <0.05).Conclusion The method containing kallikrein and ozagrel has exact clinical efficacy,can effectively improve blood rheology and cerebral blood perfusion ischemic area,promote neurological deficits and recover the ability of daily life,and its security is good,which is worthy of promotion.