AIM:To investigate the effects of Panax notoginseng compound formula(PN)on endometrial fibro-sis by regulating inflammatory reaction and intestinal flora(IF)in a rat model of intrauterine adhesion(IUA).METHODS:The rat IUA model was established by following the mechanical injury method.A total of 50 rats were randomly divided in-to sham group,model group,low-dose(210 mg/kg)PN group,medium-dose(420 mg/kg)PN group and high-dose(840 mg/kg)PN group.After 8 weeks of intragastric administration,the uterus was collected to observe morphological changes with naked eye.The degree of uterine tissue damage and fibrosis was evaluated through hematoxylin-eosin(HE)and Mas-son staining.The collagen type Ⅰ(Col Ⅰ)was detected by immunohistochemistry.The interleukin-6(IL-6)and IL-10 pro-tein expression was detected by Western blot.The levels of IL-6,IL-1β,tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor B(VEGFB)were detected by enzyme-linked immunosorbent assay(ELISA).The IF diversity and population structure were observed by 16S amplicon.RESULTS:Compared with the sham group,the uteruses of rats in the model group showed:reduced elasticity,accompanied by congestion and edema;decreased number of glands and blood vessels,and thinned endometrium(P<0.01);increased collagen fibers and Col Ⅰ protein expression(P<0.01);sig-nificantly increased IL-1β,IL-6,TNF-α and VEGFB levels in the uterine tissue(P<0.01);decreased IL-10 level(P<0.01);and reduced IF diversity(P<0.05).Compared with the model group,the drug intervention groups exhibited:re-covered elasticity of the uterus and relieved congestion and edema;increased number of endometrial glands and blood ves-sels(P<0.05);decreased collagen fibers and Col Ⅰ protein expression(P<0.01);reduced IL-1β,IL-6,and TNF-α lev-els to varying degrees in the uterine tissue(P<0.05);elevated IL-10 level(P<0.01);and improved IF diversity(P<0.05).CONCLUSION:The PN is able to significantly improve the endometrial tissue fibrosis in IUA rats.The under-lying mechanisms may be related to the inhibition of IL-6,IL-1β and TNF-α expression,up-regulation of IL-10,and im-provement of IF diversity.

Objective:To investigate the alterations of brain resting-state functional connectivity in patients with leukoaraiosis(LA), and to explore its neuropathological mechanism of cognitive dysfunction.Methods:From August 2022 to February 2023, 28 patients with LA(LA group) and 30 gender, age and education level matched normal controls(NC group) in Jiangsu Shengze Hospital affiliated to Nanjing Medical University were prospectively recruited.Mini mental state examination, trail-making test, and Stroop color-word test were used to evaluate the cognitive function of participants, rs-fMRI images were processed by DPABI V6.1 based on MATLAB R2022a.Voxel-mirrored homotopic connectivity(VMHC) values were calculated and two-sample t test were performed to compare the differences in local brain activity between the two groups.The brain regions with significant differences were selected as the seeds to calculate the functional connectivity(FC) values of the whole brain, and Pearson correlation analyses were performed to evaluate the correlation between the FC values and neuropsychological scores. Results:The VMHC values of the calcarine fissure and surrounding cortex(CAL) (x=±18, y=-63, z=15), postcentral gyrus(PoCG) (x=±39, y=-27, z=48), lingual gyrus(LING) (x=±12, y=-51, z=-6), middle occipital gyrus(x=±27, y=-75, z=24) and insula(x=±36, y=6, z=3) in the LA group were lower than those in the NC group( P<0.05). The seed points FC results showed, FC values between right CAL(CAL.R) and bilateral precuneus(PCUN), right dorsolateral prefrontal cortex(DLPFC.R) and right temporal_mid were reduced in the LA group( P<0.05); FC values between PoCG.R and left CAL, left temporal_mid and right LING were reduced too( P<0.05). Additionally, the FC value in the LA group between CAL.R and DLPFC.R was negatively correlated with the Stroop C score( r=-0.39, P<0.05). The FC value in LA group and NC group between CAL.R and DLPFC.R was negatively correlated with the Stroop C score( r=-0.48, P<0.001)and also negatively correlated with the trail making test B(TMT-B) score( r=-0.40, P<0.01), and the FC value between CAL.R and PCUN.L was negatively correlated with the TMT-B score( r=-0.45, P<0.001). Conclusion:Desynchronized interhemispheric functional connectivity and abnormal cortical circuit functional connectivity were probably associated with the underlying neural mechanisms of cognitive impairment in LA.

Objective To investigate the prevalence of allergic and infectious diseases in children， and to assess the influence of indoor and outdoor environmental factors on these two common diseases in children. Methods A questionnaire was used to investigate the prevalence of allergic and infectious diseases in 140 children of 7 years old in Laizhou Bay， Shandong Province. Logistic regression was used to analyze the associations between indoor and outdoor environmental factors and children’s allergic and infectious diseases， respectively. Results The prevalence of previous eczema and other allergic diseases for the past year in children was 37.9% and 15.0%， respectively， and the prevalence of infectious diseases for the past year was 35.7%. As for allergic diseases， eye irritation due to outdoor air （ OR =2.977； 95% CI ： 1.407‒6.296） and nose irritation due to outdoor air （ OR =5.147； 95% CI ： 1.272‒20.827） were the risk factors for previous eczema in children. Indoor musty taste increased the risks of urticaria （ OR =4.306； 95% CI ： 1.062‒17.454） and previous eczema （ OR =3.853； 95% CI ： 1.080‒13.743）. The use of cockroach killers indoors increased the risk of rhinitis （ OR =6.102； 95% CI ：1.297‒28.697）. As for infectious diseases， having outdoor pollution sources increased the risk of gastrointestinal infection （ OR =4.937； 95% CI ： 1.050‒23.216）， and the use of mosquito coils and clothing mothproofing agents increased the risks of respiratory （ OR =6.333； 95% CI ： 1.397‒28.714） and gastrointestinal infections （ OR =3.218； 95% CI ： 1.074‒9.644）， respectively. However， we did not find associations between indoor passive smoking and allergic or infectious diseases. Conclusion Except outdoor passive smoking， all the other indoor and outdoor environmental factors increase the risks of children’s allergies and infectious diseases.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*

Objective:To investigate the correlation between subclinical hypothyroidism (SCH) and clinical outcomes of patients with acute ischemic stroke.Methods:From July 2014 to October 2017, patients with acute ischemic stroke admitted to Jiangsu Shengze Hospital Affiliated to Nanjing Medical University were enrolled retrospectively. Their demographic and baseline clinical and laboratory data were collected. The modified Rankin Scale was used to evaluate the clinical outcome at 3 months after the onset of symptoms. Multivariate logistic regression analysis was used to determine the independent correlation between SCH and clinical outcome of patients with acute ischemic stroke. Results:A total of 200 patients with acute ischemic stroke were enrolled, including 107 males (53.5%) and 93 females (46.5%). Their age was 69.67±11.38 years. There were 45 patients (22.5%) with SCH, 160 (80.0%) with good outcomes, and 40 (20.0%) had poor outcomes. Univariate analysis showed that there were significant differences in the baseline National Institutes of Health Stroke Scale (NIHSS) score, stroke etiology classification and the proportion of patients with SCH between the poor outcome group and the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that high NIHSS score (odds ratio 2.884, 95% confidence interval 2.005-4.147; P=0.001) and SCH (odds ratio 19.527, 95% confidence interval 2.334-163.386; P=0.006) were the independent risk factors for poor outcomes. Conclusion:High NIHSS score and SCH were associated with the poor outcomes at 3 months after the onset of acute ischemic stroke.

Objective To investigate the correlation between subclinical hypothyroidism (SCH) and carotid atherosclerosis in patients with acute ischemic stroke.Methods Patients with acute ischemic stroke admitted to Nanjing Shengze Hospital Affiliated to Nanjing Medical University from July 2014 to July 2017 were enrolled retrospectively.SCH was defined as elevated levels of serum thyroid stimulating-hormone (TSH),but the free thyroxine (FT4) and free-triiodothyronine (FT3) levels were normal.Carotid plaque and carotid stenosis were assessed using carotid ultrasound.Multivariate logistic regression analysis was used to determine the correlation between SCH and carotid atherosclerosis.Resuts A total of 176 patients with acute ischemic stroke were enrolled,including 81 females and 95 males;36 complicated with SCH,126 complicated with carotid atherosclerotic plaques,and 9 had carotid stenosis.High-density lipoprotein cholesterol (1.36±0.48 mmol/L vs.1.18 ± 0.30 mmol/L;t =2.090,P =0.039) and TSH (6.29[5.44-7.01]mU/L vs.1.87[1.31-2.67] mU/L;Z =9.243,P =0.001) levels in the SCH group were significantly higher than those in the non-SCH group.There were significant differences in age (73.5[65.0-80.0]years vs.68.0[56.0-75.0]years;Z =2.707,P=0.007),stroke etiology classification (x2 =9.270,P=0.038),TSH level (2.19[1.47-3.72]mU/L vs.2.18[1.24-2.62]mU/L;Z=3.230,P=0.001),and the proportion of patients with SCH (26.98％ vs.4.00％;x2 =11.622,P =0.001) between the plaque group and the non-plaque group.There was no statistical difference in demographic and clinical data between the stenosis group and the non-stenosis group (all P ＞0.05).Multivariatelogistic regression analysis showed that advanced age (odds ratio 1.050,95％ confidence interval 1.014-1.088;P =0.006) and SCH (odds ratio 5.328,95％ confidence interval 1.322-21.468;P =0.019) were the independent risk factors for carotid atherosclerotic plaques.Conclusion Advanced age and SCH were the independent risk factors for carotid plaque in patients with acute ischemic stroke.

Objective To explore the relationship between polymorphisms of vitamin D receptor (VDR) and susceptibility of acute ischemic stroke.Methods Genotype distribution in FokI and Apa of VDR were detected by TaqManPCR,and the correlation between different genotypes and the attack of acute ischemic stroke was compared.Results The Ff genotype of FokI could significantly improve the onset risk of acute ischemic stroke (adjusted OR =1.65,95％ CI =1.18 ～2.32).Compared with fa haplotype,distribution of Fa haplotype in acute ischemic stroke was significantly lower than healthy controls (adjusted OR =0.66,95％CI =0.51 ～0.85).Conclusion Genetic variation of VDR is associated with the onset risk of acute ischemic stroke.

Objective To explore the relationship between polymorphisms of vitamin D receptor (VDR) and susceptibility of acute ischemic stroke.Methods Genotype distribution in FokI and Apa of VDR were detected by TaqManPCR,and the correlation between different genotypes and the attack of acute ischemic stroke was compared.Results The Ff genotype of FokI could significantly improve the onset risk of acute ischemic stroke (adjusted OR =1.65,95％ CI =1.18 ～2.32).Compared with fa haplotype,distribution of Fa haplotype in acute ischemic stroke was significantly lower than healthy controls (adjusted OR =0.66,95％CI =0.51 ～0.85).Conclusion Genetic variation of VDR is associated with the onset risk of acute ischemic stroke.

Objective To investigate the risk factors for acute ischemic stroke in patients with lower extremity atherosclerosis (LEA).Methods The consecutive patients with acute ischemic stroke admitted to hospital within 7 d after onset were enrolled retrospectively.Color Doppler flow imaging was used to detect LEA.The demographic characteristics,vascular risk factors,and laboratory parameters were identified and analyzed.Results A total of 156 patients with acute ischemic stroke were enrolled,including 138 with LEA.Univariate analysis showed that age (69.5± 11.8 years vs.60.4± 11.5 years;t =3.063,P =0.003) and the proportion of patients with hypertension (81.1％ vs,55.6％;x2 =2.467,P =0.014) in the LEA group were significantly higher than those in the non-LEA group.Multivariate logistic regression analysis showed that after adjustment for confounders such as gender,baseline systolic blood pressure,diabetes mellitus,and ischemic heart disease,age (odds ratio [OR] 1.059,95％ confidence interval [CI] 1.016-1.105;P=0.007),and hypertension (OR 3.128,95％ CI 1.084-9.026,P =0.035) were the independent risk factors for acute ischemic stroke complicated with LEA.Conclusions Age and hypertension are associated with acute ischemic stroke complicated with LEA.

Objective To evaluate vitamin D status in middle-aged subjects in Beijing and explore the correlation between serum 25-hydroxyvitamin D[25(OH)D] levels and dyslipidemia.Methods A total of 448 individuals over 40 years old were enrolled in the cross-sectional survey.The general information,blood biochemical and lipid profiles and serum 25 (OH) D levels were collected.The subjects were either divided into two groups (the dyslipidemia group and the non-dyslipidemia group) based on the lipid levels,or four groups according to quartiles of 25 (OH) D levels.The association between 25 (OH) D levels and dyslipidemia risk was analyzed by a logistic regression analysis.Results A total of 234 cases were in dyslipidemia group,which accounted for 52.23％ of the subjects.The serum 25 (OH) D levels were significantly lower in the dyslipidemia group than in the non-dyslipidemia group both in men and in women (all P ＜ 0.05).The median serum 25 (OH) D level in the total subjects was 15.7 (12.2,20.1) μg/L with 91.1％ subjects of serum 25 (OH) D level ＜ 30 μg/L.The proportion of subjects with dyslipidemia (high TC,high TG,high LDL-C,or low HDL-C) increased with the decrease of 25 (OH) D level quartiles (P ＜0.05).After adjustment of confounding factors,the logistic regression analysis showed that subjects in the lowest 25 (OH) D quartile group had 143％ higher risks for dyslipidemia than those in the highest quartile group.Conclusion These findings indicate that 25 (OH) D insufficiency is highly prevalent among middleaged individuals and it may be associated with the risk of dyslipidemia.