Estrogen receptors (ERs) are members of nuclear receptors and related to several diseases such as cancer, inflammation and osteoporosis. ERs have two forms, ERα and ERβ, which have different functions and organism distributions. Compounds selectively targeting ERβ can regulate important physiological functions and avoid the side effects caused by targeting ERα. Therefore, selective ERβ ligands have received considerable research interest in recent years. In this article, different kinds of selective ERβ ligands were summarized and their structure-activity relationships were also analyzed.
Estrogen Receptor beta ; chemistry ; Humans ; Ligands ; Structure-Activity Relationship

Objective To knockout Rag2 and IL2rg genes and construct severe combined immunodeficiency mice based on CRISPR/Cas9 technology. Method Design and synthesis of 25 bp sgRNA were made according to the Rag2 and IL2rg sequences in Genbank. After annealing, sgRNA was cloned into pX330 vector. Recombination plasmid Rag2?sgRNA, IL2rg?sgRN and Cas9 were then transcribed into RNA, these RNA were microinjected into zygotes and the zygotes were transplanted into recipient ICR mice. F0 founders were born and mutated F0 founders mated with wild type mice to obtain F1 generation heterozygous mice. Mutated F1 mice were crossed and got F2 generation homozygous mice. Genotype and phenotype of the knockout mice were identified by sequencing, flow cytometry and xenograft model. Results Rag2?sgRNA and IL2rg?sgRNA recombination plasmids were constructed and transcribed into RNA. After microinjection and mat? ing, F0 founders were born and F2 homozygous mice were obtained. The results of sequencing showed that there were two types of genotype in IL2rg gene, 10 bp or 11 bp deletion;however, there was only one genotype in Rag2 gene, which was 8 bp deletion. Compared with wild?type BALB/c mice, the number of CD3 +, B220 + and NKp46 + cells in peripheral blood of the knockout mice was reduced significantly. After inoculation of human breast cancer cell line SKBR?2HL cells, tumor size in the xenograft mouse model was increased gradually along with time extension. Conclusion CRISPR/Cas9 is an efficient way to mutate Rag2 and IL2rg gene in mice in vivo, leading to aberrant T cells, B cells and NK cells.

BACKGROUNDCerebral amyloid angiopathy (CAA) is one of the main causes of spontaneous intracranial hemorrhage (ICH). No established link is available between pathological scores of CAA and its outcome. This study aimed to identify the correlations between pathological severity and poor postoperative outcome in the Chinese population.

METHODSBetween May 2006 and April 2011, 367 consecutive patients who underwent surgery for CAA-related ICH in 71 hospitals throughout the mainland of China were enrolled in this study. Twelve months after surgery, we evaluated these patients' outcomes according to the modified Rankin Scale (mRS) and statistically correlated risk factors (demographics, medical history, pathological results, and surgical details) that are associated with a favorable (mRS < 3) and poor (mRS ≥ 3) outcome groups.

RESULTSRisk factors for poor postoperative outcome in 367 patients with CAA-related ICH included advanced age (OR 1.034, 95%CI 1.001 - 1.067, P = 0.042), CAA pathology severity (OR 2.074, 95%CI 7.140 - 16.25, P < 0.001), lobar hematoma (OR 0.225, 95%CI 0.104 - 0.486, P < 0.001), presence of intraventricular hemorrhage (OR 0.478, 95%CI 0.229 - 1.001, P = 0.050), and/or subarachnoid hemorrhage (OR 2.629, 95%CI, 1.051 - 6.577, P = 0.039).

CONCLUSIONSPoor postoperative outcome of patients with CAA-related ICH was more related to the severe pathological manifestation instead of other factors. Prior ischemia may present an early stage of CAA.

Aged ; Cerebral Amyloid Angiopathy ; pathology ; physiopathology ; China ; Female ; Humans ; Intracranial Hemorrhages ; pathology ; physiopathology ; Male ; Middle Aged ; Risk Factors

OBJECTIVETo observe different effects of moxibustion on extracellular potassium ion in acupoint under physiological and pathological status and provide experimental evidence for exploring action mechanism of moxibustion on acupoint local.

METHODSForty female SD rats were randomly divided into a blank group, a blank-moxibustion group, a model group and a model-moxibustion group, 10 cases in each one. The complete Freund's adjuvant(CFA) was adopted to establish model of adjuvant arthritis (AA) in the model group and model-moxibustion group. No treatment was given in the blank group and model group while moxibustion was applied at "Zusan-li" (ST 36) for 30 min in the blank-moxibustion group and model-moxibustion group. The tissue fluid in "Zusanli" (ST 36) was collected with microdialysis and real-time analyzed by electrolytic analyzer. The change of concentration of potassium ion in "Zusanli" (ST 36) was observed.

RESULTS(1) Under physiological status, the concentration of extracellular potassium ion in the blank group was not changed within 150 min (P > 0.05); before the moxibustion, the concentration of extracellular potassium ion in the blank-moxibustion group was (1.21 +/- 0.31) mmol/L, and after treatment it was gradually increased and reached its peak at (2.38 +/- 0.42) mmol/L after 60 min (P < 0.05), then it was reduced. 150 min after the treatment, concentration of potassium ion was slightly higher than that before moxibustion as well as that in the blank group. The concentration in the blank-moxibustion group at 60 min was statistically significant compared with that in the blank group (P < 0.05). (2) Under pathological status, the concentration of extracellular potassium ion in the model group was not changed within 150 min, differences of which at each time point was not statistically significant (all P > 0.05). Before the moxibustion, the concentration of extracellular potassium ion was (1.09 +/- 0.12) mmol/L in the model-moxibustion group, and it was immediately increased to (1.96 +/- 0.18) mmol/L after moxibustion. 60 min and 90 min after the moxibustion, it still maintained a higher level, which was (1.87 +/- 0.29) mmol/L and (1.59 +/- 0.16) mmol/L respectively (both P < 0.05). The differences of each time point after moxibustion in the model-moxibustion group were statistically significant compared with those in the model group (all P < 0.05).

CONCLUSIONThe moxibustion could increase the concentration of potassium ion in rat's acupoint local under physiological status but time of effect is short; with moxibustion at "Zusanli" (ST 36) under pathological status, the concentration of local potassium ion is obviously increased and maintains for a long time.

Acupuncture Points ; Animals ; Arthritis, Experimental ; metabolism ; therapy ; Disease Models, Animal ; Female ; Humans ; Moxibustion ; Potassium ; metabolism ; Rats ; Rats, Sprague-Dawley

AIMTo study the modulation of extracellular pH on the voltage-gated potassium currents (I(Kv)) in isolated pulmonary artery smooth muscle cells (PASMCs).

METHODSI(Kv) was recorded using whole-cell patch clamp technique under the external solutions with different pH. The electrophysiological characteristics of I(Kv) were then analyzed.

RESULTS(1) As compared to the normoxic group, I(K), decreased under acidic condition. When the extracellular pH were 7.0, 6.5, 6.0, the peak currents at a potential of +60 mV were inhibited by 16.93% +/- 2.47% (P < 0.01), 33.03% +/- 2.13% (P < 0.01), 41.59% +/- 6.53% (P < 0.01) respectively, and the current-voltage relationship (I/V) curve shifted to the right. (2) When the extracellular pH was 7.0, 6.5, 6.0, the voltage-depended Gk-Em was shifted to the direction of positive and the activation was sped up.

CONCLUSIONThe results suggest that with the development of hypoxic pulmonary vasoconstriction (HPV), extracellular pH may take part in the modulation of Kv channels partly, then make the cell depolarized and decrease the Kv currents, this will lead to open the L-type calcium channel and contract the pulmonary artery smooth muscle. It may be one of the mechanisms that hypoxic leads to HPV and finally accelerate the development of HPV.

Animals ; Hydrogen-Ion Concentration ; Male ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; metabolism ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Voltage-Gated ; physiology ; Pulmonary Artery ; cytology ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the correlation between moderate to severe periodontitis and coronary heart disease (CHD) and to examine the serum C-reactive protein (CRP) levels in subjects with CHD and/or moderate to severe periodontitis.

METHODSSerum CRP levels, serum lipids [low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), total cholesterol (TC) and triglyceride (TG)] and clinical periodontal parameters [clinical attachment loss (CAL), probing depth (PD), and bleeding on probing (BOP)] were measured and analyzed in coexistent moderate to severe periodontitis and CHD patients (n = 47), CHD patients (n = 28), moderate to severe periodontitis patients (n = 40), and healthy subjects (n = 40).

RESULTSThe serum CRP levels in control group, moderate to severe periodontitis patients, CHD patients and patients with both diseases were (1.30 +/- 0.15), (2.44 +/- 0.18), (5.99 +/- 0.82) and (6.88 +/- 0.71) mg/L, respectively. The differences among these four groups were significant (P < 0.001). The multivariate logistic regression revealed that moderate to severe periodontitis patients exhibited markedly elevated odds of having CHD (OR = 2.417, 95% CI: 1.126 - 6.659). The total cholesterol levels were also significantly different among the four groups (P = 0.017).

CONCLUSIONSThe moderate to severe periodontitis was associated with elevated serum CRP levels which may in turn affect the initiation and progression of CHD, and may be a risk factor for CHD.

Adult ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Coronary Disease ; blood ; Female ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Periodontitis ; blood

OBJECTIVETo investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on the expressions of Caspase-3 and Caspase-9 genes in rat Leydig cells and the apoptosis of the cells in vitro.

METHODSLeydig cells were isolated from male SD rats, primarily cultured and treated with DEHP at a low (10 nmol/L), a medium (50 nmol/L) and a high dose (100 nmol/L) for 24 hours. Then the mRNA expressions of Caspase-3 and Caspase-9 genes in the Leydig cells were detected by real time PCR, their protein expressions determined by Western blot, and the apoptosis of the Leydig cells measured by flow cytometry.

RESULTSCompared with the DMSO control group, the low-, medium- and high-dose DEHP groups showed significantly upregulated expressions of Caspase-3 mRNA (1.69 +/- 0.38 vs 3.82 +/- 0.39, 6.91 +/- 0.40 and 15.47 +/- 0.40, P < 0.05), Caspase-3 protein (0.18 +/- 0.0.09 vs 0.32 +/- 0.10, 0.61 +/- 0.08 and 0.89 +/- 0.09, P < 0.05), Caspase-9 mRNA (2.24 +/- 0.41 vs 5.16 +/- 0.43, 9.61 +/- 0.45 and 19.22 +/- 0.43, P < 0.05) and Caspase-9 protein (0.26 +/- 0.07 vs 0.40 +/- 0.08, 0.68 +/- 0.09 and 0.96 +/- 0.08, P < 0.05), as well as increased apoptosis rate of Leydig cells (4.36 +/- 1.11 vs 7.52 +/- 1.09, 12.72 +/- 1.10 and 24.59 +/- 1.11, P < 0.05), all in a dose-dependent manner.

CONCLUSIONDEHP can induce the apoptosis of rat Leydig cells by activating the apoptosis Caspase pathway, and consequently affect the function of Leydig cells.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Diethylhexyl Phthalate ; toxicity ; Leydig Cells ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

Adult ; Aged ; Aged, 80 and over ; Female ; Hepatic Encephalopathy ; diagnosis ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Psychometrics ; methods ; Young Adult

OBJECTIVETo explore the risk factors for coronary artery lesions (CAL) secondary to Kawasaki disease (KD) in children.

METHODSThe medical data of 895 children with KD were retrospectively reviewed. The patients were classified into two groups according to the presence of CAL: CAL (n=284) and control (n=611). The clinical and laboratory indices were compared between the two groups. The risk factors for the development of CAL in children with KD were identified by multiple logistic regression analysis.

RESULTSMale gender (OR=1.712), occurrence of non-CAL complications (OR=2.028), atypical KD (OR=3.655), intravenous immunoglobulin (IVIG) resistance (OR=2.912), more than 5 days of fever duration before IVIG treatment (OR=1.350), and increased serum procalcitonin (PCT) level (OR=1.068) were the independent risk factors for the development of CAL in children with KD (P<0.05), whereas increased serum albumin (Alb) level was a protective factor (OR=0.931, P<0.05). The areas under the receiver operating characteristic curve of serum PCT and ALB for prediction of the development of CAL in children with KD were 0.631 and 0.558, respectively.

CONCLUSIONSMale gender, atypical KD, occurrence of other non-CAL complications, long duration of fever and IVIG resistance are associated with an increased risk for CAL in children with KD. Serum PCT and ALB have little value in the prediction of CAL in children with KD.

Adolescent ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Child ; Child, Preschool ; Coronary Artery Disease ; etiology ; Female ; Humans ; Immunoglobulins, Intravenous ; therapeutic use ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; Protein Precursors ; blood ; Risk Factors

OBJECTIVETo investigate the 4-hydroxynonenal (4-HNE) expression changes and the impact of ulinastatin (UTI) METHODS: Seventy-two healthy Sprague-Dawley rats were randomly divided into three groups: the control group, poisoning group and treatment group, with 24 rats in each group. The model of lung injury was established by intragastric PQ (80 mg/kg) administration in poisoning group and treatment group, and 1 mL saline was administered intragastrically in the control group. The rats in treatment group were injected intraperitoneally with UTI (100 000 U/kg) 30 minutes after PQ administration, and the rats in the control group and poisoning group were intraperitoneally injected with the same volume of saline. After different treatments, the pathological changes and the expression of 4-HNE in lung tissue was detected in 12, 24, and 72 h in three groups.

RESULTSIn the poisoning group and treatment group, the expression of 4-HNE in lung tissue of rats were increased in 12 h after poisoning and reached the peak in 48 h; in 72 h after poisoning, the expression of 4-HNE in lung tissue were decreased, but they were still high. Compared with the control group, the expression of 4-HNE in lung tissue of rats were significantly increased in the poisoning group and treatment group (P < 0.05). And compared with the poisoning group, the expression of 4-HNE in lung tissue of rats were significantly decreased in the treatment group (P < 0.01). The pathological changes were observed, including alveolar capillary expansion, diffuse alveolar hemorrhage and alveolar inflammation cell infiltration, were found in lungs of rats in poisoning group and treatment group. There is no significant change in the control group. Compared with the control group, the expression of 4-HNE in lung tissue significantly increased in poisoning group and treatment group (P < 0.01), but the expression in treatment group was lower than in poisoning group (P < 0.01).

CONCLUSIONThe expression of 4-HNE increased in PQ intoxicated rats. UTI may reduce the expression of 4-HNE and reduce lung injury in PQ intoxicated rats.

Aldehydes ; metabolism ; Animals ; Glycoproteins ; pharmacology ; Lung ; drug effects ; metabolism ; pathology ; Lung Injury ; metabolism ; pathology ; Paraquat ; poisoning ; Rats ; Rats, Sprague-Dawley