Cerebrospinal Fluid Rhinorrhea ; surgery ; Endoscopy ; methods ; Female ; Humans ; Male

Haploinsuffieiency of the runt-related transcription factor 2 (Runx2) gene is widely known to be responsible for cleidocranial dysplasia (CCD).To date,more than 190 mutations in Runx2 gene have been reported to be related to CCD.In this study,a novel mutation of Runx2 gene was observed in a female with CCD.Genomic DNA was extracted from peripheral venous blood of the proband and eleven members of her family.Genetic testing on these twelve people identified a novel missense mutation (c.895T＞C,Y299H) in exon 5 of the RUNX2 gene in the proband.This mutation results in an amino acid change at codon 895 (P.Tyr 299 His.) from a tryptophan codon (TAT) to a histidine codon (CAT).Our finding may further extend the known mutation spectrum of the RUNX2 gene,and facilitate prenatal genetic diagnosis of CCD in the future.

Objective:To observe the activation of microglia and the expression of inflammatory factors in hippocampus of mice with depression-like behavior after mother-infant separation （MS） combined with lipopolysaccharide （LPS） stress， and to explore the possible anti-depression mechanisms of Wenyang （WY）， Jieyu （JY）， and Wenyang Jieyu （WYJY） prescriptions from the perspective of warming Yang and relieving depression. Method:Seventy offspring mice were randomly divided into a normal group （n=10）， a LPS stress group （n=10）， and a modeling group （n=50）. After undergoing 8 h·d^-1 mother-infant separation during postnatal day 5 （PD₅）–PD₁₄， mice in the modeling group were further divided into the MS + LPS group， WY group， JY group， WYJY group， and fluoxetine （FLU） group， with 10 in each group. The birth date of the offspring mice was recorded as PD₀. The mice in the normal， LPS， and MS + LPS groups were fed a normal diet during PD₂₁–PD₉₀， while those in the other groups were treated with the mixtures of corresponding drugs and feed， followed by seven-day intraperitoneal injection of LPS since PD₉₁ for inducing depression. The depression-like behavior of mice in each group was detected in the open-field， O-maze， and social interaction tests. The protein expression of microglia-specific ionized calcium-binding adaptor molecule 1 （Iba-1） in the hippocampus was assayed by immunohistochemistry， and the mRNA expression of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， Iba-1， and glucocorticoid receptor （GR） by real-time fluorescence quantitative PCR （Real-time PCR）. Result:Compared with the normal group， the LPS group exhibited significantly reduced residence time at the central area within 5 min （P<0.01） and shortened total exercise distance （P<0.01）. In the MS + LPS group， the open-arm activity time and the total activity distance decreased significantly （P<0.01， P<0.05）， whereas the training， discrimination and exploration time increased significantly （P<0.01）. The expression of Iba-1 in hippocampal CA1 region of mice in the LPS and MS + LPS groups was remarkably elevated （P<0.01）. Compared with the LPS group， the MS + LPS group displayed significantly prolonged distance of 5-min exercise （P<0.05）， increased training， discrimination and exploration time （P<0.05， P<0.01）， and up-regulated Iba-1 expression in hippocampal CA1 area （P<0.01）. As revealed by comparison with the MS + LPS group， both the total 5-min exercise distance （P<0.01） and the training and discrimination time （P<0.01， P<0.05） of mice in each administration group was significantly shortened. The discrimination and exploration time of mice in the JY， WYJY， and FLU groups was significantly reduced （P<0.01）， and the expression of Iba-1 in hippocampal CA1 region of mice in each administration group was significantly down-regulated （P<0.01）. Conclusion:The warming Yang and relieving depression method helps to inhibit the occurrence and development of depression due to its efficacy in activating microglia in hippocampus of depression mice and lowering the expression of IL-1β， IL-6， and TNF-α.

Objective:To observe the activation of microglia in hippocampus of depressed and anxious mice induced by maternal separation with acute restraint stress and the expression of interleukin-1β（IL-1β），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α）， investigating the mechanism of Wenyang Jieyu prescription in treating anxiety and depression. Method:Eighty four male C57BL offspring were randomly divided into control group， acute restraint stress group and model group on postnatal day 0（PD0）. Maternal separation combined with acute restraint stress was used to prepare anxious and depressed model mice， dividing the model mice into model group， Wenyang， Jieyu， Wenyang Jieyu and fluoxetine group according to random number table method. During the period of PD21-PD90， the control， acute restraint stress and model mice were fed with normal diet， with the other groups fed with corresponding medicine mixed diet. The Wenyang， Jieyu and Wenyang Jieyu groups were given 5.85， 12.03 and 16.71 g·kg^-1·d^-1 respectively. The fluoxetine group was given 2.60 mg·kg^-1·d^-1. Open field， zero maze test and social interaction tests were used to evaluate the anxiety and depression of model mice. The expression of Iba-1 in hippocampal microglia was detected by immunohistochemistry（IHC）. The mRNA expression of IL-1β， IL-6， TNF-α， Iba-1 and glucocorticoid receptor（GR）were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the control group， total movement distance and time spent in central zone in 5 min of the model mice significantly decreased（P<0.01）， time spent in opened arm and total movement distance decreased significantly（P<0.05，P<0.01）， investigation time during testing and training increased significantly（P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly increased（P<0.01）， the expression levels of GR mRNA significantly decreased（P<0.01）. The result of IHC staining showed that microglia were over activated. Compared with the model group， total movement distance and time spent in central zone in 5 min of mice in the Wenyang Jieyu and fluoxetine group significantly increased（P<0.05，P<0.01）.Time spent in opened arm significantly increased（P<0.01）. Investigation time during testing and training significantly decreased（P<0.05，P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly decreased（P<0.05，P<0.01）. The expression of GR mRNA increased significantly（P<0.05，P<0.01）. IHC staining showed the microglia recovered. Time spent in opened arm of mice in the Wenyang group and Jieyu group significantly increased （P<0.01）， time spent investigating during testing decreased significantly （P<0.05）， the expression levels of Iba-1 protein and mRNA，IL-6 mRNA significantly decreased （P<0.05，P<0.01）. The expression of GR mRNA of mice in the Wenyang group significantly increased （P<0.05）， the expression of TNF-α mRNA significantly decreased （P<0.05）. Total movement distance of mice in the Jieyu group increased significantly （P<0.01）， time spent investigating during training decreased significantly （P<0.05），the expression level of IL-1β mRNA significantly decreased （P<0.05）. IHC staining showed that microglia recovered partly in both groups. Conclusion:The comprehensive curative effect and pharmacological action of Wenyang Jieyu prescription were better than Wenyang prescription and Jieyu prescription. Wenyang Jieyu prescription can treat anxiety and depression in maternal separation and acute restraint stress mice， its possible mechanism may be related to the decreased activation of microglia， down-regulation of IL-1β，IL-6，TNF-α expression and up-regulation of GR expression.

Objective:To investigate the antitumor effect and the mechanism of Dunhuang Pingweiwan and its decomposed recipes based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway in SCG-7901 gastric cancer-mice. Method:The subcutaneous tumor bearing model of SCG-7901 gastric cancer in mice was established， and the the mice were randomized into model group， Dunhuang Pingweiwan group （14.04 g·kg^-1·d^-1）， Huoxue Jiedu group （6.50 g·kg^-1·d^-1）， Wenzhong Sanhan group （3.64 g·kg^-1·d^-1） and cisplatin group （2 mg·kg^-1·d^-1）， with 8 mice in each group. From the 8^th day of inoculation， the mice were administered for 10 consecutive days. The mice were weighed and the general conditions were observed every other day. On the next day of the last administration， the mice were sacrificed， and the tumor was removed and weighed to calculate the anti-tumor rate. The histopathological changes were observed by hematoxylin-eosin （HE） staining， and the mRNA and protein expressions of PI3K， Akt， and mTOR in tumor tissues were detected by real-time polymerase chain reaction（Real-time PCR） and immunohistochemistry （IHC）， respectively. Result:From the 10^th day of inoculation， the mice in cisplatin group were generally in poor condition and their body mass decreased. The mice in model group， Dunhuang Pingweiwan group， Huoxue Jiedu group and Wenzhong Sanhan group were generally fair， and their body mass increased without significant difference among groups. The tumor inhibition rates of Dunhuang Pingweiwan， Huoxue Jiedu， Wenzhong Sanhan and cisplatin groups were 30.74%， 24.80%， 4.19% and 63.84%， respectively. Except for Wenzhong Sanhan group， tumor weight of the other treatment groups was significantly lower than that of the model group （P<0.01）， and there was no significant difference between the Dunhuang Pingweiwan and Huoxue Jiedu group. Dunhuang Pingweiwan and Huoxue Jiedu group could significantly reduce tumor cell density and cause tumor cell necrosis. Compared with the model group， the expressions of PI3K， Akt， and mTOR mRNA and protein in the Dunhuang Pingweiwan， Huoxue Jiedu and cisplatin groups significantly decreased （P<0.05， P<0.01）， and there was no significant difference between the Dunhuang Pingweiwan group and Huoxue Jiedu group. Conclusion:Dunhuang Pingweiwan and its decomposed recipes （Huoxue Jiedu） have a certain anti-tumor effect on the SCG-7901 gastric cancer-mice， and the mechanism may be related to the down-regulation of key molecules in the PI3K/Akt/mTOR signaling pathway.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications