A role of PIEZO1 in iron metabolism in mice and humans.

Iron overload causes progressive organ damage and is associated with arthritis, liver damage, and heart failure. Elevated iron levels are present in 1%-5% of individuals; however, iron overload is undermonitored and underdiagnosed. Genetic factors affecting iron homeostasis are emerging. Individuals with hereditary xerocytosis, a rare disorder with gain-of-function (GOF) mutations in mechanosensitive PIEZO1 ion channel, develop age-onset iron overload. We show that constitutive or macrophage expression of a GOF Piezo1 allele in mice disrupts levels of the iron regulator hepcidin and causes iron overload. We further show that PIEZO1 is a key regulator of macrophage phagocytic activity and subsequent erythrocyte turnover. Strikingly, we find that E756del, a mild GOF PIEZO1 allele present in one-third of individuals of African descent, is strongly associated with increased plasma iron. Our study links macrophage mechanotransduction to iron metabolism and identifies a genetic risk factor for increased iron levels in African Americans.

Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection.

Hereditary xerocytosis is thought to be a rare genetic condition characterized by red blood cell (RBC) dehydration with mild hemolysis. RBC dehydration is linked to reduced Plasmodium infection in vitro; however, the role of RBC dehydration in protection against malaria in vivo is unknown. Most cases of hereditary xerocytosis are associated with gain-of-function mutations in PIEZO1, a mechanically activated ion channel. We engineered a mouse model of hereditary xerocytosis and show that Plasmodium infection fails to cause experimental cerebral malaria in these mice due to the action of Piezo1 in RBCs and in T cells. Remarkably, we identified a novel human gain-of-function PIEZO1 allele, E756del, present in a third of the African population. RBCs from individuals carrying this allele are dehydrated and display reduced Plasmodium infection in vitro. The existence of a gain-of-function PIEZO1 at such high frequencies is surprising and suggests an association with malaria resistance.

GPR68 Senses Flow and Is Essential for Vascular Physiology.

Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells. We identified a mechanosensitive cell line that exhibits shear stress-activated calcium transients, screened a focused RNAi library, and identified GPR68 as necessary and sufficient for shear stress responses. GPR68 is expressed in endothelial cells of small-diameter (resistance) arteries. Importantly, Gpr68-deficient mice display markedly impaired acute FMD and chronic flow-mediated outward remodeling in mesenteric arterioles. Therefore, GPR68 is an essential flow sensor in arteriolar endothelium and is a critical signaling component in cardiovascular pathophysiology.

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis.

ABSTRACT: Cell-surface exposure of phosphatidylserine (PS) is essential for phagocytic clearance and blood clotting. Although a calcium-activated phospholipid scramblase (CaPLSase) has long been proposed to mediate PS exposure in red blood cells (RBCs), its identity, activation mechanism, and role in RBC biology and disease remain elusive. Here, we demonstrate that TMEM16F, the long-sought-after RBC CaPLSase, is activated by calcium influx through the mechanosensitive channel PIEZO1 in RBCs. PIEZO1-TMEM16F functional coupling is enhanced in RBCs from individuals with hereditary xerocytosis (HX), an RBC disorder caused by PIEZO1 gain-of-function channelopathy. Enhanced PIEZO1-TMEM16F coupling leads to an increased propensity to expose PS, which may serve as a key risk factor for HX clinical manifestations including anemia, splenomegaly, and postsplenectomy thrombosis. Spider toxin GsMTx-4 and antigout medication benzbromarone inhibit PIEZO1, preventing force-induced echinocytosis, hemolysis, and PS exposure in HX RBCs. Our study thus reveals an activation mechanism of TMEM16F CaPLSase and its pathophysiological function in HX, providing insights into potential treatment.

The levels of soluble CD137 are increased in tuberculosis patients and associated with disease severity and prognosis.

Tuberculosis (TB) was the leading cause of death from a single infectious agent before the coronavirus pandemic. Therefore, it is important to search for severity biomarkers and devise appropriate therapies. A total of 139 pulmonary TB (PTB) patients and 80 healthy controls (HCs) were recruited for plasma soluble CD137 (sCD137) detection through ELISA. Moreover, pleural effusion sCD137 levels were measured in 85 TB patients and 36 untreated lung cancer patients. The plasma cytokine levels in 64 patients with PTB and blood immune cell subpopulations in 68 patients with PTB were analysed via flow cytometry. Blood sCD137 levels were higher in PTB patients (p = 0.012) and correlated with disease severity (p = 0.0056). The level of sCD137 in tuberculous pleurisy effusion (TPE) was markedly higher than that in malignant pleurisy effusion (p = 0.018). Several blood cytokines, such as IL-6 (p = 0.0147), IL-8 (p = 0.0477), IP-10 (p ≤ 0.0001) and MCP-1 (p = 0.0057), and some laboratory indices were significantly elevated in severe PTB (SE) patients, but the percentages of total lymphocytes (p = 0.002) and cytotoxic T cells (p = 0.036) were significantly lower in SE patients than in non-SE patients. In addition, the sCD137 level was negatively correlated with the percentage of total lymphocytes (p = 0.0008) and cytotoxic T cells (p = 0.0021), and PTB patients with higher plasma sCD137 levels had significantly shorter survival times (p = 0.0041). An increase in sCD137 is a potential biomarker for severe TB and indicates a poor prognosis.

Parental Migration Trajectories From Childhood Through Adolescence: Longitudinal Impact on Emotional and Behavioral Problems Among Chinese Adolescents.

It is estimated that there are about 23% of all children in China experiencing parental migration and being left behind at hometown. Existing research indicated a significant association between parental migration and children development but overlooked the dynamic changes in family structure caused by parental migration. In this study, data was derived from a nationally representative longitudinal survey-the China Family Panel Studies. The main analyses employed four waves of data (2012, 2014, 2016, and 2018) and included 1401 adolescents aged 10-15 years (Mean:12.35, SD:1.67; 54.2% female). Six typical trajectories of parental migration capturing both migration status at each timepoint and changes in the status across six years were created. Children's depression and internalizing problems and externalizing problems were concerned outcomes. The mediating roles of the caregiver-child interaction and caregiver's depression were examined. Adolescents in the trajectory group described as experiencing transitions between being left behind by both parents and non had a higher risk of depression and internalizing and externalizing problems. Caregivers' depression was a significant mediator between parental migration and adolescent depression.

Design of double-lattice GaN-PCSEL based on triangular and circular holes.

We have theoretically designed a double-lattice photonic crystal surface-emitting laser (PCSEL) based on triangular and circular holes. In the design, porous-GaN which has the properties of lower refractive index and high quality stress-free homo-epitaxy with GaN, was first proposed to be the cladding layer for GaN-PCSEL. The finite difference-time domain (FDTD), the plane wave expansion (PWE), and the rigorous coupled-wave analysis (RCWA) method were employed in the investigation. Our simulations achieved a radiation constant of up to 50 cm-1 and a slope efficiency of more than 1 W/A while maintaining a low threshold gain. We conducted a systematic study on the effects of the filling factor, etching depth, and holes shift, on the performance of the PCSEL. The findings indicate that increasing the filling factor improves the radiation constant and slope efficiency. Asymmetric hole patterns and varying etching depths have a similar effect. The introduction of asymmetric patterns and a double lattice in the photonic crystal breaks the symmetry of electric fields in the plane, while different etching depths of the two holes break the symmetry in the vertical direction. Additionally, altering the shift of the double lattice modifies the optical feedback in the resonators, resulting in variations of cavity loss and confinement factor.

Effects of functional performance and national health insurance cost on length of hospitalization for postacute care in stroke: a retrospective observational study.

BACKGROUND: The postacute care for cerebrovascular disease (PAC-CVD) program was launched in Taiwan nearly a decade ago. However, no clear regulations regarding length of stay (LOS) in the program and extension standards exist. Thus, the allocation of limited medical resources such as hospital beds is a major issue. METHODS: This novel study retrospectively investigated the effects of functional performance and national health insurance (NHI) costs on PAC-CVD LOS. Data for 263 patients with stroke who participated in the PAC-CVD program were analysed. Hierarchical multiple regression was used to estimate the effects of functional performance and NHI costs on LOS at three time points: weeks 3, 6, and 9. RESULTS: At week 3, age, NHI costs, modified Rankin scale score, and Barthel index significantly affected LOS, whereas at week 6, age and NHI costs were significant factors. However, functional performance and NHI costs were not significant factors at week 9. CONCLUSIONS: The study provides crucial insights into the factors affecting LOS in the PAC-CVD program, and the results can enable medical decision-makers and health care teams to develop inpatient rehabilitation plans or provide transfer arrangements tailored to patients. Specifically, this study highlights the importance of early functional recovery and consideration of NHI costs when managing LOS in the PAC-CVD program.

Identification of serum MiRNAs as candidate biomarkers for non-small cell lung cancer diagnosis.

BACKGROUND: Lung cancer is one of the most common solid tumors worldwide and the leading cause of cancer-associated death. Non-small cell lung cancer (NSCLC) is accounts for approximately 85% of all the lung cancers and lung squamous carcinoma (SCC) and adenocarcinoma (ADC) are the main subtypes of NSCLC. Early diagnose using serum biomarkers could improve the overall survival of patients. In this study, we aimed to identify miRNAs from serum with clinical utility in the diagnosis of NSCLC. METHODS: Ten patients with SCC, ten patients with ADC and five noncancerous individuals were enrolled in the screening cohort. miRNA expression levels in serum were measured by microarray analysis. Candidate miRNAs were validated by real-time quantitative polymerase chain reaction analysis in a validation cohort of 78 NSCLC patients and 44 noncancerous individuals. Receiver operating characteristic curves were used to assess the diagnostic performance of serum miRNAs for NSCLC. Logistic regression was used to evaluate the diagnostic value of the combination of markers. RESULTS: Six candidate miRNAs were differentially expressed between NSCLC patients and noncancerous individuals in the screening set (fold change > 2, p < 0.05). Among them, expression levels of miR-3149 and miR-4769.3p were confirmed to be significantly increased in tumor serum in the validation set. The area under the curve values of miR-3149 and miR-4769.3p in distinguishing NSCLC patients from noncancerous controls were 0.830 and 0.735, respectively. When combined with tumor markers CEA and Cyfra21-1, the joint diagnostic model increased the area under the curve to 0.898. CONCLUSION: Serum miRNAs miR-3149 and miR-4769.3p were up-regulated in NSCLC and may be potential biomarkers for early diagnosis of lung cancer.

Inter-Multilevel Super-Orthogonal Space-Time Coding Scheme for Reliable ZigBee-Based IoMT Communications.

The Internet of Things (IoT) technology has revolutionized the healthcare industry by enabling a new paradigm for healthcare delivery. This paradigm is known as the Internet of Medical Things (IoMT). IoMT devices are typically connected via a wide range of wireless communication technologies, such as Bluetooth, radio-frequency identification (RFID), ZigBee, Wi-Fi, and cellular networks. The ZigBee protocol is considered to be an ideal protocol for IoMT communication due to its low cost, low power usage, easy implementation, and appropriate level of security. However, maintaining ZigBee's high reliability is a major challenge due to multi-path fading and interference from coexisting wireless networks. This has increased the demand for more efficient channel coding schemes that can achieve a more reliable transmission of vital patient data for ZigBee-based IoMT communications. To meet this demand, a novel coding scheme called inter-multilevel super-orthogonal space-time coding (IM-SOSTC) can be implemented by combining the multilevel coding and set partitioning of super-orthogonal space-time block codes based on the coding gain distance (CGD) criterion. The proposed IM-SOSTC utilizes a technique that provides inter-level dependency between adjacent multilevel coded blocks to facilitate high spectral efficiency, which has been compromised previously by the high coding gain due to the multilevel outer code. In this paper, the performance of IM-SOSTC is compared to other related schemes via a computer simulation that utilizes the quasi-static Rayleigh fading channel. The simulation results show that IM-SOSTC outperforms other related coding schemes and is capable of providing the optimal trade-off between coding gain and spectral efficiency whilst guaranteeing full diversity and low complexity.

Orbital Compartment Syndrome and Irreversible Blindness Related to Orbital Varix Thrombosis: A Case Report.

BACKGROUND: Orbital compartment syndrome (OCS) is an ocular emergency that can severely threaten the visual potential. The most common etiologies include facial trauma-related orbital wall fractures and postoperative bleeding within the orbit. Nontraumatic cases were also reported sporadically, although they are rare. The orbital volume limits the compliance to expand when space-occupying lesions develop. Both direct compression of the optic nerve and depleted perfusion from elevated intraorbital pressure subsequently lead to ischemic optic neuropathy and vision loss. CASE REPORT: A 74-year-old man experienced headache, bulging left eye, dull pain, vision loss, nausea, and vomiting within 1 day. Computed tomography and magnetic resonance imaging revealed a heterogeneous mass extending from the orbital apex and connected with the ophthalmic vein. Lateral canthotomy and cantholysis were performed at bedside for emergent orbital decompression. The proptosis and pain relieved after surgery, but visual loss remained irreversible. Surgical exploration was conducted and pathology proved the diagnosis of varix of the ophthalmic vein with thrombosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should be aware of the presentation of OCS and perform timely orbital decompression, which could reverse visual impairment. These patients might also benefit from immediate consultants with ophthalmologists and radiologists.

A 45-year experience of uveal melanoma in Taiwan: Verification of American Joint Committee on Cancer staging system and prognostic factors.

BACKGROUND/PURPOSE: To verify the staging system of the American Joint Committee on Cancer (AJCC) 8th edition for uveal melanoma, and to propose the prognostic factors of uveal melanoma by a 45-year cohort study. METHODS: We collected patients who underwent operation with pathological proof from 1973 to 2017. The demographic data including gender, age, laterality, metastatic pattern, and histopathology type were recorded. The predictability for survival and monotonicity of gradients of the AJCC 8th edition were evaluated. The prognostic factors for survival were analyzed by univariate and multivariate analysis. RESULTS: A total of 72 patients were collected. The median age was 55 year-old (range 24-100). No specific gender predilection was revealed in our study. About 75.9% of metastases events happened in the first five-year of follow-up, and hepatic involvement was the most common. By the AJCC 8th edition, the distribution for stage I: II: III was 8 (11.1%), 37 (51.4%), and 27 (37.5%). The prognostic staging groups manifested fair predictability and monotonicity of gradients for survival outcome. The tumors with epithelioid cell type and ciliary body involvements had higher tumor-related mortality. CONCLUSION: The AJCC 8th edition prognostic staging groups for outcome prediction was validated. Periodic screening for metastases should be more frequent in the first five-year follow-up. The tumors with epithelioid cell pattern and ciliary body involvements were at risk of higher tumor-related mortality in Taiwanese patients.

Trends of dental caries in permanent teeth among 12-year-old Chinese children: evidence from five consecutive national surveys between 1995 and 2014.

BACKGROUND: Dental caries have a serious impact on general health and well-being; however, there is a lack of relevant data on the development trends of dental caries in permanent teeth among 12-year-old children in China. We aim to assess long-term trends of dental caries in permanent teeth among 12-year-old children in China and identify the susceptible subgroups based on five consecutive national surveys from 1995 to 2014. METHODS: A total of 88 972 subjects were extracted from five consecutive national surveys (1995, 2000, 2005, 2010, 2014). Standardized dental examinations were conducted and the oral health status of each subject was recorded. The prevalence of Decayed, Missing and Filled teeth (DMF%), mean Decayed, Missing, Filled teeth score (DMFT) and Caries Filling Ratio (CFR) were used as measurement indicators. Cochran-Armitage trend test was used to evaluate the trends in DMF% and CFR, and multivariate linear regression was used to evaluate the trends in DMFT. RESULTS: A V-shaped fluctuating upward trend in DMF% during 1995-2014 was observed (Z = - 13.124, P < 0.001), and the DMF% in 1995-2014 was 21.1%, 15.9%, 16.2%, 21.9% and 24.3%. The trend in DMFT was approximately consistent with DMF% (ß = 0.057, P < 0.001), but the downward volatility appeared in 2014. The DMFT in 1995-2014 was 0.38, 0.28, 0.31, 0.66 and 0.54. A continuously fluctuant trend in CFR was observed during past two decades (Z = 1.927, P > 0.05), and the CFR in 1995-2014 was 17.4%, 22.8%, 19.3%, 23.4% and 15.6%. The DMF% and DMFT of rural children had a larger absolute increase than that of urban children during 1995-2014 (DMF%-urban: Z = - 0.242, P > 0.05; DMF%-rural: Z = - 19.036, P < 0.001; DMFT-urban: ß = 0.035, P < 0.001, DMFT-rural: ß = 0.077, P < 0.001). The DMF% and DMFT in girls were higher than that in boys at each survey year (P < 0.001). CFR of urban children was higher than that of rural children at each survey year (P < 0.001). CONCLUSIONS: Over the past 20 years, DMFT and DMF% of 12-year-old children in China presented V-shaped fluctuant upward trends, with a decline trend from 1995 to 2000 and an upward trend from 2000 to 2014. CFR had no significant improvement. The rural children and girls are the more vulnerable groups in the development of dental caries and need to pay priority. Our study supports the continuation of policies to improve children' oral health.

The Clinical Significance of Serum MASP-2 and IDH1 in the Early Diagnosis of Non-Small Cell Lung Cancer.

BACKGROUND: The lack of effective means for the early diagnosis of non-small cell lung cancer (NSCLC) is the leading cause of the high mortality of NSCLC. This study aims to evaluate the clinical significance of serum mannan-binding lectin associated serine protease (MASP)-2 and isocitrate dehydrogenase 1 (IDH1) in the early diagnosis of NSCLC. METHODS: The serum levels of MASP-2 and IDH1 were detected in 139 NSCLC patients, 46 patients with benign lung diseases and 61 healthy controls, using an enzyme linked immunosorbent method. The diagnostic significance in NSCLC of the two tumor markers were analyzed by receiver operating characteristic (ROC) curves. In addition, we compared the two markers with the current commonly used tumor marker cytokeratin 19 fragment (Cy¬fra21-1). RESULTS: The serum levels of MASP-2 and IDH1 in the NSCLC patients were significantly higher than those of healthy controls and patients with benign lung diseases. The differences were statistically significant (p < 0.01). The combined sensitivity of MASP-2, IDH1, and Cyfra21-1 in the NSCLC was 68.3%, which was significantly higher than that of the single tumor marker (p < 0.01). The sensitivities of MASP-2 and IDH1 in detecting early NSCLC (stage I and stage II) were 39.0% and 41.5%, which were significantly higher than that of Cyfra21-1 (p < 0.05). The area under the ROC curves (AUCs) of MASP-2 and IDH1 in the diagnosis of NSCLC were 0.621, and 0.840, which were higher than that of Cyfra21-1 (AUC = 0.606). CONCLUSIONS: Serum MASP-2 and IDH1 may be used as potential tumor markers for the auxiliary diagnosis and early diagnosis of NSCLC.

Prognostic Significance of Serum miR-22, miR-125b, and miR-15b in Non-Small Cell Lung Cancer Patients.

BACKGROUND: Studies have shown that miRNA (miR) can be stably detected in serum, and aberrant expression of various miRNAs has shown diagnostic value in non-small cell lung cancer (NSCLC) patients. However, the role of miRNA in the context of prognosis has not been extensively investigated. Our previous study reported that miR-22, miR-125b, and miR-15b in serum had potential for use as tumor markers for auxiliary diagnosing of NSCLC. Therefore, the objective of this study was to detect the levels of miR-22, miR-125b, and miR-15b in serum from NSCLC patients and explore the potential prognostic significance of the three selected miRNAs. METHODS: The relative expression of miR-22, miR-125b, and miR-15b in 74 patients with advanced NSCLC in pre- and post-chemotherapy were detected by real-time quantitative polymerase chain reaction. RESULTS: Serum level of miR-125b significantly decreased after chemotherapy (p < 0.05) and the levels of miR-15b significantly increased (p < 0.01), while there was no change in the level of serum miR-22 (Z = 0.716, p > 0.05). Compared with pre-chemotherapy, serum miR-125b expression in advanced NSCLC patients of responders (CR + PR) were significantly decreased post-chemotherapy (p < 0.05); serum miR-15b expression in advanced NSCLC patients of responders (CR + PR) were increased (p < 0.01). The chemotherapy sensitivity of advanced NSCLC patients with high expression of miR-125b was lower than that of NSCLC patients with low expression (p < 0.05). The chemotherapy sensitivity of advanced NSCLC patients with high expression of miR-15b was higher than that of NSCLC patients with low expression (p < 0.05). High levels of serum miR-125b and low levels of serum miR-15b were related to poor overall survival (p < 0.05). CONCLUSIONS: The serum levels of miR-125b and miR-15b in advanced NSCLC patients were changed pre- and post-chemotherapy and these changes were associated with chemotherapeutic response. Serum miR-125b and miR-15b have certain potential clinical value for chemotherapeutic response in advanced NSCLC. The serum levels of miR-125b and miR-15b in patients with advanced NSCLC before treatment may be used to estimate the overall survival.

Gender differences in self-harm and drinking behaviors among high school students in Beijing, China.

BACKGROUND: Self-harm and drinking are both serious problems in adolescents and many studies presented evidence of their association. However, gender differences in this association are seldom deeply discussed. Our study aimed to evaluate the prevalence of self-harm and explore its association with drinking behaviors by gender and investigate the extent to which the gender differences exist in the association between self-harm and drinking. METHODS: A total of 32,362 students in grades 7 to 12 in Beijing, China were anonymously surveyed and included in our study using two-stage, stratified probability proportion sampling. Self-harm, drinking behaviors and other basic information were obtained from an anonymous questionnaire. Demographic variables, self-harm and drinking behaviors were analyzed using the Chi-square test and the Gamma test between genders and the gender differences in this association were analyzed by Log-binomial regression. RESULTS: The total prevalence of self-harm was 13.7% with no significant gender difference (χ2 =0.352, P = 0.553). The prevalence of self-harm in girls decreased with age (G = -0.163, P < 0.001). Self-harm was associated with drinking behaviors in both boys and girls. The Log-binomial regression demonstrated that girls in the 16-19 years old group were at lower risk of self-harm than girls in the 12-15 years old group while this association was weaker in boys (1.493 vs 1.128). The higher OR for self-harm was found among girls with early drinking experiences compared with boys (2.565 vs 1.863). Girls who had previously drunk (i.e. drunk at least once) (2.211 vs 1.636), were currently drinking (3.400 vs 2.122) and performed binge drinking (6.357 vs 3.924) were at greater risk of self-harm than boys. CONCLUSION: Among high school students, self-harm has a significant positive association with drinking and girls with drinking behaviors are at higher risk of suffering self-harm. Identifying adolescents' drinking behaviors is of vital importance to self-harm prevention and special attention should be focused on younger girls.

Hormetic Effects of Yttrium on Male Sprague-Dawley Rats.

To evaluate hormesis induced by Yttrium (Y) nitrate in male rats, Y was offered to F0 mother rats and F1 offspring at concentrations of 0, 20, 80, and 320 ppm daily from gestational day (GD) 0 through postnatal day 70 (PND 70). The F1 offspring were evaluated with respect to motor function, learning and memory, and histopathology. Administration of Y improved motor function in a dose dependent manner. In the 20 ppm group, body weight and spatial learning and memory were increased, while the latter was decreased in the 320 ppm group. Additionally, in the 20 ppm and 80 ppm, but not the 320 ppm groups, Y reduced the anogenital distance, which indicated an anti-androgen effect. These results suggest that Y follows a hormetic concentration-related trend with an inverted U-shape.

HMOX1 Promoter Microsatellite Polymorphism Is Not Associated With High Altitude Pulmonary Edema in Han Chinese.

OBJECTIVE: To investigate the relationship between microsatellite polymorphism in the Heme oxygenase-1 (HMOX1) gene promoter and high-altitude pulmonary edema (HAPE) in Han Chinese. METHODS: Eighty-three construction workers who developed HAPE 2 to 7 days after arrival at Yushu (3800 m) in Qinghai, China, and 145 matched healthy subjects were included in this study. The amplification and labeling of the polymerase chain reaction products for capillary electrophoresis were performed to identify HMOX1 genotype frequency. The alleles were classified as short (S: <25 [GT]n repeats) and long (L: ≥25 [GT]n repeats) alleles. RESULTS: Patients with HAPE have significantly higher white blood cell count, heart rate, and mean pulmonary artery pressure, but lower hemoglobin and arterial oxygen saturation than healthy subjects without HAPE. The numbers of (GT)n repeats in the HMOX1 gene promoter show a bimodal distribution. However, there is no significant difference in the genotype frequency and allele frequency between patients with HAPE and healthy subjects without HAPE. Chi-square test analysis reveals that the genotype frequency of (GT)n repeats is not associated with HAPE. CONCLUSION: The microsatellite polymorphism in the HMOX1 gene promoter is not associated with HAPE in Han Chinese in Qinghai, China.

Radial glial neural progenitors regulate nascent brain vascular network stabilization via inhibition of Wnt signaling.

The cerebral cortex performs complex cognitive functions at the expense of tremendous energy consumption. Blood vessels in the brain are known to form stereotypic patterns that facilitate efficient oxygen and nutrient delivery. Yet little is known about how vessel development in the brain is normally regulated. Radial glial neural progenitors are well known for their central role in orchestrating brain neurogenesis. Here we show that, in the late embryonic cortex, radial glial neural progenitors also play a key role in brain angiogenesis, by interacting with nascent blood vessels and regulating vessel stabilization via modulation of canonical Wnt signaling. We find that ablation of radial glia results in vessel regression, concomitant with ectopic activation of Wnt signaling in endothelial cells. Direct activation of Wnt signaling also results in similar vessel regression, while attenuation of Wnt signaling substantially suppresses regression. Radial glial ablation and ectopic Wnt pathway activation leads to elevated endothelial expression of matrix metalloproteinases, while inhibition of metalloproteinase activity significantly suppresses vessel regression. These results thus reveal a previously unrecognized role of radial glial progenitors in stabilizing nascent brain vascular network and provide novel insights into the molecular cascades through which target neural tissues regulate vessel stabilization and patterning during development and throughout life.

Danshen enhanced the estrogenic effects of Qing E formula in ovariectomized rats.

BACKGROUND: Menopause is characterized by a decrease in life quality due to the appearance of uncomfortable symptoms. Nowadays, Understanding menopause-associated pathophysiology and developing new strategies to improve the treatment of menopausal-associated symptoms is an important issue. Our study was to evaluate the synergistic effects of Danshen (salvia miltiorrhiza bunge) and the phytoestrogenic effects of 3 modified Qing E formulas, to explore a better formula for menopausal disorders. METHODS: 100 rats were randomized into 5 groups: Sham (Sham operation group), OVX (model group of ovariectomized rat), BDL (group with low concentration of Qing E Formula), BDH (group with high concentration of Qing E Formula) and BDD (group with high concentration of Qing E Formula Plus Danshen), receiving vehicle and extract of different modified Qing E formula respectively. The food intake, body weight, uterus weight, blood levels of triglycerides (TG), total cholesterol (TC) and cholesterol fractions were assessed. The mammary glands and uterus were morphologically analyzed. The bone density of tibias were measured by peripheral quantitative computed tomography (pQCT). Additionally, luciferase induction assays were performed in Hela cells with the mixtures derived from Qing E formula plus Danshen (BDD). RESULTS: Qing E formula plus Danshen significantly increased the uterus wet weight, enhanced the thickness of uterine wall, endometrial epithelium and glandular epithelium, improved trabecular bone and total density evidently, reduced the levels of low density lipoprotein cholesterol (LDL-C) and TG, possessed notable estrogen receptor beta (ERß) and estrogen receptor alpha (ERα) agonist activity. CONCLUSION: Qing E formula plus Danshen exerted more evident estrogen-like effects, thus it has a potential therapeutic use to treat menopausal disorders.