Whole-genome sequencing revealed armadillo repeat containing 5 (ARMC5) mutation in a Chinese family with ACTH-independent macronodular adrenal hyperplasia.

Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing's syndrome (CS) and is associated with bilateralenlargement of the adrenal glands. It accounts for <1% of all endogenous cases of CS. In order toidentify the pathogenic mutations in the causative gene of (AIMAH pedigrees, Whole-genome sequencing of three patients in family I was used to retrieve candidate causative genes. Meanwhile, the causative gene was identified by Sanger sequencing from the two pedigrees. Sequencing of ARMC5 exons of three patients was carried out to identify somatic mutations. Moreover, haploid clone of one tumor DNA sample was conducted. ARMC5 was the causative gene of two pedigrees confirmed by whole-genome sequencing (WGA) and Sanger sequencing. The variant sites of the two families were c.C943T (p.R315W) and c.C1960T (p.R654X), respectively. Autosomal dominant inheritance of AIMAH was confirmed by genotypes of one family member. Several somatic mutations were discovered in tumor DNA samples. In addition, haploid clone of tumor DNA was confirmed by germline mutation and somaticmutation, which suggested the pathogenic mechanism of "two-hit-model." ARMC5 was the causative gene of AIMAH pedigrees. This AIMAH in this study presented autosomal dominant inheritance, fitting to Mendelian inheritance law. However, the pathogenic mode of this disease showed as compound heterozygote.

Multi-genic pattern found in rare type of hypopituitarism: a whole-exome sequencing study of Han Chinese with pituitary stalk interruption syndrome.

Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.

Bispectral Index Can Reliably Detect Deep Sedation in Mechanically Ventilated Patients: A Prospective Multicenter Validation Study.

BACKGROUND: Excessively deep sedation is prevalent in mechanically ventilated patients and often considered suboptimal. We hypothesized that the bispectral index (BIS), a quantified electroencephalogram instrument, would accurately detect deep levels of sedation. METHODS: We prospectively enrolled 90 critically ill mechanically ventilated patients who were receiving sedation. The BIS was monitored for 24 hours and compared with the Richmond Agitation Sedation Scale (RASS) evaluated every 4 hours. Deep sedation was defined as a RASS of -3 to -5. Threshold values of baseline BIS (the lowest value before RASS assessment) and stimulated BIS (the highest value after standardized assessment) for detecting deep sedation were determined in a training set (45 patients, 262 RASS assessments). Diagnostic accuracy was then analyzed in a validation set (45 patients, 264 RASS assessments). RESULTS: Deep sedation was only prescribed in 6 (6.7%) patients, but 76 patients (84.4%) had at least 1 episode of deep sedation. Thresholds for detecting deep sedation of 50 for baseline and 80 for stimulated BIS were identified, with respective areas under the receiver-operating characteristic curve of 0.771 (95% confidence interval, 0.714-0.828) and 0.805 (0.752-0.857). The sensitivity and specificity of baseline BIS were 94.0% and 66.5% and of stimulated BIS were 91.0% and 66.5%. When baseline and stimulated BIS were combined, the sensitivity, specificity, and clinical utility index were 85.0% (76.1%-91.1%), 85.9% (79.5%-90.7%), and 66.9% (57.8%-76.0%), respectively. CONCLUSIONS: Combining baseline and stimulated BIS may help detect deep sedation in mechanically ventilated patients.

Up- and Down-regulated Leukemia-related Protein 16 Affects ERα Expression and Prolactin Secretion by GH3 Cells.

Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 (LRP16) is correlated with the progression of estrogen-related tumors, but the regulatory mechanism between LRP16 and prolactinoma remain unclear. This study demonstrates a variation in LRP16 with estrogen receptor α (ERα) in prolactinoma models and the up and downregulation effects of LRP16 on prolactin secretion of pituitary adenomas cells (GH3 cells). In our study, 50 male SD rats (30-day-old) were randomly divided into five groups of 10 rats each. After 120 days of treatment, the rats were sacrificed, and the expression of LRP16 and ERα were examined by Western blot and immunohistochemistry to explore the changes in ERα, LRP16, and prolactin. After siRNA transfection of the respective genes, the GH3 cells were cultured, and their secretory function as well as the expression of ERα mRNA and prolactin were analyzed by enzyme-linked immunosorbent assay and real-time-polymerase chain reaction analysis. The results show that secretion of prolactin by GH3 cells can be affected by up and downregulating LRP16 expression, which may provide a novel medical therapy in clinical trials.

Optical spin-sensitive Zitterbewegung in bianisotropic metamaterials.

We present a theoretical analysis on optical spin-sensitive Zitterbewegung (ZB) in metamaterials. By developing some formulas about the dispersions and eigenstates of optical modes we show that spin-sensitive ZB can be obtained in a bianisotropic metamaterial with a proper coupling between the electric and magnetic responses. A close analogue of the developed analytical results with these of Dirac equation is proposed. Numerical simulation proves the existence of ZB on the refracted optical beam along a direction determined by the optical spin of incidence. Furthermore, we show that when the incident optical field is linearly polarized, although ZB on field intensity does not exist, the optical spin possesses an interesting spatial split and trembling phenomena. Significance of this investigation is discussed.

Malignant insulinoma: Report of 6 patients and literature review.

OBJECTIVE: Patients with malignant insulinoma always present with symptoms of severe hypoglycemia and have poor life expectancy. In addition, inoperable metastatic malignant insulinomas are very difficult to manage. The aim of this report is to present our successful experiences in diagnosis and treatment of this disease in 6 patients. PATIENTS/METHODS: Six patients (male 2, female 4) with malignant insulinomas were admitted into our hospital. Their clinical histories, including clinical presentations, endocrine evaluations, radiological images, pathological examination and treatments, were reviewed. RESULTS: The diagnosis of malignant insulinoma combined with liver metastases was confirmed in all patients by endocrine evaluation and radiological images. Patients 1-3 underwent surgical management. The primary and metastasized tumors were completely resected. After successful surgery, no hypoglycemia recurred. Patients 4-6 did not undergo surgery because of systemic disease and poor health. Instead, they were administrated with diazoxide 50 mg Three Times a Day (TID), with final doses up to 200-300 mg TID. These 3 patients had good responses to diazoxide administration. After treatment, the frequency and severity of hypoglycemia were improved significantly. All 6 patients had better life quality than previously expected. CONCLUSION: Combination of surgical and medical approaches can improve life quality and prolong survival of patients with malignant insulinomas.

Correlation between Pituitary Stalk Interruption Syndrome and Prokineticin Receptor 2 and Prokineticin 2 Mutations.

OBJECTIVE: To analyze the correlation between pituitary stalk interruption syndrome (PSIS) and prokineticin receptor 2 (PROKR2) and prokineticin 2 (RROK2) mutations. METHODS: PROKR2 and RROK2 genotypes were identified by multiplex polymerase chain reaction analysis with exon-flanking primers and by automated sequencing techniques with peripheral blood DNA samples from 59 patients with PSIS. RESULTS: Of these 59 PSIS patients, 6 showed intragenic deletions at the PROKR2 locus. Of them, 5 patients exhibited intragenic subsititution of exon 2 (c.991G>A), and the remaining one patient exhibited intragenic subsititution of exon 2 (c.1057C>T). No PROK2 mutation was found in these PSIS patients. CONCLUSION: PROKR2 may be the susceptibility gene of PSIS.

Clinical Features of Pituitary Stalk Interruption Syndrome in 114 Cases.

Objective To analyze the clinical characteristics of pituitary stalk interruption syndrome(PSIS). Methods The clinical data including clinical manifestations,laboratory tests,and imaging findings of 114 PSIS patients in our hospital were retrospectively analyzed. Results Of these 114 PSIS patients,102 cases (89.4%) were male. The average age was 21.1?6.1 years. A history of breech delivery was documented in 91 cases (91.9%). Short stature was found in 89 cases (71.8%) and bone age delayed (6.1?5.1) years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone,gonadotropins,corticotropin,and thyrotropin were 100.0%,94.0%,84.2%,and 74.6%,respectively. Hyperprolactinemia was found in 28.1% of patients. Three or more pituitary hormone abnormalities were found in 105 cases(92.1%). Compared with the 5 cases with history of cephalic delivery,no difference were found in the aspects of height(t=0.297,P=0.634),penile length(t=1.205,P=0.882),testicular volume (U=99.000,P=0.348),growth hormone peak (U=89.000,P=0.186),adrenocorticotropic hormone peak(U=131.000,P=0.967),luteinizing hormone peak(U=98.500,P=0.582),thyroid-stimulating hormone (U=82.000,P=0.162),and the height of anterior pituitary (t=1.676,P=0.107) in the 53 cases with history of breech delivery. Conclusions The clinical manifestations,symptoms,hormone deficiencies were severe in our series. The condition severities were not remarkably different in patients with different delivery ways.

Experimental Study on the Characteristics of Chemiluminescence in Coal Water Slurry Diffusion Flames Based on Hot Oxygen Burner Technology.

Most published works focused on the characteristics of chemiluminescence in homogeneous flames, but the research about radiation spectrum in heterogeneous flames was still limited. In this paper, improved hot oxygen burner (HOB) technology is applied to ignite coal water slurry (CWS) directly in the open space, for stable combustion. Radiation spectrum and two-dimensional OH* chemiluminescence in methane and CWS diffusion flames are measured by a fiber optic spectrometer and a high-spatial-resolution UV imaging system. The results show that OH* (309.12 nm), CH* (431.42 nm) and C2* (463.52~563.43 nm) radicals exist in both methane and CWS diffusion flame, but Na* (589.45 nm), Li* (670.88 nm), K* (766.91, 770.06 nm), H* (816.04, 819.99 nm) radiation spectrum line and continuous black-body radiation have been detected only in the CWS flame. These differences can be used to characterize the combustion or gasification of CWS and distinguish whether CWS is ignited or not. In addition, the injection of CWS into methane flame leads to a significant reduction in OH* and an increase in C2* and CH* radiation intensity. This is because a lot of heat is absorbed in the processes of CWS combustion reactions. Then the generation of CH is inhibited, and the production of OH* is reduced. The increase of C2* and CH* is due to simple substance carbon produce more after injecting CWS. Besides, axial OH* radiation intensity increases at first then decreases, and the position of peak intensity is closer to outlet of hot oxygen burner compared with methane flames. Radial OH* radiation distribution is bimodal in methane flame because reactions take place in the thin layer where methane and oxygen meet. However, in CWS flame, radial OH* radiation distribution is always unimodal since CWS diffuses fiercely and mixes with oxygen sufficiently. As the ratio of oxygen atom to carbon atom ([O/C]e) increases, the reaction region of OH* radicals becomes larger in methane and CWS flame. This indicates that increasing oxygen can promote reactions and benefit OH* radicals' generation. Moreover, with the increase of CWS flow, reaction center is closer to burner outlet, OH* distribution range and peak intensity decrease obviously, CH*, C2*, Na*, Li*, K*, H* and black-body radiation intensities markedly rise. And these characteristics can reflect the changes of operation loads.

Expression of ATP synthase CF1 alpha subunit gene (CTL-spn) as screened by the cDNA-SRAP approach is correlated with spininess in Carthamus tinctorius L.

The safflower floret is a traditional Chinese medicine used to promote blood circulation and remove obstruction in the channels. The spines on its bracts are considered a handicap when manual harvest is involved. In this study, cDNA-SRAP was used to systematically investigate which genes are associated with the spines. Sixty pairs of possible primer combinations were used on two cDNA pools representing spininess and spinelessness. Six transcript-derived fragments were identified, of which two with low recombination were sequenced successfully and named as GPY-1 and GPY-2. By using the RACE method, the full-length cDNA of GPY-2 is cloned and named as CTL-spn. The full-length cDNA of CTL-spn was 1 679 bp long with a 1 524 bp ORF encoding a 508 aminoacid protein. The deduced amino acid sequence of the CTL-spn gene shared a high homology (97%) with other known ATP synthase CF1 alpha subunits. Semiquantitative RT-PCR analysis revealed that the mRNA of GPY-1 and GPY-2 accumulated in only spiny lines. Considering the important role of ATP synthase CF1 alpha subunit in plants, it may directly take part in the formation process of spininess and enhancing resistance reaction of spiny safflower. Also, our results provide the important insights for breeding spineless cultivars of safflower.

Nonreciprocal optical diffraction by a single layer of gyromagnetic cylinders.

We study the diffraction of optical waves by a single layer of gyromagnetic cylinders. We show that a nonvanishing rotating dipole momentum is excited in a single gyromagnetic cylinder because of the classic analog of the Zeeman effect on photonic angular momentum states (PAMSs). Consequently, different collective dipole modes are excited in a gyromagnetic cylinder array at opposite incident angles. Nonreciprocal optical diffraction effects can be observed, where the transmission and reflection coefficients depend on the sign of the incident angle. A novel phenomenon of nonreciprocal negative directional transmission is demonstrated and numerically analyzed. This work highlights the potential of PAMSs in manipulating the propagation of optical waves for various applications.

Guided modes in magneto-optical waveguides and the role in resonant transmission.

Magneto-optical (MO) effect can break the reciprocal propagation of an optical wave along a MO-metal interface. We show that this nonreciprocal property also influences the guided modes in metal-MO-metal waveguides. Especially, the field profiles of the guided modes are neither symmetric nor anti-symmetric, but asymmetric. We then study the resonant optical transmission through a thin metal film with subwavelength MO slits. Magnetic field changes the transmission spectra of the structure, and a MO-induced transparent window is open, where the MO medium becomes extremely anisotropic. The guided-mode mediated high transmission is associated with an asymmetric field distribution and a circling energy flux.

Exceptional points in extraordinary optical transmission through dual subwavelength metallic gratings.

Complex metamaterials with multiple optical resonances in constituent elements possess many similarities with open quantum systems that can be described by non-Hermitian Hamiltonian. By analogy with a two-state open quantum system, we show that a classic analogue of exceptional points can be observed in the transmission spectra of dual subwavelength metallic gratings. Anti-crossing (crossing) between the two branches λ(R) of extraordinary optical transmission, with crossing (anti-crossing) of the corresponding widths Γ(R), is observed in the parameter space spanned by the lateral displacement L and the angle of incidence φ0. Exchanges of field patterns and phases, and the variation of field profile when circling the exceptional point are discussed. This work highlights the potential to transfer the concepts and applications from open quantum systems to optical metamaterials.

Manipulation of dark photonic angular momentum states via magneto-optical effect for tunable slow-light performance.

We propose a novel scheme in realizing tunable slow-light performance by manipulating dark photonic angular momentum states (PAMSs) in metamaterials via the magneto-optical effect. We show that by applying a static magnetic field B, some pairs of sharp transmission dips can be observed in the background transparency window of a complex metamaterial design. Each pair of transmission dips are related to the excitation of dark PAMSs with opposite topological charges -m and +m, with a lifted degeneracy due to the classic analogue of Zeeman effect. Nonreciprocal characteristics can be observed in the distributions of field amplitude and transverse energy flux. The performance of slow light, including the group index ng, its abnormal feature, the associated strong absorption and the dependence with B are also discussed.

Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis.

OBJECTIVES: Pituitary stalk interruption syndrome (PSIS) is rare and its clinical features and pathogenesis are poorly understood. This study characterized the clinical and genetic features of PSIS in Chinese patients. DESIGN AND PATIENTS: Clinical data of 58 patients with PSIS and 46 patients with GH deficiency but a normal pituitary stalk (NPS) were retrospectively analysed. HESX1, LHX4, OTX2 and SOX3 polymorphisms were screened in 33 PSIS patients, and GH1 and GHRHR in 4 NPS patients. RESULTS: Deficiency of GH was 100% in both PSIS and NPS groups. Other deficiency rates for PSIS and NPS groups were as follows: ACTH, 77·6% and 23·9%; TSH, 43·1% and 10·9%; LH/FSH, 94·2% and 47·4%; and combined pituitary hormone, 93·1% and 41·3% respectively. In PSIS and NPS patients, the percentages of anterior pituitary hypoplasia were 98·3% and 54·3%, pituitary stalk abnormality were 100% and 0%, and ectopic neurohypophysis were 91·4% and 0%. A novel heterozygous sequence variant (c.142A>T, p.T48S) was found in HESX1 in one PSIS patient, 3 polymorphisms (c.63T>C, p.G21G; c.450C>T, p.N150N; and c.983A>G, p.N328S) in LHX4 in 7, 1 and 31 PSIS patients, respectively, and a hemizygous polymorphism (c.157G>C, p.V53L) in SOX3 in one PSIS patient. No OTX2 abnormality was detected in PSIS patients, and no GH1 or GHRHR polymorphisms in NPS patients. CONCLUSIONS: Compared with NPS, PSIS patients had more severe anterior pituitary hormone deficiency, lower anterior pituitary hormone secretion and higher probability of abnormal pituitary morphology. HESX1, LHX4 and SOX3 polymorphisms may be associated with PSIS.

Slow light from sharp dispersion by exciting dark photonic angular momentum states.

A photonic angular momentum state (PAMS) with a topological charge of m≠±1 is dipole forbidden at all polarizations of free-space incidence due to the existence of a unique helical phase. We show that by indirectly exciting dark PAMSs through coupling with a bright resonant element, a sharply variant transmission behavior and strong dispersion can be achieved. This behavior can subsequently be utilized in slow light. A metamaterial design, in which a group index n(g) greater than 500 can be achieved, is present.

Polarization-independent coherent perfect absorption by a dipole-like metasurface.

We show that polarization-independent coherent perfect absorption can be realized in a simple dipole-like metasurface by precisely engineering the ratio between the scattering loss γ(s) and the dissipation loss γ(l). This effect can be traced to a critical condition on the scattering matrix in a dipolar picture, which requires that the scattering and dissipation losses are equivalent, i.e., γ(s) = γ(l), at the resonant frequency f(0). This work expands the capability of metasurface in getting extreme optical properties, allowing for many potential applications.

Female sex hormones are associated with the reduction of serum sodium and hypertension complications in patients with aldosterone-producing adenoma.

This study was conducted to evaluate gender-related differences in clinical characteristics and vascular complications in patients with aldosterone-producing adenomas (APA). Clinical characteristics, biochemical markers and incidence of vascular complications were compared by gender in 187 consecutive patients with APA confirmed by pathological diagnosis. Patients were separated into two groups based on ages either older or younger than 49 years, the average age of menopause among Chinese women (<49 y and ≥49 y). Males had significantly higher BMI than females in the age group of <49 years (p = 0.017). In the <49 years group, males had significantly higher serum sodium levels (p = 0.003). However, no such gender differences in clinical characteristics were observed in patients ≥49 years. A higher proportion of vascular complications was observed in males as compared to females aged <49 years but the difference was not statistically significant (51.4% vs. 34.8%, p = 0.105). The only gender difference observed in vascular complications between patients aged ≥49 years was that a significantly greater proportion of males had cerebrovascular complication compared to females (p = 0.006). Our data suggest that female sex hormones are implicated in reducing serum sodium concentration and vascular complications in female APA patients.

[The clinical characteristics of multi-detector computed tomography of congenital adrenal hyperplasia].

OBJECTIVE: To explore the imaging features of congenital adrenal cortex hyperplasia (CAH). METHODS: A total of 45 patients clinically confirmed as CAH were retrospectively analyzed to investigate the imaging features and strengthening way of the multi-detector-row Computed tomography. RESULTS: The imaging features of all the cases presented as following: 25 with bilateral adrenal hyperplasia, 6 with unilateral adrenal hyperplasia, 6 with adrenal nodular hyperplasia, 2 with adrenal hyperplasia and unilateral solid cystic lesion, 2 with adrenal hyperplasia and double side real cystic lesion, 1 with adrenal hyperplasia and unilateral cystic changes and 3 with normal adrenal. The unilateral or bilateral hyperplasia adrenal could be homogeneously enhanced, while the enhanced performance of other cases was inequitable. CONCLUSIONS: The adrenal imaging features of CAH by multi-detector-row CT are variable, with the bilateral adrenal hyperplasia as the main form, which could be restored to normal morphology after hormone replacement therapy.No regression of the tumor size is observed in cases with adrenal mass. CT scanning combined with clinical manifestation and biochemical examination could facilitate the diagnosis of CAH.