Deswelling Mechanisms of PNIPAM Grafted in Nanochannels: A Molecular Dynamics Simulation Study.

Porous thermosensitive hydrogels exhibit a more flexible strategy for freshwater capture compared to conventional hydrogels. This study employs molecular dynamics (MD) simulation to investigate the deswelling behavior of poly(N-isopropylacrylamide) (PNIPAM) grafted within the nanochannel, aiming to elucidate the deswelling elimination process at various temperatures. Notably, a distinct phase separation is observed at specific temperatures above the lower solution temperature (LCST). Furthermore, this study takes the effect of heat flux into account, wherein distinct heat fluxes lead to varying levels of phase separation between water and the polymer. Specifically, the number of hydrogen bonds, volume of polymer chains, and density distribution of water molecules are statistically analyzed to reveal the mechanism of phase separation in a thermosensitive hydrogel. These findings provide insight into the accelerated deswelling kinetics of the PNIPAM polymer chain, which has guiding significance for the field of water harvesting by the enhancement of the water release capacity in thermosensitive hydrogels.

Serum Copper/Zinc Ratio in Overweight and Obese Children: a Cross-Sectional Study.

To assess the association between serum copper/zinc ratio (CZR) and overweight/obesity in children. Sociodemographic and clinical data of children aged 8-18 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) database in this cross-sectional study. These associations were explored using weighted univariate and multivariate logistic regression analyses with the odds ratios (ORs) and 95% confidence intervals (CIs). High serum CZR level was related to higher odds of overweight (OR = 1.74), obesity (OR = 5.26), and central obesity (OR = 2.99). Subgroup analyses showed that high serum CZR levels were associated with high odds of overweight in children aged ≥ 12 years old (OR = 2.19) and females (OR = 2.02), while the increased odds of obesity and central obesity were found in children aged ≥ 12 years old and both male and female. Elevated serum CZR level was linked to high odds of childhood overweight, obesity, and central obesity, and this relationship was also found in children with different age and gender.

Evaluation of genetic variants in ferroptosis-related genes and house dust mite-induced allergic rhinitis risk.

BACKGROUND: Ferroptosis-related genes disrupt iron homeostasis and enhance lipid peroxidation to initiate respiratory system diseases. However, the association between genetic variants in the ferroptosis-related genes with house dust mite (HDM)-induced allergic rhinitis (AR) susceptibility remains unclear. METHODS: A case-control study, involving 222 cases and 237 healthy controls from a Chinese population, was conducted to evaluate the relationship between single nucleotide polymorphisms (SNPs) in ferroptosis-related genes and HDM-induced AR risk. A gene-based analysis was performed by multi-marker analysis of genomic annotation (MAGMA) to identify candidate associated ferroptosis-related genes. A logistic regression model and joint analysis were used to assess the effect of SNPs on HDM-induced AR susceptibility. RESULTS: Two independent SNPs (rs2305128 in ENPP2 and rs1868088 in EPAS1) were significantly associated with HDM-induced AR risk (OR = 1.82, 95% CI = 1.19-2.79, P = 5.98 × 10-3, PFDR = 4.88 × 10-2; OR = 2.14, 95% CI = 1.23-3.72, P = 6.95 × 10-3, PFDR = 4.87 × 10-2, respectively). Moreover, combined analysis of these two SNPs revealed that an increased risk of HDM-induced AR was positively associated with an increasing number of risk genotypes (Ptrend = 8.48 × 10-5). The stratification analysis showed that the cumulative effect of two SNPs on HDM-induced AR risk was more pronounced among patients presenting more serious symptoms and harboring one or two risk genotypes. CONCLUSIONS: These findings suggest that the genetic variants in ferroptosis-related genes ENPP2 and EPAS1 may increase HDM-induced AR risk and serve as potential predictors of HDM-induced AR susceptibility.

Phosphorylation of KRT8 (keratin 8) by excessive mechanical load-activated PKN (protein kinase N) impairs autophagosome initiation and contributes to disc degeneration.

Excessive mechanical load (overloading) is a well-documented pathogenetic factor for many mechano stress-induced pathologies, i.e. intervertebral disc degeneration (IDD). Under overloading, the balance between anabolism and catabolism within nucleus pulposus (NP) cells are badly thrown off, and NP cells undergo apoptosis. However, little is known about how the overloading is transduced to the NP cells and contributes to disc degeneration. The current study shows that conditional knockout of Krt8 (keratin 8) within NP aggravates load-induced IDD in vivo, and overexpression of Krt8 endows NP cells greater resistance to overloading-induced apoptosis and degeneration in vitro. Discovery-driven experiments shows that phosphorylation of KRT8 on Ser43 by overloading activated RHOA-PKN (protein kinase N) impedes trafficking of Golgi resident small GTPase RAB33B, suppresses the autophagosome initiation and contributes to IDD. Overexpression of Krt8 and knockdown of Pkn1 and Pkn2, at an early stage of IDD, ameliorates disc degeneration; yet only knockdown of Pkn1 and Pkn2, when treated at late stage of IDD, shows a therapeutic effect. This study validates a protective role of Krt8 during overloading-induced IDD and demonstrates that targeting overloading activation of PKNs could be a novel and effective approach to mechano stress-induced pathologies with a wider window of therapeutic opportunity.Abbreviations: AAV: adeno-associated virus; AF: anulus fibrosus; ANOVA: analysis of variance; ATG: autophagy related; BSA: bovine serum albumin; cDNA: complementary deoxyribonucleic acid; CEP: cartilaginous endplates; CHX: cycloheximide; cKO: conditional knockout; Cor: coronal plane; CT: computed tomography; Cy: coccygeal vertebra; D: aspartic acid; DEG: differentially expressed gene; DHI: disc height index; DIBA: dot immunobinding assay; dUTP: 2'-deoxyuridine 5'-triphosphate; ECM: extracellular matrix; EDTA: ethylene diamine tetraacetic acid; ER: endoplasmic reticulum; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GPS: group-based prediction system; GSEA: gene set enrichment analysis; GTP: guanosine triphosphate; HE: hematoxylin-eosin; HRP: horseradish peroxidase; IDD: intervertebral disc degeneration; IF: immunofluorescence staining; IL1: interleukin 1; IVD: intervertebral disc; KEGG: Kyoto encyclopedia of genes and genomes; KRT8: keratin 8; KD: knockdown; KO: knockout; L: lumbar vertebra; LBP: low back pain; LC/MS: liquid chromatograph mass spectrometer; LSI: mouse lumbar instability model; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MMP3: matrix metallopeptidase 3; MRI: nuclear magnetic resonance imaging; NC: negative control; NP: nucleus pulposus; PBS: phosphate-buffered saline; PE: p-phycoerythrin; PFA: paraformaldehyde; PI: propidium iodide; PKN: protein kinase N; OE: overexpression; PTM: post translational modification; PVDF: polyvinylidene fluoride; qPCR: quantitative reverse-transcriptase polymerase chain reaction; RHOA: ras homolog family member A; RIPA: radio immunoprecipitation assay; RNA: ribonucleic acid; ROS: reactive oxygen species; RT: room temperature; TCM: rat tail compression-induced IDD model; TCS: mouse tail suturing compressive model; S: serine; Sag: sagittal plane; SD rats: Sprague-Dawley rats; shRNA: short hairpin RNA; siRNA: small interfering RNA; SOFG: safranin O-fast green; SQSTM1: sequestosome 1; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; VG/ml: viral genomes per milliliter; WCL: whole cell lysate.

Evaluation of a continuous-time random-walk diffusion model for the differentiation of malignant and benign breast lesions and its association with Ki-67 expression.

The purpose of the current study was to evaluate the performance of a continuous-time random-walk (CTRW) diffusion model for differentiating malignant and benign breast lesions and to consider the potential association between CTRW parameters and the Ki-67 expression. Sixty-four patients (46.2 ± 11.4 years) with breast lesions (29 malignant and 35 benign) were evaluated with the CTRW model, intravoxel incoherent motion model, and diffusion-weighted imaging. Echo planar diffusion-weighted imaging was conducted using 13 b-values (0-3000 s/mm2 ). Three CTRW model parameters, including an anomalous diffusion coefficient Dm , and two parameters related to temporal and spatial diffusion heterogeneity, α and ß, respectively, were obtained, and had MRI b-values of 0-3000 s/mm2 . Receiver operating characteristic (ROC) analysis was conducted to determine the sensitivity, specificity, and diagnostic accuracy of CTRW parameters for differentiating malignant from benign breast lesions. In malignant breast lesions, the CTRW parameters Dm , α, and ß were significantly lower than the corresponding parameters of benign breast lesions. In the malignant breast lesion group, the CTRW parameter Dm was significantly lower in high Ki-67 expression than in low Ki-67 expression. In ROC analysis, the combination of CTRW parameters (Dm , α, ß) demonstrated the highest area under the curve value (0.985) and diagnostic accuracy (94.23%) in differentiating malignant and benign breast lesions. The CTRW model effectively differentiated malignant from benign breast lesions. The CTRW diffusion model offers a new way for noninvasive assessment of breast malignancy and better understanding of the proliferation of malignant lesions.

Facet joint degeneration-An initial procedure of the cervical spine degeneration.

Objective: This study aims to emphasize the initiating role of facet joint (FJ) degeneration in the process of cervical spine degeneration induced by tangential load, and we further validate it in a novel cervical spine degeneration animal model. Methods: The characteristics of cervical degeneration in patients of different ages were summarized through case collection. In the rat models, Hematoxylin-Eosin, Safranin O staining, and micro-computed tomography were used to show the histopathological changes and bone fiber structure of FJ and the height of intervertebral disc (IVD) space. The ingrowth of nociceptive sensory nerve fibers was observed by immunofluorescence staining. Results: FJ degeneration without IVDs degeneration was more common in people with cervical spondylosis in young patients. The obvious degeneration phenotypes of the FJs preceded the IVDs at the same cervical segment in our animal model. The SP+ and CGRP+ sensory nerve fibers were observed in the articular subchondral bone of degenerated FJs and porous endplates of degenerated IVDs. Conclusion: The FJ degeneration may act as the major contributor to cervical spine degeneration in young people. The dysfunction of functional unit of spine, not a certain part of IVD tissue, results in the occurrence of cervical degeneration and neck pain.

SIRT5-related desuccinylation modification of AIFM1 protects against compression-induced intervertebral disc degeneration by regulating mitochondrial homeostasis.

Mitochondrial dysfunction plays a major role in the development of intervertebral disc degeneration (IDD). Sirtuin 5 (SIRT5) participates in the maintenance of mitochondrial homeostasis through its desuccinylase activity. However, it is still unclear whether succinylation or SIRT5 is involved in the impairment of mitochondria and development of IDD induced by excessive mechanical stress. Our 4D label-free quantitative proteomic results showed decreased expression of the desuccinylase SIRT5 in rat nucleus pulposus (NP) tissues under mechanical loading. Overexpression of Sirt5 effectively alleviated, whereas knockdown of Sirt5 aggravated, the apoptosis and dysfunction of NP cells under mechanical stress, consistent with the more severe IDD phenotype of Sirt5 KO mice than wild-type mice that underwent lumbar spine instability (LSI) surgery. Moreover, immunoprecipitation-coupled mass spectrometry (IP-MS) results suggested that AIFM1 was a downstream target of SIRT5, which was verified by a Co-IP assay. We further demonstrated that reduced SIRT5 expression resulted in the increased succinylation of AIFM1, which in turn abolished the interaction between AIFM1 and CHCHD4 and thus led to the reduced electron transfer chain (ETC) complex subunits in NP cells. Reduced ETC complex subunits resulted in mitochondrial dysfunction and the subsequent occurrence of IDD under mechanical stress. Finally, we validated the efficacy of treatments targeting disrupted mitochondrial protein importation by upregulating SIRT5 expression or methylene blue (MB) administration in the compression-induced rat IDD model. In conclusion, our study provides new insights into the occurrence and development of IDD and offers promising therapeutic approaches for IDD.

[Clinical characteristics and genetic analysis of three children with Congenital chlorine diarrhea].

OBJECTIVE: To explore the clinical characteristics and genetic basis for three children with Congenital chlorine diarrhea (CCD). METHODS: Three children with CCD who attended the Affiliated Children's Hospital of Capital Pediatric Institute from June 2014 to August 2020 were selected as the research subjects. Peripheral blood samples of the three children and their parents were collected for genetic testing. And the results were verified by Sanger sequencing. RESULTS: The clinical manifestations of the three children have included recurrent diarrhea, with various degrees of hypochloremia, hypokalemia and refractory metabolic alkalosis. Genetic testing revealed that the three children have all carried variants of the SLC26A3 gene, including homozygous c.1631T>A (p.I544N) variants, c.2063_1G>T and c.1039G>A (p.A347T) compound heterozygous variants, and c.270_271insAA(p.G91kfs*3) and c.2063_1G>T compound heterozygous variants. Sanger sequencing confirmed that all of the variants were inherited from their parents. CONCLUSION: The variants of the SLC26A3 gene probably underlay the CCD in these children. Above finding has enriched the spectrum of SLC26A3 gene variants.

Structure Design of Polymer-Based Films for Passive Daytime Radiative Cooling.

Passive daytime radiative cooling (PDRC), a cooling method that needs no additional energy, has become increasingly popular in recent years. The combination of disordered media and polymeric photonics will hopefully lead to the large-scale fabrication of high-performance PDRC devices. This work aims to study two typical PDRC structures, the randomly distributed silica particle (RDSP) structure and the porous structure, and systematically investigates the effects of structural parameters (diameter D, volume fraction fv, and thickness t) on the radiative properties of the common plastic materials. Through the assistance of the metal-reflective layer, the daytime cooling power Pnet of the RDSP structures is slightly higher than that of the porous structures. Without the metal-reflective layer, the porous PC films can still achieve good PDRC performance with Pnet of 86 W/m2. Furthermore, the effective thermal conductivity of different structures was evaluated. The single-layer porous structure with optimally designed architecture can achieve both good optical and insulating performance, and it is the structure with the most potential in PDRC applications. The results can provide guidelines for designing high-performance radiative cooling films.

Heat Transfer Performance of Gel Foam Layer with Nanoparticles Doping under a Radiative Heat Flux.

The risk of fire in the chemical industry's production process is fatal. Gel foam has been widely employed in petroleum storage tanks, oil pools, and other petrochemical equipment for fire extinguishing and thermal protection. Recently, nanoparticles have been doped into gel foam to enhance thermal stability and insulation. However, heat transfer behaviors of the gel foam layer containing nanoparticles are still missing. In this study, a numerical heat transfer model of a gel foam layer containing silica nanoparticles under a radiative heat flux was established. Through simulation, the changes in foam thickness and temperature distribution were analyzed. The effects of the maximum heating temperature, initial gas content, nanoparticle size, and concentration on the thermal insulation behavior of the gel foam layer were systematically studied. The results showed that the thermal stability and insulation performance of the three-phase gel foam layer decreased with the increase in the initial gas content and particle size. Increasing the nanoparticle concentration could enhance the foam's thermal stability and insulation performance. The results provide guidance for a designing gel foam with high thermal protection performance.

Value of Intravoxel Incoherent Motion (IVIM) Imaging for Differentiation between Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma.

Efficient noninvasive imaging techniques in the differentiation of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are very important because of their different management and prognosis. Our purpose was to evaluate the difference of parameters extracted from intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) between the two groups and their performance for the differentiation, as well as the significance of perfusion information. IVIM studies (9 b-values) in 41 patients with either ICC or HCC were reviewed retrospectively by two observers. Diffusion coefficient (D), pseudodiffusion coefficient (D∗), perfusion fraction (f), ADC, and the mean percentage of parenchymal enhancement (MPPE) at 30 s after contrast-enhancement were calculated and compared between ICC and HCC. The relationship between D∗, f values, and MPPE was evaluated by Spearman's correlation test. The diagnostic efficacy of all parameters was analyzed by the receiver operating characteristic (ROC) curve. Interobserver and intraobserver agreements were analyzed. The parameters (D and ADC) of ICC were distinctly higher than those of HCC; whereas the parameters (f and MPPE of arterial phase) were distinctly lower (all false discovery rate [FDR]-corrected P < 0.05). The metric D∗ value of ICC was slightly higher than that of HCC (71.44 vs 69.41) with FDR-corrected P > 0.05. Moreover, the value of parameter D was significantly lower than that of ADC (FDR-corrected P < 0.05). The parameters (D and f values) extracted from IVIM showed excellent diagnostic efficiency in the identification, and the diagnostic efficiency of D value was significantly higher than that of the ADC. There were positive correlations between perfusion-related parameters (D∗, f values) and MPPE. Interobserver and intraobserver agreements were excellent or perfect in measurements of all parameters. Parameters derived from IVIM were valuable for distinguishing ICC and HCC. Moreover, the D value showed better diagnostic efficiency for the differential diagnosis than monoexponential fitting-derived ADC value. Meanwhile, the significant correlation between perfusion-related parameters and MPPE demonstrates that specific IVIM metrics may serve as a noninvasive indicator for the vascular perfusion information of ICC and HCC.

Predicting the effective thermal conductivity of unfrozen soils with various water contents based on artificial neural network.

The effective thermal conductivity of soils is a crucial parameter for many applications such as geothermal engineering, environmental science, and agriculture and engineering. However, it is pretty challenging to accurately determine it due to soils' complex structure and components. In the present study, the influences of different parameters, including silt content (msi), sand content (msa), clay content (mcl), quartz content (mqu), porosity, and water content on the effective thermal conductivity of soils, were firstly analyzed by the Pearson correlation coefficient. Then different artificial neural network (ANN) models were developed based on the 465 groups of thermal conductivity of unfrozen soils collected from the literature to predict the effective thermal conductivity of soils. Results reveal that the parameters ofmsi,msa,mcl, andmquhave a relatively slight influence on the effective thermal conductivity of soils compared to the water content and porosity. Although the ANN model with six parameters has the highest accuracy, the ANN model with two input parameters (porosity and water content) could predict the effective thermal conductivity well with acceptable accuracy andR2= 0.940. Finally, a correlation of the effective thermal conductivity for different soils was proposed based on the large number of results predicted by the two input parameters ANN-based model. This correlation has proved to have a higher accuracy without assumptions and uncertain parameters when compared to several commonly used existing models.

Value of Magnetic Resonance Cholangiopancreatography in Santorinicele and Wirsungocele.

BACKGROUND: Former studies showed that magnetic resonance cholangiopancreatography (MRCP) is useful in diagnosing the presence of santorinicele; however, few studies have evaluated MRCP in diagnosing wirsungocele and the association between pancreatitis and santorinicele or wirsungocele. The purpose of the study was to explore the performance of MRCP in diagnosing santorinicele and wirsungocele and investigate the potential association among pancreatitis, pancreas divisum, and santorinicele or wirsungocele. METHODS: Sixty-five patients (mean age, 55.68 years; range, 11-82 years) with santorinicele or wirsungocele were included and sorted into two groups: the santorinicele group (n = 48) and the wirsungocele group (n = 17). All patients underwent MRCP. The images were evaluated for the appearance and size of santorinicele or wirsungocele. The diagnostic sensitivity of MRCP was assessed. Additionally, whether two groups are correlated with pancreas divisum or pancreatitis were investigated. RESULTS: The sensitivity of MRCP in detecting santorinicele and wirsungocele showed no difference (68.8% and 76.5%, respectively). The proportion of patients who developed pancreatitis in santorinicele and wirsungocele groups were 60.4% and 11.8%, respectively (p < 0.05). Pancreas divisum accounted for 77.1% and 11.8% of the patients in the santorinicele and wirsungocele groups, respectively (p < 0.05). Patients with santorinicele and pancreas divisum tended to be older when they acquired pancreatitis. CONCLUSION: MRCP could be an alternative imaging method to detect cystic dilation of the pancreatic duct. Pancreatitis is more common in patients with santorinicele than in those with wirsungocele. Moreover, santorinicele is more closely associated with pancreatitis than with pancreas divisum.

[Analysis of clinical features and genetic variants among 12 children with Gitelman syndrome].

OBJECTIVE: To summarize clinical manifestations and results of genetic testing in 12 children with Gitelman syndrome (GS). METHODS: Clinical data of the children was collected. Whole exome sequencing(WES) was carried out to screen potential variants of genomic DNA. Candidate variants were verified by Sanger sequencing. RESULTS: The patients have included 10 boys and 2 girls, whom were diagnosed at between 2.8 to 15.0 year old. Six patients were due to infections, 5 were due to short stature, and 1 was due to lower limb weakness. All patients were found to carry variants of SLC12A3 gene, which included 11 with compound heterozygous variants and 1 with homozygous variant. All of the 19 alleles of the SLC12A3 gene carried by the patients were delineated, which included 15 missense variants, 2 frameshift variants and 2 splice region variants. These variants were unreported previously, which included c.578_582dupCCACC (p.Asn195Profs*109), c.251C>T (p.Pro84Leu) and c.2843G>A (p.Trp948X). CONCLUSION: The clinical symptoms of GS in children are atypical and often seen in older children. For children with occasional hypokalemia associated with growth failure, GS should be suspected. The majority of GS children carry two pathogenic variants of the SLC12A3 gene, mainly compound heterozygotes, among which p.Thr60Met is the most common one. The discovery of new variants has enriched the spectrum of SLC12A3 gene variants.

Improved thermoelectric properties of WS2-WSe2 phononic crystals: insights from first-principles calculations.

Recently, two-dimensional transition metal dichalcogenide (TMDC) monolayers have attracted much attention owing to their excellent physical properties. In the present study, we systematically investigate the thermoelectric properties of different WS2-WSe2 phononic crystals by utilizing first-principles calculations. First, the thermal properties of all phononic crystals with superlattices (SL1 and SL2) and their individual components (WS2 and WSe2) are evaluated, in which the lattice thermal conductivities (kph) of WS2 and WSe2 monolayers present isotropic behaviors, while the values of SL1 and SL2 monolayers reveal weak anisotropic behaviors. It can be observed that the kph values of WS2 and WSe2 monolayers are larger than those of SL1 and SL2 monolayers, which can be attributed to the decreasing phonon group velocity and phonon lifetime. Moreover, we calculate the electronic band structures of all monolayers, indicating that all monolayers are semiconductors. Afterwards, the electrical conductivities, the Seebeck coefficients, the power factors, the electronic thermal conductivities, and the ZT values at different temperatures are evaluated. The ZTmax values of WS2, WSe2, SL1, and SL2 monolayers with p-type doping are 0.43, 0.37, 0.95, and 0.66 at 1000 K. It can be proved that the SL1 monolayer possesses the largest ZT, which is at least two times higher than those of the WS2 and WSe2 monolayer. Finally, we build two kinds of phononic crystals with periodic holes (PCH1 and PCH2) and evaluate the thermoelectric properties. It can be observed that the PCH2 structure shows the best thermoelectric performance. The ZTmax values of the PCH2 structure can reach 2.53 and 4.54 with p-type doping along the x and y directions, which are 2.66 and 6.75 times higher than those of the SL1 monolayer. This work provides a new strategy to obtain higher thermoelectric performance and demonstrates the potential applications of phononic crystals in TMDC-based nanoelectronic devices.

First-principles calculations of phonon behaviors in graphether: a comparative study with graphene.

Recently, a two-dimensional (2D) oxocarbon monolayer, graphether, has been arousing extensive attention owing to its excellent electrical properties. In this work, we calculate the lattice thermal conductivity (k) of graphether and graphene using first-principles calculations and the phonon Boltzmann transport equation. At 300 K, the lattice thermal conductivities of graphether and graphene along the armchair direction are 600.91 W m-1 K-1 and 3544.41 W m-1 K-1, respectively. Moreover, the electron localization function is employed to reveal the origin of the anisotropic k of graphether. Furthermore, the harmonic and anharmonic properties of graphether and graphene are analyzed. We attribute the lower k of graphether to the smaller phonon group velocity and shorter phonon lifetime. Finally, the size effects of phonon transport in graphether and graphene are studied, and the results show that the lattice thermal conductivities are significantly dependent on the system length. The analysis of phonon behaviors in our study contributes to an in-depth understanding of the thermal transport in graphether for the first time, which provides valuable guidelines for graphether-based phonon engineering applications and 2D nanoelectronic devices.

[Clinical and genetic analysis of a child with neonatal severe parathyroidism].

OBJECTIVE: To explore the genetic basis for a child with neonatal severe hyperparathyroidism. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Whole exome sequencing was carried out to screen potential mutations. Suspected mutation was verified by Sanger sequencing. RESULTS: The proband was found to carry compound heterozygous variants c.179G>A (p.Cys60Tyr) and c.1525G>A (p.Gly509Arg) of the CaSR gene. The c.179G>A variant was derived from her mother and was unreported previously. The c.1525G>A variant was derived from her father and known to be pathogenic. CONCLUSION: The compound heterozygous variants of c.179G>A and c.1525G>A of the CaSR gene probably underlie the disease in the patient. The results of genetic testing has enabled diagnosis and genetic counseling for her family.

Next-Generation Sequencing Revealed Disease-Causing Variants in Two Genes in a Patient With Combined Features of Spherocytosis and Antley-Bixler Syndrome With Genital Anomalies and Disordered Steroidogenesis.

Conventionally, patients with combined rare diseases are often difficult to diagnose. This is because some clinicians tend to consider the multiple disease symptoms as the presentation of a complicated "syndrome." This pattern of thinking also confines their way of filtering pathogenic mutations. Some real pathogenic mutations might be ignored due to not covering all disease presentations. Here we report the case of a girl who was suffering from spherocytosis and Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis. She remained undiagnosed even after targeted gene detection before. However, after performing next-generation sequencing and analyzing the sequencing data, we identified two mutations: c.2978T > A in ANK1 and c.1370G > A in POR. Our findings and experiences in diagnosing these mutations could contribute to the existing knowledge on the clinical and genetic diagnosis of patients with disease presentations in multiple systems.

Two-year outcome of Trabeculo-Canalectomy for Chinese Glaucoma Patients.

To evaluate the efficacy of trabeculo-canalectomy in treating glaucoma patients, a retrospective investigation of 53 glaucoma patients (53 eyes) who underwent trabeculo-canalectomy was conducted at the First Affiliated Hospital of Nanjing Medical University, China, from April 2017 to January 2019. Intraocular pressure (IOP), visual acuity, surgical success rates, medications, and complications were monitored at post-operative 1 day, 1 week, 1, 3, 6, 12 and 24 months. Surgical success criteria were defined as 6 mm Hg≤IOP≤21 mmHg with or without additional medications. Our results showed that average IOP was statistically significant between pre-operative visit and each follow-up visit (all P <0.05). The total success rate of trabeculo-canalectomy at 1, 3, 6, 12 and 24 months was 92.5%, 86.8%, 94.3%, 92.5% and 90.6% respectively. After 3 months post-operatively, all patients had no obvious filtering blebs. The main early complications included postoperative hyphema (7.5%), elevated IOP (5.7%) and anterior chamber exudation (3.8%), which were all cured after conservative treatment. No blebitis, shallow anterior chamber, choroidal detachment and endophthalmitis were observed. Logistic regression analysis showed that patients with secondary glaucoma were more likely to undergo surgical failure 24 months post-operatively (P= 0.008). Thus, we conclude that trabeculo-canalectomy is effective and safe for the treatment of glaucoma.

Diagnostic Performance of PET/CT Using 18F-FACBC in Prostate Cancer: A Meta-Analysis.

Background: Diagnostic performance of PET/CT using 18F-fluciclovine (18F-FACBC) in patients with prostate cancer (PCa) has been evaluated in only a few studies. There is no consensus on the diagnostic value of 18F-FACBC PET/CT in PCa recurrence or metastasis (except for bone metastasis), the primary diagnosis of the lesion. Hence, a meta-analysis was conducted to evaluate the performance of 18F-FACBC PET/CT. Methods: The literature published from June 2015 to June 2019 on using 18F-FACBC PET/CT for the diagnosis of PCa was retrieved from PubMed and EMBASE. Pooled sensitivity (Sen), specificity (Spe), positive and negative likelihood ratios (LR+ and LR-), area under the curve (AUC), and diagnostic odds ratio (DOR) of 18F-FACBC PET/CT in patients with PCa were calculated. An SROC map was made, and a meta-regression analysis was carried out. A Fagan plot and likelihood ratio dot plot were drawn. Sensitivity and funnel plot analysis were made. Meta-disc, Review Manager 5.3, and STATA 13 were used for the meta-analysis. Results: A total of nine articles met the strict criteria for diagnostic meta-analysis, which included 363 patients and 345 lesions. Pooled Sen, Spe, LR+, LR-, DOR were 0.88, 0.73, 3.3, 0.17, and 20, respectively. Lesions detected on the PET/CT image included primary lesions and metastases. For the lesion, the doctors considered the abnormal part as a lesion on the PET/CT image by their own experience and expertise, including primary lesions and metastases. For the patient, patients who participated in the trial can be diagnosed as PCa through 18F-FACBC. Conclusion: This study comprehensively evaluated the diagnostic value of 18F-FACBC PET/CT on PCa. Our analysis suggests that 18F-FACBC PET/CT is a valuable agent in diagnosing PCa. More studies are needed for further validation.