GGCX mutations in a patient with overlapping pseudoxanthoma elasticum/cutis laxa-like phenotype.

Pseudoxanthoma elasticum (PXE) is a multisystem disorder characterized by ectopic mineralization of connective tissues with primary manifestations in the skin, eyes and the cardiovascular system. The classic forms of PXE are caused by mutations in the ABCC6 gene encoding the ABCC6 protein, expressed primarily in the liver. Cutis laxa (CL) manifests with loose and sagging skin with loss of recoil. In 2009 we investigated a 19-year-old patient with overlapping cutaneous features of PXE and CL, together with alpha thalassaemia. Genetic analysis failed to identify pathogenic mutations in ABCC6. More recently we developed a gene-targeted panel of next-generation sequencing technology. This panel has 29 genes, 22 of which, including ABCC6 and GGCX, are associated with ectopic mineralization phenotypes. Mutation analysis in the patient identified two heterozygous GGCX mutations: c.200_201delTT in exon 2 and c.763G>A, p.V255M in exon 7. The GGCX gene encodes a γ-glutamyl carboxylase necessary for activation of blood coagulation factors in the liver. The p.V255M mutation was previously reported to result in reduced γ-glutamyl carboxylase activity in vitro, while the c.200_201delTT mutation is novel. Previous studies reported that mutations in GGCX cause overlapping PXE/CL skin phenotypes in association with or without multiple vitamin K-dependent coagulation factor deficiency. Our patient had loose redundant skin, moderate-to-severe angioid streaks and characteristic calcification of elastic structures in the mid dermis, consistent with PXE/CL overlap, but no coagulation abnormalities. Our studies expand the GGCX mutation landscape in patients with PXE-like phenotypes.

Temperature-Induced Lifshitz Transition and Possible Excitonic Instability in ZrSiSe.

The nodal-line semimetals have attracted immense interest due to the unique electronic structures such as the linear dispersion and the vanishing density of states as the Fermi energy approaching the nodes. Here, we report temperature-dependent transport and scanning tunneling microscopy (spectroscopy) [STM(S)] measurements on nodal-line semimetal ZrSiSe. Our experimental results and theoretical analyses consistently demonstrate that the temperature induces Lifshitz transitions at 80 and 106 K in ZrSiSe, which results in the transport anomalies at the same temperatures. More strikingly, we observe a V-shaped dip structure around Fermi energy from the STS spectrum at low temperature, which can be attributed to co-effect of the spin-orbit coupling and excitonic instability. Our observations indicate the correlation interaction may play an important role in ZrSiSe, which owns the quasi-two-dimensional electronic structures.

[Clinical effect of one-stage total knee arthroplasty for knee osteoarthritis with femoral extra-articular deformity].

Objective: To investigate the application and efficacy of the one-stage total knee arthroplasty (TKA) of intra-articular compensation osteotomy in knee osteoarthritis(KOA) patients with extra-articular deformity (EAD). Methods: A retrospective study of 9 patients with end-stage KOA and EAD undergoing one-stage TKA from January 2014 to December 2017 in the First Affiliated Hospital of Zhejiang Chinese Medical University was performed. There were 3 males and 6 females with an average age of 56 years(range, 19-77 years);5 cases of simple coronal deformity (varus 10°-27°, mean 18.2°), 3 cases of sagittal deformity (recurvatum15°-35°, mean 22.6°), 1 case combined with coronal and sagittal deformity (varus 16°, recurvatum 31°); hemophilia dysplasia in 1 case, fracture malformation in 8 cases. Main outcome measures included the mechanical axis, range of motion (ROM) and Hospital for Special Surgery Knee Score (HSS). Results: The mean follow-up period was 33.2 months (range, 25-47 months). The mechanical axis angle was restored from 12.4°±4.1°to 1.4°±0.9°(t=7.954, P<0.01). The HSS was improved from 28±14 preoperatively to 87±7 postoperatively (t=-11.174, P=0.013). The ROM increased from 56°±22°to 99°±8° (t=-5.480, P=0.010). There was no complications such as joint instability, infection, fracture, common peroneal nerve injury and early prosthesis loosening. Conclusions: For KOA patients with femoral EAD, one-stage TKA with intra-articular compensatory osteotomy can effectively restore the mechanical axis and obtain satisfying joint function. Through a series of measures such as preoperative measurement, soft tissue evaluation and 3D printing, the accuracy of surgery can be improved and the difficulty of surgery can be reduced.

Large Positive Thermal Expansion and Small Band Gap in Double-ReO3-Type Compound NaSbF6.

Double-ReO3-type structure compound NaSbF6 undergoes a low-temperature rhombohedral to high-temperature cubic phase between 303 and 323 K, as revealed by temperature-dependent X-ray diffractions. Although many double-ReO3-type fluorides exhibit either low thermal expansion or negative thermal expansion (NTE), NaSbF6 exhibits positive thermal expansion (PTE) with a large volumetric coefficient of thermal expansion, αv = 62 ppm/K, in its cubic phase. Raman spectroscopy reveals that the low-frequency transverse vibration of fluorine atoms is stiffened in NaSbF6, compared with the typical NTE compound CaZrF6 with the same structure. The related weak contraction associated with the polyhedral rocking would be overcome by the notable elongation of the Na-F bond length on heating, thus leading to the large volumetric PTE. Unlike ScF3 and CaZrF6 which are insulators with a wide band gap, a relative small band gap of 3.76 eV was observed in NaSbF6. The small band gap can be attributed to the hybridization between the Sb 5s and F 2p orbitals.

Critical behavior in tetragonal antiperovskite GeNFe3 with a frustrated ferromagnetic state.

Tetragonal GeNFe3 has a second-order ferromagnetic (FM) to paramagnetic transition at 76 K. Our integrated investigations indicate that the ground FM state is frustrated and the tetragonal symmetry is retained below 550 K based on the results of variable temperature X-ray diffraction. Critical behavior was analyzed by a systematic bulk magnetization study. The estimated critical exponents by three different methods (modified Arrott plot, the Kouvel-Fisher method, and critical isotherm analysis) conformably suggest that long-range magnetic coupling described by mean-field (MF) theoretical model is dominant in GeNFe3. The experimental M-T-H data collapse into two independent branches according to the scaling equations m = f±(h) with the renormalized magnetization m = ε-ßM(H, ε) and the magnetic field h = Hε-(ß+γ). The exchange distance is estimated as J(r) ∼ r-4.8 on the basis of the ß and γ values, which lies between the long-range MF model (r-4.5) and the short-range 3D Heisenberg (3DH) model (r-5). Our results indicate that the competition between local magnetic moments of iron 3d electronic state and itinerant covalent interactions of N-Fe bonds should be responsible for critical behavior in this system.

Leptin promotes apoptosis and inhibits autophagy of chondrocytes through upregulating lysyl oxidase-like 3 during osteoarthritis pathogenesis.

OBJECTIVE: Leptin has been found highly expressed in human osteoarthritis. We aimed to explore the possible effects and mechanisms of leptin on the apoptosis and autophagy of chondrocytes during osteoarthritis pathogenesis. METHODS: Gene expression profile from osteoarthritis affected and preserved cartilage were downloaded from NCBI's Gene Expression Omnibus database (GSE57218). Lysyl oxidase-like 3 (LOXL3) mRNA expression in cartilage tissues and leptin concentration in joint synovial fluid (SF) was measured in samples from 45 osteoarthritis patients and 25 healthy donors by real-time PCR and radioimmunoassay, respectively. Rat osteoarthritis model was induced by anterior cruciate ligament transection (ACLT). The expression of apoptosis regulators and autophagy markers were detected by Western blot. Cell survival and cell apoptosis were identified by CCK-8 and flow cytometry, respectively. RESULTS: Re-analysis on GSE57218 indicated that LOXL3 mRNA was upregulated in osteoarthritis affected cartilage. LOXL3 mRNA was upregulated in osteoarthritis patients, which was positively correlated with SF leptin concentration. Similar results were obtained in rat osteoarthritis model. Moreover, ACLT surgery led to a significant increase in the protein levels of cleaved caspase 3, and a notable decrease in the protein levels of Bcl-2, LC3 II/LC3 I and Beclin1. Silencing of LOXL3 in ACLT and leptin treated primary chondrocytes significantly inhibited cell apoptosis, and promoted cell proliferation and autophagy. Moreover, overexpression of LOXL3 remarkably inhibited autophagy of chondrocytes via activating mTORC1. CONCLUSIONS: LOXL3, a downstream of leptin, stimulated the apoptosis, but inhibited the autophagy of chondrocytes. LOXL3 is a potential therapy target for osteoarthritis.

Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. RESULTS: In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). CONCLUSIONS: The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia.

Physicochemical properties of skim milk powders prepared with the addition of mineral chelators.

The objective of this study was to determine the effect of mineral chelator addition during skim milk powder (SMP) manufacture on the solubility, turbidity, soluble protein, and heat stability (HS). Three chelators (sodium citrate dihydrate, sodium polyphosphate, and disodium EDTA) at 3 different concentrations (5, 15, and 25mM) were added to skim milk concentrate (30% total solids), and the pH was adjusted to 6.65 before spray drying to produce SMP. Spray-dried SMP samples were tested for solubility index (SI). Additionally, samples were reconstituted to contain 9% total solids, adjusted to pH 7.0, and tested for turbidity, protein content from supernatants of ultracentrifuged samples, and HS. Lower SI values were observed for samples treated with 5mM disodium EDTA and sodium polyphosphate than control samples or samples with 5mM sodium citrate dihydrate. Furthermore, lower SI values were observed with an increased level of chelating agents regardless of chelator type. A decreased turbidity value was found with increasing levels of mineral chelating salt treatment. Low turbidity with increasing levels of added chelators may be associated with the dissociation of caseins from micelles. Furthermore, higher protein content was observed in supernatants of ultracentrifuged samples treated with increased level of chelators as compared with the control sample. Higher HS was observed in samples treated with 5mM compared with samples treated with 25mM mineral chelator. The results suggest improved solubility and HS upon addition of mineral chelators to SMP during its manufacture.

Short communication: Effect of storage temperature on the solubility of milk protein concentrate 80 (MPC80) treated with NaCl or KCl.

A previous study in our laboratory showed that addition of 150 mM NaCl or KCl into diafiltration water improved the solubility of freshly made milk protein concentrate 80 (MPC80). In the present study, the objectives were (1) to evaluate the solubility of NaCl- or KCl-treated MPC80 samples kept at varying temperatures and then stored for extensive periods at room temperature (21 °C ± 1 °C); and (2) to determine if MPC80 samples stored at different temperatures and protein conformation can be grouped or categorized together. Freshly manufactured MPC80 samples were untreated (control), processed with NaCl, or processed with KCl. One set of sample bags was stored at 4 °C; second and third sets of bags were kept at 25 °C and 55 °C for 1 mo (31 d) and then transferred to room temperature (21 °C ± 1 °C) storage conditions for 1 yr (365 d). Samples were tested for nitrogen solubility index (NSI) and for protein changes by Fourier-transform infrared (FTIR) spectroscopy. Analysis of variance results for NSI showed 2 significantly different groupings of MPC80 samples. The more soluble group contained samples treated with NaCl or KCl and stored at either 4 °C or 25 °C. These samples had mean NSI >97.5%. The less soluble groups contained all control samples, regardless of storage temperature, and NaCl- or KCl-treated samples stored at 55 °C. These samples had mean NSI from 39.5 to 58%. Within each of these groups (more soluble and less soluble), no significant differences in solubility were detected. Pattern recognition analysis by soft independent modeling of class analogy (SIMCA) was used to assess protein changes during storage by monitoring the amide I and amide II (1,700(-1) to 1,300 cm(-1)) regions. Dominant bands were observed at 1,385 cm(-1) for control, 1,551 cm(-1) for KCl-treated samples, and 1,694 cm(-1) for NaCl-treated samples. Moreover, SIMCA clustered the MPC80 samples stored at 4 °C separately from samples stored at 25 °C and 55 °C. This study demonstrates that (1) the addition of NaCl or KCl during MPC80 manufacture reduces the deleterious changes in solubility upon prolonged storage at 4 °C or 25 °C, and (2) the solubility of samples stored at 55 °C is poor irrespective of salt treatment.

Chronic peritoneal dialysis in Chinese infants and children younger than two years.

OBJECTIVE: To review the outcome for Chinese infants and young children on chronic peritoneal dialysis. METHODS: The Paediatric Nephrology Centre of Princess Margaret Hospital is the designated site offering chronic dialysis to children in Hong Kong. Medical records of children who started chronic peritoneal dialysis before the age of 2 years, from 1 July 1995 to 31 December 2013, were retrieved and retrospectively reviewed. RESULTS: Nine Chinese patients (male-to-female ratio, 3:6) were identified. They were commenced on automated peritoneal dialysis at a median age of 4.7 (interquartile range, 1.1-13.3) months. The median duration of chronic peritoneal dialysis was 40.9 (interquartile range, 22.9-76.2) months. The underlying aetiologies were renal dysplasia (n=3), pneumococcal-associated haemolytic uraemic syndrome (n=3), ischaemic nephropathy (n=2), and primary hyperoxaluria I (n=1). Peritonitis and exit-site infection rate was 1 episode per 46.5 patient-months and 1 episode per 28.6 patient-months, respectively. Dialysis adequacy (Kt/Vurea>1.8) was achieved in 87.5% of patients. Weight gain was achieved in our patients although three required gastrostomy. Four patients were delayed in development. All patients survived except one patient with primary hyperoxaluria I who died of acute portal vein thrombosis following liver transplantation. One patient with pneumococcal-associated haemolytic uraemic syndrome had sufficient renal function to be weaned off dialysis. Four patients received deceased donor renal transplantation after a mean waiting time of 76.7 months. Three patients remained on chronic peritoneal dialysis at the end of the study. CONCLUSIONS: Chronic peritoneal dialysis is technically difficult in infants. Nonetheless, low peritonitis rate, low exit-site infection rate, and no chronic peritoneal dialysis-related mortality can be achieved. Chronic peritoneal dialysis offers a promising strategy to bridge the way to renal transplantation.

The reliability and validity of the Unified Classification System of periprosthetic femoral fractures after hip arthroplasty.

The Unified Classification System has expanded and updated the Vancouver Classification System and applied treatment principles to all periprosthetic fractures. This study assessed the reliability and validity of the Unified Classification System for femur fractures after hip arthroplasty. Thirty-eight radiographs were finally evaluated by 6 observers, 3 consultants and 3 trainees. Each observer read the radiographs on 2 separate occasions, independently, at least 2 weeks apart. Interobserver and intraobserver agreement and validity were analyzed, using weighted κ statistics. The mean κ value for interobserver agreement was found to be 0.849 (0.838-0.871) for consultants (almost perfect agreement) and 0.761 (0.707-0.836) for the trainees (substantial agreement). Intraobserver κ values ranged from 0.740 to 0.903, showing substantial to almost perfect agreement. Validity analysis of 23 type B cases revealed 79.710% agreement within B1, B2, and B3 subgroups with a mean κ value of 0.694 (0.670-0.741) (substantial agreement).

Non-linear relationship between birthweight and cardiometabolic risk factors in Chinese adolescents and adults.

AIM: To investigate the relationship between birthweight and cardiometabolic traits in two cohorts: one of Chinese adolescents and one of Chinese adults. METHODS: Birthweight and clinical data, including anthropometric traits, fasting plasma glucose and fasting plasma insulin levels, blood pressure and lipid profiles were collected from 2035 adolescents and 456 adults. A subset of 735 subjects underwent an oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min. RESULTS: Among adolescents, birthweight showed U-shaped relationships with larger body size, obesity, abdominal obesity in girls, insulin resistance and worse lipid profiles (0.0013 < P(quadratic) < 0.0499), as well as an inverse association with fasting plasma glucose (P(linear) = 0.0368). After further adjustment for adiposity, decreasing birthweight was associated with elevated fasting plasma glucose levels, greater insulin resistance and worse lipid profiles (3.1 × 10⁻5 < P(linear) < 0.0058). Among adults, high birthweight was associated with larger body size and abdominal obesity in men, while low birthweight was associated with elevated glucose levels at 15, 30, 60 and 120 min and a greater area under the curve at 0-120 min, as well as with ß-cell dysfunction (6.5 × 10⁻5 < P(linear) < 0.0437). Adjustment for adult adiposity did not substantially change the relationships. There was significant interaction between birthweight and abdominal obesity in elevating fasting plasma insulin and homeostasis model assessment of insulin resistance (P > 0.05), with abdominally obese adolescents in the lowest birthweight category (≤ 2.5 kg) having the highest risk of insulin resistance. CONCLUSIONS: Both high and low birthweights are associated with an increased risk of cardiometabolic abnormalities including obesity, abdominal obesity, hyperglycaemia, dyslipidaemia and insulin resistance, as well as with ß-cell dysfunction.

Inflammatory focal bone destruction in femoral heads with end-stage haemophilic arthropathy: a study on clinic samples with micro-CT and histological analyses.

INTRODUCTION: Focal bone destruction has a high prevalence in haemophilic arthropathy (HA) affected joints, but the mechanism remains unclear. AIM: We undertook this study on clinic samples to explore the focal bone destruction in femoral heads suffered with end-stage HA. METHODS: Twenty-one femoral heads from HA patients and 19 femoral heads from rheumatoid arthritis (RA) patients were scanned by micro-CT. Histological analysis, including TRAP staining of subchondral bone were performed to evaluate the bone destruction and osteoclasts activity. RANKL, OPG as well as pro-inflammatory cytokines, such as TNF-α and IL-1ß in subchondral bone were detected by immunohistochemistry (IHC) method. RESULTS: Severe focal lesion was observed in all the HA and RA femoral heads by micro-CT imaging and histological analysis. The mean percentage of lesion volume to total volume of the femoral heads from HA patients was significantly higher than those from RA patients. There was no significant difference in osteoclasts numbers in subchondral bone between HA and RA groups. By IHC analysis, high expression of RANKL, TNF-α, IL-1ß and low expression of OPG and RANK were observed in subchondral bone, and there were no significant differences in the expression of RANKL, OPG, RANK, TNF-α and IL-1ß in femoral heads derived from HA and RA patients. CONCLUSION: Our findings demonstrated the focal bone destruction coupled with inflammatory osteoclastogenesis at subchondral bone in femoral heads from patients with end-stage HA, and that was similar to the changes in the femoral heads of RA patients.

Early gene-diet interaction between glucokinase regulatory protein (GCKR) polymorphism, vegetable and fish intakes in modulating triglyceride levels in healthy adolescents.

BACKGROUND AND AIMS: The benefits of dietary vegetable and fish consumptions on improving glucose and lipid metabolism have been well established. Recently, the T-allele of a common genetic variant rs780094 at glucokinase regulatory protein (GCKR) was reported to be associated with elevated triglyceride (TG) levels but reduced fasting plasma glucose (FPG) and type 2 diabetes risk. However, the dietary modulation on genetic risk is not clearly understood. METHODS AND RESULTS: A cohort of 2095 Chinese adolescents (mean age 15.6 ± 2.0 years, 45.3% male) recruited from a population-based school survey for cardiovascular risk factor assessment, with dietary data including weekly vegetable and fish consumptions as well as clinical data were genotyped for the GCKR rs780094 polymorphism. In the linear regression analysis with adjustment for sex, age, body mass index, and socioeconomic status (school banding, paternal and maternal education levels), the frequency of vegetable intake per week was inversely associated with FPG (P = 0.044). Individuals with low fish intake generally had elevated TG levels but reduced TC, HDL-C and LDL-C (0.006 < P < 0.029). We also observed significant associations of the minor T-allele of GCKR rs780094 with decreased FPG (P = 0.013) and increased TG levels (P = 2.7 × 10(-8)). There were significant gene-diet interactions between rs780094 and vegetable consumption (P(interaction) = 0.009), and between rs780094 and fish consumption (P(interaction) = 0.031) in modulating TG levels. The T-allele of GCKR locus was associated with higher TG levels amongst individuals with ≥7 vegetable meals per week (P = 6.4 × 10(-9)), and among individuals with <7 fish meals per week (P = 0.020 and 7.0 × 10(-7) for 4-6 and ≤3 meals per week, respectively). High intake of vegetable exerted a reduction in TG levels only among CC genotype carriers (Ptrend = 0.020), while high intake of fish was associated with reduced TG levels only among TT genotype carriers (Ptrend = 0.026). CONCLUSIONS: In summary, our data indicated that the favorable associations of higher vegetable and fish intakes on TG levels are dependent on the genetic background of an individual. In particular, at-risk TT- genotype carriers of the GCKR variant may derive more benefits from a high fish intake, while the CC-genotype carriers may find further benefits from a high consumption of vegetable.

Partial calcium depletion during membrane filtration affects gelation of reconstituted milk protein concentrates.

Milk protein concentrate powders (MPC) with improved rehydration properties are often manufactured using processing steps, such as acidification and high-pressure processing, and with addition of other ingredients, such as sodium chloride, during their production. These steps are known to increase the amount of serum caseins or modify the mineral equilibrium, hence improving solubility of the retentates. The processing functionality of the micelles may be affected. The aim of this study was to investigate the effects of partial acidification by adding glucono-δ-lactone (GDL) to skim milk during membrane filtration on the structural changes of the casein micelles by observing their chymosin-induced coagulation behavior, as such coagulation is affected by both the supramolecular structure of the caseins and calcium equilibrium. Milk protein concentrates were prepared by preacidification with GDL to pH 6 using ultrafiltration (UF) and diafiltration (DF) followed by spray-drying. Reconstituted UF and DF samples (3.2% protein) treated with GDL showed significantly increased amounts of soluble calcium and nonsedimentable caseins compared with their respective controls, as measured by ion chromatography and sodium dodecyl sulfate-PAGE electrophoresis, respectively. The primary phase of chymosin-induced gelation was not significantly different between treatments as measured by the amount of caseino-macropeptide released. The rheological properties of the reconstituted MPC powders were determined immediately after addition of chymosin, both before and after dialysis against skim milk, to ensure similar serum composition for all samples. Reconstituted samples before dialysis showed no gelation (defined as tan δ=1), and after re-equilibration only control UF and DF samples showed gelation. The gelation properties of reconstituted MPC powders were negatively affected by the presence of soluble casein, and positively affected by the amount of both soluble and insoluble calcium present after reconstitution. This work, testing the chymosin-induced gelation behavior of various reconstituted MPC samples, clearly demonstrated that a decrease in pH to 6.0 during membrane filtration affects the integrity of the casein micelles supramolecular structure with important consequences to their processing functionality.

Homozygous loss-of-function mutation of the LEPREL1 gene causes severe non-syndromic high myopia with early-onset cataract.

High myopia is a severe visual impairment which can increase the risk of retinal degeneration, subretinal hemorrhage, choroidal neovascularization, cataract and retinal detachment. We recruited an autosomal-recessive high myopia family, with affected subjects who also present early-onset cataract, retinal degeneration and other complications. Using targeted capturing and whole exome sequencing, we identified a homozygous non-sense mutation in the LEPREL1 gene which causes premature termination of the translation at the fifth amino acid (c.13C>T; p.Q5X), co-segregating with the phenotypes. LEPREL1 encodes a proline hydroxylase called prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The results show that LEPREL1 plays an important role in eye development and homozygous loss-of-function mutation of this gene can cause severely high myopia and early-onset cataract. Our study also strongly suggests that the disruption of collagen modification is one of the pathogenic mechanisms of high myopia and cataract.

Changes in the physical properties, solubility, and heat stability of milk protein concentrates prepared from partially acidified milk.

A limiting factor in using milk protein concentrates (MPC) as a high-quality protein source for different food applications is their poor reconstitutability. Solubilization of colloidal calcium phosphate (CCP) from casein micelles during membrane filtration (e.g., through acidification) may affect the structural organization of these protein particles and consequently the rehydration and functional properties of the resulting MPC powder. The main objective of this study was to investigate the effects of acidification of milk by glucono-δ-lactone (GDL) before ultrafiltration (UF) on the composition, physical properties, solubility, and thermal stability (after reconstitution) of MPC powders. The MPC samples were manufactured in duplicate, either by UF (65% protein, MPC65) or by UF followed by diafiltration (80% protein, MPC80), using pasteurized skim milk, at either the native milk pH (~pH 6.6) or at pH 6.0 after addition of GDL, followed by spray drying. Samples of different treatments were reconstituted at 5% (wt/wt) protein to compare their solubility and thermal stability. Powders were tested in duplicate for basic composition, calcium content, reconstitutability, particle size, particle density, and microstructure. Acidification of milk did not have any significant effect on the proximate composition, particle size, particle density, or surface morphology of the MPC powders; however, the total calcium content of MPC80 decreased significantly with acidification (from 1.84 ± 0.03 to 1.59 ± 0.03 g/100 g of powder). Calcium-depleted MPC80 powders were also more soluble than the control powders. Diafiltered dispersions were significantly less heat stable (at 120°C) than UF samples when dissolved at 5% solids. The present work contributes to a better understanding of the differences in MPC commonly observed during processing.

Exome sequencing identifies UPF3B as the causative gene for a Chinese non-syndrome mental retardation pedigree.

Mental retardation (MR) is a group of common and complex disabilities affecting the central nervous system and appears before the period of brain developmental maturity. Recently, only 40% of genetic MR has been identified, however 60% remains unexplained. In this study, we applied exome sequencing to identify the mutation p.R430X in UPF3B gene in an MR pedigree, which was validated by Sanger sequencing and completely cosegregated within this family. UPF3B gene encodes a protein involved in nonsense-mediated mRNA decay (NMD). By real-time quantitative PCR, we detected the significant difference in the mRNA expression levels of the UPF3B and the classical NMD pathway target growth arrest and DNA-damage-inducible-beta (GADD45B) between the patients and the controls. Our results directly implicated that the mutation p.R430X in UPF3B gene was the genetic etiology of the MR pedigree.

A quantitative approach to histopathological dissection of elastin-related disorders using multiphoton microscopy.

BACKGROUND: Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin. OBJECTIVES: To quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilizing autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders. METHODS: Cross-sections of skin samples from elastin-related disorders were analysed by MPM and correlated to histopathology. In situ visualization of elastic fibres by MPM was conducted by en face imaging of ex vivo skin samples through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions. RESULTS: Based on the MPM-detected elastin-specific autofluorescence, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in vivo. CONCLUSIONS: MPM has the potential for noninvasive in vivo visualization of elastic fibres in the dermis with near histological resolution. DEMI allows objective assessment of elastic fibres to support diagnosis and monitoring of disease progress or therapy of elastin-related skin disorders.

Comparison of clinical efficacy between direct anterior approach and posterolateral approach in primary total hip arthroplasty.

OBJECTIVE: The aim of this study was to retrospectively analyze the clinical efficacy of the direct anterior approach (DAA) vs. posterolateral approach (PLA) in primary total hip arthroplasty (THA). PATIENTS AND METHODS: A total of 382 patients who underwent primary THA in our hospital from March 2016 to March 2021 were identified as research subjects, with 183 patients in the DAA group and 199 in the PLA group. Outcome measures included operation time, intraoperative blood loss, postoperative creatine kinase (CK), Harris score, visual analogue scale (VAS), postoperative hospital stay, and postoperative complications. RESULTS: DAA resulted in significantly longer operative time but lower intraoperative bleeding volume vs. PLA. Three months postoperatively, patients receiving DAA showed significantly lower visual analogue scale (VAS) scores and higher Harris scores than those given PLA. No hip dislocation was observed in the DAA group. CONCLUSIONS: DAA results in less intraoperative hemorrhage and muscle damage, better postoperative recovery, and a lower incidence of hip dislocation.