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Abstract Restless sleep disorder (RSD) is a newly defined sleep-related movement disorder characterized by large muscle movements (LMM) in sleep. We examined the sleep study, clinical characteristics, and daytime functioning in children with RSD and compared them to children with periodic limb movement disorder (PLMD) or restless legs syndrome (RLS). Video polysomnography from 47 children with restless sleep was retrospectively reviewed for LMM and age- and sex-matched to 34 children with PLMD and 12 children with RLS. Data examined included PSG characteristics, ferritin, Pediatric Quality of Life (PedsQL), and Epworth Sleepiness Scale (ESS). Fourteen children met the clinical criteria for RSD with an LMM index of 5 or more per hour of sleep. Mean ESS was elevated in patients with RSD compared to either the PLMD or RLS groups though the result did not reach statistical significance (RSD = 10.20 ± 6.81, PLMD = 6.19 ± 4.14, RLS = 6.25 ± 4.90). The PedsQL score was significantly decreased in the RLS group compared to RSD and was reduced overall in all three groups (PedsQL Total RSD = 70.76 ± 18.05, PLMD = 57.05 ± 20.33, RLS = 53.24 ± 16.97). Serum ferritin values were similar in all three groups (RSD = 26.89 ± 10.29, PLMD = 33.91 ± 20.31, RLS = 23.69 ± 12.94 ng/mL, p = ns). Children with RSD demonstrate increased daytime sleepiness compared to PLMD or RLS and all three disease groups showed decreased quality of life. Further studies are needed to examine long-term consequences of RSD.

Aim： Osteocalcin, a biochemical marker of bone formation, has been suggested to be involved in the regulation of energy metabolism. The aim of this study was to investigate the possible association between serum osteocalcin and markers of glucose and lipid metabolism in a large sample of healthy Chinese women. Methods： A total of 2032 healthy Chinese women in Shanghai, aged 20-94 （including 1396 discovery-study subjects and 636 postmenopausal women for a reduplication analysis） were recruited. Their serum osteocalcin, calcium and the relevant measurements were analyzed. A Spearman correlation analysis was performed between osteocalcin and the other markers of energy metabolism including triglyceride, total cholesterol, fasting plasma glucose （FPG）, serum insulin, body mass index and homeostasis model assessment-insulin resistance. Separate multiple regression analyses were performed with data from the discovery and reduplication subjects to determine whether serum osteocalcin concentration was an independent predictor of the glucose or lipid metabolism markers. Results： For the discovery-study subjects, serum osteocalcin was found to be negatively associated with weight （r=-0.08, P=0.002）, BMI （r=-0.13, P〈0.001） and FPG （r=-0.13, P=0.001）. Similar results were also found in the reduplication subjects （weight： r=-0.19, P=0.016; BMI： r=-0.23, P=0.003; FPG： r=-0.28, P〈0.001）. In the multiple regression analysis, serum osteocalcin was revealed as a potential independent predictor for FPG （β=-0.07 and -0.210 for discovery and reduplication, respectively, P〈0.01） and BMI （β=-0.127 and -0.299 for discovery and reduplication, respectively, P〈0.05）. Conclusion： Serum osteocalcin is negatively associated with weight BMI and FPG in healthy Chinese women. Therefore, osteocalcin might contribute to obesity and diabetes.

In this work, we report on synergistic effect of chloride ion and albumin on the corrosion of pure magnesium through corrosion tests. We show that the adsorption of albumin mainly affects the anodic polarization behavior of pure magnesium in NaCl solution. Low concentration of albumin enhances the reaction reactivity of pure magnesium and the initial evolvement of hydrogen at the initial immersion time. Addition of 1 g/L albumin provides limited corrosion control for pure magnesium in NaCl solution. In comparison with low concentration albumin, addition of 10 g/L albumin can effectively inhibit the further dissolution of pure magnesium in test solutions with NaCl concentration of 0.2–0.8 wt.%, but this effect lowers gradually with increasing the concentration of chloride ion.

Model-driven architecture (MDA) has become a main stream technology for software-intensive system design. The main engineering principle behind it is that the inherent complexity of software development can only be mastered by building, analyzing and manipulating system models. MDA also deals with system complexity by providing component-based design techniques, allowing independent component design, implementation and deployment, and then system integration and reconfiguration based on component interfaces. The model of a system in any stage is an integration of models of different viewpoints. Therefore, for a model-driven method to be applied effectively, it must provide a body of techniques and an integrated suite of tools for model construction, validation, and transformation. This requires a number of modeling notations for the specification of different concerns and viewpoints of the system. These notations should have formally defined syntaxes and a unified theory of semantics. The underlying theory of the method is needed to underpin the development of tools and correct use of tools in software development, as well as to formally verify and reason about properties of systems in mission-critical applications. The modeling notations, techniques, and tools must be designed so that they can be used seamlessly in supporting development activities and documentation of artifacts in software design processes. This article presents such a method, called the rCOS, focusing on the models of a system at different stages in a software development process, their semantic integration, and how they are constructed, analyzed, transformed, validated, and verified.

Wall pressure fluctuations in turbulent boundary layer flow over backward-facing step with and without entrainment were investigated. Digital array pressure sensors and multi-arrayed microphones were employed to acquire the time-averaged static pressure and fluctuating pressure, respectively. The differences of two flows were scrutinized in terms of static pressure characteristics, pressure fluctuations, cross-correlation and coherence of wall pressure. Introduction of the entrainment increased scale of large-scale vortical structure and reduced its convection velocity. However, shedding frequency of large-scale vortical structures was found to be the same for both flows.

The unsteady behavior of the large-scale vortical structures buried in a wall-bounded turbulent shear layer flow was extensively investigated using pressure-velocity joint measurements. The wall pressure fluctuations and flow field velocity fluctuations were measured simultaneously by using a microphone and an X-type hotwire, respectively. The spatially and temporally strong coupling between the convecting flow structures and the wall pressure fluctuations were meticulously investigated in terms of the continuous wavelet transform, cross-correlation and coherence of the wall pressure and flow field. The characteristics of the large-scale vortical structures, e.g., the shedding frequency, averaged convection velocity, convective motion, and structure pattern were revealed.

Aim： A previous study showed that individuals of Japanese descent affected by early onset familial Paget＇s disease of bone （PDB） carried a 27-bp duplication at position 75 （75dup27） in the TNFRSF11A gene encoding RANK. Here we report the identification of a novel mutation （78dup27） in exon I of TNFRSF11A in a Chinese family with early onset PDB. Methods： We conducted clinical and genetic studies in a non-consanguineous Chinese family with early onset PDB. The entire coding region of TNFRSF11A was amplified and directly sequenced directly. Results： A novel 27-bp duplication in exon 1 （78dup27） in TNFRSF11A was found in four affected individuals and one asymptomatic individual. Although this duplication was the same length as the previously identified mutation （27 bp, from bases 78 to 104）, in our patients the nine duplicated amino acids in the RANK signal peptide were LLLLCALLA. The phenotypes of affected individuals in this family overlapped with both early onset PDB and classic PDB, but several distinguishing features were found in our patients. The key difference between our familial PDB and the Japanese early onset PDB was the age of onset, which in most of our patients was during their late 20s （except for the propositus＇ niece）. Another notable difference was that the propositus＇ son （24 years old）, who carried the 78dup27 mutation, had no clinical symptoms or bone abnormalities, except for increased serum ALP, OC and CTX. Conclusion： Our findings may provide a better understanding of the clinical features of early onset PDB and support the notion of a hot spot for mutations in exon I of the TNFRSF11A gene.

Prostate cancer (PCa) is one of the most common malignancies in males. Despite the success of immunotherapy in many malignant cancers, strategies are still needed to improve therapeutic efficacy in PCa. This study aimed to investigate the effects of -derived extracellular vesicles ( -EVs) on PCa and elucidate the underlying immune-related mechanism. -EVs were isolated by ultracentrifugation and intravenously injected to treat syngeneic PCa-bearing immune-competent mice. Immunophenotypic changes in immune cells, such as cytotoxic T lymphocytes and macrophages, were measured via flow cytometry analysis. Histological examination was used to detect morphological changes in major organs after -EVs treatments. In vitro, flow cytometry was performed to confirm the effects of -EVs on the activation of CD8 T cells. Quantitative PCR and immunofluorescence staining were carried out to test the impact of -EVs on macrophage polarization. Cell counting kit-8 (CCK-8) analysis, colony formation assays, and scratch wound healing assays were conducted to assess the effects of -EVs-treated macrophages on the proliferation and invasion of PCa cells. CCK-8 assays also confirmed the impact of -EVs on the viability of normal cells. Intravenous injection of -EVs in immune-competent mice reduced the tumor burden of PCa without inducing obvious toxicity in normal tissues. This treatment elevated the proportion of granzyme B-positive (GZMB ) and interferon γ-positive (IFN-γ ) lymphocytes in CD8 T cells and caused macrophage recruitment, with increased tumor-killing M1 macrophages and decreased immunosuppressive M2 macrophages. In vitro, -EVs increased the number of GZMB CD8 and IFN-γ CD8 T cells and M1-like macrophages. In addition, conditioned medium from -EVs-treated macrophages suppressed the proliferation and invasion of prostate cells. Furthermore, the effective dose of -EVs was well-tolerated in normal cells. Our study revealed the promising prospects of -EVs as an efficient and biocompatible immunotherapeutic agent for PCa treatment.

Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab ( n  = 99) or undergo active surveillance ( n  = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360–0.792; P  = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655 . Results from a multicenter, randomized phase 2 trial in China show that adjuvant anti-PD-1 therapy in patients with resected hepatocellular carcinoma with microvascular invasion leads to prolonged recurrence-free survival compared to active surveillance.

We retrospectively evaluated the clinical outcome of penile prosthesis implantation （PPI） in Chinese patients with severe erectile dysfunction （SED）. From July 2000 to December 2011, 224 patients （mean age： 35.9±11.8 years, range： 20-75 years） with SED underwent PPI by experienced surgeon according to standard PPI procedure at our centre. A malleable prosthesis （AMS 650） was implanted in 45 cases （20.1%）, and a three-piece inflatable prosthesis （AMS 700 CXM or AMS 700 CXR） was implanted in 179 cases （79.9%）. Surgical outcomes, including postoperative complications, clinical efficacy and couple satisfaction, were evaluated over than 6 months postoperatively using medical record abstraction, IIEF-5, quality of life （QoL） scores, and the patient/partner sexual satisfaction score proposed by Bhojwani etaL Of the 224 patients eligible for the study, 201 subjects （89.7%） completed follow-up. All of patients could perform sexual intercourse post PPI with the mean postoperative IIEF-5 and QoL scores were 20.02±2.32 and 5.28±0.76, respectively, which were significantly improved compared with the preoperative scores （6.29±1.5 and 2.13±0.84, P〈0.01）. Of the 201 men, mechanical malfunction occurred in four cases （2.0%） and three cases were re-implanted new device, and two cases （1.0%） developed a mild curvature of the penis. Scrotal erosion with infection occurred in one case with diabetes mellitus （0.5%） and required complete removal of the implanted AMS 700 CXM. Satisfactory sexual intercourse at least twice per month was reported by 178 men （88.6%）, and overall satisfaction with the PPI surgery was reported by 89.0% of men and 82.5% of partners. Patient satisfaction in the three-piece inflatable prosthesis group was higher than in the malleable prosthesis group （P〈0.05）. Satisfaction, however, between the types of prostheses, did not differ in the partner survey. PPI is a safe and effective treatment option for Chinese patients with SED and experienced surgeon perform PPI according to standard PPI procedure could reduce the postoperative complications of PPI and could improve patient satisfaction ratio and QoL.