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Abstract Objective To analyze the influential factors of frailty in elderly patients with coronary heart disease (CHD), develop a nomogram-based risk prediction model for this population, and validate its predictive performance. Methods A total of 592 elderly patients with CHD were conveniently selected and enrolled from 3 tertiary hospitals, 5 secondary hospitals, and 3 community health service centers in China between October 2022 and January 2023. Data collection involved the use of the general information questionnaire, the Frail scale, and the instrumental ability of daily living assessment scale. And the patients were categorized into two groups based on frailty, and χ2 test as well as logistic regression analysis were used to identify and determine the influencing factors of frailty. The nomograph prediction model for elderly patients with CHD was developed using R software (version 4.2.2). The Hosmer–Lemeshow test and the area under the receiver operating characteristic (ROC) curve were employed to assess the predictive performance of the model. Additionally, the Bootstrap resampling method was utilized to validate the model and generate the calibration curve of the prediction model. Results The prevalence of frailty in elderly patients with CHD was 30.07%. The multiple factor analysis revealed that poor health status (OR = 28.169)/general health status (OR = 18.120), age (OR = 1.046), social activities (OR = 0.673), impaired instrumental ability of daily living (OR = 2.384) were independent risk factors for frailty (all P

Working fluid selection for closed-cycle turbo-refrigerators (CCTRs) for deep freezing, as a more fundamental topic, has not yet received careful consideration, leading to limitations in attempts to optimizing CCTR design in the early stages of cycle design. This paper proposed the working fluid selection criteria that to select the one leading to the lowest system weight and volume without compromising the system energy efficiency. Design criteria, such as specific speed and Reynolds number, and their dependence on fluid properties are introduced to ensure uncompromising-efficiency design of turbomachinery. Normalized heat transfer area of recuperator correlated with fluid properties is derived as the evaluation criterion for system weight and volume. Applying the proposed criteria, the comparison between potential pure gases shows the normalized heat transfer areas required for nitrogen, neon, and argon are 1, 1.54 and 2.18, respectively. Therefore, nitrogen among all pure gases has the greatest potential to reduce system weight and volume. The comparison among potential binary mixtures highlights the methane-nitrogen mixture with the molar mass of 24.1 g/mol which reduces the required heat transfer area by approximately 20 % compared to pure-nitrogen-based system and may reduce it by nearly up to 30 % for systems with larger cooling capacity levels.

Abstract Background This study delves into the correlation between Corona Virus Anxiety (CVA) and the engagement as well as academic resilience of Chinese students. The context is set against the backdrop of the global pandemic, highlighting the potential psychological impact of COVID-19 on students’ well-being and academic performance. Objectives The primary objectives of this research are to investigate the relationship between CVA and various dimensions of student engagement, including affective, behavioral, and cognitive aspects. Additionally, the study aims to explore how CVA influences academic resilience, with a focus on persistence and self-regulation. The dual-objective approach employs both quantitative and qualitative methods to provide a comprehensive understanding of the subject matter. Methodology A mixed-methods approach is employed, combining quantitative data from scales measuring CVA, engagement, and academic resilience with qualitative insights obtained through interviews. The research sample consists of 390 students from Mudanjiang Medical University. Quantitative data are analyzed using Pearson correlation tests, while thematic analysis is applied to interpret the qualitative findings from interviews. Results Quantitative data analysis reveals significant negative correlations between CVA and multiple dimensions of student engagement, indicating that higher CVA levels are associated with lower engagement levels. Academic resilience, though relatively high among participants, also exhibits negative correlations with CVA, particularly in terms of persistence and self-regulation. The qualitative findings uncover six main themes elucidating the impact of CVA on students, ranging from emotional and cognitive engagement to the social and technological challenges posed by the pandemic. Conclusions and implications The research concludes that CVA significantly influences students’ engagement and academic resilience. The qualitative insights contribute to a nuanced understanding of the diverse challenges students face during the pandemic. These findings have broad implications for students, university administrators, educators, and educational psychologists, highlighting the importance of addressing mental health concerns and providing adequate support systems in the context of global crises.

Background Previous studies have shown that intravenous normal saline (NS) may be associated with the incidence of acute kidney injury (AKI). This study aimed to evaluate the association between the volume of NS infusion and AKI in heat stroke (HS) patients.Methods This multicenter retrospective cohort study included 138 patients with HS. The primary outcome was the incidence of AKI. Secondary outcomes included the need for continuous renal replacement therapy (CRRT), admission to the intensive care unit (ICU), length of stay in the ICU and hospital, and in-hospital mortality. Multivariate regression models, random forest imputation, and genetic and propensity score matching were used to explore the relationship between NS infusion and outcomes.Results The mean volume of NS infusion in the emergency department (ED) was 3.02 ± 1.45 L. During hospitalization, 33 patients (23.91%) suffered from AKI. In the multivariate model, as a continuous variable (per 1 L), the volume of NS infusion was associated with the incidence of AKI (OR, 2.51; 95% CI, 1.43–4.40; p = .001), admission to the ICU (OR, 3.46; 95% CI 1.58–7.54; p = .002), and length of stay in the ICU (β, 1.00 days; 95% CI, 0.44–1.56; p

The turbo-expander is the crucial equipment for obtaining refrigeration capacity and power in the system, and the aerodynamic performance is vital for the system. Spontaneous condensation of moist air in a high-speed turbo expander has a significant effect on the efficiency and output power. Based on the model of non-equilibrium spontaneous condensation, the flow of moist air in a high-speed turbo expander was studied, which is verified by the experiments. The meridional surface shape affects the variation of the flow passage cross-sectional area. The impeller with a uniform variation in cross-sectional area has the highest efficiency. Based on the optimal meridional surface shape, the condensation flow of moist air with different impeller blade diversion curvature was compared. The optimal curvature can increase the efficiency of the moist air turbo-expander by 2.83 %, and the optimized impeller has 3.53 % higher output power. The largest curvature of the blade leads to an efficiency reduction by 3.06 %, but it has little droplet condensation in the impeller, which can help to avoid damage of high-speed blades.

Background: Breast cancer represents a leading cause of malignancy among Chinese women, posing a significant health burden. The diagnosis of metastatic breast cancer, particularly to uncommon sites like the skin and stomach, presents distinct challenges.Case introduction: This case report describes a 71-year-old Chinese women with a persistent back rash lasting more than 6 months. Physical examination revealed red papules on her back. Immunohistochemistry confirmed positive for cytokeratin 7(CK7), GATA-3 and GCDFP15, as well as negative staining of cytokeratin 20 (CK20), suggesting breast cancer metastasis. Further evaluation revealed a breast nodule and axillary lymph node enlargement, with biopsies confirming invasive lobular carcinoma (ILC). Abdominal computed tomography (CT) revealed thickening of the gastric and ascending colon walls. Gastroscopy revealed chronic superficial atrophic gastritis. However, gastric metastasis was further confirmed by pathology. The patient initiated endocrine therapy with fulvestrant and exemestane, resulting in rash resolution and stable breast and stomach lesions after 3 months. Overall, the patient is experiencing an improvement in her condition and remains stable while continuing treatment.Conclusion: This case highlights the importance of considering atypical metastatic patterns in breast cancer and the potential efficacy of endocrine therapies in managing such cases. Moreover, it emphasizes the need for vigilance in breast cancer patients, especially those with ILC, as gastrointestinal symptoms may indicate gastric metastasis (GMs). Ultimately, early detection and appropriate treatment strategies, such as endocrine therapy, can contribute to improved outcomes in these challenging cases.

Electrocatalytic upgrading of biomass-derived platform molecules has emerged as a sustainable and environmentally benign route to produce high-value chemicals. The main challenge lies in developing efficient catalysts for the selective activation of designated chemical bonds in the presence of various reducible groups. This work demonstrated a high-efficiency electrochemical conversion of 5-hydroxymethylfurfural (HMF) to 2,5-bis(hydroxymethyl)furan (BHMF), an important industrial synthetic reagent. A highly porous Cu-based catalyst was developed that achieved nearly 100% BHMF selectivity and long-term stability. Through comprehensive operando and ex-situ structural characterizations, an electrochemically generated catalyst with abundant Cu/Cu2O interfaces was identified as a catalytically active phase for HMF conversion. Deuterated BHMF, with the potential to produce deuterated drugs, was also synthesized using D2O as the deuterium source. Density functional theory calculations show that the Cu/Cu2O interface structure exhibits relatively low energy barriers for the hydrogenation of HMF to BHMF. This work provides insights into the origin of electrocatalytic hydrogenation activity and highlights the promising potential of the electrocatalytic synthesis of high-value chemicals.

Abstract To explore the interaction of instrumental activities of daily living (IADLs) and dual sensory function on cognition in the elderly. A cross‐sectional survey was conducted in six general hospitals in China, from October 2022 to December 2022. Data collection included general information, IADLs scale, self‐reported sensory function questionnaire, and mini‐mental state examination (MMSE). Binary logistic regression was used to examine the association between factors and cognition. The interactive effect was evaluated by synergy index (S), relative excess risk due to interaction (RERI), and attributable proportion due to interaction (AP). The odds ratio (OR) of IADLs decline in cognition is 4.412 (95% confidence interval [CI]: 3.633–5.358, p

The detection of tumor markers has significant importance in the early diagnosis of cancer. It is an important indicator for evaluating the extent of the disease and monitoring the efficacy of tumor treatment. Therefore, it is meaningful to find a convenient, fast, and sensitive method to detect tumor markers. Carbohydrate antigen 19–9 (CA19-9) is the first discovered carbohydrate antigen tumor marker with the highest sensitivity and specificity for pancreatic cancer. Carcinoembryonic antigen (CEA), as the most widely spectrum carbohydrate antigen tumor marker, can show an upward trend in many tumors. In this work, an electrochemical immunosensing platform was proposed for the detection of CEA and CA199. Nano-silicon sphere-cyclodextrin was synthesized for antibody capture. Graphene and gold nanoparticles were used to modify the electrode, improving the electronic conductivity of the electrode. The synthesized sensor can be used for highly sensitive detection of two tumor markers. This method also provides a new platform for clinical immune analysis of other biomolecules.

Abstract The authors conducted an observational study to explore the association between body fat composition and the risk of hyperhomocysteinemia (HHcy) and their combined effect on the risk of developing cardiovascular disease (CVD). Adults aged 18–74 years from the Northwest China Natural Population Cohort: Ningxia Project (CNC‐NX) were recruited in this study. Association between body fat composition and HHcy was evaluated by logistic regression model. Restricted cubic spline was used to find nonlinear association. The impact of the interaction between HHcy and body fat composition on CVD was evaluated using the addition interaction model and mediation effect model. In total, 16 419 participants were included in this research. Body fat percentage, visceral fat level, and abdominal fat thickness were positively associated with overall HHcy (p for trend

BackgroundObservational studies have revealed associations between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. However, these studies are susceptible to unavoidable confounding factors, leading to ongoing debates regarding their conclusions and making causal relationships challenging to infer. In light of these challenges, Mendelian randomization was employed in this study to investigate the causal relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction.MethodsThis study employed a two-sample Mendelian randomization approach using genetic variation as instrumental variables to investigate causal relationships. Genetic variation data were sourced from summary data of genome-wide association studies in European populations. Instrumental variables were selected based on the principles of Mendel's three assumptions. The study utilized the inverse variance weighted method to assess the relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. Supplementary analyses were conducted using MR-Egger regression, the weighted median method, and the weighted median mode to complement the IVW results. Furthermore, the study conducted heterogeneity, horizontal pleiotropy, and sensitivity analyses to evaluate the robustness of the results.ResultsBased on the inverse variance weighted method, it was found that there exists a causal relationship between childhood obesity (OR = 1.378, 95% CI: 1.113∼1.705, p = 0.003), age at menarche (OR = 0.639, 95% CI: 0.468∼0.871, p = 0.005), and ovarian dysfunction, while no causal relationship was observed between birth weight and ovarian dysfunction. Heterogeneity tests, multiplicity tests, and leave-one-out sensitivity analyses did not detect any heterogeneity or multiplicity effects in the estimated impact of these three exposure factors on the risk of ovarian dysfunction.ConclusionsThis study represents the first evidence suggesting a potential causal relationship between childhood obesity, age at menarche, and ovarian dysfunction. Childhood obesity was found to increase the risk of ovarian dysfunction, while a later age at menarche was associated with a reduced risk of ovarian dysfunction.

Defect-engineered carbon materials have been emerged as promising electrocatalysts for oxygen reduction reaction (ORR) in metal-air batteries. Developing a facile strategy for the preparation of highly active nanocarbon electrocatalysts remains challenging. Herein, a low-cost and simple route is developed to synthesize defective graphene by pyrolyzing the mixture of glucose and carbon nitride. Molecular dynamics simulations reveal that the graphene formation is ascribed to two-dimensional layered feature of carbon nitride, and high compatibility of carbon nitride/glucose systems. Structural measurements suggest that the graphene possesses rich edge and topological defects. The graphene catalyst exhibits higher power density than commercial Pt/C catalyst in a primary Zn-air battery. Combining experimental results and theoretical thermodynamic analysis, it is identified that graphitic nitrogen-modified topological defects at carbon framework edges are responsible for the decent ORR performance. The strategy presented in this work can be can be scaled up readily to fabricate defective carbon materials.

BackgroundLung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer (NSCLC), remains a pervasive global public health concern. Disulfidoptosis, a nascent form of regulated cell death (RCD), presents an emerging field of inquiry. Currently, investigations into disulfidoptosis are in their initial stages. Our undertaking sought to integrate single-cell RNA sequencing (scRNA-seq) in conjunction with traditional bulk RNA sequencing (bulk RNA-seq) methodologies, with the objective of delineating genes associated with disulfidoptosis and subsequently prognosticating the clinical outcomes of LUAD patients.MethodsInitially, we conducted an in-depth examination of the cellular composition disparities existing between LUAD and normal samples using scRNA-seq data sourced from GSE149655. Simultaneously, we scrutinized the expression patterns of disulfidoptosis-associated gene sets across diverse cell types. Subsequently, leveraging the bulk RNA-seq data, we formulated disulfidoptosis-related prognostic risk signatures (DRPS) employing LASSO-Cox regression. This was accomplished by focusing on genes implicated in disulfidoptosis that exhibited differential expression within endothelial cells (ECs). Sequentially, the robustness and precision of the DRPS model were rigorously verified through both internal and external validation datasets. In parallel, we executed single-cell trajectory analysis to delve into the differentiation dynamics of ECs. Concluding our study, we undertook a comprehensive investigation encompassing various facets. These included comparative assessments of enrichment pathways, clinicopathological parameters, immune cell abundance, immune response-associated genes, impacts of immunotherapy, and drug predictions among distinct risk cohorts.ResultsThe scrutiny of scRNA-seq data underscored discernible disparities in cellular composition between LUAD and normal samples. Furthermore, disulfidoptosis-associated genes exhibited marked discrepancies within endothelial cells (ECs). Consequently, we formulated the Disulfidoptosis-Related Prognostic Signature (DRPS) to facilitate prognostic prediction. The prognostic nomogram based on the risk score effectively demonstrated DRPS’s robust capacity to prognosticate survival outcomes. This assertion was corroborated by rigorous assessments utilizing both internal and external validation sets, thus affirming the commendable predictive accuracy and enduring stability of DRPS. Functional enrichment analysis shed light on the significant correlation of DRPS with pathways intrinsic to the cell cycle. Subsequent analysis unveiled correlations between DRPS and gene mutations characteristic of LUAD, as well as indications of an immunosuppressive status. Through drug prediction, we explored potential therapeutic agents for low-risk patients. Concluding our investigation, qRT-PCR experiments confirmed the heightened expression levels of EPHX1, LDHA, SHC1, MYO6, and TLE1 in lung cancer cell lines.

Abstract Acute radiation proctitis (ARP) is one of the most common complications of pelvic radiotherapy attributed to radiation exposure. The mechanisms of ARP are related to inflammation, angiogenesis, and so on. In this study we evaluated the effect of dexamethasone (DXM) combined with gentamicin (GM) enema on ARP mice, and explored its possible mechanisms by transcriptome sequencing, western blot and immunohistochemistry. C57BL/6 mice were randomly divided into 3 groups: healthy control group, ARP model group, and DXM + GM enema treatment group. ARP mice were established by using a single 6 MV X-ray dose of 27 Gy pelvic local irradiation. Transcriptome sequencing results showed that 979 genes were co-upregulated and 445 genes were co-downregulated in ARP mice compared to healthy mice. According to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, we firstly found that PI3K/AKT/NF-κB/VEGF pathways were mostly correlated with the inflammation-induced angiogenesis in ARP mice. PI3K/AKT pathway leads to the activation of NF-κB, which promotes the transcription of VEGF and Bcl-2. Interestingly, symptoms and pathological changes of ARP mice were ameliorated by DXM + GM enema treatment. DXM + GM enema inhibited inflammation by downregulating NF-κB and upregulating AQP3, as well as inhibited angiogenesis by downregulating VEGF and AQP1 in ARP mice. Moreover, DXM + GM enema induced apoptosis by increasing Bax and suppressing Bcl-2. The novel mechanisms may be related to the downregulation of PI3K/AKT/NF-κB/VEGF pathways.

A novel indoor positioning method for a pigsty based on ultra-wideband (UWB) technology is proposed via reasonably arranging the base stations and positioning tags, which can provide strong support for the accurate positioning of specific pig pens in the pig house. The distribution of Dilution of Precision (DOP) values is analyzed in different deployment schemes which include the amount, the height, the deployment shape, and the distance of the base stations through positioning simulation. Moreover, the positioning effect of dynamic following positioning, the root-mean-square error (RMSE), and the variance of static positioning are measured. It is noteworthy that the Kalman filtering algorithm is adopted to smooth the dynamic following positioning experimental data for reducing the positioning error. The simulated results show that the DOP values decrease with the increase in height and distance, and these results and laws are consistent with the experimental results. However, the DOP values are best reached when the height is from 1.75 m to 2.75 m, and the distance is over 3.00 m. Furthermore, the DOP values of quadrilateral deployment are smaller than the ones of triangular deployment. In addition, the variance of static positioning and dynamic following positioning is decreased by utilizing the Kalman filtering algorithm. Therefore, the excellent positioning system and its solutions in a pigsty can be provided by our proposed indoor positioning method.

Since tiny optical glass is the key component in various optical instruments, more and more researchers have paid attention to automatic defect detection on tiny optical glass in recent years. It remains a challenging problem, as the defects are extremely small. In this paper, we propose a video-based two-stage defect detection network to improve detection accuracy for small defects. Specifically, the detection process is carried out in a coarse-to-fine manner to improve the detection precision. First, the optical glass area is located on the down-sampled version of the input image, and then defects are detected only within the optical glass area with a higher resolution version, which can significantly reduce the false alarming rate. Since the defects may exist on any place of the optical glass, we fuse the results of multiple video frames captured from various perspectives to promote recall rates of the defects. Additionally, we propose an image quality evaluation module based on a clustering algorithm to select video frames with high quality for improving both detection recall and precision. We contribute a new dataset called OGD-DET for tiny-scale optical glass surface defect detection experiments. The datasets consist of 3415 images from 40 videos, and the size of the defect area ranges from 0.1 mm to 0.53 mm, 2 to 7 pixels on images with a resolution of 1536 × 1024 pixels. Extensive experiments show that the proposed method outperforms the state-of-the-art methods in terms of both accuracy and computation cost.

Abstract Background Hypertension is the fifth chronic disease causing death worldwide. The early prognosis and diagnosis are critical in the hypertension care process. Inspired by human philosophy, CBR is an empirical knowledge reasoning method for early detection and intervention of hypertension by only reusing electronic health records. However, the traditional similarity calculation method often ignores the internal characteristics and potential information of medical examination data. Methods In this paper, we first calculate the weights of input attributes by a random forest algorithm. Then, the risk value of hypertension from each medical examination can be evaluated according to the input data and the attribute weights. By fitting the risk values into a risk curve of hypertension, we calculate the similarity between different community residents, and obtain the most similar case according to the similarity. Finally, the diagnosis and treatment protocol of the new case can be given. Results The experiment data comes from the medical examination of Tianqiao Community (Tongling City, Anhui Province, China) from 2012 to 2021. It contains 4143 community residents and 43,676 medical examination records. We first discuss the effect of the influence factor and the decay factor on similarity calculation. Then we evaluate the performance of the proposed FDA-CBR algorithm against the GRA-CBR algorithm and the CS-CBR algorithm. The experimental results demonstrate that the proposed algorithm is highly efficient and accurate. Conclusions The experiment results show that the proposed FDA-CBR algorithm can effectively describe the variation tendency of the risk value and always find the most similar case. The accuracy of FDA-CBR algorithm is higher than GRA-CBR algorithm and CS-CBR algorithm, increasing by 9.94 and 16.41%, respectively.

Senescent cells release a variety of cytokines, proteases, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Sustained SASP contributes to a pattern of chronic inflammation associated with aging and implicated in many age-related diseases. Here, we investigated the expression and function of the immunomodulatory cytokine BAFF (B-cell activating factor; encoded by the TNFSF13B gene), a SASP protein, in multiple senescence models. We first characterized BAFF production across different senescence paradigms, including senescent human diploid fibroblasts (WI-38, IMR-90) and monocytic leukemia cells (THP-1), and tissues of mice induced to undergo senescence. We then identified IRF1 (interferon regulatory factor 1) as a transcription factor required for promoting TNFSF13B mRNA transcription in senescence. We discovered that suppressing BAFF production decreased the senescent phenotype of both fibroblasts and monocyte-like cells, reducing IL6 secretion and SA-β-Gal staining. Importantly, however, the influence of BAFF on the senescence program was cell type-specific: in monocytes, BAFF promoted the early activation of NF-κB and general SASP secretion, while in fibroblasts, BAFF contributed to the production and function of TP53 (p53). We propose that BAFF is elevated across senescence models and is a potential target for senotherapy.

PurposeAnkle fracture combined with deltoid ligament (DL) injury results in decreased stability of ankle mortise, reduced contact surface between tibial and talus, increased local stress, and increased postoperative complications. The purpose of this meta-analysis was to evaluate the postoperative effects of repairing ligaments in ankle fractures with DL rupture.MethodsAccording to the steps of the Cochrane systematic review, the related literatures from PubMed, Embase and the Cochrane Library Databases were retrieved as of September 1, 2021, and all relevant randomized controlled trials and retrospective studies were collected. The evaluation indicators include medial clear space (MCS), visual analogue scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS), complications rate. Meta-analysis was conducted by RevMan® 5.3 provided by the Cochrane collaboration.ResultsA total of 388 patients (195 patients in the ligament repair group and 193 patients in the non-repair group) were included in 7 clinical trials. Meta-analysis data showed there were no statistically significant differences between the ligament repair group and non-repair group in final follow-up VAS, final AOFAS and postoperative MCS (P = 0.50, P = 0.04, P = 0.14, P = 0.14, respectively). Final follow-up MCS and complications rate in ligament repair group were smaller than those in the non-repair group and were statistically significant (P

Abstract Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient’s hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate.

ObjectiveTo analyze the genotypes and phenotypes of mosaic male patients with PCDH19-related epilepsy (PCDH19-RE) and explore the correlation between genotype, variant allele frequency (VAF), and phenotypic severity.MethodsClinical data and peripheral blood samples of 11 male mosaic patients were collected and analyzed in our study. The VAF of the PCDH19 gene from peripheral blood was quantified using amplicon-based deep sequencing. Additional 20 mosaic male patients with PCDH19-RE were collected from the published literature, with 10 patients whose VAFs of the PCDH19 gene were available for analytic purposes.ResultsIn our cohort of 11 patients, 10 variants were identified, and four were novel. The VAF of the PCDH19 gene from peripheral blood ranged from 27 to 90%. The median seizure onset age was 6 months (range: 4–9 months). Clinical manifestations included cluster seizures (100%), fever sensitivity (73%), focal seizures (91%), developmental delay/intellectual disability (DD/ID, 82%), and autistic features (45%). Thirty-one mosaic male patients collected from our cohort and the literature developed seizures mostly (87%) within one year of age. Variant types included missense variants (42%), truncating variants (52%), splice variants (3%), and whole PCDH19 deletion (3%). Among 21 patients with a definite VAF from our cohort and the literature, nine had a low VAF ( ≤ 50%) and 12 had a high VAF (> 50%). Seventy-five percent of variants from the high VAF group were missense, whereas 89% of those from the low VAF group were truncations. The median seizure onset age was 6 months in the low VAF group and 9 months in the high VAF group (p = 0.018). Forty-four percent (4/9) of patients from the low VAF group achieved seizure-free for ≥1 year, whereas none of the 12 patients from the high VAF group did (p = 0.021). DD/ID was present in 83% (10/12) of the high VAF group and 56% (5/9) of the low VAF group (p = 0.331).ConclusionThe predominant variant types were truncating and missense variants. Missense variants tended to have higher VAFs. Patients with a high VAF were more likely to have a more severe epileptic phenotype. Our findings shed light on the phenotypic implications of VAF in mosaic males with PCDH19-RE.

Abstract Background Among recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors. Effective treatments are urgently needed to improve the outcomes of embryo transfer for RIF patients. In recent years, many researchers have focused on immunotherapy using granulocyte colony-stimulating factor (G-CSF) to regulate the immune environment. However, the study of the G-CSF for RIF patients has reached conflicting conclusions. The aim of this systematic review and meta-analysis was performed to further explore the effects of G-CSF according to embryo transfer cycle (fresh or frozen) and administration route (subcutaneous injection or intrauterine infusion) among RIF patients. Method The PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for literature published from the initial to October 2020. The meta-analysis, random-effects model and heterogeneity of the studies with I2 index were analyzed. Stata 15 was used for statistical analysis. Results A total of 684 studies were obtained through the databases mentioned above. Nine RCTs included 976 RIF patients were enrolled in this meta-analysis. Subgroup analysis indicated that G-CSF improved the clinical pregnancy rate for both the fresh and frozen embryo transfer cycles (fresh RR: 1.74, 95% CI: 1.27–2.37, I2 = 0.0%, n = 410; frozen RR: 1.44, 95% CI: 1.14–1.81, I2 = 0.0.%, n = 366), and for both subcutaneous injection and intrauterine infusion (subcutaneous RR: 1.73, 95% CI: 1.33–2.23, I2 = 0.0%, n = 497; intrauterine RR: 1.39, 95% CI: 1.09–1.78, I2 = 0.0%, n = 479), but the biochemical pregnancy rate of the RIF group was also higher than that of the control group (RR: 1.85, 95% CI: 1.28–2.68; I2 = 20.1%, n = 469). There were no significant differences in the miscarriage rate (RR: 1.13, 95% CI: 0.25–5.21: I2 = 63.2%, n = 472) and live birth rate (RR: 1.43, 95% CI: 0.86–2.36; I2 = 52.5%; n = 372) when a random-effects model was employed. Conclusion The administration of G-CSF via either subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles for RIF patients can improve the clinical pregnancy rate. However, whether G-CSF is effective in improving livebirth rates of RIF patients is still uncertain, continued research on the utilization and effectiveness of G-CSF is recommended before G-CSF can be considered mainstream treatment for RIF patients.

BackgroundHypoglycemia is a common adverse event in the treatment of diabetes. To efficiently cope with hypoglycemia, effective hypoglycemia prediction models need to be developed. ObjectiveThe aim of this study was to develop and validate machine learning models to predict the risk of hypoglycemia in adult patients with type 2 diabetes. MethodsWe used the electronic health records of all adult patients with type 2 diabetes admitted to West China Hospital between November 2019 and December 2021. The prediction model was developed based on XGBoost and natural language processing. F1 score, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were used as the main criteria to evaluate model performance. ResultsWe included 29,843 patients with type 2 diabetes, of whom 2804 patients (9.4%) developed hypoglycemia. In this study, the embedding machine learning model (XGBoost3) showed the best performance among all the models. The AUC and the accuracy of XGBoost are 0.82 and 0.93, respectively. The XGboost3 was also superior to other models in DCA. ConclusionsThe Paragraph Vector–Distributed Memory model can effectively extract features and improve the performance of the XGBoost model, which can then effectively predict hypoglycemia in patients with type 2 diabetes.

Frasier syndrome (FS) is a rare inherited disorder characterized by gonadal dysgenesis and progressive nephropathy, resulting from mutations in the intron 9 splice donor site of the Wilms tumor 1 (WT1) gene. It is associated with male gonadal dysgenesis (female external genitalia with a 46 XY karyotype), and a high risk of gonadoblastoma during adolescence. Patients with FS present early in childhood with proteinuria that progressively worsens with a high likelihood of end-stage renal disease (ESRD). Herein, we report a 15-year-old female (karyotype 46, XY) patient characterized by delayed puberty and steroid-resistant nephrotic syndrome, in whom whole genome sequencing showed a mutation in intron 9 of the WT1 gene, c.1447 + 4 C>T. This is the first case of FS with delayed puberty as the first complaint with no previous renal symptoms. We consider delayed puberty as an important manifestation of FS and summarize the diagnostic process of delayed puberty in the female phenotype. For clinicians, delayed puberty is a common disorder in pediatrics but requires vigilance for some rare causes. Etiological screening and chromosome karyotype analysis are important for the early diagnosis of FS in patients with delayed puberty.

ObjectiveThis study aimed to obtain a comprehensive understanding of the genetic and phenotypic aspects of GABRG2-related epilepsy and its prognosis and to explore the potential prospects for personalized medicine.MethodsThrough a multicenter collaboration in China, we analyzed the genotype-phenotype correlation and antiseizure medication (ASM) of patients with GABRG2-related epilepsy. The three-dimensional protein structure of the GABRG2 variant was modeled to predict the effect of GABRG2 missense variants using PyMOL 2.3 software.ResultsIn 35 patients with GABRG2 variants, 22 variants were de novo, and 18 variants were novel. The seizure onset age was ranged from 2 days after birth to 34 months (median age: 9 months). The seizure onset age was less than 1 year old in 22 patients (22/35, 62.9%). Seizure types included focal seizures (68.6%), generalized tonic-clonic seizures (60%), myoclonic seizures (14.3%), and absence seizures (11.4%). Other clinical features included fever-sensitive seizures (91.4%), cluster seizures (57.1%), and developmental delay (45.7%). Neuroimaging was abnormal in 2 patients, including dysplasia of the frontotemporal cortex and delayed myelination of white matter. Twelve patients were diagnosed with febrile seizures plus, eleven with epilepsy and developmental delay, two with Dravet syndrome, two with developmental and epileptic encephalopathy, two with focal epilepsy, two with febrile seizures, and four with unclassified epilepsy. The proportions of patients with missense variants in the extracellular region and the transmembrane region exhibiting developmental delay were 40% and 63.2%, respectively. The last follow-up age ranged from 11 months to 17 years. Seizures were controlled in 71.4% of patients, and 92% of their seizures were controlled by valproate and/or levetiracetam.ConclusionThe clinical features of GABRG2-related epilepsy included seizure onset, usually in infancy, and seizures were fever-sensitive. More than half of the patients had cluster seizures. Phenotypes of GABRG2-related epilepsy were ranged from mild febrile seizures to severe epileptic encephalopathies. Most patients with GABRG2 variants who experienced seizures had a good prognosis. Valproate and levetiracetam were effective treatments for most patients.

ObjectiveThe aim of this study was to analyze the phenotypic spectrum, treatment, and prognosis of 72 Chinese children with SCN2A variants.MethodsThe SCN2A variants were detected by next-generation sequencing. All patients were followed up at a pediatric neurology clinic in our hospital or by telephone.ResultsIn 72 patients with SCN2A variants, the seizure onset age ranged from the first day of life to 2 years and 6 months. The epilepsy phenotypes included febrile seizures (plus) (n = 2), benign (familial) infantile epilepsy (n = 9), benign familial neonatal-infantile epilepsy (n = 3), benign neonatal epilepsy (n = 1), West syndrome (n = 16), Ohtahara syndrome (n = 15), epilepsy of infancy with migrating focal seizures (n = 2), Dravet syndrome (n = 1), early infantile epileptic encephalopathy (n = 15), and unclassifiable developmental and epileptic encephalopathy (n = 8). Approximately 79.2% (57/72) patients had varying degrees of developmental delay. All patients had abnormal MRI findings with developmental delay. 91.7% (55/60) patients with de novo SCN2A variants had development delay, while only 16.7% (2/12) patients with inherited SCN2A variants had abnormal development. 83.9% (26/31) SCN2A variants that were located in transmembrane regions of the protein were detected in patients with development delay. Approximately 69.2% (9/13) SCN2A variants detected in patients with normal development were located in the non-transmembrane regions. Approximately 54.2% (39/72) patients were seizure-free at a median age of 8 months. Oxcarbazepine has been used by 38 patients, and seizure-free was observed in 11 of them (11/38, 28.9%), while 6 patients had seizure worsening by oxcarbazepine. All 3 patients used oxcarbazepine and with seizure onset age > 1 year presented seizure exacerbation after taking oxcarbazepine. Valproate has been used by 53 patients, seizure-free was observed in 22.6% (12/53) of them.ConclusionThe phenotypic spectrum of SCN2A-related epilepsy was broad, ranging from benign epilepsy in neonate and infancy to severe epileptic encephalopathy. Oxcarbazepine and valproate were the most effective drugs in epilepsy patients with SCN2A variants. Sodium channel blockers often worsen seizures in patients with seizure onset beyond 1 year of age. Abnormal brain MRI findings and de novo variations were often related to poor prognosis. Most SCN2A variants located in transmembrane regions were related to patients with developmental delay.

Abstract Background Progressive myoclonic epilepsy (PME) is a group of neurodegenerative diseases with genetic heterogeneity and phenotypic similarities, and many cases remain unknown of the genetic causes. This study is aim to summarize the clinical features and study the genetic causes of PME patients. Methods Sanger sequencing of the target gene, Next Generation Sequencing (NGS) panels of epilepsy, trio-based Whole Exome Sequencing (WES) and detection of cytosine-adenine-guanine (CAG) repeat number were used to investigate the genetic causes of PME patients. Results Thirty-eight children with PME whose seizure onset age ranged from 3 months to 12 years were collected from February 2012 to November 2019 in three hospitals in Beijing, China. The seizure types included myoclonic seizures (n = 38), focal seizures (n = 19), generalized tonic-clonie seizure (GTCS) (n = 13), absence seizures (n = 4), atonic seizures (n = 3), epileptic spasms (n = 2) and tonic seizures (n = 1). Twenty-seven cases were sporadic and 11 had family members affected. Established PME-related genes were identified in 30 out of 38 (78.9%) patients who had either recessively inherited or de novo heterozygous mutations. Among these 30 cases, there were 12 cases (31.6%) of neuronal ceroid lipofuscinoses (the causing gene contains TPP1, PPT1, CLN5, CLN6 and MFSD8), two cases of sialidosis (the causing gene is NEU1), two cases of neuronopathic Gaucher disease (the causing gene is GBA), one case of spinal muscular atrophy-progressive myoclonic epilepsy (the causing gene is ASAH1), four cases of KCNC1 mutation-related PME, four cases of KCTD7 mutation-related PME, two cases of TBC1D24 mutation-related PME, one case of GOSR2 related PME, and two of dentatorubral-pallidoluysian atrophy (the causing gene is ATN1). In total, 13 PME genes were identified in our cohort. The etiology was not clear in eight patients. Conclusion PME is a group of clinically and genetically heterogeneous diseases. Genetic diagnosis was clear in 78.9% of PME patients. Various of genetic testing methods could increase the rate of genetic diagnosis. Neuronal ceroid lipofuscinoses (NCL) is the most common etiology of PME in children. Nearly one third PME children were diagnosed with NCL. GOSR2 related PME was in our cohort in Asia for the first time.

Urban multi-energy systems (UMESs) are integrated energy systems (IESs) which can alleviate the current energy crisis, improve energy utilization and realize multi-energy complementarity of modern. Various subsystems involved in the coupling of UMESs, including power grids, gas pipeline networks, cold/heat networks, transportation networks, and energy cyber-physical system, exhibit coupling characteristics such as multi-energy source modeling, complex uncertainty factor modeling, mutual influence of information and physical coupling. At present, the modeling and reliability assessments of UMESs are the most urgent tasks. In this paper, the latest research results on the reliability modeling and evaluation of UMESs are analyzed by considering their coupling components. In addition, the reliability modeling methods and the evaluation indexes of UMESs, including power-gas systems, power-thermal systems, power-traffic systems, and energy cyber-physical systems, are presented in this paper, with specific UMES modeling methods divided into model-driven modeling and data-driven modeling. Finally, future challenges for the reliability modeling and evaluation of UMESs are proposed, such as the dispatch strategy of the coupling components needs to be developed and continuously optimized to improve the reliability of UMESs, and the resilience of UMESs under the extreme scenarios needs to be further studied.

With the rapid development of society, global energy is in short supply. China has put forward an integrated energy system focusing on interconnecting energy resources and harnessing their complementary advantages to address the energy crisis, thus no longer pursuing the production, transportation and supply of a single source of energy. In the continuous development of integrated energy systems, the elements of participation and interaction are becoming more complex. Game theory, which can effectively solve the problems arising from multi-agent trading, is naturally introduced to the integrated energy system. This paper provides a comprehensive overview of the introduction of game theory into the integrated energy system. First, the development of integrated energy is briefly introduced, game scenarios in integrated energy systems is proposed, and game scenarios considering the energy supply side, distribution network, demand side and common planning and dispatching problems in integrated energy systems are summarized. Secondly, main game theory models in the integrated energy system are summarized, such as cooperative game theory model, the non-cooperative game theory model and the Stackelberg game theory model. Finally, the future prospect and challenge for the application of game theory in integrated energy systems is proposed. The new game models are introduced to the integrated energy system, and a mixed game is considered to solve related problems. It is hoped that this work can serve as a reference for the researchers in this field.

The addition of supplemental light (SL) is an effective way to offset insufficient lighting. Although it is commonly believed that SL increases leaf photosynthesis and therefore improves yield and fruit flavor, the mechanism underlying the effects of SL on the photosystem II (PSII) apparatus remains unclear, and SL leads to high energy consumption. In order to save energy, we investigated the physiological status of the PSII apparatus, plant growth parameters and fruit parameters under two types of overhead SL with a low daily energy consumption of 0.0918 kWh m-2. The results showed that SL significantly increased the leaf chlorophyll content from full unfolding to yellowing. However, a remarkable increase in the absorption flux per cross-section (ABS/CS), the quantum yield of electron transport (φEo) and the performance index (PIabs) was observed only in a relatively short period of the leaf life cycle. SL also enhanced the fruit yield and quality. The obviously increased ΔVK and ΔVJ components of the chlorophyll fluorescence induction kinetic (OJIP) curve, along with the significantly decreased PIabs from days 40-60 after unfolding in the SL-treated groups, resulted in more rapid leaf aging and earlier fruit ripening compared with the control plants (CK). Therefore, an energy-friendly SL strategy can alter the physiological status of the PSII apparatus, affecting yield and fruit quality and maturity.

The mathematical model of optimal water quantity allocation for a single main canal in a large-scale irrigation area was constructed that took the minimal sum of the squared deviation of water shortage for water receiving areas controlled by the single main canal in one given irrigation period as the study target, and the total irrigation quantity of the single main canal as a constraint condition. Taking the optimal allocation of water quantity of each branch canal as decision variables, and several branch canals under the irrigation sequence of the main canal as a state variable, this model was solved by the one-dimensional dynamic programming (DP) method, by which the minimal water shortage and corresponding optimal water quantity allocation of each branch canal was calculated. The proposed method could provide a decision-making reference for optimal water resources allocation of single main canal irrigation areas, and also provide the theoretical basis for optimal water quantity allocation of a main canal with rotation irrigation by strips or with segmented rotation irrigation mode in China’s large-scale irrigation areas. Taking Hengliu Main Canal of Zhouqiao Irrigation Area in Jiangsu Province as a study case, optimization results showed that in a medium drought year (p = 75%) and a special drought year (p = 95%), minimal water shortage for water receiving areas controlled by Hengliu Main Canal was respectively 2.57 × 104 m3 and 23.31 × 104 m3 during the ponding period of rice. The corresponding water quantity allocation for each branch canal has reflected a compellent model solution precision and efficiency.

The SCN1A gene encodes the voltage-gated Na+ channel alpha subunit Nav1.1 and is the most clinically relevant epilepsy gene. Variants in SCN1A result in a broad phenotypic spectrum of epilepsy syndromes, from mild genetic epilepsy with febrile seizures plus to severe Dravet syndrome (DS). Here, we generated a SCN1A-knockout human iPSC line via CRISPR/Cas9 gene editing. The resulting iPSCs had a normal karyotype, were free of genomically integrated epitomal plasmids, expressed pluripotency markers, and maintained trilineage differentiation potential.

With the increasing interest in value-added maize products, the interaction of zein with bioactive molecules to become more nutritional and beneficial to human health has gained a lot of attention. To broaden the application of ellagic acid (EA) in maize flour products, we investigated the interaction between zein and EA. The fluorescence quenching type of zein interacting with EA was mainly static quenching through hydrophobic interaction, as demonstrated by quenching behavior modeling, and ultraviolet-visible spectroscopy confirmed the formation of zein–EA complexes. Synchronous fluorescence spectroscopy showed that EA reduced the polarity of zein around tyrosine residues, which were exposed to a more hydrophobic microenvironment. Meanwhile, circular dichroism suggested that EA noticeably changed the secondary structure of zein, which was mainly reflected in the increase of α-helix and β-sheet content and the decrease of random coil content. Finally, the molecular docking simulation found that zein could have five active sites binding to EA and there was hydrogen bond interaction besides hydrophobic interaction. The findings of this study provided a basis for a theory for the interaction mechanism between zein and EA, which could be essential for developing value-added plant-derived protein products using EA as a functional component.

Biaxial plastic geogrid is a polymer mesh formed by biaxial stretching. When making biaxial plastic geogrids, generally, the polymer sheet made by extrusion is pre-punched first, and then the biaxial stretching is carried out at an appropriate temperature. Different sizes of pre-punched holes will affect the subsequent stretching process, thereby changing the mechanical properties of the grid. In this study, geogrids made of different pre-punched diamond-shaped hole plates were subjected to room temperature tensile test. Influence of diameter-to-distance ratio and the percentage difference of longitudinal and transverse spacing on the mechanical properties of biaxial geogrids were studied experimentally and numerically. The results show that when the holes are appropriately small and the longitudinal spacing between the holes is slightly larger than the transverse spacing, the mechanical properties of the grid can be the best, and transverse stretching process will affect the longitudinal ribs in different aspects.

Background: Metformin, a commonly used antidiabetic medication, is available in both an immediate-release (IR) formulation and a long-acting formulation (metformin extended-release; XR).Objective: We performed a systematic review to compare the effectiveness, safety, and patient compliance and satisfaction between the metformin IR and XR formulations.Method: We searched for randomized control trials (RCTs) and observational studies comparing the effectiveness, safety, or patient compliance and satisfaction of metformin XR with metformin IR using the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Following report screening, data collection, and risk of bias assessment, we separately pooled data from RCTs and observational studies using the Grading of Recommendation Assessment, Development, and Evaluation approach to rate the quality of evidence.Result: We included five RCTs, comprising a total of 1,662 patients, and one observational study, comprising 10,909 patients. In the meta-analyses, no differences were identified in outcomes of effectiveness and safety between the two forms of metformin (including change in HbA1c: mean difference (MD), 0.04%, 95% confidence interval [CI], −0.05–0.13%, fasting blood glucose: MD, −0.03 mmol/L, 95% CI, −0.22–0.15 mmol/L, postprandial blood glucose: MD, 0.50 mmol/L, 95% CI, −0.71–1.72 mmol/L, adverse events of abdominal pain: relative risk (RR), 1.15, 95% CI, 0.57–2.33, all-cause death (RR, 3.02, 95% CI 0.12–73.85), any adverse events (RR, 1.14, 95% CI 0.97–1.34), any adverse events leading to treatment discontinuation: RR, 1.51, 95% CI, 0.82–2.8, any gastrointestinal adverse events: RR, 1.09, 95% CI, 0.93–1.29, diarrhea: RR, 0.82, 95% CI, 0.53–1.27, flatulence: RR, 0.43, 95% CI, 0.15–1.23, nausea: RR, 0.97, 95% CI, 0.64–1.47, severe adverse events: RR, 0.64, 95% CI, 0.28–1.42, and vomiting: RR, 1.46, 95% CI, 0.6–3.56). Data from both the RCTs and the observational study indicate mildly superior patient compliance with metformin XR use compared with metformin IR use; this result was attributable to the preference for once-daily administration with metformin XR.Conclusion: Our systematic review indicates that metformin XR and IR formulations have similar effectiveness and safety, but that metformin XR is associated with improved compliance to treatment.

This study aimed to analyze the genotypes and phenotypes of GNAO1 variants in a Chinese cohort. Seven male and four female patients with GNAO1 variants were enrolled, including siblings of brothers. Ten different GNAO1 variants (nine missense and one splicing site) were identified, among which six were novel. All the variants were confirmed to be de novo in peripheral blood DNA. Eight (73%, 8/11) patients had epilepsy; the seizure onset age ranged from 6 h after birth to 4 months (median age, 2.5 months). Focal seizures were observed in all eight patients, epileptic spasms occurred in six (75%, 6/8), tonic spasm in four (50%, 4/8), tonic seizures in two, atypical absence in one, and generalized tonic–clonic seizures in one. Seven patients had multiple seizure types. Eight (73%, 8/11) patients had movement disorders, seven of them having only dystonia, and one having dystonia with choreoathetosis. Varying degrees of developmental delay (DD) were present in all 11 patients. The phenotypes were diagnosed as early infantile epileptic encephalopathy (EIEE) in two (18%) patients, which were further diagnosed as West syndrome. Movement disorders (MD) with developmental delay were diagnosed in two (18%) brothers. EIEE and MD were overlapped in six (55%) patients, among which two were diagnosed with West syndrome, one with Ohtahara syndrome, and the other three with non-specific EIEE. One (9%) patient was diagnosed as DD alone. The onset age of GNAO1-related disorders was early infancy. The phenotypic spectrum of GNAO1 included EIEE, MD with DD, and DD alone.

Cryptococcus neoformans is an environmental fungal pathogen that causes opportunistic infections and severe disseminated meningoencephalitis, mainly in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS). In this study, the clinical characteristics, treatment protocols, and outcomes of 70 patients with AIDS and Cryptococcus neoformans infection at Beijing Ditan Hospital were retrospectively analyzed. We performed antimicrobial sensitivity tests and multilocus sequence typing (MLST) on C. neoformans isolates from these patients. The most common symptoms were headache (58.6%), fever (54.3%), and high cerebrospinal fluid pressure (≥200 mm H 2 O) (71.4%). All patients were positive for C. neoformans antigen in blood or cerebrospinal fluid. The CD4 cell counts of 92.8% (65/70) of patients were

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by an excessive systemic inflammatory response, which can be classified as primary HLH (pHLH) and secondary HLH (sHLH). Viruses are the primary pathogens causing sHLH. Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantaviruses. Its main characteristics include fever, circulatory collapse with hypotension, hemorrhage, and acute kidney injury. The case of HFRS presented with sHLH is very rare in clinic. We reported the HFRS inducing by Hantaan virus (HTNV) presented with sHLH as the first case in Shaanxi province of west China. Case presentation A case of HFRS in 69-year-old Chinese woman, which had persistent fever, cytopenia, coagulopathy, ferritin significantly increased, hepatosplenomegaly and superficial lymphadenopathy. The hemophagocytosis was found in bone marrow, which was consistent with the characteristics of the HLH. The patient recovered completely after timely comprehensive treatments. Conclusions HTNV should be considered as one of the underlying viruses resulting in hemophagocytosis, and if occurs, the early diagnosis and rapid therapeutic intervention are very important to the prognosis of sHLH.

As a requirement for sustainable development, air-cycle refrigeration has received wide attention as a candidate for environmentally friendly air conditioning technology. In this study, the thermodynamic performance of air refrigeration cycles is investigated in compartment air conditioning. The effects of compressor efficiency, expander efficiency, ambient humidity, all-fresh-air supply and ambient pressure on the cycle performance are presented. The effects of compressor arrangement in the high-pressure cycle and the low-pressure cycle are compared. An open-loop high-pressure cycle has a larger COP than that of an open-loop low-pressure cycle but requires larger heat exchange. The performance of air refrigeration cycles with full fresh air is studied, and the influence of fresh air is discussed. Schemes for condensed water recirculation with wet compression are proposed, which can improve the COPs of open-loop low-pressure cycles by 44.7%, 48.8% and 48.4%. In the air conditioning of plateau trains, open-loop high-pressure cycles have slightly lower COPs, but they can supply air with elevated pressure and oxygen concentration.

Background Although the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Taskforce recently defined primary and secondary resistance to anti-programmed cell death protein 1 (anti-PD-1) therapy, there is lack of real-world data regarding differences in these resistance subtypes with respect to radiological dynamics and clinical manifestations.Methods We performed single-blind re-evaluations of radiological images by independent radiologists on a retrospectively assembled cohort of patients with advanced melanoma (n=254, median follow-up 31 months) receiving anti-PD-1 monotherapy at Massachusetts General Hospital and Peking University Cancer Hospital. Radiological characteristics and timing at multiple crucial time points were analyzed and correlated with each other and with survival. Primary and secondary resistance was defined as per the SITC Immunotherapy Resistance Taskforce definitions.Results The most significant target lesion measurement change took place within the first 3 months after anti-PD-1 initiation. Patients with stable disease with versus without tumor shrinkage at the initial evaluation exhibited distinct disease trajectory, as the rate of further upgrade to a partial or complete remission (CR/PR) was 44% and 0%, respectively. Eleven per cent of PR patients ultimately achieved a CR. In multivariate analyses, deeper response depth was independently associated with a more limited progression pattern, fewer involved organs, lower tumor burden, slower growth rate at disease progression (PD) (all p≤0.001), and longer post-progression survival (PPS) (bivariate analysis, p=0.005). Compared with primary resistance, secondary resistance was associated with less widespread PD pattern, lower tumor burden and slower tumor growth (all p≤0.001). Patients with secondary resistance were less likely to receive further systemic therapy (28% vs 57%, p

Background: Emergence agitation (EA) is one of the most common and intractable postoperative complications among children undergoing surgery under general anesthesia. Dexmedetomidine, an α(2)-adrenoceptor agonist, offers an ideal sedation, reduces preoperative anxiety, and facilitates smooth induction of anesthesia, and it is widely used in pediatric surgery. We aimed to evaluate the efficacy of dexmedetomidine for preventing emergence agitation in children after general anesthesia.Methods: We comprehensively reviewed PubMed, Cochrane Library, EMBASE, and Web of Science databases to search all randomized controlled trials, published before April 22, 2020, investigating the efficacy of dexmedetomidine in preventing the emergence agitation in children after general anesthesia. The meta-analysis was performed using Review Manager 5.3. The primary outcome was the incidence of emergence agitation. Secondary outcomes included the number of patients requiring rescue analgesic, number of patients with postoperative nausea and vomiting, emergence time, extubation time, and time to discharge from the post-anesthesia care unit.Results: We included a total of 33 studies, comprising 2,549 patients in this meta-analysis. Compared with saline, dexmedetomidine significantly reduced the emergence agitation incidence [risk ratio (RR) 0.29; 95% confidence interval (CI) 0.22–0.37; p < 0.00001], incidence of postoperative nausea and vomiting (RR 0.46; 95% CI 0.3–0.69; p = 0.0002), and the requirement of rescue analgesic (RR 0.29; 95% CI 0.18–0.44; p < 0.00001). Furthermore, children in the dexmedetomidine group experienced a longer emergence time [mean difference (MD) 2.18; 95% CI 0.81–3.56; p = 0.002] and extubation time (MD 0.77; 95% CI 0.22–1.31; p = 0.006) compared with those in the saline group. However, no significant difference was observed in the time to discharge from the post-anesthesia care unit (MD 2.22; 95% CI −2.29–6.74; p = 0.33) between the two groups. No significant differences were observed between the effects of dexmedetomidine and other drugs like midazolam, propofol, fentanyl, tramadol, and clonidine in terms of the emergence agitation incidence and other parameters, except for the requirement of rescue analgesic (RR 0.45; 95% CI 0.33–0.61; p < 0.00001).Conclusions: Dexmedetomidine can prevent emergence agitation, relieves postoperative pain, decreases the requirement of rescue analgesic, and decreases the postoperative nausea and vomiting events.

Beef is rich in amino acids and vitamin B6, carnitine, potassium, protein, and other nutrients. It can improve the body’s ability to resist disease and is especially suitable for growth, development, and postoperation and postrehabilitation care. Under such circumstances, the demand for beef consumption in various countries continues to grow steadily. At present, domestic beef prices continue to rise, and beef supply is insufficient. In addition, fresh beef is easy to be infected with microorganisms in the process of cold storage, which makes fresh beef deteriorated. Therefore, it is very important to add preservatives to prolong the shelf life of chilled beef. In this paper, the preservation of chilled beef with nanocapsules made of natural essential oil from plant extracts was studied. In this study, cumin, Zanthoxylum, ginger, cinnamon, clove, and thyme were selected to study the effect of six kinds of essential oils on beef preservation through comparative experiments. On the basis of such research data, the six kinds of essential oils were compounded, respectively, and different nanoessential oil capsules were applied to the fresh-keeping of chilled beef to make different kinds of nanoessential oil capsules. Through the experiment, the compound essential oil with better preservation effect was obtained. And through the comparison, cinnamon essential oil has obvious antibacterial activity, while ginger essential oil has the worst antibacterial effect. The pH value of beef can be changed and the degradation rate of protein in beef will be slowed down by applying appropriate amount of decomposed plant essential oil to beef samples. Through the above experimental results, we applied the compound essential oil to the preservation of cold and fresh beef at nanometer level and found that the effect was significant, which was worthy of application in major beef products processing plants.

Background: Findings by epidemiologic studies on menopausal hormone replacement therapy (HRT) and the risk of ovarian cancer are inconsistent. This study aimed to assess the association of menopausal HRT with the risk of ovarian cancer by histological subtype.Methods: A literature search was performed in PubMed, Web of Science, and EmBase for relevant articles published from inception to August 2018. Pooled relative risk ratios (RRs) with 95% confidence intervals (CIs) were determined with a random-effects model.Results: Thirty-six studies involving 4, 229, 061 participants were included in this meta-analysis. The pooled RR of ovarian cancer was 1.29 (95%CI 1.19–1.40, I2 = 57.4%) for menopausal HRT. In subgroup analysis by study design, pooled RRs of ovarian cancer in cohort and case-control studies were 1.35 (95%CI 1.19–1.53) and 1.24 (95%CI 1.11–1.38), respectively. In subgroup analysis by continent, association of menopausal HRT with ovarian cancer was significant for North America (1.41 [1.23–1.61]), Europe (1.22 [1.12–1.34]), and Asia (1.76 [1.09–2.85]), but not Australia (0.96 [0.57–1.61]). Association differed across histological subtypes. Increased risk was only found for two common types, including serous (1.50 [1.35–1.68]) and endometrioid (1.48 [1.13–1.94]) tumors.Conclusion: This meta-analysis suggests that menopausal HRT may increase the risk of ovarian cancer, especially for serous and endometrioid tumors.

MALAT1 is well documented to be highly expressed in non-small cell lung cancer (NSCLC) and its overexpression closely associates the malignant phenotype of NSCLC cells and poor prognosis of NSCLC patients. MALAT1 is also identified to enhance β-catenin expression and under the negative regulation of miR-142-3p. However, the role of miR-142-3p/MALAT1/β-catenin in the occurrence and development of NSCLC remains unclear. The objective of this study was to explore it. The results showed that miR-142-3p expression was reduced in NSCLC tissues, while β-catenin and MALAT1 expression levels were elevated. MTT, transwell chamber, flow cytometry assays demonstrated that up-regulation of miR-142-3p with mimic transfection significantly inhibited the proliferation, migration and promoted the apoptosis of NSCLC H1299 cells, and induced a G0/G1 phase arrest and S phase reduction. Besides, miR-142-3p negatively decreased MALAT1 expression as detected by RT-PCR and luciferase reporter assays. Moreover, up-regulation of miR-142-3p decreased β-catenin expression through down-regulating MALAT1 in H1299 cells. And in vivo experiment showed that miR-142-3p up-regulation, as well as the knockdown of either β-catenin or MALAT1 significantly reduced the tumorigenesis of NSCLC cells. Taken together, our study makes clear that miR-142-3p functions as a tumor suppressor in NSCLC progression through inhibiting MALAT1/β-catenin signaling.

Objective: To evaluate the efficacy and safety of ketogenic diet (KD) in patients with Dravet syndrome (DS).Methods: 60 DS patients receiving treatment of KD for more than 12 weeks from 2009 to 2018 were analyzed retrospectively. Modified Johns Hopkins protocol was used to initiate KD. Seizure frequency, electroencephalogram (EEG), cognition, language, and motor function of the patients were assessed. Side effects were monitored and adjusted accordingly. SPSS 23.0 software was used for all statistical analysis.Results: In total, 60 DS patients (34 boys, 26 girls) received treatment of KD for more than 12 weeks, and among them 41 (68.3%) patients remained on the diet for more than 24 weeks, 22 (36.7%) patients for more than 48 weeks. Seizures in 35 patients (58.3%) were reduced by over 50% at 12 weeks, and the KD effect was observed within 2 weeks in most of them. At 24 weeks, 61.1% (25/41) of the patients had a >50% seizure reduction. At 48 weeks, 77.3% (17/22) had an over 50% reduction in their seizure frequency. With the treatment of KD in the 60 DS patients, 10 patients had ever been seizure free for 12 months to 24 months (The median duration was 20 months). In 10 KD-effective patients, the background rhythm of their EEG showed obvious improvement, and interictal epileptic discharges decreased significantly. Cognitive function of 22 patients was improved. Language progressed in 14 patients. Motor function was improved in 13 patients. The efficacy of KD in DS patients did not correlate with the seizure onset age, the starting age of KD treatment, the SCN1A mutation and the numbers of antiepileptic drugs combined with KD treatment. The main adverse reactions of KD in the treatment process were gastrointestinal symptoms and metabolic disorders.Conclusions: KD treatment in DS patients has many advantages, including working rapidly, being effective in more than half of the DS patients and tolerable adverse reactions. Pharmoco-resistant DS patients are suggested to receive KD treatment.

MicroRNAs (miRNAs) are small noncoding RNAs that critically regulate gene expression. Their abundance and function have been linked to a range of physiologic and pathologic processes. In aged monkey muscle, miR-451a and miR-144-3p were far more abundant than in young monkey muscle. This observation led us to hypothesize that miR-451a and miR-144-3p may influence muscle homeostasis. To test if these conserved microRNAs were implicated in myogenesis, we investigated their function in the mouse myoblast line C2C12. The levels of both microRNAs declined with myogenesis; however, only overexpression of miR-451a, but not miR-144-3p, robustly impeded C2C12 differentiation, suggesting an inhibitory role for miR-451a in myogenesis. Further investigation of the regulatory influence of miR-451a identified as one of the major targets Sparc mRNA, which encodes a secreted protein acidic and rich in cysteine (SPARC) that functions in wound healing and cellular differentiation. In mouse myoblasts, miR-451a suppressed Sparc mRNA translation. Together, our findings indicate that miR-451a is downregulated in differentiated myoblasts and suggest that it decreases C2C12 differentiation at least in part by suppressing SPARC biosynthesis.

In this work, we obtained a nonmatrix analytic expression for the generator of the Peano curve. Applying the iteration method of fractal, we established a simple arithmetic-analytic representation of the Peano curve as a function of ternary numbers. We proved that the curve passes each point in a unit square and that the coordinate functions satisfy a Hölder inequality with index α=1/2, which implies that the curve is everywhere continuous and nowhere differentiable.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels. Accordingly, HNRNPH levels decline while TRF2-S levels increase during neuronal differentiation. In addition, CRISPR/Cas9-mediated deletion of hnRNPH2 selectively accelerates the NGF-triggered differentiation of rat pheochromocytoma cells into neurons. In sum, HNRNPH is a splicing regulator of Trf2 pre-mRNA that prevents the expression of TRF2-S, a factor implicated in neuronal differentiation.