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Joint diseases greatly impact the daily lives and occupational functioning of patients globally. However, conventional treatments for joint diseases have several limitations, such as unsatisfatory efficacy and side effects, necessitating the exploration of more efficacious therapeutic strategies. Mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have demonstrated high therapeutic efficacyin tissue repair and regeneration, with low immunogenicity and tumorigenicity. Recent studies have reported that EVs-based therapy has considerable therapeutic effects against joint diseases, including osteoarthritis, tendon and ligament injuries, femoral head osteonecrosis, and rheumatoid arthritis. Herein, we review the therapeutic potential of various types of MSC-EVs in the aforementioned joint diseases, summarise the mechanisms underlying specific biological effects of MSC-EVs, and discuss future prospects for basic research on MSC-EV-based therapeutic modalities and their clinical translation. In general, this review provides an in-depth understanding of the therapeutic effects of MSC-EVs in joint diseases, as well as the underlying mechanisms, which may be beneficial to the clinical translation of MSC-EV-based treatment.The translational potential of this article: MSC-EV-based cell-free therapy can effectively promote regeneration and tissue repair. When used to treat joint diseases, MSC-EVs have demonstrated desirable therapeutic effects in preclinical research. This review may supplement further research on MSC-EV-based treatment of joint diseases and its clinical translation.

Abstract The prevalence of isolated systolic hypertension (ISH) has doubled between 2002−2005 and 2014 among the oldest‐old population in China. However, the prevalence and characteristics of ISH among the oldest‐old population in southwestern China remain less known. This study aimed to investigate the prevalence of ISH among the oldest‐old population in Chengdu and identify associated factors to provide valuable information for disease etiology and prevention. We recruited 1,312 participants aged over 80 years by using a stratified cluster sampling method between September 2015 and June 2016, from three districts (Jinjiang, Qingyang, and Longquanyi) of Chengdu, the largest city of southwest China. A structured questionnaire, anthropometric data, and blood pressure were collected according to the standard method. Blood pressure was measured three times by using a standardized mercury sphygmomanometer after a 10‐minute seated rest. Of 1312 participants, 53.0% (n = 695) had ISH. The prevalence of ISH in men and women was 54.7% and 51.3%, respectively, with no significant sex difference (P = .222). The prevalence of ISH increased with advanced age in men (P for trend = 0.029), 52.5% for the 80−84 years group, 55.2% for the 85−89 years group, and 70.4% for the 90–98 years group, respectively. Multivariable logistic regression analyses found that drinking (OR = 1.85, 95%CI = 1.26−2.71), being overweight (OR = 1.88, 95%CI = 1.19−2.96), and having a higher heart rate (OR = 0.66, 95%CI = 0.51−0.86) were associated with ISH. Stratified by sex, these three factors remained significant in men. Our work highlights that the burden of ISH is substantial among the oldest‐old population in southwestern China.

Abstract Background Ulcerative colitis (UC) is one chronic and relapsing inflammatory bowel disease. Macrophage has been reputed as one trigger for UC. Recently, phosphodiesterase 4 (PDE4) inhibitors, for instance roflumilast, have been regarded as one latent approach to modulating macrophage in UC treatment. Roflumilast can decelerate cyclic adenosine monophosphate (cAMP) degradation, which impedes TNF-α synthesis in macrophage. However, roflumilast is devoid of macrophage-target and consequently causes some unavoidable adverse reactions, which restrict the utilization in UC. Results Membrane vesicles (MVs) from probiotic Escherichia coli Nissle 1917 (EcN 1917) served as a drug delivery platform for targeting macrophage. As model drugs, roflumilast and MnO2 were encapsulated in MVs (Rof&MnO2@MVs). Roflumilast inhibited cAMP degradation via PDE4 deactivation and MnO2 boosted cAMP generation by activating adenylate cyclase (AC). Compared with roflumilast, co-delivery of roflumilast and MnO2 apparently produced more cAMP and less TNF-α in macrophage. Besides, Rof&MnO2@MVs could ameliorate colitis in mouse model and regulate gut microbe such as mitigating pathogenic Escherichia–Shigella and elevating probiotic Akkermansia. Conclusions A probiotic-based nanoparticle was prepared for precise codelivery of roflumilast and MnO2 into macrophage. This biomimetic nanoparticle could synergistically modulate cAMP in macrophage and ameliorate experimental colitis. Graphical Abstract

Abstract Background Evidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability. Methods This prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality. Results The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index

Abstract Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.

Abstract Osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disease, severely impacting the function of patients and potentially leading to disability, especially among the elderly population. Natural products (NPs), obtained from components or metabolites of plants, animals, microorganisms etc., have gained significant attention as important conservative treatments for various diseases. Recently, NPs have been well studied in preclinical and clinical researches, showing promising potential in the treatment of OA. In this review, we summed up the main signaling pathways affected by NPs in OA treatment, including NF-κB, MAPKs, PI3K/AKT, SIRT1, and other pathways, which are related to inflammation, anabolism and catabolism, and cell death. In addition, we described the therapeutic effects of NPs in different OA animal models and the current clinical studies in OA patients. At last, we discussed the potential research directions including in-depth analysis of the mechanisms and new application strategies of NPs for the OA treatment, so as to promote the basic research and clinical transformation in the future. We hope that this review may allow us to get a better understanding about the potential bioeffects and mechanisms of NPs in OA therapy, and ultimately improve the effectiveness of NPs-based clinical conservative treatment for OA patients.

Abstract Background Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that predominantly affects children, and no specific diagnostic biomarkers for KD are available. Platelet-derived growth factor CC (PDGF-CC) is a peptide with angiogenic properties that has been amply demonstrated to play a critical role in the cardiovascular system. This study aimed to investigate the serum expression of PDGF-CC in children with KD and to evaluate the ability of PDGF-CC to diagnose KD. Methods A total of 96 subjects, including 59 KD patients, 17 febrile controls (FC), and 20 healthy controls (HC), were enrolled. Serum levels of PDGF-CC were measured via enzyme-linked immunosorbent assay. The associations between PDGF-CC and clinical laboratory parameters were investigated by correlation analysis. The diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis. Results Serum PDGF-CC levels in the KD group were significantly higher than in the FC and HC groups. Serum PDGF-CC levels in the KD group were positively correlated with white blood cell counts, percentage of neutrophils, IL-2, IL-12p70, TNF-α, and IL-1β levels, and negatively correlated with the percentage of lymphocytes. In the analysis of ROC curves, the area under the curve was 0.796 (95% confidence interval 0.688–0.880; P

We designed a generative adversarial network and an attention network to solve the brainwave emotion-classification problem. Using spatial attention and channel attention superposition to normalize and enhance the raw EEG data, we effectively solved the defects in the EEG data with weak features and easily disturbed them. First, a cognitive map of the brain in the emotional state was constructed by extracting graphical features from EEG signals. Simultaneously, generative adversarial networks are used to add noise to the cognitive map to generate similar data. The volume of the brain cognitive map has been expanded. The problem of insufficient EEG signal data was solved, and the accuracy and robustness were improved. Finally, we compared the processing abilities of different neural networks using EEG and adversarial signals. Compared with other deep learning models and parameter optimization methods, the proposed model achieved a detection accuracy of 94.87% on the SEED dataset.

High altitude environment is mainly characterized by low oxygen. Due to persistent hypoxia, nonhealing wounds are common in high-altitude areas. Moreover, Basic fibroblast growth factor (bFGF) is a versatile biologically active substance that has crucial impact on wound healing. Given the limited availability of atmospheric oxygen and reduced blood oxygen saturation in high-altitude area, and the challenge that arises from direct oxygen and bFGF delivery to wounds through the traumatized vascular structure, it necessitates an innovative solution for local and permeable delivery of oxygen and bFGF. In this study, we present a strategy that involves revamping traditional gel-based wound dressings through the incorporation of nanoparticles encapsulating oxygen and bFGF, engineered to facilitate the localized delivery of dissolved oxygen and bFGF to wound surfaces. The prospective evaluation of this delivery technique's therapeutic impacts on epithelial, endothelial and fibroblasts cells can be materialized. Further experiment corroborated these effects on a high-altitude wounds' murine model. Given its biocompatibility, efficacy, and utility, we posit that NOB-Gel exhibits remarkable translational potential for managing and hastening the healing process of an array of clinical wounds, more so for wounds inflicted at high altitudes.

Abstract Background The prevalence of obese children in China is increasing, which poses a great challenge to public health. Gut microbes play an important role in human gut health, and changes in gut status are closely related to obesity. However, how gut microbes contribute to obesity in children remains unclear. In our study, we performed shotgun metagenomic sequencing of feces from 23 obese children, 8 overweight children and 22 control children in Chengdu, Sichuan, China. Results We observed a distinct difference in the gut microbiome of obese children and that of controls. Compared with the controls, bacterial pathogen Campylobacter rectus was significantly more abundant in obese children. In addition, functional annotation of microbial genes revealed that there might be gut inflammation in obese children. The guts of overweight children might belong to the transition state between obese and control children due to a gradient in relative abundance of differentially abundant species. Finally, we compared the gut metagenomes of obese Chinese children and obese Mexican children and found that Trichuris trichiura was significantly more abundant in the guts of obese Mexican children. Conclusions Our results contribute to understanding the changes in the species and function of intestinal microbes in obese Chinese children.

Similar material model experiment is an important means to study mining subsidence and damage, and it is very important to obtain high-precision model deformation information in the experiment. There are still some limitations in the accuracy and efficiency of data acquisition in many existing model deformation measurement methods. In this paper, the simulation experiment of similar materials is carried out by taking the circular mining and filling mining of multiple coal seams in a mine in northern Shaanxi as models, and the high-resolution sequence images are obtained by using the non-measurement camera at close range. Through image distortion correction, automatic stitching and feature recognition, the deformation of similar material models can be obtained with high precision. Firstly, the influence of model measuring point marks and camera parameters on deformation measurement accuracy is analyzed, and the best model shooting scheme is determined, that is, the non-measurement camera is used to take an orthographic photo at a distance of 1.5−2.0 m from the model, forming an image sequence with a horizontal overlap of more than 55% and a vertical overlap of more than 30%; Furthermore, the bilinear interpolation method is used to correct the distortion of the obtained image, the automatic and robust image mosaic algorithm is used, the Harris corner detection operator is used to extract the feature points, the RANSAC algorithm is used to classify the pseudo-matching points, and a series of automatic processing processes such as color transition and smoothing at the butt edges are used to mosaic the image sequence. The resolution of the generated panoramic image of the model is about 10 times higher than that of the conventional fixed camera. In the process of image processing, the measuring point mark is used as the training network, the confidence level is added based on Faster R-CNN algorithm, and the appropriate sliding template is selected for region analysis, which significantly improves the recognition rate and accuracy of the measuring point mark. The results show that the precision of measuring point coordinate extraction in model experiment is better than 0.027 mm, which is equivalent to the field measurement precision of 5.4 mm, which fully meets the requirements of mine similar material model experiment. By making an experimental model with a scale of 1∶200, the deformation and failure characteristics of overlying strata caused by cyclic mining of multiple coal seams are simulated and analyzed, and the maximum surface subsidence reaches −18.937 mm; When the mined-out area is filled, the lower part of overlying rock is slightly deformed, and the surface subsidence is not more than 2 mm. The experimental results provide an effective technical means for the efficient and accurate collection of experimental data of similar material models in mines.

Several exogenous probiotics are applicable in fish culture; however, challenges in isolation and verification have hindered the full utilization of numerous host probiotics. Therefore, this study aimed to apply the host probiotic Exiguobacterium acetylicum G1-33 to hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) cultures and explore its mechanism of action. In total, 360 hybrid grouper were divided into four groups, which were fed the following for 60 days: three received commercial feed with varying concentrations of E. acetylicum G1-33 (106, 108, and 1010 CFU/g), while a control group received commercial feed. The results showed that supplementation with 106 and 108 CFU/g of E. acetylicum G1-33 enhanced gut morphology, upregulated growth-related genes (ghr1, igf-2, s6k1, tor), and promoted growth, with supplementation with 108 CFU/g resulting in the most notable enhancement. However, supplementation with 1010 CFU/g inhibited growth, possibly because of changes in intestinal morphology. Additionally, supplementation with E. acetylicum G1-33 upregulated the expression of immune-related genes (c3, myd88, Cu/Zn-sod, tlr3, and tnf2) in the liver and head kidney but led to an increase in malondialdehyde content, as well as a decrease in alkaline phosphatase and acid phosphatase activities, in the liver and serum, indicating increased oxidative stress. Moreover, supplementation with 106 and 108 CFU/g E. acetylicum G1-33 enhanced the widespread expression of immune-related genes in the head kidney and liver, respectively, and improved resistance to Vibrio harveyi, whereas supplementation with 1010 CFU/g weakened this resistance. In conclusion, E. acetylicum G1-33, particularly at 108 CFU/g, emerged as an effective probiotic, optimizing growth performance and immunity in hybrid grouper. This research is pioneering in its application of E. acetylicum in mariculture, potentially broadening the range of probiotic strategies in aquaculture.

Background: Schizophrenia is a serious psychiatric disorder that significantly affects the quality of life of patients. The objective of this study is to discover a novel antipsychotic candidate with highly antagonistic activity against both serotonin and dopamine receptors, demonstrating robust efficacy in animal models of positive, negative, and cognitive symptoms of schizophrenia.Methods: In the present study, we examined the activity of antipsychotic drug (NH300094) on 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1B, 5-HT7, H1, M1, Alpha1A, D2L, D2S, Alpha2A, D3 receptor functional assay in vitro. In addition, multiple animal models, including dizocilpine (MK-801) induced hyper-locomotion; APO induced climbing; Conditioned Avoidance Response (CAR); DOI-Induced Head Twitch; Forced swimming test; Scopolamine induced cognitive impairment model, were used to verify the antipsychotic activity of NH300094 in preclinical.Results:In vitro functional assays have indicated that NH300094 is a potent antagonist of 5-HT receptors and dopamine receptors, with higher relative antagonistic activity against 5-HT2A receptor (5-HT2A IC50 = 0.47 nM) than dopamine receptors (D2L IC50 = 1.04 nM; D2S IC50 = 11.71 nM; D3 IC50 = 31.55 nM). Preclinical in vivo pharmacological study results showed that NH300094 was effective in multiple models, which is more extensive than the clinic drug Risperidone. Furthermore, the safety window for extrapyramidal side effects of NH300094 is significantly wider than that of Risperidone (For NH300094, mice catalepsy model ED50/ Mice MK-801 model ED50 = 104.6-fold; for Risperidone, mice catalepsy model ED50/ Mice MK-801 model ED50 = 12.9-fold), which suggests a potentially better clinical safety profile for NH300094.Conclusion: NH300094 is a novel potent serotonin and dopamine receptors modulator, which has good safety profile and therapeutic potential for the treatment of schizophrenia with cognition disorders.

Activation of simulator of interferon genes (STING), which induces the production of proinflammatory factors and immune effector cell activation, is considered a promising strategy for enhanced anti-cancer intervention. However, several obstacles prevent STING signaling in solid tumors, such as delivered molecules’ rapid degradation, restriction to tumor sites, insufficient intracellular concentrations, and low responsivity. Well-designed, multifunctional nano-formulations have emerged as optimized platforms for STING activation. Recently, a variety of nano-formulations have been developed and used in STING activation, thus facilitating immunotherapy in preclinical and clinical stages. Herein, we summarize recent advances in nanotechnology-based delivery, activation, and application strategies, which have advanced various aspects of immunotherapy. Novel STING agonists and their mechanisms in STING-activation-mediated tumor interventions are highlighted herein, to provide a comprehensive overview and discuss future directions for boosting immunotherapy via STING regulation.

Abstract Due to potentially hostile behaviors and elusive habitats, moray eels (Muraenidae) as one group of apex predators in coral reefs all across the globe have not been well investigated. Here, we constructed a chromosome-level genome assembly for the representative Reeve’s moray eel (Gymnothorax reevesii). This haplotype genome assembly is 2.17 Gb in length, and 97.87% of the sequences are anchored into 21 chromosomes. It contains 56.34% repetitive sequences and 23,812 protein-coding genes, of which 96.77% are functionally annotated. This sequenced marine species in Anguilliformes makes a good complement to the genetic resource of eel genomes. It not only provides a genetic resource for in-depth studies of the Reeve’s moray eel, but also enables deep-going genomic comparisons among various eels.

Neuromuscular blocking agents (NMBAs) are routinely used during anesthesia to relax skeletal muscle. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels; NMBAs can induce muscle paralysis by preventing the neurotransmitter acetylcholine (ACh) from binding to nAChRs situated on the postsynaptic membranes. Despite widespread efforts, it is still a great challenge to find new NMBAs since the introduction of cisatracurium in 1995. In this work, an effective ensemble-based virtual screening method, including molecular property filters, 3D pharmacophore model, and molecular docking, was applied to discover potential NMBAs from the ZINC15 database. The results showed that screened hit compounds had better docking scores than the reference compound d-tubocurarine. In order to further investigate the binding modes between the hit compounds and nAChRs at simulated physiological conditions, the molecular dynamics simulation was performed. Deep analysis of the simulation results revealed that ZINC257459695 can stably bind to nAChRs’ active sites and interact with the key residue Asp165. The binding free energies were also calculated for the obtained hits using the MM/GBSA method. In silico ADMET calculations were performed to assess the pharmacokinetic properties of hit compounds in the human body. Overall, the identified ZINC257459695 may be a promising lead compound for developing new NMBAs as an adjunct to general anesthesia, necessitating further investigations.

It is important to elaborate on versatile strategies for achieving the perfect nonreciprocal reflection amplification, which is the key technology of high-quality nonreciprocal photonic devices. In this work, we ingeniously design a coherent four-level N-type atomic system to harness the nonreciprocal light amplification, in which the uniform distribution of atoms is driven by two strong coupling fields and a weak probe field. In our regime, the strength of the two control fields is designed with linear variation along the x direction to destroy the spatial symmetry of the probe susceptibility, leading to the nonreciprocity of the reflection. In particular, the closed-loop transitions to amplify the probe field are due to the combined effect of the control fields and spontaneous emissions. The numerical simulation indicates that the perfect nonreciprocal reflection amplification can be realized and modulated by the appropriate settings of the control fields and the detuning, Δc. Our results will open a new route toward harnessing nonreciprocity, which can provide more convenience and possibilities in experimental realization.

The thermal structure of the lithosphere is key to understanding its thickness, properties, evolution, and geothermal resources. Cratons are known for their low heat flow and deep lithospheric roots. However, present-day cratons in East China have geothermal characteristics that are highly complex, with variable heat flow values, diverging from the typical thermal state of cratons. In this study, we conducted a detailed analysis of the geothermal geological background of the cratons in East China, summarizing the thermal state and tectono-thermal processes of different tectonic units, calculating the temperature at various depths, and discussing differences in temperature and thermal reservoirs at different depths. The observed lithospheric thermal thickness within the North Jiangsu Basin and the Bohai Bay Basin is notably reduced in comparison to that of the Jianghan Basin and the Southern North China Basin. The phenomenon of craton destruction during the Late Mesozoic emerges as a pivotal determinant, enhancing the geothermal resource prospects of both the Bohai Bay Basin and the North Jiangsu Basin. Our findings contribute significantly to the augmentation of theoretical frameworks concerning the origins of heat sources in global cratons. Furthermore, they offer invaluable insights for the methodical exploration, evaluation, advancement, and exploitation of geothermal resources.

Abstract Sarcopenia is the age‐related loss of skeletal muscle mass and muscle strength or physical function. It is most common in elderly individuals. Due to its high incidence, insidious onset, and extensive impact on the body, it has a huge impact on the family medical burden and the social public health expenditure in China. The understanding of sarcopenia in China is still lacking, and the recommendations for prevention, control, and intervention are not clear and unified. The purpose of this consensus report is to standardize the prevention, control, and intervention methods for sarcopenia in elderly patients in China; improve the efficacy of intervention; reduce complications during the intervention process; and reduce the risk of falls, fractures, disability, hospitalization, and even death in elderly individuals.

Abstract Blood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism in these processes remains unclear. The present study finds that ovariectomized mice exhibit reduced blood vessel density in the bone and reduced expression of the endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Endothelial cell (EC)‐specific deletion of Pkm2 impairs osteogenesis and worsens osteoporosis in mice. This is attributed to the impaired ability of bone mesenchymal stem cells (BMSCs) to differentiate into osteoblasts. Mechanistically, EC‐specific deletion of Pkm2 reduces serum lactate levels secreted by ECs, which affect histone lactylation in BMSCs. Using joint CUT&Tag and RNA sequencing analyses, collagen type I alpha 2 chain (COL1A2), cartilage oligomeric matrix protein (COMP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and transcription factor 7 like 2 (TCF7L2) as osteogenic genes regulated by histone H3K18la lactylation are identified. PKM2 overexpression in ECs, lactate addition, and exercise restore the phenotype of endothelial PKM2‐deficient mice. Furthermore, serum metabolomics indicate that patients with osteoporosis have relatively low lactate levels. Additionally, histone lactylation and related osteogenic genes of BMSCs are downregulated in patients with osteoporosis. In conclusion, glycolysis in ECs fuels BMSC differentiation into osteoblasts through histone lactylation, and exercise partially ameliorates osteoporosis by increasing serum lactate levels.

Background: Catheter-related bladder discomfort (CRBD) is a frequent occurrence following urinary catheterization during surgical procedures, as well as a commonly experienced bladder pain syndrome after surgery. There have been various studies on drugs and interventions to manage CRBD, but their comparative efficacy and safety are still a topic of debate. We conducted a meta-analysis to assess the efficacy and safety of nefopam for managing postoperative CRBD.Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to find randomized controlled trials (RCTs) on using nefopam in postoperative CRBD. The study employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data analysis was performed using RevMan version 5.4.1.Results: Five RCTs with 405 patients were analyzed to evaluate the efficacy of nefopam on postoperative CRBD. Short-term and long-term periods were defined as within 6 h and longer than 12 h after surgery, respectively. The incidence and severity of CRBD were compared between the two groups during these time periods. The analysis proved that nefopam reduced the short-term incidence of postoperative CRBD (RR 0.36; 95% CI, 0.18–0.70; p = 0.003, I2 = 78%) and the long-term incidence (RR 0.49; 95% CI, 0.32–0.74; p = 0.0007, I2 = 0%) significantly. We compared the incidence of moderate-to-severe CRBD between groups based on the scaling system (none, mild, moderate, and severe). This was used to assess the severity of postoperative CRBD. The results showed that patients in the nefopam group had a significantly lower incidence of moderate-to-severe CRBD compared to those in the placebo group in the short-term (RR 0.19; 95% CI, 0.10–0.34; p < 0.00001; I2 = 0%). However, there were no significant differences between the two groups in the incidence of moderate-to-severe CRBD in the long-term (RR 0.61; 95% CI, 0.21–1.76; p = 0.36; I2 = 0%). There were no significant variations in the occurrence of adverse events between the nefopam and control groups, mainly including postoperative nausea and vomiting (PONV) (RR 1.14; 95% CI, 0.40–3.21; p = 0.81), and tachycardia (RR 0.25; 95% CI, 0.03–2.11, p = 0.20).Conclusion: The findings of this meta-analysis indicate that nefopam significantly reduced the incidence of short or long-term postoperative CRBD. Nefopam decreased the severity of postoperative CRBD, particularly significantly reducing the occurrence of moderate to severe CRBD in the short-term. Overall, patients have good tolerance and no apparent side effects.Systematic Review Registration: identifier PROSPERO (CRD42023475012)

Abstract Older adults are at high risk for functional impairment, which is closely related to sarcopenia, falls, and frailty. This seriously affects their quality of life and health, and places a heavy burden on society and families. Although domestic and foreign sports recommendations and prevention and control guidelines/expert consensus have been issued for healthy older adults and functional impairment‐related diseases, there is no guidance on prevention and control interventions for older adults with physical functional impairment. In China, there is insufficient understanding of the importance of prevention and control interventions for functional impairment in older adults, and there are many drawbacks, such as unstandardized diagnosis and treatment, and relatively simple intervention methods. Therefore, the consensus expert group formulated a consensus based on domestic and foreign guidelines related to functional impairment in older adults to provide guidance for Chinese medical professionals working in the field of geriatrics.

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.

Abstract Glutamine metabolism plays an essential role in cell growth, and glutamate dehydrogenase (GDH) is a key enzyme. GDH promotes the metabolism of glutamate and glutamine to generate ATP, which is profoundly increased in multiple human cancers. Through in vitro and in vivo experiments, we verified that the small-molecule GDH inhibitor EGCG slowed the progression of fibrosis by inhibiting GDH enzyme activity and glutamine metabolism. SIRT4 is a mitochondrial enzyme with NAD that promotes ADP ribosylation and downregulates GDH activity. The role of SIRT4 in liver fibrosis and the related mechanisms are unknown. In this study, we measured the expression of SIRT4 and found that it was downregulated in liver fibrosis. Modest overexpression of SIRT4 protected the liver from fibrosis by inhibiting the transformation of glutamate to 2-ketoglutaric acid (α-KG) in the tricarboxylic acid cycle (TCA), thereby reducing the proliferative activity of hepatic stellate cells (HSCs). Collectively, our study reveals that SIRT4 controls GDH enzyme activity and expression, targeting glutamine metabolism in HSCs and alleviating liver fibrosis.

Abstract Cognitive impairment is a term that refers to the impairment of one or more cognitive domains to varying degrees caused by a variety of reasons. It is under a high prevalence, many risk factors, complex etiology, and great harm to the elderly population. Early screening, diagnosis, and intervention for cognitive impairment in the elderly are of great importance. However, at present, the recognition rate of cognitive impairment for the elderly in China is low, the rate of missed diagnosis is high, and the evaluation is not standardized. This consensus integrates the commonly used cognitive function assessment scales in China and abroad, and aims to popularize the screening of cognitive impairment, standardize the evaluation methods and procedures of cognitive impairment in the elderly, and establish clinical diagnoses, interventions, and follow‐up plans in a timely manner.

Abstract Malnutrition is a state of altered body composition and body cell mass due to inadequate intake or utilization of energy or nutrients, leading to physical and mental dysfunction and impaired clinical outcomes. As one of the most common geriatric syndromes, malnutrition in the elderly is a significant risk factor for poor clinical outcomes, causing a massive burden on medical resources and society. The risk factors for malnutrition in the elderly are diverse and include demographics, chronic diseases, and psychosocial factors. Presently, recommendations for the prevention and intervention of malnutrition in the elderly are not clear or consistent in China. This consensus is based on the latest global evidence and multiregional clinical experience in China, which aims to standardize the prevention and intervention of malnutrition in the elderly in China and improve the efficacy of clinical practice and the prognosis of elderly patients.

Abstract Background Mitochondria play an essential role in cellular redox homeostasis maintenance and meanwhile serve as an important target for organelle targeted therapy. Photodynamic therapy (PDT) is a promising strategy for organelle targeted therapy with noninvasive nature and highly spatiotemporal selectivity. However, the efficacy of PDT is not fully achieved due to tumor hypoxia. Moreover, aerobic respiration constantly consumes oxygen and leads to a lower oxygen concentration in mitochondria, which continuously limited the therapeutic effects of PDT. The lack of organelle specific oxygen delivery method remains a main challenge. Methods Herein, an Oxygen Tank is developed to achieve the organelle targeted synergistic hypoxia reversal strategy, which not only act as an oxygen storage tank to open sources and reduce expenditure, but also coated with red blood cell membrane like the tank with stealth coating. Within the oxygen tank, a mitochondrion targeted photosensitizer (IR780) and a mitochondria respiration inhibitor (atovaquone, ATO) are co-loaded in the RBC membrane (RBCm) coated perfluorocarbon (PFC) liposome core. Results Inside these bio-mimic nanoparticles, ATO effectively inhibits mitochondrial respiration and economized endogenous oxygen consumption, while PFC supplied high-capacity exogenous oxygen. These Oxygen modulators reverse the hypoxia status in vitro and in vivo, and exhibited a superior anti-tumor activity by mitochondria targeted PDT via IR780. Ultimately, the anti-tumor effects towards gastric cancer and colon cancer are elicited in vivo. Conclusions This oxygen tank both increases exogeneous oxygen supply and decreases endogenous oxygen consumption, may offer a novel solution for organelle targeted therapies.

Cancer immunotherapy, which use the own immune system to attack tumors, are increasingly popular treatments. But, due to the tumor immunosuppressive microenvironment, the antigen presentation in the tumor is limited. Recently, a growing number of people use bacteria to stimulate the body’s immunity for tumor treatment due to bacteria themselves have a variety of elements that activate Toll-like receptors. Here, we discuss the use of motility of flagellate bacteria to transport antigens to the tumor periphery to activate peritumoral dendritic cells to enhance the effect of in situ tumor vaccines.

Background/Aim: Polypharmacy is prevalent among older inpatients and associated with adverse outcomes. To determine whether a geriatrician-led multidisciplinary team (MDT) management mode could reduce medications use among older inpatients.Methods: A retrospective cohort study was conducted in a geriatric department of a tertiary hospital in China with 369 older inpatients, including 190 patients received MDT management (MDT cohort), and 179 patients received usual treatment (non-MDT cohort). The primary outcome was to compare the changes of the amount of medications before and after hospitalization in two cohorts.Results: We reported that MDT management significantly reduced the number of medications used in older inpatients at discharge (at home: n = 7 [IQR: 4, 11] vs at discharge: n = 6 [IQR: 4, 8], p < 0.05). Hospitalization with the MDT management had a significant effect on the change in the amount of medications (F = 7.813, partial-η2 = 0.011, p = 0.005). The discontinuance of medications was associated with polypharmacy at home (OR: 96.52 [95% CI: 12.53-743.48], p < 0.001), and the addition of medications was associated with a diagnosis of chronic obstructive pulmonary disease (COPD) (OR: 2.36 [95% CI: 1.02-5.49], p = 0.046).Conclusion: The results indicated that the geriatrician-led MDT mode during hospitalization could reduce the number of medications used by older patients. The patients with polypharmacy were more likely to “deprescription” after MDT management, while the patients with COPD were more likely to be under-prescription at home, polypharmacy which could be made up for after MDT management.

This article explores Hangzhou’s multifaceted role in shaping Chinese Buddhist culture and contributing to knowledge production. As a vital hub of Chinese material and intellectual culture, Hangzhou’s significant contributions to Buddhism are emphasized, shedding light on its key role in disseminating Buddhist teachings and preserving knowledge. The study delves into the rich history of Buddhist reference works, particularly leishu, showcasing how these compilations were pivotal in organizing and transmitting Buddhist wisdom. The article connects Hangzhou’s intellectual legacy to the broader context of Chinese Buddhism, emphasizing its crucial position in the development and dissemination of Buddhist doctrines. Additionally, it highlights ongoing academic efforts to compile an Encyclopedia of Hangzhou Buddhist Culture, underscoring Hangzhou’s continued importance in contemporary Buddhist scholarship.

In contrast to Rydberg blockade, Rydberg anti-blockade allows multiple atoms to be simultaneously excited in the presence of significant nonlocal interactions and can lead to distinct phenomena and applications. This inspires us to examine here general conditions, numerical verifications, and realistic restrictions regarding the collective anti-blockade excitations of N Rydberg atoms equally arranged along a ring. We find that by adjusting the detuning of a pump field to compensate for nonlocal interactions between one atom and all others, it is viable to realize resonant excitations of N atoms but suppress far-detuned excitations of N−1 and fewer atoms under different conditions for an odd and an even number of atoms. Population dynamics of this Rydberg ring further show that one-step anti-blockade implementation can be attained at a cutoff time of the pump field, which increases quickly with the number of atoms. Hence, roughly perfect anti-blockade excitations are attainable only for a not-too-large N due to inevitable spontaneous Rydberg decay.

The ideal photodynamic therapy (PDT) should effectively remove the primary tumor, and produce a stronger immune memory effect to inhibit the tumor recurrence and tumor metastasis. However, limited by the hypoxic and immunosuppressive microenvironment, the PDT efficiency is apparently low. Here, Chlorella (Chl.) is exploited to enhance local effect by producing oxygen to reverse hypoxia, and release adjuvants to reverse immunosuppressive microenvironment to enhance abscopal effect afterwards. Results from different animal models indicated that Chl. could enhance local effect and PDT related immune response. Ultimately, Chl. coupled PDT elicited anti-tumor effects toward established primary tumors (inhibition rate: 90%) and abscopal tumors (75%), controlled the challenged tumors (100%) and alleviated metastatic tumors (90%). This Chl. coupled PDT strategy can also produce a stronger anti-tumor immune memory effect. Overall, this Chl. coupled PDT strategy generates enhanced local tumor killing, boosts PDT-induced immune responses and promotes anti-tumor immune memory effect, which may be a great progress for realizing systemic effect of PDT.

ObjectiveTo propose and validate a new classification of surgical methods for patients with subaxial cervical hemivertebrae.MethodThis article reviewed cases diagnosed with subaxial cervical hemivertebrae in our hospital from January 2008 to December 2019. The results of preoperative (initial visit), postoperative and/or final follow-up were assessed using the Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI) score, spinal balance parameters, and Scoliosis Research Society-22 Questionnaire (SRS-22). We also performed a reliability study to assess this classification.ResultThe classification includes three types. Each type can be divided into two subtypes, and a preliminary algorithm is proposed. Type I: There is an obvious appearance deformity in the neck, there are hemivertebrae in the cervical spine, and only a single hemivertebra of the subaxial cervical hemivertebra needs to be resected. Type II: There is an obvious appearance deformity in the neck, there are hemivertebrae in the cervical spine, and multiple subaxial cervical hemivertebrae need to be removed. Type III: No apparent deformity in the neck, at least one subaxial cervical hemivertebra existed or Klipper-Feil syndrome. Each type is divided into two subtypes, A and B, according to whether the upper and lower adjacent vertebral bodies of the rescected hemivertebra(e) are fused. We propose corresponding treatment methods for different types. We included a total of 121 patients and reviewed the prognosis for each type of patient. All patients achieved satisfactory results. The reliability study showed that the mean interobserver agreement was 91.8% (89.3%–93.4%), and the κ value was 0.845 (0.800–0.875). The intraobserver agreement ranged from 93.4% to 97.5%, with a mean κ value of 0.929 (0.881 to 0.954).ConclusionIn our study, we proposed and validated a new classification of subaxial cervical hemivertebrae and proposed corresponding treatment plans for different classifications.

Radiotherapy remains the major therapeutic intervention for tumor patients. However, the hypoxic tumor microenvironment leads to treatment resistance. Recently, a burgeoning number of nano-radiosensitizers designed to increase the oxygen concentration in tumors were reported. These nano radiosensitizers served as oxygen carriers, oxygen generators, and even sustained oxygen pumps, attracting increased research interest. In this review, we focus on the novel oxygen-enrich nano radiosensitizers, which we call oxygen switches, and highlight their influence in radiotherapy through different strategies. Physical strategies-based oxygen switches carried O2 into the tumor via their high oxygen capacity. The chemical reactions to generate O2in situ were triggered by chemical strategies-based oxygen switches. Biological strategies-based oxygen switches regulated tumor metabolism, remodeled tumor vasculature, and even introduced microorganisms-mediated photosynthesis for long-lasting hypoxia alleviating. Moreover, the challenges and perspectives of oxygen switches-mediated oxygen-enrich radiotherapy were discussed.

Abstract Background The purpose of this study was to investigate the diagnosis and treatment experience of traumatic duodenal ruptures in children. Methods Clinical data were collected from four children suffering from a traumatic duodenal rupture who were admitted to and treated by our hospital from January 2012 to December 2020. The early diagnosis and treatment, surgical plan, postoperative management, complications, and prognosis of each child were analyzed. The key points and difficulties of the diagnosis and treatment for this type of injury are summarized. Results One child had an extreme infection caused by drug-resistant bacteria, which resulted in severe complications, including wound infection, dehiscence, and an intestinal fistula. One child developed an anastomotic stenosis after the duodenostomy, which improved following an endoscopic balloon dilatation. The other two children had no relevant complications after their operations. All four patients were cured and discharged from hospital. The average hospital stay was 48.25 ± 26.89 days. The follow-up period was 0.5 to 1 year. No other complications occurred, and all children had a positive prognosis. Conclusions The early identification of a duodenal rupture is essential, and surgical exploration should be carried out proactively. The principles of damage-control surgery should be followed as much as possible during the operation. Multidisciplinary cooperation and management are both important to reduce the occurrence of postoperative complications and improve cure rates.

Abstract The targeted transport of nanomedicines is often impeded by various biological events in the body. Viruses can hijack host cells and utilize intracellular transcription and translation biological events to achieve their replication. Inspired by this, a strategy to hijack endogenous products of biological events to assemble into intracellular functional nanoparticles is established. It has been shown that, following tumor vessel destruction therapy, injected cell permeable small molecule drugs bisphosphonate can hijack the hemorrhagic product iron and self‐assemble into peroxidase‐like nanoparticles within tumor‐infiltrating macrophages. Unlike free drugs, the generated intercellular nanoparticles can specifically stress mitochondria, resulting in immune activation of macrophages in vitro and polarizing tumor‐associated macrophages (TAMs) from immunosuppressive to tumoricidal and increasing the recruitment of T cells deep within tumor. The hijacking self‐assembly strategy significantly inhibits tumor growth compared with the treatment of vascular‐disrupting agents alone. Using bisphosphonate to hijack the metabolite associated with hemorrhage, iron, to fabricate functional nanoparticles within specific cells, which may open up new nanotechnology for drug delivery and small molecular drug development.

PurposeTo provide reference data on CBT pedicle screws from CT measurements of L1 to L5 in the Chinese Han population and to assess the treatment efficacy of CBT pedicle screws in cases of lumbar degenerative disease.MethodsIn total, 100 patients were identified from the CT database for CBT morphometric measurement of the lumbar spine. According to sex and age, patients were divided into four groups. The diameter, length, and angle of the vertebral pedicle and trajectory were measured. Then, a total of 36 patients with lumbar degenerative disease were included in this study for clinical and radiographic evaluation. Demographic characteristics, health-related quality of life (HRQOL), and extent of intervertebral disc herniation and spondylolisthesis were evaluated.ResultsThe mean diameter and the mean length varied from L1 to L5 in Groups I to IV. The lateral angles ranging from L1 to L5 were 8.9 to 9.2°, 8.7 to 12.2°, 8.7 to 11.2°, and 9.2 to 10.1° in Groups I to IV, respectively. The cephalad angles from L1 to L5 were 23.5 to 28.6°, 24.7 to 26.6°, 25.0 to 28.2°, and 24.7 to 27.9° in Groups I to IV, respectively. In the case series, all patients’ neurological function and HRQOL were significantly improved at the final follow-up (p

Objectives: Polypharmacy and potentially inappropriate medication (PIM) use among elderly Chinese patients have not yet been investigated by systematic review and meta-analysis. The purposes of this study were to investigate the prevalence of polypharmacy and PIM use and the risk factors associated with PIM use in elderly Chinese patients.Methods: Databases including PubMed, EMBase, and Web of Science were searched to collect studies which used Chinese criteria, Beers criteria, or STOPP criteria to evaluate the PIM status of elderly Chinese patients from inception to August 2021 (PROSPERO Code No: CRD42021262821). Observational studies reporting the prevalence of polypharmacy and PIM use in elderly Chinese patients were meta-analyzed. The pooled prevalence and risk ratio (RR) were calculated with a 95% confidence interval (CI).Results: A total of 8 articles involving 4,558,786 patients were included. The overall prevalence of polypharmacy (concomitant use of more than 5 medicines) and PIM use pooled by meta-analysis in Chinese older patients was 48% (95% CI: 0.17, 0.79, p = 0.003) (inpatients 73%, outpatients 23%) and 39% (95% CI: 0.25, 0.54, p < 0.001) (inpatients 50%, outpatients 29%), respectively. Polypharmacy (RR: 2.03, 95% CI: 1.13, 3.64) was significantly associated with PIM use.Conclusion: This meta-analysis demonstrated a high prevalence of polypharmacy and PIM use among elderly patients in China. Affected by the quantity and quality of the included studies, the aforementioned conclusions need to be confirmed by large samples and high-quality studies.

To improve the precision of velocity measurements for high-speed underwater projectiles and meet the requirements for device terminal alarms, a method for identifying and measuring high-speed underwater projectiles with a large-area laser barrier was proposed. The absorption of laser transmission underwater and the relationship between scattering and suspended particles were simulated and analyzed. An optical system consisting of a waterproof modulated laser transceiver probe, multifiber transmission and a retroreflector was designed to decrease the large optical energy dissipation. The laser beam was expanded to form a triangular barrier with a Powell prism. The fiber array surrounding the prism receives the reflected laser light from the retroreflector. The other end of the optical fiber is coupled to a PIN-PD detector through a narrowband filter. The output electric signal is then processed by an amplifier, demodulator and low-pass filter. The shortcomings of traditional split-type and multielement optical structures in water were effectively overcome by this compact integrated probe structure, and the effective area was expanded to $2 m \times 2 m$ . The velocity of high-speed underwater steel balls and lead blocks, the simulated projectiles, was acquired accurately to verify the feasibility of velocity measurement for high-speed underwater projectiles with laser barriers.

Radiotherapy has the potential to induce immunogenic cell death (ICD), however radiation-induced immune responses are often limited. Here the authors design gadolinium-based nanoscale coordination polymers to amplify radiation-mediated oxidative stress, promoting ICD and anti-tumor immune responses.

Infrapatellar fat pad (IPFP) inflammation is a common pathological manifestation in knee osteoarthritis (OA). However, the significance of IPFP signal intensity alteration for clinical diagnosis and treatment of knee OA needs further research. We assessed IPFP signal intensity alteration (0–3), IPFP maximum cross-sectional area (CSA) and IPFP depth, meniscus injury, bone marrow edema, and cartilage injury from magnetic-resonance imaging (MRI) in 41 non-KOA patients (K-L grade 0 and grade I) and 68 KOA patients (K-L grade 2,3 and 4). We found that IPFP signaling was altered in all patients with KOA whose alteration was closely related to the K-L grading. We found that the IPFP signal intensity was increased in most OA patients, especially the ones in the late stage. There were significant differences in IPFP maximum CSA and IPFP depth between groups in KOA and non-KOA patients. Moreover, Spearman correlation analysis showed that IPFP signal intensity was moderately positively correlated with age, meniscal injury, cartilage injury, and bone marrow edema, and negatively correlated with height, while not correlated with visual analogue scale (VAS) scoring and body mass index (BMI). In addition, women have higher IPFP inflammation scores on MRI than men. In conclusion, IPFP signal intensity alteration is associated with joint damage in knee OA, which may have clinical significance for diagnosing and treating KOA.

Population aging is an inevitable problem nowadays, and the elderly are going through a lot of geriatric symptoms, especially cognitive impairment. Irisin, an exercise-stimulating cleaved product from transmembrane fibronectin type III domain-containing protein 5 (FNDC5), has been linked with favorable effects on many metabolic diseases. Recently, mounting studies also highlighted the neuroprotective effects of irisin on dementia. The current evidence remains uncertain, and few clinical trials have been undertaken to limit its clinical practice. Therefore, we provided an overview of current scientific knowledge focusing on the preventive mechanisms of irisin on senile cognitive decline and dementia, in terms of the possible connections between irisin and neurogenesis, neuroinflammation, oxidative stress, and dementia-related diseases. This study summarized the recent advances and ongoing studies, aiming to provide a better scope into the effectiveness of irisin on dementia progression, as well as a mediator of muscle brain cross talk to provide theoretical support for exercise therapy for patients with dementia. Whether irisin is a diagnostic or prognostic factor for dementia needs more researches.

Both cognitive impairment and cardiovascular diseases have a high incidence in the elderly population, increasing the burden of care and reducing the quality of life. Studies have suggested that cognitive impairment interacts with cardiovascular diseases such as coronary heart disease, abnormal blood pressure, heart failure, and arrhythmia. On one hand, cognitive impairment in the elderly influences the progression and self-management of cardiovascular diseases and increases the risk of cardiovascular-related adverse events. On the other hand, coronary heart disease, heart failure, higher blood pressure variability, orthostatic hypotension, and atrial fibrillation may aggravate cognitive impairment. The role of blood pressure levels on cognition remains controversial. Several shared biological pathways have been proposed as the underlying mechanism for the association. Cardiovascular diseases may lead to cognitive decline even dementia through cerebral perfusion damage, brain structural changes, inflammation, β-amyloid deposition, and neuroendocrine disorders. It is of great significance to study the interaction and put forward effective interventions in an overall perspective to reduce care burden and improve the quality of life of the elderly patients.

Liver fibrosis is a reversible disease course caused by various liver injury etiologies, and it can lead to severe complications, such as liver cirrhosis, liver failure, and even liver cancer. Traditional pharmacotherapy has several limitations, such as inadequate therapeutic effect and side effects. Nanotechnology in drug delivery for liver fibrosis has exhibited great potential. Nanomedicine improves the internalization and penetration, which facilitates targeted drug delivery, combination therapy, and theranostics. Here, we focus on new targets and new mechanisms in liver fibrosis, as well as recent designs and development work of nanotechnology in delivery systems for liver fibrosis treatment.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely employed to examine brain functional connectivity (FC) alterations in various neurological disorders. At present, various computational methods have been proposed to estimate connectivity strength between different brain regions, as the edge weight of FC networks. However, little is known about which model is more sensitive to Alzheimer’s disease (AD) progression. This study comparatively characterized topological properties of rs-FC networks constructed with Pearson correlation (PC), dynamic time warping (DTW), and group information guided independent component analysis (GIG-ICA), aimed at investigating the sensitivity and effectivity of these methods in differentiating AD stages. A total of 54 subjects from Alzheimer’s Disease Neuroimaging Initiative (ANDI) database, divided into healthy control (HC), mild cognition impairment (MCI), and AD groups, were included in this study. Network-level (global efficiency and characteristic path length) and nodal (clustering coefficient) metrics were used to capture groupwise difference across HC, MCI, and AD groups. The results showed that almost no significant differences were found according to global efficiency and characteristic path length. However, in terms of clustering coefficient, 52 brain parcels sensitive to AD progression were identified in rs-FC networks built with GIG-ICA, much more than PC (6 parcels) and DTW (3 parcels). This indicates that GIG-ICA is more sensitive to AD progression than PC and DTW. The findings also confirmed that the AD-linked FC alterations mostly appeared in temporal, cingulate, and angular areas, which might contribute to clinical diagnosis of AD. Overall, this study provides insights into the topological properties of rs-FC networks over AD progression, suggesting that FC strength estimation of FC networks cannot be neglected in AD-related graph analysis.

Abstract A 32-month-old girl with patent ductus arteriosus, false tendon of left ventricle, mild pulmonary hypertension, and chronic cardiac insufficiency (cardiac function level I-II) was misdiagnosed with Marfan Syndrome and there was no improvement in her physical growth after operation for this disease. The preterm baby was finally diagnosed with Myhre Syndrome by clinical phenotypes and mutation of SMAD4 gene.

Positive Pressure Protective Clothing (PPPC) is the most important personal protective equipment for BSL-4 laboratory and a primary barrier to avoid exposure to pathogenic microorganisms. However, during the process of storage, utilization, disinfection and inspection, it will be inevitable damaged in varying degrees. PPPC is expensive; therefore, effective repairs become an important procedure to prolong service life of PPPC and to ensure their protective function. This paper analyzed those common damages in PPPC during routine BSL-4 laboratory operations and provided repair plans which can be used as references for users and maintenance personnel.

Biosafety equipment is the key barrier enabling high containment laboratories to handle high risk agents that may cause serious and potentially lethal infections. This perspective thoroughly analyzes the development of many kinds of key biosafety technologies, and equipment for protection of laboratory workers and for high containment laboratory facilities in China. Over more than ten years of rapid development, China has had remarkable achievements in key biosafety technologies and equipment in high containment laboratories. These technologies basically meet the needs of high containment laboratories construction in China. Furthermore, according to the current global situation regarding the prevention and control of infectious diseases and the technical development level of biosafety equipment, this paper proposes targeted suggestions and notes that China still needs to increase investment in scientific research to provide further technical and equipment support enabling us to build a community with a bright future in terms of human biosafety.

The frequent and sudden occurrence of both known and unknown infectious diseases can cause global social panic. If the source of infection can be effectively controlled in the early stages of an outbreak, the spread of infectious diseases can be prevented. In view of this situation, this study developed for infectious or suspected infectious patients a negative pressure isolation hood which effectively achieves direct individual isolation during the early stages of disease outbreak, and facilitates long-distance transport. The hood body is made of flexible transparent polyvinyl chloride (PVC) material, and the combination of the hood material is airtight. The unique inflatable column support structure and the design of the inflatable neck sleeve effectively ensure both stiffness and air tightness of the hood body. The electrical exhaust system maintains a stable negative pressure environment inside the hood, and polluted air inside the hood can be purified by a high efficiency filter. Test results showed that the internal noise of the hood was 68 ± 1 dB (A), the air exhaust volume of the electric exhaust system was not 99.99%, indicating that the hood achieved effective isolation protection for patients with respiration infectious diseases.