Objective To develop GTKO (α-1,3-galactosyltransferase gene-knockout, GTKO)/hCD55 (human CD55) gene-edited xenotransplant donor pigs and verify their function. Methods In this study, CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated nuclease 9), PiggyBac transposon technology and somatic cell nuclear transfer technology were used to construct GTKO/hCD55 gene-edited Diannan miniature pigs. The phenotype and function of GTKO/hCD55 pigs were analyzed by Sanger sequencing, real-time fluorescence quantitative PCR, flow cytometry, immunofluorescence, bisulfite sequencing, antigen-antibody binding assays, and complement-dependent cytotoxicity assays. Results After transfection of PX458 and PiggyBac gene editing vectors into wild-type fetal pig fibroblasts, 48 single-cell colonies were obtained through puromycin drug screening. Two single-cell colonies were selected for somatic cell nuclear transfer, resulting in two fetal pigs at 33 days of gestation. The GGTA1(α-1,3-galactosyltransferase) genotypes of fetal pig F01 were -17 bp and wild type (WT), while the GGTA1 genotypes of fetal pig F02 were -26 bp/+2 bp and -3 bp. The hCD55 mRNA expression levels of both fetal pigs were significantly higher than those of WT pigs (P＜0.01). The fetal pig F02 was selected as the donor cell source for recloning, 11 surviving piglets were obtained, all identified as GTKO/hCD55 gene-edited pigs. These pigs showed absence of α-Gal antigen expression, but weak or no expression of hCD55 was observed. Methylation analysis of the hCD55 gene's CpG island showed hypermethylation in kidney tissue lacking hCD55 expression, whereas it was not methylated or partially methylated in kidney tissue expressing hCD55. Moreover, codon optimization of the CpG island of the hCD55 gene to reduce CG content could achieve stable expression of the hCD55 gene. In addition, antigen-antibody binding experiment showed that the amount of human IgM binding to GTKO/hCD55 gene-edited pig fibroblasts was significantly lower than that of WT pigs (P＜0.01). Complement-dependent cytotoxicity experiment showed that the survival rate of fibroblasts in GTKO/hCD55 pigs was significantly higher than that in WT pigs (P＜0.01). Conclusion This study demonstrates the successful generation of GTKO/hCD55 gene-edited xenotransplant donor pigs. Methylation-induced gene silencing of the hCD55 gene can be effectively avoided by reducing the CG content of the CpG island through codon optimization. This study provides a reference for the development of xenotransplant donor pigs and guides subsequent research on xenotransplantation.

Objective: To evaluates the association between maternal overweight/obesity during pregnancy and offspring risk of metabolic dysfunction associated steatotic liver disease (MASLD), providing theoretical evidence for early life MASLD prevention. Methods: An online search was conducted across ten databases (CNKI, Wanfang, SinoMed, PubMed, Embase, Web of Science, Cochrane Library, PROSPERO, PQDT Global, ScienceDirect) for research literature on the association between maternal overweight/obesity during pregnancy and the development of MASLD in offspring, with the search period spanning from January 2014 to December 2024. Two researchers independently screened literature, extracted data, and assessed study quality. Statistical analysis was performed using R 4.3.3. Results: Ten studies involving 10 229 participants were included, comprising 4 cohort studies and 6 case control studies. Cohort studies showed that maternal overweight and obesity significantly increased offspring MASLD risk ( RR=1.59, 95%CI=1.06-2.39, P <0.05), with moderate heterogeneity ( I 2=56.9%, P =0.07). Case control studies indicated a positive association between maternal overweight/obesity during pregnancy and offspring risk of MASLD( OR=2.00, 95%CI=1.68-2.39, P < 0.05), with low heterogeneity ( I 2=48.8%, P =0.08). Conclusions Maternal overweight/obesity during pregnancy positively correlates with offspring MASLD risk. Gestational weight management may reduce the risk.

Objective To investigate the sputum metabolic profiles of patients with occupational coal workers' pneumoconiosis (CWP) by an untargeted metabolomics method, and to identify relevant differential metabolic pathways and potential biomarkers. Methods A total of 12 male patients with stage Ⅰ CWP were selected as the CWP group, and 16 healthy male individuals were selected as the control group, using a judgmental sampling method. Sputum metabolites of individuals in both groups were detected to perform non-targeted metabolomic analysis using the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differential metabolites (DMs) and their pathways were screened using principal component analysis, partial least squares discriminant analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Potential biomarkers were analyzed and identified via the receiver operating characteristic curve (ROC). Results There were apparent metabolic alterations observed in sputum of CWP patients compared with healthy controls. In the positive ion mode, a total of 42 DMs were identified in sputum from CWP patients, including 19 downregulated and 23 upregulated metabolites. In the negative ion mode, a total of 25 DMs were identified in sputum from CWP patients, including 16 downregulated and 9 upregulated metabolites. KEGG enrichment analysis of sputum from CWP patients showed that seven DMs pathways were enriched in ABC transporters, histidine metabolism, phenylalanine metabolism, arachidonic acid metabolism, linoleic acid metabolism, purine metabolism, and oxidative phosphorylation, involving 26 DMs. ROC analysis indicated that 16(R)-hydroxyarachidonic acid, pyrophosphate, and 2-hydroxyphenylacetate of these 26 DMs may serve as potential biomarkers for CWP. Conclusion Sputum metabolomic profiles were altered in CWP patients compared with healthy controls. The potential biomarkers of CWP prevention and treatment are 16(R)-hydroxyarachidonic acid, pyrophosphate, and 2-hydroxyphenylacetate.

OBJECTIVE: To explore the characteristics and rules of the locations of acupoints selected in weight loss after syndrome differentiation of acupuncture and moxibustion, and provide quantitative evidence for the location specificity of acupoint selection in weight loss. METHODS: Clinical research articles on acupoint selection based on syndrome differentiation of acupuncture and moxibustion in weight loss were retrieved in China National Knowledge Infrastructure (CNKI), from the inception to September 20th, 2024, and the data about acupoints and differentiated syndromes were extracted. Based on graph theory, the acupoint-syndrome network was established and its topological parameters such as node degree, value of betweenness centrality, description length and number of community were calculated. RESULTS: ①The description length of the limbs was 4 255.592, and that of the trunk was 3 274.312. The information contained in the acupoint-syndrome network for the acupoints on the limbs was greater than that for those on the trunk. ②The value of betweenness centrality and node degree showed a nonlinear relationship, with R²of 0.812 1 for the trunk and 0.321 8 for the limbs. The values of betweenness centrality for the acupoints on the trunk were uniformly distributed, and the difference among these values was much smaller than that for the acupoints on the limbs. It suggested that the distance from each trunk acupoint to network center was similar, and the importance among these acupoints to network was similar, while the importance among acupoints located on the limbs was different significantly. ③The frequency proportion of acupoints on the trunk showed uniform distribution among different syndromes, while that of some acupoints located on the limbs such as Taichong (LR3), Neiting (ST44) and Taixi (KI3) presented a correlation with the syndromes. CONCLUSION In weight loss with acupuncture and moxibustion, the correlation between the limb acupoints and syndromes is more diverse and specific than that between the trunk acupoints and syndromes. The differences in acupoint selection for simple obesity treated with acupuncture and moxibustion are mostly reflected in the acupoints on the four limbs rather than those on the trunk. It provides an approach to acupoint selection for "local weight loss" and "general regulation" in treatment with acupuncture and moxibustion.
Humans ; Acupuncture Points ; Moxibustion ; Weight Loss ; Acupuncture Therapy ; Obesity/physiopathology*

Collagen-based materials, renowned for their biocompatibility and minimal immunogenicity, serve as exemplary substrates in a myriad of biomedical applications. Collagen-based micro/nanogels, in particular, are valued for their increased surface area, tunable degradation rates, and ability to facilitate targeted drug delivery, making them instrumental in advanced therapeutics and tissue engineering endeavors. Although extensive reviews on micro/nanogels exist, they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials. The current review offers an in-depth look into the manufacturing technologies, drug release mechanisms, and biomedical applications of collagen-based micro/nanogels to address this gap. First, we provide an overview of the synthetic strategies that allow the precise control of the size, shape, and mechanical strength of these collagen-based micro/nanogels by controlling the degree of cross-linking of the materials. These properties are crucial for their performance in biomedical applications. We then highlight the environmental responsiveness of these collagen-based micro/nanogels, particularly their sensitivity to enzymes and pH, which enables controlled drug release under various pathological conditions. The discussion then expands to include their applications in cancer therapy, antimicrobial treatments, bone tissue repair, and imaging diagnosis, emphasizing their versatility and potential in these critical areas. The challenges and future perspectives of collagen-based micro/nanogels in the field are discussed at the end of the review, with an emphasis on the translation to clinical practice. This comprehensive review serves as a valuable resource for researchers, clinicians, and scientists alike, providing insights into the current state and future directions of collagen-based micro/nanogel research and development.
Collagen/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Tissue Engineering/methods* ; Animals ; Biocompatible Materials/chemistry*

To address the challenges faced by current brain midline segmentation techniques, such as insufficient accuracy and poor segmentation continuity, this paper proposes a deep learning network model based on a two-stage framework. On the first stage of the model, prior knowledge of the feature consistency of adjacent brain midline slices under normal and pathological conditions is utilized. Associated midline slices are selected through slice similarity analysis, and a novel feature weighting strategy is adopted to collaboratively fuse the overall change characteristics and spatial information of these associated slices, thereby enhancing the feature representation of the brain midline in the intracranial region. On the second stage, the optimal path search strategy for the brain midline is employed based on the network output probability map, which effectively addresses the problem of discontinuous midline segmentation. The method proposed in this paper achieved satisfactory results on the CQ500 dataset provided by the Center for Advanced Research in Imaging, Neurosciences and Genomics, New Delhi, India. The Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetric surface distance (ASSD), and normalized surface Dice (NSD) were 67.38 ± 10.49, 24.22 ± 24.84, 1.33 ± 1.83, and 0.82 ± 0.09, respectively. The experimental results demonstrate that the proposed method can fully utilize the prior knowledge of medical images to effectively achieve accurate segmentation of the brain midline, providing valuable assistance for subsequent identification of the brain midline by clinicians.
Humans ; Brain/diagnostic imaging* ; Deep Learning ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Magnetic Resonance Imaging/methods* ; Neural Networks, Computer

As a new type of high-risk packaging container, prefilled syringes are more widely used, and concerns regarding their effectiveness, stability and safety in clinical use have become prominent increasingly. However, the leachable substances from prefilled syringes may cause harm to humans in different degrees. Therefore, this paper reviews the research progress of leachable substances in prefilled syringes, which is not only of great significance for the quality control of prefilled syringe products, but also contributes to the healthy development of the industry.
Syringes ; Drug Packaging ; Quality Control

Objective: To explore the associations between caregivers nutrition literacy and pediatric nonalcoholic fatty liver disease (NAFLD), so as to provide scientific evidence for the key contents of family intervention measures. Methods: In September 2022, a study involving 1 609 thirdgrade students and their caregivers from six schools in Yinzhou, Haishu, and Zhenhai Districts of Ningbo City, Zhejiang Province, was conducted. Venous blood samples were collected to measure lipid profiles and investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) among the children. Family Food Environment Questionnaire was used to assess the nutrition literacy levels of the caregivers. Generalized linear regression analysis was employed to explore the correlation between caregivers nutrition literacy levels and the prevalence of NAFLD in children. Results: Among the surveyed students, 191 were in the NAFLD group, whereas 1 418 were in the nonNAFLD group. The median nutrition literacy score of caregivers in the NAFLD group and nonNAFLD group all were 11.00 (9.00,12.00), which was not significantly different (Z=-0.40, P=0.71). The generalized linear regression results revealed that the level of nutrition literacy of caregivers had no significant effect on childrens Triglyceride-glucose (TyG) index and Triglyceride-glucose-Waisttoheight ratio (TyG-WHtR) [β(95%CI) were 0.001(-0.005-0.006) and 0.000(-0.014-0.014), P>0.05]. Conclusions The nutrition literacy level of caregivers has no significant correlation with the direct incidence of NAFLD in children. As for family intervention measures, it is necessary not only to improve the nutrition literacy level of caregivers but also to effectively apply nutritional knowledge in practice to optimize health management.

[Objective]To research the efficacy of Hewei Xiaoliu Formula in inhibiting gastric cancer and its effect on the polarization of tumor-associated macrophages(TAM),and to explore its mechanism.[Methods]The mouse model of HGC-27 gastric cancer was established to observe the effect of Hewei Xiaoliu Formula on the tumor weight,volume and the TAM phenotype as well as the protein expression of prospero homeobox1(PROX1)/interferon-γ(IFN-γ)of transplanted tumor.The effect of supernatant of gastric cancer cell intervened by Hewei Xiaoliu Formula on TAM phenotype was detected by flow cytometry.Enzyme linked immunosorbent assay(ELISA)and Western blot were used to detect the effect of Hewei Xiaoliu Formula on the expression of IFN-γ in the supernatant of gastric cancer cells and protein expression of PROX1/IFN-γ in gastric cancer cells.Co-culture system of macrophages and gastric cancer cells transfected with small interfering RNA(siR)-IFN-γ were established,and the phenotypic changes of TAM were detected after the intervention with Hewei Xiaoliu Formula.[Results]Hewei Xiaoliu Formula could reduce the volume and weight of transplanted tumor(P＜0.05),increase the proportion of M1 TAM and decrease the proportion of M2 TAM in tumor tissue(P＜0.05),decrease the expression of PROX1 protein and increase the expression of IFN-γ(P＜0.01).After the intervention of Hewei Xiaoliu Formula,the gastric cancer supernatant could increase the proportion of M1 TAM and decrease the proportion of M2 TAM(P＜0.01).Hewei Xiaoliu Formula could increase the expression of IFN-γ in the supernatant of gastric cancer(P＜0.05),decrease the expression of PROX1 protein(P＜0.05),and increase the expression of IFN-γ protein in gastric cancer cells(P＜0.05).In addition,after siR-IFN-γ transfection into gastric cancer cells,the proportion of M1 TAM after intervention with Hewei Xiaoliu Formula was lower than that in siR-negative control(NC)+Hewei Xiaoliu Formula group(P＜0.05).[Conclusion]Hewei Xiaoliu Formula can inhibit the growth of HGC-27 gastric cancer and promote the polarization of TAM to M1 phenotype in tumor microenvironment.The mechanism may be related to the regulation of PROX1/IFN-γsignaling pathway and the increase of IFN-γ expression in gastric cancer.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.