To address issues such as loss of detailed information, blurred target boundaries, and unclear structural hierarchy in medical image fusion, this paper proposes an adaptive feature medical image fusion network based on a full-scale diffusion model. First, a region-level feature map is generated using a kernel-based saliency map to enhance local features and boundary details. Then, a full-scale diffusion feature extraction network is employed for global feature extraction, alongside a multi-scale denoising U-shaped network designed to fully capture cross-layer information. A multi-scale feature integration module is introduced to reinforce texture details and structural information extracted by the encoder. Finally, an adaptive fusion scheme is applied to progressively fuse region-level features, global features, and source images layer by layer, enhancing the preservation of detail information. To validate the effectiveness of the proposed method, this paper validates the proposed model on the publicly available Harvard dataset and an abdominal dataset. By comparing with nine other representative image fusion methods, the proposed approach achieved improvements across seven evaluation metrics. The results demonstrate that the proposed method effectively extracts both global and local features of medical images, enhances texture details and target boundary clarity, and generates fusion image with high contrast and rich information, providing more reliable support for subsequent clinical diagnosis.
Humans ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Neural Networks, Computer ; Diagnostic Imaging/methods* ; Image Interpretation, Computer-Assisted/methods*

Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fine motor control difficulties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was significantly downregulated in the medial prefrontal cortex of young mice after multiple sevoflurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fine motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.
Animals ; Sevoflurane/toxicity* ; Microglia/drug effects* ; Anesthetics, Inhalation/adverse effects* ; Mice ; Mice, Inbred C57BL ; Receptors, Erythropoietin/metabolism* ; Neuronal Plasticity/drug effects* ; Male ; Prefrontal Cortex/drug effects* ; Erythropoietin/pharmacology* ; Signal Transduction/drug effects*

Objective:To investigate the influence and mechanism of stromal interaction molecule 1 (STIM1) in microglia/macrophages M1 activation after cerebral ischemia-reperfusion injury.Methods:(1) Animal experiment: 20 male C57BL/6J mice were randomly divided into sham-operated (Sham) group, middle cerebral artery occlusion and reperfusion (MCAO/R) group, MCAO/R+si-Ctrl group, and MCAO/R+si-STIM1 group ( n=5); MCAO/R models were established in mice of the latter 3 groups; empty vector control virus and STIM1 gene knockout lentivirus were transfected into mice in the MCAO/R+si-Ctrl group and MCAO/R+si-STIM1 group. The transfection efficiency of STIM1 and the expression of microglia/macrophages M1 activation marker cluster of differentiation 86 (CD86) in each group were observed. (2) Cell experiment: primary microglia were divided into Ctrl group, oxygen-glucose deprivation/re-oxygenation (OGD/R) group, OGD/R+si-Ctrl group, OGD/R+si-STIM1 group, OGD/R+solvent group, and OGD/R+4-phenylbutyric acid (4-PBA) group; OGD/R models were established in the later 5 groups; empty vector control virus and STIM1 gene knockout lentivirus were transfected into mice in the OGD/R+si-Ctrl group and OGD/R+si-STIM1 group; cells in the OGD/R+4-PBA group were pre-treated with 1 mmol/L 4-PBA for 1 h at 24 h before OGD/R modelling to inhibit endoplasmic reticulum stress (ERS), and cells in the OGD/R+solvent group were pre-treated with 0.5% dimethyl sulfoxide (DMSO) for 1 h at the same time. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), ELISA, Western blotting and other methods were used to detect the levels of CD86, tumour necrosis factor-α ( TNF-α) mRNA, interleukin (IL)-1β, and ERS-related proteins (transcription factor C/EBP homologous protein [CHOP], activated transcription factor 4 [ATF4]) in these cells. Results:(1) Animal experiment: the STIM1 expression in MCAO/R+si-STIM1 group was significantly lower than that in Sham group, MACO/R group and MCAO/R+si-Ctrl group ( P<0.05); as compared with that in the MACO/R group and MCAO/R+si-Ctrl group, the number of microglia/macrophages co-expressing CD86 and Iba-1 around the ischemic foci of mice in the MCAO/R+si-STIM1 group was significantly decreased ( P<0.05). (2) Cell experiment: as compared with those in the OGD/R group and OGD/R+si-Ctrl group, the expression levels of STIM1, CD86, and TNF-α mRNA, and supernatant IL-1β content in the OGD/R+si-STIM1 group were significantly decreased ( P<0.05); as compared with those in the OGD/R group and OGD/R+si-CTRL group, the ATF4 and CHOP expression levels in OGD/R+si-STIM1 group were significantly decreased ( P<0.05); as compared with those in the OGD/R group and OGD/R+solvent group, the CD86 level, TNF-α mRNA expression level and IL-1β content in the OGD/R+4-PBA group were significantly decreased ( P<0.05). Conclusion:STIM1 affects microglia/macrophages M1 activation after ischemia-reperfusion injury by regulating ERS level.

Objective:To analyze and evaluate caring experience of caregivers of patients undergoing tracheotomy.Methods:PubMed, Web of Science, Cochrane Library, EBSCO, Embase, Chinese National Knowledge Infrastructure (CNKI) , Wanfang Database, VIP Database and SinoMed were searched by computer, and literature on quality studies on caring experience of caregivers of patients undergoing tracheostomy were searched. The time limit for retrieval was from the establishment of the database to November 30, 2020. The quality of literature was evaluated by using the quality evaluation standards of Australia Joanna Briggs Institute (JBI) Evidence-based Health Care Center. The results were analyzed by the collective integration method.Results:A total of 7 articles were included, including 5 English articles and 2 Chinese articles. Among them, 6 articles were phenomenological studies and 1 article was grounded theory research. In the end, it was summarized into 10 categories and integrated into 3 integrated results. The first integration result was psychological overload of caregivers, difficulties in role adaptation and social interaction and negative state. The second integrated result was that the caregivers' ability to care for was insufficient and they were exhausted. For them, the transition period after discharge was difficult to adapt and they were eager for support. The third integrated result was that caregivers gradually adapted, actively faced reality, changed their concepts and learned to be grateful while achieving self-growth.Conclusions:The status of caregivers of patients undergoing tracheotomy has both negative and positive aspects, and there are many psychological, social and family problems as well as nursing guidance needs. Medical staff should pay attention to the psychological pressure of caregivers of patients undergoing tracheotomy, provide them with disease care guidance, help caregivers strengthen the social and family support system, reduce the caregiver burden and improve the quality of care.

Objective:To evaluate the therapeutic efficacy and side effects of P-Gemox regimen combined with intensity modulated radiotherapy in the treatment of extranodal NK/T cell lymphoma, nasal type (ENKTL).Methods:The data of 60 patients with ENKTL confirmed by pathomorphology and immunohistochemistry in Guizhou Cancer Hospital from July 2014 to October 2019 were retrospectively analyzed. All patients received P-Gemox chemotherapy combined with intensity modulated radiotherapy (at least 2 cycles), and the efficacy and adverse reactions were evaluated.Results:The complete remission rate of 60 patients was 65.0% (39/60), the partial remission rate was 25.0% (15/60), and the total effective rate was 90.0% (54/60). The main side reactions were myelosuppression, transaminase elevation and radiation mucositis; most of them were mild to moderate, which were relieved after treatment or the withdrawal of radiotherapy and chemotherapy. No treatment-related death cases were found. The overall survival rate of 1-year, 2-year, 3-year was 91%, 75% and 69%; the progression-free survival rate of 1-year, 2-year, 3-year was 86%, 68% and 62%. During the treatment, 3 cases died due to the progress of the disease and infection. Multivariate analysis showed that with and without hemophagocytic syndrome and radiotherapy dose were related to prognosis (all P < 0.05). Conclusion:P-Gemox, as the first-line induction chemotherapy regimen combined with intensity modulated radiotherapy has good short-term efficacy and safety for patients with ENKTL.

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estima-tions and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10-4 per site per year with a 95％ confidence interval (CI) of [8.61 × 10-4, 8.77 × 10-4], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95％ CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism ofSARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Objective:To investigate the risk factors of dysplasia in patients with ulcerative colitis (UC) in China.Methods:From March 1st, 2012 to December 30th, 2013, a total of 154 UC patients were prospectively enrolled from the following 11 hospitals, Xijing Hospital of Digestive Diseases, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Peking Union Medical College Hospital, Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Nanfang Hospital affiliated to Southern Medical University, China-Japan Friendship Hospital, The Second Hospital of Hebei Medical University, West China Hospital affiliated to Sichuan University, The Seventh Medical Center of PLA General Hospital, Zhongshan Hospital affiliated to Xiamen University, and the First Affiliated Hospital of Anhui Medical University. The patients were followed up till December 1st, 2017. All the UC patients underwent colon endoscopy and histopathological evaluation. T test and Chi-square test were used for statistical analysis. Cox proportional risk model was used for identifying the risk factors of dysplasia in UC patients. Results:Finally, 133 UC patients were enrolled, the age was (50.0±11.9) years, the diagnosis age was (35.5±11.6) years, the course of disease was (14.5±6.7) years, and the number of endoscopic examinations was (3.4±1.6) times. A total of 21 patients were detected with dysplasia. No patients were detected with colorectal cancer. The results of univariate analysis revealed that the diagnosis age (hazard ratio ( HR)=1.05, 95% confidence interval ( CI) 1.01 to 1.10, P=0.009) and extensive colitis ( HR=2.92, 95% CI 0.97 to 8.79, P=0.057) were factors with statistically significant difference. The results of multivariate analysis revealed that the old age at diagnosis ( HR=1.06, 95% CI 1.02 to 1.11, P=0.003) and extensive colitis ( HR=3.68, 95% CI 1.21 to 11.19, P=0.022) were independent risk factors of dysplasia in UC patients. The cumulative incidence of dysplasia of UC patients with extensive colitis was higher than that of patients with left-sided colitis (24.3%, 17/70 vs. 6.3%, 4/63), and the difference was statistically significant ( χ2=8.023, P=0.005). Conclusions:Extensive colitis and older age at diagnosis are two independent risk factors of dysplasia in UC patients of our country. The cancer monitoring should be strengthened in UC patients with long course of disease and extensive colitis.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.