Establishing a three-generation family cohort enables the investigation of the effects of genetic, epigenetic, lifestyle, and parenting factors in the grandparental (F0) and parental (F1) generations on the growth, development, and disease onset and progression of the offspring (F2). It facilitates further exploration of the biological mechanisms underlying the impact of intergenerational factors on the health of the offspring (F2), providing evidence for the formulation of public health policies and measures related to child health management and infant and young child care. Currently, the development of multi-generational cohorts in China remains in a preliminary stage, with no systematic multi-generational research framework yet established. Drawing on prior evidence-based scientific research, existing cohort studies, and the practical experience of multidisciplinary experts in maternal and child health, this consensus defines the scope of three-generation family cohorts regarding their definition, significance, key technologies, and application scenarios. It provides technical recommendations for establishing relevant cohorts, aiming to support research areas such as the intergenerational transmission of childhood diseases, the maternal intrauterine environment, and the tracing of family rearing environments. This will facilitate the early prevention and control of diseases manifesting in childhood and adulthood, ultimately promoting the comprehensive and healthy development of children.

Objective To sort out the current situation and research hotspots of the application of information technology in drug safety in China，reveal the latest research frontier, and provide a basis for the follow-up research. Methods The literature about the application of information technology in the field of drug safety were searched from 2012 to 2022 in three major databases of CNKI, WanFang and VIP databases, and visual analysis was conducted with the help of Citespace software. Results A total of 848 valid papers were included, and the number of annual publications showed a phased growth trend, and the cooperation between authors and publishers was not close enough. The application of information technology in drug safety was mainly reflected in pharmaceutical service, intravenous drug dispensing center and antibacterial drugs. The main technical means of information construction in the field of drug safety were prescription pre-audit system, knowledge base and automation. The research frontiers were mainly intelligence, knowledge base, prescription audit, and proprietary Chinese medicines. Conclusion The application of information technology in drug safety in China is in a period of vigorous development, and cooperation among different regions, institutions, and authors should be strengthened to promote information sharing. In the future, the related research of information technology in the field of Chinese patent medicine should be focused, and the research content of information technology application in drug safety could be further improved.

Objective To propose a classification model based on a pseudo-bag strategy and feature adjustment for whole slide imaging in pathology.Methods A pseudo-bag generator was constructed to divide a parent bag into 3 pseudo-bags for increasing the number of training bags.Then,a pseudo-bag learning method based on Nystr?m-based algorithm for approximating self-attention and a selective feature fusion method were employed to process the pseudo-bags.Specifically,the pseudo-bag learning method based on Nystr?m-based algorithm for approximating self-attention reduced computational complexity through an improved multi-head self-attention mechanism while deeply extracting instance features to obtain pseudo-bag classification predictions,thereby enhancing pseudo-bag classification accuracy;and the selective feature fusion method refined pseudo-bag features by filtering and extracting relevant instances.Finally,the model adjusted bag features by extracting confounding factors to avoid interference from irrelevant information and further improve classification accuracy.Results The proposed model was evaluated on two datasets(CAMELYON-16 and TCGA-NSCLC)and compared with 10 other methods,and the results demonstrated that the proposed model achieved the best performance.The proposed method reached an accuracy of 0.943 on the CAMELYON-16 dataset and 0.906 on the TCGA-NSCLC dataset.Conclusion The proposed model can significantly improve the accuracy of whole-slide pathological image classification by effectively mitigating the overfitting and avoiding interference from irrelevant information.

Objective:To study the clinical and pathological features, immunophenotypes, molecular genetics characteristics, differential diagnosis, and prognostic factors of pulmonary and tracheal glomus tumors.Method:Eight cases of pulmonary and tracheal glomus tumors were collected in Jiangsu Provincial Hospital (including 1 consultation, from Gaochun People's Hospital, Nanjing, China) between May 2015 and April 2023, and their clinical and imaging data, pathological morphology, and immunohistochemical characteristics were retrospectively analyzed. Gene testing and follow-up were performed.Result:There were 5 males and 3 females with onset ages ranging from 29 to 75 years old, median age 63.5 years. Among the patients, 5 cases were located in the trachea and 3 cases in the lungs. Under light microscopy, 5 cases were benign glomus tumors with clear boundaries, diffuse sheet or nest-like distribution, small, round or short spindle-shaped tumor cells, rounded and centered nuclei, and no obvious nuclear mitosis was seen. Two cases of glomus tumor of uncertain malignant potential showed an infiltrative growth pattern involving smooth muscle, nerves and blood vessels with necrosis and calcification, the tumor cells were more uniform in size, round or short spindle-shaped nuclei, and no obvious nuclear mitosis was seen; One case of malignant glomus tumor was seen in sarcomatous areas, lung membrane invasion and necrosis, the tumor cells were highly heterogeneous, binucleated and multinucleated, with nuclear mitoses of 20/50 high power field (HPF), and pathologic nuclear mitoses were easy to be seen. Immunohistochemically, SMA, Calponin, H-caldesmon, Vimentin and Collagen Ⅳ were all positive (8/8). Some cases expressed Syn (3/8) and Bcl-2 (4/8). The Ki-67 proliferation index was 1-2% (7/8) and 40% (1/8). BRAF V600E were detected as wild-type (8/8), and no mutations were detected in exons 2, 3, and 4 of KRAS human EML4- ALK fusion gene were negative in 5 surgical cases. Case 6 showed HMBOX1- ALK gene fusion, TERT gene mutation and CDKN2A gene deletion, and case 8 showed CARMN- NOTCH2 gene fusion. Seven cases were followed up (8-103 months, median follow-up time 30 months), 1 case was lost, 1 case recurred 21 months after surgery, and others with no evidence of recurrence or metastasis. Conclusions:Pulmonary and tracheal glomus tumors are very rare and need to be differentiated from other common tumors by combining pathological morphology and immunohistochemistry. Maybe there are some differences in the malignant diagnostic criteria and molecular genetic characteristics between visceral derived glomus tumors and soft tissue derived tumors of the same kind, such as limbs and skin. More data accumulation is needed.

Objective:To analyze the genetic mutation characteristics of the first reported case of DNA ligase Ⅳ syndrome primarily presenting as eczematous dermatitis and purpura in China.Methods:Clinical data were collected from a child with DNA ligase Ⅳ syndrome, and whole-exome sequencing was performed to identify genetic mutations.Results:The patient presented with generalized eczematous dermatitis and purpura, accompanied by pancytopenia, growth retardation, and immunodeficiency. Genetic testing revealed compound heterozygous mutations at three sites in the DNA ligase Ⅳ gene, namely c.467C>T (p.A156V) , c.833G>T (p.R278L) , and c.1271-c.1275del (p.K424fs*20) , among which c.467C>T (p.A156V) had not been previously reported.Conclusion:Children with DNA ligase Ⅳ syndrome may present with eczematous dermatitis and purpura, and compound heterozygous mutations in the DNA ligase Ⅳ gene may represent the genetic cause of this condition.

Although the COVID-19 pandemic has subsided, the risk of the outbreak of new emerging infectious diseases remained constantly present. As such an outbreak can have devastating consequences to the society and economy, development of warning strategies before it takes place is a critical and urgent research task. However, there are currently no validated methods that are both effective and practically feasible for giving pre-outbreak alerts. As such, timely identification and rapid response after an outbreak takes place is still a feasible and effective method for responding to new emerging infectious diseases. The speed and efficiency of the response are largely contingent upon preparedness during the inter-epidemic periods. This paper aims to outline our thinking about the framework for infectious disease early warning and propose some recommendations. Implementation of such a strategy in practice necessitates the establishment of pilot initiatives to test the early warning system according to our proposed principles. These pilots may use severe influenza or hypothetical outbreak scenarios as examples, define warning signals, develop the mechanisms for epidemiological investigation, reporting and response so as to conduct feasibility assessments.

A VLi-net based cell nucleus segmentation method integrating convolutional neural networks(CNN)and Vision Transformer(ViT)is proposed to address the limitation that the U-Net with CNN as its backbone is only proficient in capturing local features and has a restricted receptive field.Firstly,to mitigate challenges such as high cost of data annotation and insufficient annotated data,text annotations are introduced to enhance the network's understanding of image information.Secondly,to improve the segmentation performance of VLi-net,ViT and CNN are combined to fully extract global and local features,with multi-receptive field convolution features incorporating into the ViT structure for effectively mitigating the issues of limited local information interaction and single feature representation in ViT.Finally,an interactive fusion module(ViFusion)is used to efficiently fuse the multi-level features from the CNN and ViT branches.Experimental results show that VLi-net achieves a Dice coefficient of 80.85%and a mean intersection over union(MIoU)of 66.83%on the MoNuSeg dataset,obtains a Dice coefficient of 80.53%and a MIoU of 67.54%on the DSB-2018 dataset,and has a Dice coefficient of 86.87%and a MIoU of 77.44%on the TNBC dataset.These findings confirm that VLi-net outperforms other methods across multiple experimental metrics.

Objective To construct an animal model of dilated cardiomyopathy(DCM)with heart failure toxin syndrome that conforms to the characteristics of traditional Chinese medicine(TCM)syndrome and identify potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.Methods Fifteen male SD rats were divided into a blank control,doxorubicin,or DCM with heart failure toxin syndrome group using a random number table method,with five rats per group.The doxorubicin group received intraperitoneal injection of doxorubicin at a dose of 1.25 mg/kg,administered on the first and fourth days of each week,along with a standard diet.The DCM with heart failure toxin syndrome group,in addition to the doxorubicin treatment,was given 42％white liquor(10 mL/kg)via gavage every other day,along with a 45％high-fat feed and 10％fructose water.The blank control group received intraperitoneal injection of an equivalent volume of phosphate-buffered saline at the same time points as the doxorubicin group,along with a standard diet.The model was established for 10 weeks.At the fourth and tenth weeks of modeling,echocardiography was performed to measure left ventricular ejection fraction(LVEF),fractional shortening(FS),systolic left ventricular posterior wall thickness(LVPWs),diastolic left ventricular posterior wall thickness,systolic left ventricular internal diameter(LVIDs),and diastolic left ventricular internal diameter(LVIDd);macroscopic changes in fur color of the rats were assessed using the red-green-blue colorimetric method.After modeling,the open field test was conducted to evaluate the exercise tolerance of the rats,and the grip strength test was performed to assess changes in forelimb grip strength.Hematoxylin-eosin,Masson,and wheat germ agglutinin staining were used to evaluate pathological changes in cardiac tissue.Bulk RNA sequencing analysis was performed to identify differentially expressed genes(DEGs)in the hearts of rats between the blank control and the DCM with heart failure toxin syndrome groups.Using DCM,the Blue value of rat fur color,and forelimb grip strength as phenotypic traits,weighted gene co-expression network analysis(WGCNA)was performed to screen for characteristic module gene sets(MEs)associated with DCM with heart failure toxin syndrome.Overlapping analysis was performed on DEGs,immune-related gene sets,and MEs,and the intersecting genes were identified as potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.The sensitivity and specificity of these targets were evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared with the blank control group,at the tenth week of modeling,the LVEF,FS,and LVPWs of rats in the doxorubicin group and the DCM with heart failure toxin syndrome group decreased,whereas LVIDs and LVIDd increased,and the movement distance of the open field test and forelimb grip strength were reduced(P＜0.05).At the 10th week of modeling,the Blue value of fur color in the DCM with heart failure toxin syndrome group was significantly lower than that of the blank control and doxorubicin groups(P＜0.05).Compared with the blank control group,rats in the doxorubicin and DCM with heart failure toxin syndrome groups exhibited significant cardiac dilation and increased immune cell infiltration in cardiac tissue,accompanied by collagen deposition and cardiomyocyte hypertrophy.Bulk RNA sequencing identified 2,003 DEGs,including 1,082 downregulated genes and 921 upregulated genes.WGCNA results revealed that the MEturquoise module had the strongest positive correlation with DCM and the strongest negative correlation with the Blue value and forelimb grip strength.The overlapping analysis identified four intersecting genes:bone morphogenetic protein 6(Bmp6),serine-threonine-protein kinase 1(Pak1),proto-oncogene JunD(JunD),and S100 calcium-binding protein A3(S100A3).ROC curve analysis demonstrated that these four genes exhibited high sensitivity and specificity for DCM with heart failure toxin syndrome.Conclusion The rat model constructed by intraperitoneal injection of doxorubicin combined with a high-fat feed,fructose water,and white liquor gavage closely aligns with the characteristics of the DCM with heart failure toxin syndrome.Bmp6,JunD,Pak1,and S100A3 are potential biomarkers or therapeutic targets for DCM heart failure toxin syndrome.

Objective:To analyze the genetic mutation characteristics of the first reported case of DNA ligase Ⅳ syndrome primarily presenting as eczematous dermatitis and purpura in China.Methods:Clinical data were collected from a child with DNA ligase Ⅳ syndrome, and whole-exome sequencing was performed to identify genetic mutations.Results:The patient presented with generalized eczematous dermatitis and purpura, accompanied by pancytopenia, growth retardation, and immunodeficiency. Genetic testing revealed compound heterozygous mutations at three sites in the DNA ligase Ⅳ gene, namely c.467C>T (p.A156V) , c.833G>T (p.R278L) , and c.1271-c.1275del (p.K424fs*20) , among which c.467C>T (p.A156V) had not been previously reported.Conclusion:Children with DNA ligase Ⅳ syndrome may present with eczematous dermatitis and purpura, and compound heterozygous mutations in the DNA ligase Ⅳ gene may represent the genetic cause of this condition.

Although the COVID-19 pandemic has subsided, the risk of the outbreak of new emerging infectious diseases remained constantly present. As such an outbreak can have devastating consequences to the society and economy, development of warning strategies before it takes place is a critical and urgent research task. However, there are currently no validated methods that are both effective and practically feasible for giving pre-outbreak alerts. As such, timely identification and rapid response after an outbreak takes place is still a feasible and effective method for responding to new emerging infectious diseases. The speed and efficiency of the response are largely contingent upon preparedness during the inter-epidemic periods. This paper aims to outline our thinking about the framework for infectious disease early warning and propose some recommendations. Implementation of such a strategy in practice necessitates the establishment of pilot initiatives to test the early warning system according to our proposed principles. These pilots may use severe influenza or hypothetical outbreak scenarios as examples, define warning signals, develop the mechanisms for epidemiological investigation, reporting and response so as to conduct feasibility assessments.