BACKGROUND: Cervical squamous cell carcinoma (CESC), the most common subtype of cervical cancer, is primarily caused by the high-risk human papillomavirus (HPV) infection and genetic susceptibility. Single-cell RNA sequencing (scRNA-seq) has been widely used in CESC research to uncover the diversity of cell types and states within tumor tissues, enabling a detailed study of the tumor microenvironment (TME). This technology allows precise mapping of HPV infection in cervical tissues, providing valuable insights into the initiation and progression of HPV-mediated malignant transformation. METHODS: We performed the scRNA-seq to characterize gene expression in tumor tissues and paired adjacent para-cancerous tissues from four patients with early-stage CESC using the 10× Genomics platform. The HPV infection and its subtypes were identified using the scRNA data and viral sequence mapping, and trajectory analyses were performed using HPV+ or HPV- cells. Interactions between different types of keratinized cells and their interactions with other cell types were identified, and pathways and specificity markers were screened for proliferating keratinized cells. The Cancer Genome Atlas (TCGA) dataset was used to verify the prognostic correlation between tumor-specific PI3+S100A7+ keratinocyte infiltration and CESC, and the localization relationship between PI3+S100A7+ keratinocytes and macrophages was verified by immunofluorescence staining. RESULTS: Various types of keratinocytes and fibroblasts were the two cell types with the most significant differences in percentage between the tumor tissue samples and paired adjacent non-cancerous tissue samples in the early stages of CESC. We found that PI3+S100A7+ keratinocytes were associated with early HPV-positive CESC, and PI3+S100A7+ keratinocytes were more abundant in tumors than in adjacent normal tissues in the TCGA-CESC dataset. Analysis of clinical information revealed that the infiltration of PI3+S100A7+ keratinocytes was notably higher in tumors with poor prognosis than in those with good prognosis. Additionally, multiplex immunofluorescence analysis showed a specific increase in PI3+S100A7+ expression within tumor tissues, with PI3+S100A7+ keratinocytes and CD163+ macrophages being spatially very close to each other. In the analysis of cell-cell interactions, macrophages exhibited strong crosstalk with PI3+S100A7+ proliferating keratinocytes in HPV-positive CESC tumors, mediated by tumor necrosis factor (TNF), CCL2, CXCL8, and IL10, highlighting the dynamic and tumor-specific enhancement of macrophage-keratinocyte interactions, which are associated with poor prognosis and immune modulation. Using CIBERSORTx, we discovered that patients with high infiltration of both PI3+S100A7+ proliferating keratinocytes and macrophages had the shortest overall survival. In the analysis of cell-cell interactions, PI3+S100A7+ proliferating keratinocytes and macrophages were found to be involved in highly active pathways that promote differentiation and structure formation, including cytokine receptor interactions, the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, and TNF signaling pathway regulation. Further subtyping of fibroblast populations identified four subtypes. The C1 group, characterized by its predominance in tumor tissues, is a subtype enriched with cancer-associated fibroblasts (CAFs), whereas the C3 group is primarily enriched in adjacent non-cancerous tissues and consists of undifferentiated cells. Moreover, the distinct molecular and cellular differences between HPV16- and HPV66-associated tumors were demonstrated, emphasizing the unique tumor-promoting mechanisms and microenvironmental influences driven by each HPV subtype. CONCLUSIONS We discovered a heterogeneous population of keratinocytes between tumor and adjacent non-cancerous tissues caused by HPV infection and identified macrophages and specific CAFs that play a crucial role during the early stage in promoting the inflammatory response and remodeling the cancer-promoting TME. Our findings provide new insights into the transcriptional landscape of early-stage CESC to understand the mechanism of HPV-mediated malignant transformation in cervical cancer.
Humans ; Female ; Papillomavirus Infections/genetics* ; Uterine Cervical Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Keratinocytes/metabolism* ; Single-Cell Analysis/methods* ; Tumor Microenvironment/genetics*

Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

Objective: The study aims to explore the neural mechanism of cognitive differences in college students with posttraumatic stress disorder under verbal fluency task based on functional near infrared spectroscopy (fNIRS), so as to provide neuroimaging support for the evaluation, diagnosis and treatment of posttraumatic stress disorder(PTSD). Methods: Posttaumatic Stress Disorder Checklist Combat(PCL-C) was used to screen the subjects, including 21 students in PTSD group (PCL-C≥38) and 30 students in control group from September to Novenber in 2020. A 53 channel near infrared spectroscopy device was used to collect cerebral blood oxygen signals under the verbal fluency task, and correlation analysis, Mann Whitney U test and independent sample t test were performed on the results. Results: The difference in the total average score of PCL-C Scale between PTSD group and the control group(46.38±6.96，25.57±6.09) was statistically significant ( t=11.33, P <0.05). Correlation analysis showed that Avg-HbO in left dorsolateral prefrontal lobe was negatively correlated with PCL-C Score ( r=-0.37, P <0.05). Mann Whitney U test showed that in the left dorsolateral prefrontal lobe (Ch6), the Avg-HbO change in PTSD group [0.19(-0.09, 0.86)mmol/(L〖KG*7〗·mm)] was significantly lower than the control group [0.79( 0.37 , 1.47)mmol/(L ·mm)] ( Z=2.16, P <0.05), which was statistically significant. Conclusions The degree of PTSD was negatively correlated with the index of oxygenated hemoglobin in the left dorsolateral prefrontal lobe, and the oxygenated hemoglobin content in the PTSD group was lower than that in the normal group. In the future, fNIRS may be used to collect blood oxygen signals from the left dorsolateral prefrontal lobe in cognitive tasks to provide imaging evidence for the identification of PTSD.

Objective To understand the impact of system reform of salt industry on iodine nutrition of people in Gansu Province, and to provide a scientific basis for policy adjustment of relevant departments. Methods The investigation period (2014-2021) was divided into two sub-periods: before system reform of salt industry (2014-2016) and after system reform of salt industry (2017-2021). Thirty counties were selected according to the method of ^“population proportional probability sampling (PPS)^” in 2014. According to the iodine deficiency disease monitoring program of Gansu Province, from 2016 to 2021, children aged 8-10 years and pregnant women were taken as research objects to collect urine samples for urine iodine detection. Children in 2014 and 2018 were selected to measure thyroid volume. Results A total of 90 989 children urine iodine samples were investigated, and the median urinary iodine (MUI) of children was 194.70µg/L; 7 663 and 83,326 children's urinary iodine samples were investigated in the two periods, the MUI was 180.73 µg/L and 196.00 µg/L, respectively, and the difference was statistically significant (P<0.05). A total of 44 741 pregnant women's urinary iodine samples were investigated, and the MUI of pregnant women was 176.50 µg/L; 4 480 and 40 261 pregnant women's urinary iodine samples were investigated in the two periods, the MUI was 160.61 µg/L and 178.10 µg/L, respectively, and the difference was statistically significant (P<0.05). The thyroid volume of 1 555 children and 8 509 children was investigated in the two periods, the median thyroid volume was 2.70 mL and 2.55 mL , respectively, and the difference was statistically significant (P<0.05). The rates of goiter in children were 3.15% and 1.26%, respectively, and the difference was statistically significant (P<0.05). Conclusion The iodine nutrition of people in Gansu Province has not fluctuated significantly after the reform of salt industry system and has maintained an appropriate level. It is necessary to pay attention to the potential risk of insufficient iodine nutrition level and thyroid health of key populations such as children and pregnant women and strengthen health education of scientific iodine supplementation.

There are millions of patients with taxane-induced peripheral neuropathy （TIPN）， and there is no effective treatment or prevention measure in clinical practice. The occurrence of TIPN may be related to the dosage form of paclitaxel drugs， genetic and molecular markers， drug dosage and chemotherapy cycle， patient factors， etc. At present， drugs for treating TIPN mainly include those that inhibit axonal degeneration （such as dosazosin， tamsulosin）， prevent mitochondrial dysfunction （such as glutathione trisulfides， antioxidants α -lipoic acid）， improve calcium imbalance in the internal environment （Shaoyao gancao decoction， N-type voltage-gated calcium channel inhibitor IPPQ）， and inhibit neuroinflammation （such as chemokine inhibitors and selective interleukin-8 receptor inhibitors DF2726A）. Further exploration of drug treatment strategies targeting different induction mechanisms is expected to become a new direction for precise clinical prevention and personalized treatment of TIPN.

Objective:To investigate the intelligence status of children aged 10 - 12 in rural areas of Linxia Hui Autonomous Prefecture (referred to as Linxia) in Gansu Province.Methods:From September to November 2019, a cross-sectional study was carried out to investigate the intelligence status of children aged 10 to 12 in 8 counties (cities) of Linxia. Chinese Raven's Progressive Matrices (rural version) was used for intelligence test and children's intelligence quotient (IQ) was calculated by regular mold to evaluate children's intelligence level.Results:A total of 1 721 children in Linxia were tested for intelligence, with an average IQ of 103.2. Among them, low intelligence (≤69) accounted for 1.0% (18/1 721), borderline (70 - 79) accounted for 3.0% (52/1 721), middle and lower (80 - 89) accounted for 8.4% (144/1 721), moderate (90 - 109) accounted for 56.6% (974/1 721), middle and upper (110 - 119) accounted for 21.9% (377/1 721), excellent (120 - 129) accounted for 7.8% (135/1 721), extremely excellent (≥130) accounted for 1.2% (21/1 721). There were 635, 598 and 488 children aged 10, 11 and 12, respectively, with an average IQ of 106.1, 103.3 and 99.2. There were 919 males and 802 females, with an average IQ of 102.9 and 103.4, respectively.Conclusion:In 2019, the intelligence of children aged 10 to 12 in rural areas of Linxia has reached the moderate level.

Objective:To evaluate the testing capability of urinary iodine laboratories in Gansu Province and analyze the existing problems.Methods:Z-score method and uncertainty analysis were used to analyze the external quality control assessment results of urinary iodine laboratories in Gansu Province from 2017 to 2021 (data were collected from Gansu Center for Disease Prevention and Control).Results:From 2017 to 2021, the participation rate in the assessment of urinary iodine laboratories in the province was 100.0% (473/473), the feedback rate was 99.8% (472/473), and the pass rate was 91.9% (434/472). The pass rates for assessment from 2017 to 2021 were 82.7% (62/75), 93.9% (93/99), 94.9% (93/98), 92.0% (92/100), and 94.0% (94/100), respectively. The pass rates for provincial, municipal, and county assessments were 5/5, 98.6% (69/70), and 90.7% (360/397), respectively. The proportions of │Z│≤2, 2 <│Z│ < 3, and│Z│≥3 between laboratories in the province were 84.5% (399/472), 9.3% (44/472), and 6.2% (29/472), respectively. The proportions of│Z│≤2, 2 <│Z│ < 3, and│Z│≥3 within the laboratories were 88.6% (418/472), 9.1% (43/472), and 2.3% (11/472), respectively. There was a significant difference in the composition of │Z│ scores between laboratories annually (χ 2 = 24.60, P = 0.002), the proportion of│Z│≤2 increased from 66.7%(50/75) in 2017 to 90.0% (90/100) in 2021. The│Z│ scores between and within provincial laboratories were both ≤2. The proportion of │Z│≤2 between municipal and county-level laboratories was 91.4% (64/70) and 83.1% (330/397), respectively, the proportion of│Z│≤2 within laboratories was 92.9% (65/70) and 87.7% (348/397), respectively. There was no difference in the composition of│Z│ scores between and within provincial, municipal, and county-level laboratories( P < 0.05). The proportion of two concentration quality control blind sample results in the province that were both within the uncertainty range was 89.2% (421/472). From 2017 to 2021, they were 81.3% (61/75), 91.9% (91/99), 84.7% (83/98), 92.0% (92/100), and 94.0% (94/100), respectively, with statistically significant differences (χ 2 = 9.69, P = 0.021); provinces, cities, and counties were 5/5, 95.7% (67/70), and 87.9% (349/397), respectively, with statistically significant differences (χ 2 = 23.60, P = 0.023). Conclusions:Through continuous external quality control assessments of all established urinary iodine laboratories in Gansu Province, the overall testing capacity of urinary iodine laboratories at all levels has been continuously improved. However, in the future, it is still necessary to strengthen laboratory testing capabilities and improve the level of urine iodine detection.

Objective To explore the correlation between the expression levels of neutrophil extracellular traps(NETs)markers circulating free DNA(cfDNA),citrullinated histone 3(CitH3),myeloperoxidase(MPO)-DNA in plasma and the degree of retinopathy in patients with type 2 diabetes mellitus(T2MD).Methods A sum of 80 patients with type 2 diabetes mellitus(T2DM)in First Affiliated Hospital of Henan University of Science and Technology from January to September 2023 were selected as the study objects.According to the retinopathy of T2DM patients,they were divided into non-diabetic retinopathy(NDR)group(n=30),nonproliferative diabetic retinopathy(NPDR)group(n=26)and proliferative diabetic retinopathy(PDR)group(n=24).General data of enrolled patients were collected and plasma cfDNA,CitH3,MPO-DNA levels were detected.Spearman correlation was used to analyze the relationship between cfDNA,CitH3,MPO-DNA and the severity of retinopathy in T2DM patients.ROC curves were used to analyze the efficacy of cfDNA,CitH3,MPO-DNA and their combination in predicting the occurrence of diabetic retinopathy(DR)in T2DM patients.Results The levels of cfDNA(65.13±18.28,83.34±20.10,114.52±32.36 ng/ml),CitH3(17.76±4.24,22.03±5.01,26.06±8.13 ng/ml)and MPO-DNA(0.31±0.04,0.35±0.05,0.45±0.05)in NDR group,NPDR group and PDR group were increased successively,and the differences were statistically significant(F=28.755,13.335,62.470,all P＜0.001).The levels of cfDNA,CitH3 and MPO-DNA in PDR group and NPDR group were higher than those in NDR group(t=7.076,4.837,11.436;3.550,3.455,3.324),and the levels of cfDNA,CitH3,and MPO-DNA in PDR group were higher than those in NPDR group(t=4.127,2.128,7.065),and the differences were statistically significant(all P＜0.05).Spearman correlation analysis showed that cfDNA,CitH3 and MPO-DNA were positively correlated with the severity of retinopathy in T2DM patients(r=0.659,0.470,0.744,all P＜0.001).ROC curves showed that the AUC(95%CI)of cfDNA,CitH3,MPO-DNA and combined detection were 0.846(0.758～0.934),0.776(0.674～0.878),0.847(0.764～0.930)and 0.938(0.889～0.987),respectively,and it had certain predictive value for DR in T2DM patients.Conclusion The levels of NETs markers cfDNA,MPO-DNA and CitH3 in the plasma of DR Patients are increased,and their levels are positively correlated with the degree of diabetic retinopathy,which can predict the occurrence of DR in T2DM patients to a certain extent,and the combined prediction value is the highest.

In automatic skin damage analysis,segmentation is a challenging and critical operation due to factors such as the shape and contrast of hair and skin lesions on the skin.Compared with traditional segmentation methods,deep learning seamlessly integrates feature extraction and task-specific decision-making,achieving segmentation tasks more accurately and efficiently,and effectively reducing the burden and cost of skin cancer screening.This article first introduces the background of dermoscopic segmentation and deep learning models,and introduces the application of deep learning in dermoscopic segmentation.Secondly,this article introduces the algorithm models of convolutional neural networks and attention mechanisms,reviews the application of fused attention convolutional neural networks in dermoscopic segmentation since Jan 2022,and summarizes the improvement strategies,the advantages and disadvantages of the model.The model is further analyzed based on commonly used datasets of dermoscopy and evaluation indicators of image segmentation.Finally,the application of fused attention convolutional neural network in dermoscopic segmentation is summarized and prospected.