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*

Objective To study the corrosion-fatigue properties of a novel low modulus Ti-3Zr-2Sn-3Mo-25Nb(TLM)titanium alloy subjected to simulated body fluid(SBF).Methods Ti-6Al-4V(TC4)alloy was used as the control group.The electrochemical corrosion polarization curves of the two titanium alloys were measured in SBF.The pre-corroded TC4 and TLM titanium alloy samples were subjected to rotational bending fatigue tests.The loading stress amplitude and fatigue fracture cycle relationship was established using the experimental data,and the stress life curves were drawn.Subsequently,the fracture mechanism was analyzed by analyzing the corrosion fatigue micro-fracture morphology of the sample,and fatigue analysis on the titanium alloy sample was then conducted combined with the finite element software.Results The self-corrosion potential of the TC4 titanium alloy under stress annealing was lower than that of the TLM titanium alloy after heat treatment.The TLM titanium alloy was most sensitive to changes in cyclic stress.A comparison between the simulation and experimental results showed that the TC4 titanium alloy under stress annealing had a higher fatigue strength and stronger resistance to crack propagation than the TLM titanium alloy did after heat treatment,whereas its corrosion resistance was the opposite.Compared to the specimens without pre-corrosion treatment,the brittleness of the TLM titanium alloy increased,and its fatigue performance decreased after pre-immersion in SBF.Conclusions Through comparative analysis,the reliability of the test results proved to be high,and the COMSOL finite element software could effectively predict the fatigue life of titanium alloy materials.

Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.

Objective: To understand the social adaptation in the association between attitude towards parents with academic anxiety among middle school students in Chongqing, so as to provide a basis and thinking method for theoretical framework of family education and youth development. Methods: Convenient and clustering sampling method was used to select 34 097 middle school students aged 13-18 years during September to November 2023. All the participants were investigated with self designed questionnaire, Social Adaptability Scale and Mental Health Test. The mediating effect of social adaptability in the relationship between students attitudes towards their parents academic anxiety was evaluated by using Logistic regression analysis and structural equation model. Results: The proportion of high school students in Chongqing with academic anxiety was 48.80%. Academic anxiety differed significantly by sex, academic grade, attitude towards parents, and social adaptability ( χ 2=948.45, 173.92, 537.51, 4 770.04, P < 0.01). The results of Logistic regression analysis showed that positive attitudes towards parents were positively correlated with moderate academic anxiety ( OR=1.13, 95%CI =1.08-1.18) and high academic anxiety ( OR=1.14, 95%CI =1.09-1.19) ( P < 0.05 ). The results of the mediation effect analysis showed that positive attitude of middle school students towards their parents negatively predicted academic anxiety ( β= -0.12 , P <0.01), but when social adaptation ability was used as a control variable, the original negative relationship between the positive attitude towards parents and academic anxiety of middle school students changed ( β=0.02, P <0.01), and social adaptation ability played a masking effect in the relationship. The social adaptation ability of middle school students played a mediating role in the relationship between their positive attitudes towards their parents and academic anxiety, with a mediating effect of -0.63. Conclusions The attitude of middle school students towards their parents will directly affect academic anxiety, and also have an indirect impact on academic anxiety through social adaptability, but there is a cover effect. Pay more attention to family education and actively focus on students social adaptability can contribute to improve the mental health level of adolescents.

Cognitive reserve referred to the cumulative flexibility of an individual's cognitive processes,whereas accurately assessing an individual's cognitive reserve and intervening was important for preventing the occurrence of cognitive dysfunction as well as promoting cognitive health.This article reviewed the main contents and applications of cognitive reserve assessment tools,and compared the characteristics and limitations of each assessment tool.The purpose was to provide ideas for the development of cognitive reserve assessment tools suitable for China's cultural background and population characteristics,and to provide a basis for accurately assessing the current status of China's cognitive reserve and formulating targeted cognitive reserve enhancement programs.

Objective:To investigate the chain mediation effect of psychological flexibility and dyadic coping between perceived social support and family function in parents of pediatric liver transplant recipients.Methods:Totally 320 parents of pediatric liver transplant recipients who were treated at the Department of Pediatric Organ Transplantation, Tianjin First Central Hospital from April to October 2023 were selected by convenience sampling. The participants were surveyed using a general information questionnaire, the Perceived Social Support Scale (PSSS), the Acceptance and Action Questionnaire-Ⅱ (AAQ-Ⅱ), the Dyadic Coping Inventory (DCI), and the Family APGAR Index (APGAR). Pearson correlation analysis was used to examine the relationships between perceived social support, psychological flexibility, dyadic coping, and family function in these parents. Structural equation modeling (SEM) was performed using Amos 26.0 to analyze the chain mediation effect of psychological flexibility and dyadic coping between perceived social support and family function, with the Bootstrap method used for model testing.Results:A total of 320 questionnaires were distributed, with 312 valid responses, yielding a response rate of 97.50% (312/320). The scores for the 312 parents were as follows: PSSS (59.29±15.64), AAQ-Ⅱ (20.35±9.07), DCI (124.64±32.65), and APGAR (6.98±2.74). Family function was positively correlated with perceived social support and dyadic coping ( P<0.01), and perceived social support was positively correlated with dyadic coping ( P<0.01). Psychological flexibility was negatively correlated with family function, perceived social support, and dyadic coping ( P<0.01). SEM results showed that psychological flexibility and dyadic coping had a significant chain mediation effect between perceived social support and family function, with a mediation effect value of 0.059. The chain mediation effect of psychological flexibility and dyadic coping accounted for 13.81% of the total effect (0.059/0.427) . Conclusions:Perceived social support directly affects family function in parents of pediatric liver transplant recipients and also indirectly influences family function through the chain mediation effect of psychological flexibility and dyadic coping.

Objective:To systematically evaluate the life experiences of young-onset dementia (YOD) patients and provide a basis for healthcare professionals to develop effective support service strategies.Methods:Qualitative studies on the life experiences of YOD patients were retrieved from PubMed, Embase, Medline, CINAHL, PsycINFO, Scopus, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP, WanFang data, and China Biology Medicine disc. The search timeframe was from the establishment of the databases to December 10, 2023. A Meta-synthesis approach was used to integrate the results.Results:A total of 17 articles were included, from which 69 findings were extracted, forming 11 categories and synthesizing into four integrated results: the heavy physical and psychological burden borne by YOD patients, impairment in multiple roles and social isolation, unique needs of YOD patients, and various coping strategies of YOD patients.Conclusions:Healthcare professionals should focus on the personal stories of YOD patients, pay attention to their physiological, psychological, and social challenges, and continuously improve supportive care services to alleviate their psychological burden, promote social connections, assist in resuming life, and enhance their quality of life.

OBJECTIVE To study the chemical constituents in S henfu injection and the anti-inflammatory activities of its polyacetylene compounds. METHODS Shenfu injection was separated and purified by macroporous adsorption resin ，medium pressure liquid chromatography ，preparative thin layer chromatography and reversed-phase semi-preparative high-performance liquid chromatography，and the compound structure was identified according to the physicochemical properties and spectral data. RAW 264.7 cell inflammation model was used to evaluate the anti-inflammatory activities of polyacetylene compounds . The effects of active polyacetylene compounds on the expressions of cyclooxygenase- 2（COX-2）protein were evaluated by Western blot assay. RESULTS Twelves compounds were isolated and identified from Shenfu injection ，including 8 ginsenoside compounds ，i.e. ginsenoside Rg 1（1），ginsenoside Re （2），ginsenoside Rb 1（3），ginsenoside Rk 1（4），20（R）-ginsenoside Rh 1（5），20（S）-ginsenoside Rg3 （6），notoginsenoside R 1（7），panaxatriol（8）；4 polyacetylene compounds ，i.e.（3R，9R，10R）-panaxytriol（9），panaxydol（10）， heptadeca-1，8-dien-4，6-diyne-3，10-diol（11）and panaxynol （12）. Among 4 polyacetylene compounds ，only compound 10 had anti-inflammatory activity. Compound 10 was not toxic to normal RAW 264.7 cells；when the concentration of compound 10 ranged 12.5-50.0 μmol/L，it could significantly reverse the lipopolysaccharide-induced NO content increase in cell supernatant （P＜0.05 or P＜0.01）；when the concentration of co mpound 10 was 50.0 μmol/L，it could significantly reverse the lipopolysaccharide-induced protein expression increase of COX- 2 in cells （P＜0.05）. CONCLUSIONS Compounds 4，7，10-12 are identified and reported in Shenfu injection for the first time ，and panaxydol possesses a certain anti-inflammatory effect.

Objective:Objective The inhibitory effect of Niuhuang Qinggan Capsule on 2019-nCoV virus was studied to provide experimental evidence for drug screening and treatment of 2019-nCoV acute respiratory disease.Methods:The 2019-nCoV virus GS048 strain was isolated and cultured by Vero-E6 cells. The solution of Niuhuang Qinggan capsule was incubated with virus in vitro to determine the change of virus titer. The effect of Niuhuang Qinggan capsule on the proliferation of 2019-nCoV virus was determined by cell culture medium method.Results:It was found that the concentration of 274.3 μg/ml was not toxic to the cells when the concentration of drugs was lower. When the drug was incubated with virus, the titer of virus decreased from 10 4.4TCID 50/ml to 10 2.8TCID 50/ml. In vitro 2019-nCoV virus culture experiment showed that the addition of the drugs reduced the cytopathy, and the logarithmic value of virus titer decreased by 40% -50%. Conclusion:In this study, in vitro inhibition experiments suggest that Niuhuang Qinggan capsule has the potential to inhibit the proliferation of 2019-nCoV. It can be used as a candidate drug to further verify the therapeutic effect of the 2019-nCoV acute respiratory disease.