A significant relationship is present between childhood hunger experiences (CHEs) and health, but explorations of the longitudinal persistence of this relationship and its mediating mechanisms are still lacking. This study aims to evaluate the effects of CHEs on health in middle and old age and determine the underlying mechanisms. Using data from the five 2011—2020 China Health and Retirement Longitudinal Study (CHARLS) and the 2014 China Life History Survey Questionnaire, a sample of 9,909 individuals aged 45 years and older who participated in all six surveys was obtained. We conducted panel analyses, used Probit and ordinary least squares regression models to analyze the effects of CHEs on the health in middle and old age, and used stepwise regression tests to analyze the mediators of the relationship. CHEs significantly predicted self-assessment of health (β = −0.18; 95

BackgroundCervical cancer treatments, including radical hysterectomy and chemoradiotherapy, often lead to urinary, anorectal, and sexual dysfunctions. Nerve-sparing radical hysterectomy (NSRH) aims to reduce such complications, but evidence on long-term quality of life (QoL) remains limited.ObjectiveTo compare QoL outcomes in cervical cancer survivors after NSRH, conventional radical hysterectomy (CRH), or concurrent chemoradiotherapy (CCR).MethodsA cross-sectional study enrolled 427 patients (241 NSRH, 60 CRH, 126 CCR) aged ≤60 years with ≥6 months post-treatment follow-up. QoL was assessed using EORTC QLQ-C30/CX24, Female Sexual Function Index (FSFI), and a self-reported questionnaire. Statistical analyses included ANOVA and chi-square tests.ResultsUrinary symptoms occurred in 27.4% (NSRH), 40.0% (CRH), and 18.6% (CCR) (*p*=0.004). Anorectal symptoms were reported in 23.2% (NSRH), 25.0% (CRH), and 18.6% (CCR) (*p*=0.360). Among sexually active patients, FSFI total scores were higher in NSRH (23.8) vs. CRH (23.3) and CCR (21.6) (*p*=0.026). NSRH also showed superior sexual desire, arousal, and orgasm scores. QoL scores (EORTC QLQ-C30/CX24) indicated better outcomes in constipation (*p*=0.003), lymphedema (*p*<0.001), and sexual activity (*p*=0.027) for NSRH. Subgroup analysis confirmed NSRH alone had fewer complications than NSRH with adjuvant radiation.ConclusionNSRH demonstrates significant advantages in preserving urinary, anorectal, and sexual functions, thereby improving QoL compared to CRH or CCR. It is a preferable option for early-stage cervical cancer, particularly in younger patients.

ObjectiveRecent studies investigated that triglyceride glucose (TyG) index and triglyceride (TG) are associated with an elevated likelihood of developing and worsening chronic kidney disease (CKD). We aimed to evaluate the correlation between the TyG index and TG with lupus nephritis (LN), respectively, and explore its value in monitoring LN.Methods1,192 Systemic Lupus Erythematosus (SLE) patients were involved in this cross-sectional investigation. The presence or absence of LN was used to divide the individuals involved into two distinct categories. Multivariate logistic regression, restricted cubic spline, and subgroup analyses were applied to explore the connection between the TyG index and TG with LN, respectively.ResultsAccording to the study, the TyG index and TG were dose-dependently positively correlated with LN. After accounting for additional factors, each standard deviation of an upsurge in the TyG index and TG corresponded to a higher risk for LN by 36.4 and 34%, respectively. Besides, the adjusted ORs (with 95% CIs) for LN were precisely 1.625 (1.097, 2.405) and 1.756 (1.193, 2.585) when comparing the highest tertile to the lowest tertile of the TyG index and TG, respectively. Additionally, both TyG index and TG were significantly positively correlated with LN in age and body mass index (BMI) subgroups, and these two indicators were independently associated with LN in female SLE patients but not in male SLE patients, respectively.ConclusionBoth the elevated TyG index and TG were linked to LN on their own and gender disparity in SLE patients, which suggests that the TyG index and TG could be beneficial in the early screening for those with LN.

Icaritin (ICA) is a prenylflavonoid natural product extracted from plants of the Epimedium genus. The approval of ICA softgel capsules as a class 1.2 traditional Chinese medicine (TCM) innovative drug represents a major advancement offering a novel therapeutic approach for patients with advanced hepatocellular carcinoma (HCC). Class 1.2 TCM innovative drugs generally denote extracts and formulations derived from single plants, animals, minerals, or other substances. ICA exhibits diverse pharmacological effects, encompassing anti-inflammatory, immune-regulatory, anti-oxidation, anti-osteoporosis, anti-depression, and notably anti-cancer properties. This review presents a comprehensive overview of the molecular mechanisms underlying the anti-cancer properties of ICA, and further highlights recent progress in use of ICA in cancer research, discusses present challenges, and examines potential opportunities for ICA application and further development.

Tuberculosis remains a public health concern, and electronic monitors show promise in improving treatment adherence and health outcomes among patients with tuberculosis. This Review aims to provide a comprehensive understanding of the implementation barriers and facilitators of electronic monitors for patients with tuberculosis, by use of an implementation science framework. A literature search was done across Ovid MEDLINE, CINAHL, Embase, Cochrane Library, Web of Science, and Global Health databases from their inception to April 25, 2024. Studies reporting on the barriers and facilitators of electronic monitors among patients with tuberculosis were included and study characteristics and evidence were tabulated. Implementation factors were synthesised applying the updated Consolidated Framework for Implementation Research framework. This Review was registered with PROSPERO (CRD42023395747). Of 8816 records, 31 eligible studies were included. Barriers mainly included the information technology infrastructure, materials, and equipment resources, whereas facilitators included access to knowledge and information, communications, and reflecting and evaluating. Innovation design and patients' motivation were identified as both common barriers and facilitators. Inter-relationships between these factors were also explored. Cooperative and patient-centred efforts are required to address the barriers identified. Specific recommendations include improving education and training, eliminating stigma, and resolving technical challenges with feedback to boost patients' treatment adherence and outcomes.

Poor adherence to anti-tuberculosis treatment is a main threat for the treatment success. Digital health interventions such as electronic monitors (e-monitors) and the WeChat application (app) may improve treatment adherence in TB patients. The study aimed to examine the key facilitators, barriers, and drivers of barriers of implementing e-monitors and the WeChat app. Personal, semi-structured interviews with workers in healthcare institutions in three cities in Inner Mongolia were conducted between June and December 2023 when e-monitors and the WeChat app were introduced as part of a TB treatment strategy. The consolidated framework for implementation research (CFIR) was used to develop interview questions. A total of 143 healthcare workers were interviewed. The key facilitators included the e-monitors helped to improve medication adherence. Second, the intervention itself was cost-effective. Respondents took the initiative to learn about the intervention. Finally, the indicators were implemented through a top-down process, which increased the efficiency of the implementation of this policy decision. The key barriers were insufficient external financial incentives, available resources are inadequate in primary healthcare setting, negative attitudes of the implementers, a lack of feedback in implementation. Drivers of barriers included the values with limited utility of the intervention, rigid organizational administrative hierarchy, and rights and responsibilities mismatch. policymakers should pay attention to the barriers and its drivers to implementing the intervention. Adherence to patient-cantered, cultivate a teamwork atmosphere, and improve incentives and performance evaluation systems are necessary to improve the implementation of the intervention. ISRCTN15169616. Registered on 29 July 29, 2023

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Previous studies have indicated that various blood cell traits are associated with a higher risk of venous thromboembolism (VTE). However, the causal relationship remains uncertain. We collected data from the China pulmonary thromboembolism registry study and the China pulmonary health study, using propensity score matching and two-sample Mendelian randomization analyses with summary statistics from genome-wide association studies of blood cell traits and VTE in the East Asian population. Our findings revealed that platelet (PLT) count and hemoglobin (Hb) levels were significantly higher in VTE patients compared to the general population (p value <0.01). Genetically predicted Hb levels were positively associated with VTE, with an odds ratio (OR) of 2.38 (1.13-5.01), p value = 0.022. Similarly, genetically predicted PLT count was positively correlated with VTE, with an OR of 1.33 (1.02-1.74), p value = 0.038. These results suggest a causal relationship and potential targets for prevention.

Herbal plants that contain aristolochic acids (AAs) have been widely used for medicinal purposes for centuries. However, human exposure to AAs via herbal or dietary intake is thought to be a causative factor for aristolochic acid nephropathy (AAN), hepatotoxic effects, and carcinomas. At present, the molecular mechanisms underlying AA-induced hepatotoxicity and carcinogenesis and the corresponding detoxification strategies are unclear. This review summarizes the exposure, absorption, distribution, metabolism, and excretion (ADME) process of AAs. Importantly, to more objectively determine the emerging correlation between AAs and liver cancer, this review summarizes the possible direct and indirect connections between AAs and liver cancer. In brief, this review comprehensively summarizes and analyzes the molecular mechanisms underlying AA-induced hepatotoxicity and carcinogenesis, as well as an assessment of current detoxification strategies. At the same time, a new view on the prevention and detoxification of AA-induced hepatotoxicity is proposed. Chinese medicines that contain AAs might induce liver cancer but this is a controversial notion. This review summarizes relevant views from the past and provides novel insight into AA-induced liver injury or cancer to lay the foundation for AA detoxification.

Abstract Hyperuricemia as one of the key factors for gout, and quercetin could reduce the uric acid (UA) content. However, the mechanism of quercetin reduces UA content is still uncovered. Herein, we found quercetin can reduce UA content, induce antioxidant enzyme activity, inhibit the enzyme activity of xanthine oxidase (XOD) in hyperuricemia mice. Moreover, the UA reabsorption was also significantly reduced in the kidney and the kidney inflammation was alleviated by quercetin in hyperuricemia mice. Meanwhile, the protein level of ATP‐binding cassette super‐family G member 2 (ABCG2) was markedly induced and the protein levels of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were significantly repressed by quercetin in hyperuricemia mice and HK‐2 cells and by quercetin‐3‐O‐glucuronide in HK‐2 cells. Additionally, the docking mode indicated that quercetin is stable bound to the active site of XOD. Overall, the data reveal that quercetin alleviates hyperuricemia by repressing the activity of XOD, reducing the UA absorption via enhancing ABCG2 expression, and repressing URAT1 and GLUT9 expression.

BRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells. BRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 assay, Annexin V/PI staining and transwell assay. The concentrations of soluble cytokines were detected by ELISA. The membrane expression of immuno-modulatory molecules and the pattern of tumor infiltrating lymphocyte were evaluated by flow cytometry. The molecular mechanism was explored by RNA sequencing. Immunohistochemistry (IHC) staining was used for the detection of CD8α in tumor tissues. qRT-PCR and western blot were performed to assess the mRNA and protein expression. Anti-PD-L1 treatment and cytokines neutralization experiments were conducted in in vivo models. D594A mutant cells displayed lower grade malignancy characteristics than V600E (class I) and G469V (class II) mutant cells. Meanwhile, D594A mutation led to evident immuno-modulatory features including upregulation of MHC Class I and PD-L1. In vivo experiments displayed that the frequency of infiltrated CD8+ T cells was significantly high within D594A mutant tumors, which may provide potential response to anti-PD-L1 therapy. RNA sequencing analysis showed that D594A mutation led to enhanced expression of ATF3 and THBS1, which thus facilitated CXCL9 and CXCL10 production upon IFN-γ treatment. In addition, CXCL9 or CXCL10 neutralization reduced the infiltration of CD8+ T cells into THBS1-overexpressing tumors. D594A mutant CRC exhibited lower aggressiveness and immune-activated phenotype. ATF3-THBS1-CXCL9/CXCL10 axis mediated functional CD8+ T cells infiltration into the microenvironment of D594A mutant CRC. Our present study is helpful to define this mutation in CRC and provide important insights in designing effective immunotherapeutic strategies in clinic.

Background Tuberculosis (TB) has been regarded as ‘a relentless scourge’, increasing morbidity and mortality and burdening vulnerable populations. Poor adherence to TB treatment and ineffective traditional interventions hinders TB control. A novel TB approach called ‘electronic monitors’, equipping medication boxes with daily audio or visual reminders for electronically monitoring medication intake, seems promising in improving adherence and health outcomes and overcoming the weaknesses of traditional interventions. However, no review has systematically examined and synthesized the influencing factors of implementing electronic monitors. Implementation research offers the means to analyse the influencing factors of the implementation and its process, fitting well with the aim of this review. Therefore, the widely recognized Consolidated Framework for Implementation Research (CFIR), which offers a common taxonomy for evaluating intervention implementation, will be adopted to systematically identify barriers and facilitators of the electronic monitors for improving adherence and health outcomes in patients with TB. Methods and analysis The systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature research will be conducted in five electronic databases (Ovid MEDLINE, CINAHL, EMBASE, Cochrane Library and Web of Science) to identify the barriers and facilitators of implementing electronic monitors in patients with TB. The CFIR will be used as a guide for categorizing and synthesizing the barriers and facilitators. Study screening, data extraction, quality appraisal and data analysis will be conducted by two independent reviewers. The use of additional reviewers will solve any disagreements between the two reviewers. Discussion Given the increased prominence of TB epidemiology and the adherence problem of electronic monitors, there is a solid rationale for synthesizing the existing studies via the CFIR. The findings and conclusion of this review will lay bare the achievements and effectiveness of implementing electronic monitors, as well as the attendant gaps and limitations. Further strategies for facilitating the implementation of electronic monitors will also be explored. This review will be of essential significance for research and practice, supporting future academic research initiatives centred on patients with TB and aiding electronic monitor design in lowering the morbidity and mortality associated with TB disease. Trial registration number: PROSPERO: CRD42023395747.

Objectives Equity in health service utilisation is a central objective for health systems. Middle-aged and elderly patients with multiple chronic conditions (MCCs) are particularly vulnerable to healthcare inequity. This study aimed to update the information on the trends in the incidence and equity of outpatient health service utilisation (OHSU) and inpatient health service utilisation (IHSU) for middle-aged and elderly MCCs patients in China, identify socioeconomic determinants that may contribute to inequity, and suggest optimisation strategies to mitigate this disparity.Methods Panel data obtained from four waves of the China Health and Retirement Longitudinal Study (CHARLS) were used to determine the trends in OHSU and IHSU. The inequity in OHSU and IHSU was measured by the Concentration Index (CI) and Horizontal Inequity Index (HI), which is a valid measure of health service utilisation equity. The decomposition model of the CI was set up to explore the contribution of various determinants of overall equity.Results The annual rate of OHSU gradually decreased from 29.32% in 2011 to 27.27% in 2018. The HI remained positive and decreased from 0.0803 in 2011 to 0.0662 in 2018, indicating the existence of pro-rich inequity. The annual rate of IHSU gradually increased from 13.31% in 2011 to 19.89% in 2018. The HI remained positive and showed a declining trend from 0.2363 in 2011 to 0.0574 in 2018, evidencing pro-rich inequity; however, a trend towards the easing of inequity was observed.Conclusions Pro-rich inequity was present in both OHSU and IHSU among middle-aged and elderly MCCs patients in China. Economic status, area, education and age were the main contributors to pro-rich inequity. Concerted efforts are needed to allocate resources for mitigating health service utilisation inequity in middle-aged and elderly people with MCCs.

Background Catastrophic health expenditure (CHE) is an important indicator of measuring health inequality. Previous studies mainly focused on specific vulnerable populations rather than a wider range of vulnerable areas through panel data. Rural China is often associated with an underdeveloped economy and insufficient health resources. This study aims to update the information on the extent of and trends in the incidence and inequality of CHE among the households of rural China through longitudinal survey data. Methods Data were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS): 2013, 2015, and 2018. In total, 2,575 households were included in the analysis. CHE was defined as household health expenditures exceeding 40% of non-food expenditures. Inequality in CHE was measured using the concentration curve and concentration index. The contribution to CHE inequality was decomposed using the concentration index decomposition method. Results The incidence of CHE was 0.2341 (95% CI: 0.22, 0.25) in 2013, 0.2136 (95% CI: 0.20, 0.23) in 2015, and 0.2897 (95% CI: 0.27, 0.31) in 2018 in rural China. The concentration curve lay above the equality line, and the concentration index was negative: −0.1528 (95% CI: −0.1941, −0.1115) in 2013, −0.1010 (95% CI: −0.1442, −0. 0577) in 2015, and −0.0819 (95% CI: −0.1170, −0.0467) in 2018. Economic status, age, and chronic diseases were the main contributors to inequality in CHE. Conclusions The incidence of CHE in rural China displayed an upward trend from 2013 to 2018, although it was not continuous. Furthermore, a strong pro-low-economic inequality in CHE existed in rural China. Mainly economic status, age, and chronic diseases contributed to this pro-low-economic inequality. Health policies to allocate resources and services are needed to satisfy the needs of rural households and provide more accessible and affordable health services. More concern needs to be directed toward households with chronic diseases and older persons to reduce the incidence of CHE and promote health equality.

Improvement of glucose and insulin sensitivity remains an unmet medical need in diabetes management, in which the underlying cause of type 2 diabetes(T2D) was not well addressed by current treatment. We report the findings of a randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03173391) to evaluate the efficacy and safety of dorzagliatin, a dual-acting glucokinase (GK) allosteric modulator, which enhances the GK activity in T2D patients in a glucose dependent manner, and has demonstrated its effects in blood glucose control through improvement of glucose sensitivity in T2D patients. Eligible drug-naïve T2D patients (n=463) were randomly assigned to dorzagliatin group or placebo group in a 2:1 ratio for a 24-week double-blind treatment, then followed by a 28-week open-label treatment with dorzagliatin in all patients. The primary efficacy endpoint was the change from baseline in the glycated hemoglobin (HbA1c) level at week 24. Safety was assessed throughout the trial. At week 24, the change from baseline in HbA1c was -1.07% in the dorzagliatin group and -0.50% with placebo (ETD, -0.57%; 95%CI, -0.79 to -0.36; P<0.001), and the effects sustained through 52 weeks. Improvement of β-cell function was demonstrated by an increase of HOMA2-β in dorzagliatin group over placebo group (2.56 vs -0.72; 95% CI, 0.44 to 6.11; P<0.05) at week 24. The incidence of adverse events(AEs) was similar between the two groups during the 24 weeks and most AEs were mild during 52 weeks. There were no severe hypoglycemia events and drug related serious adverse events. The incidence of hypoglycemia was 1 of 310 patients (0.3%) in the dorzagliatin group during the 24 weeks. There was no body weight gain during the study period. In drug-naïve T2D patients, dorzagliatin demonstrated fast onset and sustained glycemic control with a good safety and tolerability profile for 52 weeks.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24-weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile (NCT03141073).

Abstract Background: Catastrophic health expenditure (CHE) is an important indicator for measuring health inequality. Previous studies mainly focused on whole populations rather than specific vulnerable groups through the regional survey or cross-sectional data. China’s rural area is often associated with an underdeveloped economy and insufficient health resources. This study aims to update the information on the extent and trends in incidence and inequality of CHE among the households of rural China through CHARLS panel data. Methods：Data were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS): 2013, 2015, and 2018. CHE was defined as the proportion of household health expenditures to the non-food expenditure more than 40% threshold. The inequality of CHE was measured by the concentration index. Decomposition methods were used to decompose the concentration index into its determining components. Results：The incidence of CHE was 23.41% (95% CI: 0.22, 0.25) in 2013, 21.36% (95% CI: 0.20, 0.23) in 2015 and 28.97% (95% CI: 0.27, 0.31) in 2018 in rural households. The concentration index was negative: -0.1528 (95% CI: -0.1941, -0.1115) in 2013, -0.1010 (95% CI: -0.1442, -0. 0577) in 2015 and -0.0819 (95% CI: -0.1170, -0.0467) in 2018. Economic status, age, and chronic disease were the main contributors to the inequality of CHE. Conclusions：The incidence of CHE in rural households of China displayed an upward trend. Furthermore, there existed a strong pro-poor inequality of CHE in rural China. Economic status, age, and chronic diseasewere the main contributors to the pro-poor inequality. Health policies to allocate resources and services are needed to satisfy the needs of rural households and provide more accessible and affordable health services. More concerns need to be directed toward households with chronic diseases and households with the elderly. Meanwhile, policymakers need to pay more attention to relieving the incidence of CHE and promoting health equality.

AIMS:To assess relationships between characteristics of methadone maintenance treatment and long-term cessation of injecting (> or = 1 year).DESIGN AND PARTICIPANTS:The incidence of cessation of injecting and relapse from non-injecting to injecting was estimated among 488 participants of the Amsterdam cohort study among drug users. We used a nested matched case-control design to identify methadone treatment characteristics significantly and independently related to cessation of injecting. To ensure detailed and valid assessment of methadone treatment, data of the Central Methadone Register were linked with cohort data. For 339 of 488 subjects of the initial study group methadone data were available.FINDINGS:The incidence of cessation of injecting increased from 2.2/100 person years in 1985-89 to 5.5/100 per year in 1995-97 (Ptrend = 0.005). Relapse to injecting was high: 17.2/100 person years (no trend). Methadone dosage and frequency of methadone programme attendance in themselves were not significantly related to cessation of injecting. However, an individual increase of 5 mg or more per year (OR 4.20, 95% CI 1.54-11.46) and receiving methadone mainly via the outpatient clinic for drug-abusing prostitutes and foreigners (OR 0.18, 95% CI 0.05-0.59) were independent predictors of cessation of injecting. After cessation of injecting, there were no HIV-seroconversions during the period of non-injecting (129 person years). After relapse to injecting there was one seroconverter; however, follow-up was small (23 person years). The HIV-incidence of those who continued injecting was 3.2/100 per year.CONCLUSIONS:Steadily increasing the methadone dosage in a harm reduction setting may be useful in supporting injecting drug users in the process of cessation of injecting and reducing the spread of HIV-infection.

The association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV- groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV- group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV- group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

Abstract Background This study aimed to explore the risk factors for lymph node metastasis (LNM) in patients with endometrial cancer (EC) and develop a clinically useful nomogram based on clinicopathological parameters to predict it. Methods Clinical information of patients who underwent staging surgery for EC was abstracted from Qilu Hospital of Shandong University from January 1st, 2005 to June 31st, 2019. Parameters including patient-related, tumor-related, and preoperative hematologic examination-related were analyzed by univariate and multivariate logistic regression to determine the correlation with LNM. A nomogram based on the multivariate results was constructed and underwent internal and external validation to predict the probability of LNM. Results The overall data from the 1517 patients who met the inclusion criteria were analyzed. 105(6.29%) patients had LNM. According the univariate analysis and multivariate logistic regression analysis, LVSI is the most predictive factor for LNM, patients with positive LVSI had 13.156-fold increased risk for LNM (95%CI:6.834–25.324; P < 0.001). The nomogram was constructed and incorporated valuable parameters including histological type, histological grade, depth of myometrial invasion, LVSI, cervical involvement, parametrial involvement, and HGB levels from training set. The nomogram was cross-validated internally by the 1000 bootstrap sample and showed good discrimination accuracy. The c-index for internal and external validation of the nomogram are 0.916(95%CI:0.849–0.982) and 0.873(95%CI:0.776–0.970), respectively. Conclusions We developed and validated a 7-variable nomogram with a high concordance probability to predict the risk of LNM in patients with EC.