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To characterize the epidemiological trends and sociodemographic variation of pediatric and adolescent neurological cancers by histological subtypes over time in the USA.A total of 16,511 patients aged 0-19 years diagnosed with neurological cancers between 2000 and 2018, including 13,024 with central nervous system (CNS) neoplasms and 3,487 with neuroblastomas, were identified from 18 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Incidence trends over time and incidence rate ratios by race/ethnicity, sex, and age were calculated for histological subtype. Age-standardized incidence rates (ASIR) by year of diagnosis and average annual percent changes (AAPC) were calculated to measure incidence rates. ASIR by race/ethnicity, sex, and age were calculated to examine the incidence variation by these factors.Overall, age-standardized annual incidence per 100,000 person-years increased from 2.20 in 2000 to 3.21 in 2018 with an AAPC of 1.4% (95% confidence interval or CI: 0.5% to 2.4%); however, that of Hispanic decreased from 2.93 in 2000 to 2.59 in 2018 with an AAPC of - 0.8% (95% CI: - 1.2% to - 0.3%). Non-Hispanic Black children and adolescents had a statistically significantly lower incidence than non-Hispanic White peers both for CNS neoplasms (incidence rate ratio or IRR: 0.67; 95% CI: 0.63 to 0.71) and neuroblastomas (IRR: 0.75; 95% CI: 0.68 to 0.83). Females generally had a lower incidence than males, especially among those with intracranial and intraspinal embryonal tumors (IRR: 0.69; 95% CI: 0.64 to 0.75). The highest incidence rate of neuroblastoma was among newborns aged less than 1 year, and the highest incidence rate of CNS neoplasms was among children aged 1-4 years.The incidence of neurological cancers has increased among children and adolescents from 2000 to 2018, with wide variation across demographic groups.

Purpose Protein tyrosine phosphatase receptor type T (PTPRT), which is a well‐known phosphatase and mutates frequently in melanoma and non‐small cell lung cancer (NSCLC). Our research aims to elucidate its mutation association with immune checkpoint inhibitors (ICI) efficacy. Methods We integrated whole‐exome sequencing (WES)‐based somatic mutation profiles and clinical characteristics of 631 melanoma samples received ICI agents from eight studies and 109 NSCLC samples from two studies. For validation, 321 melanoma and 350 NSCLC immunotherapy samples with targeted next‐generation sequencing (NGS) were employed. Besides, an independent NSCLC cohort contained 240 samples was also collected for further corroboration. Distinct immune infiltration was evaluated according to the PTPRT mutational status. Results In the WES melanoma cohort, patients with PTPRT mutations harbored a significantly elevated ICI response rate (40.5% vs. 28.6%, p = 0.036) and a prolonged survival outcome (35.3 vs. 24.9 months, p = 0.006). In the WES NSCLC cohort, the favorable response and immunotherapy survival were also observed in PTPRT‐mutated patients (p = 0.036 and 0.019, respectively). For the validation cohorts, the associations of PTRPT mutations with better prognoses were identified in melanoma, NSCLC, and pan‐cancer patients with targeted‐NGS (all p

The aim of the study was to assess the effectiveness of a combined treatment modality of salvage chemotherapy and pulmonary resection in chemo-resistant/relapsed gestational trophoblastic neoplasia (GTN) with lung metastasis and identify predictors of treatment failure. Data of patients with chemo-resistant/relapsed GTN with lung metastasis who received salvage chemotherapy combined with pulmonary resection were retrospectively analyzed. Among 134 included patients, the number of preoperative chemotherapy regimens ranged from 2–8 (median, 3), and courses ranged from 4–37 (median, 14). Pulmonary lobectomies, segmentectomies, wedge resections, and lobectomies plus wedge resections were performed in 84, 5, 35, and 10 patients, respectively. After completion of treatment, 130 (97.0%) patients achieved complete remission. In the entire cohort, the 5-year overall survival (OS) rate was 87.6%. OS rates were similar between stage III and stage IV disease cohorts (89.4% vs. 75.0%, p = 0.137). Preoperative β-human chorionic gonadotropin (β-hCG) levels > 10 IU/L (p = 0.027) and number of preoperative chemotherapy regimens > 3 (p = 0.018) were predictors of treatment failure. The combined treatment modality of salvage chemotherapy and pulmonary resection is effective in patients with chemo-resistant/relapsed GTN with lung metastasis, improving their prognoses. Patients with preoperative serum β-hCG >10 IU/L and those with >3 chemotherapy regimens preoperatively may not benefit from this multidisciplinary treatment.

Summary Background Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapy and antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGF receptor inhibitor) in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Methods This was a single-arm, open-label, phase 2 trial, done at a single tertiary health-care centre in Beijing, China. Women (18–70 years) with high-risk (International Federation of Gynecology and Obstetrics score ≥7) chemorefractory or relapsed gestational trophoblastic neoplasia who had received at least two lines of previously unsuccessful multidrug chemotherapy regimens and had an Eastern Cooperative Oncology Group performance status of 0–2 were eligible for inclusion. Patients received 4-week cycles of intravenous camrelizumab 200 mg every 2 weeks plus oral apatinib 250 mg once per day until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed according to serum human chorionic gonadotrophin concentration. Activity and safety were analysed in all patients who received at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov , NCT04047017 . Findings Between Aug 7, 2019, and March 18, 2020, 20 patients enrolled; 19 (95%) were diagnosed with choriocarcinoma and one (5%) had placental site trophoblastic tumour. The median follow-up duration was 18·5 months (IQR 14·6–20·9). The objective response rate was 55% (95% CI 32–77); ten (50%; 95% CI 27–73) patients had complete response. The most common grade 3 treatment-related adverse events were hypertension (five [25%] patients), rash (four [20%] patients), neutropenia (two [10%]), leukocytopenia (two [10%]), and aspartate aminotransferase increase (two [10%]). One patient had a treatment-related serious adverse event (aspartate aminotransferase 19-times higher than the upper limit of normal). No grade 4 or 5 treatment-related adverse events were reported. Interpretation Camrelizumab plus apatinib showed promising antitumour activity and acceptable toxicity and could be a salvage therapy option for the treatment of high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combined with chemotherapy for heavily-treated patients and upfront use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia are under investigation in phase 2 trials. Funding National Natural Science Foundation of China, Jiangsu Hengrui Pharmaceuticals.

Post-traumatic stress disorder (PTSD) is associated with traumatic stress experiences. This condition can be accompanied by learning and cognitive deficits, contributing to increased rates of disability in people with PTSD. Studies have shown that that ketamine can rapidly and significantly alleviate symptoms in patients with chronic PTSD. Nevertheless, the effects of ketamine on neurocognitive impairment and its mechanism of action in PTSD remain unclear. In this study, the gradient dose-related effects of ketamine (5, 10, 15, and 20 mg/kg, i.p.) on spatial and fear memory were evaluated in a rat model of single prolonged stress and electric foot shock (SPS&S). Expression levels of brain-derived neurotrophic factor (BDNF) and post-synaptic density-95 (PSD-95) in the hippocampus (HIP) and amygdala (AMG) were determined by Western blot analysis, immunohistochemistry, and quantitative real-time PCR assays. The data showed that rats subjected to SPS&S exhibited significant PTSD-like cognitive impairment.The effect of ketamine on SPS&S-induced neurocognitive function showed a U-shaped dose effect in rats. A single administration of ketamine at a dosage of 10 ~ 15mg/kg resulted in significant changes in behavioral outcomes. And these improvements in cognitive function and molecular changes were reversed at high doses (15 ~ 20mg/kg). Overall, Ketamine reversed SPS&S-induced fearand spatial memory impairment and down-regulation of BDNF and BDNF-related PSD-95 signaling in the HIP and AMG. And the dose of 15 mg/kg reversed behavioral and molecular changes rapidly, and promoted the amelioration of cognitive dysfunction. The enhanced association of BDNF signaling with PSD-95 influences could participate in the therapeutic efficiency of ketamine for PTSD.

ObjectionThe objective of this study was to assess attitudes towards the use of Traditional Chinese Medicine (TCM) for COVID-19 among Chinese immigrants in Canada during the early stage of the COVID-19 pandemic.MethodsA cross-sectional study was conducted in April 2020 in Canada. Individuals aged 16 or older who were of Chinese origin and living in Canada at the time of the survey were invited to participate in an online survey. Descriptive and univariate statistics were performed to describe participant attitudes towards various preventive and treatment measures for COVID-19. Multiple logistic regression was used to identify independent associations with sociodemographic factors and attitudes.ResultsA total of 754 eligible respondents were included in the analysis. 65.8% of the participants were female, 77.2% had a university degree or higher and 28.6% were 55 years of age or older. Overall, 48.8% of the study participants believed that TCM was effective in preventing COVID-19% and 46.2% would use TCM if they had COVID-19-related symptoms. However, the corresponding numbers for western medicine were 20.8% and 39.9%, which were statistically lower (pConclusionDespite the lack of scientific evidence to support its use, TCM was widely believed by Chinese immigrants in Canada to be an effective means of preventing COVID-19 and many also stated they would use it if they were experiencing symptoms of COVID-19.

Vitamin D, Ca and dairy products are negatively associated with colorectal cancer (CRC) incidence, but little is known of their influence on CRC survival. To investigate prediagnostic intakes of vitamin D, Ca and dairy products for their relevance to CRC prognosis, we analysed 504 CRC patients enrolled in the Newfoundland Colorectal Cancer Registry Cohort Study who were diagnosed for the first time with CRC between 1999 and 2003. Follow-up for mortality and cancer recurrence was through April 2010. Data on diet and lifestyle factors were gathered via a validated, semi-quantitative FFQ and a Personal History Questionnaire. Multivariate Cox models estimated hazard ratios (HR) and 95 % CI for the relationship of prediagnostic intakes of vitamin D, Ca and dairy products with all-cause mortality (overall survival, OS) and disease-free survival (DFS) among CRC patients. We found that prediagnostic Ca intake from foods, but not total Ca intake, was negatively associated with all-cause mortality (HR for Q2 v. Q1, 0·44; 95 % CI, 0·26, 0·75). An inverse relationship was also seen in a dose–response fashion for prediagnostic cheese intake (HR for Q4 v. Q1, 0·57, 95 % CI, 0·34, 0·95, Ptrend = 0·029). No evidence for modification by sex, physical activity, alcohol drinking and cigarette smoking was observed. In summary, high prediagnostic intakes of cheese and Ca from foods may be associated with increased survival among CRC patients. By manipulating diet, this study may contribute to the development of novel therapies that add to the armamentarium against CRC. Replication studies are required before any nutritional interventions are made available.

This study is intended to investigate oral exostoses of 5 sample populations, spanning over 6000 years, from the same region of Northern China, to determine the significance of sex and age on the development of oral exostoses during each time period. The samples analyzed were 306 dry jaws from human skeletons, which were excavated from 4 archeological sites: Banpo (6700-5600 y BP), Shaolingyuan (3000 y BP), Shanren (2200 y BP), and Chang'an (1000-1300 y BP), as well as the modern Xi'an district. The sex and the age of the samples at death were estimated. The degree of buccal exostosis (BE), torus mandibularis (TM), and torus palatinus (TP) and the TP shape were recorded. The results showed BEs in the Banpo and Chang'an regions, TMs in the Banpo region were more often diagnosed in males than in females. Conversely, females in Shaolingyuan showed a higher prevalence and severity of TM than that in males. The occurrence of BEs in the Shanren and Xi'an regions, TMs in the Banpo, Chang'an, and Xi'an regions, as well as TPs in the Banpo region significantly increased with age at death. In conclusion, sex differences and increasing trends with age in relation to oral exostoses were found in samples from Northern China during the past six millennia.

Although programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) have been successfully applied in the treatment of tumors, their efficiency is still not high enough. New immune targets need to be identified in order to seek alternative treatment strategies for patients with refractory tumors. Immune targets can be divided into stimulating and inhibiting molecules according to their function after receptor-ligand binding. We herein present a compendious summary of emerging immune targets in gynecologic tumors. These targets included coinhibitory molecules, such as T cell immunoglobulin-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte activation gene-3 (LAG-3), V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA), and B7-H3 and B7-H4, and co-stimulatory molecules, such as CD27, OX40, 4-1BB, CD40, glucocorticoid-induced tumor necrosis factor receptor (GITR) and inducible co-stimulator (ICOS). In this review, the characteristics and preclinical/clinical progress of gynecological malignancies are briefly discussed. However, the potential mechanisms and interactions of immune targets need to be elucidated in further studies.

Fuyan Shi,1 Chen Wang,2 Yujia Kong,1 Liping Yang,3 Juan Li,1 Gaopei Zhu,1 Jing Guo,4 Qingfeng Zheng,5 Bo Zhang,6 Suzhen Wang1 1Department of Health Statistics, School of Public Health, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China; 2Department of Computer Science, Rutgers University, Piscataway, NJ 08854, USA; 3Center for Health and Medicine, Xijing Hospital, an Affiliated Hospital of Air Force Military Medical University, Xi’an, Shannxi 710032, People’s Republic of China; 4Department of Health Policy and Management, School of Public Health, Peking University, Beijing 100191, People’s Republic of China; 5Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 6Department of Neurology and ICCTR Biostatistics and Research Design Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA, 02115, USACorrespondence: Bo Zhang; Suzhen Wang Email bo.zhang@childrens.harvard.edu; wangsz@wfmc.edu.cnObjective: To evaluate the survival benefit of surgery and radiation for hepatocellular carcinoma (HCC) after adjusting for patient-specific and tumor-specific factors.Methods: This study analyzed HCC patients who enrolled in the Surveillance, Epidemiology, and End Results (SEER) registry between January 2004 and December 2013. Of the 5552 HCC patients, 4597 received surgery and 955 received radiation. Patients who received radiation were further divided into 3 subgroups: 541 who received beam radiation (BR), 197 who received radioactive implants (RI), and 217 who received radioisotopes (RIT). Propensity score weighting analysis derived from generalized boosted models (GBMs) was performed to ensure well-balanced characteristics in all comparison groups.Results: Overall survival rates and HCC-specific survival rates were higher in those receiving surgery compared with those receiving radiotherapy. This was confirmed by Cox proportional hazard regression both before and after inverse probability of treatment weighting (IPTW). Before IPTW, the RIT group had a better outcome than the BR group in terms of overall and HCC-specific survival rates, but there was no significant difference between the RI and BR groups. After IPTW, Cox proportional hazard regression demonstrated that both the RIT and RI groups had higher survival rates than the BR group.Conclusion: In HCC patients, surgery was associated with higher survival rates compared with radiotherapy while adjusting for other factors. Among those who received radiotherapy, RIT and RI granted survival benefits.Keywords: hepatocellular carcinoma, survival analysis, propensity score, generalized boosted models, inverse probability of treatment weighting, Cox proportional hazard models

Objective We investigated the clinical characteristics, treatments, and survival of patients with gestational trophoblastic neoplasia (GTN) who experienced recurrence. Factors predictive of recurrence were also investigated. Methods Patients with GTN who recurred after completing chemotherapy at Peking Union Medical College Hospital Trophoblastic Disease Center were identified between January 2004 and December 2017. Logistic regression analysis was used to identify factors predictive of GTN recurrence. Results A total of 1827 patients with GTN achieved complete remission (CR) at our center, of whom 118 (6.5%) experienced recurrence during follow‐up. The recurrence rates for patients initially treated at our center and those referred to us were 2.7% and 14.6%, respectively. The majority of recurrent patients received floxuridine‐based multiagent chemotherapy (n = 64). Patients who underwent surgery achieved a significantly higher CR rate than those who did not (88.6% vs 61.1%, P = .001). Although 94.1% of recurrent patients reachieved CR, 33.3% of them recurred for a second time. The 5‐year survival rate of the entire cohort was 80.4%. An interval between antecedent pregnancy and chemotherapy >12 months (OR: 6.600, 95% CI [3.217‐13.540], P 14 weeks (OR: 2.226, 95% CI [1.080‐4.588], P = .030) were predictors of recurrence. Conclusions Patients with recurrent GTN are prone to recurring for a second time. Surgery plays a beneficial role in the management of recurrent GTN. An interval between antecedent pregnancy and chemotherapy >12 months, and an interval from first chemotherapy to achieving β‐hCG normalization >14 weeks were predictors of recurrence., The recurrence rate for patients with gestational trophoblastic neoplasia (GTN) was 6.5%, while the re‐recurrence rate for these recurrent patients increased to 33.3%. Surgery plays a beneficial role in the management of patients with recurrent GTN. An interval between antecedent pregnancy and chemotherapy >12 months, and an interval from first chemotherapy to achieving β‐human chorionic gonadotropin normalization >14 weeks were predictors of recurrence.

The function of the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and the expression of brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of post-traumatic stress disorder (PTSD). This study aims to explore the role of the HCN1 channel, BDNF, and mTOR in the actions of PTSD and to examine whether synaptic transmission or plasticity is involved in the regulation of this disease. In the present study, rats were exposed to the single prolonged stress and electric foot shock (SPS&S) procedure, which can induce PTSD-like behaviors in rats. ZD7288 was administered by intracerebroventricular (i.c.v.) injection to one experimental group to inhibit the function of the HCN1 ion channel while 8-Br-cAMP was administered to another group to activate the function of the HCN1 ion channel. A series of behavioral tests and biochemical assessments of certain proteins (HCN1, BDNF, and pmTOR) and synaptic ultrastructure in the prefrontal cortex (PFC) and hippocampus (Hip) were then conducted. The SPS&S procedure induced apparent PTSD-like symptoms in rats. The administration of ZD7288 reduced the immobility time and escape latency time in the forced swim test (FST) and water maze test (WMT) with a decreased level of HCN1, upregulated BDNF-mTOR signaling pathways in the PFC and Hip, and synaptic ultrastructure changes in the PFC. In contrast, the administration of 8-Br-cAMP, which led to a higher level of HCN1 in PFC and Hip, resulted in a decreased number of entries to the open arms without significant change in total arm entries in the elevated plus maze test (EPMT) as well as a shorter center square distance and total distance in the open field test (OFT). Extended escape latency time was also observed in the WMT although there was no alteration of BDNF-mTOR signaling pathways and synaptic ultrastructure in the PFC and Hip. Overall, the inhibition of HCN1, which can alleviate PTSD-like behavior of rats by relieving depression and improving learning ability, may be related to the upregulated BDNF-mTOR signaling pathways and synaptic transmission.

Aging has been demonstrated to play vital roles in the prognosis and treatment efficacy of cancers, including lung adenocarcinoma (LUAD). This novel study aimed to construct an aging-related risk signature to evaluate the prognosis and immunogenicity of LUAD. Transcriptomic profiles and clinical information were collected from a total of 2518 LUAD patients from 12 independent cohorts. The risk signature was developed by combining specific gene expression with the corresponding regression coefficients. One cohort treated with the immune checkpoint inhibitor (ICI) was also used. Subsequently, a risk signature was developed based on 21 aging-related genes. LUAD patients with low-risk scores exhibited improved survival outcomes in both the discovery and validation cohorts. Further immunology analysis revealed elevated lymphocyte infiltration, decreased infiltration of immune-suppressive cells, immune response-related pathways, and favorable ICI predictor enrichment in the low-risk subgroup. Genomic mutation exploration indicated the enhanced mutation burden and higher mutation rates in significantly driver genes of TP53, KEAP1, SMARCA4, and RBM10 were enriched in patients with a low-risk signature. In the immunotherapeutic cohort, it was observed that low-risk aging scores were markedly associated with prolonged ICI prognosis. Overall, the estimated aging signature proved capable of evaluating the prognosis, tumor microenvironment, and immunogenicity, which further provided clues for tailoring prognosis prediction and immunotherapy strategies, apart from promoting individualized treatment plans for LUAD patients.

Primary liver tumors are rare pediatric malignancies. Knowledge of the epidemiology of pediatric liver tumors is limited. This study aims to present the national incidence trends of pediatric liver tumors over 18 years, according to sociodemographic and histological subtype variation.The Surveillance, Epidemiology, and End Results registry was queried from 2000 to 2017 for 1,099 patients between ages 0 and 19 with liver tumors. Age-standardized incidence rates by age, sex, and race/ethnicity were examined among histological subtypes. Annual percentage change (APC) was calculated via joinpoint regression for various sociodemographic and histotype subgroups.An increase of age-adjusted incidence rate of pediatric hepatic cancers was observed between 2000 and 2017 (APC, 1.7% [95% confidence interval or CI: 0.6%-2.8%], p-value = 0.006), which may likely attribute to the increasing incidence of hepatoblastoma and mesenchymal tumors (APC, 2.5% [95% CI: 1.1%-3.8%], p-value = 0.001). The incidence trend of hepatocellular carcinoma remained stable in the study period. The non-Hispanic Asian/Pacific Islander children and adolescents had a higher risk of hepatic tumors (incidence rate ratio or IRR, 1.42 [95% CI: 1.16-1.72], p-value = 0.0007) when compared with the non-Hispanic white subgroup, while a non-Hispanic black child was associated with a lower incidence rate (IRR, 0.64 [95% CI: 0.50-0.80], p-value 0.0001). Significantly lower hepatic tumor incidence occurred in females than males, with an incidence rate ratio of 0.69 (95% CI: 0.61-0.78; p-value 0.0001). Hepatic tumor incidence was also significantly lower in those aged 1-4 years (IRR, 0.47 [95% CI: 0.40-0.54]; p-value 0.001) and 5-19 years (IRR, 0.09 [95% CI: 0.08-0.10]; p-value 0.001) when compared with the youngest age group aged less than 1 year. These significant differences were also detected for the subgroup of hepatoblastoma and mesenchymal liver tumors but less among hepatocellular carcinomas (all p-values less than 0.0001).Continued increasing incidence of pediatric hepatoblastoma and mesenchymal liver tumors was discovered and warranted further investigation. Additional findings include a lower incidence of hepatic cancer among non-Hispanic black individuals and higher incidence of hepatic cancer in non-Hispanic Asian/Pacific Islander, male, and aged 1-4-year children and adolescents.

Fatty acid synthase (FASN) acts as the central member in fatty acid synthesis and metabolism processes, which regulate oncogenic signals and tumor immunogenicity. To date, no studies have reported the connection of FASN mutations with ICI efficacy. In this study, from 631 melanoma and 109 NSCLC patients who received ICI treatments, we retrospectively curated multiomics profiles and ICI treatment data. We also explored the potential molecular biological mechanisms behind FASN alterations. In melanoma patients, FASN mutations were observed to associate with a preferable immunotherapeutic prognosis and response rate (both p < 0.01). These connections were further corroborated by the NSCLC patients (both p < 0.01). Further analyses showed that a favorable tumor immunogenicity and immune microenvironment were involved in FASN mutations. This work confirms the clinical immunotherapy implications of FASN mutation-mediated fatty acid metabolism and provides a possible indicator for immunotherapy prognosis prediction.

Background: Stroke has become one of the diseases with the highest mortality and disability rates in the world, especially in low-income and developing countries. Our objective was to discuss the relationship between the longitudinal dynamic changes of TG and stroke onset in healthy population by constructing different parametric joint models.Methods: 298 participants aged 23 to 69 in Xijing hospital of Xi’an City in Shanxi Province from 2008 to 2015 were included. The Cox proportional hazards model was performed to analyze the correlation between TG and stroke incidence at baseline. Different parameterized joint models were used to analyze the impact of dynamic changes of TG on the incidence of stroke under longitudinal data.Results: Of the 298 participants, a total of 70 (23.49%) subjects developed stroke during the study period. Cox proportional hazards model showed that the risk of disease increased by 1.056 times (95%CI=0.920-0.975) for each 1 unit of baseline age decrease. Each 1 mmol/L increase in sqrt(TG) increased the risk by 1.816 times (95%CI=1.017-3.245). Joint model showed that the risk of sqrt (TG) increased by 4.869 times (95%CI=3.987-8.857) for each 1 mmol/L increase in longitudinal direction.The lagged effects (HR=5.284, 95%CI=4.397-9.680) and cumulative effects (HR=1.786, 95%CI=1.613-3.399) of sqrt (TG) dynamic trajectory were also statistically related to the incidence of stroke.Conclusions: Over time, the longitudinal growth of TG levels in individuals will increase the risk of stroke even more. People should pay more attention to the dynamic changes of individual TG value, as well as the lagged effect and cumulative effect, to reduce the incidence of stroke.

Purpose The incidence of cervical cancer in young women is increasing. This study aimed to analyze the clinicopathological characteristics, treatment, and prognoses of women aged ≤25 years with cervical cancer. Patients and methods Medical record data of 60 cervical cancer patients aged ≤25 years treated at Peking Union Medical College Hospital between January 1986 and December 2017 were reviewed. The overall survival rate was estimated using the Kaplan-Meier method. Prognosis-related risk factors were analyzed using univariate and multivariate analyses. Results Among the 60 patients, 44 (73.3%) were diagnosed with cervical carcinoma and 16 (26.7%) with cervical sarcoma. In the cervical carcinoma group, the most common histology was squamous cell carcinoma (n=22, 50.0%) followed by adenocarcinoma (n=18, 40.9%). Notably, clear cell carcinoma dominated cervical adenocarcinomas at 61.1% (11/18). In the cervical sarcoma group, embryonal rhabdomyosarcoma comprised 50% of the cases (8/16). A total of eleven patients with cervical carcinoma underwent fertility-sparing surgeries, and the live birth rate approached 66.7%. The estimated 5-year overall survival rate of the entire cohort was 79.8% with no statistically significant difference between the carcinoma and sarcoma groups (74.3% vs 93.3%, P=0.14). Stage (RR 6.71, 95% CI 1.366-32.970, P=0.019) and lymph node metastasis (RR 9.09, 95% CI 1.050-78.732, P=0.045) were independent risk factors for poor prognosis in those young patients with cervical carcinoma. Conclusion Adenocarcinoma and sarcoma of the cervix comprise the majority of cervical cancer in young women; their overall prognoses are not worse than older patients; the survival rates tend to vary widely according to histologic subtypes.

Immune checkpoint inhibitors (ICIs) markedly promote the survival outcome of advanced melanoma and non-small cell lung cancer (NSCLC). Clinically, favorable ICI treatment efficacy is noticed only in a smaller proportion of patients. Heparan sulfate proteoglycan 2 (HSPG2) frequently mutates in both tumors. Herein, we aim to investigate the immunotherapeutic and immunological roles of HSPG2 mutations in melanoma and NSCLC. A total of 631 melanoma samples and 109 NSCLC samples with both somatic mutational profiles and clinical immunotherapy data were curated. In addition, by using The Cancer Genome Atlas data, genomic and immunological traits behind HSPG2 mutations were elucidated. Melanoma patients with HSPG2 mutations had a markedly extended ICI outcome than other patients. An association between HSPG2 mutations and the improved outcome was further confirmed in NSCLC. In addition, an elevated ICI response rate was presented in HSPG2-mutated NSCLC patients (81.8% vs. 29.7%, p = 0.002). Subsequent analyses revealed that HSPG2-mutated patients had a favorable abundance of response immunocytes, an inferior abundance of suppression immunocytes, enhanced mutational burden, and interferon response-relevant signaling pathways. We uncovered that HSPG2 mutations were predictive of a better ICI response and associated with preferable immunogenicity, which may be considered as a genomic determinant to customize biotherapy strategies.

Background 5-fluorouracil-based multiagent chemotherapy has been used as the primary treatment for high-risk gestational trophoblastic neoplasia (GTN) in China for a few decades. This study aims to assess the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who had International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. Materials and Methods A total of 207 patients with GTN who had FIGO scores ≥5 were treated with FAEV as first-line chemotherapy at Peking Union Medical College Hospital between January 2002 and December 2017. Complete remission (CR), resistance, survival, toxicity, and reproductive outcomes were analyzed. Results Of the 207 patients treated with FAEV, 9 (4.3%) required a change of chemotherapy owing to toxicity and 1 (0.5%) died of cerebral hernia 5 weeks after commencing treatment. The remaining 197 patients were assessable to determine the response to FAEV; among them, 168 (85.3%) achieved CR with FAEV and 29 (14.7%) developed resistance to FAEV. The 5-year overall survival rate of the entire cohort was 97.4%. Grade 3–4 neutropenia, thrombocytopenia, and anemia occurred in 28.4%, 6.8%, and 6.2% of cycles, respectively. No acute toxicity-related deaths occurred. Five patients developed acute myeloid leukemia 10–50 months after exposure to chemotherapy; another patient developed duodenal cancer 2 years after completing therapy. Sixty-one patients who preserved fertility wanted to become pregnant; 56 of them conceived. Conclusion The FAEV regimen is an effective primary treatment for patients with GTN who have FIGO scores ≥5 and has predictable and manageable toxicity. Implications for Practice The most commonly used multiagent chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) is etoposide, methotrexate and actinomycin D/cyclophosphamide and vincristine (EMA/CO) worldwide. However, 5-fluorouracil-based multiagent chemotherapy has been used as a primary treatment for high-risk GTN in China for a few decades. This study evaluated the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who have International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. The study's data demonstrated that FAEV as a primary treatment achieved favorable outcomes for patients with FIGO scores ≥5. Toxicities that result from the FAEV regimen are predictable and manageable. The FAEV regimen may provide another option for the treatment of GTN.

Background We investigated the accuracy and safety of a new HURWA robotic-assisted total knee arthroplasty (TKA) system in a sheep model. Methods Ten male Small-tailed Han sheep were used in this study. Sheep were imaged by computed tomography scan before and after bone resection and the cutting errors between actual bone preparation and preoperative planning of the femur and tibia in 3 dimensions were measured . Results The overall accuracies after surgery compared with that from preoperative surgical planning of the left and right femurs were 1.93±1.02° and 1.93±1.23°, respectively. Additionally, similarly high overall accuracies for the left and right tibia of 1.26±1.04 and 1.68±0.92°, respectively, were obtained. The gap distances of the distal cut, anterior chamfer, anterior cut, posterior chamfer, and posterior cut on the medial side were 0.47±0.35 mm, 0.41±0.37 mm, 0.12±0.26 mm, 0.41±0.44 mm, and 0.12±0.23 mm, respectively. No intraoperative complications, such as intraoperative fracture, massive bleeding or death, occurred CONCLUSION: This new HURWA robotic-assisted TKA system is an accurate and safe tool for TKA surgery based on the sheep model. This article is protected by copyright. All rights reserved.

Background : The impact of COVID-19 on the emotions and behaviors of overseas Chinese immigrants and their families living in Canada has been poorly studied. The purpose of this study was to describe the knowledge, protective behaviors, and psychological impact of COVID-19 on Chinese immigrants and determine whether having school-age children was associated with adverse psychological outcomes. Methods: Using an online survey of 757 Chinese immigrants in Canada from April 2020, data regarding the perceptions of COVID-19, psychological impact, protective behaviors, and sociodemographic characteristics were collected and analyzed. A total of 747 eligible respondents were finally included in the analysis. Most of the participants (65.8%) were female and 77.2% had a university degree or higher. Results: There were no significant differences in knowledge of COVID-19 in participants with or without children aged 16 years or under. Participants with children aged 16 years or under were more likely to perceive themselves as being at greater risk of contracting COVID-19 than those without (P=0.023). Participants with children aged 16 years and under were also more likely to feel depressed (P = 0.007) or stressed (P = 0.010). In addition, parents with children aged 16 years and under were more likely to adopt protective behaviors, for example, washing and sanitizing hands frequently or disinfecting work and living spaces. Conclusions: For the most part, Chinese immigrants with children aged 16 years and under were more prone to negative emotions, such as stress, anxiety, and fear. These findings may assist key stakeholders with the identification and implementation of policies and interventions to support the needs of parents with young children, during and after the COVID-19 pandemic.

Maternal separation (MS) causes long-lasting epigenetic changes in the brain and increases vulnerability to traumatic events in adulthood. Of interest, there may be sex-specific differences in these epigenetic changes. In this study, the extent of histone acetylation in the hippocampus (HIP) and the expression of BDNF were measured to determine whether BDNF influences risk of PTSD following MS in early life. Rat offspring were separated from their dams (3 h/day or 6 h/day from PND2~PND14). Then, pups were treated with a single prolonged stress (SPS) procedure when they reached adulthood (PND80). In animals stressed with the SPS procedure in adulthood, those that had increased MS intensity in childhood demonstrated more significant changes in performance on tests of anxiety, depression, and contextual fear memory. Reduced levels of total BDNF mRNA and protein were observed after SPS treatment and further declined in groups with greater MS time in childhood. Interestingly, these changes were correlated with decreased H3K9ac levels and increased HDAC2 levels. Additional MS also led to more severe ultrastructural synaptic damage in rats that experienced the SPS procedure, particularly in the CA1 and CA3 region of the HIP, reflecting impaired synaptic plasticity in these regions. Interestingly, male rats in the MS3h-PTSD group showed decreased anxiety, but no similar changes were found in female rats, suggesting a degree of gender specificity in coping with stress after mild MS. In summary, this study suggests that the epigenetic signatures of the BDNF genes can be linked to HIP responses to stress, providing insights that may be relevant for people at risk of stress-related psychopathologies.

Background This study investigated the beliefs about cancer treatment, outcomes, and screening among older adults ages 50–74 in Newfoundland and Labrador and whether these beliefs or sociodemographic factors were associated with differences in colorectal cancer (CRC) screening behavior. Methods This analysis uses data collected online survey of adults on cancer awareness and prevention in NL. Chi-square tests were used to assess whether there were differences in distributions of beliefs based on CRC screening behaviour. Logistic regression was used to identify sociodemographic factors independently associated with CRC screening behavior. Results Most people held positive beliefs about cancer outcomes and treatment, though only 57.36% ever had CRC screening. Interestingly, 56.5% of participants believed that cancer treatment is worse than cancer itself. However, no beliefs about cancer treatment and outcomes were associated with CRC screening behavior. People who never had CRC screening were more likely to believe that: their worries about what might be found would prevent them from screening (χ2 = 9.380, P = .009); screening is only necessary if they have symptoms (χ2 = 15.680, P χ2 = 6.824, P = .032). Similarly, people who never had CRC screening were less likely to believe that regular screening would give them a feeling of control over their health (χ2 = 12.255, P = .002). Logistic regression identified that men had higher odds of having had CRC screening than women in our study (OR(95% CI):1.689(1.135–2.515)), as did all other age groups compared to people ages 50–54. No differences were found in CRC screening behaviour based on ethnicity, BMI classification, geography, education, income, or history of cancer in self, or history of cancer in a first-degree relative. Conclusion Although the majority NL residents in our sample held positive beliefs towards cancer screening, treatment and outcomes, only just over half of participants have ever had CRC screening. This discordance should be investigated further. Participants with more negative beliefs about screening were more likely to have never participated in CRC screening. Our findings further suggest that NL’s CRC screening program is equitably reaching people from different socioeconomic backgrounds, though we observed a disparity in participation among genders in our sample.

The function of the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and the expression of brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of post-traumatic stress disorder (PTSD). This study aims to explore the role of the HCN1 channel, BDNF, and mTOR in the actions of PTSD and to examine whether synaptic transmission or plasticity is involved in the regulation of this disease. In the present study, rats were exposed to the single prolonged stress and electric foot shock (SPS&S) procedure, which can induce PTSD-like behaviors in rats. ZD7288 was administered by intracerebroventricular (i.c.v.) injection to one experimental group to inhibit the function of the HCN1 ion channel while 8-Br-cAMP was administered to another group to activate the function of the HCN1 ion channel. A series of behavioral tests and biochemical assessments of certain proteins (HCN1, BDNF, and pmTOR) and synaptic ultrastructure in the prefrontal cortex (PFC) and hippocampus (Hip) were then conducted. The SPS&S procedure induced apparent PTSD-like symptoms in rats. The administration of ZD7288 reduced the immobility time and escape latency time in the forced swim test (FST) and water maze test (WMT) with a decreased level of HCN1, upregulated BDNF-mTOR signaling pathways in the PFC and Hip, and synaptic ultrastructure changes in the PFC. In contrast, the administration of 8-Br-cAMP, which led to a higher level of HCN1 in PFC and Hip, resulted in a decreased number of entries to the open arms without significant change in total arm entries in the elevated plus maze test (EPMT) as well as a shorter center square distance and total distance in the open field test (OFT). Extended escape latency time was also observed in the WMT although there was no alteration of BDNF-mTOR signaling pathways and synaptic ultrastructure in the PFC and Hip. Overall, the inhibition of HCN1, which can alleviate PTSD-like behavior of rats by relieving depression and improving learning ability, may be related to the upregulated BDNF-mTOR signaling pathways and synaptic transmission.

To observe the clinical manifestations and salivary secretion of xerostomia patients in submariners who engaged in a three-month deployment. The general conditions and clinical examination of the 136 submariners were evaluated, by which the patients with xerostomia were screened out and their clinical manifestations were recorded. Besides, the flow rate of unstimulated saliva and stimulated saliva was measured and calculated. Subsequently, the related factors of xerostomia were quantitatively classified and statistically analyzed. In all the involved submariners, 42 were diagnosed to have xerostomia by physical examination after they returned from the task, among which 71.4% showed a decrease in unstimulated salivary flow rate and it was significantly correlated with the accompanying symptoms and their general conditions. Therefore, it was concluded that the occurrence of xerostomia could be related to the service life and job responsibilities of the submariners. The main manifestations were the reduction of unstimulated salivary secretion and the accompanying clinical symptoms such as cheilosis and angular cheilitis. Noticeably, the high psychological pressure and harsh living conditions need to be concerned, and further study should place more concentrations on these comprehensive influence factors and preventive actions of xerostomia.