A real-world observation on thrombopoietic agents for patients with cancer treatment-induced thrombocytopenia in China: A multicenter, cross-sectional study.

BACKGROUND: Studies on various thrombopoietic agents for cancer treatment-induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens. METHODS: In this retrospective, cross-sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL-11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO-RA). The outcomes, compliance, and safety of different treatments were analyzed. RESULTS: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL-11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL-11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy-induced thrombocytopenia (CIT) than rhIL-11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 109/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO-RA alone than with rhTPO and rhIL-11. CONCLUSIONS: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL-11, rhTPO, and TPO-RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding. PLAIN LANGUAGE SUMMARY: To provide an overview of the outcome of cancer treatment-induced thrombocytopenia in China, our cross-sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL-11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL-11.

Overexpression of TPD52L2 in HNSCC: prognostic significance and correlation with immune infiltrates.

BACKGROUND: Evidence has been presented that the tumor protein D52 (TPD52) family plays a critical role in tumor development and progression. As a member of the TPD52 family, the changes in TPD52L2 gene status are instrumental in kinds of cancer development. However, its effects on patient prognosis and immune infiltration in Head and Neck Squamous Carcinoma (HNSCC) are still poorly understood. METHODS: The Tumor Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and c-BioPortal database was used to explore the expression pattern, prognostic value, and variation of gene status in HNSCC. The LinkedOmics database was used to obtain the co-expression genes of TPD52L2 and identify the diagnostic value of TPD52L2 in HNSCC. The correlations between TPD52L2 expression and six main types of immune cell infiltrations and immune signatures were explored using Tumor Immune Estimation Resource (TIMER). The correlation between TPD52L2 expression and immune checkpoint genes (ICGs) was analyzed by TCGA database. Immunohistochemistry (IHC) was performed to validate the expression of three ICGs (PDL1, PDL2, EGFR) and TPD52L2 using 5 paired HNSCC and normal head and neck tissues. Polymerase Chain Reaction (PCR) and Western Blot (WB) of HNSCC and normal head and neck cell lines were performed to verify the high level of TPD52L2 mRNA and protein expression. protein expression of TPD52L2 in pan-cancer was also validated using UALCAN. RESULTS: TPD52L2 was overexpressed in tumor tissues, and it predicted worse survival status in HNSCC. ROC analysis suggested that TPD52L2 had a diagnostic value. Multivariate Cox analysis identified TPD52L2 as an independent negative prognostic marker of overall survival. Functional network analysis suggested that TPD52L2 was associated with immune-related signaling pathways, cell migration pathways, and cancer-related pathways. High expression of TPD52L2 was associated with a more mutant frequency of TP53. Notably, we found that the expression of TPD52L2 was closely negatively correlated with the infiltration levels of 15 types of immune cells and positively correlated with several immune markers. PCR, WB experiments, and UALCAN database verified the high level of TPD52L2 mRNA and protein expression. CONCLUSION: TPD52L2 is upregulated in HNSCC, which is an independent factor for adverse prognosis prediction. It probably plays a role in the negative regulation of immune cell infiltration. TPD52L2 might be a promising prognostic biomarker and therapeutic target in HNSCC.

Construction of the optimization prognostic model based on differentially expressed immune genes of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathology subtype of lung cancer. In recent years, immunotherapy, targeted therapy and chemotherapeutics conferred a certain curative effects. However, the effect and prognosis of LUAD patients are different, and the efficacy of existing LUAD risk prediction models is unsatisfactory. METHODS: The Cancer Genome Atlas (TCGA) LUAD dataset was downloaded. The differentially expressed immune genes (DEIGs) were analyzed with edgeR and DESeq2. The prognostic DEIGs were identified by COX regression. Protein-protein interaction (PPI) network was inferred by STRING using prognostic DEIGs with p value< 0.05. The prognostic model based on DEIGs was established using Lasso regression. Immunohistochemistry was used to assess the expression of FERMT2, FKBP3, SMAD9, GATA2, and ITIH4 in 30 cases of LUAD tissues. RESULTS: In total,1654 DEIGs were identified, of which 436 genes were prognostic. Gene functional enrichment analysis indicated that the DEIGs were involved in inflammatory pathways. We constructed 4 models using DEIGs. Finally, model 4, which was constructed using the 436 DEIGs performed the best in prognostic predictions, the receiver operating characteristic curve (ROC) was 0.824 for 3 years, 0.838 for 5 years, 0.834 for 10 years. High levels of FERMT2, FKBP3 and low levels of SMAD9, GATA2, ITIH4 expression are related to the poor overall survival in LUAD (p < 0.05). The prognostic model based on DEIGs reflected infiltration by immune cells. CONCLUSIONS: In our study, we built an optimal prognostic signature for LUAD using DEIGs and verified the expression of selected genes in LUAD. Our result suggests immune signature can be harnessed to obtain prognostic insights.

Moschamindole induces glioma cell apoptosis by blocking Mia40-dependent mitochondrial intermembrane space assembly and oxidative respiration.

Glioblastoma multiforme (GBM) is the most frequent, lethal, and aggressive tumor of the central nervous system in adults. In this study, we found for the first time that moschamindole (MCD), a rare phenolic amide with 8/6/6/5/5 rings, is a major bioactive constituent derived from Phragmites communis Trin (Poaceae) that exhibits a potential cytotoxic effect on both TMZ-resistant GBM cell lines and xenograft models. MCD-induced intrinsic apoptosis signals and mitochondrial dysfunction were confirmed by cell cycle arrest, caspase-3/7 activation, and membrane potential depolarization. Furthermore, investigations exploring the mechanism showed that MCD specifically inhibits Mia40-mediated oxidative folding of mitochondrial intermembrane space (IMS) proteins via PCR assay and immunoblot analysis. MCD relies on its positive charge to associate with mitochondrial oxidative respiration, thus blocking energy metabolism and inducing apoptosis. Overexpression and upregulation of Mia40 were proven to reverse MCD-induced apoptosis and were correlated with the chemoresistance of GBM in vitro and in vivo, respectively. Taken together, our study demonstrates that Mia40 is a potential target of the chemoresistance of glioblastoma and suggests that MCD might be a potential agent for the individualized treatment of chemoresistant GBM based on mitochondrial metabolic characteristics and Mia40 expression.

Effectiveness of WeChat for Improving Exclusive Breastfeeding in Huzhu County China: Randomized Controlled Trial.

BACKGROUND: The benefits of breastfeeding for both infants and mothers have been well recognized. However, the exclusive breastfeeding rate in China is low and decreasing. Mobile technologies have rapidly developed; communication apps such as WeChat (one of the largest social networking platforms in China) are widely used and have the potential to conveniently improve health behaviors. OBJECTIVE: This study aimed to assess the effectiveness of using WeChat to improve breastfeeding practices. METHODS: This 2-arm randomized controlled trial was conducted among pregnant women from May 2019 to April 2020 in Huzhu County, Qinghai Province, China. Pregnant women were eligible to participate if they were aged 18 years or older, were 11 to 37 weeks pregnant with a singleton fetus, had no known illness that could limit breastfeeding after childbirth, used WeChat through their smartphone, and had access to the internet. A total of 344 pregnant women were recruited at baseline, with 170 in the intervention group and 174 in the control group. Women in the intervention group received breastfeeding knowledge and promotion information weekly through a WeChat official account from their third month of pregnancy to 6 months postpartum. The primary outcome of exclusive and predominant breastfeeding rate was measured 0-1 month, 2-3 months, and 4-5 months postpartum. RESULTS: At 0-1 month postpartum, the exclusive breastfeeding rate was significantly higher in the intervention group than that in the control group (81.1% vs 63.3%; odds ratio [OR] 2.75, 95% CI 1.58-4.78; P<.001). Similarly, mothers in the intervention group were more likely to provide predominantly breast milk (OR 2.77, 95% CI 1.55-4.96; P<.001) and less likely to give dairy products to their children (OR 0.40, 95% CI 0.21-0.75; P=.005). There was no statistically significant difference for exclusive breastfeeding rate 2-3 months (P=.09) and 4-5 months postpartum (P=.27), though more children in the intervention group were exclusively breastfed than those in the control group 2-3 months postpartum (intervention: 111/152, 73.0%; control: 96/152, 63.2%) and 4-5 months postpartum(intervention: 50/108, 46.3%; control: 46/109, 42.2%). CONCLUSIONS: This study is the first effort to promote exclusive breastfeeding through WeChat in China, which proved to be an effective method of promoting exclusive breastfeeding in early life. WeChat health education can be used in addition to local breastfeeding promotion programs. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800017364; http://www.chictr.org.cn/showproj.aspx?proj=29325. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-019-7676-2.

The Rates and Medical Necessity of Cesarean Delivery in the Era of the Two-Child Policy in Hubei and Gansu Provinces, China.

OBJECTIVES: To describe the cesarean rates in different child policy periods and assess the medical necessity of cesareans during the 2-child policy period. METHODS: We collected hospital-level aggregate data on 93 745 deliveries and individual-level data on 27 977 deliveries from 6 hospitals in the Hubei and Gansu provinces of China from 2013 to 2016. Experts in gynecology and obstetrics assessed the medical necessity of 1024 randomly selected cesareans in 2016. RESULTS: The overall cesarean rate decreased significantly from 45.1% in the 1-child policy period (January 2013-September 2014) to 40.4% in the selective 2-child policy period (October 2014-July 2016) and further to 38.9% in the universal 2-child policy period (August 2016-December 2016). The rate of cesarean delivery on maternal request decreased by 46.3%, whereas the rate of cesarean delivery indicated by a previous cesarean delivery increased by 118.8% (P < .001). The experts assessed 222 (21.6%) cesareans as lacking medical necessity. CONCLUSIONS: The overall cesarean rate in Hubei and Gansu provinces decreased after the implementation of the 2-child policy, and one fifth of cesareans might be nonessential.

PKM2 promotes stemness of breast cancer cell by through Wnt/ß-catenin pathway.

Metastasis is one of the main causes of breast cancer (BCa)-related deaths in female. It has been reported that cancer stem cell played an important role in metastasis. Here we first revealed a specific role of pyruvate kinase isozymes M2 (PKM2) in the stemness of breast cancer cells. Breast cancer tissue analysis confirmed the upregulation of PKM2 in breast cancer, and high PKM2 levels were associated with poor prognosis of breast cancer patients. Holoclone assay and colony formation assay significantly elucidated the role of PKM2 in the self-renewal of breast cancer cells. Moreover, PKM2 elevated the proportion of stem cell and the ability of sphere formation in breast cancer cells. PKM2 played its functional role in stemness by regulating ß-catenin. Collectively, we identified critical roles of PKM2 in the stemness of breast cancer cells which may elevate the therapeutic effect on breast cancer patients.

[Analysis of quality of life and its influencing factors among MSM].

OBJECTIVE: To investigate the quality of life ( QOL) and its influencing factors among men who have sex with men ( MSM) in Chongqing city. METHODS: Snowball sampling and internet investigation techniques were applied to recruit MSM and 803 MSM in Chongqing were collected. The WHOQOL-BREF and SSRS questionnaire were used among MSM. RESULTS: Scores of the physiological domain, psychological domain, social relation domain, environmental domain and total score of QOL were (14. 03 +/- 2. 14) (13.38 +/- 2.44), (13.45 +/- 2.88), (12.52 +/- 2.48) and (13.29 +/- 2.05), respectively. Except for the environmental domain, scores of other domains of MSM were lower than that of common residents. The factors of social support and the domains of the quality of life were positive correlation. The multivariate analysis indicated that the main factors involved in influenced the QOL of the MSM were monthly income and scores of total social support. Frequency of condom, objective support, presence of regular homo-sex partners, the number of friends in gay circles, presence of regular sexual partner, the situation of only child,utilization of support, profession, knowing the VCT or not,native place had impacts on a few domains of the QOL. CONCLUSION: According to different demographic characteristics, and combining HIV health education and psychological intervention is helpful to improve the quality of life among MSM.

The Accumulative Effect of Multiple Postnatal Risk Factors with the Risk of Being Overweight/Obese in Late Childhood.

Most past studies focused on the associations of prenatal risk factors with the risks of childhood overweight/obesity. Instead, more postnatal risk factors are modifiable, with less knowledge of their cumulative effects on childhood obesity. We analyzed data of 1869 children in an Australian birth cohort. Key postnatal risk factors included: maternal and paternal overweight/obesity during the child's infancy, tobacco exposure, low family socioeconomic score, breastfeeding duration < 6 months, early introduction of solid foods, and rapid weight gain during infancy. The risk score was the sum of the number of risk factors. The primary outcome is overweight/obesity in late childhood (11-12 years); secondary outcomes are high-fat mass index (FMI), body fat percentage (BF%), and waist-to-height ratio (WHtR). Poisson regression models were used in the analyses. Children with higher risk scores had higher risks of overweight/obesity (p-for-trends < 0.001). After adjusting covariates, compared with those with 0-1 risk factors, children with 4-6 risk factors had 4.30 (95% confidence interval: 2.98, 6.21) times higher risk of being overweight/obesity; the relative risks for high FMI, BF%, and WHtR were 7.31 (3.97, 13.45), 4.41 (3.00, 6.50), and 6.52 (3.33, 12.74), respectively. Our findings highlighted that multiple postnatal risk factors were associated with increased risks of being overweight/obesity in late childhood.

Associations of BMI growth rates and body composition with cardiometabolic risks in Chinese preschool children.

OBJECTIVE: To examine the relationship between body mass index (BMI) growth rates, body composition, and cardiometabolic markers in preschool children. METHODS: Three-year-old children were recruited for this cohort study. BMI and body composition measurements were obtained at enrollment, with multiple BMI measurements spanning ages 1 month to 3 years extracted from medical records. Levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-cholesterol (non-HDL-C), remnant cholesterol (RC), uric acid (UA), and fasting plasma glucose (FPG) were measured at 3 years. Data analyses employed piecewise linear mixed models and logistic regression models. RESULTS: Out of 3822 children recruited, 3015 were included in the analysis. The accelerated zBMI growth rate between 6 and 24 months was positively correlated with high TG and LDL-C levels, with sex, birthweight, and size-for-gestational age disparities. Obesity increased the risks of high TG level and the highest RC quartile in boys. Fat mass index (FMI) and percentage of fat mass (FM%) were linked with high UA level and dyslipidemia, particularly high TG and non-HDL-C levels, in boys. Fat-free mass index (FFMI) showed negative associations with high levels of TC and non-HDL-C in boys and high LDL-C level in girls (P<0.05). CONCLUSIONS: This study underscores the significant impact of BMI growth rates and body composition on cardiometabolic markers in 3-year-old children. The effects of BMI growth rates in specific periods varied by sex, birthweight, and size-for-gestational age, and boys exhibiting a higher susceptibility to adverse outcomes.

Adenylate kinase 4 promotes neuronal energy metabolism and mitophagy in early cerebral ischemia via Parkin/PKM2 pathway.

Mitochondrial dysfunction is closely related to brain injury and neurological dysfunction in ischemic stroke. Adenylate kinase 4 (AK4) plays a critical role in energy metabolism and mitochondrial homeostasis. However, the underlying mechanisms remain unclear. In the present study, we demonstrated an important role of AK4 in mitochondrial dysfunction in the early cerebral ischemia. Early focal cerebral ischemia induced decrease of AK4 protein expression in ischemic hemispheric brain tissue in mice. Exposure of cultured primary neuron to oxygen-glucose deprivation (OGD) also induced AK4 downregulation. Overexpression of AK4 in neuron using adeno-associated virus (AAV-AK4) in mice promoted neuronal survival reflected by decreased infarction volume and TUNEL staining. AK4 overexpression inhibited mitochondrial decline and downregulation of energy metabolism-associated proteins (p-AMPK and ATP1A3) induced by MCAO. Moreover, AK4 knock-in using lentivirus carried AK4 vector (LV-AK4) induced energy metabolism shift from glycolysis to oxidation in neuron. Using transmission electron microscope and western blot, we revealed that AK4 overexpression promoted mitophagy and mitophagy-associated proteins expression PINK1 and Parkin after MCAO. Mass spectrometry and co-immunoprecipitation revealed an interaction between AK4 and PKM2. Mechanistically, AK4 indirectly decreased PKM2 expression via enhancing its ubiquitination by increasing the interaction between PKM2 and its ubiquitin E3 ligase Parkin, and inhibits Parkin downregulation. In conclusion, our data demonstrate that AK4/ Parkin /PKM axis prevents cerebral ischemia damage via regulation of neuronal energy metabolism model and mitophagy. AK4 was a new target for intervention of early ischemic neuron injury.

Body mass index growth trajectories and body composition influencing factors: An ambidirectional preschooler cohort.

OBJECTIVES: The purpose of the present study was to explore the latent growth trajectory of body mass index (BMI) from birth to 24 months and comprehensively analyze body composition development influencing factor in preschool children. METHODS: This ambidirectional cohort study was conducted in Tianjin, China, from 2017 to 2020, and children's regular medical check-up data from birth to 24 months were retrospectively collected. The growth models were used to fit BMI z-score trajectories for children aged 0-24 months. Crossover analysis and interaction model were used to explore the interaction of influencing factors. RESULTS: We analyzed the growth trajectories of 3217 children, of these, 1493 children with complete follow-up data were included in the influencing factors analysis. Trajectories and parental prepregnancy BMI (ppBMI) were independent factors influencing children's body composition. When paternal ppBMI ≥24 kg/m2, regardless of maternal ppBMI, the risk of overweight and obesity in senior-class children was increased. The high trajectories played a partial mediating role in the association between paternal ppBMI and body composition in preschool children. CONCLUSIONS: BMI growth in children aged 0-24 months can be divided into three latent trajectories: low, middle, and high. These trajectories and parental ppBMI were independent and interactive factors influencing children's body composition. The high trajectories played a partial mediating role in the association between paternal ppBMI and body composition in preschool children. It is necessary to pay attention to the BMI growth level of children aged 0-24 months, which plays an important role in the development of body fat in the future.

Associations of Obstructive Sleep Apnea Risk with Obesity, Body Composition and Metabolic Abnormalities in School-Aged Children and Adolescents.

The objective of this study is to explore the associations between obesity, body composition, and the self-reported risk of obstructive sleep apnea (OSA) and to examine whether the risk of OSA is related to metabolic abnormalities in children and adolescents aged 6-17 years. Utilizing data from the 2022 to 2023 Beijing Children and Adolescents Health Cohort baseline survey, 5000 school-aged participants were analyzed. OSA risk was assessed via the Pediatric Sleep Questionnaire, with anthropometric and body composition measurements taken. Metabolic markers included blood pressure, lipid levels, blood glucose, and uric acid. Associations were analyzed using logistic regression and generalized linear models. Results showed that 88.6% were low-risk and 11.4% were high-risk for OSA. Overweight (aOR 1.53, 95% CI 1.22-1.92), obesity (aOR 1.94, 95% CI 1.57-2.40), and abdominal obesity (aOR 1.59, 95% CI 1.31-1.93) significantly increased OSA risk. High fat mass was a critical factor, while muscle mass was not, especially in those who were overweight and obese. Associations of OSA risk with metabolic abnormalities were non-significant after adjusting for BMI. Our research highlights the significant associations of obesity and body composition with OSA risk, with child BMI influencing the relationship between OSA and metabolic abnormalities. Future research should explore causative relationships and the enduring impacts of OSA on metabolic health in children.

The association between cytomegalovirus infection and neurodegenerative diseases: a prospective cohort using UK Biobank data.

Background: Certain viral infections have been linked to the development of neurodegenerative diseases. This study aimed to investigate the association between cytomegalovirus (CMV) infection and five neurodegenerative diseases, spinal muscular atrophy (SMA) and related syndromes, Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and disorders of the autonomic nervous system (DANS). Methods: This prospective cohort included white British individuals who underwent CMV testing in the UK Biobank from January 1, 2006 to December 31, 2021. A Cox proportional hazard model was utilized to estimate the future risk of developing five neurodegenerative diseases in individuals with or without CMV infection, adjusted for batch effect, age, sex, and Townsend deprivation index in Model 1, and additionally for type 2 diabetes, cancer, osteoporosis, vitamin D, monocyte count and leukocyte count in Model 2. Bidirectional Mendelian randomization was employed to validate the potential causal relationship between CMV infection and PD. Findings: A total of 8346 individuals, consisting of 4620 females (55.4%) and 3726 males (44.6%) who were white British at an average age of 56.74 (8.11), were included in this study. The results showed that CMV infection did not affect the risk of developing AD (model 1: HR [95% CI] = 1.01 [0.57, 1.81], P = 0.965; model 2: HR = 1.00 [0.56, 1.79], P = 0.999), SMA and related syndromes (model 1: HR = 3.57 [0.64, 19.80], P = 0.146; model 2: HR = 3.52 [0.63, 19.61], P = 0.152), MS (model 1: HR = 1.16 [0.45, 2.97], P = 0.756; model 2: HR = 1.16 [0.45, 2.97], P = 0.761) and DANS (model 1: HR = 0.65 [0.16, 2.66], P = 0.552; model 2: HR = 0.65 [0.16, 2.64], P = 0.543). Interestingly, it was found that participants who were CMV seronegative had a higher risk of developing PD compared to those who were seropositive (model 1: HR = 2.37 [1.25, 4.51], P = 0.009; model 2: HR = 2.39 [1.25, 4.54], P = 0.008) after excluding deceased individuals. This association was notably stronger in males (model 1: HR = 3.16 [1.42, 7.07], P = 0.005; model 2: HR = 3.41 [1.50, 7.71], P = 0.003), but no significant difference was observed in the female subgroup (model 1: HR = 1.28 [0.40, 4.07], P = 0.679; model 2: HR = 1.27 [0.40, 4.06], P = 0.684). However, a bidirectional Mendelian randomization analysis did not find a genetic association between CMV infection and PD. Interpretation: The study found that males who did not have a CMV infection were at a higher risk of developing PD. The findings provided a new viewpoint on the risk factors for PD and may potentially influence public health approaches for the disease. Funding: National Natural Science Foundation of China (81873776), Natural Science Foundation of Guangdong Province, China (2021A1515011681, 2023A1515010495).

CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line.

BACKGROUND: Gastric cancer is a common and highly lethal malignancy in the world, but its pathogenesis remains elusive. In this study, we focus on the biological functions of CDK-associated Cullin1 (CAC1), a novel gene of the cullin family, in gastric cancer, which may help us to further understand the origin of this malignancy. METHODS: The AGS and MGC803 gastric cancer cell lines and the GES-1 gastric mucosa cell line were selected for study. At first, CAC1 expressions of those cell lines were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blot examinations, then CAC1 small interfering RNA (CAC1-siRNA) were designed and transfected into the AGS cell line with a relatively high level of CAC1. Once CAC1 was silenced, a series of biological characteristics of AGS cells such as cell proliferation, cell cycle, apoptosis, and expressions of apoptosis-related genes (P53, BCL2 and BAX) were determined by MTT, flow cytometry, qRT-PCR and western blot, respectively. RESULTS: CAC1 expression of AGS or MGC803 was much higher than that of GES-1. After CAC1 expression was effectively depressed by RNA interference in AGS cells, significant cell growth inhibition occurred. Furthermore, the proportion of cells treated with CAC1-siRNA increased in the G1 phase and decreased in the S phase, indicative of G1 cell cycle arrest. More importantly, the proportions of early/late apoptosis in AGS cells were enhanced with cis-diaminedichloroplatinum (cisplatin, CDDP) treatment, but to a higher extent with cisplatin plus CAC1-siRNA. Interestingly, BCL2 mRNA copies showed about a 30% decrease in the cisplatin group, but dropped by around 60% in the cisplatin plus CAC1-siRNA group. Conversely, the P53 mRNA expressions obtained nearly a two-fold increase in the cisplatin group, in addition to a five-fold increase in the cisplatin plus CAC1-siRNA group, and the BAX mRNA levels had almost a two- and four-fold augmentation, respectively. Meanwhile, P53, BAX and BCL2 showed the same alteration patterns in western blot examinations. CONCLUSIONS: CAC1 can promote cell proliferation in the AGS gastric cancer cell line. Moreover, it can prevent AGS cells from experiencing cisplatin-induced apoptosis via modulating expressions of P53, BCL2 and BAX.

HNF4G accelerates glioma progression by facilitating NRP1 transcription.

Hepatocyte nuclear factor 4γ (HNF4G) is considered to be a transcription factor and functions as an oncogene in certain types of human cancer. However, the precise functions and the potential molecular mechanisms of HNF4G in glioma remain unclear. Therefore, the present study aimed to elucidate the role of HNF4G in glioma and the underlying mechanism. Western blotting and reverse transcription-quantitative PCR (RT-qPCR) demonstrated that HNF4G was highly expressed in glioma tissues and cell lines. The overexpression of HNF4G in LN229 and U251 glioma cells promoted cell proliferation and cell cycle progression, and inhibited apoptosis, while the knockdown of HNF4G suppressed cell proliferation, cell cycle progression and tumor growth, and induced apoptosis. A significant positive association was detected between HNF4G and neuropilin-1 (NRP1) mRNA expression in glioma tissues. Bioinformatics analysis, chromatin immunoprecipitation-RT-qPCR and promoter reporter assays confirmed that HNF4G promoted NRP1 transcription in glioma by binding to its promoter. NRP1 overexpression facilitated glioma cell proliferation and cell cycle progression, and suppressed apoptosis in vitro, while the knockdown of NRP1 inhibited cell proliferation and cell cycle progression, and facilitated apoptosis. NRP1 overexpression reversed the effects induced by HNF4G knockdown on glioma cell proliferation, cell cycle progression and apoptosis. In summary, the present study demonstrated that HNF4G promotes glioma cell proliferation and suppresses apoptosis by activating NRP1 transcription. These findings indicate that HNF4G acts as an oncogene in glioma and may thus be an effective therapeutic target for glioma.

Impact of Early Life Factors on Metabolic Phenotypes of Obesity in Preschool Children.

OBJECTIVE: To investigate the impact of factors in the first 1,000 days of life on metabolic phenotypes of obesity in preschool children in a cohort study. RESEARCH DESIGN AND METHODS: We recruited 3-year-old children for the study. Early life factors included maternal age at delivery, maternal education, prepregnancy BMI, gestational weight gain, gravidity, history of gestational diabetes mellitus, delivery mode, gestational age, family history of metabolic disorders, paternal education, annual family income, child sex, birth weight, and breastfeeding duration. According to BMI and metabolic status, children were classified as metabolically healthy (no metabolic risk factors) with normal weight (MHNW), metabolically unhealthy (one or more metabolic risk factors) with normal weight (MUNW), metabolically healthy with overweight or obesity (MHO), and metabolically unhealthy with overweight or obesity (MUO). RESULTS: We recruited 3,822 children for the study, with 3,015 analyzed. Accelerated BMI z score growth rate between 6 and 24 months was associated with MHO (ß = 0.022; 95% CI 0.009, 0.036) and MUO (ß = 0.037; 95% CI 0.018, 0.056). Maternal overweight (odds ratio [OR] 3.16; 95% CI 1.55, 6.42) and obesity (OR 8.14; 95% CI 3.73, 17.76) before pregnancy and macrosomia (OR 2.47; 95% CI 1.32, 4.59) were associated with MHO, and maternal obesity before pregnancy (OR 6.35; 95% CI 2.17, 18.52) increased the risk of MUO. CONCLUSIONS: Early life factors, such as maternal obesity and accelerated BMI growth rate between 6 and 24 months, were related not only to MHO but also to MUO. Children with these early life factors should be given interventions for weight control to prevent metabolic abnormalities.

Effectiveness and safety of human type 5 recombinant adenovirus (H101) in malignant tumor with malignant pleural effusion and ascites: A multicenter, observational, real-world study.

BACKGROUND: The aim of this study was to analyze the effectiveness and safety of H101 in Chinese patients with malignant pleural effusion and ascites (MPE/MA) in the real world. METHODS: This multicenter, observational, real-world study recruited patients with MPE/MA caused by malignant tumor receiving H101-containing treatment between January 2020 and June 2022. Effectiveness was evaluated by overall remission rate (ORR), and safety was evaluated based on adverse events (AEs). Subgroup analysis was performed on patients grouped according to tumor type, the volume of MPE and MA, and dosage of H101. RESULTS: A total of 643 eligible patients were enrolled, and 467 received H101 monotherapy and 176 received H101 combined with chemotherapy. The ORR of total patients was60.3% with 388 case of PR. In the H101 monotherapy group, the decrease of MPE or MA was achieved in 282 (60.4%, PR) patients, 176 (37.7%, NC) patients showed no change in volume of MPE or MA, and nine (1.9%, PD) patients showed an increase, yielding an ORR of 60.4% (282/467). The ORR for the combination therapy group was 60.2% (106/176), with 106 cases of PR, 69 cases of NC and one case of PD. Subgroup analyses based on tumor type, volume of MPE and MA, and dosage of H101 all showed high ORR, approximately 60%. The main AEs associated with H101-containing regimens were fever, nausea and vomiting. No serious AEs occurred in both groups. CONCLUSION: Encouraging clinical benefits and manageable toxicity of H101 against MPE/MA were preliminarily observed in the real-world clinical setting, indicating that the H101-containing regimen is reliable, safe, and feasible, providing a novel and effective option for the treatment of this disease.

A comparison of bioelectrical impedance analysis and air displacement plethysmography to assess body composition in children.

Background: Accurate assessment of body composition (BC) is important to investigate the development of childhood obesity. A bioelectrical impedance analysis (BIA) device is portable and inexpensive compared with air displacement plethysmography (ADP) for the assessment of BC and is widely used in children. However, studies of the effectiveness of BIA are few and present different results, especially in pediatric populations. The aim of this study was to evaluate the agreement between BIA and ADP for estimating BC. Methods: The BC of 981 Chinese children (3-5 years) was measured using the BIA device (SeeHigher BAS-H, China) and ADP (BOD POD). Results: Our results showed that BIA underestimated fat mass (FM) and overestimated fat-free mass (FFM) in normal weight children (P < 0.05), but the opposite trend was shown in children with obesity (P < 0.05). The agreement between FM and FFM measured by the two methods was strong (CCC > 0.80). The linear regression equation of 5-year-old children was constructed. Conclusion: The SeeHigher BAS-H multi-frequency BIA device is a valid device to evaluate BC in Chinese preschool children compared with ADP (BOD POD), especially in 5-year-old children or children with obesity. Further research is needed to standardize the assessment of BC in children.

Validation of different personalized risk models of chemotherapy-induced nausea and vomiting: results of a randomized, double-blind, phase III trial of fosaprepitant for cancer patients treated with high-dose cisplatin.

BACKGROUND: Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis. The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid malignant tumors, determine risk factors and externally validate different personalized risk models for CINV. METHODS: This phase III trial was designed to test the non-inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single-day cisplatin chemotherapy. The primary endpoint was complete response (CR) during the overall phase (OP) with a non-inferiority margin of 10.0%. Logistic regression models were used to assess the risk factors of CR and no nausea. To validate the personalized risk models, the accuracy of the risk scoring systems was determined by measuring the specificity, sensitivity and area under the receiver operating characteristic (ROC) curve (AUC), while the predictive accuracy of the nomogram was measured using concordance index (C-index). RESULTS: A total of 720 patients were randomly assigned. CR during the OP in the fosaprepitant group was not inferior to that in the aprepitant group (78.1% vs. 77.7%, P = 0.765) with a between-group difference of 0.4% (95% CI, -5.7% to 6.6%). Female sex, higher cisplatin dose (≥ 70 mg/m2 ), no history of drinking and larger body surface area (BSA) were significantly associated with nausea. The AUC for the acute and delayed CINV risk indexes was 0.68 (95% CI: 0.66-0.71) and 0.66 (95% CI: 0.61-0.70), respectively, and the C-index for nomogram CINV prediction was 0.59 (95% CI, 0.54-0.64). Using appropriate cutoff points, the three models could stratify patients with high- or low-risk CINV. No nausea and CR rate were significantly higher in the low-risk group than in the high-risk group (P < 0.001). CONCLUSIONS: Fosaprepitant-based triple prophylaxis demonstrated non-inferior control for preventing CINV in patients treated with cisplatin-base chemotherapy. Female cancer patients without a history of alcohol consumption, with larger BSA and received high-dose cisplatin might be more vulnerable to CINV. Three personalized prediction models were well-validated and could be used to optimize antiemetic therapy for individual patients.