A Novel Germline Mutation of BRCA1 and Integrated Analysis With Somatic Mutation in a Chinese Multi-Cancer Family.

The presence of mutations in the BRCA1 gene (MIM: 113705) is widely recognized as a significant genetic predisposition for ovarian cancer. This study investigated the genomic mutations in a Chinese family with a history of ovarian, breast, and rectal adenocarcinoma. A novel germline mutation (Phe1695Val) in BRCA1 was identified through whole-exome sequencing. Subsequently, we performed whole-genome sequencing to identify somatic mutations and analyze mutational signatures in individuals carrying the novel germline mutation. Our findings revealed a correlation between somatic mutational signatures and the BRCA1 germline mutation in the proband with ovarian cancer, while no such association was observed in the tumor tissue from the patient with breast cancer. Furthermore, distinct somatic driver mutations were identified, a truncated mutation in the TP53 gene in the ovarian tumor tissue, and a hotspot mutation in the PIK3CA gene in the breast cancer. According to our findings, the BRCA1 F1695V mutation is linked to ovarian cancer susceptibility in the family and causes specific somatic mutational profiles.

Cancer occurrence after SLE: effects of medication-related factors, disease-related factors and survival from an observational study.

OBJECTIVES: To explore the survival and risk factors for cancer occurrence after SLE (SLE-CA). METHODS: Patients with cancer diagnosed after SLE in Peking Union Medical College Hospital between January 2006 and September 2017 were recruited and followed. Data regarding medication-related and disease-related factors and survival were collected and compared with matched controls. Logistic regressions were applied to identify risk factors. The Kaplan-Meier method with a log-rank test was performed to evaluate survival. RESULTS: Forty-five SLE-CA patients and 128 controls were included, with the most common cancer site being the female genital system. SLE-CA patients were exposed to a higher cumulative dosage of CYC, with less mucocutaneous and haematologic involvement and higher anti-dsDNA positivity. At the time of cancer diagnosis, SLE-CA patients had lower SLEDAI 2000 (SLEDAI-2K), tended to achieve Definitions of Remission in SLE remission and minimal disease activity, but had higher SLICC/ACR Damage Index. Multivariable analysis identified high dosage of CYC [odds ratio (OR) 1.027, 95% CI 1.008, 1.046; P = 0.005] and low SLEDAI-2K at cancer diagnosis (OR 0.756, 95% CI 0.579, 0.986; P = 0.039) as risk factors. Mucocutaneous (OR 0.330, 95% CI 0.110, 0.991; P = 0.048) and haematologic involvement (OR 0.304, 95% CI 0.103, 0.902; P = 0.032) were negatively associated with cancer occurrence after SLE. The 5- and 10-year survival rates in SLE-CA patients were 95.2% and 92.1%, respectively. No significant difference of survival was observed between SLE-CA patients and controls (P = 0.177). CONCLUSION: High dosage of CYC and disease-related factors (low SLEDAI-2K, less mucocutaneous and haematologic involvement) were related factors for cancer occurrence after SLE, while no survival difference was observed.

The association of serum magnesium with infection in new-onset systemic lupus erythematosus patients.

OBJECTIVE: To assess the association of serum magnesium with infection in new-onset systemic lupus erythematosus (SLE) patients. METHODS: We conducted a single-center retrospective cohort study of new-onset SLE patients from 2012 to 2021. The hospitalized SLE patients were divided into infection and noninfection groups. Logistic regression analysis was conducted to examine the association of hypomagnesemia with infection. RESULTS: A total of 476 new-onset SLE patients were included, with 299 cases in the infection group and 177 cases in the noninfection group. The patients were mostly females (81.7%). The average age at diagnosis was 43.7 years. The median duration was 1.0 month. The prevalence of hypomagnesemia (<0.70), normomagnesemia (0.70-1.10), and hypermagnesemia (>1.10) in new-onset SLE patients was 14.3%, 83.4%, and 2.3%, respectively. The prevalence of hypomagnesemia was 18.4% in the infection group and 7.3% in the noninfection group (p = .001). The baseline value of serum magnesium was 0.819 mmol/L, with values of 0.799 mmol/L in the infection group and 0.854 mmol/L in the noninfection group (p = .000). The following clinical variables were significantly different between the two groups (p < .05): age, duration, hospitalization stay, fever, serositis, and SLE Disease Activity Index 2000 (SLEDAI 2K). The laboratory parameters, including hemoglobin, white blood cell count, albumin level, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and complement C3 were also significantly different between the two groups (p < .05). The mortality was 4.4% (21/476), with 20 cases occurring in the infection group. Logistic regression analysis showed that hypomagnesemia was associated with an increased risk of infection (p = .001) and poor prognosis (p = .015). CONCLUSION: Hypermagnesemia was rare in new-onset SLE patients. Hypomagnesemia was common and was associated with an increased risk of infection in new-onset SLE patients.

The impact of early-life antibiotics and probiotics on gut microbial ecology and infant health outcomes: a Pregnancy and Birth Cohort in Northwest China (PBCC) study protocol.

BACKGROUND: Unreasonable use of antibiotics and probiotics can alter the gut ecology, leading to antibiotic resistance and suboptimal health outcomes during early life. Our study aims are to clarify the association among antibiotic and probiotic exposure in early life, the microecology of the gut microbiota, and the development of antibiotic resistance; to investigate the long-term impact of antibiotics and probiotics on the health outcomes of infants and young children; and to provide a theoretical basis for the rational use of antibiotics and probiotics from a life course perspective. METHODS: The study is a prospective, longitudinal birth cohort study conducted in Shaanxi Province, China from 2018 to 2024. A total of 3,000 eligible mother-child pairs will be enrolled from rural, suburban, and urban areas. The recruitment of the participants begins at pregnancy, and the newborns will be followed up for 2 years at successive timepoints: within 3 days after birth, 42 days after birth, and at 3, 6, 12, 18, and 24 months of age. Sociodemographic data, environmental exposures, dietary patterns, psychological conditions, and medical and drug histories are collected. Cognitive and behavioural development among infants and young children and questionnaires on antibiotic knowledge and behaviour among caregivers will be collected at 12 and 24 months of age. The faecal samples are collected and analysed by 16S rRNA high-throughput sequencing and quantitative PCR (qPCR) for antibiotic resistance genes. DISCUSSION: The findings will inform antibiotic and probiotic use for pregnant women and infants and contribute to establishing rational use strategies of antibiotics and probiotics for paediatricians, health practitioners, and drug administration policy-makers. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Registry (ChiCTR) platform, http://www.chictr.org.cn (Record ID: ChiCTR2100047531, June 20, 2021).

Local treatment for triple-negative breast cancer patients undergoing chemotherapy: breast-conserving surgery or total mastectomy?

BACKGROUND: Because there is no exact therapeutic target, the systemic treatment of triple-negative breast cancer (TNBC) still relies on chemotherapy. In terms of local treatment, based on the highly malignant characteristics of TNBC, it is still uncertain whether patients should be given more aggressive local treatment. METHODS: This study was based on the SEER database. 13,262 TNBC patients undergoing chemotherapy were included. According to local treatment methods, patients were divided into breast-conserving surgery with radiotherapy (BCS + RT), total mastectomy alone and total mastectomy with radiotherapy (Mastectomy+RT). Kaplan-Meier survival analysis drew the survival curves of Overall Survival (OS) and Breast Cancer Specific Survival (BCSS), and Cox proportional risk regression models were used to analyze the impact of different local treatments on OS and BCSS. RESULTS: After adjusting confounding factors, Mastectomy alone group (HR = 1.57; 95%CI: 1.40-1.77) and Mastectomy+RT group (HR = 1.28; 95%CI: 1.12-1.46) were worse in OS than BCS + RT group, and Mastectomy+RT group (HR = 0.81; 95%CI: 0.73-0.91) was better in OS than Mastectomy alone group. The effect of local treatment for BCSS was similar to that of OS. After stratification according to age, tumor size and lymph node status, when the age was less than 55 years old, at T4, N2 or N3 category, there was no statistical significance between the BCS + RT group and the Mastectomy+RT group in OS or BCSS (all P > 0.05). When the age was less than 65 years old, at T1, T2 or N0 category, there was no statistical significance between the Mastectomy alone group and the Mastectomy+RT group in OS or BCSS (all P > 0.05). The results of other stratified analyses were basically consistent with the results of total population analysis. CONCLUSION: The survival benefit of breast-conserving surgery with radiotherapy was higher than or similar to that of total mastectomy TNBC patients.

Development and validation of nomograms for epithelial ovarian cancer: a SEER population-based, real-world study.

Aim: To develop and internally validate nomograms to predict the overall survival (OS) and the cancer-specific survival (CSS) of patients with epithelial ovarian cancer (EOC). Methods: A total of 9001 EOC patients diagnosed between 2010 and 2013 were randomly divided into the training (n = 6301) and validation (n = 2700) cohorts. Nomogram and bootstrap validation were used to assess the predictive values of the models, including discrimination, calibration and clinical benefit. Results: In the validation cohort, the concordance statistic values were 0.733 for OS and 0.747 for CSS. Calibration plots and decision curve analyses demonstrated moderate accuracy and clinical applicability. Conclusion: Nomograms were user-friendly tools for guiding clinical treatment and estimating prognosis.

Continuous Observation of Serum Total Magnesium Level in Patients Undergoing Hemodialysis.

BACKGROUND: Magnesium is an indispensable cation and plays an important physiological role in the body. Most previous studies focused on the single measurement of serum magnesium in patients undergoing hemodialysis. However, scant studies focused on continuous observations of serum magnesium levels. OBJECTIVE: To provide continuous observations of serum magnesium levels in patients on maintenance hemodialysis (MHD). The levels of magnesium in patients initiating hemodialysis are also recorded and analyzed in the present study. METHODS: In this retrospective study, we serially investigated the measurements of serum total magnesium in MHD patients and patients initiating hemodialysis. Our data were followed up for one year. We provided real-time update on the levels of serum magnesium in patients on hemodialysis. RESULTS: On January 1, 2019, a total of 356 end-stage renal disease patients were receiving hemodialysis in our hospital. On December 31, 2019, the number had increased to 383. We found that serum total magnesium levels were in the normal range before initiating hemodialysis. With the initiation of hemodialysis, the levels of serum total magnesium increased. In patients on MHD, hypermagnesemia was very common. Hypomagnesemia was rare when 0.5 mmol/L magnesium dialysate was used. We did not find proton pump inhibitor associated hypomagnesemia. CONCLUSION: We find that serum total magnesium levels are in the normal range before initiating hemodialysis. However, in patients on MHD, hypermagnesemia is common when 0.5 mmol/L magnesium dialysate is used. Hypomagnesemia is very rare. Hypomagnesemia in patients on MHD is an indicator of poor condition.

Anemia and associated factors among adolescent girls and boys at 10-14 years in rural western China.

BACKGROUND: Evidence on anemia and associated factors among young adolescent girls and boys in rural western China is limited. METHODS: We used data from a follow-up study of adolescents (10-14 years) born to women who participated in a randomized trial of antenatal micronutrient supplementation in western China. Anemia was defined by World Health Organization standards. Logistic regression was used to examine the factors associated with anemia. RESULTS: The overall prevalence of anemia was 11.7% (178/1517). Female adolescents were 1.73 (95% CI 1.21, 2.48) times more likely to have anemia as compared to males. Adolescents whose mothers had completed high school were 0.35 (95% CI 0.13, 0.93) times less likely to be anemic, compared to those of whom had < 3 years of formal education. Household wealth was also inversely associated with anemia. The association of puberty status with anemia was modified by adolescent sex (P-value for interaction was 0.04); males with greater than mild pubertal development had reduced odds (OR 0.35, 95% CI 0.15, 0.83) of anemia while there was no association among females (OR 0.72, 95% CI 0.29, 1.78). Consumption of flesh foods (OR 0.58, 95% CI 0.38, 0.89), eggs (OR 0.60, 95% CI 0.38, 0.93), and having a meal frequency of three times or more per day (OR 0.68, 95% CI 0.48, 0.96) were also associated with a lower likelihood of anemia. CONCLUSIONS: Anemia was a mild public health problem among young adolescents in rural western China. Nutritional and social determinants were identified as predictors, warranting interventions to reduce the risk of anemia among this critical age group.

Calculating the overall survival probability in patients with cervical cancer: a nomogram and decision curve analysis-based study.

BACKGROUND: Cervical cancer has long been a common malignance troubling women. However, there are few studies developing nomogram with comprehensive factors for the prognosis of cervical cancer. Hence, we aimed to build a nomogram to calculate the overall survival (OS) probability in patients with cervical cancer. METHODS: Data of 9876 female patients in SEER database and diagnosed as cervical cancer during 2010-2015, was retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression model were applied to select predicted factors and a nomogram was developed to visualize the prediction model. The nomogram was compared with the FIGO stage prediction model. Harrell's C-index, receiver operating curve, calibration plot and decision curve analysis were used to assess the discrimination, accuracy, calibration and clinical utility of the prediction models. RESULT: Eleven independent prognostic variables, including age at diagnosis, race, marital status at diagnosis, grade, histology, tumor size, FIGO stage, primary site surgery, regional lymph node surgery, radiotherapy and chemotherapy, were used to build the nomogram. The C-index of the nomogram was 0.826 (95% CI: 0.818 to 0.834), which was better than that of the FIGO stage prediction model (C-index: 0.785, 95% CI: 0.776 to 0.793). Calibration plot of the nomogram was well fitted in 3-year overall OS prediction, but overfitting in 5-year OS prediction. The net benefit of the nomogram was higher than the FIGO prediction model. CONCLUSION: A clinical useful nomogram for calculating the overall survival probability in cervical cancer patients was developed. It performed better than the FIGO stage prediction model and could help clinicians to choose optimal treatments and precisely predict prognosis in clinical care and research.

Changing trends of birth weight with maternal age: a cross-sectional study in Xi'an city of Northwestern China.

BACKGROUND: Most studies have shown that maternal age is associated with birth weight. However, the specific relationship between each additional year of maternal age and birth weight remains unclear. The study aimed to analyze the specific association between maternal age and birth weight. METHODS: Raw data for all live births from 2015 to 2018 were obtained from the Medical Birth Registry of Xi'an, China. A total of 490,143 mother-child pairs with full-term singleton live births and the maternal age ranging from 20 to 40 years old were included in our study. Birth weight, gestational age, neonatal birth date, maternal birth date, residence and ethnicity were collected. Generalized additive model and two-piece wise linear regression model were used to analyze the specific relationships between maternal age and birth weight, risk of low birth weight, and risk of macrosomia. RESULTS: The relationships between maternal age and birth weight, risk of low birth weight, and risk of macrosomia were nonlinear. Birth weight increased 16.204 g per year when maternal age was less than 24 years old (95%CI: 14.323, 18.086), and increased 12.051 g per year when maternal age ranged from 24 to 34 years old (95%CI: 11.609, 12.493), then decreased 0.824 g per year (95% CI: -3.112, 1.464). The risk of low birth weight decreased with the increase of maternal age until 36 years old (OR = 0.917, 95%CI: 0.903, 0.932 when maternal age was younger than 27 years old; OR = 0.965, 95%CI: 0.955, 0.976 when maternal age ranged from 27 to 36 years old), then increased when maternal age was older than 36 years old (OR = 1.133, 95%CI: 1.026, 1.250). The risk of macrosomia increased with the increase of maternal age (OR = 1.102, 95%CI: 1.075, 1.129 when maternal age was younger than 24 years old; OR = 1.065, 95%CI: 1.060, 1.071 when maternal age ranged from 24 to 33 years old; OR = 1.029, 95%CI: 1.012, 1.046 when maternal age was older than 33 years old). CONCLUSIONS: For women of childbearing age (20-40 years old), the threshold of maternal age on low birth weight was 36 years old, and the risk of macrosomia increased with the increase of maternal age.

Knowledge, attitude and practice level of women at the periconceptional period: a cross-sectional study in Shaanxi China.

BACKGROUND: Identifying and understanding the knowledge, attitude and practice (KAP) level of women at the periconceptional period has implications for formulating and measuring the adverse pregnancy outcomes for primary prevention. METHODS: A cross-sectional study among pregestational and pregnant women was conducted in Shaanxi during 2016-2017. RESULTS: Among 791 participants, the average score of periconceptional healthcare knowledge awareness was 6.32 ± 1.78, whereas 28.8% of women have failed. Women who planned to or had undergone premarital and pre-pregnancy examinations accounted for 50.2, and 62.5%, respectively. Less than half (42.0%) of the women started taking folic acid (FA) before pregnancy, and only 37.9% of them took FA regularly at the right time. Multivariate analysis showed that age was the main factor influencing the Attitude and Practice level of women at the periconceptional period, and demonstrated a positive effect on the awareness of right timing of folic acid supplementation, and high rates of premarital and pre-pregnancy examinations. Also, the knowledge pass rate was increased with education level. Fewer women who have birth experience were willing to take FA consistently at the right time compared to those women without birth. CONCLUSIONS: The women at the periconceptional period in Shaanxi lacked the total KAP level of periconceptional healthcare, especially those who live in rural areas and have less education. Government agencies should reinforce more effective primary preventive measures and policies for the prevention of adverse pregnancy outcomes.

High starchy food intake may increase the risk of adverse pregnancy outcomes: a nested case-control study in the Shaanxi province of Northwestern China.

BACKGROUND: There was a wider disparity in the diet characterization among most studies on diet and pregnancy outcomes in different countries, and the research in northern China is limited. Therefore, the purpose of the present study that was conducted in northwest China was to understand the dietary characteristics of periconceptional women and to explore the relationship between and specific dietary patterns with adverse pregnancy outcomes. METHODS: A nested case-control study was conducted from October 2017 to November 2018 in Shaanxi, China. Based on a prospective cohort of 368 women who were pregnant or prepared for pregnancy, 63 participants who developed the outcomes of gestational hypertension, gestational diabetes, preterm birth, low birth weight, and birth defects were included in the case group. A total of 237 healthy pregnant women were included during the same period in the control group. Dietary intake was assessed using a validated food frequency questionnaire for the three months before pregnancy and the first trimester. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records. Dietary patterns were derived using factor analysis. Stratified analysis was performed on the overall, single and multiple adverse pregnancy outcomes categories. Adjustment was made for sociodemographic characteristics and nutritional supplement status. RESULTS: Six major dietary patterns were identified. The 'starchy' dietary pattern, composed of high intake in noodle and flour products and/or rice and its products, was associated with the odds of developing of adverse pregnancy outcomes (OR: 2.324, 95% CI: 1.293-4.178). This risk remained significant following adjustment for potential confounders of maternal demographic characteristics and nutritional status (aOR: 2.337, 95% CI:1.253-4.331). Strong association were found during the first trimester of pregnancy, but showed no association during the three months before pregnancy (aOR:1.473, 95% CI: 0.682-3.234). CONCLUSIONS: High starchy food intake was associated with adverse pregnancy outcomes, particularly during the first trimester of pregnancy. Health education focusing on periconceptional dietary patterns could be a practical strategy for preventing adverse pregnancy outcomes.

Maternal exposure to PM2.5 may increase the risk of congenital hypothyroidism in the offspring: a national database based study in China.

BACKGROUND: Maternal exposure to air pollution is related to fetal dysplasia. However, the association between maternal exposure to air pollution and the risk of congenital hypothyroidism (CH) in the offspring is largely unknown. METHODS: We conducted a national database based study in China to explore the association between these two parameters. The incidence of CH was collected from October 1, 2014 to October 1, 2015 from the Chinese Maternal and Child Health Surveillance Network. Considering that total period of pregnancy and consequently the total period of particle exposure is approximately 10 months, average exposure levels of PM2.5, PM10 and Air Quality Index (AQI) were collected from January 1, 2014 to January 1, 2015. Generalized additive model was used to evaluate the association between air pollution and the incidence of CH, and constructing receiver operating characteristic (ROC) curve was used to calculate the cut-off value. RESULTS: The overall incidence of CH was 4.31 per 10,000 screened newborns in China from October 1, 2014 to October 1, 2015. For every increase of 1 µg/m3 in the PM2.5 exposure during gestation could increase the risk of CH (adjusted OR = 1.016 per 1 µg/m3 change, 95% CI, 1.001-1.031). But no significant associations were found with regard to PM10 (adjusted OR = 1.009, 95% CI, 0.996-1.018) or AQI (adjusted OR = 1.012, 95% CI,0.998-1.026) and the risk of CH in the offspring. The cut-off value of prenatal PM2.5 exposure for predicting the risk of CH in the offspring was 61.165 µg/m3. CONCLUSIONS: The present study suggested that maternal exposure to PM2.5 may exhibit a positive association with increased risk of CH in the offspring. We also proposed a cut-off value of PM2.5 exposure that might determine reduction in the risk of CH in the offspring in highly polluted areas.

The extent and nature of television food advertising to children in Xi'an, China.

BACKGROUND: To explore the extent and nature of television food advertising especially unhealthy food advertising to primary school children in Xi'an, China. METHODS: Television data were recorded for 2 weekdays and 2 weekend days between 6:00 and 22:00 during May and June in 2012 from a total of five television channels most popular with children in Xi'an. Pearson χ (2) tests and logistic regression were applied to determine differences in the proportion of healthy food, unhealthy food and miscellaneous food advertisements for different channels, programs, dates, viewing periods and the use of persuasive marketing tactics. RESULTS: Of the 5527 advertisements transcribed, 25.5 % were for food, among which 48.1 % were considered to be unhealthy. The frequency of food advertisements was 6 per hour per channel, including 3 unhealthy food advertisements. Compared with healthy and miscellaneous food advertisements, more unhealthy food advertisements were shown during afternoon, weekends and children's non-peak viewing times as well as on children's television channels, central television channels and non-children's programmes. Unhealthy foods contributed the highest proportion of all food advertisements containing promotional characters (51.7 %) and premium offers (59.1 %). Both promotional characters and premium offers appeared more on non-children's television channels. CONCLUSIONS: The majority of food advertisements were for unhealthy food. More unhealthy food ads were shown in children's non-peak time and afternoon as well as non-children's channels. More children-oriented persuasive marketing tactics were used in unhealthy food ads especially in non-children's channels. Therefore, intervening in the entrance of unhealthy foods into the market and establishing regulations related to food advertising especially unhealthy food advertisements are important strategies to prevent children's exposure to unhealthy food and childhood obesity.

Prenatal Micronutrient Supplementation Is Not Associated with Intellectual Development of Young School-Aged Children.

BACKGROUND: Micronutrient supplementation is often prescribed during pregnancy. The effects of prenatal iron and multimicronutrient supplementation on intellectual development in young school-aged children are less than clear. OBJECTIVE: The aim of this study was to examine the long-term effects of prenatal iron plus folic acid or multiple micronutrient (including iron and folic acid) supplementation vs. folic acid supplementation on the intellectual development of young school-aged children in rural China. METHODS: Young school-aged children (aged 7-10 y, n = 1744) of women who had participated in a trial of prenatal supplementation with various combinations of micronutrients and remained residents in 2 rural counties in China were followed. We measured their intellectual development by Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV). The WISC-IV generated the Full-Scale Intelligence Quotient (FSIQ), Verbal Comprehension Index (VCI), Working Memory Index (WMI), Perceptual Reasoning Index (PRI), and Processing Speed Index (PSI). Multilevel analyses were used to assess the effect of prenatal micronutrient supplementation on the intellectual development of children. RESULTS: The mean differences in FSIQ, VCI, WMI, PRI, and PSI, respectively, were not significant between prenatal folic acid supplementation and either iron plus folic acid [-0.34 (P = 0.65), -0.06 (P = 0.95), -0.22 (P = 0.76), -0.01 (P = 0.99), and -1.26 (P = 0.11)] or multimicronutrient [-0.39 (P = 0.60), -0.64 (P = 0.48), 0.11 (P = 0.87), -0.43 (P = 0.59), and -0.34; (P = 0.65)] supplementation after adjusting for confounders. CONCLUSIONS: There is no evidence to suggest a different effect on intellectual development between prenatal iron plus folic acid, multimicronutrient supplementation, and prenatal folic acid supplementation in children aged 7-10 y. This trial was registered at www.isrctn.com as ISRCTN08850194.

Famine exposure in early life increases risk of cataracts in elderly stage.

Background: Epidemiological studies have shown that early-life nutritional deficiencies are associated with an increased risk of diseases later in life. This study aimed to explore the correlation between famine exposure during the early stages of life and cataracts. Methods: We included 5,931 participants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2018 cross-sectional data in our study. Subjects were categorized into three groups by their age during the famine: adulthood group, school age famine exposure group, and teenage famine exposure group. Utilizing binary logistic regression models, we investigated the relationship between early-life famine exposure and cataracts. Results: Compared to the adulthood group, both the school age exposure group (OR = 2.49, 95%CI = 1.89-3.27) and teenage exposure group (OR = 1.45, 95%CI = 1.20-1.76) had a heightened risk of developing cataracts in elderly stage. And the sex differences in the impact of famine during early years on elderly cataract risk were observed, particularly indicating a higher risk among women who experienced childhood famine compared to men with similar exposure. Conclusion: Famine exposure during the early stages of life is associated with a heightened risk of developing cataracts in old age. To prevent cataracts in elderly individuals, particularly in females, measures should be taken to address nutritional deficiencies in these specific periods.

Identification of SUMOylation-related signature genes associated with immune infiltration in ulcerative colitis through bioinformatics analysis and experimental validation.

OBJECTIVE: Ulcerative colitis (UC) is a chronic inflammatory disorder challenging to diagnose clinically. We focused on identifying and validating SUMOylation-related signature genes in UC and their association with immune infiltration. METHODS: Five eligible gene expression profiles were selected from the Gene Expression Omnibus (GEO) database and merged into a single dataset comprising 260 UC patients and 76 healthy controls (HC). Differentially expressed genes (DEGs) were identified, and these were intersected with SUMOylation-related genes to obtain differentially expressed SUMOylation-related genes (DESRGs). Next, we identify the signature genes and validate them through comprehensive analyses employing GO, KEGG, GSVA, Lasso-cox regression, ROC curves, and clustering analysis. The infiltrating immune cells were analyzed using the CIBERSORT algorithm and Pearson correlation analysis. Finally, in vitro and in vivo experiments validated the identified signature genes. RESULTS: PALMD, THRB, MAGED1, PARP1, and SLC16A1 were identified. Next, an excellent predictive model for UC was established and distinct subgroups of patients associated with SUMOylation were identified. Moreover, the NF-κB signaling pathway likely plays a pivotal role in the regulation of SUMOylation in UC. Additionally, we validated that the alterations in PALMD, THRB, and MAGED1 expression in LPS-induced Caco-2 cells concurred with our bioinformatics findings, particularly demonstrating statistically significant differences in PALMD and THRB expression. Finally, in a DSS-induced mouse colitis model, we observed a significant upregulation of PALMD expression. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation. CONCLUSION: This study comprehensively elucidates the biological roles of SUMOylation-related genes in UC, identifying PALMD, MAGED1, THRB, PARP1, and SLC16A1 as signature genes that represent promising biomarkers for UC diagnosis and prognosis.

From structural design to delivery: mRNA therapeutics for cancer immunotherapy.

mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence-known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen-presenting cells (APCs) can synthesize mutant neo-antigens and multi-antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T-cell receptor (TCR), CD134, and immune-modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large-scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA-based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA-based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA-based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA-based cancer immunotherapy are also discussed.

Near-infrared AIEgens with high singlet-oxygen yields for mitochondria-specific imaging and antitumor photodynamic therapy.

AIE-active photosensitizers (PSs) are promising for antitumor therapy due to their advantages of aggregation-promoted photosensitizing properties and outstanding imaging ability. High singlet-oxygen (1O2) yield, near-infrared (NIR) emission, and organelle specificity are vital parameters to PSs for biomedical applications. Herein, three AIE-active PSs with D-π-A structures are rationally designed to realize efficient 1O2 generation, by reducing the electron-hole distribution overlap, enlarging the difference on the electron-cloud distribution at the HOMO and LUMO, and decreasing the ΔEST. The design principle has been expounded with the aid of time-dependent density functional theory (TD-DFT) calculations and the analysis of electron-hole distributions. The 1O2 quantum yields of AIE-PSs developed here can be up to 6.8 times that of the commercial photosensitizer Rose Bengal under white-light irradiation, thus among the ones with the highest 1O2 quantum yields reported so far. Moreover, the NIR AIE-PSs show mitochondria-targeting capability, low dark cytotoxicity but superb photo-cytotoxicity, and satisfactory biocompatibility. The in vivo experimental results demonstrate good antitumor efficacy for the mouse tumour model. Therefore, the present work will shed light on the development of more high-performance AIE-PSs with high PDT efficiency.

How the marketing practices of commercial milk formula companies impact infant breastfeeding practices in China.

BACKGROUND: The marketing practices used by commercial milk formula (CMF) companies undermine breast feeding. However, it remains unclear how specific types of marketing practices result in suboptimal breast feeding. OBJECTIVES: We aimed to examine the associations of CMF marketing practices with breastfeeding outcomes, determine the influencing pathways, how it changes the perceptions and attitudes of mothers towards CMF, and how it impacts breastfeeding outcomes. METHODS: A cross-sectional survey was conducted in Beijing and Jinan, China that mapped the CMF marketing practices in 2020. Mothers were interviewed about the feeding practices for the youngest child under the age of 18 months. Maternal attitude towards CMF was assessed using a set of five questions. Six common CMF marketing practices were reviewed. A logistic regression was performed to examine the associations between the CMF marketing practices and predominant breast feeding, with adjustments for maternal age, education, occupation, socioeconomic class and caesarean section. Furthermore, a path analysis was conducted to explore the pathways between the CMF marketing practices, maternal attitude towards CMF and predominant breast feeding. RESULTS: A total of 750 mothers were interviewed, with 20.0% of mothers predominantly breast feeding their young children. Two marketing practices, online engagement with CMF companies and promotions and discounts, were statistically associated with a lower likelihood of predominant breast feeding, with an adjusted ORs of 0.53 (95% CI 0.35 to 0.82) and 0.45 (95% CI 0.22 to 0.92). Furthermore, per CMF marketing practice increase mothers concurrently exposed to was associated with a 0.79 (95% CI 0.68 to 0.92) times lower likelihood of predominant breast feeding. In addition, online engagement and free formula samples distributed in hospitals had indirect effects on suboptimal breastfeeding outcomes, which was partly mediated by positive maternal attitude towards CMF. CONCLUSIONS: CMF marketing practices were associated with a lower likelihood of optimal breastfeeding through influencing the maternal attitude towards CMF.