Vulnerable brain regions in adolescent major depressive disorder: A resting-state functional magnetic resonance imaging activation likelihood estimation meta-analysis.

BACKGROUND: Adolescent major depressive disorder (MDD) is a significant mental health concern that often leads to recurrent depression in adulthood. Resting-state functional magnetic resonance imaging (rs-fMRI) offers unique insights into the neural mechanisms underlying this condition. However, despite previous research, the specific vulnerable brain regions affected in adolescent MDD patients have not been fully elucidated. AIM: To identify consistent vulnerable brain regions in adolescent MDD patients using rs-fMRI and activation likelihood estimation (ALE) meta-analysis. METHODS: We performed a comprehensive literature search through July 12, 2023, for studies investigating brain functional changes in adolescent MDD patients. We utilized regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) analyses. We compared the regions of aberrant spontaneous neural activity in adolescents with MDD vs healthy controls (HCs) using ALE. RESULTS: Ten studies (369 adolescent MDD patients and 313 HCs) were included. Combining the ReHo and ALFF/fALFF data, the results revealed that the activity in the right cuneus and left precuneus was lower in the adolescent MDD patients than in the HCs (voxel size: 648 mm3, P < 0.05), and no brain region exhibited increased activity. Based on the ALFF data, we found decreased activity in the right cuneus and left precuneus in adolescent MDD patients (voxel size: 736 mm3, P < 0.05), with no regions exhibiting increased activity. CONCLUSION: Through ALE meta-analysis, we consistently identified the right cuneus and left precuneus as vulnerable brain regions in adolescent MDD patients, increasing our understanding of the neuropathology of affected adolescents.

Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review.

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.

Efficient organized colorectal cancer screening in Shenzhen: a microsimulation modelling study.

BACKGROUND: Colorectal cancer (CRC) is a global health issue with noticeably high incidence and mortality. Microsimulation models offer a time-efficient method to dynamically analyze multiple screening strategies. The study aimed to identify the efficient organized CRC screening strategies for Shenzhen City. METHODS: A microsimulation model named CMOST was employed to simulate CRC screening among 1 million people without migration in Shenzhen, with two CRC developing pathways and real-world participation rates. Initial screening included the National Colorectal Polyp Care score (NCPCS), fecal immunochemical test (FIT), and risk-stratification model (RS model), followed by diagnostic colonoscopy for positive results. Several start-ages (40, 45, 50 years), stop-ages (70, 75, 80 years), and screening intervals (annual, biennial, triennial) were assessed for each strategy. The efficiency of CRC screening was assessed by number of colonoscopies versus life-years gained (LYG). RESULTS: The screening strategies reduced CRC lifetime incidence by 14-27 cases (30.9-59.0%) and mortality by 7-12 deaths (41.5-71.3%), yielded 83-155 LYG, while requiring 920 to 5901 colonoscopies per 1000 individuals. Out of 81 screening, 23 strategies were estimated efficient. Most of the efficient screening strategies started at age 40 (17 out of 23 strategies) and stopped at age 70 (13 out of 23 strategies). Predominant screening intervals identified were annual for NCPCS, biennial for FIT, and triennial for RS models. The incremental colonoscopies to LYG ratios of efficient screening increased with shorter intervals within the same test category. Compared with no screening, when screening at the same start-to-stop age and interval, the additional colonoscopies per LYG increased progressively for FIT, NCPCS and RS model. CONCLUSION: This study identifies efficient CRC screening strategies for the average-risk population in Shenzhen. Most efficient screening strategies indeed start at age 40, but the optimal starting age depends on the chosen willingness-to-pay threshold. Within insufficient colonoscopy resources, efficient FIT and NCPCS screening strategies might be CRC initial screening strategies. We acknowledged the age-dependency bias of the results with NCPCS and RS.

Analysis of abnormal expression of signaling pathways in PQ-induced acute lung injury in SD rats based on RNA-seq technology.

Background: Paraquat (PQ) plays an important role in agricultural production due to its highly effective herbicidal effect. However, it has led to multiple organ failure in those who have been poisoned, with damage most notable in the lungs and ultimately leading to death. Because of little research has been performed at the genetic level, and therefore, the specific genetic changes caused by PQ exposure are unclear.Methods: Paraquat poisoning model was constructed in Sprague Dawley (SD) rats, and SD rats were randomly divided into Control group, paraquat (PQ) poisoning group and Anthrahydroquinone-2,6-disulfonate (AH2QDS) treatment group. Then, the data was screened and quality controlled, compared with reference genes, optimized gene structure, enriched at the gene expression level, and finally, signal pathways with significantly different gene enrichment were screened.Results: This review reports on lung tissues from paraquat-intoxicated Sprague Dawley (SD) rats that were subjected to RNA-seq, the differentially expressed genes were mainly enriched in PI3K-AKT, cGMP-PKG, MAPK, Focal adhesion and other signaling pathways.Conclusion: The signaling pathways enriched with these differentially expressed genes are summarized, and the important mechanisms mediated through these pathways in acute lung injury during paraquat poisoning are outlined to identify important targets for AH2QDS treatment of acute lung injury due to paraquat exposure, information that will be used to support a subsequent in-depth study on the mechanism of PQ action.

Imaging diagnosis and differential diagnosis of extraskeletal osteosarcoma.

OBJECTIVE: The aim of this study was to investigate the clinical, imaging and pathological features of extraskeletal osteosarcoma (EOS) and to improve the understanding of this disease and other similar lesions. METHODS: The data for 11 patients with pathologically confirmed extraosseous osteosarcoma, including tumour site and size and imaging and clinical manifestations, were analysed retrospectively. RESULTS: Six patients were male (60%), and 5 were female (40%); patient age ranged from 23 to 76 years (average age 47.1 years). Among the 11 patients, 7 had clear calcifications or ossification with different morphologies, and 2 patients showed a massive mature bone tumour. MRI showed a mixed-signal mass with slightly longer T1 and T2 signals in the tumour parenchyma. Enhanced CT and MRI scans showed enhancement in the parenchyma. Ten patients had different degrees of necrosis and cystic degeneration in the mass, 2 of whom were complicated with haemorrhage, and MRI showed "fluid‒fluid level" signs. Of the 11 patients, five patients survived after surgery, and no obvious recurrence or metastasis was found on imaging examination. One patient died of lung metastasis after surgery, and 2 patients with open biopsy died of disease progression. One patient died of respiratory failure 2 months after operation. 2 patients had positive surgical margins, and 1 had lung metastasis 6 months after operation and died 19 months after operation. Another patient had recurrence 2 months after surgery. CONCLUSION: The diagnosis of EOS requires a combination of clinical, imaging and histological examinations. Cystic degeneration and necrosis; mineralization is common, especially thick and lumpy mineralization. Extended resection is still the first choice for localized lesions. For patients with positive surgical margins or metastases, adjuvant chemoradiotherapy is needed.

Modifiable Risk Factors in High-Risk Groups of Colorectal Cancer Screening: A Cross-Sectional Study with Propensity Score Method.

Aim: The rising incidence and death rate of colorectal cancer (CRC) have posed a severe danger to the lives and health of residents. Individuals at high risk of CRC are drawing growing attention as the majority of the population impacted by CRC. Hence, it is imperative to examine the detection rates and modifiable factors affecting the populations at high risk for CRC in Shenzhen. Methods: The multi-stage stratified cluster sampling method was used to select residents aged 45-74 years old from September 2020 to December 2021. The community-based CRC screening was attended by a total of 30,921 residents from urban and suburb regions. The association between modifiable risk factors and the detection rate of high-risk groups was analyzed using multinomial logistic regression with the inverse probability treatment weighting (IPTW) based on the propensity score. Results: The cross-sectional analysis included 24,613 people after excluding 6308 people who had missing or invalid fecal occult blood test (FOBT) results. The detection rate for high-risk groups during CRC screening was 28.50%. Higher rate of high-risk groups was detected among those who were male, aged 60 or above, college or above, other marital status, and living in urban (P < 0.05). Demographic characteristics after IPTW showed a weak correlation coefficient with the detection rate of CRC high-risk both in high-risk and general-risk groups (SMD < 0.1), suggesting a balanced group of participants. The results of logistic regression with IPTW indicated that smoking, drinking, obesity, lack of exercise, vegetable or fruit eating infrequently, red meat, processed meat, cereal food and their clustering status were more inclined to be risk indicators of CRC (P < 0.05). Conclusion: The detection rate for high-risk CRC groups was comparatively high in Shenzhen. The distribution characteristics of lifestyle and dietary risk factors of high-risk groups should be given consideration when adopting individualized intervention measures and comprehensive prevention and control strategies.

Machine learning for differentiation of lipid-poor adrenal adenoma and subclinical pheochromocytoma based on multiphase CT imaging radiomics.

BACKGROUND: There is a paucity of research investigating the application of machine learning techniques for distinguishing between lipid-poor adrenal adenoma (LPA) and subclinical pheochromocytoma (sPHEO) based on radiomic features extracted from non-contrast and dynamic contrast-enhanced computed tomography (CT) scans of the abdomen. METHODS: We conducted a retrospective analysis of multiphase spiral CT scans, including non-contrast, arterial, venous, and delayed phases, as well as thin- and thick-thickness images from 134 patients with surgically and pathologically confirmed. A total of 52 patients with LPA and 44 patients with sPHEO were randomly assigned to training/testing sets in a 7:3 ratio. Additionally, a validation set was comprised of 22 LPA cases and 16 sPHEO cases from two other hospitals. We used 3D Slicer and PyRadiomics to segment tumors and extract radiomic features, respectively. We then applied T-test and least absolute shrinkage and selection operator (LASSO) to select features. Six binary classifiers, including K-nearest neighbor (KNN), logistic regression (LR), decision tree (DT), random forest (RF), support vector machine (SVM), and multi-layer perceptron (MLP), were employed to differentiate LPA from sPHEO. Receiver operating characteristic (ROC) curves and area under the curve (AUC) values were compared using DeLong's method. RESULTS: All six classifiers showed good diagnostic performance for each phase and slice thickness, as well as for the entire CT data, with AUC values ranging from 0.706 to 1. Non-contrast CT densities of LPA were significantly lower than those of sPHEO (P < 0.001). However, using the optimal threshold for non-contrast CT density, sensitivity was only 0.743, specificity 0.744, and AUC 0.828. Delayed phase CT density yielded a sensitivity of 0.971, specificity of 0.641, and AUC of 0.814. In radiomics, AUC values for the testing set using non-contrast CT images were: KNN 0.919, LR 0.979, DT 0.835, RF 0.967, SVM 0.979, and MLP 0.981. In the validation set, AUC values were: KNN 0.891, LR 0.974, DT 0.891, RF 0.964, SVM 0.949, and MLP 0.979. CONCLUSIONS: The machine learning model based on CT radiomics can accurately differentiate LPA from sPHEO, even using non-contrast CT data alone, making contrast-enhanced CT unnecessary for diagnosing LPA and sPHEO.

Association between thermal stress and cardiovascular mortality in the subtropics.

Hazardous thermal conditions resulting from climate change may play a role in cardiovascular disease development. We chose the Universal Thermal Climate Index (UTCI) as the exposure metric to evaluate the relationship between thermal conditions and cardiovascular mortality in Shenzhen, China. We applied quasi-Poisson regression non-linear distributed lag models to evaluate the exposure-response associations. The findings suggest that cardiovascular mortality risks were significantly increased under heat and cold stress, and the adverse effects of cold stress were stronger than heat stress. Referencing the 50th percentile of UTCI (25.4°C), the cumulative risk of cardiovascular mortality was 75% (RRlag0-21 =1.75, 95%CI: 1.32, 2.32) higher in the 1st percentile (3.5°C), and 40% (RRlag0-21=1.40, 95%CI: 1.09, 1.80) higher in the 99th percentile (34.1°C). We observed that individuals older than 65 years were more vulnerable to both cold and heat stress, and females were identified as more susceptible to heat stress than males. Moreover, increased mortality risks of hypertensive disease and cerebrovascular disease were observed under cold stress, while heat stress was related to higher risks of mortality for hypertensive disease and ischemic heart disease. We also observed a stronger relationship between cold stress and ischemic heart disease mortality during the cold season, as well as a significant impact of heat stress on cerebrovascular disease mortality in the warm season when compared to the analysis of the entire year. These results confirm the significant relationship between thermal stress and cardiovascular mortality, with age and sex as potential effect modifiers of this association. Providing affordable air conditioning equipment, increasing the amount of vegetation, and establishing comprehensive early warning systems that take human thermoregulation into account could all help to safeguard the well-being of the public, particularly vulnerable populations, in the event of future extreme weather.

Impact of changing the prevalence of smoking, alcohol consumption and overweight/obesity on cancer incidence in China from 2021 to 2050: a simulation modelling study.

Background: Smoking, alcohol consumption and overweight/obesity are key cancer risk factors contributing to the cancer burden in China. We aimed to quantify the cancer burden in China associated with smoking, alcohol consumption and overweight/obesity, and estimate the potential effect for cancer prevention interventions under different scenarios. Methods: We used a macro-simulation approach called Prevent Model to estimate for a 30-year study period (2021-2050) numbers and proportions of future avoidable cancer cases under different scenarios of reducing the prevalence of smoking, alcohol consumption and overweight/obesity in Chinese adults. Cancer incidence was predicted under three scenarios: elimination, ambitious target (between elimination and manageable target) and manageable target (from national policy or global action plan). Risk factor prevalence was obtained from China Chronic Disease and Risk Factor Surveillance, and cancer incidence data were derived from the China Cancer Registry Annual Report. Relative risks were obtained from several recent large-scale studies or high-quality meta-analysis. Population data were extracted from the China Population & Employment Statistical Yearbook, China Health Statistical Yearbook and World Population Prospects. Findings: Estimates of the avoidable cancer burden varied with different scenarios. In the theoretical maximum intervention scenario, where the prevalence of smoking, alcohol consumption and overweight/obesity would be eliminated, 9.17% (males: 13.50%; females: 1.47%) of smoking-related cancer cases, 7.06% (males: 11.49%; females: 1.00%) of cancer cases related to alcohol consumption and 8.22% (males: 7.91%; females: 8.52%) of overweight/obesity-related cancer cases were estimated to be avoidable during 2021-2050. Other scenarios, with more moderate goals in the exposure prevalence of smoking, alcohol use and overweight/obesity were also found to be associated with substantial reductions in the future cancer burden. Interpretation: Our results suggested that a substantial number of future cancer cases could be avoided in Chinese adults by reducing the prevalence of smoking, alcohol consumption and overweight/obesity. Funding: National Science & Technology Fundamental Resources Investigation Program of China; Sanming Project of Medicine in Shenzhen.

Effect of a two-phase tobacco control regulation on incidence from ischemic stroke and hemorrhagic stroke, Shenzhen, China, 2007-2016.

INTRODUCTION: The Shenzhen government is widely considered to be most efficiently implementing smoke-free legislation in China. We evaluated and compared the impact of Shenzhen's two-phase smoke-free regulation on the incidence rates for ischemic and hemorrhagic stroke. METHODS: An interrupted time series design was used to capture immediate and annual incidence changes from 2007 to 2016 for both ischemic and hemorrhagic stroke due to two-phase smoke-free regulation in Shenzhen, China, by using a generalized additive model. The first phase, implemented on 9 March 2010, required five main public places to be smoke-free. In the second phase, the comprehensive law was expanded to the whole city on 1 March 2014. RESULTS: The regulation implementation during phase I was associated with a strong immediate decline in the incidence rate of ischemic stroke (-14.2%, 95% CI: -19.6 - -8.4) and hemorrhagic stroke (-10.1%, 95% CI: -18.2 - -1.2), but without showing the annual changes (p>0.05). Following the implementation of the comprehensive law, the gradual annual effect showed a significant change in ischemic stroke, with a 6.3% (95% CI: 8.9 - -3.6) reduction. Neither the immediate nor gradual decreases in hemorrhagic stroke incidences associated with the comprehensive regulation were statistically significant during phase II (p>0.05). Subgroup analyses indicate that a much larger health effect of the regulation during phase I was greater among those aged ≥65 years than among those aged 35-64 years. CONCLUSIONS: Shenzhen's two-phase smoke-free regulation was well implemented. Even though the regulation did not extend to the whole city, the immediate health benefits on the incidence rates of ischemic stroke and hemorrhagic stroke could be seen. However, the health benefits brought by the implementation of comprehensive smoke-free legislation were attenuated by previous smoke-free regulations in five main public places, which were more evident in hemorrhagic stroke.

Impact of Smoke-Free Legislation on Acute Myocardial Infarction and Subtypes of Stroke Incidence in Shenzhen, China, 2012-2016: An Interrupted Time Series Analysis.

Objective: This study assesses the impact of smoke-free legislation on the incidence rate for acute myocardial infarction (AMI) and stroke in Shenzhen. Methods: Data on ischemic ( n = 72,945) and hemorrhagic ( n = 18,659) stroke and AMI ( n = 17,431) incidence covering about 12 million people in Shenzhen from 2012 to 2016 were used. Immediate and gradual changes in incidence rates were analyzed using segmented Poisson regression. Results: Following the smoke-free legislation, a 9% (95% CI: 3%-15%) immediate reduction was observed in AMI incidence, especially in men (8%, 95% CI: 1%-14%) and in those aged 65 years and older (17%, 95% CI: 9%-25%). The gradual annual benefits were observed only in hemorrhagic and ischemic stroke incidence, with a 7% (95% CI: 2%-11%) and 6% (95% CI: 4%-8%) decrease per year, respectively. This health effect extended gradually to the 50-64 age group. In addition, neither the immediate nor gradual decrease in stroke and AMI incidence rates did not show statistical significance among the 35-49 age group ( P > 0.05). Conclusion: Smoke-free legislation was enforced well in Shenzhen, which would generate good experiences for other cities to enact and enforce smoke-free laws. This study also provided more evidence of the health benefits of smoke-free laws on stroke and AMI.

Cyberchondria and Chinese Adolescent Mental Health in the Age of COVID-19 Pandemic.

One of the far-reaching impacts of the COVID-19 pandemic is that it has become the fertile soil of cyberchondria. Adolescents' mental health was severely hit by this by-product of the COVID-19 pandemic both due to the direct effects and its indirect effects on security. This study investigated whether and how cyberchondria was associated with Chinese adolescents' mental health (i.e., well-being and depressive symptoms). Based on a large Internet sample (N = 1,108, 67.5 percent female, Mage = 16.78 years), cyberchondria, psychological insecurity, mental health, and a series of covariates were assessed. Preliminary analyses were conducted in SPSS Statistics software and main analyses were conducted in Mplus. Path analyses indicated that (a) cyberchondria was negatively associated with well-being (b = -0.12, p = 0.001) and positively associated with depressive symptoms (b = 0.17, p < 0.001); (b) psychological insecurity could fully mediate the association between cyberchondria and mental health (indirect effect well-being = -0.15, 95% confidence interval [CI -0.19 to -0.12] and indirect effect depressive symptoms = 0.15, 95% CI [0.12 to 0.19]); (c) the two dimensions (social insecurity and uncertainty) of psychological insecurity could play the mediating role in the associations between cyberchondria and mental health, uniquely and parallelly; and (d) these results did not vary by gender. This study suggests that cyberchondria may arouse individuals' psychological insecurity about interpersonal interaction and the development of events, which ultimately decreases their well-being and increases the risk of depressive symptoms. These findings facilitate the establishment and implementation of relevant prevention and intervention programs.

Mechanism of Action for an All-in-One Monoclonal Antibody Against Staphylococcus aureus Infection.

Staphylococcus aureus is a major human pathogen associated with high mortality rates. The extensive use of antibiotics is associated with the rise of drug resistance, and exotoxins are not targeted by antibiotics. Therefore, monoclonal antibody (mAb) therapy has emerged as a promising solution to solve the clinical problems caused by refractory S aureus. Recent research suggests that the synergistic effects of several cytotoxins, including bicomponent toxins, are critical to the pathogenesis of S aureus. By comparing the amino acid sequences, researchers found that α-toxin and bicomponent toxins have high homology. Therefore, we aimed to screen an antibody, designated an all-in-one mAb, that could neutralize α-toxin and bicomponent toxins through hybridoma fusion. We found that this mAb has a significant pharmacodynamic effect within in vivo mouse models and in vitro experiments.

Identification of a novel KLHL3-interacting motif in the C-terminal region of WNK4.

Mutations in with-no-lysine [K] kinase 4 (WNK4) and kelch-like 3 (KLHL3) are linked to pseudohypoaldosteronism type 2 (PHAII, also known as familial hyperkalemic hypertension or Gordon's syndrome). WNK4 is degraded by a ubiquitin E3 ligase with KLHL3 as the substrate adaptor for WNK4. Several PHAII-causing mutations, e.g. those in the acidic motif (AM) of WNK4 and in the Kelch domain of KLHL3, impair the binding between WNK4 and KLHL3. This results in a reduction in WNK4 degradation and an increase in WNK4 activity, leading to PHAII. Although the AM is important in interacting with KLHL3, it is unclear whether this is the only motif in WNK4 responsible for KLHL3-interacting. In this study, a novel motif of WNK4 that is capable of mediating the degradation of the protein by KLHL3 was identified. This C-terminal motif (termed as CM) is located in amino acids 1051-1075 of WNK4 and is rich in negatively charged residues. Both AM and CM responded to the PHAII mutations in the Kelch domain of KLHL3 in a similar manner, but AM is dominant among the two motifs. The presence of this motif likely allows WNK4 protein to respond to the KLHL3-mediated degradation when the AM is dysfunctional due to a PHAII mutation. This may be one of the reasons why PHAII is less severe when WNK4 is mutated compared to KLHL3 is mutated.

Trends in Incidence Rates, Mortality Rates, and Age-Period-Cohort Effects of Female Breast Cancer - China, 2003-2017.

Introduction: This study reported the trends in female breast cancer incidence and mortality rates in China, and analyzed the corresponding age-period-cohort effects. Methods: Data from 22 population-based cancer registries in China between 2003 and 2017 were analyzed. Age-standardized incidence rates (ASIR) and mortality rates (ASMR) were calculated using Segi's world standard population. Joinpoint regression was employed to evaluate trends, and age-period-cohort effects were examined using the intrinsic estimator method. Results: The ASIR for female breast cancer exhibited a more rapid increase in rural areas compared to urban areas across all age groups. The most substantial increase was observed in the 20-34 age group in rural areas [annual percent change (APC)=9.0%, 95% confidence interval (CI): 7.0%-11.0%, P<0.001]. The ASMR for females under 50 years old remained stable from 2003 to 2017 in both urban and rural areas. However, the ASMR for females over 50 in rural areas and those over 65 in urban areas demonstrated a significant increase, with the most pronounced increase observed among females over 65 in rural areas (APC=4.9%, 95% CI: 2.8%-7.0%, P<0.001). Age-period-cohort analysis revealed increasing period effects and decreasing cohort effects for female breast cancer incidence and mortality rates in both urban and rural settings. Notably, the cohort effect for incidence displayed a slight upward trend for females born between 1983 and 1992 in rural areas. Conclusions: Our study revealed a rapid increase in breast cancer incidence among younger generations and an accelerated mortality rate in older populations residing in rural areas. To effectively address the growing burden of female breast cancer in China, it is essential to develop and implement targeted intervention strategies.

Influence of occupational exposure to antineoplastic agents on adverse pregnancy outcomes among nurses: A meta-analysis.

AIM: This study aimed to explore the relationship between nurses' occupational exposure to antineoplastic agents and adverse pregnancy outcomes. DESIGN: Meta-analysis. METHODS: Data were retrieved from studies published before April 2022 in PubMed, the Cochrane Library, the Web of Science, Embase databases, the China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), China Science and Technology Journal databases (VIP) and Wan Fang databases (WF). Stata MP (Version 17.0) was used to conduct this meta-analysis. RESULTS: The current evidence shows that occupational exposure to antineoplastic agents increases nurses' risk of spontaneous abortions, stillbirths, and congenital abnormalities. It is necessary to pay attention to occupational exposures caused by antineoplastic agents, especially for female nurses of reproductive age. Managers should take timely and effective countermeasures to ensure their occupational safety and reduce the risk of adverse pregnancy outcomes.

The meta-analysis of cytogenetic biomarkers as an assessment of occupational risk for healthcare workers exposed to antineoplastic drugs.

OBJECTIVE: Antineoplastic drugs (ADs) are widely used in clinical practice and have been demonstrated to be effective in treating malignant tumors. However, they carry a risk of cytogenotoxicity for healthcare workers. Studies have reported that genotoxic biomarkers can be applied to assess the occupational health status of healthcare workers at an early stage, but results of different studies are variable. The objectives of the review were examine the association between long-term exposure to ADs and cytogenetic damage to healthcare workers. METHODS: We systematically reviewed studies between 2005 and 2021 using PubMed, Embase and Web of Science databases that used cytogenetic biomarkers to assess occupational exposure to ADs in healthcare workers. We used RevMan5.4 to analyze the tail length parameters of the DNA, frequency of the chromosomal aberrations, sister chromatid exchanges and micronuclei. A total of 16 studies were included in our study. The studies evaluate the quality of the literature through the Agency for Healthcare Research and Quality. RESULTS: The results revealed that under the random-effects model, the estimated standard deviation was 2.37 (95% confidence interval [CI] 0.92-3.81, P = 0.001) for the tail length parameters of the DNA, 1.48 (95% CI 0.71-2.25, P = 0.0002) for the frequency of chromosomal aberrations, 1.74 (95% CI 0.49-2.99, P = 0.006) for the frequency of sister chromatid exchanges and 1.64 (95% CI 0.83-2.45, P < 0.0001) for the frequency of micronuclei. CONCLUSIONS: The results indicate that there is a significant association between occupational exposure to ADs and cytogenetic damage, to which healthcare workers should be alerted.

Circadian Disruption and Breast Cancer Risk: Evidence from a Case-Control Study in China.

Studies had suggested an association between circadian disruptors (including night shift work, domestic light exposure at night, sleep duration, and circadian gene polymorphism) and breast cancer, while rare studies had been conducted in the Chinese population. This study was a case-control study conducted to explore the impact of circadian disruptors on the risk of breast cancer in China. Four hundred and sixty-four cases and 464 controls, admitted from the Department of Breast Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, were included in this study. Adjusting age, BMI group, smoking, alcohol consumption, menopausal status, family history of breast cancer, duration of breastfeeding, age at menarche, number of pregnancies, age at first full-term pregnancy, use of estrogen and use of oral contraceptive, multivariate logistic regression analysis showed that the risk of breast cancer was higher in short sleep duration group (OR = 4.86, 95%CI: 1.73-17.33). Meanwhile, rs2292912 in CRY2, rs2253820 in PER1, rs2289591 in PER1 and rs3027188 in PER1 were positively associated with the risk of breast cancer. This study supported that the short duration of sleep and four SNPs in crucial circadian genes played a role in the development of breast cancer.

Molecular insights into the structural and dynamical changes of calcium channel TRPV6 induced by its interaction with phosphatidylinositol 4,5-bisphosphate.

Transient receptor potential vanilloid subfamily member 6 (TRPV6) is an epithelial calcium channel that regulates the initial step of the transcellular calcium transport pathway. TRPV6 is expressed in the kidney, intestine, placenta, and other tissues, and the dysregulation of the channel is implicated in several human cancers. It has been reported that phosphatidylinositol 4,5-bisphosphate (PIP2) activates TRPV6 and its close homologue TRPV5; however, the underlying molecular mechanism is less clear. Recently, a structure of rabbit TRPV5 in complex with dioctanoyl (diC8) PIP2, a soluble form of PIP2, was determined by cryo-electron microscopy. Based on this structure, the structural model of human TRPV6 with PIP2 was set up, and then molecular dynamics simulations were performed for TRPV6 with and without PIP2. Simulation results show that the positively charged residues responsible for TRPV5 binding of diC8 PIP2 are conserved in the interactions between TRPV6 and PIP2. The binding of PIP2 to TRPV6 increases the distance between the diagonally opposed residues D542 in the selectivity filter and that between the diagonally opposed M578 residues in the lower gate of TRPV6. A secondary structural analysis reveals that residues M578 in TRPV6 undergo structural and position changes during the binding of PIP2 with TRPV6. In addition, principal component analysis indicates that the binding of PIP2 increases the dynamical motions of both the selectivity filter and the lower gate of TRPV6. These changes induced by PIP2 favor the channel opening. Thus, this study provides a basis for understanding the mechanism underlying the PIP2-induced TRPV6 channel activation.Communicated by Ramaswamy H. Sarma.

Real-World Practice of Gastric Cancer Prevention and Screening Calls for Practical Prediction Models.

INTRODUCTION: Some gastric cancer prediction models have been published. Still, the value of these models for application in real-world practice remains unclear. We aim to summarize and appraise modeling studies for gastric cancer risk prediction and identify potential barriers to real-world use. METHODS: This systematic review included studies that developed or validated gastric cancer prediction models in the general population. RESULTS: A total of 4,223 studies were screened. We included 18 development studies for diagnostic models, 10 for prognostic models, and 1 external validation study. Diagnostic models commonly included biomarkers, such as Helicobacter pylori infection indicator, pepsinogen, hormone, and microRNA. Age, sex, smoking, body mass index, and family history of gastric cancer were frequently used in prognostic models. Most of the models were not validated. Only 25% of models evaluated the calibration. All studies had a high risk of bias, but over half had acceptable applicability. Besides, most studies failed to clearly report the application scenarios of prediction models. DISCUSSION: Most gastric cancer prediction models showed common shortcomings in methods, validation, and reports. Model developers should further minimize the risk of bias, improve models' applicability, and report targeting application scenarios to promote real-world use.