The influence of night shift work and associated factors on serum uric acid in aircraft maintenance workers.

BACKGROUND AND OBJECTIVE: The prevalence of 12-hour shift work is increasing in various occupations. Shift work has been linked to circadian rhythm disruption, which may lead to hormonal changes and metabolic disorders, including alterations in glucose, lipid, and purine metabolism. Despite this, there is limited research on the potential connection between work shifts and abnormal serum uric acid (SUA) levels. Furthermore, the factors that contribute to abnormal SUA levels in shift workers are not well-understood. Therefore, this study aimed to analyze the SUA levels of shift workers employed in an aircraft maintenance company, investigate the potential association between shift work and SUA levels, and explore the factors that may influence abnormal SUA levels in shift workers. METHODS: A total of 2263 male workers from an aircraft maintenance company were included in this study using the cluster sampling method. The workers were divided into two groups based on their working shifts: night shift (N = 1047, 46.27%) and day working (N = 1216, 53.73%). A survey was conducted between April 1st and June 30th, 2022 to gather information on work, lifestyle, physical examination results, and other relevant factors. The survey included a self-designed demographic information questionnaire to collect data on workers' characteristics, medical history, years of employment, smoking and drinking habits, and main lifestyle behaviors. The workers' SUA levels were measured using uricase colorimetry. One-way ANOVA was used to compare the difference in the abnormal detection rate of SUA between the two groups, and multi-factor logistic regression analysis was used to identify the factors that influence abnormal SUA levels. RESULTS: The study indicated that 48.9% of night shift workers and 43.8% in the regular day workers had abnormal SUA levels, with a significant difference between the two groups (χ2 = 6.125, P = 0.013). Factors such as circadian rhythm type, shift work, age, the taste of diet, type of diet, smoking, overweight or obesity based on body mass index (BMI), concentration of urine creatinine (CREA), total cholesterol, triglyceride, and low-density lipoprotein cholesterol were found to be correlated with SUA abnormalities (P < 0.05). The risk of developing SUA abnormalities was found to be higher in individuals with an intermittent (OR = 1.34, 95% CI: 0.83-2.12, P < 0.05) or evening circadian rhythm type (OR = 1.45, 95% CI: 0.86-2.43, P > 0.05) compared to those with a morning type. Additionally, factors such as night shift work, a high-sodium diet, smoking, a diet high in meat and low in vegetables, being overweight or obese, and higher levels of CREA were also found to increase the risk of developing SUA abnormalities. The study also revealed a significant dose-response relationship between BMI and abnormal uric acid levels. After controlling for other factors, the risk of developing SUA abnormalities was found to be 1.18 times higher in the night shift work group than in the day work group (OR = 1.18, 95% CI:1.02-1.34, P = 0.01). CONCLUSION: Shift work has been linked to a higher risk of developing SUA abnormalities, and there are several factors that may contribute to this risk. To prevent diseases, it is recommended that enterprises implement better health monitoring and management practices for shift workers.

Targeting HMGCS1 restores chemotherapy sensitivity in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common hematological malignancy with overall poor prognosis. Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory (RR) AML patients. Through clinical specimens, animal models and cell-level studies, we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1) in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation, increase chemotherapy sensitivity and improve the occurrence and development of AML. Here, we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival (OS). Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity, while stable overexpression of HMGCS1 had the opposite effects. Mechanistically, we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase (MAPK) pathway activity, while overexpression of HMGCS1 could remarkably enhance the pathway. U0126, a MEK1 inhibitor, offset the effects of HMGCS1 overexpression, indicating that HMGCS1 promotes RR AML through the MAPK pathway. Further, we verified that hymeglusin, a specific inhibitor of HMGCS1, decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients. Furthermore, combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin (ADR) had synergistic toxic effects on AML cells. Our study demonstrates the important role of HMGCS1 in AML, and targeting this protein is promising for the treatment of RR AML.

Thoracoscopic Intercostal Nerve Block with Cocktail Analgesics for Pain Control After Video-Assisted Thoracoscopic Surgery: A Prospective Cohort Study.

Objective: To evaluate whether using a cocktail of intercostal nerve blocks (TINB) during thoracoscopic surgery results in better clinical outcomes than patient-controlled analgesia (PCIA). Methods: Patients in two medical groups undergoing video-assisted thoracoscopic surgery (VATS) for pulmonary nodules in West China Hospital of Sichuan University were collected consecutively between March 2022 and December 2022. The groups were divided into two subgroups based on their analgesic program, which were TINB group and PCIA group. The primary outcome was the visual analogue scale (VAS) of the two groups at different stage after surgery and after discharge. Any analgesic related adverse events (ARAEs) were also recorded. Results: A total of 230 patients who underwent VATS were enrolled, in which 113 patients (49.1%) received a cocktail TINB after surgery, and 117 patients (50.9%) received a PCIA. After PSM, 62 patients in each group were selected. The difference of resting VAS (RVAS) and active VAS (AVAS) at different stage during hospitalization was only related to the change of period (p < 0.05, p < 0.05), and the two groups showed no significant differences in RVAS or AVAS during hospitalization (p = 0.271, p = 0.915). However, the rates of dizziness (4.84% vs 25.81%, p = 0.002), nausea and vomiting (0 vs 22.58%, p < 0.05), fatigue (14.52% vs 34.87%, p = 0.012), and insomnia (0 vs 58.06%, p < 0.05) in TINB group were lower than that in PCIA group. Besides, AVAS and RVAS at 7, 14, and 30 days after discharge in TINB group were both significantly lower than that in PCIA group (p < 0.05, p < 0.05). Conclusion: Cocktail TINB provided better analgesia after discharge and reduced the incidence of ARAEs in patients undergoing VATS.

Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.

Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.

BMP and activin receptor membrane bound inhibitor: BAMBI has multiple roles in gene expression and diseases (Review).

BMP and activin membrane-bound inhibitor (BAMBI) is a transmembrane glycoprotein, known as a pseudo-receptor for TGFß, as, while its extracellular domain is similar to that of type I TGFß receptors, its intracellular structure is shorter and lacks a serine/threonine phosphokinase signaling motif. BAMBI can regulate numerous biological phenomena, including glucose and lipid metabolism, inflammatory responses, and cell proliferation and differentiation. Furthermore, abnormal expression of BAMBI at the mRNA and protein levels contributes to various human pathologies, including obesity and cancer. In the present review, the structure of BAMBI is briefly introduced and its associated signaling pathways and physiological functions are described. Understanding of BAMBI structure and function may contribute to knowledge regarding the occurrence of diseases, including obesity and diabetes, among others. The present review provides a theoretical foundation for the development of BAMBI as a potential biomarker or therapeutic target.

An Analysis of Public Perception and Concern Toward Electronic Cigarettes: Exploring Attitudes and Profiles.

Introduction The emergence of electronic cigarettes (e-cigarettes) poses a new challenge to tobacco control efforts. With their increasing popularity, particularly among youth, public concerns have been raised in Mainland China. Further investigation is necessary to fully understand the safety and potential adverse effects of e-cigarettes. Methods The Baidu search index (BSI) was employed using e-cigarette related terms from January 1, 2011, to April 4, 2022. The search volume for each term was recorded and analyzed for the search trend module, geodemographic module, search-demand module, regional preferences, demographic preferences, and user demand. Results According to our analysis, the total BSI for the 18 e-cigarette related search keywords was 39,027,819. The average annual percentage change of BSI indicated an upward trend for each of these categories, including health issues (p < 0.05), definition (p < 0.05), product and promotions (p < 0.05), and policy and regulations. Of all inquiries, 59.38% originated from females and 40.62% from males. The total valid BSI for e-cigarette related words was 165,076,588, and 11.59% of all search inquiries were from individuals aged 19 years and younger. Our analysis also revealed that the public's primary concerns regarding e-cigarettes were related to their quality and potential health issues. Conclusions E-cigarettes enjoy great popularity nationwide, but product quality and safety are major public concerns. Regulation of e-cigarettes for their standard production, quality control, advertisement, and target customers should be implemented promptly, and the public needs to have a clear perception of e-cigarettes, especially adolescents. E-cigarette related health damages or consequences require further investigation, and advertisements and promotions for e-cigarettes should be strictly controlled by the government.

A redox-responsive nanosystem to suppress chemoresistant lung cancer through targeting STAT3.

Cancer stem cells (CSCs) have been demonstrated to be involved in tumor initiation and relapse, and the presence of CSCs in the tumor tissue often leads to therapeutic failure. BBI608 has been identified to eliminate CSCs by inhibiting signal transducer and activator of transcription 3 (STAT3). In this study, we confirm that BBI608 can efficiently suppress the proliferation and migration of non-small cell lung cancer (NSCLC) cells, and specifically kill the stemness-high population in chemoresistant NSCLC cells. To improve its bioavailability and tumor accumulation, BBI608 is successfully encapsulated into redox-responsive PEGylated branched N-(2-hydroxypropyl) methacrylamide (HPMA)-deoxy cholic acid (DA) polymeric nanoparticles (BBI608-SS-NPs). The BBI608-SS-NPs can release the drug in response to high concentrations of intracellular glutathione, and exhibit cytotoxicity against lung cancer cells and CSCs comparable to the free drug BBI608. Furthermore, the BBI608-SS-NPs preferentially accumulate in tumor sites, resulting in a superior anti-tumor efficacy in both cisplatin-resistant cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of NSCLC. Mechanistic studies demonstrate that BBI608-SS-NPs not only directly inhibit the downstream genes of the STAT3 pathway, but also indirectly inhibit the Wnt pathway. Overall, this stimuli-responsive polymeric nanoformulation of BBI608 shows great potential in the treatment of chemoresistant NSCLC by targeting CSCs.

Comparison of the short- and long-term prognosis of early-onset colorectal cancer compared with later-onset colorectal cancer: A systematic review and meta-analysis.

Background and Aims: The annual incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate. The prognosis of EOCRC remains controversial, and whether the early onset is a risk factor for colorectal cancer remains unclear. Methods: We searched four electronic bibliographic databases from database inception to April 25, 2022 for studies that included both early- and later-onset patients and performed a prognostic analysis. Random-effects models were used to summarize the prognostic information extracted by the investigators, including overall survival (OS), cancer-special survival (CSS), and disease-free survival (DFS). Network meta-analysis (NMA) was used to compare patients' long-term prognoses in different age subgroups. Results: After 694 reports were screened, 13 studies were included in the final analysis, with a total of 448,781 CRC cases. In the meta-analysis of the 5-year OS, EOCRC had a better prognosis compared to LOCRC (hazard ratio [HR] 0.87, 95% confidence interval [CI], 0.74-0.99; relative risk [RR] 0.83, 95% CI, 0.78-0.89). No difference in prognosis was found between the two groups in terms of 5-year CSS (RR 0.99, 95% CI, 0.93-1.05), 5-year DFS (RR 0.90, 95% CI, 0.74-1.09), and short-term OS. In the NMA, patients aged <30 years had the worst outcome (surface under the cumulative ranking curve [SUCRA], 15.8%) in 5-year OS; consistent results were observed in the analysis of 5-year CSS (<30 years, SUCRA 4.5%), but the difference was not statistically significant. Conclusion: Although patients with early-onset CRC had better OS than those with later-onset CRC, there was no difference in the CSS. Meanwhile, the trend for survival was worse in younger patients, especially in those ages 18-29 years. Thus, more attention should be paid to early diagnosis and treatment of EOCRC. Systematic Review and Meta­Analysis Registration: The systematic review and Meta-analysis protocol was registered with PROSPERO (registration number CRD42022334697).

Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis.

BACKGROUND: Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0. RESULTS: A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42-2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27-1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients. CONCLUSIONS: In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor.

MiR-210 improves postmenopausal osteoporosis in ovariectomized rats through activating VEGF/Notch signaling pathway.

BACKGROUND: To explore the effect and mechanism of action of miR-210 on postmenopausal osteoporosis (PMPO) in ovariectomized rats in vivo. METHODS: An ovariectomized (OVX) rat model was established by ovariectomy. Tail vein injection was performed to overexpress and knock down miR-210 in OVX rats, followed by the collection of blood and femoral tissues from each group of rats. And quantitative real-time polymerase chain reaction (qRT-PCR) was applied to assess the expression level of miR-210 in femoral tissues of each group. Micro computed tomography (Micro CT) was adopted to scan the microstructure of the femoral trabecula in each group to obtain relevant data like bone mineral density (BMD), bone mineral content (BMC), trabecular bone volume fraction (BV/TV), trabecular thickness (Tb.Th), bone surface-to-volume ratio (BS/BV), and trabecular separation (Tb.Sp). ELISA was used for determining the level of bone alkaline phosphatase (BALP), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OCN), and C-terminal telopeptide of type I collagen (CTX-1) in serum; and Western blot for the protein level of Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and collagen type I alpha 1 (COL1A1) in femoral tissues. RESULTS: MiR-210 expression was significantly decreased in femoral tissues of OVX rats. Overexpression of miR-210 could obviously increase BMD, BMC, BV/TV and Tb.Th, whereas significantly decrease BS/BV and Tb.Sp in femurs of OVX rats. Moreover, miR-210 also downregulated BALP and CTX-1 level, upregulated PINP and OCN level in the serum of OVX rats promoted the expression of osteogenesis-related markers (Runx2, OPN and COL1A1) in the femur of OVX rats. Additionally, further pathway analysis revealed that high expression of miR-210 activated the vascular endothelial growth factor (VEGF)/Notch1 signaling pathway in the femur of OVX rats. CONCLUSION: High expression of miR-210 may improve the micromorphology of bone tissue and modulate bone formation and resorption in OVX rats by activating the VEGF/Notch1 signaling pathway, thereby alleviating osteoporosis. Consequently, miR-210 can serve as a biomarker for the diagnosis and treatment of osteoporosis in postmenopausal rats.

Neurologic symptoms among solar greenhouse workers and field workers in China.

It has been widely reported that the farmers were at increased risk of neurologic disorders, which probably be related with agricultural risk factors. The intensity of agricultural risk factors was rather high in the solar greenhouse than those in the agricultural farm, while the risk and prevalence of neurologic symptoms among solar greenhouse workers are unclear, which may provide evidence of neurologic dysfunction before clinically measurable signs are evident. This study aimed to evaluate the association among solar greenhouse working, field working, and neurologic symptoms. A cross-sectional study was conducted in China, and 986 Chinese Han population consisting 711 solar greenhouse workers (greenhouse worker group) and 275 field farmers (field worker group) were included. Participants provided information on demographic information, number of solar greenhouses owned (only solar greenhouse workers), working lifetime, and neurologic symptoms through an established questionnaire Q16 to assess the impact of occupational exposure to neurotoxicants, and the total scores were calculated. Multiple linear regression models were used to analyze the association among solar greenhouse working, field working, and neurologic symptoms. The total scales of the neurologic symptoms were higher in the solar greenhouse worker group (20.29 ± 4.79) than those in the field worker group (19.44 ± 4.22) (p < 0.05). Multivariate multiple linear regression showed that solar greenhouse working was positively associated with the scales of the neurologic symptoms (ß = 0.248, 95% CI: (0.112, 0.383)). And the age, working lifetime, and current smoking were also positively associated with the scores of the neurologic symptoms, ß = 0.007, 0.006 and 0.485 respectively (All p < 0.05). Solar greenhouse workers probably be at an increased risk of neurologic symptoms scores, and the age, working lifetime, and current smoking were also risk factors.

Physical activity (PA) influences the risk of depression associated with long working hours.

BACKGROUND: Growing evidences showed that long working hours is associated with depression epidemic, but few studies investigate whether physical activity (PA) could modify the risk of depression associated with long working hours, which was the purpose of the present study. METHODS: A cross-sectional data obtained from the National Health and Nutrition Examination Survey 2015-2018. According to the criteria of International Labour Organization, long working hours was defined as >40 h/wk. The Nine-item Patient Health Questionnaire (PHQ-9) was used to identify depression. Binary logistic regression and restricted cubic spline (RCS) models were used to estimate the associations between long working hours and depression, furthermore to estimate the association of PA. RESULTS: 5958 participants were included in the study. The results indicated that 3074 (51.6 %) of participants worked >40 h/wk. The prevalence of depression was 7.7 %. Logistic regression analysis indicated a positive association between long working hours and depression [OR = 1.738, 95 CI (1.427, 2.117)], and the results were still robust after controlling other confounding factors. RCS models indicated that the high intensity PA group had the lowest risk of depression, followed by low intensity PA group and no PA group. CONCLUSION: Long working hours probably be associated with depression, while PA can modify the risk to some degree.

Endometrial transcriptome profiling of patients with recurrent implantation failure during hormone replacement therapy cycles.

Background: The molecular mechanisms underlying window of implantation (WOI) displacement in patients with recurrent implantation failure (RIF) remain unclear. This study aims to explore the transcriptomic signatures of endometrium with normal and displaced WOIs and to identify the causes of endometrial receptivity (ER) abnormalities and WOI displacement in RIF patients. Methods: In this study, 40 RIF patients were recruited and underwent personalized embryo transfer (pET) guided by the predicted results of endometrial receptivity diagnosis (ERD) model. Transcriptome analysis of endometrium from patients with clinical pregnancies after pET was performed to identify differentially expressed genes (DEGs) associated with WOI displacement. Gene expression data from HRT and natural cycle endometrium were compared to identify specific gene expression patterns of ER-related genes during WOI. Results: The ERD results indicated that 67.5% of RIF patients (27/40) were non-receptive in the conventional WOI (P+5) of the HRT cycle. The clinical pregnancy rate in RIF patients improved to 65% (26/40) after ERD-guided pET, indicating the effectiveness of transcriptome-based WOI prediction. Among the 26 patients with clinical pregnancy, the gene expression profiles of P+5 endometrium from advanced (n=6), normal (n=10) and delayed (n=10) WOI groups were significantly different from each other. Furthermore, 10 DEGs identified among P+5 endometrium of 3 groups were involved in immunomodulation, transmembrane transport and tissue regeneration, which could accurately classify the endometrium with different WOIs. Additionally, a large number of ER-related genes showed significant correlation and similar gene expression patterns in P+3, P+5, and P+7 endometrium from HRT cycles and LH+5, LH+7, and LH+9 endometrium from natural cycles. Conclusion: Our study shows that ER-related genes share similar gene expression patterns during WOI in both natural and HRT cycles, and their aberrant expression is associated with WOI displacements. The improvement of pregnancy outcomes in RIF patients by adjusting ET timing according to ERD results demonstrates the importance of transcriptome-based endometrial receptivity assessment and the clinical efficiency of ERD model.

Genetically predicted testosterone and cancers risk in men: a two-sample Mendelian randomization study.

OBJECTIVE: In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. METHODS: We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. RESULTS: Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09-1.26, P = 2.51E-05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48-0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36-0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001-1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. CONCLUSION: This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

The genomic and transcriptome characteristics of lung adenocarcinoma patients with previous breast cancer.

BACKGROUND: Breast cancer and lung cancer are the top two malignancies in the female population and the number of patients with breast cancer and subsequent primary lung cancer has increased significantly in recent years. However, the unique molecular characteristics of this group of patients remains unclear. PURPOSE: To identify the genomic and transcriptome characteristics of primary lung adenocarcinoma patients with previous breast cancer by comparison with single primary lung adenocarcinoma (SPLA) patients. METHODS: The tumor and normal pulmonary tissue specimens of ten primary pulmonary adenocarcinoma patients with previous breast cancer (multiple primary cancer, MPC) and ten SPLA patients were prospectively collected. The whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed to analyze the gene mutation and expression differences between MPC and SPC patients. RESULTS: The results of WES indicated that the mutations of TRIM73, DLX6 and CNGB1 only existed in MPC patients. The results of RNA-seq manifested the occurrence of second primary lung adenocarcinoma in breast cancer patients was closely associated with cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Besides, the expression levels of FGF10 and VEGFA genes were significantly increased in MPC patients. CONCLUSION: The occurrence of second primary lung adenocarcinoma may be related to the cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Furthermore, the mutations of TRIM73, DLX6 and CNGB1 and high expression of FGF10 and VEGFA might play an important role in the development of lung adenocarcinoma in breast cancer patients. However, more in-depth investigations are needed to verify above findings.

Chronic kidney disease among greenhouse workers and field workers in China.

BACKGROUND: Agricultural workers are at increased risk of developing chronic kidney disease of non-traditional etiology (CKDnt). The environment in solar greenhouse has high-intensity agricultural hazard factors. However, the association between solar greenhouse work and CKDnt remains unknown. OBJECTIVES: We aimed to evaluate the relationship among solar greenhouse work, field work, and CKDnt risk, and to explore gender differences in CKDnt risk among solar greenhouse workers. METHODS: Solar greenhouse workers and field workers were selected as the greenhouse worker and field worker groups in a cross-sectional study. Individuals with an estimated glomerular filtration rate (eGFR) of <60 ml/min per 1.73 m2 were defined as CKDnt patients. Binary logistic regression and generalized linear regression models were used to estimate the association among solar greenhouse workers, field workers and CKDnt. Furthermore, gender differences in CKDnt were also analyzed. RESULTS: A total of 638 solar greenhouse workers and 231 field workers were included. The prevalence of CKDnt was 2.8% in the solar greenhouse workers and 0.4% in the field workers, and the prevalence of CKDnt was higher in female solar greenhouse workers than in males. The eGFR reduced by 20.0% (19.74 ml/min per 1.73 m2) in the greenhouse worker group compared with that in the field worker group (p < 0.05). Generalized linear analysis showed that the level of eGFR was lower in women than that in men after adjusting for parameters (ß = -10.99 [-12.79, -9.10]). CONCLUSION: Solar greenhouse workers may be at an increased risk of CKDnt, and women are more vulnerable.

Human umbilical cord mesenchymal stem cells contribute to the reconstruction of bladder function after acute spinal cord injury via p38 mitogen-activated protein kinase/nuclear factor-kappa B pathway.

The association between spinal cord injury (SCI) and bladder symptoms has been intensively described. Human umbilical cord mesenchymal stem cell (hUC-MSC) treatment is beneficial to the recovery of bladder function after SCI, but its mechanism is unclear. We established an SCI model, and prepared hUC-MSCs in advance, followed by verification using flow cytometry. The Basso, Beattie and Bresnahan (BBB) score and urodynamic index were employed to evaluate motor function and bladder functions, respectively. Hematoxylin-eosin staining, luxol fast blue staining, and Masson's trichrome staining were utilized to assess pathological changes. Real-time quantitative PCR and Western blot were used to determine the mRNA and protein expressions in bladder tissues. The immunophenotypes of the HUC-MSCs were CD90+ and CD105+, but CD34-, CD45- and HLA-DR-. Rats appeared severe motor dysfunction after SCI, but the BBB score was increased in hUC-MSCs after the second week. Pathologically, the improvement of the lesion area on the dorsal spinal cord, augmented anterior gray horn neuron cells of the spinal cord and lessened bladder tissue remodeling (fibrosis, collagen deposition) as well as modulated inflammation could be observed. Besides, SCI increased bladder weight, bladder capacity, urine volume and residual urine volume, and decreased urination efficiency. HUC-MSCs ameliorated SCI-induced pathological changes and bladder functions, the expressions of Collagen I, Collagen III, fibroblast growth factor 2 (FGF2), phospho-p38, transient receptor potential vanilloid 1, Toll-like receptor 4 and phospho-nuclear factor-kappa B (p-NF-κB). To sum up, HUC-MSCs contribute to the reconstruction of bladder function after SCI by repressing p38 MAPK/NF-κB pathway.

Discovery of an insulin-induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element-binding protein-mediated lipogenesis.

BACKGROUND AND AIMS: NASH is associated with high levels of cholesterol and triglyceride (TG) in the liver; however, there is still no approved pharmacological therapy. Synthesis of cholesterol and TG is controlled by sterol regulatory element-binding protein (SREBP), which is found to be abnormally activated in NASH patients. We aim to discover small molecules for treating NASH by inhibiting the SREBP pathway. APPROACH AND RESULTS: Here, we identify a potent SREBP inhibitor, 25-hydroxylanosterol (25-HL). 25-HL binds to insulin-induced gene (INSIG) proteins, stimulates the interaction between INSIG and SCAP, and retains them in the endoplasmic reticulum, thereby suppressing SREBP activation and inhibiting lipogenesis. In NASH mouse models, 25-HL lowers levels of cholesterol and TG in serum and the liver, enhances energy expenditure to prevent obesity, and improves insulin sensitivity. 25-HL dramatically ameliorates hepatic steatosis, inflammation, ballooning, and fibrosis through down-regulating the expression of lipogenic genes. Furthermore, 25-HL exhibits both prophylactic and therapeutic efficacies of alleviating NASH and atherosclerosis in amylin liver NASH model diet-treated Ldlr-/- mice, and reduces the formation of cholesterol crystals and associated crown-like structures of Kupffer cells. Notably, 25-HL lowers lipid contents in serum and the liver to a greater extent than lovastatin or obeticholic acid. 25-HL shows a good safety and pharmacokinetics profile. CONCLUSIONS: This study provides the proof of concept that inhibiting SREBP activation by targeting INSIG to lower lipids could be a promising strategy for treating NASH. It suggests the translational potential of 25-HL in human NASH and demonstrates the critical role of SREBP-controlled lipogenesis in the progression of NASH by pharmacological inhibition.

Transcriptomic profiling reveals gene expression in human peripheral blood after exposure to low-dose ionizing radiation.

Although the health effects of exposure to low-dose ionizing radiation have been the focus of many studies, the affected biological functions and underlying regulatory mechanisms are not well-understood. In particular, the influence of radiation exposure at doses of less than 200 mGy on the regulation of genes and pathways remains unclear. To investigate the molecular alterations induced by varying doses of low-dose radiation (LDR), transcriptomic analysis was conducted based on ribonucleic acid (RNA) sequencing following exposure to 50 and 150 mGy doses. Human peripheral blood was collected, and the samples were divided into three groups, including two treatments and one control (no radiation). A total of 876 (318 upregulated and 558 downregulated) and 486 (202 upregulated and 284 downregulated) differentially expressed genes (DEGs) were identified after exposure to 50 mGy and 150 mGy, respectively. Most upregulated genes in both the 50 mGy and 150 mGy groups were associated with 'antigen processing and presentation,' which appeared to be the major targets affected by LDR exposure. Several interacting genes, including HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRB1, and HLA-DRB5 were mapped to 'antigen processing and presentation,' 'immune system-related diseases' and the 'cytokine-mediated signaling pathway,' suggesting that these genes might drive the downstream transmission of these signal transduction pathways. Our results suggest that exposure to LDR may elicit changes in key genes and associated pathways, probably helping further explore the biological processes and molecular mechanism responsible for low-dose occupational or environmental exposures in humans.