Application of the PDCA cycle for implementing the WHO Safe Childbirth Checklist in women with vaginal deliveries.

The World Health Organization Safe Childbirth Checklist (SCC) has been recommended globally. However, the results are inconsistent. The aim of this study was to investigate the effectiveness of implementing the SCC based on plan-do-check-act (PDCA) cycle management. From November 2019 to October 2020, women who were hospitalized and had vaginal deliveries were enrolled in this study. Before October 2020, the PDCA cycle was not applied for the SCC, and women who had vaginal deliveries were included in the pre-intervention group. From January 2021 to December 2021, the PDCA cycle was applied for the SCC, and women who had vaginal deliveries were included in the post-intervention group. The SCC utilization rate and the incidence of maternal and neonatal complications were compared between the 2 groups. The SCC utilization rate in the post-intervention group was higher than that in the pre-intervention group (P < .01). The postpartum infection rate in the post-intervention group was lower than that in the pre-intervention group, and the difference was statistically significant (P < .05). After the intervention, postpartum hemorrhage, neonatal mortality, and neonatal asphyxia rates were also reduced, although no significant differences were observed between the 2 groups. There was no significant difference in the third-degree perineal laceration or neonatal intensive care unit hospitalization rate between the 2 groups (P > .05). Application of the PDCA cycle can improve the SCC utilization rate, and the SCC combined with the PDCA cycle can effectively reduce the postpartum infection rate.

Carboxyl-containing components delineation via feature-based molecular networking: A key to processing conditions of fermented soybean.

Carboxyl-containing components (CCCs) was the key chemical markers for fermented soybean, whose composition and content would be dramatically changed during the fermentation processes. To select the optimal fermented conditions, a rapid and sensitive 5-(diisopropylamino)amylamine derivatization, ultra-high performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry and feature-based molecular networking method was established for determination CCCs and the developed method was successfully applied to compare the dynamic changes of CCCs under different processing conditions. A total of 120 components were identified, the optimum fermentation conditions were the temperature at 30 °C, 50% humidity, with a 2-hour steaming time. Sixteen chemical markers with significant differences were screened. Furthermore, molecular docking technology was used to verify the antiperoxidative effect of these chemical markers. Accordingly, we focused on the high-content, little-studied active CCCs rather than the low-content and well-studied flavonoids. This study was helpful for the nutraceutical development and contributed scientific basis to further exploring quality evaluation of fermented food.

Resveratrol inhibits autophagy against myocardial ischemia-reperfusion injury through the DJ-1/MEKK1/JNK pathway.

Resveratrol (RES), a natural polyphenolic compound found in red wine and grape skins, has attracted significant attention due to its cardioprotective properties. DJ-1, a multifunctional protein that participated in transcription regulation and antioxidant defense, was shown to provide a significant protective impact in cardiac cells treated with ischemia-reperfusion. We created a myocardial ischemia-reperfusion (I/R) model in vivo and in vitro by ligating the left anterior descending branch of rats and subjecting H9c2 cells to anoxia/reoxygenation (A/R) to investigate whether RES reduces myocardial ischemia-reperfusion injury by upregulating DJ-1. We discovered that RES dramatically enhanced cardiac function in rats with I/R. Subsequently, we found that RES prevented the rise in autophagy (P62 degradation and LC3-II/LC3-I increase) induced by cardiac ischemia-reperfusion in vitro and in vivo. Notably, the autophagic agonist rapamycin (RAPA) eliminated RES-induced cardioprotective effects. In addition, Further data showed that RES significantly increased the expression of DJ-1 in the myocardium with the treatment of I/R. At the same time, pretreatment with RES reduced phosphorylation of MAPK/ERK kinase kinase 1 (MEKK1) and Jun N-terminal Kinase (JNK) stimulated by cardiac ischemia-reperfusion, and Beclin-1 mRNA and protein levels while decreasing lactate dehydrogenase (LDH) and improving cell viability. However, the lentiviral shDJ-1 and JNK agonist anisomycin disrupted the effects of RES. In summary, RES could inhibit autophagy against myocardial ischemia-reperfusion injury through DJ-1 modulation of the MEKK1/JNK pathway, providing a novel therapeutic strategy for cardiac homeostasis.

De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity.

Oncogenic stress induces DNA damage repair (DDR) that permits escape from mitotic catastrophe and allows early precursor lesions during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in DNA damage repair process. However, its role in tumorigenesis remains largely unknown. Here, we show that SAMHD1 is up-regulated in early-stage human carcinoma tissues and cell lines under oxidative stress or genotoxic insults. We further demonstrate that de-ubiquitinating enzyme USP7 interacts with SAMHD1 and de-ubiquitinates it at lysine 421, thus stabilizing SAMHD1 protein expression for further interaction with CtIP for DDR, which promotes tumor cell survival under genotoxic stress. Furthermore, SAMHD1 levels positively correlates with USP7 in various human carcinomas, and is associated with an unfavorable survival outcome in patients who underwent chemotherapy. Moreover, USP7 inhibitor sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1 in vitro and in vivo. These findings suggest that de-ubiquitination of SAMHD1 by USP7 promotes DDR to overcome oncogenic stress and affect chemotherapy sensitivity.

Exposure to phenols, chlorophenol pesticides, phthalate and PAHs and mortality risk: A prospective study based on 6 rounds of NHANES.

OBJECTIVES: Human exposure to various endocrine disrupting chemicals (EDCs) is widespread and long-lasting. The primary objective of this study was to prospectively evaluate the association of combined exposure of phenols, chlorophenol pesticides, phthalate and polycyclic aromatic hydrocarbons (PAHs) and mortality risk in a representative US population. METHODS: The data on urinary levels of phenols, chlorophenol pesticides, phthalates, and PAH metabolites, were collected from participants aged ≥20 years in six rounds of the National Health and Nutrition Examination Survey (NHANES) (2003-2014). NHANES-linked death records up to December 31, 2015 were used to ascertain mortality status and cause of death. Cox proportional hazards and competing risk models were mainly used for chemical and mortality risk association analysis. The weighted quantile sum (WQS) regression and the least absolute shrinkage and selection operator regression were employed to estimate the association between EDC co-exposure and mortality risk. RESULTS: High levels of mono-n-butyl phthalate, monobenzyl phthalate, and 1-napthol were significantly associated with increased risk of all cause, cardiovascular disease (CVD) and cancer mortality among all participants. WQS index was associated with the risks of all-cause (hazard ratio [HR] = 1.389, 95%CI: 1.155-1.669) and CVD mortality (HR = 1.925, 95%CI: 1.152-3.216). High co-exposure scores were associated with elevated all-cause (HR = 2.842, 95% CI: 1.2.094-3.858), CVD (HR = 1.855, 95% CI: 1.525-2.255), and cancer mortality risks (HR = 2.961, 95% CI: 1.468-5.972). The results of subgroup analysis, competing risk model, and sensitivity analysis were generally consistent with the findings from the main analyses, indicating the robustness of our findings. CONCLUSIONS: This study provided the first epidemiological evidence that co-exposure to EDC at fairly low levels contributed to elevated mortality risk among US adults. The underlying mechanisms for the effects of EDC co-exposure on human health are worthy of future exploration.

Gypenosides ameliorate high-fat diet-induced nonalcoholic fatty liver disease in mice by regulating lipid metabolism.

Gypenosides (GP), extracted from the traditional Chinese herb Gynostemma pentaphyllum (Thunb.) Makino, have been used to treat metabolic disorders, including lipid metabolism disorders and diabetes. Although recent studies have confirmed their beneficial effects in nonalcoholic fatty liver disease (NAFLD), the underlying therapeutic mechanism remains unclear. In this study, we explored the protective mechanism of GP against NAFLD in mice and provided new insights into the prevention and treatment of NAFLD. Male C57BL6/J mice were divided into three experimental groups: normal diet, high-fat diet (HFD), and GP groups. The mice were fed an HFD for 16 weeks to establish an NAFLD model and then treated with GP for 22 weeks. The transcriptome and proteome of the mice livers were profiled using RNA sequencing and high-resolution mass spectrometry, respectively. The results showed that GP decreased serum lipid levels, liver index, and liver fat accumulation in mice. Principal component and heatmap analyses indicated that GP significantly modulated the changes in the expression of genes associated with HFD-induced NAFLD. The 164 differentially expressed genes recovered using GP were enriched in fatty acid and steroid metabolism pathways. Further results showed that GP reduced fatty acid synthesis by downregulating the expression of Srebf1, Fasn, Acss2, Acly, Acaca, Fads1, and Elovl6; modulated glycerolipid metabolism by inducing the expression of Mgll; promoted fatty acid transportation and degradation by inducing the expression of Slc27a1, Cpt1a, and Ehhadh; and reduced hepatic cholesterol synthesis by downregulating the expression of Tm7sf2, Ebp, Sc5d, Lss, Fdft1, Cyp51, Nsdhl, Pmvk, Mvd, Fdps, and Dhcr7. The proteomic data further indicated that GP decreased the protein expression levels of ACACA, ACLY, ACSS2, TM7SF2, EBP, FDFT1, NSDHL, PMVK, MVD, FDPS, and DHCR7 and increased those of MGLL, SLC27A1, and EHHADH. In conclusion, GP can regulate the key genes involved in hepatic lipid metabolism in NAFLD mice, providing initial evidence for the mechanisms underlying the therapeutic effect of GP in NAFLD.

A nomogram based on endothelial function and conventional risk factors predicts coronary artery disease in hypertensives.

BACKGROUND: There is currently a lack of a precise, concise, and practical clinical prediction model for predicting coronary artery disease (CAD) in patients with essential hypertension (EH). This study aimed to construct a nomogram to predict CAD in patients with EH based on flow-mediated dilation (FMD) of brachial artery and traditional risk factors. METHODS: Clinical data of 1752 patients with EH were retrospectively collected. High-resolution vascular ultrasound was used to detect FMD in all patients at the Fujian Hypertension Research Institute, China. Patients were divided into two groups, i.e. training group (n = 1204, from August 2000 to December 2013) and validation group (n = 548, from January 2014 to May 2016) according to the time of enrollment. Independent predictors of CAD were analyzed by multivariable logistic regression in the training group, and a nomogram was constructed accordingly. Finally, we evaluated the discrimination, calibration, and clinical applicability of the model using the area under curve (AUC) of receiver operating characteristic analysis, calibration curve combined with Hosmer-Lemeshow test, and decision curve, respectively. RESULTS: There were 263 (21.8%) cases of EH combined with CAD in the training group. Multivariate logistic regression showed that FMD, age, duration of EH, waist circumference, and diabetes mellitus were independent influencing factors for CAD in EH patients. Smoking which was close to statistical significance (P = 0.062) was also included in the regression model to increase the accuracy. Ultimately, the nomogram for predicting CAD in EH patients was constructed according to above predictors after proper transformation. The AUC values of the training group and the validation group were 0.799 (95%CI 0.770-0.829) and 0.836 (95%CI 0.787-0.886), respectively. Calibration curve and Hosmer-Lemeshow test showed that the model had good calibration (training group: χ2 = 0.55, P = 0.759; validation group: χ2 = 1.62, P = 0.446). The decision curve also verified the clinical applicability of the nomogram. CONCLUSION: The nomogram based on FMD and traditional risk factors (age, duration of EH disease, smoking, waist circumference and diabetes mellitus) can predict CAD high-risk group among patients with EH.

Integrative taxonomy of a new species of Rhyacodrilus (Annelida: Clitellata: Rhyacodrilinae) from Tibet Plateau rivers, with a preliminary assessment of its phylogenetic position.

A new Qinghai-Tibet Plateau species, Rhyacodrilus tanggulaensis Jiang & Cui sp. nov. (Annelida, Clitellata, Naididae, Rhyacodrilinae), is described, and its phylogenetic relationships within the genus is assessed on the basis of both mitochondrial (16S rDNA, COⅠ gene) and nuclear (ITS2) markers. Data from 32 species of Naididae, representing 7 subfamilies and 25 genera are used. Ten species were chosen as outgroup taxa. The molecular data were analyzed by Bayesian inference. The new species is distinguished from other species of Rhyacodrilus by the following combination of characters: dorsal and ventral chaetae with distal tooth 2-3 times longer than proximal, spermathecal and penial chaetae present, atria long and tubular, atrial duct conspicuous. The analyses of the combined molecular data corroborate the close relationship between Naidinae and the rhyacodriline genera Rhyacodrilus, Monopylephorus, and Ainudrilus, and show that the new species is more closely related to R. falciformis, R pigueti, R. okamikae and R. subterraneus, than to R. sinicus, another Chinese species, R. hiemalis and R. coccineus.

ADCY9 functions as a novel cancer suppressor gene in lung adenocarcinoma.

Background: The process of lucubrating into lung adenocarcinoma (LUAD) is of profound clinical and practical significance in improving the prognosis of LUAD patients. Multiple biomarkers are reportedly involved in the proliferation or metastasis of adenocarcinoma. However, whether the ADCY9 gene influences the development of LUAD remains unknown. Therefore, we aimed to elucidate the relationship between the expression of ADCY9 and the proliferation and migration of LUAD. Methods: The ADCY9 gene was filtered via a survival analysis of LUAD acquired from the Gene Expression Omnibus (GEO). Then, we conducted a validation analysis and ADCY9-microRNA, microRNA-lncRNA, and ADCY9-lncRNA targeting relationship analysis through the data obtained from The Cancer Genome Atlas (TCGA) dataset. The survival curve, correlation, and prognostic analysis were implemented through bioinformatics methods. Both protein and mRNA expression levels of LUAD cell lines and LUAD patient samples (80 pairs) were detected using western blot assays and quantitative real-time polymerase chain reaction (qRT-PCR). An immunohistochemistry assay was performed to display the correlation between the expression level of the ADCY9 gene and prognosis in LUAD patients (2012-2013; n=115). Overexpression of cell lines SPCA1 and A549 were used for a series of cell function assays. Results: Compared with the expression level in adjacent normal tissues, ADCY9 expression was downregulated in LUAD tissues. Based on the result of the survival curve analysis, high expression of ADCY9 may lead to a better prognosis and may be seen as an independent predictor for LUAD patients. High expression of ADCY9-related microRNA hsa-miR-7-5p may lead to a worse prognosis, and high expression of hsa-miR-7-5p-related lncRNAs may lead to the opposite effects. Overexpression of ADCY9 restrained the proliferation, invasion, and migration abilities of SPCA1, A549 cells. Conclusions: Results indicate that the ADCY9 gene acts as a tumor suppressor to restrain the proliferation, migration, and invasion in LUAD and can lead to a better survival or prognosis in LUAD patients.

Flexible Room-Temperature Ammonia Gas Sensors Based on PANI-MWCNTs/PDMS Film for Breathing Analysis and Food Safety.

Gas sensors have played a critical role in healthcare, atmospheric environmental monitoring, military applications and so on. In particular, flexible sensing devices are of great interest, benefitting from flexibility and wearability. However, developing flexible gas sensors with a high sensitivity, great stability and workability is still challenging. In this work, multi-walled carbon nanotubes (MWCNTs) were grown on polydimethylsiloxane (PDMS) films, which were further modified with polyaniline (PANI) using a simple chemical oxidation synthesis. The superior flexibility of the PANI-MWCNTs/PDMS film enabled a stable initial resistance value, even under bending conditions. The flexible sensor showed excellent NH3 sensing performances, including a high response (11.8 ± 0.2 for 40 ppm of NH3) and a low limit of detection (10 ppb) at room temperature. Moreover, the effect of a humid environment on the NH3 sensing performances was investigated. The results show that the response of the sensor is enhanced under high humidity conditions because water molecules can promote the adsorption of NH3 on the PANI-MWCNTs/PDMS films. In addition, the PANI-MWCNTs/PDMS film sensor had the abilities of detecting NH3 in the simulated breath of patients with kidney disease and the freshness of shrimp. These above results reveal the potential application of the PANI-MWCNTs/PDMS sensor for monitoring NH3 in human breath and food.

Cancer-related symptoms among young and middle-aged women undergoing chemotherapy for breast cancer: Application of latent class analysis and network analysis.

PURPOSE: To identify subgroups and symptom networks of cancer-related symptoms for women under 60 years who are undergoing chemotherapy for breast cancer. METHODS: A cross-sectional survey in Mainland China was conducted between August 2020 and November 2021. Participants completed questionnaires that collected demographic and clinical characteristics and featured the PROMIS-57 and the PROMIS-Cognitive Function Short Form. RESULTS: A total of 1033 participants were included in the analysis, and three-class model was identified: "severe symptom group" (17.6%; Class 1), "moderately severe anxiety, depression, and pain-interference group" (38.0%; Class 2), and "mild symptom group" (44.4%; Class 3). Patients who were in menopause (OR = 3.05, P < .001), undergoing a combination of medical treatments (OR = 2.39, P = .003), and who had experienced complications (OR = 1.86, P = .009) were more likely to belong to Class 1. However, having two or more children increased the likelihood of belonging to Class 2. Additionally, network analysis showed that severe fatigue level was the core symptom among the full sample. As for Class 1, feeling helpless and severe fatigue level were the core symptoms. Regarding Class 2, the impact of pain interfere on the ability to participate in social activities and feeling hopeless were found to be the targeted symptoms for intervention. CONCLUSION: Menopause, receiving a combination of medical treatments, and experiencing complications characterize the group with the most symptom disturbance. Moreover, different interventions should be performed for core symptoms in patients with varied symptom disturbances.

Classification of symptom subtypes in patients with multiple myeloma during treatment: a cross-sectional survey study in China.

OBJECTIVES: To classify subgroups of cancer-related symptoms in patients with multiple myeloma (MM) during treatment and examine between-group differences in demographic and clinical characteristics in addition to functional status. DESIGN: Cross-sectional survey study. SETTING: Haematology department of two tertiary hospitals affiliated with Guilin Medical University in China. PARTICIPANTS: Using a convenience sampling method, questionnaires were distributed to patients with MM visiting two hospitals in Guilin, China. INTERVENTIONS: The patients were categorised into subgroups based on cancer-related symptoms using a latent class analysis. An analysis of covariance was performed to examine how demographic and clinical characteristics and functional status differed among the subgroups. RESULTS: In total, 216 patients completed the survey, with an average age of 60.3 years. A three-class solution was identified: low symptom burden group (class 1, 36.6%), moderate symptom burden group (class 2, 34.2%) and high symptom burden group (class 3, 29.2%). Patients with low monthly family income (OR=3.14, p=0.010) and complications of MM bone disease (OR=2.95, p=0.029) were more likely to belong to class 2. The predictors of high-burden symptoms were treated with painkillers, antidepressants or hypnotic drugs (OR=3.68, p=0.012) and <5000 daily step counts (OR=2.52, p=0.039) in class 3. Functional status was correlated with symptom burden, with patients in classes 3 and 1 reporting significantly higher and lower functional status, respectively (p<0.05). CONCLUSIONS: Patients with MM experienced varying degrees of symptoms during treatment. The identification of patients with high symptom burden management should focus on the assessment of demographic and clinical characteristics, in addition to functional status.

Effects of shear emulsifying/ball milling/autoclave modification on structure, physicochemical properties, phenolic compounds, and antioxidant capacity of lotus (Nelumbo) leaves dietary fiber.

Lotus (Nelumbo) leaves are rich in polyphenols and dietary fiber, which have the potential as a high-quality fiber material in functional food. However, lotus leaves exhibit dense structure and poor taste, it is vital to develop appropriate modification methods to improve the properties of lotus leaves dietary fiber. In this study, the effects of three modification methods with shear emulsifying (SE), ball milling (BM), and autoclave treatment (AT) on structure, physicochemical properties, phenolic compounds, and antioxidant capacity of lotus leave dietary fiber (LDF) were evaluated. SEM indicated that there were significant differences in the microstructure of modified LDFs. FT-IR spectra and X-ray diffraction pattern of modified LDFs revealed similar shapes, while the peak intensity and crystalline region changed by modification. SE showed the greatest effect on crystallization index. SE-LDF had the highest water holding capacity, water swelling capacity, and bound phenolic content in LDFs, which increased by 15.69, 12.02, and 31.81%, respectively, compared with the unmodified LDF. BM exhibited the most dramatic effect on particle size. BM-LDF had the highest free phenolic and total phenolic contents in LDFs, which increased by 32.20 and 29.05% respectively, compared with the unmodified LDF. Phenolic compounds in LDFs were mainly free phenolic, and modifications altered the concents of flavonoids. The BM-LDF and SE-LDF exhibited higher antioxidant capacity than that of AT-LDF. Overall, SE-LDF showed better physical properties, and BM-LDF showed better bioactive components. SE and BM were considered to be appropriate modification methods to enhance the properties of LDF with their own advantages.

Bioinformatics analysis of Omp19 and Omp25 proteins for designing multi-epitope vaccines against Brucella.

Brucellosis is a zoonotic disease caused by Brucella. There is no effective vaccine against human brucellosis. Omp19 and Omp25 are the outer membrane proteins of Brucella. They are widely expressed and highly conserved in Brucella and have high immunogenicity. Herein, we aim to identify multi-epitope vaccine candidates based on Omp19 and Omp25. We analyzed the physicochemical properties and protein structure of Omp19 and Omp25, and predicted the corresponding B cell and T cell epitopes using bioinformatics analysis. Omp19 and Omp25 were composed of 177 amino acids and 213 amino acids, respectively. They were both stable hydrophilic proteins. The instability indices were 44.8 and 23, respectively. The hydrophilicity was -0.1 and -0.317, respectively. In the secondary structure of Omp19 and Omp25 proteins, the α-helix accounted for 12.43% and 23.94%, the ß-sheet was 18.64% and 23.47%, the ß-turn was 6.78% and 4.23%, and the random coil was 62.15% and 48.36%. Finally, 5 B cell epitopes, 3 Th-cell epitopes and 5 CTL cell epitopes of Omp19 protein, and 4 B cell epitopes, 3 Th-cell epitopes, and 5 CTL cell epitopes of Omp25 protein were selected as vaccine candidates. In conclusion, we obtained potential B cell and T cell epitopes of the Brucella outer membrane Omp19 and Omp25 proteins. This lays the foundation for the further design of multi-epitope vaccine of Brucella.

Effect of endodontic treatment on clinical outcome in type 2 diabetic patients with apical periodontitis.

Background: Previous research has demonstrated that poor controlled diabetic showed higher prevalence of AP compared to well-controlled patients and endodontic treatment may improve metabolic control of patients with diabetes. The purpose of this trial was to clinically assess the effects of endodontic treatment on glycemic control in patients with type 2 diabetes mellitus (T2DM) and apical periodontitis (AP). Study design: For present trial, AP + T2DM with patients insulin injection (Group1, G1,n = 65), AP + T2DM patients with hypoglycaemic agents (Group2, G2, n = 82), and AP patients without DM (Group3, G3, n = 86) were enrolled. After demographic characteristics and clinical examination were achieved, root canal treatment (RCT) was performed for each patient. Subjects were followed up at 2-week, 3- and 6-month. At each visit, blood samples were taken and clinical laboratory studies were performed. At 6-month follow-up, Periapical Index (PAI) score was used to assess the periapical status. Results: A total of 237 subjects who met the including criteria were allocated in three groups and 223 subjects (94.1%) completed the treatments and the follow-up assessments. After treatment, taking PAI into consideration, both groups showed significant improvement of AP in each group (P < 0.05). Patients in G3 had a continued significant lower concentration of fasting plasma glucose (FPG) levels at follow-up (P < 0.05). A continued reduction of hemoglobin glycation (HbA1c) was observed in most of time points (P < 0.05). Throughout the trial, there are also significant changes in inflammatory factors in short-term. Conclusion: Endodontic therapy improved AP healing, glycemic control and systemic inflammation in patients with T2DM and/or AP in each group. However, a continued reduction in inflammatory factors and decreasing of HbA1c in short-term could not be observed in this trial.

Identification of age differences in cancer-related symptoms in women undergoing chemotherapy for breast cancer in China.

BACKGROUND: Both contextual and cancer-related factors could be identified as causes of the interindividual variability observed for symptoms experienced during breast cancer treatment with chemotherapy. Understanding age differences and the predictors of latent class memberships for symptom heterogeneity could contribute to personalized interventions. This study aimed to identify the role of age differences on cancer-related symptoms in women undergoing chemotherapy for breast cancer in China. METHODS: A cross­sectional survey was conducted among patients with breast cancer in three tertiary hospitals in central China between August 2020 to December 2021. The outcomes of this study included sociodemographic and clinical characteristics, Patient-Reported Outcomes Measurement Information System (PROMIS)-57 and PROMIS-cognitive function short form scores. RESULTS: A total of 761 patients were included, with a mean age of 48.5 (SD = 11.8). Similar scores were observed across age groups for all symptoms except for fatigue and sleep disturbance domains. The most central symptoms varied among each group, and were fatigue, depression, and pain interference for the young-aged, middle-aged, and elderly-aged groups, respectively. In the young-aged group, patients without health insurance (OR = 0.30, P = 0.048) and in the fourth round of chemotherapy or above (OR = 0.33, P = 0.005) were more likely to belong to low symptom classes. In the middle-aged group, patients in menopause (OR = 3.58, P = 0.001) were more likely to belong to high symptom classes. In the elderly-aged group, patients with complications (OR = 7.40, P = 0.003) tended to belong to the high anxiety, depression, and pain interference classes. CONCLUSIONS: Findings from this study indicated that there is age-specific heterogeneity of symptoms present for Chinese women being treated for breast cancer with chemotherapy. Tailored intervention should consider the impact of age to reduce patients' symptom burdens.

Single-Cell RNA Transcriptome Profiling of Liver Cells of Short-Term Alcoholic Liver Injury in Mice.

Alcoholic liver disease (ALD) is currently considered a global healthcare problem with limited pharmacological treatment options. There are abundant cell types in the liver, such as hepatocytes, endothelial cells, Kupffer cells and so on, but little is known about which kind of liver cells play the most important role in the process of ALD. To obtain a cellular resolution of alcoholic liver injury pathogenesis, 51,619 liver single-cell transcriptomes (scRNA-seq) with different alcohol consumption durations were investigated, 12 liver cell types were identified, and the cellular and molecular mechanisms of the alcoholic liver injury were revealed. We found that more aberrantly differential expressed genes (DEGs) were present in hepatocytes, endothelial cells, and Kupffer cells than in other cell types in alcoholic treatment mice. Alcohol promoted the pathological processes of liver injury; the specific mechanisms involved: lipid metabolism, oxidative stress, hypoxia, complementation and anticoagulation, and hepatocyte energy metabolism on hepatocytes; NO production, immune regulation, epithelial and cell migration on endothelial cells; antigen presentation and energy metabolism on Kupffer cells, based on the GO analysis. In addition, our results showed that some transcription factors (TFs) are activated in alcohol-treated mice. In conclusion, our study improves the understanding of liver cell heterogeneity in alcohol-fed mice at the single-cell level. It has potential value for understanding key molecular mechanisms and improving current prevention and treatment strategies for short-term alcoholic liver injury.

Histone phosphorylation integrates the hepatic glucagon-PKA-CREB gluconeogenesis program in response to fasting.

The glucagon-PKA signal is generally believed to control hepatic gluconeogenesis via the CREB transcription factor. Here we uncovered a distinct function of this signal in directly stimulating histone phosphorylation for gluconeogenic gene regulation in mice. In the fasting state, CREB recruited activated PKA to regions near gluconeogenic genes, where PKA phosphorylated histone H3 serine 28 (H3S28ph). H3S28ph, recognized by 14-3-3ζ, promoted recruitment of RNA polymerase II and transcriptional stimulation of gluconeogenic genes. In contrast, in the fed state, more PP2A was found near gluconeogenic genes, which counteracted PKA by dephosphorylating H3S28ph and repressing transcription. Importantly, ectopic expression of phosphomimic H3S28 efficiently restored gluconeogenic gene expression when liver PKA or CREB was depleted. These results together highlight a different functional scheme in regulating gluconeogenesis by the glucagon-PKA-CREB-H3S28ph cascade, in which the hormone signal is transmitted to chromatin for rapid and efficient gluconeogenic gene activation.

Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice.

The early phase lipid accumulation is essential for liver regeneration. However, whether this acute lipid accumulation can serve as signals to direct liver regeneration rather than simply providing building blocks for cell proliferation remains unclear. Through in vivo CRISPR screening, we identify MIER1 (mesoderm induction early response 1) as a key epigenetic regulator that bridges the acute lipid accumulation and cell cycle gene expression during liver regeneration in male animals. Physiologically, liver acute lipid accumulation induces the phosphorylation of EIF2S1(eukaryotic translation initiation factor 2), which consequently attenuated Mier1 translation. MIER1 downregulation in turn promotes cell cycle gene expression and regeneration through chromatin remodeling. Importantly, the lipids-EIF2S1-MIER1 pathway is impaired in animals with chronic liver steatosis; whereas MIER1 depletion significantly improves regeneration in these animals. Taken together, our studies identify an epigenetic mechanism by which the early phase lipid redistribution from adipose tissue to liver during regeneration impacts hepatocyte proliferation, and suggest a potential strategy to boost liver regeneration.