CytoCellDB: a comprehensive resource for exploring extrachromosomal DNA in cancer cell lines.

Recently, the cancer community has gained a heightened awareness of the roles of extrachromosomal DNA (ecDNA) in cancer proliferation, drug resistance and epigenetic remodeling. However, a hindrance to studying ecDNA is the lack of available cancer model systems that express ecDNA. Increasing our awareness of which model systems express ecDNA will advance our understanding of fundamental ecDNA biology and unlock a wealth of potential targeting strategies for ecDNA-driven cancers. To bridge this gap, we created CytoCellDB, a resource that provides karyotype annotations for cell lines within the Cancer Dependency Map (DepMap) and the Cancer Cell Line Encyclopedia (CCLE). We identify 139 cell lines that express ecDNA, a 200% increase from what is currently known. We expanded the total number of cancer cell lines with ecDNA annotations to 577, which is a 400% increase, covering 31% of cell lines in CCLE/DepMap. We experimentally validate several cell lines that we predict express ecDNA or homogeneous staining regions (HSRs). We demonstrate that CytoCellDB can be used to characterize aneuploidy alongside other molecular phenotypes, (gene essentialities, drug sensitivities, gene expression). We anticipate that CytoCellDB will advance cytogenomics research as well as provide insights into strategies for developing therapeutics that overcome ecDNA-driven drug resistance.

Effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy.

Objective: To find out the effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy. Methods: This was a retrospective study. Sixty six patients with nasopharyngeal carcinoma who received radiotherapy in the Affiliated Hospital of Hebei University from March 2021 to March 2022 were included and randomly divided into the observation group and the control group, with 33 cases in each group. Patients in the control group were given conventional care measures, while those in the observation group were given psychological support intervention on top of conventional care measures. The nursing effects between the two groups were compared. Results: After the intervention, the psychological resilience score of the observation group was significantly higher than that of the control group, with a statistically significant difference (P<0.05). The psychological resilience scores after the intervention were significantly higher in the observation group than before the intervention, and those in the control group were higher than before the intervention, with a statistically significant difference(P<0.05). The overall health score of quality of life in the observation group was significantly higher than that in the control group after the intervention, with a statistically significant difference(P<0.05). Moreover, the skin reaction in the observation group after radiotherapy was significantly better than that of the control group (P<0.01). Conclusion: Psychological support intervention is an effective means to treat patients with nasopharyngeal carcinoma, which results in various benefits such as improving patients' mental resilience and quality of life and reducing the incidence of adverse reactions after radiotherapy.

Structural basis of psychedelic LSD recognition at dopamine D1 receptor.

Understanding the kinetics of LSD in receptors and subsequent induced signaling is crucial for comprehending both the psychoactive and therapeutic effects of LSD. Despite extensive research on LSD's interactions with serotonin 2A and 2B receptors, its behavior on other targets, including dopamine receptors, has remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound dopamine D1 receptor (DRD1)-legobody complexes, accompanied by a ß-arrestin-mimicking nanobody, NBA3, shedding light on the determinants of G protein coupling versus ß-arrestin coupling. Structural analysis unveils a distinctive binding mode of LSD in DRD1, particularly with the ergoline moiety oriented toward TM4. Kinetic investigations uncover an exceptionally rapid dissociation rate of LSD in DRD1, attributed to the flexibility of extracellular loop 2 (ECL2). Moreover, G protein can stabilize ECL2 conformation, leading to a significant slowdown in ligand's dissociation rate. These findings establish a solid foundation for further exploration of G protein-coupled receptor (GPCR) dynamics and their relevance to signal transduction.

Hepatocyte Uptake and Loss Assay (HUpLA): Proof-of-Concept of an All-in-One System for Measuring Hepatic Influx, Egress, and Metabolic Clearance Based on the Extended Clearance Concept.

Hepatic clearance (CLH) prediction is a critical parameter to estimate human dose. However, CLH underpredictions are common, especially for slowly metabolized drugs, and may be attributable to drug properties that pose challenges for conventional in vitro ADME assays, resulting in non-valid data, which prevents in-vitro-to-in-vivo extrapolation and CLH predictions. Other processes, including hepatocyte and biliary distribution via transporters, can also play significant roles in CLH Recent advances in understanding the interplay of metabolism and drug transport for clearance processes have aided in developing the Extended Clearance Model (ECM). In this study, we demonstrate proof-of-concept of a novel two-step assay enabling measurement of multiple kinetic parameters from a single experiment in plated human primary hepatocytes with and without transporter and CYP inhibitors - the Hepatocyte Uptake and Loss Assay (HUpLA). HUpLA accurately predicted the CLH of 8 of the 9 drugs (within 2-fold of the observed CLH). Distribution clearances were within 3-fold of observed literature values in standard uptake and efflux assays. In comparison, the conventional suspension hepatocyte stability assay poorly predicted the CLH CLH of only 2 drugs were predicted within 2-fold of the observed CLH Therefore, HUpLA is advantageous by enabling the measurement of enzymatic and transport processes concurrently within the same system, alleviating the need for applying scaling factors independently. The use of primary human hepatocytes enables physiologically relevant exploration of transporter-enzyme interplay. Most importantly, HUpLA shows promise as a sensitive measure for low-turnover drugs. Further evaluation across different drug characteristics is needed to demonstrate method robustness. Significance Statement HUpLA involves measuring four commonly derived in vitro hepatic clearance endpoints. Since endpoints are generated within a single test system, it blunts experimental error originating from assays otherwise conducted independently. A key advance is the concept of removing drug-containing media following intracellular drug loading, enabling measurement of drug reappearance rate in media, as well as measurement of loss of total drug in the test system unencumbered by background quantities of drug in media otherwise present in a conventional assay.

Alleviating effects of microplastics together with tetracycline hydrochloride on the physiological stress of Closterium sp.

Microplastics have significant influence on both freshwater cyanobacteria and marine microalgae, especially under co-exposure with other pollutants such as heavy metals, antibiotics, and pharmaceuticals. In the present study, combined effects of microplastics (polyethylene terephthalate (PET) or polybutylene terephthalate (PBT)) and tetracycline hydrochloride (TCH) on the microalgae Closterium sp. were studied to evaluate their acute toxicity, and the cell density, total chlorophyll concentration, photosynthetic activity, antioxidant system, and subcellular structure of Closterium sp. under different treatments were used to explain the physiological stress mechanism of the combined effects. The results indicate that both the single and combined treatments have inhibition effects on the cell growth and photosynthetic activity, with inhibition efficiencies (in terms of cell density) of 5.0%, 9.2%, 66.7%, 55.1%, and 59.8% for PET (100 mg L-1), PBT (100 mg L-1), TCH (10 mg L-1), PET/TCH (PET 100 mg L-1 and TCH 10 mg L-1), and PBT/TCH (PBT 100 mg L-1 and TCH 10 mg L-1), respectively, and relative electron-transport rates (rETRs) of 7.3%, 12.7%, 66.8%, 54.0%, and 59.9%, respectively, for each treatment compared with the control on the 7th day. Moreover, both PET and PBT have positive effects in alleviating TCH toxicity toward Closterium sp., and at the same time, the malondialdehyde level (MDA), superoxide dismutase (SOD) activity, and catalase (CAT) activity induced by the combined treatments were much higher than those from the single microplastic treatments but lower than those from TCH treatment after 7 days. It was demonstrated that TCH causes a much more serious oxidative stress than PET/TCH and PBT/TCH, and the lower oxidative stress of the PET/TCH and PBT/TCH groups could be attributed to the adsorption of TCH to PET or PBT. This work improves the understanding of the combined toxicity effects of microplastics and TCH on Closterium sp.

Screening and Exploring the Application of the Multifunctional Antioxidant Peptides MSWLC and TSWLC.

In this study, an antioxidant pentapeptide library is created based on antioxidant characteristics. The peptides are then purified and separated using liquid chromatography/mass spectrometry (LC/MS) and time-of-flight mass spectrometry (TOF). Chemical evaluations identify four peptides with excellent antioxidant activity. The four peptides undergo biocompatibility testing with L-929, NIH 3T3, and Hep-G2 cells. A model of hydrogen peroxide-induced cellular damage in G2 cells shows the peptides' protective and reparative effects against oxidative damage. Two peptides, MSWLC and TSWLC, which perform best overall, are chosen for further analysis. To explore the peptides' potential multifunctionality, acute liver inflammation, keratitis, and aging models are established in mice. MSWLC and TSWLC demonstrate anti-inflammatory and anti-aging properties. An antioxidant emulsion prepared by emulsification is found to be non-irritant in a mouse skin irritation test. In a mouse model exposed to ultraviolet radiation, the sunscreen exhibits excellent UV protection and antioxidant effects. These peptides possess potent antioxidant properties and multifunctionality, indicating broad application potential.

Electroencephalographic Measures of Delirium in the Perioperative Setting: A Systematic Review.

Postoperative delirium (POD) is frequent in older adults and is associated with adverse cognitive and functional outcomes. In the last several decades, there has been an increased interest in exploring tools that easily allow the early recognition of patients at risk of developing POD. The electroencephalogram (EEG) is a widely available tool used to understand delirium pathophysiology, and its use in the perioperative setting has grown exponentially, particularly to predict and detect POD. We performed a systematic review to investigate the use of EEG in the pre-, intra-, and postoperative settings. We identified 371 studies, and 56 met the inclusion criteria. A range of techniques was used to obtain EEG data, from limited 1-4 channel setups to complex 256-channel systems. Power spectra were often measured preoperatively, yet the outcomes were inconsistent. During surgery, the emphasis was primarily on burst suppression (BS) metrics and power spectra, with a link between the frequency and timing of BS, and POD. The EEG patterns observed in POD aligned with those noted in delirium in different contexts, suggesting a reduction in EEG activity. Further research is required to investigate preoperative EEG indicators that may predict susceptibility to delirium.

Predicting mine water inflow volumes using a decomposition-optimization algorithm-machine learning approach.

Disasters caused by mine water inflows significantly threaten the safety of coal mining operations. Deep mining complicates the acquisition of hydrogeological parameters, the mechanics of water inrush, and the prediction of sudden changes in mine water inflow. Traditional models and singular machine learning approaches often fail to accurately forecast abrupt shifts in mine water inflows. This study introduces a novel coupled decomposition-optimization-deep learning model that integrates Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN), Northern Goshawk Optimization (NGO), and Long Short-Term Memory (LSTM) networks. We evaluate three types of mine water inflow forecasting methods: a singular time series prediction model, a decomposition-prediction coupled model, and a decomposition-optimization-prediction coupled model, assessing their ability to capture sudden changes in data trends and their prediction accuracy. Results show that the singular prediction model is optimal with a sliding input step of 3 and a maximum of 400 epochs. Compared to the CEEMDAN-LSTM model, the CEEMDAN-NGO-LSTM model demonstrates superior performance in predicting local extreme shifts in mine water inflow volumes. Specifically, the CEEMDAN-NGO-LSTM model achieves scores of 96.578 in MAE, 1.471% in MAPE, 122.143 in RMSE, and 0.958 in NSE, representing average performance improvements of 44.950% and 19.400% over the LSTM model and CEEMDAN-LSTM model, respectively. Additionally, this model provides the most accurate predictions of mine water inflow volumes over the next five days. Therefore, the decomposition-optimization-prediction coupled model presents a novel technical solution for the safety monitoring of smart mines, offering significant theoretical and practical value for ensuring safe mining operations.

A multicenter cross-sectional study in China revealing the intrinsic relationship between medical students' grade and their perceptions of the learning environment.

BACKGROUND: Medical school learning environment (MSLE) has a holistic impact on students' psychosomatic health, academic achievements, and personal development. Students in different grades perceive MSLE in different ways. Thus, it is essential to investigate the specific role of student's grade in the perception of MSLE. METHODS: Using the Johns Hopkins Learning Environment Scale (JHLES) as a quantification instrument for the perception level of MSLE, 10,901 medical students in 12 universities in China were categorized into low or high JHLES group according to their questionnaires. We investigated the relationship between student's grade and JHLES category by univariate analysis employing Pearson Chi-square test and Welch's ANOVA. Then multivariable logistic regression analysis confirmed the predictive efficacy of student's grade. A nomogram concerning the prediction of low JHLES score probability in medical students was also constructed. RESULTS: A significant difference between two JHLES categories among students in different grades was observed (p < 0.001), with the proportion of the high JHLES group dominating in grade 1, 5, and the graduate subgroups (p < 0.001). The mean JHLES score declined especially in the third and fourth graders compared to freshmen (p < 0.001), while the mean score among the fifth graders had a remarkable rebound from the third graders (p < 0.001). Most imperatively, identified by multivariable logistic regression analysis, students in grade 3 (OR = 1.470, 95% CI = 1.265-1.709, p < 0.001) and 4 (OR = 1.578, 95% CI = 1.326-1.878, p < 0.001) perceived more negatively than freshmen. The constructed nomogram provided a promising prediction model for student's low JHLES score probability, with accuracy, accordance, and discrimination (area under the curve (AUC) = 0.627). CONCLUSION: The student's grade was a significant influencing factor in medical students' perception of MSLE. The perceptions among the third and fourth graders got worse, probably due to the worrying changes in various aspects of MSLE during that period. The relevant and appropriate interventions to improve medical students' perceptions are urgently needed.

The association between visceral fat obesity and prefrailty in Chinese older adults: a cross-sectional study.

BACKGROUND: The prevalence of obesity is escalating. Previous research has concentrated on the link between frailty and obesity; however, the association between prefrailty and obesity has been less studied. Prefrailty screening and intervention may prevent or postpone frailty in older persons. OBJECTIVE: The study was to investigate into the relationship between prefrailty and several obesity indicators in Chinese community-dwelling older individuals. METHODS: This research employed the Frailty Screening Index to investigate the frailty phenotype of people living in Shanghai. Bioelectrical impedance analysis was used for evaluating body composition. RESULTS: There were 510 participants (39.0%) with high visceral adipose areas. Participants with a high visceral adipose area showed a higher risk of prefrailty (adjusted OR, 1.53; 95% CI, 1.19-1.96), according to multivariate models. When body mass index (BMI) and visceral fat area (VFA) were combined, it was discovered that having an overweight BMI with normal VFA was a protective factor for prefrailty (corrected OR, 0.62; 95% CI, 0.43-0.90), but having a normal weight but excess VFA increased the risk of prefrailty (corrected OR, 1.87; 95% CI, 1.15-3.03). CONCLUSION: Visceral fat obesity is an independent risk factor for prefrailty in Chinese older adults. Implementing targeted interventions, such as dietary modifications, increased physical activity, and other lifestyle changes, could play a crucial role in reducing the risk of prefrailty and improving overall health outcomes in this population.

MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

A novel peptide encoded by circ-SLC9A6 promotes lipid dyshomeostasis through the regulation of H4K16ac-mediated CD36 transcription in NAFLD.

BACKGROUND: As the leading cause of end-stage liver disease, nonalcoholic fatty liver disease (NAFLD) is mainly induced by lipid dyshomeostasis. The translation of endogenous circular RNAs (circRNAs) is closely related to the progression of various diseases, but the involvement of circRNAs in NAFLD has not been determined. METHODS: Combined high-throughput circRNA profiles were used to identify circRNAs with translational potential. The underlying molecular mechanisms were investigated by RNA sequencing, pull-down/MS and site-specific mutagenesis. RESULTS: In this study, we focused on circ-SLC9A6, an abnormally highly expressed circRNA in human and mouse liver tissue during NAFLD development that exacerbates metabolic dyshomeostasis in hepatocytes by encoding a novel peptide called SLC9A6-126aa in vivo and in vitro. YTHDF2-mediated degradation of m6A-modified circ-SLC9A6 was found to be essential for the regulation of SLC9A6-126aa expression. We further found that the phosphorylation of SLC9A6-126aa by AKT was crucial for its cytoplasmic localization and the maintenance of physiological homeostasis, whereas high-fat stress induced substantial translocation of unphosphorylated SLC9A6-126aa to the nucleus, resulting in a vicious cycle of lipid metabolic dysfunction. Nuclear SLC9A6-126aa promotes transcriptional activation of the target gene CD36 and enhances its occupancy of the CD36 promoter locus by regulating MOF-mediated histone H4K16 acetylation. Hepatic CD36 depletion significantly ameliorated hyperactivated MAPK signalling and lipid disturbance in SLC9A6-126aa transgenic mice. Clinically, increasing levels of SLC9A6-126aa were observed during NAFLD progression and were found to be positively correlated with the CD36 and MAPK cascades. CONCLUSION: This study revealed the role of circ-SLC9A6-derived SLC9A6-126aa in the epigenetic modification-mediated regulation of lipid metabolism. Our findings may provide promising therapeutic targets for NAFLD and new insights into the pathological mechanisms of metabolic diseases. HIGHLIGHTS: Under normal circumstances, driven by m6A modification, YTHDF2 directly recognizes and degrades circ-SLC9A6, thereby inhibiting the translation of SLC9A6-126aa. Additionally, AKT1 phosphorylates and inhibits the nuclear translocation of SLC9A6-126aa. In NAFLD, lipid overload leads to YTHDF2 and AKT1 deficiency, ultimately increasing the expression and nuclear import of SLC9A6-126aa. Nuclear SLC9A6-126aa binds directly to the CD36 promoter and initiates CD36 transcription, which induces lipid dyshomeostasis.

Carbapenem-resistant Enterobacterales sepsis following endoscopic retrograde cholangiopancreatography: risk factors for 30-day all-cause mortality and the development of a nomogram based on a retrospective cohort.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has become a routine endoscopic procedure that is essential for diagnosing and managing various conditions, including gallstone extraction and the treatment of bile duct and pancreatic tumors. Despite its efficacy, post-ERCP infections - particularly those caused by carbapenem-resistant Enterobacterales (CRE) - present significant risks. These risks highlight the need for accurate predictive models to enhance postprocedural care, reduce the mortality risk associated with post-ERCP CRE sepsis, and improve patient outcomes in the context of increasing antibiotic resistance. OBJECTIVE: This study aimed to examine the risk factors for 30-day mortality in patients with CRE sepsis following ERCP and to develop a nomogram for accurately predicting 30-day mortality risk. METHODS: Data from 195 patients who experienced post-ERCP CRE sepsis between January 2010 and December 2022 were analyzed. Variable selection was optimized via the least absolute shrinkage and selection operator (LASSO) regression model. Multivariate logistic regression analysis was then employed to develop a predictive model, which was evaluated in terms of discrimination, calibration, and clinical utility. Internal validation was achieved through bootstrapping. RESULTS: The nomogram included the following predictors: age > 80 years (hazard ratio [HR] 2.61), intensive care unit (ICU) admission within 90 days prior to ERCP (HR 2.64), hypoproteinemia (HR 4.55), quick Pitt bacteremia score ≥ 2 (HR 2.61), post-ERCP pancreatitis (HR 2.52), inappropriate empirical therapy (HR 3.48), delayed definitive therapy (HR 2.64), and short treatment duration (< 10 days) (HR 5.03). The model demonstrated strong discrimination and calibration. CONCLUSIONS: This study identified significant risk factors associated with 30-day mortality in patients with post-ERCP CRE sepsis and developed a nomogram to accurately predict this risk. This tool enables healthcare practitioners to provide personalized risk assessments and promptly administer appropriate therapies against CRE, thereby reducing mortality rates.

Characterizing seed dormancy in Epimedium brevicornu Maxim.: Development of novel chill models and determination of dormancy release mechanisms by transcriptomics.

PURPOSE: Epimedium brevicornu Maxim. is a perennial persistent C3 plant of the genus Epimedium Linn. in the family Berberaceae that exhibits severe physiological and morphological seed dormancy.We placed mature E. brevicornu seeds under nine stratification treatment conditions and explored the mechanisms of influence by combining seed embryo growth status assessment with related metabolic pathways and gene co-expression analysis. RESULTS: We identified 3.9 °C as the optimum cold-stratification temperature of E. brevicornu seeds via a chilling unit (CU) model. The best treatment was variable-temperature stratification (10/20 °C, 12/12 h) for 4 months followed by low-temperature stratification (4 °C) for 3 months (4-3). A total of 63801 differentially expressed genes were annotated to 2587 transcription factors (TFs) in 17 clusters in nine treatments (0-0, 0-3, 1-3, 2-3, 3-3, 4-3, 4-2, 4-1, 4-0). Genes specifically highly expressed in the dormancy release treatment group were significantly enriched in embryo development ending in seed dormancy and fatty acid degradation, indicating the importance of these two processes. Coexpression analysis implied that the TF GRF had the most reciprocal relationships with genes, and multiple interactions centred on zf-HD and YABBY as well as on MYB, GRF, and TCP were observed. CONCLUSION: In this study, analyses of plant hormone signal pathways and fatty acid degradation pathways revealed changes in key genes during the dormancy release of E. brevicornu seeds, providing evidence for the filtering of E. brevicornu seed dormancy-related genes.

miR-143-3p modulates depressive-like behaviors via Lasp1 in the mouse ventral hippocampus.

Depression is a prevalent and intricate mental disorder. The involvement of small RNA molecules, such as microRNAs in the pathogenesis and neuronal mechanisms underlying the depression have been documented. Previous studies have demonstrated the involvement of microRNA-143-3p (miR-143-3p) in the process of fear memory and pathogenesis of ischemia; however, the relationship between miR-143-3p and depression remains poorly understood. Here we utilized two kinds of mouse models to investigate the role of miR-143-3p in the pathogenesis of depression. Our findings reveal that the expression of miR-143-3p is upregulated in the ventral hippocampus (VH) of mice subjected to chronic restraint stress (CRS) or acute Lipopolysaccharide (LPS) treatment. Inhibiting the expression of miR-143-3p in the VH effectively alleviates depressive-like behaviors in CRS and LPS-treated mice. Furthermore, we identify Lasp1 as one of the downstream target genes regulated by miR-143-3p. The miR-143-3p/Lasp1 axis primarily affects the occurrence of depressive-like behaviors in mice by modulating synapse numbers in the VH. Finally, miR-143-3p/Lasp1-induced F-actin change is responsible for the synaptic number variations in the VH. In conclusion, this study enhances our understanding of microRNA-mediated depression pathogenesis and provides novel prospects for developing therapeutic approaches for this intractable mood disorder.

Effectiveness and mechanisms of mesenchymal stem cell therapy in preclinical animal models of hepatic fibrosis: a systematic review and meta-analysis.

Background: Liver damage due to long-term viral infection, alcohol consumption, autoimmune decline, and other factors could lead to the gradual development of liver fibrosis. Unfortunately, until now, there has been no effective treatment for liver fibrosis. Mesenchymal stem cells, as a promising new therapy for liver fibrosis, can slow the progression of fibrosis by migrating to the site of liver injury and by altering the microenvironment of the fibrotic area. Aim: By including all relevant studies to date to comprehensively assess the efficacy of mesenchymal stem cells for the treatment of hepatic fibrosis and to explore considerations for clinical translation and therapeutic mechanisms. Methods: Data sources included PubMed, Web of Science, Embase, and Cochrane Library, and were constructed until October 2023. Data for each study outcome indicator were extracted for comprehensive analysis. Results: The overall meta-analysis showed that mesenchymal stem cells significantly improved liver function. Moreover, it inhibited the expression level of transforming growth factor-ß [SMD = 4.21, 95% CI (3.02,5.40)], which in turn silenced hepatic stellate cells and significantly reduced the area of liver fibrosis [SMD = 3.61, 95% CI (1.41,5.81)]. Conclusion: Several outcome indicators suggest that mesenchymal stem cells therapy is relatively reliable in the treatment of liver fibrosis. The therapeutic effect is cell dose-dependent over a range of doses, but not more effective at higher doses. Bone-marrow derived mesenchymal stem cells were more effective in treating liver fibrosis than mesenchymal stem cells from other sources. Systematic Review Registration: Identifier CRD42022354768.

VPA-induced autism impairs memory ability through disturbing neural oscillatory patterns in offspring rats.

Autism spectrum disorder (ASD) is a general neurodevelopmental disease characterized by unusual social communication and rigid, repetitive behavior patterns. The purpose of this study was to investigate the effects of ASD on the alteration of neural oscillatory patterns and synaptic plasticity, which commonly supported a wide range of basic and higher memory activities. Accordingly, a prenatal valproic acid (VPA) exposure rat model was established for studying autism. The behavioral experiments showed that the social orientation declined and the memory ability was significantly impaired in VPA rats, which was closely associated with the synaptic plasticity deficits. Neural oscillation is the rhythmic neuron-activity, and the pathological characteristics and neurological changes in autism may be peeped at the neural oscillatory analysis. Interestingly, neural oscillatory analysis showed that prenatal VPA exposure reduced the low-frequency power but increased high-frequency gamma (HG) power in the hippocampus CA1 area. Meanwhile, the coherence and synchronization between CA3 and CA1 were abnormally increased in the VPA group, especially in theta and HG rhythms. Furthermore, the cross-frequency coupling strength of theta-LG in the CA1 and CA3 → CA1 pathway was significantly attenuated, but the theta-HG coupling strength was increased. Additionally, prenatal VPA exposure inhibited the expression of SYP and NR2B but enhanced the expression of PSD-95 along with decreased synaptic plasticity. The neural oscillatory patterns in VPA-induced offspring were disturbed with the intensity and direction of neural information flow disordered, which are consistent with the changes in synaptic plasticity, suggesting that the decline in synaptic plasticity is the underlying mechanism.

Association Between Visceral Obesity and Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Retrospective Study.

Purpose: To investigate the association between visceral obesity and glycemic control in patients with type 2 diabetes mellitus. Patients and Methods: A retrospective analysis involved 714 patients diagnosed with type 2 diabetes mellitus from the National Metabolic Management Center from November 2021 to February 2024. Medical data included sociodemographic data, lifestyle behaviors, and anthropometric and biochemical measurements. Multivariate logistic regression analysis was used to analyze their associations. Results: Among the patients, 251 (35.2%) achieved good glycemic control (HbA1c < 7.0%). On univariate analysis, higher diastolic blood pressure, longer duration of type 2 diabetes mellitus, tobacco smoking, alcohol drinking, insulin treatment, higher levels of fasting plasma glucose, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, and low-density lipoprotein cholesterol, visceral obesity (visceral fat area ≥ 100cm2) and diabetic peripheral neuropathy were all positively correlated with poor glycemic control; female, older age, higher levels of C peptide and serum uric acid were inversely associated with poor glycemic control (all P < 0.05). On multivariate logistic regression analysis, the results suggested that higher diastolic blood pressure [OR: 1.021, 95% CI (1.002, 1.040), P = 0.030], insulin treatment [currently used: OR = 2.156, 95% CI (1.249, 3.724), P = 0.006], higher level of fasting plasma glucose [OR: 1.819, 95% CI (1.598, 2.069), P < 0.001], and visceral obesity [OR: 1.876, 95% CI (1.158, 3.038), P = 0.011] were risk factors for poor glycemic control. Conclusion: This study indicated that visceral obesity (visceral fat area ≥ 100cm2) is positively associated with poor glycemic control, and serves as an independent risk factor for poor glycemic control (HbA1c ≥ 7.0%) in patients with type 2 diabetes mellitus. Screening for visceral obesity should be emphasized, and targeted interventions should be taken to improve glycemic control in patients with type 2 diabetes mellitus.

Risk factors of chronic endometritis in women who have undergone hysteroscopy: a prospective nested case-control study.

There is limited research on risk factors for chronic endometritis regarding reproductive history and clinical symptoms. Thus, this nested case-control study identified risk factors for chronic endometritis in women who have undergone hysteroscopy. Endometrial tissue sections were obtained from 502 women with intrauterine disorders who underwent hysteroscopy. Chronic endometritis was diagnosed via CD138 immunostaining. The women were divided into two groups: 271 women without chronic endometritis and 231 women with chronic endometritis. The prevalence of chronic endometritis was 46%. Univariate logistic regression revealed that prolonged menstruation and intermenstrual bleeding were associated with chronic endometritis, and subsequent multivariate logistic regression analyses showed that these were further independently associated. With univariable logistic regression, the gravidity and abortion history were correlated with chronic endometritis; however, no significant correlation was found with the adjusted odds ratio (OR) of 0.74 (95% confidence interval [CI] 0.46-1.19) or 0.76 (95% CI 0.58-1.11), respectively. No significant correlation was found between caesarean section history and the rates of chronic endometritis. No significant difference was found in all other variables between the three groups with > 5, ≤ 5 plasma cells and in a unknown group. Prolonged menstruation and intermenstrual bleeding were risk factors associated with chronic endometritis. Chronic endometritis should be considered and CD138 immunohistochemical examination should be recommended in women with these symptoms.