Thalamocortical dysconnectivity is associated with pain in patients with knee osteoarthritis.

Previous studies have suggested that the morphology and function of the thalamus and cortex are abnormal in patients with knee osteoarthritis (KOA). However, whether the thalamocortical network is differentially affected in this disorder is unknown. In this study, we examined functional and effective connectivity between the thalamus and major divisions of the cortex in 27 healthy controls and 27 KOA patients using functional magnetic resonance imaging. We also explored the topological features of the brain via graph theory analysis. The results suggested that patients with KOA had significantly reduced resting-state functional connectivity (rsFC) of the thalamo-sensorimotor pathway; enhanced rsFC of the thalamo-medial/lateral frontal cortex (mFC/LFC), parietal, temporal and occipital pathways; reduced effective connectivity of the left sensorimotor-to-thalamus pathway; and enhanced effective connectivity of the right thalamus-to-sensorimotor pathway compared with healthy controls. The functional connectivity of the thalamo-sensorimotor and thalamo-mFC pathways was enhanced when patients performed the multisource interference task. Moreover, patients with KOA presented altered nodal properties associated with thalamocortical circuits, including the thalamus, amygdala, and regions in default mode networks, compared with healthy controls. The correlation analysis suggested a significant negative correlation between thalamo-mFC rsFC and pain intensity, between thalamo-sensorimotor task-related connectivity and disease duration/depression scores, and a positive correlation between right frontal nodal properties and pain intensity in KOA patients. Taken together, these findings establish abnormal and differential alterations in the thalamocortical network associated with pain characteristics in KOA patients, which extends our understanding of their role in the pathophysiology of KOA.

Mid-term outcome of catheter ablation of idiopathic non-outflow tract ventricular arrhythmias.

BACKGROUND: Catheter ablation is recommended in patients with frequent and symptomatic ventricular arrhythmias (VAs) in an otherwise normal heart. Right or left outflow tract (OT) are the most common origins, and catheter ablation is highly effective with low complication rates. However, outcome of catheter ablation of VAs other than the OT (non-OTVAs) is limited. The aim of this single-center study was to assess the safety and mid-term outcome of catheter ablation for non-OTVAs. METHOD AND RESULTS: From 2013 to 2018, 251 patients who underwent catheter ablation for idiopathic non-OTVAs were enrolled and grouped according to the origins including His-Purkinje system (HPS, n = 108), papillary muscle / moderator band (PM/MB, n = 47), tricuspid annulus (TA, n = 70), and mitral annulus (MA, n = 26), 244 (97.2%) had acute elimination of VAs. The time of VAs recurrence of the single procedure was 1.69 (0.12,9.72) months, with 66% occurring within the first 3 months. The recurrence rate was significantly higher in the PM/MB group than in the TA (p = 0.025) and MA groups (p = 0.023). The single procedure success rate in all patients was 70.1%, in which 66.7%, 59.6%, 80%, and 76.9% were achieved in the HPS, PM/MB, TA, and MA groups, respectively (p = 0.284). After multiple procedures, the total success rate was 76.5% at the follow-up of 4.38 ± 2.42 years. The rate was significantly lower in the PM/MB group than in the TA group (p = 0.035). In subgroup analysis, no significant difference was observed in the recurrence rate of single procedure in patients with different VA origins within the PM/MB (log-rank test, p = 0.546). CONCLUSION: Despite a certain percentage of recurrences observed in the mid-term follow-up, catheter ablation remained feasible and effective for idiopathic non-OTVAs.

Nomogram Based on Clinical Characteristics to Predict 28-Day Mortality Among Patients with CRAB-BSI.

BACKGROUND: The drug resistance of carbapenem-resistant Acinetobacter baumannii bloodstream infections (CRAB-BSI), especially hospital-acquired infections, has promoted their rapid and vast spread. It is necessary to use reliable methods to establish better prediction models. According to Cox proportional hazards regression, a nomogram was established. METHODS: A retrospective cohort study among patients who were diagnosed with CRAB-BSI was performed from January 2020 to December 2022. Univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors regarding CRAB-BSI. Then, nomograms were used to calculate the area under the curve (AUC), C-index, and calibration curve to determine the predictive accuracy and dis-criminability. Decision curve analysis (DCA) was employed to further confirm the clinical effectiveness of the nomogram. RESULTS: A total of 98 cases were included in the comparison between the 28-day mortality group consisting of 32 patients and the 28-day survival group with 66 patients. The use of cefoperazone-sulbactam was significantly higher among patients who survived than among those who died. Univariable analysis revealed that factors such as primary diagnosis, time to inadequate antimicrobial therapy, and high serum creatinine and procalcitonin (PCT) levels were more prevalent in the mortality group. However, only primary diagnosis, time to inadequate antimicrobial therapy, and high PCT levels emerged as statistically significant risk factors for death in multivariate analysis and were used to construct the nomogram. The nomogram validation exhibited excellent performance. CONCLUSIONS: The nomogram was sufficiently accurate to predict the risk and prognostic factors of CRAB-BSI, allowing for individualized clinical decisions for future clinical work. The cefoperazone-sulbactam did have an effect, but more studies are needed to interpret it.

PENet: Prior evidence deep neural network for bladder cancer staging.

Bladder cancer is a heterogeneous, complicated, and widespread illness with high rates of morbidity, death, and expense if not treated adequately. The accurate and exact stage of bladder cancer is fundamental for treatment choices and prognostic forecasts, as indicated by convincing evidence from randomized trials. The extraordinary capability of Deep Convolutional Neural Networks (DCNNs) to extract features is one of the primary advantages offered by these types of networks. DCNNs work well in numerous real clinical medical applications as it demands costly large-scale data annotation. However, a lack of background information hinders its effectiveness and interpretability. Clinicians identify the stage of a tumor by evaluating whether the tumor is muscle-invasive, as shown in images by the tumor's infiltration of the bladder wall. Incorporating this clinical knowledge in DCNN has the ability to enhance the performance of bladder cancer staging and bring the prediction into accordance with medical principles. Therefore, we introduce PENet, an innovative prior evidence deep neural network, for classifying MR images of bladder cancer staging in line with clinical knowledge. To do this, first, the degree to which the tumor has penetrated the bladder wall is measured to get prior distribution parameters of class probability called prior evidence. Second, we formulate the posterior distribution of class probability according to Bayesian Theorem. Last, we modify the loss function based on posterior distribution of class probability which parameters include both prior evidence and prediction evidence in the learning procedure. Our investigation reveals that the prediction error and the variance of PENet may be reduced by giving the network prior evidence that is consistent with the ground truth. Using MR image datasets, experiments show that PENet performs better than image-based DCNN algorithms for bladder cancer staging.

Blockage of PD-L1 by FERMT3-mediated Wnt/ß-catenin signalling regulates chemoresistance and immune evasion of colorectal cancer cells.

Colorectal cancer (CRC) constitutes a major public health problem because of the high rate of morbidity and mortality. Chemotherapy and immunotherapy are the major and promising strategies for cancer patients including CRC; nevertheless, chemoresistance and immune escape limit the final efficacy of the above approaches. FERMT3 has proven to exert a critical role in the immune system and has contradictive effects on cancer progression. In this study, bioinformatics database analysis and clinical specimen detection both corroborated the downregulation of FERMT3 in CRC tissues and cells. Of interest, overexpression of FERMT3 suppressed CRC cell invasion and sensitized cells to 5-fluorouracil (5-FU) by reducing cell viability and increasing cell apoptosis and caspase 3 activity. Noticeably, FERMT3 upregulation enhanced natural killer (NK) cells activation by increasing secretions of interferon γ (IFN-γ) and tumour necrosis factor α (TNF-α) when NK cells were co-cultured with CRC cells. Importantly, upregulation of FERMT3 promoted NK cell-mediated killing of CRC cells. Mechanically, FERMT3 inhibited the aberrant activation of Wnt/ß-catenin signalling and the subsequent programmed death-ligand 1 (PD-L1) expression in CRC cells. Moreover, knockdown of PD-L1 suppressed CRC cell invasion, 5-FU resistance and NK cells-mediated tumour killing. Additionally, reactivating the Wnt/ß-catenin signalling with a specific WNT agonist CAS 853220-52-7 overturned the efficacy of FERMT3 overexpression against CRC cell invasion, 5-FU chemoresistance and cell susceptibility to NK cell-mediated cytotoxicity. Therefore, the current findings substantiate that FERMT3 elevation may attenuate CRC cell chemoresistance and NK cell-mediated immune response to tumour cells by inhibiting Wnt/ß-catenin-PD-L1 signalling. Therefore, FERMT3 elevation may be a promising therapeutic approach to overcome chemoresistance and immune evasion in CRC.

Intensivists' cognizance of nutrition management and its determinants in ICUs in Guizhou province, China.

BACKGROUND AND OBJECTIVES: To investigate the Intensivists' cognizance of nutritional management and its determinants, and to provide evidence for standardizing nutritional therapy with protocols. METHODS AND STUDY DESIGN: From April to July 2021, a multi-stage sampling method was used to investigate the nutritional cognizance of critical care physicians in secondary and tertiary hospitals in Guizhou Province, China; Questionnaires and scales were used as survey tools. The questionnaires sought general information about the respondents and documented their nutrition cognizance and practice. Five scalar dimensions explored nutritional management, with answers scored for 1-5 points, 3 points being the pass score. RESULTS: 322 respondents from 147 hospitals were surveyed. The average score was passable, but not good at 3.37±0.71 (p<0.01 with 3.0 as reference). Among the five dimensions, evaluation and monitoring of nutritional status had the highest score (3.79±0.67, p<0.01), the understanding of nutritional preparations had the lowest (3.09±0.86, p>0.05), and the scores of other dimensions ranged from 3.21 to 3.49. Almost 70% of intensivists said that they would give priority to other than nutritional therapeutic measures in actual clinical practice. But 96% thought it necessary to strengthen and emphasise nutritional management. CONCLUSIONS: Critical care physicians' knowledge and understanding of nutritional therapy are limited, especially in the use of supportive preparations; Recourse to protocols and standardized nutritional management of assistance may depend on training, assigned role, peer expectations and health system policy, each of which has the potential for advancement in the interest of better nutritional care in provincial Guizhou.

Anatomical deviations of vertebral artery in hemifacial spasm: a quantitative study.

PURPOSE: There exist different opinions on whether the anatomical laterality of vertebral artery (VA) is related to the unilateral onset of hemifacial spasm (HFS). In this study, we intended to qualitatively explore the potential correlation between the anatomical deviations of VA and the clinical characteristics of HFS. METHODS: Two hundred and forty patients who underwent microvascular decompression for HFS between January 2018 and December 2019 were recruited. Clinical data including medical records and preoperative MRI images were retrospectively reviewed. A score system was specially designed for VAs to illustrate their distribution, and a score-weighted cross-sectional area of VA was proposed to represent the relative thickness of VA on each side. Then, the anatomical deviations of VA were comparatively analyzed between the symptomatic side and asymptomatic side and between VA-involved cases and non-VA-involved cases. RESULTS: The score and weighted cross-sectional area (WCSA) of VA in symptomatic side were significantly greater than those in asymptomatic side (P = 0.000, P = 0.000). And in symptomatic side, the score and WCSA of VA in VA-involved cases were significantly greater than those in non-VA-involved cases (P = 0.000). Moreover, with higher score (P = 0.000) and greater WCSA (P = 0.001) on the left side, the VA-involved cases showed a preference (74%) of left HFS. CONCLUSIONS: In HFS, the symptomatic side tends to have an ipsilaterally deviated and relatively larger VA, especially in VA-involved cases. And it is the VA-involved cases that are prone to have a prevalence of left HFS, but not the non-VA-involved cases.

Knocking down Stard3 decreases adipogenesis with decreased mitochondrial ROS in 3T3-L1 cells.

Start domain-containing protein 3 (Stard3) plays roles in intracellular cholesterol distribution, however, the role of Stard3 in the adipogenesis of 3T3-L1 preadipocytes remains unclear. We demonstrated that Stard3 expression was significantly increased during the adipogenesis of 3T3-L1 preadipocytes, accompanied by an increase of mitochondrial Reactive oxygen species (ROS). Stard3 knocking-down inhibited 3T3-L1 preadipocyte adipogenesis with decreased mitochondrial ROS levels, while ROS inducer rescued the stard3 silencing 3T3 cells with increased ROS. Moreover, Stard3 silencing reduced the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein (C/EBP)α in 3T3- L1 cells. In conclusion, Stard3 enhanced the adipogenesis of preadipocytes by enhancement of cholesterol redistribution to the mitochondrial, increasing mitochondrial ROS production. These results suggest that Stard3 is an essential factor for the 3T3-L1 cells' differentiation.

Pathogenicity of Conidiobolus coronatus and Fusarium solani in mouse models.

To study the pathogenicity of Conidiobolus coronatus (C. coronatus) and Fusarium solani (F. solani) in animal models. Immunocompromised mice were treated with cyclophosphamide and prednisolone via intraperitoneal injection before and after inoculation. According to pathogenic characteristics of different fungi, C. coronatus was used to infect mice via intravenous inoculation, intraperitoneal inoculation, gastrointestinal infusion and intradermal inoculation methods. And F. solani was used to infect mice by inoculation via the abraded or normal skin. In the group of immunocompromised mice, C. coronatus was isolated from the lung tissues of one mouse on day 7 and another on day 10 respectively. The corresponding histopathology revealed infiltration of local inflammatory cells in the lung tissue. Pathogenic lesions were observed in all normal and immunocompromised mice infected with F. solani via abraded skin. The lesions in the immunocompromised mice were more severe and persisted longer than those in the normal mice. Moreover, hyphae were mostly observed in the histopathological examination and fungal culture from the immunocompromised mouse. The pathogenicity of C. coronatus was relatively weak as it did not induce local infections and did not disseminate the disease in immunocompetent and immunocompromised mice. Therefore, F. solani is a type of opportunistic pathogenic fungus, and abraded skin is one of the causative routes of infection.

Significant MRI indicators of malignancy for breast non-mass enhancement.

OBJECTIVE: To explore and evaluate new malignant predictors of breast non-mass enhancement lesions using the new BI-RADS MRI lexicon. METHODS: A dataset involving 422 consecutive women underwent breast 3.0 T MRI between January 2014 and July 2016 was assembled for this study. Each case was retrospectively reviewed by 3 radiologists. Eighty-four lesions that present non-mass enhancement in 79 patients were identified in the study. Dynamic contrast-enhanced MRI features were analyzed using univariate and multivariate analyses to identify significant indicators of malignancy. RESULTS: Of 84 non-mass enhancement lesions, 52 (61.9%) were malignant and 32 (38.1%) were benign. Segmental distribution (P = 0.015 from univariate analysis; OR = 4.739, P = 0.008 from multivariate analysis), cluster ring enhancement (P = 0.017 from univariate analysis; OR = 3.601, P = 0.032 from multivariate analysis), time-intensity curve of plateau (P = 0.002 from univariate analysis; OR = 3.525, P = 0.027 from multivariate analysis) and phase to peak (P = 0.06 from univariate analysis; OR = 6.327, P = 0.015 from multivariate analysis) were significantly different between malignant and benign lesions. CONCLUSIONS: This study demonstrated that segmental distribution, clustered ring enhancement, and short time to peak could act as new malignant predictors for breast non-mass enhancement detected on 3.0 T MRI.

Explaining the improving effect of dough crumb-sheet composite rolling on fresh noodle quality: From microstructure and moisture distribution perspective.

A new technique known as dough crumb-sheet composite rolling (DC-SCR) was used to improve the quality of fresh noodles. However, there is a dearth of theoretical investigations into the optimal selection of specific parameters for this technology, and the underlying mechanisms are not fully understood. Therefore, the effects of dough crumb addition times in DC-SCR on the texture, cooking, and eating quality of fresh noodles were first studied. Then, the underlying regulation mechanism of DC-SCR technology on fresh noodles was analyzed in terms of moisture distribution and microstructure. The study demonstrated that the most significant enhancement in the quality of fresh noodles was achieved by adding dough crumbs six times. Compared with fresh noodles made without the addition of dough crumbs, the initial hardness and chewiness of fresh noodles made by adding six times of dough crumbs increased by 25.32% and 46.82%, respectively. In contrast, the cooking time and cooking loss were reduced by 28.45% and 29.69%, respectively. This quality improvement in fresh noodles made by DC-SCR came from the microstructural differences of the gluten network between the inner and outer layers of the dough sheet. A dense structure on the outside and a loose structure on the inside could endow the fresh noodles made by DC-SCR with higher hardness, a shortened cooking time, and less cooking loss. This study would provide a theoretical and experimental basis for creating high-quality fresh noodles.

Association between maternal polycystic ovarian syndrome undergoing assisted reproductive technology and pregnancy complications and neonatal outcomes: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is recognized as the most prevalent endocrine disorder among women of reproductive age. While the utilization of assisted reproductive technology (ART) has resulted in favorable outcomes for infertility treatment in PCOS patients, the inherent pathophysiological features of the condition give rise to complications and consequences during pregnancy and delivery for both the mother and offspring. This study was to assess the correlation between maternal PCOS and various pregnancy complications and neonatal outcomes undergone ART. METHODS: A systematic search was conducted on PubMed, EmBase, and the Cochrane Library to identify observational studies that investigated the association between PCOS and the risk of various pregnancy complications and neonatal outcomes, including gestational diabetes mellitus (GDM), hypertension in pregnancy (PIH), preeclampsia (PE), preterm birth, abortion, congenital malformations (CA), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, neonatal intensive care unit (NICU) admission and birth weight. Eligible studies were selected based on predetermined inclusion and exclusion criteria. The meta-analysis was conducted using Review Manager and Stata software, with odds ratios (ORs) or mean difference (MD), confidence intervals (CIs), and heterogeneity (I2) being calculated. The search was conducted up to March 2023. RESULTS: A total of 33 studies with a combined sample size of 92,810 participants were identified. The findings indicate that PCOS is significantly associated with an increased risk of GDM (OR 1.51, 95% CI:1.17-1.94), PIH (OR 1.72, 95% CI:1.25-2.39), PE (OR 2.12, 95% CI:1.49-3.02), preterm birth (OR 1.29, 95% CI:1.21-1.39), and LBW (OR 1.29, 95% CI:1.14-1.47). In subgroup analyses, the risks of GDM (OR 1.80, 95% CI:1.23-2.62) and abortion (OR 1.41, 95% CI:1.08-1.84) were elevated in fresh embryo transferred (ET) subgroup, whereas elevated risk of PE (OR 1.82, 95% CI:1.17-2.83) and preterm birth (OR 1.31, 95% CI:1.21-1.42) was identified in frozen ET subgroup. Whatever with or without hyperandrogenism, patients with PCOS had a higher risk in preterm birth (OR 1.69, 95% CI: 1.31-2.18; OR 1.24, 95% CI:1.02-1.50) and abortion (OR 1.38, 95% CI:1.12-1.71; OR 1.23, 95% CI:1.06-1.43). CONCLUSION: Our findings suggest that individuals with PCOS undergone ART are at a notably elevated risk for experiencing pregnancy complications and unfavorable neonatal outcomes. Nevertheless, to establish a definitive association between PCOS and pregnancy-related outcomes, it is necessary to conduct extensive prospective, blinded cohort studies and effectively control for confounding variables.

Ovarian response determines the luteinizing hormone suppression threshold for patients following the gonadotrophin releasing hormone antagonist protocol: A retrospective cohort study.

Background: Ovarian reactivity to gonadotrophin stimulation varies, and individual adjustments to the timing and dose of gonadotrophin-releasing hormone (GnRH) antagonist administration are necessary to prevent excessive increases and decreases in luteinizing hormone (LH) levels in patients with different ovarian response following the GnRH antagonist (GnRH-A) protocol. The present study aims to investigate optimal LH suppression thresholds for patients with normal ovarian response (NOR), high ovarian response (HOR), and poor ovarian response (POR) following the GnRH-A protocol respectively. Methods: A total of 865 in vitro fertilization (IVF) cycles using a flexible or fixed GnRH-A protocol were included. Patients were categorized into the HOR, NOR, or POR group according to their anti-Müllerian hormone (AMH) levels. Then, patients in each group were stratified into one of four subgroups according to the quartile (Q1-Q4) of the basal LH level to LH on triggering day ratio (bLH/hLH). The primary outcomes were the clinical pregnancy and live birth rates, and the secondary outcomes were the number of oocytes retrieved, MII oocytes, two pronucleus (2PN) embryos, and good-quality embryos. Results: There were 526 patients with NOR, 180 with HOR, and 159 with POR. Basal LH level, LH on triggering day and bLH/hLH were identified as independent predictors of clinical pregnancy rate and live birth rate by logistics regression analysis. Compared to those with NOR, patients with POR had the lowest embryo implantation rate (22.6% vs. 32.8%, P < 0.05), clinical pregnancy rate (32.3% vs. 47.3%, P < 0.05) and live birth rate (22.6 vs. 37.8%, P < 0.05) of fresh embryo transfer (ET). The embryo implantation, clinical pregnancy and live birth rates of frozen embryo transfer (FET) were not significantly different among the three groups. In the subgroup analysis, patients with HOR had the highest embryo implantation rate (51.6%, P < 0.05), clinical pregnancy rate (68.4%, P < 0.05) and live birth rate (52.6%, P < 0.05) of ET in Q3, with a bLH/hLH ratio of 2.40-3.69. In the NOR group, the embryo implantation rate (41.9%, P < 0.05), clinical pregnancy rate (61.5%, P < 0.05) and live birth rate (50.8%, P < 0.05) of ET and live birth rate (53.1%, P < 0.05) of FET were highest in Q2, with a bLH/hLH ratio of 1.29-2.05. Patients with POR had the highest clinical pregnancy rate (57.1%, P < 0.05) and live birth rate (42.9%, P < 0.05) of ET in Q2, with a bLH/hLH ratio of 0.86-1.35. Conclusions: In the present study, the bLH/hLH ratio represented the LH suppression threshold. The subgroup analysis of HOR, NOR and POR showed that, the LH suppression threshold varies according to ovarian response. We recommend LH suppression thresholds of 2.40-3.69 for HOR, 1.29-2.05 for NOR, and 0.86-1.35 for POR to obtain the highest clinical pregnancy rate and live birth rate. This study provides comprehensive and precise references for clinicians to monitor LH levels individually during controlled ovarian stimulation (COS) according to the patient's ovarian response following the GnRH-A protocol.

Caffeic Acid Reduces Ferroptosis to Dampen Inflammation of Keratinocytes in Psoriasis by Inhibiting EGR1-induced Transcription Activation of CHAC1.

BACKGROUND: Ferroptosis of keratinocytes is closely associated with amplification of skin inflammation in psoriasis. This study focuses on unlocking the role of caffeic acid (CA), a polyphenol compound, in keratinocyte ferroptosis and understanding the underlying mechanistic basis. METHODS: The interaction between early growth response protein 1 (EGR1) and chac glutathione specific γ­glutamylcyclotransferase 1 (CHAC1) was predicted by bioinformatics and validated via chromatin immunoprecipitation and dual-luciferase reported assays. Their expressions in primary human epidermal keratinocytes were altered by transfection of EGR1/CHAC1 overexpression or knockdown plasmids, and then keratinocytes were followed by CA treatment and Erastin (ferroptosis inducer). Keratinocyte viability was determined by CCK-8 assay, and the ferroptotic effect was evaluated using colorimetric assay and flow cytometry. Proinflammatory cytokine secretion by keratinocytes was detected via ELISA. Expressions of EGR1 and CHAC1 in keratinocytes were analyzed by qRT-PCR or Western blot. RESULTS: Increased expressions of EGR1 and CHAC1 were detected in keratinocytes with Erastin treatment. CA (100 µM) antagonized Erastin (10 µM)-induced decrease in viability, increases in EGR1 and CHAC1 expressions, upregulation of MDA, ROS, and Fe2+, downregulation of GSH and SOD, and secretion of proinflammatory cytokines from keratinocytes. EGR1 overexpression potentiated Erastin-induced effects. Moreover, EGR1 overexpression and CA mutually counteracted their effects on Erastin-induced keratinocytes. EGR1 transcriptionally activated and positively regulated CHAC1. The above Erastin-induced effects were neutralized by EGR1 knockdown but potentiated by CHAC1 overexpression. Moreover, EGR1 knockdown and CHAC1 overexpression reversed each other's effects. CONCLUSION: CA reduces ferroptosis by inhibiting EGR1-induced activation of CHAC1 to dampen inflammation of keratinocytes in psoriasis. This study providing new compounds and candidate targets for the clinical treatment of psoriasis.

lncRNA CASC7 contributes to the progression of LPS-induced liver injury by targeting miRNA-217/TLR4 axis

It has been reported that long non-coding RNAs (lncRNAs) are involved in sepsis-induced liver injury, while the role of cancer susceptibility candidate 7 (CASC7) in liver injury induced by sepsis remains elusive. In our study, 62 patients and 55 healthy controls were enrolled from our hospital, from whom CASC7 and microRNA-217 (miR-217) in serum samples were detected by quantitative real-time PCR (qRT-PCR). Then the sepsis-induced liver injury mice model was established by lipopolysaccharide (LPS). The effect of CASC7 on liver injury induced by sepsis was confirmed by hematoxylin and eosin (HE) staining, ELISA assay, TUNEL assay, Annexin V-FITC apoptosis assay and cell counting kit-8 (CCK-8) assay, respectively. Besides, RNA pull-down, luciferase reporter gene assay, qRT-PCR, and western blot were used to evaluate the underlying mechanisms. In this study, lncRNA CASC7 was significantly increased while miR-217 was significantly decreased in patients with sepsis-induced liver injury compared with that in healthy controls. There was a negative association of CASC7 and miR-217 in serum samples from patients with sepsis-induced liver injury and healthy controls. CASC7 was upregulated in a time-dependent manner in liver tissues of LPS-treated mice. It was found that knockdown of CASC7 reduced the liver injury induced by LPS in mice. In vitro, LPS treatment enhanced cell apoptosis, while knockdown of CASC7 inhibited the role of LPS in cell apoptosis. Moreover, knockdown of CASC7 suppressed the LPS-enhanced tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) expression. In addition, miR-217 was found to be a target of CASC7, and miR-217 mimic could reverse CASC7-promoted liver injury. Furthermore, toll-like receptor 4 (TLR4) was identified as the target of miR-217, and both CASC7 and miR-217 could downregulate the mRNA and protein level of TLR4. Additionally, TLR4 overexpression could reverse miR-217-inhibited or CASC7-promoted liver injury. Taken together, CASC7 contributes to the progression of LPS-induced liver injury via the miR-217/TLR4 axis.

Species-specific responses of C and N allocation to N addition: evidence from dual 13C and 15N labeling in three tree species.

Soil nitrogen (N) availability affects plant carbon (C) utilization. However, it is unclear how various tree functional types respond to N addition in terms of C assimilation, allocation, and storage. Here, a microcosm experiment with dual 13C and 15N labeling was conducted to study the effects of N addition (i.e., control, 0 g N kg-1; moderate N addition, 1.68 g N kg-1; and high N addition, 3.36 g N kg-1 soil) on morphological traits, on changes in nonstructural carbohydrates (NSC) in different organs, as well as on C and N uptake and allocation in three European temperate forest tree species (i.e., Acer pseudoplatanus, Picea abies and Abies alba). Our results demonstrated that root N uptake rates of the three tree species increased by N addition. In A. pseudoplatanus, N uptake by roots, N allocation to aboveground organs, and aboveground biomass allocation significantly improved by moderate and high N addition. In A. alba, only the high N addition treatment considerably raised aboveground N and C allocation. In contrast, biomass as well as C and N allocation between above and belowground tissues were not altered by N addition in P. abies. Meanwhile, NSC content as well as C and N coupling (represented by the ratio of relative 13C and 15N allocation rates in organs) were affected by N addition in A. pseudoplantanus and P. abies but not in A. alba. Overall, A. pseudoplatanus displayed the highest sensitivity to N addition and the highest N requirement among the three species, while P. abies had a lower N demand than A. alba. Our findings highlight that the responses of C and N allocation to soil N availability are species-specific and vary with the amount of N addition.

Disrupted Resting-State Functional Connectivity and Effective Connectivity of the Nucleus Accumbens in Chronic Low Back Pain: A Cross-Sectional Study.

Purpose: Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP. Methods: Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc. Results: Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistent with the whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton's Depression Scale (HAMD) scores (r = -0.402, p = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores (r = 0.406, p = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc (p = 0.012) as compared with HC. Conclusion: Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.

Hepatitis B virus in oocytes and embryos: pregnancy outcomes and children's health.

Objective: To investigate whether the presence of hepatitis B virus (HBV) in oocytes and embryos affects pregnancy outcomes for in vitro fertilization and embryo transfer (ET) as well as is related to the vertical transmission of HBV to children. Design: Retrospective cohort study. Setting: A university-affiliated fertility center. Patients: This study included 167 couples with at least 1 hepatitis B surface antigen-seropositive partner. These couples underwent in vitro fertilization-ET, and the discarded oocytes and embryos had been tested for HBV. Couples with HBV-positive oocytes or embryos were categorized as the positive group, whereas those couples with HBV-negative oocytes and embryos served as the negative group. Interventions: None. Main Outcome Measures: Pregnancy outcomes and the rate of children's HBV infection. Results: The pregnancy outcomes of fresh and frozen ETs were not associated with the presence of HBV in the oocytes and embryos. Of the 106 infants born, 1 child whose mother tested positive for hepatitis B surface antigen but had negative oocytes and embryos was infected with HBV. Additionally, 26.09% of children who had been administered passive immunization and active vaccinations did not reach protective levels of anti-HBV antibodies (hepatitis B surface antibodies) and became nonresponders. The negative rate of children's hepatitis B surface antibody was associated with the presence of HBV in oocytes and embryos (odds ratio, 3.01; 95% confidence interval, 1.04-9.25). Conclusions: The presence of HBV in oocytes and embryos did not affect pregnancy outcomes or result in the vertical transmission of HBV to the offspring of HBV carriers. Follow-up is needed for HBV-vaccinated children with an HBV-infected parent. Booster vaccinations are necessary for continued protection.

Exploration of a Predictive Model for Keloid and Potential Therapeutic Drugs Based on Immune Infiltration and Cuproptosis-Related Genes.

The aim of this study was to investigate the correlation between cuproptosis-related genes and immunoinfiltration in keloid, develop a predictive model for keloid occurrence, and explore potential therapeutic drugs. The microarray datasets (GSE7890 and GSE145725) were obtained from Gene Expression Omnibus database to identify the differentially expressed genes (DEGs) between keloid and nonkeloid samples. Key genes were identified through immunoinfiltration analysis and DEGs and then analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, followed by the identification of protein-protein interaction networks, transcription factors, and miRNAs associated with key genes. Additionally, a logistic regression analysis was performed to develop a predictive model for keloid occurrence, and potential candidate drugs for keloid treatment were identified. Three key genes (FDX1, PDHB, and DBT) were identified, showing involvement in acetyl-CoA biosynthesis, mitochondrial matrix, oxidoreductase activity, and the tricarboxylic acid cycle. Immune infiltration analysis suggested the involvement of B cells, Th1 cells, dendritic cells, T helper cells, antigen-presenting cell coinhibition, and T cell coinhibition in keloid. These genes were used to develop a logistic regression-based nomogram for predicting keloid occurrence with an area under the curve of 0.859 and good calibration. We identified 32 potential drug molecules and extracted the top 10 compounds based on their P-values, showing promise in targeting key genes and potentially effective against keloid. Our study identified some genes in keloid pathogenesis and potential therapeutic drugs. The predictive model enhances early diagnosis and management. Further research is needed to validate and explore clinical implications.