Effect of CD4 count on Mycobacterium tuberculosis infection rates in people living with HIV: a comparative study in prison and community.

To evaluate the impact of the CD4 count on ESAT6-CFP10 (EC) skin test, QuantiFERON-TB Gold In-tube test (QFT) and tuberculin skin test (TST) in a large prison and communities in Jiangsu Province among people living with HIV (PLHIV). Participants in communities were tested with the QFT and EC skin test and in prison were tested with the QFT, TST and EC skin test. A 4-knotted restricted cubic spline fitted for Logistic models was used to explore the cutoff point of CD4 count and the associations between changes in CD4 count and Mycobacterium tuberculosis (M.tb) infection. Among 1,815 PLHIV included, 19.3% (350) were from prisons and 80.7% (1465) were identified through community screenings. M.tb infection rates were 12.2% and 8.3% through QFT and EC tests, respectively. Odd Ratios (ORs) for infection increased with CD4 counts, peaking at 618 cells/mm3 for EC, 392 cells/mm3 for QFT, then plateaued. However, the pattern differed for EC between prison and screening scenarios. In prison settings, M.tb infection increased with CD4 count from 0 to 350 cells/mm3, plateaued until 500 cells/mm3, and then persistently increased. Conversely, for community, ORs decreased until 300 cells/mm3, followed by an increase between 300 and 729 cells/mm3, after which they continued to rise persistently. Our cross-sectional study among PLHIV revealed a higher rate of M.tb infection in prison compared to the community. The relationship between CD4 count and infection became negative after a certain threshold. This pivotal point differed with detection methods, with QFT showing lower CD4 thresholds than EC.

Development of a Predictive Nomogram Model for Early Deep Vein Thrombosis in Postoperative Spontaneous Intracerebral Hemorrhage Patients.

Background: This study explores risk determinants for participants' lower extremities deep vein thrombosis (DVT) in the perioperative phase after spontaneous intracerebral hemorrhage (SICH), thereby informing more effective clinical prevention and treatment strategies. Methods: During the period spanning October 2021 to March 2024, clinical data from 96 participants who received surgical treatment for spontaneous cerebral hemorrhage was analyzed in a retrospective study. Participants were classified into DVT and negative-DVT groups within the first week post-surgery. We used univariate logistic regression and multivariate logistic regression analyses to assess the impact of various clinical variables on DVT. A nomogram model was constructed to forecast the occurrence of early DVT following SICH surgery. The model's performance was assessed and validated using receiver operating characteristic (ROC) curves and bootstrap resampling. Results: Among the 96 participants, 46 developed DVT. Significant differences were noted in age, D-dimer levels, fibrinogen degradation products, Caprini scores, and total surgical bleeding volume between the groups. Multivariate analysis revealed that Caprini score (the values of OR, 95% CI, and P are 1.962, 1.124-3.424, and 0.018, respectively) and total surgical bleeding volume (the values of OR, 95% CI, and P are 1.010, 1.002-1.018, and 0.017, respectively) were risk variables contributing to DVT occurrence. The area under the receiver operating characteristic curve was 0.918 (95% CI, 0.821-0.988). The calibration curve showed good prediction accuracy. Conclusion: The Caprini score and total surgical bleeding volume are meaningful self-reliant risk variables contributing to DVT occurrence in postoperative participants with SICH. We have created a straightforward and efficient model to predict early DVT post-SICH surgery. This model serves as a valuable clinical tool for evaluating individual risk and enhancing decision-making processes.

Long noncoding RNA UCA1 inhibits epirubicin-induced apoptosis by activating PPARα-mediated lipid metabolism.

Metabolic reprogramming is a hallmark of cancer, and abnormal lipid metabolism is associated with drug resistance in bladder cancer cells. The long noncoding RNA (lncRNA) UCA1 is overexpressed in bladder cancer, but its functional contribution to lipid metabolism remains uncharacterized. In this study, we demonstrated that lncRNA UCA1 inhibits epirubicin-induced cell apoptosis by supporting abnormal lipid metabolism in bladder cancer cells. Mechanistically, lncRNA UCA1 promotes lipid accumulation in vitro and in vivo by upregulating PPARα mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPARα and downstream p-AKT/p-GSK-3ß/ß-catenin signaling. Furthermore, mixed free fatty acids upregulated lncRNA UCA1 expression by promoting recruitment of the transcription factor RXRα to the lncRNA UCA1 promoter. These findings were verified in a mouse xenograft model and are consistent with the expression patterns in human bladder cancer patients. Overall, these findings establish the role of lncRNA UCA1 in lipid metabolism and bladder cancer cell resistance to epirubicin, suggesting that lncRNA UCA1 may serve as a candidate target for enhancing bladder cancer chemotherapy.

Structure-function coupling changes in first-episode, treatment-naïve schizophrenia correlate with cell type-specific transcriptional signature.

BACKGROUND: First-episode schizophrenia (FES) is a complex and progressive psychiatric disorder. The etiology of FES involves genetic, environmental, and neurobiological factors. This study investigates the association between alterations in structural-functional (SC-FC) coupling and transcriptional expression in FES. METHODS: This study encompassed a cohort of 214 participants, comprising 111 FES patients and 103 healthy controls (HC). Furthermore, we examined the abnormalities within SC-FC coupling in FES and their correlations with meta-analytic cognitive terms, neurotransmitters, and transcriptional patterns through partial least squares regression (PLS), involving similarity with other psychiatric disorders or psychiatric-related diseases, functional enrichments, special cell types, peripheral inflammation, and cortical layers. RESULTS: FES patients exhibited lower SC-FC coupling in the visual, sensorimotor, and ventral attention networks compared to controls. Furthermore, case-control t-maps revealed a negative correlation with neurotransmitters such as serotonin and dopamine, while showing a positive correlation with opioids. Positive t-maps were associated with cognitive functions, including reasoning, judgment, and action, whereas negative t-maps correlated with cognitive functions such as learning, stress, and mood. Moreover, there was a significant overlap between genes linked to abnormalities in SC-FC coupling and those dysregulated in inflammatory bowel diseases. PLS2- genes linked to SC-FC coupling demonstrated significant enrichment in pathways related to immunity and inflammation, as well as in cortical layers I and V. Conversely, PLS2 + genes were primarily enriched in synaptic signaling processes, specific excitatory neurons, and layers II and IV. Additionally, changes in SC-FC coupling were negatively associated with gene expression related to antipsychotics and lymphocytes. CONCLUSIONS: These findings offer a new perspective on the complex interplay between SC-FC coupling abnormalities and transcriptional expression in the initial phases of schizophrenia.

Virus-Induced galactinol-sucrose galactosyltransferase 2 Silencing Delays Tomato Fruit Ripening.

Tomato fruit ripening is an elaborate genetic trait correlating with significant changes at physiological and biochemical levels. Sugar metabolism plays an important role in this highly orchestrated process and ultimately determines the quality and nutritional value of fruit. However, the mode of molecular regulation is not well understood. Galactinoal-sucrose galactosyltransferase (GSGT), a key enzyme in the biosynthesis of raffinose family oligosaccharides (RFOs), can transfer the galactose unit from 1-α-D-galactosyl-myo-inositol to sucrose and yield raffinose, or catalyze the reverse reaction. In the present study, the expression of SlGSGT2 was decreased by Potato Virus X (PVX)-mediated gene silencing, which led to an unripe phenotype in tomato fruit. The physiological and biochemical changes induced by SlGSGT2 silencing suggested that the process of fruit ripening was delayed as well. SlGSGT2 silencing also led to significant changes in gene expression levels associated with ethylene production, pigment accumulation, and ripening-associated transcription factors (TFs). In addition, the interaction between SlGSGT2 and SlSPL-CNR indicated a possible regulatory mechanism via ripening-related TFs. These findings would contribute to illustrating the biological functions of GSGT2 in tomato fruit ripening and quality forming.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and diabetic kidney disease in patients with diabetes in the United States: a cross-sectional study.

BACKGROUND: This paper investigated the link between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and diabetic kidney disease (DKD) in adult diabetic patients and identified the optimal NHHR value for impacting DKD. METHODS: This cross-sectional research made use of records from the National Health and Nutrition Examination Survey (NHANES) executed between 2005 and 2016. The link of NHHR to DKD risk was analyzed by logistic regression and restricted cubic spline (RCS) models. The stability and reliability of the results were assessed by subgroup analysis and sensitivity analysis. RESULTS: In total, 4,177 participants were involved. As a continuous variable, NHHR was markedly connected to an increased risk of DKD (OR 1.07, 95% CI 1.02, 1.12, P < 0.01). When NHHR was grouped in quartiles, relative to the reference set, the highest NHHR group was also linked to a heightened risk of DKD (OR 1.23, 95% CI 1.01, 1.50, P < 0.05). The outcome of RCS show a "J" shaped correlation between NHHR and DKD risk (P for nonlinear = 0.0136). The risk of developing DKD was the lowest when NHHR equals 2.66. Subgroup analysis revealed that the link of NHHR to DKD persisted in participants aged below 40, females, non-smokers, and those without hyperuricemia. Sensitivity analysis demonstrated a certain robustness in this association. CONCLUSION: A meaningful link is present between NHHR and DKD. An NHHR value of around 2.66 could represent the ideal cutoff for assessing DKD risk.

The Role of a New Stabilizer in Enhancing the Mechanical Performance of Construction Residue Soils.

Urban construction generates significant amounts of construction residue soil. This paper introduces a novel soil stabilizer based on industrial waste to improve its utilization. This stabilizer is primarily composed of blast furnace slag (BFS), steel slag (SS), phosphogypsum (PG), and other additives, which enhance soil strength through physical and chemical processes. This study investigated the mechanical properties of construction residue soil cured with this stabilizer, focusing on the effects of organic matter content (Oo), stabilizer dosage (Oc), and curing age (T) on unconfined compressive strength (UCS). Additionally, water stability and wet-dry cycle tests of the stabilized soil were conducted to assess long-term performance. According to the findings, the UCS increased with the higher stabilizer dosage and longer curing periods but reduced with the higher organic matter content. A stabilizer content of 15-20% is recommended for optimal stabilization efficacy and cost-efficiency in engineering applications. The samples lost their strength when immersed in water. However, adding more stabilizers to the soil can effectively enhance its water stability. Under wet-dry cycle conditions, the UCS initially increased and then decreased, remaining lower than that of samples cured under standard conditions. The findings can provide valuable data for the practical application in construction residual soil stabilization.

Development and validation of a nomogram model for predicting 28-day mortality in patients with sepsis.

Background: This study aimed to develop and validate a nomogram model for predicting 28-day mortality in patients with sepsis in the intensive care unit (ICU). Methods: We retrospectively analyzed data from 331 patients with sepsis admitted to the ICU as a training set and collected a validation set of 120 patients. Both groups were followed for 28 days. Logistic regression analyses were performed to identify the potential prognostic factors for sepsis-related 28-day mortality. A nomogram model was generated to predict 28-day mortality in patients with sepsis in the ICU. Receiver operating characteristic (ROC) curve analysis, calibration curves, and decision curve analysis (DCA) were used to evaluate the model's prediction performance and clinical application. In addition, we used ROC curve analysis and DCA to compare this model with the sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores and further assessed the clinical value of our model. Results: Logistic multivariate regression analysis revealed that mechanical ventilation, oxygenation index, and lactate and blood urea nitrogen (BUN) levels were independent predictors of 28-day mortality in patients with sepsis in the ICU. We developed a nomogram model based on these results to further predict 28-day mortality. The model demonstrated satisfactory calibration curves for both training and validation sets. Additionally, in the training set, the area under the ROC curve (AUC) for this model was 0.80. In the validation set, the AUC was 0.82. DCA showed that the high-risk thresholds ranged between 0 and 0.86 in the training set and between 0 and 0.75 in the validation set. We compared the ROC curve and DCA of this model with those of SOFA and APACHE II scores in both the training and validation sets. In the training set, the AUC of this model was significantly higher than those of the SOFA (P = 0.032) and APACHE II (P = 0.004) scores. Although the validation set showed a similar trend, the differences were not statistically significant for the SOFA (P = 0.273) and APACHE II (P = 0.320) scores. Additionally, the DCA showed comparable clinical utility in all three assessments. Conclusion: The present study used four common clinical variables, including mechanical ventilation, oxygenation index and lactate and BUN levels, to develop a nomogram model to predict 28-day mortality in patients with sepsis in the ICU. Our model demonstrated robust prediction performance and clinical application after validation and comparison.

Hsa_circ_0001359 in Serum Exosomes: A Promising Marker to Predict Bronchopulmonary Dysplasia in Premature Infants.

Objective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD). Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤32 weeks). The classical lung biological markers in serum were also measured simultaneously. Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738-0.968; adjusted odds ratio:6.033, 95% CI:2.373-13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058. Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤32 weeks.

Inhibitory Properties of Cinnamon Bark Oil against Postharvest Pathogen Penicillium digitatum In Vitro.

Penicillium digitatum is a major postharvest pathogen that threatens the global citrus fruit industry and causes great economic losses annually. In the present study, inhibitory properties of cinnamon bark oil (CBO) against P. digitatum in vitro were investigated. Results indicated that 0.03% CBO could efficiently inhibit the spore germination, germ tube elongation, mycelial growth, colonial expansion and conidial accumulation of P. digitatum. The results of fluorescein diacetate (FDA) and MitoTraker Orange (MTO) staining also proved the suppression effects of CBO against P. digitatum. Meanwhile, CBO could inhibit green mold rots induced by P. digitatum in citrus fruit when the working concentration of CBO exceeded 0.06%. In addition, the expressions of 12 genes critical for the growth and virulence of P. digitatum were also significantly regulated under CBO stress. Through a transcriptomic analysis, a total of 1802 common differentially expressed genes (DEGs) were detected in P. digitatum after 4 h and 8 h of CBO treatment. Most of the DEG products were associated with carbohydrate, amino acid and lipid metabolism. They directly or indirectly led to the disturbance of the membrane and the generation of reactive oxygen species (ROS). Our results may deepen the understanding of antifungal properties of CBO against P. digitatum and provide the theoretical foundation to uncover the antifungal mechanism of CBO at the molecular level.

The innovative design of high-performance layered transition metal oxides for sodium-ion batteries from a commercial perspective.

Sodium-ion batteries (SIBs), which have ample reserves and low production costs, are receiving more and more attention. As promising cathode candidates, layered transition metal oxides (LTMOs) have attracted intensive interest for their nontoxicity, high theoretical capacities, ease of manufacture, suitable voltage, abundant resources, and potential low cost. However, the commercial implementation of LTMOs is still hampered by their low rate capability, low energy density, insufficient cycling stability, and air instability. Therefore, this review comprehensively summarizes the research progress and modification strategies for LTMOs to enhance the stability of SIBs from microscopic heterostructure regulation to macroscale interface engineering modification. With the aim of realizing commercial applications of SIBs, more attention and research for improving the coulombic efficiency of LTMOS and close communication between academic and industrial organizations are also needed. It is expected that we will be able to provide unique perspectives for the design of powerful LTMOs in SIBs and guide the development of commercial application.

Prospective cohort study on tuberculosis incidence and risk factors in the elderly population of eastern China.

Background: Tuberculosis continues to be a significant public health concern in China, particularly among the elderly population. This study aimed to assess the risk factors of tuberculosis among elderly individuals in China through a cohort study, focusing on this high-risk population. Methods: The population-based census was strategically designed to cover diverse regions and demographics across the city. The survey captured demographic and lifestyle information, as well as a clinical examination. Participants were prospectively followed up over a specified duration to monitor the incidence of tuberculosis cases. Results: After a follow-up period of more than 7 years, 246 individuals developed tuberculosis, resulting in an incidence rate of 92.21 per 100,000 person-years (95 % CI 81.2-104.3). In multivariate analysis, the following factors were found to have significant associations with active tuberculosis. Increasing age correlated with a higher risk of active tuberculosis (AHR = 1.03 per 1-year increase in age, 95%CI: 1.01, 1.04, P < 0.001). Males continued to have a higher risk compared to females (HR = 2.73, 95%CI: 2.08, 3.58, P < 0.001). Individuals with a normal Body Mass Index (BMI) faced nearly three times higher risk compared to their obese counterparts (HR = 2.87, 95 % CI: 1.51, 5.46, P = 0.001). Conversely, those with an underweight BMI had a ten-fold higher risk compared to the obese group (HR = 9.89, 95 % CI: 4.92, 19.85, P < 0.001). Elderly individuals who quit smoking had a 1.35-fold increased risk compared to non-smokers (HR = 1.35, 95%CI: 1.12, 1.64, P < 0.001). Conclusions: Tuberculosis incidence among the elderly population in China remained alarmingly high. This finding emphasizes the urgent need for implementing proactive case detection measures specifically tailored to address the specific needs of this vulnerable demographic, particularly in individuals who are male, have a history of former or current smoking, and have a low BMI. Moreover, we must not underestimate the influence of former smoking on tuberculosis risk.

N-acetylcysteine protects against neurodevelopmental injuries induced by methylmercury exposure during pregnancy and lactation.

As an extremely dangerous environmental contaminant, methylmercury (MeHg) results in detrimental health effects in human brain nervous system, one of its main targets. However, as a developmental toxicant, the brain of offspring is vulnerable to MeHg during pregnancy and lactation exposure. Unfortunately, mechanisms of neurodevelopmental injuries induced by MeHg have not been fully elucidated. N-acetylcysteine (NAC) has been used for several decades as an antioxidant to antagonize oxidative stress. However, the molecular mechanisms of NAC alleviating MeHg-induced neurodevelopmental toxicity are not clear. Here, for evaluation of the dose-dependent effects of MeHg exposure on neurodevelopmental injuries of offspring, and the possible protective effects of NAC, the pregnant female mice were exposed to MeHg (4, 8, 12 mg/L, respectively) and NAC (50, 100, 150 mg/kg, respectively) from gestational day 1 (GD1) to postnatal day 21 (PND21). Our results indicated that administering MeHg caused behavioral impairment and neuronal injuries in the cerebral cortex of newborn mice. MeHg dose-dependently caused reactive oxygen species (ROS) overproduction and oxidative stress aggravation, together with expression of Nrf2, HO-1, Notch1, and p21 up-regulation, and CDK2 inhibition. NAC treatment dose-dependently antagonized MeHg-induced oxidative stress that may contribute to alleviating neurobehavioral and neurodevelopmental impairments. These results give insight into that NAC can protect against MeHg-induced neurodevelopmental toxicity by its antioxidation capacity.

Construction and identification of lncRNA/circRNA-coregulated ceRNA networks in gemcitabine-resistant bladder carcinoma.

OBJECTIVES: To explore the regulatory networks that underlie the development of chemoresistance in bladder cancer. METHODS: We analyzed profiles of differentially expressed long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs) and messenger RNA (mRNAs) in gemcitabine-resistant/sensitive bladder cancer cells using next-generation sequencing data. RESULTS: Hundreds of differentially expressed lncRNAs and miRNAs and thousands of circRNAs and mRNAs were identified. Bioinformatics analysis revealed the chromosomal localizations, classification and coexpression of mRNAs, as well as candidates for cis and trans regulation by lncRNAs. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed mRNAs and circRNAs indicated important functional roles of coregulated RNAs, thus establishing competing endogenous RNA (ceRNA) and protein-protein interactions networks that may underlie chemoresistance in bladder cancer. We demonstrated that lncRNA LINP1 can act as a ceRNA by inhibiting miR-193a-5p to increase TP73 expression; and that lncRNA ESRG and hsa_circ_0075881 can simultaneously bind miR-324-3p to increase ST6GAL1 expression. Modulation of ceRNA network components using ablation and overexpression approaches contributed to gemcitabine resistance in bladder cancer cells. CONCLUSIONS: These results elucidate mechanisms by which lncRNAs and circRNAs coregulate the development of bladder cancer cell resistance to gemcitabine, thus laying the foundation for future research to identify biomarkers and disease targets.

The Identification and Comparative Analysis of Non-Coding RNAs in Spores and Mycelia of Penicillium expansum.

Penicillium expansum is the most popular post-harvest pathogen and causes blue mold disease in pome fruit and leads to significant economic losses worldwide every year. However, the fundamental regulation mechanisms of growth in P. expansum are unclear. Recently, non-coding RNAs (ncRNAs) have attracted more attention due to critical roles in normalizing gene expression and maintaining cellular genotypes in organisms. However, the research related to ncRNAs in P. expansum have not been reported. Therefore, to provide an overview of ncRNAs on composition, distribution, expression changes, and potential targets in the growth process, a comparative transcriptomic analysis was performed on spores and mycelia of P. expansum in the present study. A total of 2595 novel mRNAs, 3362 long non-coding RNAs (lncRNAs), 10 novel microRNAs (miRNAs), 86 novel small interfering RNAs (siRNAs), and 11,238 circular RNAs (circRNAs) were predicted and quantified. Of these, 1482 novel mRNAs, 5987 known mRNAs, 2047 lncRNAs, 40 miRNAs, 38 novel siRNAs, and 9235 circRNAs were differentially expressed (DE) in response to the different development stages. Afterward, the involved functions and pathways of DE RNAs were revealed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database enrichment analysis. The interaction networks between mRNAs, lncRNAs, and miRNAs were also predicted based on their correlation coefficient of expression profiles. Among them, it was found that miR168 family members may play important roles in fungal growth due to their central location in the network. These findings will contribute to a better understanding on regulation machinery at the RNA level on fungal growth and provide a theoretical basis to develop novel control strategies against P. expansum.

An Intraoperative Sub-Anesthetic Dose of Esketamine on Postoperative Depressive Symptoms in Perimenopausal Women with Breast Cancer Undergoing Modified Radical Mastectomy: Protocol for a Randomized, Triple-Blinded, Controlled Trial.

Background: Depressive symptoms are common among perimenopausal women with breast cancer having modified radical mastectomy. Esketamine exerts antidepressant effects. This study aims to assess whether an intraoperative sub-anesthetic dose of esketamine prevents postoperative depressive symptoms in these patients. Methods: In this randomized, triple-blinded, placebo-controlled trial, we will enroll 130 perimenopausal women (aged 45-60 years) with breast cancer undergoing unilateral modified radical mastectomy. Patients will be randomly assigned with a 1:1 ratio to receive either esketamine (0.25 mg/kg i.v.) or normal saline after anesthesia induction and before skin incision. The primary outcome is the incidence of depressive symptoms at day 30 postoperatively, assessed using the Beck's Depression Inventory (BDI). Secondary outcomes include incidence of depressive symptoms and BDI scores at day 1, 3, and 180 postoperatively, anxiety symptoms and scores at day 1, 3, 30, and 180 postoperatively, pain intensity and quality of recovery at day 1 and 2 postoperatively, nausea and vomiting within 48 hours postoperatively, length of postoperative hospital stay, and cancer-specific outcomes. Data will be analyzed in the modified intention-to-treat population. Discussion: This is the first trial to evaluate the effects of a sub-anesthetic dose of esketamine on depressive symptoms in perimenopausal women after modified radical mastectomy. The results of this study will help to improve their mental health and recovery after breast cancer surgery. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200064348).

Development and validation of an in-hospital mortality risk prediction model for patients with severe community-acquired pneumonia in the intensive care unit.

BACKGROUND: A high mortality rate has always been observed in patients with severe community-acquired pneumonia (SCAP) admitted to the intensive care unit (ICU); however, there are few reported predictive models regarding the prognosis of this group of patients. This study aimed to screen for risk factors and assign a useful nomogram to predict mortality in these patients. METHODS: As a developmental cohort, we used 455 patients with SCAP admitted to ICU. Logistic regression analyses were used to identify independent risk factors for death. A mortality prediction model was built based on statistically significant risk factors. Furthermore, the model was visualized using a nomogram. As a validation cohort, we used 88 patients with SCAP admitted to ICU of another hospital. The performance of the nomogram was evaluated by analysis of the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve analysis, and decision curve analysis (DCA). RESULTS: Lymphocytes, PaO2/FiO2, shock, and APACHE II score were independent risk factors for in-hospital mortality in the development cohort. External validation results showed a C-index of 0.903 (95% CI 0.838-0.968). The AUC of model for the development cohort was 0.85, which was better than APACHE II score 0.795 and SOFA score 0.69. The AUC for the validation cohort was 0.893, which was better than APACHE II score 0.746 and SOFA score 0.742. Calibration curves for both cohorts showed agreement between predicted and actual probabilities. The results of the DCA curves for both cohorts indicated that the model had a high clinical application in comparison to APACHE II and SOFA scoring systems. CONCLUSIONS: We developed a predictive model based on lymphocytes, PaO2/FiO2, shock, and APACHE II scores to predict in-hospital mortality in patients with SCAP admitted to the ICU. The model has the potential to help physicians assess the prognosis of this group of patients.

Adipose-derived stem cell exosomes ameliorate traumatic brain injury through the NLRP3 signaling pathway.

The exosomes of mesenchymal stem cells have immunoregulatory properties and can effectively mitigate secondary neuroinflammation due to traumatic brain injury (TBI). In this study, we found that adipose-derived stem cell exosomes (ADSCs-Exo) could reduce the inflammatory response after traumatic brain injury by reducing NLRP3 inflammasome secretion by microglial. ADSCs-Exo were monitored by Western blot and electron microscopy. An in-vitro lipopolysaccharide (LPS)-caused primary microglia model and a TBI rat model were constructed. Functional recovery was examined using the modified neurological severity score and foot fault tests. Inflammasome inactivation in LPS-stimulated microglial, ADSCs-Exo can reduce the secretion of interleukin (IL)-1ß, IL-6 and tumor necrosis factor α. Compared with PBS-processed controls, the sensorimotor functional recovery was significantly improved by exosome treatment after injury at 14-35 days. Additionally, NLRP3 inflammasome was stimulated within 24 h after TBI. ADSCs-Exo application led to remarkable down-expression of NLRP3 and caspase-1. ADSCs-Exo can ameliorate LPS-induced inflammatory activation by reducing microglial pro-inflammatory cytokines. Moreover, the neuroprotective effect of ADSCs-Exo may be partially attributed to the inhibition thereof on the formation of NLRP3-mediated inflammasome. Such findings imply a potential function of ADSCs-Exo in treating TBI.

The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.