Obesity and septic patient outcomes: Shaping the puzzle through age and sex perspectives.

BACKGROUND & AIMS: While obesity has been reported as a protective factor in septic patients, little is known about the potential modifying effects of age and sex. The objective of this study is to investigate age and sex-specific associations between obesity and the prognosis of septic patients. METHODS: A retrospective analysis was conducted on a cohort of 15,464 septic patients, categorized by body mass index (BMI) into four groups: underweight (<18.5 kg/m2, n = 483), normal (18.5-24.9 kg/m2, n = 4344), overweight (25-29.9 kg/m2, n = 4949) and obese (≥30 kg/m2, n = 5688). Multivariable logistic regression and inverse probability weighting were employed to robustly confirm the protective effect of a higher BMI on 28-day mortality, with normal weight serving as the reference category. Subgroup analyses based on age (young: 18-39, middle-aged: 40-64 and elderly: ≥65) and sex were performed. RESULTS: The findings demonstrate that high BMI independently confers a protective effect against 28-day mortality in septic patients. However, the relationship between BMI and 28-day mortality exhibits a non-linear trend, with a BMI of 34.5 kg/m2 displaying the lowest odds ratio. Notably, the survival benefits associated with a high BMI were not observed in the young group. Moreover, being underweight emerges as an independent risk factor for middle-aged and elderly female patients, while in males it is only a risk factor in the elderly group. Interestingly, being overweight and obese were identified as independent protective factors in middle-aged and elderly male patients, but not in females. CONCLUSIONS: The effect of BMI on mortality in septic patients varies according to age and sex. Elderly individuals with sepsis may derive more prognostic benefits from obesity.

Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is the most common complication of sepsis, with increased morbidity and mortality. To date, there has still been no established pharmacological therapy. Memantine, as an NMDA (N-methyl-d-aspartate) receptor antagonist, exhibited neuroprotective effects against cognitive and emotional dysfunction in many disorders. We performed cecal ligation and puncture (CLP) inducing sepsis as the ideal animal model of SAE. CLP-induced septic mice were given a memantine treatment through intragastric administration. The novel object recognition test indicated that memantine significantly improved cognitive dysfunction in septic mice. The open field test revealed that the anxiety-like behaviors and locomotion ability of septic mice were relieved by memantine. The pole test further confirmed the protective effects of memantine against immobility. Memantine significantly inhibited the excessive glutamate production and improved impaired neurogenesis on first and seventh day after sepsis, accompanying with reducing proinflammatory cytokines production (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1beta (IL-1ß), and IL-10) and microglia activation in the brain of SAE. In addition, memantine treatment also reducing sepsis-induced brain blood barrier disruption via inhibiting the expression of metalloproteinase-9 (MMP-9). In conclusion, memantine exerted neuro-protective effects against cognitive and emotional defects, which might be considered as a promising therapy for SAE.

Comprehensive single-cell analysis reveals novel anergic antigen-presenting cell subtypes in human sepsis.

Background: Sepsis is a life-threatening condition with high mortality. A few studies have emerged utilizing single-cell RNA sequencing (scRNA-seq) to analyze gene expression at the single-cell resolution in sepsis, but a comprehensive high-resolution analysis of blood antigen-presenting cells has not been conducted. Methods: All published human scRNA-seq data were downloaded from the single cell portal database. After manually curating the dataset, we extracted all antigen-presenting cells, including dendritic cells (DCs) and monocytes, for identification of cell subpopulations and their gene profiling and intercellular interactions between septic patients and healthy controls. Finally, we further validated the findings by performing deconvolution analysis on bulk RNA sequencing (RNA-seq) data and flow cytometry. Results: Within the traditional DC populations, we discovered novel anergic DC subtypes characterized by low major histocompatibility complex class II expression. Notably, these anergic DC subtypes showed a significant increase in septic patients. Additionally, we found that a previously reported immunosuppressive monocyte subtype, Mono1, exhibited a similar gene expression profile to these anergic DCs. The consistency of our findings was confirmed through validation using bulk RNA-seq and flow cytometry, ensuring accurate identification of cell subtypes and gene expression patterns. Conclusions: This study represents the first comprehensive single-cell analysis of antigen-presenting cells in human sepsis, revealing novel disease-associated anergic DC subtypes. These findings provide new insights into the cellular mechanisms of immune dysregulation in bacterial sepsis.

Synergistic therapeutic effect of nanomotors triggered by Near-infrared light and acidic conditions of tumor.

Due to the complexity of tumors, multimodal therapy for them has always been of concern to researchers. How to design a multifunctional drug nanoplatform with cascade effect and capable of responding to specific stimuli in the tumor microenvironment is the key to achieve efficient multimodal synergistic therapy of cancer. Here, we prepare a kind of GNRs@SiO2@PDA-CuO2-l-Arg (GSPRs-CL) nanomotors for systematic treatment of tumor. First, under near-infrared (NIR) irradiation, GSPRs-CL can generate heat and exhibit excellent photothermal therapy effect. Then under acidic conditions, CuO2 can be decomposed to release Cu2+ and generate H2O2, which not only complemented the limited endogenous H2O2 in cells, but also further triggered Fenton-like reaction, converting H2O2 into •OH to kill cancer cells, thereby achieving chemodynamic therapy. Furthermore, both endogenous and exogenous H2O2 can release nitric oxide (NO) in response to the occurrence of l-Arg of nanomotors to enhance gas therapy. In addition, as a dual-mode drive, NIR laser and NO can promote the penetration ability of nanomotors at tumor sites. The experimental results in vivo show that the drug nanoplatform had good biosafety and significant tumor killing effect triggered by NIR light and acidic conditions of tumor. It provide a promising strategy for the development of advanced drug nanoplatform for cancer therapy.

Biodegradable CuMoO4 Nanodots with Multienzyme Activities for Multimodal Treatment of Tumor.

Due to their complexity and variability, tumors need to be treated with multimodal combined therapy, which requires the development of therapeutic agents that can provide multimodal therapeutic effects. Herein, CuMoO4 nanodots smaller than 10 nm that can be prepared by simple hydrothermal method are reported. These nanodots can be well dispersed in water and have good biosafety and biodegradability. Further studies show that these nanodots also present multienzyme activities, such as catalase, peroxidase and glutathione peroxidase. In addition, CuMoO4 nanodots exhibit high photothermal conversion efficiency (41%) under 1064 nm near-infrared laser irradiation. In vitro and in vivo experimental results indicate that CuMoO4 nanodots can effectively inhibit the instinctive regulation of tumor cells to oxidative stress, provide sustained treatment to achieve photothermal synergistic ferroptosis, and trigger immune responses to immunogenic cell death. It is worth mentioning that the CuMoO4 nanodots also cause cuproptosis of tumor cells. This study provides a promising nanoplatform for multimodal combined therapy of cancer.

[Protective effect of barium chloride pretreatment on lung in mice with acute respiratory distress syndrome].

OBJECTIVE: To explore whether barium chloride (BaCl2) preconditioning has the protective effect on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model in mice and the possible mechanism. METHODS: Sixty 8-12 week old healthy C57BL/6 male mice were randomly divided into control group, ARDS model group and BaCl2 pretreatment group, with 20 mice in each group. The BaCl2 pretreatment group was continuously injected with BaCl2 (4 mg/kg through the tail vein) for 3 days before ARDS model establishment. ARDS model was established by intratracheally injecting (3 mg/kg) LPS. The control group was intratracheally given the same volume of 0.9% normal saline. On 24th hour after ARDS model establishment, some mice were sacrificed for obtaining fresh lung tissue. And the right lower lobe of the lung was separated for observing the pathological changes of lung tissue while the left lung tissue was used to measure the wet/dry weight ratio (W/D) of the lung. Some mice were sacrificed for observing pulmonary microvascular permeability at 2nd hours after injecting Evans blue (EB) through tail vein. The left mice were killed for alveolar lavage to measure the levels of tumor necrosis factor-α (TNF-α) via enzyme linked immunosorbent assay (ELISA). RESULTS: Comparing with the control group, ARDS model group showed typical ARDS pathological changes, which included the increased W/D ratio (4.951±0.161 vs. 3.449±0.299, P < 0.01) and the content of EB in the lung tissue (µg/g: 0.130±0.027 vs. 0.085±0.011, P < 0.01), the damaged alveolar wall structure, lung congestion and exudates in the alveoli, as well as amounts of inflammatory cells. The pathological score of lung injury (10.33±1.15 vs. 1.67±0.58) and the level of TNF-α in BALF (ng/L: 900.85±247.80 vs. 68.21±5.79) were significantly increased in the ARDS model group (both P < 0.01). Comparing with the ARDS model group, the lung W/D ratio (4.620±0.125 vs. 4.951±0.161) and the EB content in the lung tissue (µg/g: 0.108±0.011 vs. 0.130±0.027) of BaCl2 pretreatment group were significantly reduced (both P < 0.01). And the damaged pulmonary structural BaCl2 pretreatment group were significantly alleviated. In addition, the pulmonary pathological score (5.00±1.00 vs. 10.33±1.15) and the level of TNF-α in BALF (ng/L: 169.16±73.33 vs. 900.85±247.80) were significantly decreased (both P < 0.01). CONCLUSIONS: Barium chloride pretreatment can improve the lung histopathological changes of ARDS model mice induced by LPS by reducing the permeability of pulmonary capillaries and local inflammatory reaction.Barium chloride has the protective effect against LPS attack in mice model of ARDS.

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor.

A kind of drug-loaded nanomotors with deep penetration was developed to improve the therapeutic effect of ferroptosis on tumor. The nanomotors were constructed by co-loading hemin and ferrocene (Fc) on the surface of bowl-shaped polydopamine (PDA) nanoparticles. The near-infrared response of PDA makes the nanomotor have high tumor penetration capability. In vitro experiments show that the nanomotors can exhibit good biocompatibility, high light to heat conversion efficiency, and deep tumor permeability. It is worth noting that under the catalysis of H2O2 overexpressed in the tumor microenvironment, the Fenton-like reagents hemin and Fc loaded on the nanomotors can increase the concentration of toxic •OH. Furthermore, hemin can consume glutathione in tumor cells and trigger the up-regulation of heme oxygenase-1, which can efficiently decompose hemin to Fe2+, thus producing the Fenton reaction and causing a ferroptosis effect. Notably, thanks to the photothermal effect of PDA, it can enhance the generation of reactive oxygen species and thus intervene in the Fenton reaction process, thereby enhancing the ferroptosis effect photothermally. In vivo antitumor results show that the drug-loaded nanomotors with high penetrability showed an effective antitumor therapeutic effect.

Combining Serum Procalcitonin Level, Thromboelastography, and Platelet Count to Predict Short-term Development of Septic Shock in Intensive Care Unit.

OBJECTIVE: Despite the recent advances in diagnosis and treatment, sepsis continues to lead to high morbidity and mortality. Early diagnosis and prompt treatment are essential to save lives. However, most biomarkers can only help to diagnose sepsis, but cannot predict the development of septic shock in high-risk patients. The present study determined whether the combined measurement of procalcitonin (PCT), thromboelastography (TEG) and platelet (PLT) count can predict the development of septic shock. METHODS: A retrospective study was conducted on 175 septic patients who were admitted to the intensive care unit between January 2017 and February 2021. These patients were divided into two groups: 73 patients who developed septic shock were assigned to the septic shock group, while the remaining 102 patients were assigned to the sepsis group. Then, the demographic, clinical and laboratory data were recorded, and the predictive values of PCT, TEG and PLT count for the development of septic shock were analyzed. RESULTS: Compared to the sepsis group, the septic shock group had statistically lower PLT count and TEG measurements in the R value, K value, α angle, maximum amplitude, and coagulation index, but had longer prothrombin time (DT), longer activated partial thromboplastin time (APTT), and higher PCT levels. Furthermore, the Sequential Organ Failure Assessment (SOFA) score was higher in the septic shock group. The multivariate logistic regression analysis revealed that PCT, TEG and PLT count were associated with the development of septic shock. The area under the curve analysis revealed that the combined measurement of PCT, TEG and PLT count can be used to predict the development of septic shock with higher accuracy, when compared to individual measurements. CONCLUSION: The combined measurement of PCT, TEG and PLT count is a novel approach to predict the development of septic shock in high-risk patients.

Polydopamine nanomotors loaded indocyanine green and ferric ion for photothermal and photodynamic synergistic therapy of tumor.

The limited penetration depth of nanodrugs in the tumor and the severe hypoxia inside the tumor significantly reduce the efficacy of photothermal-photodynamic synergistic therapy (PTT-PDT). Here, we synthesized a methoxypolyethylene glycol amine (mPEG-NH2)-modified walnut-shaped polydopamine nanomotor (PDA-PEG) driven by near-infrared light (NIR). At the same time, it also loaded the photosensitizer indocyanine green (ICG) via electrostatic/hydrophobicinteractions and chelated with ferric ion (Fe3+). Under the irradiation of NIR, the asymmetry of PDA-PEG morphology led to the asymmetry of local photothermal effects and the formation of thermal gradient, which can make the nanomotor move autonomously. This ability of autonomous movement was proved to be used to improve the permeability of the nanomotor in three-dimensional (3D) tumor sphere. Fe3+ can catalyze endogenous hydrogen peroxide to produce oxygen, so as to overcome the hypoxia of tumor microenvironment and thereby generate more singlet oxygen to kill tumor cells. Animal experiments in vivo confirmed that the nanomotors had a good PTT-PDT synergistic treatment effect. The introduction of nanomotor technology has brought new ideas for cancer optical therapy.

Construction of a matchstick-shaped Au@ZnO@SiO2-ICG Janus nanomotor for light-triggered synergistic antibacterial therapy.

The drug-resistance of bacteria poses a serious threat to public health, so the exploration of new antibacterial materials has attracted extensive attention. Here, we report Au@ZnO@SiO2-ICG nanomotors as an antibacterial candidate. Firstly, we prepared the Janus structure Au@ZnO loaded with indocyanine green (ICG) and constructed a synergistic antibacterial platform with photothermal and photodynamic properties triggered by dual light sources. Specifically, the metal/semiconductor heterostructure of Au@ZnO has a synergistic effect under ultraviolet (UV) irradiation, which can adjust the transfer of interface electrons, so as to greatly improve the generation of cytotoxic ROS for photodynamic sterilization. The loaded ICG is an effective photosensitizer, and can induce a stronger photothermal effect in collaboration with Au under near-infrared light (NIR). In addition, the asymmetric structures of nanomotors have autonomous movement with the help of generated temperature gradient when exposed to NIR light, conducive to breaking through the bacterial membrane and improving the membrane insertion ability of antibacterial therapeutic agents. The results indicate that the prepared Au@ZnO@SiO2-ICG nanomotors show excellent light responses and synergistic sterilization ability to Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). This study will provide a new idea for the application of metal-semiconductor nanocomposites in the treatment of bacterial infection.

Doxorubicin-Loaded Walnut-Shaped Polydopamine Nanomotor for Photothermal-Chemotherapy of Cancer.

The combination of photothermal therapy and chemical drug therapy shows good prospects in cancer treatment, but there are also some limitations such as low permeability of therapeutic agents and uneven photothermal therapy. Here, we synthesized a walnut-shaped polydopamine (PDA) nanomotor driven by near infrared (NIR) light. The nanomotor was modified by methoxy polyethylene glycol amine (mPEG-NH2) for improving water solubility. PDA-PEG loaded adriamycin through π-π accumulation and hydrogen bonding. The experimental results showed that the PDA nanomotors had good biocompatibility and photothermal effect. Further, the NIR light irradiation and tumor cell microenvironment are conducive to drug release. In addition, under the irradiation of an NIR laser, the asymmetry of walnut-shaped nanoparticles makes the particles obtain the ability of autonomous movement, which can improve the permeability of particles in 3D tumor balls, which can provide support for drug penetration and heat dispersion. This strategy offers potential innovative materials for photothermal/chemotherapy synergistic therapy of tumors.

Ten-Year Changes in Bloodstream Infection With Acinetobacter Baumannii Complex in Intensive Care Units in Eastern China: A Retrospective Cohort Study.

Background: There is little evidence on the changing prevalence, microbiological profile, and outcome of nosocomial Acinetobacter baumannii complex (ABC)-caused bloodstream infection (ABCBSI) specified in intensive care units (ICUs) in long-term studies, especially in China. Objective: We aimed to investigate changes in incidence, antibiotic resistance, therapy, and prognosis of ABCBSI in ICUs in eastern China during 2009-2018. Methods: A multicenter retrospective cohort study was conducted, and microbiological and clinical data for patients with ABCBSI acquired in nine adult ICUs in eastern China from 2009 to 2018. Results: A total of 202 cases were enrolled. For the years 2009-2010, 2011-2012, 2013-2014, 2015-2016, and 2017-2018, the incidence of ABCBSI increased significantly, as did the percentage of pan-drug-resistant isolates and resistant rates to most of antimicrobial agents; the percentage of drug-sensitive isolates decreased (all P < 0.05). The frequency of treatment with carbapenems and tigecycline increased, and that of cephalosporins decreased. Compared with those in the first years (2009-2012), ABCBSI patients in the lattermost years (2017-2018) were less often treated with appropriate empirical therapy, more often underwent pneumonia-related ABCBSI and mechanical ventilation support, and had higher 28-day mortality rates. Multivariate Cox regression indicated that increase in the degree of ABC antibiotics resistance, pneumonia-related ABCBSI, and septic shock were risk factors of 28-day mortality and associated with significant lower survival days. Conclusions: The past decade has witnessed a marked increase in the incidence of ABCBSI and in antibiotic resistance, with increasing pneumonia-related infections and worrisome mortality in ICUs in China. Controlling increasing resistance and preventing nosocomial pneumonia may play important roles in combatting these infections.

Case Report: Life-Threatening Post-operative Hemorrhage in Klippel-Trenaunay Syndrome Associated With Hypofibrinogenemia.

Klippel-Trenaunay Syndrome (KTS) is a rare congenital disorder, characterized by venous and lymphatic malformations of the skin, soft tissue, and bone, causing limb hypertrophy. Although, a ruptured hemorrhagic corpus luteum is a rare condition in women of reproductive age, it can result in lethal outcomes. Here, we have described a patient with KTS and hypofibrinogenemia who went through recurrent lethal postoperative bleeding due to a ruptured hemorrhagic corpus luteum. This case suggested that conservative therapy might be the first choice and effective therapy for the patients with KTS, who suffered from bleeding complications of surgical therapy.

Colonization With Extensively Drug-Resistant Acinetobacter baumannii and Prognosis in Critically Ill Patients: An Observational Cohort Study.

Background: Acinetobacter baumannii is one of the most frequently isolated opportunistic pathogens in intensive care units (ICUs). Extensively drug-resistant A. baumannii (XDR-AB) strains lack susceptibility to almost all antibiotics and pose a heavy burden on healthcare institutions. In this study, we evaluated the impact of XDR-AB colonization on both the short-term and long-term survival of critically ill patients. Methods: We prospectively enrolled patients from two adult ICUs in Qilu Hospital of Shandong University from March 2018 through December 2018. Using nasopharyngeal and perirectal swabs, we evaluated the presence of XDR-AB colonization. Participants were followed up for 6 months. The primary endpoints were 28-day and 6-month mortality after ICU admission. The overall survival rate was estimated by the Kaplan-Meier method. We identified risk factors associated with 28-day and 6-month mortality using the logistic regression model and a time-dependent Cox regression model, respectively. Results: Out of 431 patients, 77 were colonized with XDR-AB. Based on the Kaplan-Meier curve results, the overall survival before 28 days did not differ by colonization status; however, a significantly lower overall survival rate was obtained at 6 months in colonized patients. Univariate and multivariate analysis results confirmed that XDR-AB colonization was not associated with 28-day mortality, but was an independent risk factor of lower overall survival at 6 months (HR = 1.749, 95% CI = 1.174-2.608). Conclusions: XDR-AB colonization has no effect on short-term overall survival, but is associated with lower long-term overall survival in critically ill patients.

A Novel Human Acute Encephalitis Caused by Pseudorabies Virus Variant Strain.

BACKGROUND: Pseudorabies virus (PRV) is a common pathogen in multiple animal species, particularly in pigs. However, PRV infection in humans is rare and, to the best of our knowledge, PRV has never been isolated from human cases before. METHODS: Four acute encephalitis cases in humans were confirmed as PRV infection based on clinical symptoms, laboratory diagnosis, and metagenomic next-generation sequencing (mNGS). Cerebrospinal fluid (CSF) samples were collected and applied for virus isolation. Etiological and genetic characteristics of this PRV human isolate were further determined. RESULTS: The patients manifested respiratory dysfunction and acute neurological symptoms. The mNGS revealed PRV-specific nucleotide sequences in patients' CSF samples (7-6198 reads and 0.2446%-80.58% coverage). The PRV envelope glycoprotein B antibody, glycoprotein E antibody, and neutralizing antibody were positively detected. For the first time, a PRV strain, designated hSD-1/2019, was isolated and identified from a CSF sample, and transmission electron microscopy revealed that hSD-1/2019 had typical morphology similar to that of swine PRV. Phylogenetic analysis illustrated that hSD-1/2019 was genetically closest to those PRV variant strains currently circulating in pigs in China, and this strain showed similar etiological characteristics to Chinese PRV variant strains, while different from Chinese classical strain. Moreover, hSD-1/2019 showed high pathogenicity and induced acute neurological symptoms in pigs. CONCLUSIONS: A PRV strain was isolated from an acute human encephalitis case. This isolate showed close phylogenetic relationships and similar etiological characteristics to Chinese PRV variant strains, implying the great risk of PRV transmission from pigs to humans.

Retraction: Neural stem cell conditioned medium alleviates Aß25-35 damage to SH-SY5Y cells through the PCMT1/MST1 pathway.

On behalf of the coauthors and with much regret, I must retract our publication entitled "Neural stem cell conditioned medium alleviates Aß25-35 damage to SH-SY5Y cells through the PCMT1/MST1 pathway" published on European Journal of Histochemistry 2020;64(s2):3135 for the following reasons: In Figure 1A, the data of 20 µM Aß25-35 for different time were confused with the data of 30 µM Aß25-35 for different time. In Figure 2, the differential expression of PCMT1 is poor in repeatability. The authors need to revise the experimental design and steps to verify it again, re-do the experiment and conduct a more in-depth study. Dr. Congcong Sun Department of Neurology Qilu Hospital Cheeloo College of Medicine Shandong University China.

Mesenchymal stem cells from human umbilical cord regulate the expression of major histocompatibility complex in human neural stem cells and their lineages.

hNSCs (human neural stem cells) derived from embryonic tissue and aborted fetal brains are considered to be the most promising candidates for neurodegenerative and other CNS(central nervous system) diseases. However, the most common problem, which limited successful use of these allogeneic hNSC therapy, is immune rejection. Mesenchymal stem cells (MSCs) from human umbilical cord (hUC-MSCs) are receiving increasing attention for their immune-modulatory properties. In the current studies, we firstly investigated the immunogenecity of hNSCs as well as their lineages in cultures with the presence or absence of interferon gamma (IFNγ), a pro-inflammatory factors. Our data revealed that the majority of hNSCs and astrocytes expressed MHCI (major histocompatibility complex class I) while neurons hardly expressed MHCI (<5%) in the absence of IFNγ. In addition, neither hNSCs nor neurons expressed MHCII while a subpopulation (about 18 %) of astrocytes expressed MHCII without IFNγ stimulation. However, the addition of IFNγ in cultures significantly increased the expressions of MHCII on hNSCs and astrocytes. However, IFNγ did not affect the expression of MHCI on hNSCs and astrocytes. We then investigated whether hUC-MSCs had the capacity of regulating the immunogenecity of hNSCs as well as their lineages in a co-culture system. We found that hUC-MSCs did not affect the expression of MHCI on hNSCs and their lineages, however, these cells were able to significantly inhibit the IFNγ-induced up-regulation of MHCII on hNSCs and astrocytes (p < 0.001). Thus, our results suggest that hUC-MSCs may serve as potentially useful modulators to reduce the immunogenicity of allogeneic hNSCs in clinical application.

Listeria rhombencephalitis mimicking acute disseminated encephalomyelitis in a patient without predisposing medical conditions.

Listeria rhombencephalitis (L. rhombencephalitis) is an uncommon form of central nervous system infection caused by Listeria monocytogenes (LM). It often occurs to immunocompetent individuals. Here, we described the case of a 45-year-old female patient without medical histories, who presented for high-grade fever, headache, and focal neurological manifestations. She was initially empirically diagnosed with acute disseminated encephalomyelitis (ADEM) because of clinical symptoms, acute clinical course, and neuroimaging. However, the biochemical analysis of cerebral spinal fluid (CSF) questioned the diagnosis of ADEM. The final diagnosis of L. rhombencephalitis was based on CSF culture for LM. Thus, L. rhombencephalitis should be preferentially and empirically considered for a patient with significantly elevated lactic acid and moderately increased red cells in CSF at early time, accompanied with rapidly progressive neurological dysfunctions involved in the brain stem.

Neural stem cell conditioned medium alleviates Aß25-35 damage to SH-SY5Y cells through the PCMT1/MST1 pathway.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that protein isoaspartate methyltransferase 1 (PCMT1) is highly expressed in brain tissue (substantia nigra, blue plaque, paraventricular nucleus). In this study, we investigated the effect of neural stem cell conditioned medium alleviates Aß25-35 damage to SH-SY5Y cells by PCMT1/MST1 pathway. Results demonstrated that Aß25-35 significantly decreased the cell viability in time and dose dependent manner. However, Neural stem cell-complete medium (NSC-CPM) or NSC-CDM had inhibitory effect on toxicity when fibrillation of Aß25-35 occurred in their presence and NSC-CDM had a better inhibitor result. An increase of the PCMT1 expression levels was found in Aß25-35 + NSC-CDM group. sh-PCMT1 significantly reduced the PCMT1, the cell viability and inhibited the protective effect; induced apoptosis and increased the expression of p-MST1. Overexpression of PCMT1 group reversed the effect of Aß25-35 inhibited the cell viability and Aß25-35 induced the apoptosis. In conclusion, NSC-CDM corrects the damage of Aß25-35 to cells by increasing PCMT1, reducing MST phosphorylation.