EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates.

BACKGROUNDS: It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD. METHODS: The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan-Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed. RESULTS: In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p < 0.05). Smoking was associated with elevated EZH2 expression (p < 0.001). EZH2 was highly expressed in lung cancers with positive KRAS expression, and the correlation was significant in lung adenocarcinoma (r = 0.3129, p < 0.001). CMap was applied to determine the top 15 positively correlated drugs/molecules and the top 15 negatively correlated drugs/molecules. MK-1775, MK-5108, fenbendazole, albendazole, BAY-K8644, evodiamine, purvalanol-a, mycophenolic-acid, PHA-793887, and cyclopamine are potential drugs for patients with lung adenocarcinoma and high EZH2 expression. CONCLUSIONS: Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes.

Streptococcus dysgalactiae subsp. dysgalactiae presents with progressive weakness in limbs: a case report and literature review.

BACKGROUND: Streptococcus dysgalactiae subsp. dysgalactiae has been identified as an animal pathogen that is thought to occur only in animal populations. Between 2009 and 2022, humans infected with SDSD were reported rarely. There is a lack of details on the natural history, clinical features, and management of disease caused by this pathogen. This case outlines a human SDSD with muscle aches and progressive loss of muscle strength leading to immobility and multi-organ dysfunction syndrome. CASE PRESENTATION: She presented with muscle pain and weakness, and later developed a sore throat, headache and fever with a maximum temperature of 40.5 °C. The muscle strength of the extremities gradually decreased to grade 1 and the patient was unable to move on his own. Next-generation blood sequencing and multi-culture confirmed the presence of Streptococcus dysgalactiae and Streptococcus dysgalactiae subsp. Dysgalactiae, respectively. A Sequential Organ Failure Assessment score of 6 indicated septicemia, and therapeutic antibiotics were prescribed empirically. After 19 days of inpatient treatment, the patient's condition greatly improved and completely recovered within a month. CONCLUSION: Symptoms of Streptococcus dysgalactiae subsp. dysgalactiae presenting with progressive limb weakness resemble polymyositis, so a precise differential diagnosis is essential. Multidisciplinary consultation is helpful when polymyositis cannot be ruled out and facilitates the choice of an optimal treatment protocol. In the context of this case, penicillin is an effective antibiotic for Streptococcus dysgalactiae subsp. dysgalactiae infection.

The potential value of serum GP73 in the ancillary diagnosis and grading of liver cirrhosis.

This study is to evaluate the potential value of serum GP73 in ancillary cirrhosis diagnosis. 150 cirrhotic subjects and healthy subjects were retrospectively analyzed, and the two groups were compared in terms of Child‒Pugh grade. Serum GP73 was detected by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were drawn to evaluate the diagnostic value of GP73, and the quantitative relationship between cirrhosis and GP73 was verified by logistic regression. The result showed in regard to serum biomarkers related to cirrhosis, the serum levels of GP73, TBIL, DBIL, and PT were higher and the ALB and PLT were lower in the cirrhosis group than in the control group (p = 0.000), and the area under the ROC curve of GP73 for diagnosing cirrhosis was 0.823 (p = 0.000), the cutoff value was 135 ng/ml, the sensitivity was 60.0%, and the specificity was 88.67%. Logistic regression analysis showed that GP73 > 135 ng/ml had an odds ratio of 11.735 (ß= 2.463, 95% CI: 6.432-21.411, p = 0.000) for diagnosing cirrhosis. Additionally, the Child‒Pugh A, B, and C groups had different levels of GP73 (χ2 =17.840, p = 0.000). A pairwise comparison between the groups showed that there was a significant difference between grades A and B (p = 0.004) and between grades A and C (p = 0.002), but there was no significant difference between grades B and C (p = 1.000). We found serum GP73 levels were elevated in patients with cirrhosis. When the GP73 level was >135 ng/ml, the potential risk of a cirrhosis diagnosis increased approximately 12-fold.

Inhibition of visfatin alleviates sepsis-induced intestinal damage by inhibiting Hippo signaling pathway.

BACKGROUND: The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. METHODS: C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. RESULTS: The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. CONCLUSION: In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.

Association between the HLA-B*1502 gene and mild maculopapular exanthema induced by antiepileptic drugs in Northwest China.

BACKGROUND: The relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. In this study, we investigated the association between AED-induced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China. METHODS: We enrolled 165 subjects including nine patients with AED-MPE and 156 AED-tolerant patients as controls. HLA-B*1502 gene polymorphism was detected using digital fluorescence molecular hybridization (DFMH). The results of HLA genotyping were expressed as positive or negative for the HLA-B*1502 allele. An analysis of AED-MPE risk factors was performed using binary logistic regression, and differences in genotype frequencies between groups were assessed with the continuity correction chi-square test. RESULTS: We found that the HLA-B*1502 gene was a risk factor for AED-MPE (P = 0.028). The incidence of MPE induced by the two types of AEDs was different, and the incidence of aromatic AEDs use was higher that of non-aromatic AEDs use (P = 0.025). The comparison of the gene frequencies of the HLA-B*1502 allele between the two groups taking aromatic AEDs was also statistically significant (P = 0.045). However, there were no significant differences in terms of age, gender, ethnicity, or region in patients with MPE induced by AEDs. In addition, no association between the HLA-B1502 allele and CBZ- or OXC-induced MPE was found. CONCLUSIONS: In northwestern China, the HLA-B*1502 allele was associated with aromatic AED-MPE. Since MPE can develop into Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the HLA-B*1502 gene should be evaluated before administering AEDs.

Office-based salivary gland ductal irrigation in patients with chronic sialoadenitis: A preliminary study.

BACKGROUND/PURPOSE: To evaluate the therapeutic responsiveness of office-based salivary gland ductal irrigation in patients with chronic sialoadenitis. METHODS: Between August 2017 and April 2019, 55 patients comprising the following three disease groups were enrolled: Sjogren's syndrome: 39 patients; postradiotherapy sialoadenitis: ten patients; and post-RAI sialoadenitis: six patients. Quantitative salivary scintigraphy was recorded, and a formulated questionnaire including the Summated Xerostomia Inventory was utilized to assess acute/chronic symptoms. All patients received at least three serial salivary gland ductal irrigations with a one-month interval in our outpatient department. RESULTS: The general response rates for each disease groups are as follows: Sjogren's syndrome: 61.5% (24/39); postradiotherapy: 60% (6/10); and post-RAI: 83.3% (5/6). Among the patients with Sjogren's syndrome, the parotid scintigraphic Tmin showed a significant positive correlation with the responsiveness of salivary irrigation (P = 0.046), whereas the treatment tended to be irresponsive in patients who previously took medicine for their related discomfort (P = 0.009). In the postradiotherapy and post-RAI groups, no significant factors were found to be associated with the responsiveness of irrigation. CONCLUSION: Simple salivary ductal irrigation without complex equipment can be performed as an outpatient procedure to alleviate glandular swelling or xerostomia in patients with Sjogren's syndrome, postradiotherapy sialoadenitis or post-RAI sialoadenitis, and it can be considered an alternative management approach for patients refractory to conventional strategies.

Combination of fractional QSRL and IPL for melasma treatment in Chinese population.

BACKGROUND: Melasma is the most common and distressing pigmentary disorder presenting to dermatology clinics. Various treatment protocols for melasma have been suggested in the previous literature and applied in various clinical settings. However, no satisfactory therapy has been widely accepted. OBJECTIVE: To evaluate the efficiency and safety of a combination treatment with fractional Q-switched ruby laser (QSRL) and intense pulsed light (IPL) for melasma in Chinese population. METHODS: Fifty-three Chinese melasma patients were enrolled in this study. Each patient underwent 2 courses of treatments at 2-week interval. One course was composed of 3 successive sessions of 694-nm fractional QSRL at intervals of two weeks followed by one IPL. The efficacy was evaluated by non-invasive measurements and subjective assessments. The adverse effects were recorded. RESULTS: Mean melanin index (MI) and erythema index (EI) significantly decreased from 216.1 and 381.8 pre-treatment to 167.8 and 310.3 post-treatment, respectively. Mean melasma area and severity index (MASI) decreased dramatically from 14.66 before treatment to 5.70 after the final treatment. These values remained at low levels at 3-month follow-up. The percentage of patients who achieved moderate or significant improvements was 73.6%. Adverse effects of QSRL and IPL were minimal. CONCLUSION: The combination treatment of fractional QSRL and IPL would be a promising modality for managing melasma in Chinese patients.

A Split-Face Study of Dual-Wavelength Laser on Neck and Facial Port-Wine Stains in Chinese Patients.

BACKGROUND: Although pulsed dye laser (PDL) has long been regarded as the gold standard in treating port-wine stain (PWS), advanced PWS with deeper coloration may display resistance because of limited penetration depth of 585 or 595-nm light. Recently, a dual-wavelength laser system has been reported to achieve pronounced fading in many patients. OBJECTIVE: The objective was to evaluate the efficacy and safety of a dual-wavelength laser device in treatment of neck and facial PWS in a direct side-by-side comparison. METHODS: Sixteen Chinese patients with neck and/or facial PWSs were enrolled in the study. All lesions were randomly divided into two area, treated area and adjacent untreated area. Five successive treatments using a dual-wavelength laser system (595-nm PDL combined with 1,064-nm Nd:YAG laser) were delivered on treated areas at 4- to 6-week intervals. The adjacent area was not treated as self control. Two blinded dermatologists evaluated the clinical changes by comparing the before and after photos. Erythema index (EI) values were measured with a non-invasive instrument. RESULTS: After five sessions of treatment, over 62.5% (10/16) patients achieved more than 50% (moderate or significant) improvement. The efficacy maintained at the 3-month follow-up visit. The values of EI on treated area showed a significant decrease. Adverse effects of treated area were limited. CONCLUSION: Using this split-face module, the dual-wavelength laser system is proved to be effective and well tolerated in treating neck and facial PWSs in Chinese patients. Adverse effects were minimal and acceptable.

Survival disparities among racial groups with hepatic malignant tumors.

BACKGROUND: Investigating the impact of race on the clinicopathologic characteristics and prognosis of hepatic malignant tumors represents a complex and significant area of research. Notably, distinct differences exist among various racial groups in terms of the clinical manifestations, pathologic features, and prognosis of hepatic malignant tumors. AIM: To explore the effect of race on clinicopathologic features and prognosis of hepatic malignancies. METHODS: Data from patients with hepatic malignancies diagnosed between 2000 and 2019 were collected from the Surveillance, Epidemiology, and End Results database and statistically analyzed. RESULTS: This study included 123558 patients with hepatic malignant tumors, among whom 21078 (17.06%) were Asian, 14810 (11.99%) were Black, and 87670 (70.95%) were white. The median survival times for patients with hepatic malignant tumors of different races were 12.56, 7.70, and 9.35 months for Asian patients, Black patients, and white patients, respectively. The 3-year survival rates for Asian, Black, and white patients were 29%, 19%, and 21%, respectively, and the 5-year survival rates were 22%, 13%, and 15%, respectively. The Kruskal-Wallis test indicated a significant difference in the survival time of patients with hepatic malignant tumors between different races (P < 0.001). Univariate analysis revealed gender disparities in the prognosis among different ethnic groups (Asian: P > 0.05; Black: P < 0.001; White: P < 0.05). Among Black patients, the prognosis was less affected by the degree of hepatic fibrosis than among Asian patients and white patients (Black patients: P < 0.05; Asian patients: P < 0.001; White patients: P < 0.001). Significant differences were observed in the median survival time among patients with hepatic neuroendocrine tumors and hepatoblastomas during pathologic staging between races. Tumor number was inversely related to the prognosis. Cox regression analyses revealed that T stage, M stage, surgery, chemotherapy, alpha-fetoprotein, and tumor size independently influenced prognosis. Age was a specific independent prognostic factor for white patients. Among the tumor stages, N stage is a self-reliant prognostic element specific to white patients. Conversely, radiotherapy and liver fibrosis were not self-reliant prognostic factors for Black patients. Income alone did not independently influence the prognosis of Asian patients. CONCLUSION: The prognosis of hepatic malignant tumors is better among Asian patients than among Black patients. The prognosis of hepatic malignant tumors among white patients is affected by multiple factors, including age and N stage.

[Evolution Characteristics of PM2.5 and O3 and Their Synergistic Effects on Atmospheric Compound Pollution in Tangshan].

The concentrations of atmospheric pollutants PM2.5, O3, SO2, NO2, and CO together with the meteorological factors of temperature （T）, relative humidity （RH）, wind speed, and other relevant data in Tangshan from 2015 to 2021 were collected to study the variation characteristics of PM2.5 and O3 at different periods in Tangshan City in the past seven years and their influencing factors, to discuss the contributions of air mass transport to PM2.5 and O3 pollution, and to reveal the synergistic influence mechanism of PM2.5 and O3 on atmospheric compound pollution by using correlation analysis and backward trajectory cluster analysis techniques. The results showed that PM2.5 concentrations in Tangshan decreased year by year from 2015 to 2021, whereas O3 concentration showed a unimodal trend, with the peak appearing in 2017. Both PM2.5 and O3 concentrations showed obvious seasonal variation trends； PM2.5 was characterized by the highest concentration in winter and the lowest concentration in summer, whereas O3 was characterized by the highest concentration in summer and the lowest concentration in winter. In addition, the diurnal variation in PM2.5 showed a bimodal distribution, with the peak occurring during the morning and evening on weekdays, and O3 showed a unimodal distribution, with the peak value appearing during the period with strong ultraviolet radiation in the afternoon. PM2.5 had a significant positive correlation with SO2, NO2, and CO, whereas O3 had a significant positive correlation with radiation and temperature. Under the different pollution conditions, PM2.5 and O3 were affected by air mass transports from different directions. Being impacted by various factors, the synergistic effect of PM2.5 and O3 on atmospheric compound pollution showed an obvious negative effect in winter, whereas there was an obvious positive effect in spring, summer, and autumn. Under the backgrounds of different pollutions, when the concentration of PM2.5 exceeded 150 µg·m-3, the synergistic effect of PM2.5 and O3 showed an obvious negative effect.

ANRIL overexpression globally induces expression and alternative splicing of genes involved in inflammation in HUVECs.

Long non­coding (lnc)RNAs serve important cellular functions and certain lncRNAs have roles in different mechanisms of gene regulation. lncRNA­antisense non­coding RNA in the INK4 locus (ANRIL) affects cell inflammation; however, the potential genes underlying the inflammatory response regulated by ANRIL remain unclear. In the present study, the potential function of ANRIL in regulating gene expression and alternative splicing was assessed. ANRIL­regulated human umbilical vein endothelial cell (HUVEC) transcriptome was obtained using high­throughput RNA sequencing (RNA­seq) to evaluate the potential role of ANRIL. Following plasmid transfection, gene expression profile and alternative splicing pattern of HUVECs overexpressing ANRIL were analyzed using RNA­seq. ANRIL overexpression affected the transcription levels of genes associated with the inflammatory response, NF­κB signaling pathway, type I interferon­mediated signal transduction pathway and innate immune response. ANRIL regulated the alternative splicing of hundreds of genes with functions such as gene expression, translation, DNA repair, RNA processing and participation in the NF­κB signaling pathway. Many of these genes serve a key role in the inflammatory response. ANRIL­regulated inflammatory response may be achieved by regulating alternate splicing and transcription. The present study broadened the understanding of ANRIL­mediated gene regulation mechanisms and clarified the role of ANRIL in mediating inflammatory response mechanisms.

Specific antagonist of receptor for advanced glycation end­products attenuates delirium­like behaviours induced by sevoflurane anaesthesia with surgery in aged mice partially by improving damage to the blood­brain barrier.

Postoperative delirium (POD), which occurs in hospital up to 1-week post-procedure or until discharge, is a common complication, especially in older adult patients. However, the pathogenesis of POD remains unclear. Although damage to blood-brain barrier (BBB) integrity is involved in the neuropathogenesis of POD, the specific role of the BBB in POD requires further elucidation. Anaesthesia using 2% isoflurane for 4 h results in the upregulation of hippocampal receptor for advanced glycation end-products (RAGE) expression and ß-amyloid accumulation in aged rats. The present study investigated the role of RAGE in BBB integrity and its mechanisms in POD-like behaviours. The buried food, open field and Y maze tests were used to evaluate neurobehavioural changes in aged mice following 2.5% sevoflurane anaesthesia administration with exploratory laparotomy. Levels of tight junction proteins were assessed by western blotting. Multiphoton in vivo microscopy was used to observe the ultrastructural changes in the BBB in the hippocampal CA1 region. Anaesthesia with surgery decreased the levels of tight junction proteins occludin and claudin 5, increased matrix metalloproteinases (MMPs) 2 and 9, damaged the ultrastructure of the BBB and induced POD-like behaviour. FPS-ZM1, a specific RAGE antagonist, ameliorated POD-like behaviour induced by anaesthesia and surgery in aged mice. Furthermore, FPS-ZM1 also restored decreased levels of occludin and claudin 5 as well as increased levels of MMP2 and MMP9. The present findings suggested that RAGE signalling was involved in BBB damage following anaesthesia with surgery. Thus, RAGE has potential as a novel therapeutic intervention for the prevention of POD.

Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson's Disease.

Parkinson's disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier's disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut-brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut-brain axis inflammation.

Study on the Association of Homocysteine and C-Reactive Protein with Neurofunctional Changes in Patients with Acute Ischemic Stroke After Endovascular Stent Treatment.

Objective: To examine the association of homocysteine (HCY) and C-reactive protein (CRP) with neurofunctional changes in patients with acute ischemic stroke (AIS) after stent treatment. Methods: A total of 110 patients with AIS treated with stents were divided into a high HCY group (n = 59) and a normal HCY group (n = 51) based on the HCY level. Pearson correlation analysis and logistic linear regression analysis were used to analyze the related factors that affect the National Institutes of Health Stroke Scale (NIHSS) score changes after stent treatment. Results: (1) The area under the receiver operating characteristic (ROC) curve for HCY was 0.995 (95% confidence interval [CI]: 0.984-1.005, P = 0.000), and the best predictive value was 12.75 µmol/L (sensitivity 89.9%, specificity 98.0%). The area under the ROC curve for CRP was 0.665 (95% CI: 0.564-0.767, P = 0.003), and the best predictive value was 9.7 mg/L; (2) comparison between the high HCY group and the normal HCY group showed statistical differences (P < 0.05) in HCY, CRP, and the NIHSS score at admission, the NIHSS score after treatment, gender, history of diabetes, and history of atrial fibrillation; (3) both HCY and CRP were proven to be correlated with the NIHSS score after treatment (0.188, P = 0.050) and (0.194, P = 0.042), respectively, using Pearson correlation analysis; (4) HCY, low-density lipoprotein, CRP, cystatin C, glucose, history of atrial fibrillation, history of diabetes, and the NIHSS score at admission as the risk factors. Conclusion: High HCY and CRP levels are related to the neurofunctional changes in patients with AIS treated with stents and can be used as indicators to assess the risk of treating AIS with stents and as serum markers to predict prognoses.

Leptospira infection complicated by demyelinating disease: A case report.

Leptospirosis is a zoonotic disease, found worldwide, that is caused by bacteria of the genus Leptospira. People can be infected with Leptospira if they come in direct contact with the urine of an infected animal. Leptospirosis may be associated with demyelinating lesions of the central nervous system. This case report describes a 66-year-old female patient who presented with fever and generalized aches and progressed to unconsciousness within a few hours of admission. Laboratory tests showed Leptospira infection, and brain magnetic resonance imaging revealed acute demyelinating lesions. The patient responded well to penicillin and intravenous methylprednisolone therapy. Leptospirosis presenting with acute disseminated encephalomyelitis is rare. In this patient, an interdisciplinary collaboration involving the neurologist, radiologist, and pathologist was crucial for diagnosis and management. Further studies are warranted to investigate whether there is a correlation between demyelinating lesions and leptospiral infection.

Neuroprotective Effects of Sodium Butyrate and Monomethyl Fumarate Treatment through GPR109A Modulation and Intestinal Barrier Restoration on PD Mice.

Research has connected Parkinson's disease (PD) with impaired intestinal barrier. The activation of G-protein-coupled receptor 109A (GPR109A) protects the intestinal barrier by inhibiting the NF-κB signaling pathway. Sodium butyrate (NaB), which is a GPR109A ligand, may have anti-PD effects. The current study's objective is to demonstrate that NaB or monomethyl fumarate (MMF, an agonist of the GPR109A) can treat PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) via repairing the intestinal barrier. Male C57BL/6J mice were divided into four groups randomly: control, MPTP + vehicle, MPTP + NaB, and MPTP + MMF. Modeling mice received MPTP (20 mg/kg/day, i.p.) for a week, while control mice received sterile PBS. Then, four groups each received two weeks of sterile PBS (10 mL/kg/day, i.g.), sterile PBS (10 mL/kg/day, i.g.), NaB (600 mg/kg/day, i.g.), or MMF (100 mg/kg/day, i.g.). We assessed the expression of tight junction (TJ) proteins (occludin and claudin-1), GPR109A, and p65 in the colon, performed microscopic examination via HE staining, quantified markers of intestinal permeability and proinflammatory cytokines in serum, and evaluated motor symptoms and pathological changes in the substantia nigra (SN) or striatum. According to our results, MPTP-induced defected motor function, decreased dopamine and 5-hydroxytryptamine levels in the striatum, decreased tyrosine hydroxylase-positive neurons and increased activated microglia in the SN, and systemic inflammation were ameliorated by NaB or MMF treatment. Additionally, the ruined intestinal barrier was also rebuilt and NF-κB was suppressed after the treatment, with higher levels of TJ proteins, GPR109A, and decreased intestinal permeability. These results show that NaB or MMF can remedy motor symptoms and pathological alterations in PD mice by restoring the intestinal barrier with activated GPR109A. We demonstrate the potential for repairing the compromised intestinal barrier and activating GPR109A as promising treatments for PD.

FGF10 Therapeutic Administration Promotes Mobilization of Injury-Activated Alveolar Progenitors in a Mouse Fibrosis Model.

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease with dire consequences and in urgent need of improved therapies. Compelling evidence indicates that damage or dysfunction of AT2s is of central importance in the development of IPF. We recently identified a novel AT2 subpopulation characterized by low SFTPC expression but that is enriched for PD-L1 in mice. These cells represent quiescent, immature AT2 cells during normal homeostasis and expand upon pneumonectomy (PNX) and were consequently named injury-activated alveolar progenitors (IAAPs). FGF10 is shown to play critical roles in lung development, homeostasis, and injury repair demonstrated in genetically engineered mice. In an effort to bridge the gap between the promising properties of endogenous Fgf10 manipulation and therapeutic reality, we here investigated whether the administration of exogenous recombinant FGF10 protein (rFGF10) can provide preventive and/or therapeutic benefit in a mouse model of bleomycin-induced pulmonary fibrosis with a focus on its impact on IAAP dynamics. C57BL/6 mice and SftpcCreERT2/+; tdTomatoflox/+ mice aged 8-10 weeks old were used in this study. To induce the bleomycin (BLM) model, mice were intratracheally (i.t.) instilled with BLM (2 µg/g body weight). BLM injury was induced after a 7-day washout period following tamoxifen induction. A single i.t. injection of rFGF10 (0.05 µg/g body weight) was given on days 0, 7, 14, and 21 after BLM injury. Then, the effects of rFGF10 on BLM-induced fibrosis in lung tissues were assessed by H&E, IHC, Masson's trichrome staining, hydroxyproline and Western blot assays. Immunofluorescence staining and flow cytometry was used to assess the dynamic behavior of AT2 lineage-labeled SftpcPos (IAAPs and mature AT2) during the course of pulmonary fibrosis. We observed that, depending on the timing of administration, rFGF10 exhibited robust preventive or therapeutic efficacy toward BLM-induced fibrosis based on the evaluation of various pathological parameters. Flow cytometric analysis revealed a dynamic expansion of IAAPs for up to 4 weeks following BLM injury while the number of mature AT2s was drastically reduced. Significantly, rFGF10 administration increased both the peak ratio and the duration of IAAPs expansion relative to EpCAMPos cells. Altogether, our results suggest that the administration of rFGF10 exhibits therapeutic potential for IPF most likely by promoting IAAP proliferation and alveolar repair.

Potential roles of gut microbiota and microbial metabolites in Parkinson's disease.

Parkinson's disease (PD) is a complicated neurodegenerative disease attributed to multifactorial changes. However, its pathological mechanism remains undetermined. Accumulating evidence has revealed the emerging functions of gut microbiota and microbial metabolites, which can affect both the enteric nervous system and the central nervous system via the microbiota-gut-brain axis. Accordingly, intestinal dysbiosis might be closely associated with PD. This review explores alterations to gut microbiota, correlations with clinical manifestations of PD, and briefly probes the underlying mechanisms. Next, the highly controversial roles of microbial metabolites including short-chain fatty acids (SCFAs), H2 and H2S are discussed. Finally, the pros and cons of the current treatments for PD, including those targeting microbiota, are assessed. Advancements in research techniques, further studies on levels of specific strains and longitudinal prospective clinical trials are urgently needed for the identification of early diagnostic markers and the development of novel therapeutic approaches for PD.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms.

BACKGROUND: Poorly differentiated gastric neuroendocrine neoplasms (PDGNENs) include gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma, which are highly malignant and rare tumors, and their incidence has increased over the past few decades. However, the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated. AIM: To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs. METHODS: The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively. RESULTS: Among the 232 patients with PDGNENs, 191 (82.3%) were male, with an average age of 62.83 ± 9.11 years. One hundred and thirteen (49.34%) of 229 patients had a stage III disease and 86 (37.55%) had stage IV disease. Three (1.58%) of 190 patients had no clinical symptoms, while 187 (98.42%) patients presented clinical symptoms. The tumors were mainly (89.17%) solitary and located in the upper third of the stomach (cardia and fundus of stomach: 115/215, 53.49%). Most lesions were ulcers (157/232, 67.67%), with an average diameter of 4.66 ± 2.77 cm. In terms of tumor invasion, the majority of tumors invaded the serosa (116/198, 58.58%). The median survival time of the 232 patients was 13.50 mo (7, 31 mo), and the overall 1-year, 3-year, and 5-year survival rates were 49%, 19%, and 5%, respectively. According to univariate analysis, tumor number, tumor diameter, gastric invasion status, American Joint Committee on Cancer (AJCC) stage, and distant metastasis status were prognostic factors for patients with PDGNENs. Multivariate analysis showed that tumor number, tumor diameter, AJCC stage, and distant metastasis status were independent prognostic factors for patients with PDGNENs. CONCLUSION: The overall prognosis of patients with PDGNENs is poor. The outcomes of patients with a tumor diameter > 5 cm, multiple tumors, and stage IV tumors are worse than those of other patients.

The establishment and application of sialoscintigraphic reference values from patients with obstructive sialadenitis.

AIM: To evaluate feasibility of establishing a clinically applicable reference value through those unaffected salivary gland on sialoscintigraphic data obtained from patients presented with obstructive sialadenitis affected a single gland. MATERIALS AND METHODS: Ninety-one patients suffered from single salivary gland swelling, pain/tenderness and received sialoscintigraphic examinations were retrospectively enrolled. The quantitative data parameters, including the uptake ratio, maximal accumulation, maximal excretion, time to maximal (Tmax) and time to minimal (Tmin) activity of the affected and unaffected glands, were calculated for analysis. Data were also obtained and recorded for comparison from 50 patients who fulfill the American-European criteria for the diagnosis of Sjogren's syndrome. RESULTS: The maximal excretion appeared to be the best indicator for distinguishing affected and unaffected glands of obstructive diseases, for parotid and submandibular glands (P = 0.0002 and P < 0.0001, respectively). The area under the receiver-operating characteristic curve (AUC) is 0.82 for submandibular glands. In patients with Sjogren's syndrome, the maximal excretion and Tmin were the best parameters, for parotid (P = 0.002 and P < 0.0001, respectively) and submandibular glands (P < 0.0001 and P = 0.002, respectively). Uptake ratio was a good parameter for submandibular gland (P < 0.0001). The AUC of maximal excretion and uptake ratio for submandibular glands is 0.81 and 0.77, respectively. CONCLUSION: Quantitative data obtained from the unaffected glands of patients with obstructive sialadenitis could be used as reference values for the functional evaluation of salivary gland disorders with maximal excretion as one of the reliable parameters.