Metabolomic profiling between vitiligo patients and healthy subjects in plateau exhibited significant differences with those in plain.

Vitiligo is the most common disorder of depigmentation, which is caused by multiple factors like metabolic abnormality, oxidative stress and the disorders of immune. In recent years, several studies have used untargeted metabolomics to analyze differential metabolites in patients with vitiligo, however, the subjects in these studies were all in plain area. In our study, multivariate analysis indicated a distinct separation between the healthy subjects from plateau and plain areas in electrospray positive and negative ions modes, respectively. Similarly, a distinct separation between vitiligo patients and healthy controls from plateau and plain areas was detected in the two ions modes. Among the identified metabolites, the serum levels of sphingosine 1-phosphate (S1P) were markedly higher in vitiligo patients compare to healthy subjects in plain and markedly higher in healthy subjects in plateau compare to those in plain. There are significant differences in serum metabolome between vitiligo patients and healthy subjects in both plateau and plain areas, as well as in healthy subjects from plateau and plain areas. S1P metabolism alteration may be involved in the pathogenesis of vitiligo.

Herb-induced hepatitis secondary to artemisinin: A case report.

This report describes a rare case of severe liver injury secondary to a herbal supplement containing artemisinin. The patient received plasma exchange with bilirubin filtration adsorption therapy. The case is unique in its severe cholestasis. Bilirubin decreased to baseline after 62 days. This will help to improve clinicians' awareness of the diagnosis and treatment of drug-induced liver injury.

Case Report: Prompt Response to Savolitinib in a Case of Advanced Gastric Cancer With Bone Marrow Invasion and MET Abnormalities.

Gastric cancer is one of the most common malignant tumors and patients show a short survival, those combined with bone marrow invasion have a median survival of only 37 days. Here we reported the treatment of a 47-year-old male with advanced gastric cancer and complicated with bone marrow invasion and extensive metastases, who did not tolerate chemotherapy, under monotherapy with savolitinib, a MET receptor tyrosine kinase inhibitor. Before treatment, the patient was in severe pain and presented with thrombocytopenia and hemorrhagic anemia. Savolitinib was given based on amplification and rearrangement of the MET gene in his tumor. After savolitinib treatment, the patient's condition promptly improved, efficacy evaluation indicated partial remission, and the patient was alive and remained progression-free at 15 weeks at the time of reporting. No obvious adverse reactions occurred. Besides, another case of a female gastric cancer patient with MET amplification who received savolitinib monotherapy as a third-line treatment that remained progression-free at 12 weeks was also reported. This report provides a new reference for understanding MET abnormalities in gastric cancer and offers a possibility for future application of MET tyrosine kinase inhibitors in the therapy of gastric cancer with MET abnormalities. Also, it suggests that sequencing of MET can be considered a routine target in advanced gastric cancer patients.

Caveolin­1 modulates hypertensive vascular remodeling via regulation of the Notch pathway.

Hypertension is one of the critical risk factors of cerebrovascular disease. Caveolin­1 (Cav­1) has been suggested to be involved in the development of hypertension; however, the underlying mechanism remains largely unknown. Therefore, the present study aimed to investigate the mechanism underlying Cav­1 in hypertension. In the present study, the hypertension model was induced by infusion of angiotensin II (Ang­II) in rats. Cell Counting Kit­8 assay was used to detect the viability of human umbilical vein endothelial cells (HUVECs). Flow cytometry was used to determine the apoptosis of HUVECs. Transmission electron microscopy was utilized to address the thickness of the vessel walls. Reverse transcription­quantitative PCR, western blotting and immunofluorescence staining were used to assess the mechanism of cav­1/Notch1 involved in hypertensive vascular remodeling. In the present study, an Ang­II­induced hypertension model was successfully established in rats. With this model, it was found that the expression levels of cav­1 and Notch1 were significantly increased in brain tissues in the hypertension group compared with the sham­operated group. In cultured HUVECs, knockdown of cav­1 regulated Ang­II­induced HUVEC viability and apoptosis, and modulated hypertensive vascular remodeling, which was mediated by the Notch pathway. The data of the present study demonstrated that the cav­1/Notch signaling plays an important role in the regulation of Ang­II­induced hypertension and vascular remodeling.

Clinical Features and Co-Infections in Invasive Pulmonary Aspergillosis in Elderly Patients.

INTRODUCTION: Invasive pulmonary aspergillosis (IPA) is a potentially lethal opportunistic infection. Old age is one of the important risk factors of IPA. However, data regarding the clinical characteristics and prognostic factors of elderly patients with IPA are limited, with data regarding co-infection of other bacteria or fungi even scarcer. METHODS: We performed a retrospective study of elderly patients (aged≥60) with IPA diagnosed in the First Affiliated Hospital of Sun Yat-sen University from January 2000 to December 2019. Data collection included demographic characteristics, premorbid conditions, underlying diseases, clinical manifestations, therapeutic procedures, and pathogenic detection. Associated factors were analyzed by logistic regression analysis. RESULTS: A total of 97 elderly patients (75 males, 22 females) with IPA were included. The all-cause mortality rate was 36.1% (35/97). Body mass index (BMI) (adjusted odds ratio (OR) 1.27, 95% confidence interval (CI) 1.08-1.50, P=0.01), solid organ malignancy (adjusted OR 5.37, 95% CI 1.35-21.33, P=0.02), and co-infections (adjusted OR 5.73, 95% CI 1.40-23.51, P=0.02) were associated with mortality in the elderly patients with IPA. Nearly, 76.3% (74/97) of the patients developed co-infections. Most of the infections (55/74, 74.3%) involved the lung. A total of 77 strains of bacteria were isolated, and Gram-negative bacteria (63/77, 81.3%) were predominant. Patients with co-infections are older (72.3±7.6 vs 67.4±7.4, P=0.04), prone to admit to the intensive care unit (ICU) (59.5% vs 26.1%, P=0.01), and present lymphopenia (60.8% vs 26.1%, P=0.004). In multivariate analysis, ICU admission (adjusted OR 4.57, 95% CI 1.53-13.67, P=0.01), and lymphopenia (adjusted OR 4.82, 95% CI 1.62-14.38, P=0.01) were significantly associated with co-infection in the elderly patients with IPA. CONCLUSION: IPA is a fatal disease in the elderly population. Co-infection is closely associated with mortality. Lymphopenia could be an indicator for co-infection in the elderly patients with IPA.

CD40 Accelerates the Antigen-Specific Stem-Like Memory CD8+ T Cells Formation and Human Papilloma Virus (HPV)-Positive Tumor Eradication.

Antigen-specific stem-like memory CD8+ T cells (Tscm) have a series of stem cell characteristics, including long-term survival, self-renewal, anti-apoptosis and persistent differentiation into cytotoxic T cells. The effective induction of tumor-specific CD8+ Tscm could persistently eradicate tumor in pro-tumor hostile microenvironment. This study was to investigate the role of CD40 in HPV16-specific CD8+ Tscm induction and its anti-tumor function. We found that CD40 activation accelerated vaccine-induced HPV16 E7-specific CD8+ Tscm formation. Comparing to other HPV-specific CD8+ T cells, CD8+ Tscm were found to be stronger and long-term anti-tumor function, in vivo and in vitro, even in the adoptive cellular transferring model. Furthermore, high frequencies of Tscm might prevent the HPV infection to move on to the development of cancer. And the CD40 effect on Tscm involved Wnt/ß-catenin activation. Our study suggest that CD40 activation supports the generation of tumor-specific CD8+ Tscm, thus providing new insight into cancer immunotherapy.

Epidemiology and Mortality-Associated Factors of Invasive Fungal Disease in Elderly Patients: A 20-Year Retrospective Study from Southern China.

INTRODUCTION: Invasive fungal disease (IFD) is a life-threatening infection. The epidemiology and clinical features of IFD in the elderly population are less discussed. The aim of this study was to explore the epidemiology and mortality-associated factors for IFD in the elderly inpatients. METHODS: A retrospective study enrolling 512 elderly inpatients from The First Affiliated Hospital of Sun Yat-sen University during the last two decades was performed. RESULTS: The annual prevalence of IFD was 0.1-0.5%. Candidiasis was the most common (236/521, 45.3%). An increasing trend was observed in aspergillosis from 11.1% in year 1998 to 28.8% in year 2018. The common infective sites of candidiasis were abdominal cavity (83/236, 35.2%) and bloodstream (55/236, 23.3%). Invasive aspergillosis mainly developed in the sinus (74/149, 49.7%) and lung (65/149, 43.6%). Patients with diabetes mellitus (DM) (59/126, 46.8%), solid organ malignancy (84/114, 73.7%), chronic kidney disease (CKD) (40/62, 64.5%) or receiving operation (109/147, 74.1%) were prone to develop candidiasis, while aspergillosis was usually complicated in patients with chronic obstructive pulmonary disease (COPD) (25/51, 49.0%). The all-cause mortality rate was 25.9% (135/521), and patients aged ≥80 years were the riskiest (20/51, 39.2%). Lymphopenia (59.5% vs 17.3%, P<0.001) was significant in deceased patients with mold infection. Higher proportion of non-survivors with invasive candidiasis received central venous catheterization (CVC) (68.4% vs 40.6%, P<0.001) or indwelling urinary catheter (68.4% vs 46.3%, P=0.001). CONCLUSION: IFD is a life-threatening complication especially in the oldest-old. Surveillance on lymphopenia, prompt treatment and reduce invasive procedures could benefit the prognosis.

Opportunistic invasive fungal disease in patients with type 2 diabetes mellitus from Southern China: Clinical features and associated factors.

AIMS/INTRODUCTION: A retrospective study was carried out to investigate the clinical characteristics and associated factors for invasive fungal disease in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Demographic and clinical data were recorded. Associated factors were analyzed by logistic regression analysis. RESULTS: Invasive fungal disease was diagnosed in 120 patients with type 2 diabetes mellitus (prevalence, 0.4%). Yeast infection (56/120, 46.7%), including candidiasis (31/56, 55.4%) and cryptococcosis (25/56, 44.6%), was the most common. The urinary tract was mainly involved in candidiasis (12/31, 38.7%). More than half of the cryptococcosis (16/25, 64.0%) presented as pneumonia. Mold infection accounted for 40.8% of the cases, and predominantly involved the lung (34/49, 69.4%). A total of 15 (12.5%) patients had mixed fungal infection. Candida albicans (24/111, 21.6%), Cryptococcus neoformans (19/111, 17.1%) and Aspergillus fumigatus (14/111, 12.6%) were the leading agents. Co-infection occurred in 58 (48.3%) patients, mainly presenting as pneumonia caused by Gram-negative bacteria. The inpatient mortality rate of invasive fungal disease was 23.3% (28/120). Glycated hemoglobin levels were higher in non-survivors than survivors (8.8 ± 2.5 vs 7.7 ± 2.1%, P = 0.02). Anemia (adjusted odds ratio, 3.50, 95% confidence interval 1.95-6.27, P < 0.001), hypoalbuminemia (adjusted odds ratio, 5.42, 95% confidence interval 3.14-9.36, P < 0.001) and elevated serum creatinine (adjusted odds ratio, 2.08, 95% confidence interval 1.07-4.04, P = 0.03) were associated with invasive fungal disease in type 2 diabetes mellitus patients. CONCLUSIONS: Invasive fungal disease is a life-threatening complication in type 2 diabetes mellitus patients. C. a albicans, C. neoformans, and A. fumigatus are the leading agents. Prolonged hyperglycemia results in unfavorable outcomes. Correction of anemia and hypoalbuminemia might improve prognosis.

Anemia secondary to the use of sodium valproate for preventing postoperative seizures in a 79-year-old man: A case report.

RATIONALE: Sodium valproate is a widely used antiepileptic drug and also used to prevent postoperative seizures in neurosurgery. Anemia caused by sodium valproate is occasionally reported and most are from pediatric patients. PATIENT CONCERNS: We present the case of a 79-year-old man who developed anemia in the setting of a short-term sodium valproate therapy for the prevention of postoperative seizures. DIAGNOSIS: By testing complete blood count we found anemia and hepatic enzyme elevations arising after 3-week standard dose sodium valproate therapy for preventing postoperative seizures. Our investigations ruled out most of the known causes of anemia including infection, uncontrolled bleeding, underlying systemic disease, malnutrition, immune hemolytic anemia, and neoplasia. On the drug's discontinuation as diagnostic therapy the patient's hemoglobin began to rise spontaneously and liver function returned to normal. Thus anemia secondary to sodium valproate was considered as the most likely diagnosis. INTERVENTIONS: Sodium valproate was suspended and the patient was transfused with concentrated red blood cells. OUTCOMES: The hemoglobin recovered obviously on the drug's discontinuation. LESSONS: Hematologic toxicity of sodium valproate can occur quickly. Regular complete blood count test helps to make prompt diagnosis and drug discontinuation leads to the recovery.

Primary central nervous system lymphoma in a patient with systemic lupus erythematosus mimicking high-grade glioma: A case report and review of literature.

RATIONALE: Primary central nervous system lymphoma (PCNSL) is a rare disease. Studies of PCNSL in patients with rheumatic diseases are lacking. Neither clinical symptoms nor radiographic manifestation is specific to PCNSL. Therefore, it could be misdiagnosed with other diseases such as brain tumors. Chemotherapy is the primary treatment for PCNSL, while the role of surgery remains controversial. PATIENT CONCERNS: We reported a 39-year-old woman with systemic lupus erythematosus (SLE) developed PCNSL after 15-year treatment with multiple immunosuppressants. DIAGNOSES: Cranial magnetic resonance imaging (MRI) showed multi-focal lesions with ring-like enhancement post-contrast in the right hemisphere, which mimicked glioma radiographically. Owing to the severe symptoms of intracranial hypertension, gross tumor resection was performed. Pathological exam showed perivascular infiltration of atypical lymphoid cells with CD20 and Epstein-Barr virus (EBV) -encoded RNA (EREB) positive. The patient was diagnosed with diffuse large B-cell lymphoma (DLBCL). INTERVENTIONS: The patient received six cycles of chemotherapy and autologous stem cell transplantation (ASCT) subsequently. OUTCOMES: The patient remained complete remission until this article was written. LESSONS: PCNSL in immunocompromised hosts may present heterogeneous contrast enhancement, which should be differentiated from other diseases especially high-grade glioma.

Overlapping Autoimmune Syndromes in Patients With Glial Fibrillary Acidic Protein Antibodies.

BACKGROUND: Glial fibrillary acidic protein (GFAP) astrocytopathy, an autoimmune central nervous system disorder with a specific GFAP-IgG, often coexists with other antibodies. OBJECTIVE: The aim of this article was to study overlapping syndromes in autoimmune GFAP astrocytopathy. METHODS: Antibody was detected by indirect immunofluorescence assay. Patient data were analyzed retrospectively. RESULTS: Thirty patients with positive GFAP-IgG were included, of whom 10 were defined as overlapping syndrome. Four patients with positive aquaporin-4 (AQP4)-IgG, two with N-methyl-d-aspartate receptor-IgG, three with unknown neuronal antibodies, and one with double AQP4 and myelin oligodendrocyte glycoprotein-IgG were identified. GFAP-IgG and other specific antibodies occurred simultaneously at the initial attack in eight patients. The main symptoms included fever, headache, ataxia, psychosis, hypersomnia, dyskinesia, dementia, seizure, myelitis, and optical symptoms. Brain magnetic resonance imaging in four patients revealed characteristic radial enhancing patterns in the white matter. Cortical abnormalities were found in four patients. Other brain abnormalities occurred in the hypothalamus, midbrain, pons, medulla, cerebellum, and meninges. Six patients exhibited lesions in the spinal cord. In a subgroup study, patients with overlapping syndrome were younger at onset than those with non-overlapping syndrome. CONCLUSION: Overlapping antibodies are common in GFAP astrocytopathy.

Downregulation of miR-139-5p contributes to the antiapoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1.

Liraglutide is administered as glucagon-like peptide-1 (GLP-1) receptor agonist for diabetic patients and can protect pancreatic ß-cells by inhibiting their apoptosis. MicroRNA-139-5p (miRNA-139-5p) participates in the regulation of cancer cell apoptosis. However, it is not clear whether miR-139-5p contributes to the anti-apoptotic effect of liraglutide in ß-cells. The objective of the present study was to investigate the role of miR-139-5p on apoptosis of pancreatic ß-cells. MicroRNA levels in pancreatic tissue from diabetic rats and INS-1 cells treated with liraglutide were measured by real-time quantitative RT-PCR. The role of miR-139-5p on apoptosis was studied by transfecting INS-1 cells with miR-139-5p mimics. The mRNA and protein expression of the target gene, insulin receptor substrate-1 (IRS1), were measured by qRT-PCR and Western blot, respectively. Apoptosis in rat pancreatic tissue and INS-1 cells was detected by TUNEL and annexin V/propidium iodide costaining. Apoptosis of pancreatic tissue from diabetic rats and INS-1 cells was decreased by administration of liraglutide. The expression of miR-139-5p increased in the pancreas of diabetic rats and decreased with liraglutide treatment. Incubation with liraglutide (100 nM) for 48 h attenuated the expression of miR-139-5p and increased the mRNA and protein levels of IRS1. Direct regulatory effects of miR-139-5p on IRS1 were found by a dual-luciferase reporter assay. Transfection of INS-1 cells with miR-139-5p mimics led to decreases in the mRNA and protein expression of IRS1. In conclusion, our observations suggest that decreased miR-139-5p expression contributes to the anti-apoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1.

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5,6,7,8-tetrahydrobiopterin degradation and endothelial nitric oxide synthase uncoupling.