BACKGROUND: To investigate the clinical characteristics and risk factors of human immunodefi ciency virus (HIV)-negative patients with Talaromyces marneff ei (T. marneff ei) infection. METHODS:We retrospectively collected the clinical information of HIV-negative patients with T. marneff ei infection from January 1, 2010 to June 30, 2019, and analyzed the related risk factors of poor prognosis.RESULTS: Twenty-fi ve cases aging 22 to 79 years were included. Manifestations of T. marneff ei infection included fever, cough, dyspnea, chest pain or distress, lymphadenopathy, ear, nose, and throat (ENT) and/or skin lesions, bone or joint pain, edema and pain in the lower extremities, digestive symptoms, icterus, malaise, and hoarseness. Two cases had no comorbidity, while 23 cases suff ered from autoimmune disease, pulmonary disease, cancer, and other chronic diseases. Sixteen cases had a medication history of glucocorticoids, chemotherapy or immunosuppressors. Pulmonary lesions included interstitial infiltration, nodules, atelectasis, cavitary lesions, pleural effusion or hydropneumothorax, bronchiectasis, pulmonary fibrosis, pulmonary edema, and consolidation. The incidence of osteolytic lesions was 20%. Eight patients received antifungal monotherapy, and 11 patients received combined antifungal agents. Fifteen patients survived and ten patients were dead. The Cox regression analysis showed that reduced eosinophil counts, higher levels of blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), myoglobin (Mb), procalcitonin (PCT), and galactomannan were related to poor prognosis (hazard ratio [HR]>1, P<0.05).CONCLUSIONS: Bone destruction is common in HIV-negative patients with T. marneffei infection. Defective cell-mediated immunity, active infection, multiple system, and organ damage can be the risk factors of poor prognosis.

Background Adverse left ventricular remodeling after myocardial infarction (MI) compromises cardiac function and increases heart failure risk. Till now, comprehension of the role transcription factor EB (TFEB) plays after MI is limited.ObjectivesThe purpose of this study was to describe the effects of TFEB on cell death and fibroblast differentiation after MI.MethodsAAV9 mediated up- and down-regulated TFEB expressions were generated in C57BL/6 mice two weeks before the MI modeling. Echocardiography, Masson, HE, Sirius red staining immunofluorescence, and wheat germ agglutinin staining were performed at 3 days, and 1, 2, and 4 weeks after MI modeling. Fibroblasts and myocytes collected from SD neonatal rats were transfected by adenovirus and siRNA, and cell counting kit-8 (CCK8), Cell Proliferation EdU Image (EDU), immunofluorescence, and Transwell assay were conducted. Myocardial fibrosis-related proteins and autophagy-related protein were identified by Western blot.ResultsThe up-regulation of TFEB resulted in reduced myocardial cell death, delayed fibroblasts proliferation and its differentiation into myofibroblasts, and up-regulated expression of LC3B three days after MI. Similar results were observed in vitro studies. Meanwhile, a significant up-regulation of EF, decrease in the ratio of the infarction length, and decreased protein level of collagen III were observed four weeks after MI modeling. The over-expression of TFEB slowed down myofibroblast migration and resulted in a significant down-regulation of collagen I level in myofibroblasts.ConclusionsTFEB demonstrated potential in improving cell death after MI by mediating autophagy and regulating fibroblast proliferation and transformation. Its molecular impacting mechanism deems further investigation.