Objective:To understand the clinical characteristics of Pneumocystis carinii pneumonia (PCP) in immunocompromised patients. Methods:Clinical data of 15 patients with PCP hospitalized in Shanghai East Hospital, Tongji University from March 2018 to March 2019 were retrospectively analyzed. Clinical manifestations, laboratory index examinations, imaging characteristics, comorbidities, treatment and outcome were observed.Results:Among the 15 cases, 11 were cases with hematological malignancies and four cases received allogenetic hematopoietic stem cell transplantation (AHSCT). The onset time was (5.82±2.33) months after transplantation. Chest computed tomography (CT) of all 15 patients showed diffuse ground glass-like exudation of the lungs surrounding hilar. Peripheral blood CD4 + T cell count decreased to (135.17±74.83)/μL and oxygenation index to (188.47±41.03) mmHg(1 mmHg=0.133 kPa), while lactic acid dehydrogenase (LDH) elevated to (576.18±228.01) U/L.Levels of 1, 3-β-D-glucan in serum and bronchoalveolar lavage fluid (BALF) increased to (1 862.81±157.73) ng/L and (1 216.97±957.16) ng/L, respectively. Metagenomic next-generation sequencing (mNGS) of BALF showed that the numbers of sequence of Pneumocystis carinii were 120 to 14 383. There were nine patients co-infected with cytomegalovirus (CMV), four patients with Epstein-Barr virus, and two patients with gram-negative bacilli. All the patients received compound sulfamethoxazole and caspofungin treatment, and 13 cases improved and two died. Conclusions:Patients with hematological malignancies and AHSCT are at high-risk of PCP. Serum counts of CD4 + T cells decrease, while serum levels of LDH and 1, 3-β- D-glucan increase.mNGS is valuable for early diagnosis.

Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor eff ects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory eff ect of S109 on CRM1 is reversible. Our data demonstrated that S109 signifi cantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the eff ects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.
Active Transport, Cell Nucleus ; Cell Cycle Checkpoints* ; Cell Cycle* ; Cell Proliferation* ; Cyclin D1 ; Kidney Neoplasms* ; Tumor Suppressor Proteins

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cell Culture Techniques ; methods ; Child ; Female ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Male ; Middle Aged