Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Prospective Cohort Study

Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.

/pdf/microenvironmental-regulation-of-tumor-progression-and-4528oymlw6.pdf

Microenvironmental regulation of tumor progression and metastasis.

Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune-mediated tissue damage. The PD-1:PD-L pathway also has been usurped by microorganisms and tumors to attenuate antimicrobial or tumor immunity and facilitate chronic infection and tumor survival. The identification of B7-1 as an additional binding partner for PD-L1, together with the discovery of an inhibitory bidirectional interaction between PD-L1 and B7-1, reveals new ways the B7:CD28 family regulates T cell activation and tolerance. In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential.

PD-1 and its ligands in tolerance and immunity

Severely immunosuppressed AIDS patients with recurrent opportunistic infections (OIs) represent an unmet medical need even in the era of antiretroviral therapy (ART). Here we report the development of a human leukocyte antigen (HLA)-mismatched allogeneic adaptive immune therapy (AAIT) for severely immunosuppressed AIDS patients. Twelve severely immunosuppressed AIDS patients with severe OIs were enrolled in this single-arm study. Qualified donors received subcutaneous recombinant granulocyte-colony-stimulating factor twice daily for 4-5 days to stimulate hematopoiesis. Peripheral blood mononuclear cells were collected from these donors via leukapheresis and transfused into the coupled patients. Clinical, immunological, and virological parameters were monitored during a 12-month follow-up period. We found AAIT combined with ART was safe and well-tolerated at the examined doses and transfusion regimen in all 12 patients. Improvements in clinical symptoms were evident throughout the study period. All patients exhibited a steady increase of peripheral CD4+ T cells from a median 10.5 to 207.5 cells/μl. Rapid increase in peripheral CD8+ T-cell count from a median 416.5 to 1206.5 cells/μl was found in the first 90 days since initiation of AAIT. In addition, their inflammatory cytokine levels and HIV RNA viral load decreased. A short-term microchimerism with donor cells was found. There were no adverse events associated with graft-versus-host disease throughout the study period. Overall, AAIT treatment was safe, and might help severely immunosuppressed AIDS patients to achieve a better immune restoration. A further clinical trial with control is necessary to confirm the efficacy of AAIT medication.

/pdf/hla-mismatched-allogeneic-adoptive-immune-therapy-in-4lt1y5pdua.pdf

HLA-mismatched allogeneic adoptive immune therapy in severely immunosuppressed AIDS patients

Objective
To summarize clinical experience on the clinical feature, etiology and treatment of patients with spontaneous bloody tears as the initial symptom.


Methods
Retrospective series of case studies. The clinical data and follow-up data of 27 cases of bloody tears as the first symptom in Lacrimal Center of Ophthalmology, the Third Medical Center of Chinese PLA General Hospital from June 2015 to December 2018 were reviewed. The clinical feature, specific cause, diagnosis, treatment and prognosis of these cases were evaluated.


Results
A total of 27 cases were collected in this study. The patients were 10 males (37.0%) and 17 females (63.0%), including 21 adults (≥ 18 years old, 77.8%) and 6 minors (<18 years old, 22.2%). There were 22 monocular cases (81.5%) and 5 binocular cases (18.5%). Five cases (18.5%) were bleeding from the eye and other parts of the body, and 22 cases (81.5%) were bleeding only from the eye. There were 19 cases (70.4%) with hematic epiphora and secretions from the punctum, 3 cases (11.1%) with blood-stained tears, and 7 cases (25.9%) with blood-like tears. With regard to etiology, 6 cases (22.2%) were combined with systemic lesions, one of which was granulomatosis with polyangiitis and five of which (<18 years old) were idiopathic bloody tears. Twenty-one cases (77.8%) were local lesions, including 18 cases only involving the lacrimal system, 2 cases only involving the ocular surface, and 1 case involving both the lacrimal system and the ocular surface. Among the 21 cases with local lesions, 5 cases were induced by foreign body, 6 cases were induced by simple inflammation, and 10 cases were induced by tumor including 1 case with conjunctival benign tumor and 9 cases with tumor of the lacrimal system (5 with malignant tumor and 4 with benign tumor). Patients with idiopathic bloody tears received psychological and medical treatment, and interictal discharge was lengthened. One case of granulomatosis with polyangiitis was treated by trans-nasal endoscopic dacryocystorhinostomy. With the recurrence of granulomatosis and polyangiitis, bloody tears recurred after surgery. One patient with conjunctival hemangioma was untreated. Lesions in the lacrimal duct system were removed and dacryocystorhinostomy was performed. In this study, 2 patients (1 with small cell neuroendocrine carcinoma and 1 with adenoid cystic adenocarcinoma) died and the other had a good prognosis.


Conclusions
Among the cases of bloody tears, adults and local lesions are more common. Most of the lesions are located in the lacrimal system and are tumors. The main treatment is to remove the lesions, and if necessary, to expand the resection and reconstruct the lacrimal duct. Idiopathic bloody tears occur in minors, who are gave psychotherapy and necessary medical treatment. (Chin J Ophthalmol, 2020, 56: 53-58)


Key words: 
Eye hemorrhage; Tears; Lacrimal apparatus diseases

[Retrospective investigation of spontaneous bloody tears: a report of 27 cases].

OBJECTIVE To examine the expressions of B7-H1 and its receptor programmed death-1 (PD-1) on circulating T cells and myeloid dendritic cells (mDCs) in patients with chronic hepatitis B virus (HBV) infection and to investigate the correlation between their expressions and their disease status. METHODS The expressions of B7-H1 and PD-1 on mDCs and T lymphocytes in 30 patients with chronic HBV infection and 28 healthy controls were analyzed by a fluorescence-activated cell sorter (FACS). Real time-polymerase chain reaction (RT-PCR) was used to measure the serum HBV DNA load. RESULTS Both B7-H1 and PD-1 were significantly upregulated on T cells and mDCs in those patients. Their expressions were positively correlated with the patients serum ALT levels and HBV DNA loads. CONCLUSION B7-H1 and PD-1 expressions in our patients with chronic hepatitis B are closely associated with their disease status.

[Expressions and significance of B7-H1 and programmed death-1 in lymphocytes from patients with chronic hepatitis B virus infection].

OBJECTIVE To investigate the features of circulating plasmacytoid dendritic cells (pDCs) in patients with chronic hepatitis B for a better understanding of the immunopathogenesis of HBV infection. METHODS Fresh blood samples were collected from 20 patients with chronic hepatitis B (CHB) and from 15 healthy individuals who served as controls. pDCs were isolated from peripheral blood mononuclear cells (PBMCs) using immunomagnetic assay and detected by flow cytometry. Fresh PBMCs and isolated pDCs were stimulated in vitro using CpG ODN2216. The supernatants were measured for IFNa production using ELISA. RESULTS The peripheral pDCs frequency in CHB patients (0.192%+/-0.110%) was markedly lower than that in the healthy controls (0.287%+/-0.142%). After being pulsed with CpG ODN2216, the isolated pDCs produced lower levels of IFNa and expressed lower levels of CD80 and CD40 in the CHB patients when compared to those of the healthy controls. The level of IFNa was (972.6+/-705.5) pg/ml in the patients and (3 142.9+/-1 292.2) pg/ml in the controls. Moreover, the pDCs frequency was reversely correlated with serum ALT levels in these HBV infected patients. CONCLUSION The reduced number and impaired function of circulating pDCs in patients with CHB may be related to their disease progression.

[Identification of circulating plasmacytoid dendritic cells in chronic HBV-infected patients].

Evaluation on the efficacy of human umbilical cord derived-mesenchymal stem cell transplantation in liver cirrhosis patients with ascites in a prospective and control trial

Fu-Sheng Wang

Papers

HLA-mismatched allogeneic adoptive immune therapy in severely immunosuppressed AIDS patients

[Retrospective investigation of spontaneous bloody tears: a report of 27 cases].

[Expressions and significance of B7-H1 and programmed death-1 in lymphocytes from patients with chronic hepatitis B virus infection].

[Identification of circulating plasmacytoid dendritic cells in chronic HBV-infected patients].

Evaluation on the efficacy of human umbilical cord derived-mesenchymal stem cell transplantation in liver cirrhosis patients with ascites in a prospective and control trial