As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

Child ; Electrocardiography ; Humans ; Male ; Ventricular Fibrillation ; physiopathology

OBJECTIVETo investigate the influential factors of total blood loss during unilateral artificial total hip arthroplasty (THA).

METHODSFrom January 2014 to July 2016, 131 patients undergwent primary unilateral total hip arthroplasty, including 55 males and 76 females, ranging in age from 40 to 89 years old, with an average of 64.5 years old. The data of patients with unilateral total hip arthroplasty were collected, and the data of hemodynamics, coagulation function, hemoglobin and hematocrit values were recorded according to the observation data. The blood loss of the patients was calculated by Gross equation, and the data were analyzed by a statistical software.

RESULTSThe total blood loss of the patients was significantly affected by the factors of pathogenesis and deep venous thrombosis of the lower limbs. The results were statistically significant(<0.05). The gender, age, body mass index, prosthesis and anesthesia had little effects on the blood loss volume after replacement.

CONCLUSIONSThe data in this study indicate that the volume of actual blood loss can be controlled by adjusting non-surgical factors such as gender, age, body mass index, prosthetic material, and risk factors, and surgical factors(postoperative complications, anesthesia).

OBJECTIVETo investigate the changes in the expression level of sRNA SpR19 and its potential target protein GroEL in clinical isolates of Streptococcus mutans with different cariogenicity exposed to different pH conditions and explore the possibility of using these molecules as biomarkers for assessing the cariogenicity of the bacteria.

METHODSThe total RNAs were extracted from the clinical isolates of Streptococcus mutans with high (strain 17) and low cariogenicity (strain 5) for high-throughput sequencing for profiling of the differentially expressed sRNAs. The candidate sRNA, SpR19, was selected for further study on the basis of bioinformatics analysis considering the role of its potential target in the cariogenic process. The differential expression levels of SpR19 in the strains exposed to both pH5.5 and pH7 culture conditions were verified by quantitative real-time PCR. The expression of the potential target of SpR19, GroEL, was also investigated at both the protein and mRNA level using Western blotting and quantitative real-time PCR.

RESULTSBioinformatic analysis suggested multiple potential target sites of SpR19 both in GroEL mRNA and in the upstream and downstream inter-genic regions. Under different pH conditions, the highly cariogenic strain 17 expressed consistently low levels of SpR19 as compared with the strain 5 with a low cariogenicity; GroEL showed a reverse expression pattern in the 2 strains. An inverse correlation was found between the expressions of SpR19 and GroEL.

CONCLUSIONThe highly cariogenic strain 17 expressed low levels of SpR19 and high levels of GroEL in both acidic and neutral culture conditions. SpR19 may negatively regulate the cariogenicity of Streptococcus mutants by targeting at GroEL.

OBJECTIVESTo explore the category, quantity and clinical significance of autoantibodies on bone marrow hematopoietic cells in patients with immunorelated cytopenia and evaluate the sensitivity of direct antiglobulin reaction (Coombs test ) of bone marrow mononuclear cells (BMMNC).

METHODSThe category and the positive rate of autoantibodies on bone marrow hematopoietic stem cells, nucleated erythrocytes, granulocytes in 32 patients with uncertain immunorelated cytopenia were investigated by using BMMNC-Coombs test and double immunofluorescence flow cytometry.

RESULTSThe positive rate of autoantibodies on bone marrow hematopoietic cells tested by flow cytometry was 90.63% which was higher than that by BMMNC-Coombs test (50.0%) (p < 0.05). In 29 positive cases, IgG autoantibody accounted for 6.90%, IgM13.8%, IgG+IgA 3.4%, IgG+IgM 31.0%, and IgG+IgM+IgA 44.8%. Of the 29 Patients, 25 (86.2%) with IgG autoantibody, 26 (89.7%) with IgM and 14 (48.3%) with IgA. The patients with IgG autoantibody alone had the lowest hemoglobin levels, and those with IgM autoantibody might have intravascular hemolytic findings. The response time of patients with IgG and IgG+IgM was shorter than that of the other patients. 91.3% of the patients had autoantibodies on bone marrow hematopoietic stem cells and showed pancytopenia, and 50% of the patients had autoantibodies on nucleated erythrocytes and granulocytes. Eleven of 13 patients with negative BMMNC-Coombs tests had autoantibodies on bone marrow hematopoietic stem cells detected by FACS. There was no significant difference of the quantities of the three categories of autoantibodies of nucleated erythrocytes and stem cells. The quantities of IgA on granulocytes were lower than that of IgG and IgM. There was no significant difference between IgG and IgM on granulocytes. The quantity of IgA on hematopoietic stem cells was significantly higher than that on nucleated erythrocytes or granulocytes.

CONCLUSIONSThe sensitivity of double immunofluorescence flow cytometry assay was higher than that of BMMNC-Coombs test for detecting autoantibodies. In immunorelated cytopenia patients, the predominant autoantibody was IgM which could cause intravascular hemolysis, and the second one was IgG which could cause severe anemia. Most immunorelated cytopenia patients had autoantibodies on hematopoietic stem cells and showed pancytopenia. IgA was more easily seen on the hematopoietic stem cells.

Adolescent ; Adult ; Aged ; Autoantibodies ; classification ; metabolism ; Autoimmune Diseases ; immunology ; Bone Marrow Cells ; immunology ; Child ; Coombs Test ; Female ; Flow Cytometry ; Humans ; Immunoglobulin A ; metabolism ; Immunoglobulin G ; metabolism ; Immunoglobulin M ; metabolism ; Male ; Middle Aged ; Pancytopenia ; immunology

OBJECTIVETo investigate the effects of dexmedetomidine on inflammatory reaction, oxidative stress, and renal pathologies in a rat model of lipopolysaccharide (LPS)-induced sepsis.

METHODSThirty-two SD rats were randomly divided into 4 groups, including a sham-operated group, LPS group with LPS (5 mg/kg) injection via the caudal vein 30 min before the operation, dexmedetomidine (Dex) +LPS group with additional Dex (10 µg/kg) injection via the caudal vein 10 min before LPS injection, and yohimbine+DEX+LPS group with intraperitoneal yohimbine (1 mg/kg) injection 40 min before and Dex injection 10 min before LPS injection. The levels of IL-1β, SOD and MDA in the plasma and renal tissues were determined, and the renal pathologies were examined.

RESULTSCompared with the sham-operated rats, the rats in LPS group showed significantly increased IL-1β and MDA levels and lowered SOD activity in the plasma and renal tissues (P<0.05) with obvious renal pathologies. Dex pretreatment obviously lowered IL-1β and MDA levels and enhanced SOD activity in the plasma and renal tissues in LPS-challenged rats (P<0.05), and significantly lessened LPS-induced renal pathologies.

CONCLUSIONDex can protect the rats against LPS-induced renal injury by alleviating the inflammatory reactions and cytokine oxidative stress, and this effect is mediated possibly by α2 receptors.

Acute Kidney Injury ; drug therapy ; Animals ; Dexmedetomidine ; pharmacology ; Inflammation ; drug therapy ; Interleukin-1beta ; metabolism ; Kidney ; drug effects ; physiopathology ; Lipopolysaccharides ; Malondialdehyde ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Sepsis ; chemically induced ; drug therapy ; Superoxide Dismutase ; metabolism

OBJECTIVETo detect the quantity, proportion and function of producing cytokines of Th1 and Th2 cells in aplastic anemia (AA) patients and their contribution to the hematopoietic failure.

METHODS(1) Eleven patients with severe aplastic anemia (SAA) at diagnosis were observed by Marsh's method for the CFU-E, BFU-E and CFU-GM before and after depletion of CD(4)(+) T lymphocytes from bone marrow mononuclear cells (BMMNC); (2) Th1 (CD(4)(+) IFN-gamma(+)) and Th2 (CD(4)(+) IL-4(+)) cells in peripheral blood mononuclear cells (PBMNC) of 21 SAA patients and 17 normal controls were counted by FACS. (3) mRNA expression of IFN-gamma and IL-4 gene in unstimulated BMMNC from 16 SAA patients, 11 chronic aplastic anemia (CAA) patients, 26 other hematological diseases patients and 11 normal controls were measured by reverse transcriptase polymerase chain reaction (RT-PCR).

RESULT(1) CFU-E, CFU-GM and BFU-E increased significantly after depletion of CD(4)(+) T lymphocytes from BMMNC of SAA patients. (2) The percentage of IFN-gamma producing CD(4)(+) T cell (Th1) of SAA patients was significantly higher than that of controls, the percentages of IL-4 producing CD(4)(+) T cells (Th2) had no difference between SAA patients and normal controls. (3) IFN-gamma mRNA was detected in unstimulated BMMNC in 13 of 16 SAA patients, 6 of 11 CAA patients and one of 6 paroxysmal nocturnal hemoglobinuria (PNH) patients. The IFN-gamma mRNA was not detected in unstimulated BMMNC of 11 normal controls and other hematological diseases patients.

CONCLUSIONSDisbalance of CD(4)(+) T lymphocytes subsets and increases in quantity and IFN-gamma producing function of Th1 cells might be important for the development of bone marrow failure in AA and in distinguishing AA from other kinds of pancytopenic diseases.

Adolescent ; Adult ; Anemia, Aplastic ; blood ; etiology ; Colony-Forming Units Assay ; Erythroid Precursor Cells ; cytology ; Female ; Granulocytes ; cytology ; Hematopoietic Stem Cells ; cytology ; Humans ; Interferon-gamma ; genetics ; Interleukin-4 ; genetics ; Macrophages ; cytology ; Male ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Th1 Cells ; cytology ; metabolism ; physiology ; Th2 Cells ; cytology ; metabolism

OBJECTIVETo examine the quantity and apoptosis-related protein level of B lymphocyte in the patients with immunorelated pancytopenia (IRP) and explore the role of B lymphocyte in the pathogenetic mechanism of IRP.

METHODSQuantities of all B lymphocytes and CD(5)(+) B lymphocytes and the expressions of Fas and bcl-2 on B lymphocytes in 25 patients with untreated IRP, 15 IRP patients in complete remission (CR) and 10 normal controls were assayed by FACS.

RESULTSThe percentages of B lymphocyte and CD(5)(+) B lymphocytes were significantly higher in untreated IRP patients than in CR IRP patients and normal controls (P < 0.05); there was no significant difference between the latter two groups (P > 0.05). There was no significant difference of Fas expression in B lymphocytes among the three groups (P > 0.05). The expression of bcl-2 on B lymphocytes was significantly higher in untreated patients than in CR patients or normal controls (P < 0.05), and so did in CR patients than in normal controls (P < 0.01). The apoptosis-related index was significantly lower in untreated patients than in CR patients or normal controls (P < 0.01), and was lower in CR patients than in normal controls (P < 0.05). The percentage of B lymphocyte was positively correlated with the duration from the beginning of treatment to response.

CONCLUSIONThe production of auto-antibodies in IRP patients probably has some relationships with the abnormal quantities of B lymphocyte and its subsets, and with the inhibition of B lymphocyte apoptosis.

Adolescent ; Adult ; Apoptosis ; physiology ; B-Lymphocytes ; classification ; immunology ; pathology ; Bone Marrow ; physiopathology ; CD5 Antigens ; immunology ; Cell Count ; Child ; Female ; Flow Cytometry ; Humans ; Immune System Diseases ; immunology ; metabolism ; physiopathology ; Male ; Middle Aged ; Pancytopenia ; immunology ; metabolism ; physiopathology ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; metabolism ; fas Receptor ; analysis ; immunology ; metabolism

OBJECTIVETo evaluate the long-term outcome of immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA).

METHODSHematopoietic recovery (peripheral blood cell counts, bone marrow aspirates, bone marrow biopsy, in vitro culture of hematopoietic progenitors), immunity of T lymphocyte, quality of life and side-effects of the therapy were assessed in 50 SAA patients who have survived more than 3 years after IST.

RESULTSAt 3 years, 4 years and 5 years follow-up, 81.5% (13 cases), 86.7% (13 cases) and 89.5% (17 cases) of the SAA patients reached and maintained normal peripheral blood cell counts, 93.4% (15 cases), 93.3% (14 cases) and 94.7% (18 cases) showed normal bone marrow pictures, and 37.5% (6 cases), 40.0% (6 cases) and 73.7% (14 cases) had normal yields of bone marrow cell culture, respectively. Overall, 86.0% (43 cases), 94.0% (47 cases) and 52.0% (26 cases) of the total SAA patients were normalized in peripheral blood counts, bone marrow picture and culture of hematopoietic progenitor yields, respectively. During the follow-up, 88.0% (44 cases) of the patients achieved 100 of Karnofsky scores; 26 of the 31 patients (83.9%) who received bone marrow biopsy showed normal histological pictures, and 29 of 37 patients (78.4%) tested had normal subsets of T lymphocytes. No clonal disease was found. The late side-effects of IST were mild. All of the parameters tested were normal in 24 patients.

CONCLUSIONAfter IST, the hematopoietic function of bone marrow, the immunity of the T lymphocyte and the life quality were normalized with few side-effects in patients with SAA. These patients would probably be cured.

Adolescent ; Adult ; Anemia, Aplastic ; drug therapy ; mortality ; Blood Cell Count ; Bone Marrow Examination ; Child ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hematopoietic Stem Cells ; cytology ; physiology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Karnofsky Performance Status ; standards ; Male ; Middle Aged ; Recovery of Function ; physiology ; Survival Rate ; Treatment Outcome

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.