Chronic pulmonary aspergillosis (CPA) is a rare disease. It is usually diagnosed in immunocompromised patients with other chronic respiratory disorders. Diagnosis can be challenging due to non-specific symptoms. It is based on clinical, radiological, and microbiological criteria and excludes other causes of the symptoms. The outcomes of antifungal treatment may be unpredictable as optimal treatment duration has not yet been standardized. This is the case of a 74-year-old male who presented via teleconsultation with hemoptysis. GeneXpert for pulmonary tuberculosis was negative. Chest radiograph showed a cavitary lesion with an aspergilloma within. This led to a longstanding treatment effort with voriconazole, as he was a poor candidate for surgical resection due to the risk of post-operative complications. Three months into the treatment, the patient unexpectedly suffered from a severe episode of dyspnea, culminating in cardiac arrest. While the patient has been resuscitated with no residuals, it is only one of the many steps on his road to recovery and his second lease on life, this time coming to terms with his own preferences and values regarding his medical care. The patient showed clinical improvement and the promise of a cure in his fifth month of treatment. Learning points include the role of family physicians in a patient’s well-being even in specialized cases, the value of individualized care and the application of technology in hybrid consultation and monitoring.
Aspergillosis ; hemoptysis ; voriconazole

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(C_min) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole C_min were analyzed, and the changes of voriconazole C_min after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole C_min and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole C_min was negatively correlated with albumin level (r=-2.673). Voriconazole C_min in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole C_min showed that compared with voriconazole C_min 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole C_min> 5.0 mg/L group was increased (χ²=4.318, P=0.038). CONCLUSION The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole C_min, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole C_min of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Humans ; Male ; Female ; Voriconazole/therapeutic use* ; Antifungal Agents/therapeutic use* ; C-Reactive Protein ; Creatinine ; Glucocorticoids ; Retrospective Studies ; Drug Monitoring ; Hematologic Diseases

Introduction: Histoplasmosis is a disease of global distribution with diverse manifestations caused by the dimorphic fungus Histoplasma capsulatum. It is frequently described in severely immunocompromised and Human Immunodeficiency Virus (HIV)-positive individuals. Despite being widely reported in Southeast Asia, few cases have been reported in the Philippines. Case Report: A 53-year-old Filipino male who presented with umbilicated papules resembling molluscum contagiosum, and a previous history of a left lung mass with initial complaints of cough and hemoptysis. Gram stain of his sputum revealed the presence of fungal elements, otherwise not specified. In relation to this, a fine-needle aspiration biopsy of the suspected lung mass was done. However, findings were negative for malignant cells and fungi. Dermoscopy revealed central ulceration and necrosis with faint peripheral arborizing telangiectasia and surrounding superficial scaling. Histopathologic analysis revealed a diffuse granulomatous dermatitis, and Periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) stains showed numerous small yeast-like structures measuring approximately 3.74µm in diameter. Tissue culture of the skin lesion on the right thigh isolated fungal elements but was not specified. As histoplasmosis is an AIDS-defining infection and often found in immunocompromised states, screening for HIV was done which revealed negative results. Interestingly, disease distribution of histoplasmosis in the Philippines was frequently found in HIV-negative patients. Due to persistent serum creatinine elevation of over 300 µmol/L, renal biopsy was also done and revealed similar fungal elements. With these findings, a diagnosis of disseminated histoplasmosis was made. After a month of treatment with oral itraconazole, there was marked improvement of the patient’s skin lesions. Conclusion This case highlights the importance of recognizing cutaneous manifestations and maintaining a high index of suspicion for histoplasmosis in HIV-seronegative patients.
systemic fungal infections ; disseminated histoplasmosis ; itraconazole

Histoplasmosis is well-characterized as a fungal disease that more commonly occurs in North America, mostly endemic in Ohio and Mississippi river valleys. The clinical spectrum of histoplasmosis ranges from asymptomatic infection to a fatal disease. Progressive disseminated histoplasmosis is typically seen in immunocompromised individuals and presents with non-specific systemic symptoms associated with cutaneous manifestations of papules and nodules.? We report a case of a 28-year old Filipino female with a history of exposure to soil activities months before consult. The patient presented with a 3-week history of erythematous macules, vesicles, and pustules over the face, arms, and trunk, which evolve into papules and plaques with hemorrhagic crusting. Patient was initially diagnosed and treated as a case of varicella but had no improvement with initial management. Histopathologic findings were consistent with histoplasmosis. The patient was started with oral itraconazole, but unexpectedly expired before any improvement in cutaneous symptoms were noted.
Disseminated histoplasmosis ; Itraconazole

Humans ; Child ; Voriconazole/adverse effects* ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy* ; Renal Dialysis ; Seizures ; Antibodies, Antineutrophil Cytoplasmic

Non-Hodgkin lymphoma (NHL) is a common lymphoid hematological malignancy, the treatment and prognosis of NHL have always been the focus of clinical attention. Chemotherapy is the main first-line treatment, but there is still no effective treatment for patients with poor response to chemotherapy, recurrence or progression within a short period of time after treatment, and new and effective drugs need to be developed clinically. As the only clinically validated oral selective inhibitor of nuclear export (SINE), Selinexor has been approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma and multiple myeloma, clinical attempts are being made to apply it to the treatment of other hematological malignancies.This article reviews the anti-tumor mechanism of Selinexor and the latest research progress in its application in NHL, and provides ideas for a more diverse, standardized and effective applications of Selinexor in NHL.
Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Active Transport, Cell Nucleus ; Hydrazines/pharmacology* ; Triazoles/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.
Female ; Animals ; Humans ; Mice ; Candidiasis, Vulvovaginal/drug therapy* ; Inflammasomes/genetics* ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; 1-Butanol/pharmacology* ; Fluconazole/therapeutic use* ; Interleukin 1 Receptor Antagonist Protein/therapeutic use* ; Mice, Inbred C57BL ; Candida albicans ; Cytokines ; Drugs, Chinese Herbal/pharmacology* ; Ethanol ; RNA, Messenger ; Calcium-Binding Proteins/therapeutic use*

Objective: To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C. tropicalis isolates from 2017 to 2021 in East China. Methods: Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected C. tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired t-test. Results: In total, 305 C. tropicalis isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of C. tropicalis to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC₅₀, and MIC₉₀ of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (t=9.95, P<0.05), posaconazole (t=9.99, P<0.05), and voriconazole (t=10.01, P<0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (t=1.17, P>0.05), both of which were significantly higher than MICA (t=11.56, P<0.05; t=4.15, P<0.05). Conclusion: The clinical isolates of C. tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in C. tropicalis.
Humans ; Antifungal Agents/pharmacology* ; Fluconazole/pharmacology* ; Candida tropicalis ; Voriconazole/pharmacology* ; Itraconazole/pharmacology* ; Retrospective Studies ; Candida ; China/epidemiology* ; Echinocandins/pharmacology* ; Microbial Sensitivity Tests

Objective: To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C. tropicalis isolates from 2017 to 2021 in East China. Methods: Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected C. tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired t-test. Results: In total, 305 C. tropicalis isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of C. tropicalis to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC₅₀, and MIC₉₀ of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (t=9.95, P<0.05), posaconazole (t=9.99, P<0.05), and voriconazole (t=10.01, P<0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (t=1.17, P>0.05), both of which were significantly higher than MICA (t=11.56, P<0.05; t=4.15, P<0.05). Conclusion: The clinical isolates of C. tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in C. tropicalis.
Humans ; Antifungal Agents/pharmacology* ; Fluconazole/pharmacology* ; Candida tropicalis ; Voriconazole/pharmacology* ; Itraconazole/pharmacology* ; Retrospective Studies ; Candida ; China/epidemiology* ; Echinocandins/pharmacology* ; Microbial Sensitivity Tests

OBJECTIVE: To investigate the effects and mechanism of bromodomain and extra-terminal (BET) inhibitor JQ1 on the double-expressor lymphoma (DEL) cell lines. METHODS: Protein expressions of cMyc and BCL-2 in 3 lymphoma cell lines were checked by Western blot so as to identify DEL cell lines. CCK-8 assay was used to detect the effects of JQ1 on anti-proliferation in the DEL cell lines. Western blot and RT-PCR were used to measure the protein and mRNA expressions of cMyc, BCL-2 and BCL-6 in DEL cell lines which treated by JQ1. Flow cytometry was used to detect the effect of JQ1 on cell apoptosis. RESULTS: Based on the expressions of cMyc and BCL-2, the SU-DHL6 and OCILY3 cell lines were confirmed as DEL cell lines. CCK-8 assay showed that the proliferation of DEL cell lines was inhibited by JQ1, which was similar to non-DEL cell lines and mainly regulated the expression of cMyc and BCL-6 but not BCL-2. JQ1 had no effects on apoptosis in the DEL cell lines. CONCLUSION BET inhibitor JQ1 has anti-tumor effect in the DEL cell lines, thus providing evidence for the therapeutic potential of BET inhibitor JQ1.
Apoptosis ; Azepines/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Proto-Oncogene Proteins c-myc/metabolism* ; Sincalide/pharmacology* ; Triazoles/pharmacology* ; Xenograft Model Antitumor Assays