Talaromyces marneffei infection in non-HIV-infected patients in mainland China.

BACKGROUND: Talaromyces marneffei, formerly known as Penicillium marneffei, is a significant emerging pathogenic fungus in Southeast Asia which can generate life-threatening systemic infections. Human immunodeficiency virus (HIV) infection is considered as the most underlying disease among systemic infections. However, infections due to T. marneffei without HIV are increasing in recent years. OBJECTIVES: Research the characteristics of T. marneffei infection in non-HIV individuals in mainland China. METHODS: In this study, we searched Pubmed, China National Knowledge Infrastructure (CNKI) and WanFang from inception to 31 December 2019 for studies reporting T. marneffei infection. Our research concentrates on non-HIV-infected cases and their epidemiology, clinical manifestations, laboratory findings, treatment methods and prognosis. RESULTS: T. marneffei infections in non-HIV individuals are increasing. Due to frequent present with atypical symptoms, these non-HIV-infected cases were usually misdiagnosed as other diseases, containing tuberculosis (80.7%), bacterial pneumonia (20.5%), lung cancer (5.1%) or other diseases (5.1%). CONCLUSIONS: T. marneffei infection in non-HIV individuals should be taken seriously. Their symptoms and signs are not typical. Accurate diagnosis and timely antifungal agent treatment is the key to the treatment for the disease.

Subcutaneous botulinum toxin-A injection for treating postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a debilitating disease characterized by continuous, intense pain following an outbreak of herpes zoster. The pain associated with PHN can severely affect a patient's quality of life, quality of sleep, and ability to participate in activities of daily living. The aim of this study was to explore the clinical efficacy of the subcutaneous injection of botulinum toxin-A (BTX-A) for the treatment of PHN. Thirteen patients with PHN were enrolled in this study and treated once with BTX-A. The effects of BTX-A on pain were measured with the visual analogue scale (VAS) 1, 2, 4, 8, 12, and 16 weeks after administration. Compared with pretreatment scores, VAS pain scores decreased at 2 weeks post-treatment in all patients. All patients felt varying degrees of pain relief but remained comfortable. Compared with oral analgesic drugs, VAS scores were significantly different at 2, 4, 8, 12, and 16 weeks post-treatment (p < .05). These results demonstrated that subcutaneous administration of BTX-A can decrease pain in patients with PHN.

Clinical efficacy of paiteling in the treatment of condyloma acuminatum infected with different subtypes of HPV.

Condyloma acuminatum (CA) is a type of mucosal benign hyperplasia skin disease that is caused by human papillomavirus (HPV) infection, which mainly occurs in the genitalia and anus. The aim of the present study was to explore the clinical efficacy underlying the traditional Chinese medicine paiteling in the treatment of CA via the detection of HPV. One hundred CA patients were enrolled in the current study and were externally treated with paiteling for 5 weeks. HPV subtypes were examined both before the treatment and at 6 months after the treatment. After the external paiteling therapy, 92 cases were cured, and the apparent efficiency was 92.0% (92/100), while 8 cases exhibited recurrence. Before the external paiteling therapy, the numbers of cases of low-risk, high-risk, and mixed types of HPV were 40, 35, and 25, respectively. At 6 months after treatment, the numbers of negative cases of low-risk, high-risk, and mixed types of HPV were 38, 32, and 20, respectively. The results demonstrated that external paiteling treatment has a good curative effect on the treatment of CA.

Effects of CO2 fractional laser therapy on peripheral blood cytokines in patients with vitiligo.

Vitiligo is a disease pathologically characterized by specific damage to melanocytes. The aim of this study was to explore the mechanism underlying CO2 fractional laser treatment of vitiligo by detecting the levels of Th1 cytokines (IL-2 and IFN-γ), Th2 cytokines (IL-4 and IL-10), and Th17 cytokines (IL-17 and IL-23) in peripheral blood. Twenty five vitiligo patients were enrolled in this study and were treated with a CO2 fractional laser four to eight times. The cytokines of 25 vitiligo patients and 20 healthy volunteers were measured by enzyme-linked immunosorbent assay. After CO2 fractional laser therapy, six cases were cured, and the apparent efficiency was 72.0% (18/25), while the efficiency was 92.0% (23/25). Before CO2 fractional laser therapy, IL-2 and IFN-γ levels in vitiligo patients were higher than those in the control group, but the difference was not statistically significant (p > .05). IL-4, IL-10, IL-17, and IL-23 levels were also higher in vitiligo patients than those in the control group (p < .05). After treatment, IL-2 and IFN-γ levels in vitiligo patients were lower than before treatment, but the difference was not statistically significant (p > .05), while IL-4, IL-10, IL-17, and IL-23 levels were significantly lower compared with before treatment (p < .05). The results show that CO2 fractional laser treatment has a good curative effect in the treatment of vitiligo.

A Case Report of Widespread Majocchi's Granuloma in a Patient with Systemic Lupus Erythematosus.

Majocchi's granuloma is an intracutaneous or subcutaneous granulomatous inflammation caused by invasion of dermatophytic fungus, especially Trichophyton rubrum. This type of lesion is misdiagnosed frequently without proper auxiliary examination. Here, we report a case of widespread Majocchi's granuloma caused by T. rubrum in a 35-year-old woman with systemic lupus erythematosus for 9 years. The patient was initially misdiagnosed as SLE-associated skin lesions, which delayed her treatment and resulted in severe multiple disseminated lesions. After confirmed as Majocchi's granuloma, the patient was cured after 11-month treatment with terbinafine.

A Case Report of Penile Infection Caused by Fluconazole- and Terbinafine-Resistant Candida albicans.

Candida albicans is the most common pathogen that causes balanoposthitis. It often causes recurrence of symptoms probably due to its antifungal resistance. A significant number of balanitis Candida albicans isolates are resistant to azole and terbinafine antifungal agents in vitro. However, balanoposthitis caused by fluconazole- and terbinafine-resistant Candida albicans has rarely been reported. Here, we describe a case of a recurrent penile infection caused by fluconazole- and terbinafine-resistant Candida albicans, as well as the treatments administered to this patient. The isolate from the patient was tested for drug susceptibility in vitro. It was sensitive to itraconazole, voriconazole, clotrimazole and amphotericin B, but not to terbinafine and fluconazole. Thus, oral itraconazole was administrated to this patient with resistant Candida albicans penile infection. The symptoms were improved, and mycological examination result was negative. Follow-up treatment of this patient for 3 months showed no recurrence.

Photodynamic therapy combined with terbinafine against chromoblastomycosis and the effect of PDT on Fonsecaea monophora in vitro.

Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue caused by dematiaceous fungi, is associated with low cure and high relapse rates. Among all factors affecting clinical outcome, etiological agents have an important position. In southern China, Fonsecaea pedrosoi and Fonsecaea monophora are main causative agents causing Chromoblastomycosis. We treated one case of chromoblastomycosis by photodynamic therapy (PDT) of 5-aminolevulinic acid (ALA) irradiation combined with terbinafine 250 mg a day. The lesions were improved after two sessions of ALA-PDT treatment, each including nine times, at an interval of 1 week, combined with terbinafine 250 mg/day oral, and clinical improvement could be observed. In the following study, based on the clinical treatment, the effect of PDT and antifungal drugs on this isolate was detected in vitro. It showed sensitivity to terbinafine, itraconazole or voriconazole, and PDT inhibited the growth. Both the clinic and experiments in vitro confirm the good outcome of ALA-PDT applied in the inhibition of F. monophora. It demonstrated that combination of antifungal drugs with ALA-PDT arises as a promising alternative method for the treatment of these refractory cases of chromoblastomycosis.

FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1.

Objective: This research aims to investigate the role and underlying biological mechanism of FBXO45 in regulating ferroptosis of renal fibrocytes in a diabetic nephropathy (DN) model. Methods: C57BL/6 mice were fed with a high-fat diet and injected with streptozotocin to induce diabetes. Human renal glomerular endothelial cells stimulated with d-glucose. Results: Serum FBXO45 mRNA expression was found to be down-regulated in patients with DN. There was a negative correlation between the expression of serum FBXO45 mRNA and serum α-SMA, Collagen I, and E-cadherin mRNA in patients with DN. Additionally, the expression of serum FBXO45 mRNA showed a negative correlation with blood sugar levels. Based on a 3D model prediction, it was observed that FBXO45 interacts with polo-like kinase 1 (PLK1) at GLY-271, ILE-226, GLY-166, LEU-165, ARG-245, and ASN-220, while PLK1 interacts with FBXO45 at TYR-417, ARG-516, HIS-489, TYR-485, GLN-536, and ARG-557. This interaction was confirmed through immunoprecipitation assay, which showed the interlinking of FBXO45 protein with PLK1 protein. Conclusions: These findings indicate that FBXO45 plays a role in mitigating ferroptosis in DN through the regulation of the PLK1/GPX4/SOX2 pathway. This highlights the potential of targeting FBXO45 as a therapeutic approach to ameliorate ferroptosis in DN.

A Cutaneous Phaeohyphomycosis Case Caused by Paraconiothyrium cyclothyrioides in Southern China.

Paraconiothyrium cyclothyrioides is a coelomycetous fungus species that was recently identified. We present a case of an elderly farmer with chronic skin lesions of the opisthenar caused by P. cyclothyrioides.

Chromoblastomycosis in Mainland China: a systematic review on clinical characteristics.

Chromoblastomycosis is one of the most frequent chronic infections caused by melanized fungi. In order to evaluate the clinical characteristics of chromoblastomycosis in Mainland China, we performed an evidence-based review of published literature. PubMed and Chinese-language database of CNKI, VIP and Wanfang data during January 1990-August 2011 were searched. Epidemiology, clinical features, laboratory findings, therapy and prognosis were analyzed. Cladophialophora carrionii was the most common causative agent in the north of the Mainland China, and Fonsecaea monophora and F. pedrosoi were the most common agents in the southern part of the Mainland China. Infection commonly initiated after the etiologic agents gain entrance through puncture wounds and more common involved extremities of the males. Skin lesions were found in different sites, like the extremities, buttocks, trunk and face, and presented diversity morphology. There were about seven different clinical types found in Mainland China: plaque type, tumoral type, cicatricial type, verrucous type, pseudo-vacuole type, eczymatous type and mixed type of lesions. The success of treatment for chromoblastomycosis was related to the causative agent, the clinical form and severity of the lesions. Most of the patients could be treated successfully with the physical treatment, chemotherapy and/or combination therapy. The itraconazole, terbinafine or a combination of both were commonly medication for these mycosis patients. Physical methods were usually indicated to support chemotherapy with some severe forms and long-lasting cases. Photodynamic therapy has been extended from the oncological field to that of antimicrobial chemotherapy in these years. We applied it on some recalcitrant cases of chromoblastomycosis and found its good clinical response, and hopeful it could be a promising therapy in near future.

Development of in vitro macrophage system to evaluate phagocytosis and intracellular fate of Penicillium marneffei conidia.

Penicillium marneffei is a pathogenic fungus that can cause a life-threatening systemic mycosis in the immunocompromised hosts. We established the model for the phagocytosis of P. marneffei conidia by RAW264.7 murine macrophages and designated the fate of P. marneffei in RAW264.7 cells with respect to persistence, phagosome-lysosome-fusion. And we impaired the immune status of mouse and compared the fate and phagosome-lysosome-fusion of P. marneffei in immunocompetent and immunosuppressed mouse peritoneal macrophages cells. We found that conidia could germinate and survive in macrophages. Within 30 min and up to 2 h of heat-killed conidia internalization, the majority of all phagosome types were labeled for the EEA1 (endosomal markers) and LAMP-1 (lysosomal markers), respectively. But both the percentages of LAMP-1 and EEA1 that associated with live conidia were significantly lower than that with heat-killed conidia. Administration of cyclophosphamide resulted in a significant suppression of macrophages function (phagocytic and fungicidal) against P. marneffei that were not apparently seen. Our data provide the evidence that (i) intracellular conversion of P. marneffei conidia into yeast cells still could be observed in macrophages. (ii) Phagosomes containing live Penicillium marneffei conidia might inhibit the phagosome-lysosome-fusion and result to no acidification surrounding the organisms. (iii) Immunity impaired by cyclophosphamide could not influence the function, including phagocytosis, fungicidal activity and phagosome-lysosome-fusion, of macrophages against P. marneffei.

Penicillium marneffei infection: an emerging disease in mainland China.

Penicillium marneffei is an emerging pathogenic fungus that can cause a life-threatening systemic mycosis in immunocompromised hosts, especially in patients with AIDS. This infection is endemic in Southeast Asia. With the prevalence of AIDS in this area, the number of patients with systemic penicilliosis marneffei is found to be increasing rapidly in mainland China in recent years. We recently reviewed 668 cases of penicilliosis marneffei in mainland China from January 1984 to December 2009 in cnki, cqvip, CBMdisc and PubMed. We analyzed epidemiological and clinical features, laboratory findings, reaction to therapy and prognosis of the disease. We found that 99.4% of the cases were reported in the southern part of China; among these cases, 42.8% were from Guangxi (286 cases) and 40.6% were from Guangdong province (271 cases). Five hundred and eighty-six cases (87.7%) of penicilliosis marneffei were reported with infection by the human immunodeficiency virus, 25 cases (3.8%) with other immunocompromised diseases, and 57 cases (8.5%) without any documented underlying diseases. Fever, weight loss, anemia, lymphadenopathy, hepatosplenomegaly, respiratory signs and skin lesions were the common clinical manifestations of P. marneffei infections. The 569 cases received antifungal therapy with a mortality of 24.3% (138 cases), 99 cases who had not received antifungal therapy had a mortality of 50.6%. P. marneffei was an emerging pathogenic fungus and become a medical and public health importance in mainland China. The immunocompromised patients should pay more attention to P. marneffei infection in the endemic areas.

Melanin in a meristematic mutant of Fonsecaea monophora inhibits the production of nitric oxide and Th1 cytokines of murine macrophages.

Melanin is a complex polymer which is secreted outside or constitutes the structure of fungal cell wall. It is considered as an important virulence factor in opportunistic pathogenic fungi. In this study, one albino mutant (CBS 125149) was generated from a parent meristematic mutant (CBS 122845) of Fonsecaea monophora. Transmission electron microscopy profiles showed that melanin in the parent strains appeared as electron-dense granules which located on the cell wall surface. We extracted the cell wall fractions from the two different strains by an alkali-acid method. The different strains or its cell wall fractions were interacted with the activated RAW264.7. The pigmented strain and its cell wall fraction could reduce the expression of inducible nitric oxide synthase gene and inhibit the synthesis of nitric oxide in vitro (P < 0.05). Exacerbated Th2 and inhibited Th1 response occurred in the interaction between activated RAW264.7 and the pigmented strain or its cell wall fraction. Collectively, our results suggest that melanin plays an important role in escaping the killing of oxidative burst in vitro. The exacerbated Th2 response probably accelerates the persistence of the fungus.

Involvement of RAGE, MAPK and NF-κB pathways in AGEs-induced MMP-9 activation in HaCaT keratinocytes.

Advanced glycation end products (AGEs) exert divergent effects on the pathogenesis of diabetes complications. Excessive expression of matrix metalloproteinases-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. However, the effect of AGEs on MMP-9 induction in skin cells and the exact molecular mechanisms involved are still poorly understood. In this study, we investigated the effect of AGEs on the production of MMP-9 in HaCaT keratinocytes and characterized the signal transduction pathways activated by AGEs that are involved in MMP-9 regulation. We showed that AGE-BSA increased MMP-9 expression in HaCaT cells at both the protein and mRNA levels. The stimulatory effect of AGE-BSA on MMP-9 was attenuated by inhibitors of extracellular-signal-regulated kinase (ERK1/2, U0126), p38 mitogen-activated protein kinase (MAPK, SB203580) and NF-κB, but not c-Jun N-terminal kinase. Furthermore, receptor for advanced glycation end products (RAGE) was expressed in keratinocytes, and incubation with AGE-BSA resulted in a significant upregulation of RAGE expression in a dose-dependent manner. Silencing of the RAGE gene prevented AGE-BSA-induced MMP-9 activation and the phosphorylation of ERK1/2 and p38 MAPK. We also observed the involvement of NF-κB in AGE-BSA-induced MMP-9 activation, which was not blocked by U0126 and SB203580. These results suggest that AGEs may play an important role in the impairment of diabetic wound healing by upregulating MMP-9 expression in keratinocytes via the RAGE, ERK1/2 and p38 MAPK pathways; activation of NF-κB is also involved in this process. These pathways may represent potential targets for drug interventions to improve diabetic wound healing, a process in which MMP-9 plays a critical role.

A refractory case of chromoblastomycosis due to Fonsecaea monophora with improvement by photodynamic therapy.

Chromoblastomycosis is one of the most frequently encountered mycoses in tropical and temperate regions caused by the implantation of the infectious structures and one which is associated with low cure and high relapse rates. The etiologic agents play a critical role affecting clinical outcome and in southern China, Fonsecaea pedrosoi and F. monophora are the main causative agents of chromoblastomycosis. We treated, for two years, a 55-year-old male patient with chromoblastomycosis caused by F. monophora with itraconazole and terbinafine, two antifungals recommend in earlier papers in the literature but without any positive response. As a result we introduced the photodynamic therapy (PDT) employing 5-aminolevulinic acid (ALA) irradiation. The lesions were improved after two periods of ALA-PDT treatment, each consisting of exposures at weekly intervals for 5 weeks but new lesions developed with the cessation of ALA-PDT treatment. Thereafter, positive clinical improvement was obtained when voriconazole at 200 mg was combined with terbinafine at 250 mg in treating the patient. The in vitro susceptibility of the F. monophora isolate to terbinafine, itraconazole, and voriconazole was assessed and the fungus was found to be sensitive to all three, with the minimal inhibitory concentrations of 0.125, 1, 0.0625 µg/ml, respectively. However, the determination of in vitro susceptibility profiles may not predict clinical response.

Photodynamic Therapy for the Treatment of Fungal Infections.

Cutaneous fungal infections are common in humans and are associated with significant physical and psychological distress to patients. Although conventional topical and/or oral anti-fungal medications are commonly recommended treatments, drug resistance has emerged as a significant concern in this patient population, and safer, more efficacious, and cost-effective alternatives are warranted. Recent studies have reported effectiveness of photodynamic therapy (PDT) against fungal infections without severe adverse effects. In this review, we briefly discuss the mechanisms underlying PDT, current progress, adverse effects, and limitations of this treatment in the management of superficial and deep fungal infections.

A Retrospective Study of Clinical Efficacy of Cantharidin Cream for Verruca Plantaris.

Verruca plantaris (plantar wart) is a type of benign feet hyperplasia that is caused by a human papillomavirus (HPV) infection. In this study, we aimed to assess the clinical efficacy underlying cantharidin cream in the treatment of Verruca plantaris compared to CO2 laser and liquid nitrogen cryotherapy. One hundred and fifty patients affected with Verruca plantaris were enrolled in this retrospective clinical study. The treatment efficacy rate in the three groups was assessed 4 and 12 weeks after treatment. After 4 weeks of treatment, 46 cases in the externally applied cantharidin cream therapy group were cured with an apparent efficiency of 92.0% (46/50). Contrarily, 42 cases in the CO2 laser group were cured with 84.0% (42/50) efficiency, while 40 cases in the liquid nitrogen cryotherapy group were cured with an apparent efficiency of 80.0% (40/50). Although the clinical cure rate of Verruca plantaris in the Cantharidin group was greater than in the CO2 laser group and in the liquid nitrogen cryotherapy group, there were no statistical differences found among the three groups (P = 0.225). After 12 weeks of treatment, 43 cases in the external cantharidin cream therapy group were cured with an apparent efficiency of 86.0% (43/50). Similarly, 39 cases in the CO2 laser group were cured with an apparent efficiency of 78.0% (39/50), while 36 cases in the liquid nitrogen cryotherapy group were cured with an apparent efficiency of 72.0% (36/50). The statistical differences among the three groups were not found (P =0.230), but the resolution rate of warts in Cantharidin group was the highest among the three groups. The results from this study demonstrated that external cantharidin cream therapy could be served as an alternative treatment for Verruca plantaris.

Systemic nocardiosis caused by Nocardia concava in China.

A 42-year-old man with polychondritis and a 2-year history of using low-dose prednisone and other immunosuppressive drugs was admitted to our hospital due to persistent high fever of 10 days duration. A strain of Nocardia was twice isolated from his blood and subsequently identified to be N. concava. The patient was initially treated with sulphadiazine sodium, vancomycin and imipenema for 7 days but the symptoms persisted. Consequently, the regimen was changed to sulphadiazine sodium, ciprofloxacin and amikacin sulfate based on the antibiotic susceptibility tests of the Nocardia isolate. The fever disappeared and the patient's condition improved after 10 days of this treatment to the extent that he was discharged. However, 7 days later, the patient's condition deteriorated and he died due to multiple organ failure. This is the first report of N. concava causing systemic nocardiosis in China.

Retrospective Analysis of Drug Sensitivity of Neisseria gonorrhoeae in Teaching Hospitals of South China.

The aim of this study was retrospective analysis of drug sensitivity of Neisseria gonorrhoeae in two teaching hospitals of South China. A total of 304 Neisseria gonorrhoeae isolates obtained from patients in South China from 2016 to 2020 were evaluated. The MICs of penicillin, cefuroxime, ceftriaxone (CRO), cefepime, ciprofloxacin, ceftazidime and azithromycin (AZM) against the isolates were determined by the agar dilution method. Then, Neisseria gonorrhoeae isolates were categorized into sensitive, moderately sensitive and resistant according to MICs. Also, ß-lactamases were detected by enzyme linked immunosorbent assay (ELISA). Ureaplasma urealyticum and Mycoplasma hominis were determined by culture in liquid medium, and Chlamydia was detected by rapid antigen test. The result showed there was 50.99%, 20.72%, 9.87%, 14.47%, 86.84%, 7.57%, 6.91%, 11.18% resistance to penicillin, cefuroxime, ceftriaxone, cefepime, ciprofloxacin, ceftazidime and azithromycin, respectively. Also, ß-lactamase positivity was 53.29% and Chlamydia antigen positivity was 20.07%. Ureaplasma urealyticum and Mycoplasma hominis positivity was 11.84% and 6.25%, respectively. From 2016 to 2020, the resistant rate of ceftriaxone and azithromycin gradually increased. In conclusion, Southern China is among the area reporting gonococci with high-level resistance to AZM and CRO, so N. gonorrhoeae culture and drug sensitivity test will be vital for monitoring trends in antimicrobial resistance.