Exploration and Practice of the "One Combination, Two Highlights, Three Combinations, Four in One" Innovative Talents Training Mode in Forensic Medicine.

Talent is one of the basic and strategic supports for building a modern socialist country in all aspects. Since the 1980s, the establishment of forensic medicine major and the cultivation of innovative talents in forensic medicine have become hot topics in higher education in forensic medicine. Over the past 43 years, the forensic medicine team of Shanxi Medical University has adhered to the joint education of public security and colleges, and made collaborative innovation, forming a training mode of "One Combination, Two Highlights, Three Combinations, Four in One" for innovative talents in forensic medicine. It has carried out "5+3/X" integrated reform, and formed a relatively complete talent training innovation mode and management system in teaching, scientific research, identification, major, discipline, team, platform and cultural construction. It has made a historic contribution to China's higher forensic education, accumulated valuable experience for the construction of first-class major and first-class discipline of forensic medicine, and provided strong support for the construction of the national new forensic talent training system. The popularization of this training mode is conducive to the rapid and sustainable development of forensic science, and provides more excellent forensic talents for national building, regional social development and the discipline construction of forensic science.

Effects of phosphorus application on yield, quality and phosphorus use efficiency of edible sweetpotato: A case study of Xushu 32.

To explore the appropriate amount of phosphorus (P) fertilizer and improve economic yield and P use efficiency of edible sweetpotato, we took Xushu 32 as an example and compared the effects of different P application rates on yield, quality, P accumulation and P use efficiency of edible sweetpotato based on a two-year field experiment (soil available P content was 31.70 mg·kg-1) from 2018 to 2019. There were five P application levels (P2O5), including 0 (P0), 25 (P25), 50 (P50), 75 (P75) and 100 kg·hm-2(P100). The results showed that, 1) compared with P0, P application significantly increased the yield of fresh sweetpotao and commodity potato, with the effects being the stongest under P75 treatment, followed by P50 treatment. However, there was no significant difference between the two treatments. 2) P application significantly increased the contents of starch and reducing sugar in storage root. The contents of soluble sugar and protein increased significantly under P50 treatment. 3) Du-ring the growth period of 90 to 120 d, P fertilizer supply significantly increased P accumulation and dry matter accumulation of sweetpotato. 4) The apparent P use efficiency (APUE) decreased with increasing P application rates, while P agronomic efficiency (PAE) increased first and then decreased with the increases of P application rates, which was significantly higher under P50 than other treatments. Taking into account the yield, quality, economic yield and P utilization rate of edible sweetpotato, the optimal dosage of P2O5 is 50 kg·hm-2 under the experimental conditions.

Adjuvant Radiotherapy After Minimally Invasive Surgery in Patients With Stage IA1-IIA1 Cervical Cancer.

To estimate whether adjuvant radiotherapy is necessary for patients with stage IA1-IIA1 cervical cancer after laparoscopic hysterectomy, 221 patients were retrospectively analyzed. Sixty-two of them were treated with laparoscopic hysterectomy and adjuvant radiotherapy (group A), 115 underwent open surgery (group B) and 44 received laparoscopic hysterectomy alone (group C). Results showed that the 3-year local recurrence-free survival (LRFS) rates of group A, B and C were 98.4%, 97.4% and 86.4%, respectively. The LRFS rates of group A and B surpassed C (A vs. B, p=0.634; A vs. C, p=0.011; B vs. C, p=0.006). The inter-group differences of 3-year overall survival (OS) and distant metastasis free survival (DMFS) were not statistically significant. In subgroup analysis of stage IB disease, the 3-year LRFS rates of group A, B and C were 100%, 98.8% and 83.1%, the 3-year OS rates of group A, B and C were 100%, 98.9% and 91.5%, respectively. The 3-year LRFS and OS rates of group A and B were significantly superior to group C (p<0.05). Our findings suggest that adjuvant radiotherapy can reduce the risk of recurrence for women with early-stage cervical cancer after laparoscopic hysterectomy and bring survival benefits for patients with stage IB disease.

A new kind of filter paper comprising ultralong hydroxyapatite nanowires and double metal oxide nanosheets for high-performance dye separation.

Simultaneous enhancement in water flux and removal efficiency during the filtration process remains a big challenge for separation membranes. The porous structure of the filter paper can provide many channels for water transportation, but the separation performance is generally poor. The purpose of this study is to develop a new kind of filter paper consisting of ultralong hydroxyapatite (HAP) nanowires, cellulose fibers (CFs) and double metal oxide (LDO) nanosheets, and to achieve the simultaneous enhancement of both water flux and removal efficiency for high-performance dye separation. In this work, a novel kind of LDO/HAP/CF nanocomposite filter paper consisting of ultralong HAP nanowires and CFs and LDO nanosheets has been developed for rapid water filtration and highly efficient dye adsorption. Positively charged LDO nanosheets can adsorb on the surface of negatively charged ultralong HAP nanowires and embed in the porous networked structure of the LDO/HAP/CF nanocomposite filter paper, which can provide a porous structure for rapid water transportation and can adjust the pore size of the nanocomposite filter paper. As a result, the pure water flux of the LDO/HAP/CF nanocomposite filter paper can be adjusted. The optimized pure water flux of the LDO/HAP/CF nanocomposite filter paper can reach 783.6 L m-2 h-1 bar-1, which is 1.51 times that of the HAP/CF filter paper without LDO nanosheets (518.6 L m-2 h-1 bar-1). More importantly, the adsorption capacity of LDO nanosheets is high for dye molecules, the rejection percentage of Congo red (CR) by the as-prepared HAP/CF filter paper is only 59.8%, and its water flux is 534.7 L m-2 h-1 bar-1. The optimized rejection percentage and water flux of the LDO/HAP/CF nanocomposite filter paper for CR are significantly enhanced (98.3% and 736.8 L m-2 h-1 bar-1, respectively) compared to those of the HAP/CF filter paper. The size of LDO nanosheets has a significant effect on the water flux and dye rejection percentage of the LDO/HAP/CF nanocomposite filter paper. The as-prepared LDO/HAP/CF nanocomposite filter paper is promising for the applications in highly efficient purification of wastewater containing dye molecules.

A national survey on fungal infection diagnostic capacity in the clinical mycology laboratories of tertiary care hospitals in China.

BACKGROUND/PURPOSE: As the incidence of fungal infections in China increases, the demand for rapid and accurate diagnosis of mycoses is growing. Yet, information on current diagnostic capacity is scarce. METHODS: An online survey was conducted in February 2018 to collect information on mycology testing from tertiary care hospitals across China. Responses from 348 hospitals were analyzed, and a scoring system was designed and employed to assess the overall diagnostic capacity. RESULTS: Most of the surveyed hospitals did not have separate laboratory space, manpower, or equipment dedicated for fungal testing. Conventional staining methods were widely available (>70%), whereas GMS and fluorescent staining were less common. Fungal identification services were offered mostly with chromogenic medium, morphological characterization or automated identification systems, other than more advanced methods such as MALDI-TOF MS and DNA sequencing. Fungal serology testing was available in 81.1%, with G test being the most often used. Though 91.8% of the respondents had the ability to perform antifungal susceptibility testing for yeasts, less than 13% conducted such testing for molds. The percentage of laboratories participating in External Quality Assessment programs and research was 57.5% and 32.5%, respectively. The average score for the 348 surveyed hospitals was 37.2 (out of a maximum of 89 points), with only 15 hospitals scoring >60, suggesting a general lack of high-quality mycology laboratories. CONCLUSIONS: The overall clinical testing capacity for fungal infection in China is insufficient. More investment and training efforts are warranted to establish centers of excellence and promote access to high-quality diagnostic services.

Differences in in vitro interactions between macrophages with pathogenic and environmental strains of Prototheca.

Aim: We investigated the interactions between macrophage and different strains of Prototheca. Materials & method: J774A.1 macrophages were infected with clinical isolates of Prototheca ciferrii 18125 and P. ciferrii 50779 and environmental isolate of P. ciferrii N71. Phagocytosis activities were compared by colony-forming unit assays at 3, 6 and 9 h after infection. Cytokine levels were detected by RT-PCR and ELISA. iNOS protein expression was examined by western blotting. Results: All P. ciferrii strains were phagocytized by macrophages but induced different levels of cytokines in macrophages. Moreover, infected by P. ciferrii N71 upregulated much higher iNOS protein expression in J774A.1 than that infected by the clinical strains. Conclusion: Clinical and environmental P. ciferrii strains show differences in their interactions with macrophages, which may be attributed to their virulence.

Epidural Spinal Cord Stimulation Promotes Motor Functional Recovery by Enhancing Oligodendrocyte Survival and Differentiation and by Protecting Myelin after Spinal Cord Injury in Rats.

Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear. Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI. ESCS also significantly increased the myelinated area at 28 days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase, an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rhBMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI, and rhBMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI.

Secret Paper with Vinegar as an Invisible Security Ink and Fire as a Decryption Key for Information Protection.

Security inks based on photoluminescent materials are mostly investigated for security applications, such as information encryption and decryption, anti-counterfeiting, and data storage. Although they are invisible to the naked eye under ambient light, they can be detected under ultraviolet or near-infrared light. Herein, a new kind of secret paper made from network-structured ultralong hydroxyapatite nanowires and cellulose fibers has been developed. White vinegar, a common cooking ingredient, is used as an invisible security ink. Covert information on the secret paper written with white vinegar is totally invisible under natural light, but it can be decrypted and clearly read after exposure to fire; the response time to fire is short (<10 s). The ways of writing on the secret paper are diverse by using various pens loaded with white vinegar.

Comparative Genome and Transcriptome Study of the Gene Expression Difference Between Pathogenic and Environmental Strains of Prototheca zopfii.

Prototheca zopfii commonly exists in the environment, and causes invasive infections (protothecosis) in humans. The morbidity of protothecosis has increased rapidly in recent years, especially in systemic infections of patients with an impaired immune system. The infection in immunocompromised patients has a poor prognosis due to limited understanding of the pathogenesis of the disease, as most previous studies mainly focused on classification and recognition of pathogenic strains. In this study, we constructed the genome and transcriptome of two pathogenic strains and one environmental strain, by next generation sequencing methods. Based on our preliminary gene expression findings, genes in P. zopfii pathogenic strains are significantly up-regulated in metabolism in peroxisome, such as glyoxylate cycle, which may improve the organism's resistance to the harsh environment in phagolysosome of macrophage and its ability to survive in an anaerobic environment. We also found some significant up-regulated genes, which are related to adherence and penetration in dermatophytes, and we speculate that this may enhance the virulence capacity of pathogenic strains. Finally, the genomes and transcriptomes of P. zopfii described here provide some base for further studies on the pathogenesis of this organism.

Ultralong Hydroxyapatite Nanowire-Based Filter Paper for High-Performance Water Purification.

A new kind of environmentally friendly filter paper based on ultralong hydroxyapatite nanowires (HAPNWs) and cellulose fibers (CFs) with excellent filtration and adsorption properties has been developed for the application in high-performance water purification. The use of polyamidoamine-epichlorohydrin (PAE) resin increases the wet mechanical strength of the as-prepared HAPNW/CF filter paper. The addition of CFs enhances the mechanical strength of the HAPNW/CF filter paper. Owing to the porous structure and superhydrophilicity of the as-prepared HAPNW/CF filter paper, the pure water flux is as high as 287.28 L m-2 h-1 bar-1 under cross-flow conditions, which is about 3200 times higher than that of the cellulose fiber paper with addition of PAE. More importantly, the as-prepared HAPNW/CF filter paper shows superior performance in the removal of TiO2 nanoparticles (>98.61%) and bacteria (up to 100%) in water by the size exclusion and blocking effect. In addition, the HAPNW/CF filter paper also exhibits high adsorption capacities for methyl blue (273.97 mg g-1) and Pb2+ ions (508.16 mg g-1). The adsorption mechanism of the HAPNW/CF filter paper is investigated. The as-prepared environmentally friendly HAPNW/CF filter paper with both excellent filtration and adsorption properties has promising application in high-performance water purification to tackle the worldwide water scarcity problem.

A new kind of nanocomposite Xuan paper comprising ultralong hydroxyapatite nanowires and cellulose fibers with a unique ink wetting performance.

In the history of civilization, Xuan paper with its superior texture, durability and suitable characteristics for writing and painting, has played an important role in the dissemination of culture and art. Xuan paper has won the reputation of "the king of paper that lasts for 1000 years" and was inscribed on the Representative List of the Intangible Cultural Heritage of Humanity by the Educational, Scientific and Cultural Organization of the United Nations in 2009. However, the surface of the commercial unprocessed Xuan paper has a large number of large-sized pores with a poor resistance to water, allowing ink droplets to easily spread during the writing and painting process. In this study, we report a new kind of nanocomposite Xuan (HNXP) paper comprising ultralong hydroxyapatite (HAP) nanowires and plant cellulose fibers with unique ink wetting performance, high whiteness and excellent durability. The as-prepared HNXP paper sheets with various weight ratios of ultralong HAP nanowires ranging from 10% to 100% are all superhydrophilic with a water contact angle of zero. In contrast, the ink contact angle of the HNXP paper can be well controlled by adjusting the weight ratio of ultralong HAP nanowires, and the ink contact angle of the HNXP paper increases with increasing weight ratio of ultralong HAP nanowires. The experimental results show the unique ink wetting behavior of the as-prepared HNXP paper, which is absent in the traditional Xuan paper. This new kind of nanocomposite Xuan paper comprising ultralong hydroxyapatite nanowires and plant cellulose fibers is promising for applications in calligraphy and painting arts.

Isobaric tag for relative and absolute quantitation-based comparative proteomic analysis of human pathogenic Prototheca zopfii genotype 2 and environmental genotype 1 strains.

BACKGROUND/PURPOSE: Prototheca species are ubiquitous achlorophyllic microalgae belonging to the family Chlorellaceae, which can cause a wide range of infections in humans and animals. Mainly in individuals with immunologic defects or trauma, Prototheca spp. can cause even lethal diseases. However, the exact pathogenic mechanism of Prototheca in causing disease remains largely unknown. To investigate the differences between pathogenic and nonpathogenic Prototheca spp. genotypes on proteome level, a nonpathogenic Prototheca zopfii genotype 1 strain, isolated from cow manure, and a human pathogenic P. zopfii genotype 2, isolated from human granulomatous lymphadenitis, were studied. METHODS: Differentially expressed proteins between the two genotypes were quantified by isobaric tag for relative and absolute quantitation-based quantitative proteomics, using liquid chromatography-tandem mass spectrometry. RESULTS: A total of 245 proteins were identified from the proteomic analysis after data filtering to eliminate low-scoring spectra. Among these, 35 proteins that displayed a significant (p<0.05) 1.5-fold change were considered as differentially expressed proteins. CONCLUSION: The differentially expressed proteins were associated with suppressed energy production and conversion, carbohydrate transport and metabolism, and enhanced translation in the genotype 2 strain, and are thus potentially relevant in the pathogenic mechanism of P. zopfii genotype 2, but need further investigation.

In vitro and in vivo evidence for amphotericin B as a P-glycoprotein substrate on the blood-brain barrier.

Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain barrier (BBB). The uptake of AMB by primary brain capillary endothelial cells in vitro was significantly enhanced after inhibition of P-gp by verapamil. The impact of two model P-gp inhibitors, verapamil and itraconazole, on brain/plasma ratios of AMB was examined in both uninfected CD-1 mice and those intracerebrally infected with Cryptococcus neoformans. In uninfected mice, the brain/plasma ratios of AMB were increased 15 min (3.5 versus 2.0; P < 0.05) and 30 min (5.2 versus 2.8; P < 0.05) after administration of verapamil or 45 min (6.0 versus 3.9; P < 0.05) and 60 min (5.4 versus 3.8; P < 0.05) after itraconazole administration. The increases in brain/plasma ratios were also observed in infected mice treated with AMB and P-gp inhibitors. The brain tissue fungal CFU in infected mice were significantly lower in AMB-plus-itraconazole or verapamil groups than in the untreated group (P < 0.005), but none of the treatments protected the mice from succumbing to the infection. In conclusion, we demonstrated that P-gp inhibitors can enhance the uptake of AMB through the BBB, suggesting that AMB is a P-gp substrate.

Identification of clinically relevant fungi and prototheca species by rRNA gene sequencing and multilocus PCR coupled with electrospray ionization mass spectrometry.

BACKGROUND: Multilocus PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) is a new strategy for pathogen identification, but information about its application in fungal identification remains sparse. METHODS: One-hundred and twelve strains and isolates of clinically important fungi and Prototheca species were subjected to both rRNA gene sequencing and PCR/ESI-MS. Three regions of the rRNA gene were used as targets for sequencing: the 5' end of the large subunit rRNA gene (D1/D2 region), and the internal transcribed spacers 1 and 2 (ITS1 and ITS2 regions). Microbial identification (Micro ID), acquired by combining results of phenotypic methods and rRNA gene sequencing, was used to evaluate the results of PCR/ESI-MS. RESULTS: For identification of yeasts and filamentous fungi, combined sequencing of the three regions had the best performance (species-level identification rate of 93.8% and 81.8% respectively). The highest species-level identification rate was achieved by sequencing of D1/D2 for yeasts (92.2%) and ITS2 for filamentous fungi (75.8%). The two Prototheca species could be identified to species level by D1/D2 sequencing but not by ITS1 or ITS2. For the 102 strains and isolates within the coverage of PCR/ESI-MS identification, 87.3% (89/102) achieved species-level identification, 100% (89/89) of which were concordant to Micro ID on species/complex level. The species-level identification rates for yeasts and filamentous fungi were 93.9% (62/66) and 75% (27/36) respectively. CONCLUSIONS: rRNA gene sequencing provides accurate identification information, with the best results obtained by a combination of ITS1, ITS2 and D1/D2 sequencing. Our preliminary data indicated that PCR/ESI-MS method also provides a rapid and accurate identification for many clinical relevant fungi.

Cutaneous protothecosis in patient with diabetes mellitus and review of published case reports.

Protothecosis is an opportunistic infection caused by Prototheca, usually called as saprophytes, and is frequently found in natural and living surroundings with low virulence, but may cause chronic infection in immunocompromised individuals. We report a case of cutaneous protothecosis with zopfii var. portoricensis infection in a 66-year-old diabetic woman following hand surgery on middle right finger. Mycology study showed that smooth, creamy white, yeast-like colonies grown after necrotic tissue was cultured on Sabouraud dextrose agar at both 37 and 25°C. The organism was then identified as Prototheca zopfii var. portoricensis by molecular identification and also found from histopathology of the lesion. The lesion got improved with intravenous amphotericin B and itraconazole.

[Antifungal susceptibility test of genotypes of Candida albicans from patients with atrophic or erosive oral lichen planus].

PURPOSE: To study the antifungal susceptibility of genotypes of Candida albicans from patients with atrophic or erosive oral lichen planus and provide evidence for the treatment of candidiasis. METHODS: Polymerase chain reaction(PCR) was adopted to analyze 101 Candida albicans which were isolated from atrophic or erosive oral lichen planus.Microdilution broth method was carried out for antifungal susceptibility test. SPSS16.0 software package was used for Chi-square test. RESULTS: A total of 101 strains of Candida albicans were divided into three types, 39 were genotype A strains,17 genotype B stains and 45 genotype C stains.Strains of genotype A were significantly more resistant to 5-fluorocytosine than strains of genotypes B and C(P<0.05). Strains of genotype B were significantly more resistant to fluconazole than strains of genotype A(P<0.05). Strains of genotype C were significantly more resistant to itraconazole than strains of genotype A(P<0.05).None of the strains of genotypes B and C presented drug resistance to nystatin. There was no significant difference among genotypes A,B and C(P>0.05). CONCLUSIONS: There is a correlation between Candida albicans genotypes and antifungal susceptibility. The use of antifungal agent should be based on the genotypes and antifungal susceptibility test of Candida albicans. For the treatment of candidiasis in patients with atrophic or erosive oral lichen planus, the value of nystatin should be addressed.

Suction blister epidermal grafting using a modified suction method in the treatment of stable vitiligo: a retrospective study.

BACKGROUND: Of various surgical therapies used for the replenishment of melanocytes in recalcitrant and stable vitiligo, suction blister epidermal grafting (SBEG) is one of the simplest and most effective methods. OBJECTIVE: To evaluate the effectiveness and potential complications of SBEG in the treatment of stable vitiligo through the use of a modified dermis-epidermis separator designed by the authors. MATERIALS AND METHODS: One thousand one hundred people with stable vitiligo unresponsive to other medical treatments were treated with SBEG therapy. The negative pressure generated by the dermis-epidermis separator raised blisters at recipient and donor sites. Repigmentation was assessed 6 months after epidermis transplantation. RESULTS: Complete repigmentation was observed in 227 patients (20.6%), and excellent repigmentation (>50%) was observed in 568 (51.6%)-a success rate of 72.3%. No superficial scarring was observed at the grafted or donor sites, and no serious complications were encountered. CONCLUSION: SBEG is an established, simple, and effective treatment for resistant and stable vitiligo. Patients suffer few complications and are receptive to this type of therapy.

Cutaneous malasseziasis: four case reports of atypical dermatitis and onychomycosis caused by Malassezia.

BACKGROUND: This study investigates four special cases associated with Malassezia. METHODS: The special clinical manifestations, mycologic examination, and treatment were reviewed intensively. RESULTS: An abundance of Malassezia hyphae were found in the scales of the three cases presenting with erythematous patches and in another case presenting with dystrophic nails. Malassezia globosa was identified and confirmed by culture. Antifungal agents were effective in the treatment of all cases. CONCLUSIONS: Malassezia is an opportunistic fungus that may induce dermatosis other than classical pityriasis versicolor. Hyphae from the lesions may be induced by a change in the microenvironment of the fungus caused by the local application of corticosteroids.

[The polymorphism of cytochrome P(450) 2C19 gene in patients with invasive fungal infections.].

OBJECTIVE: To investigate the polymorphism profile of cytochrome P(450) 2C19 (CYP2C19) in Chinese patients with invasive fungal infections. METHODS: Two major single nucleotide polymorphism loci of the CYP2C19 gene (CYP2C19*2 and CYP2C19*3) were genotyped with PCR and restriction fragment length polymorphism (PCR-RFLP) in 134 patients with invasive fungal infections and 134 healthy volunteers. Allele frequencies and the proportions of metabolizer phenotypes were compared. RESULTS: In patients with invasive fungal infections, CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles showed frequencies of 58.2%, 36.6% and 5.2%. In healthy volunteers, the frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 63.4%, 34.3% and 2.2%. There was no significant difference in allele frequencies between the two groups. Of the patients with invasive fungal infections, 33.6% were homozygous extensive metabolizers, 50.0% heterozygous extensive metabolizers and 16.4% poor metabolizers. Of the healthy volunteers, 40.3% were homozygous extensive metabolizers, 48.5% heterozygous extensive metabolizers and 11.2% poor metabolizers. The proportions of metabolizer phenotypes were similar between the two groups. CONCLUSIONS: Significant CYP2C19 polymorphism was detected in both groups. Approximately two thirds of the Chinese patients were either heterozygous extensive metabolizers or poor metabolizers. The genetic polymorphism may have important effect on drug metabolism in these patients.

Cryptococcal meningitis in non-HIV-infected patients in a Chinese tertiary care hospital, 1997-2007.

Information remains sparse about non-HIV patients with cryptococcal meningitis in the era of triazole therapy. Particularly of interest are the clinical manifestations and prognosis of the infection in these previously healthy patients. We retrospectively reviewed 154 non-HIV-infected patients with cryptococcal meningitis who presented in our hospital from 1997 to 2007. We compared the clinical features and outcomes between predisposed and otherwise healthy hosts. The number of cases per year showed a steady increase over time. The majority of patients were otherwise apparently healthy (103 patients, 66.9%) and predisposing factors were identified in only 51 (33.1%) patients. Corticosteroid medication accounted for the most common underlying factor in these cases (n = 21). Morbidity was appallingly high, with seizures in 28.6%, cranial nerves palsies in 51.5% and cerebral herniation in 19.5%. Despite these complications, overall mortality during 1 year was 28.7% (41/143), close to that reported from other centers with non-HIV patients. Death attributed to cryptococcosis occurred in 19.6% (28/143) patients with most receiving amphotericin B as a component of their initial therapy. Among surviving patients who had lumbar punctures at weeks 2 and 10, those given amphotericin B for initial therapy achieved higher rates of overall response than those receiving initial fluconazole therapy at either week 2 (84.4% of 96 patients vs. 33.3% of 24 patients, P <0.001) or week 10 (85.0% of 93 patients vs. 66.7% of 24 patients, P = 0.041). In multivariate analysis, coma, cerebral herniation, and initial antifungal therapy without amphotericin B were independently correlated with both increased overall and attributable mortality, while advanced age (>/= 60 years) was correlated with increased overall mortality only. Patients with apparently normal immune status were overall younger than those who were immunocompromised. In addition, previously healthy patients for whom diagnosis was delayed had more severe disease, experiencing more brain herniation, coma, seizures, hydrocephalus and more surgical shunt procedures. On the other hand, immunocompromised patients were more commonly found to have high fever and brain parenchymal involvement. However, both groups had a similar treatment response and 1-year survival.