Case Report: Cutaneous Mycosis Caused by Purpureocillium lilacinum.

Purpureocillium lilacinum, widely used as a commercial biocontrol agent for controlling plant-parasitic nematodes, is an emerging opportunistic pathogen in humans and is increasingly reported, especially among immunocompromised patients. We report a classic case of cutaneous mycosis caused by P. lilacinum. A 51-year-old Chinese woman who received tacrolimus and glucocorticoid therapy for 3 years for nephrotic syndrome experienced recurrent papules, pustules, and ulceration on her right ring finger and subcutaneous nodules on her forearm 6 months ago. A lesion biopsy on the right ring finger revealed multiple epithelioid granulomas in the dermis and fat layer containing slender, pigmented fungal hyphae. The fungal culture showed the growth of violet floccose colonies. Lactophenol cotton blue culture stain demonstrated brush-like phialides, with a swollen basal part attached to chains of conidia. Sequencing of the internal transcribed spacer regions of ribosomal DNA, alignment with GenBank, and use of a Basic Local Alignment Search Tool analysis led to the identification of P. lilacinum. Treatment with oral voriconazole was successful.

MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway.

Preeclampsia (PE) is a common pregnancy-specific syndrome with an incidence of 4.6% in all pregnant women. Numerous studies have uncovered the functions and mechanisms of microsomal glutathione transferase 1 (MGST1) in different diseases and cellular processes, but whether MGST1 plays a role in PE remains unclear. Our study aimed to investigate the regulatory role of MGST1 in PE progression. In this study, the HTR8/SVneo cells were incubated with CoCl2 (250 µM) to mimic hypoxia in trophoblasts. Real-time quantitative polymerase chain reaction revealed that MGST1 was dramatically reduced in the placenta of PE patients. The proliferation of HTR8/SVneo cells was assessed via the Cell Counting Kit-8 and colony formation assays, and the results showed that MGST1 upregulation increased the cell viability of HTR8/SVneo cells. In addition, wound healing and Transwell assays unveiled that the elevation of MGST1 enhanced trophoblast cell migration and invasion. Moreover, the upregulation of MGST1 alleviated the hypoxia-induced oxidative stress in trophoblast cell. Mechanically, we found that MGST1 regulated PE progression by activating the phosphoinositide-3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway. In conclusion, MGST1 alleviated the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promoted cell proliferation, migration, and invasion via the activation of the PI3K/AKT/mTOR pathway in PE. These results suggested that MGST1 can be a potential target for the prevention and treatment of PE.

A Cross-Sectional Nationwide Study on Accessibility and Availability of Neonatal care Resources in Hospitals of China: Current Situation, Mortality and Regional Differences: Neonatal Care Resources and Newborn Mortality in China.

BACKGROUND: To investigate the current situation of neonatal care resources (NCR), newborn mortality rates (NMR), regional differences and existing challenges in China. METHODS: By using a self-designed questionnaire form and the cross-sectional method, we conducted a survey of all hospitals equipped with neonatal facilities in China from March 2019 to March 2020 with respect to the level and nature of these hospitals, the number of newborn beds and NICU beds, the number of neonatal pediatricians, and the development of therapeutic techniques. The data about the newborn births and deaths were retrieved from the annual statistics of the health commissions of the related provinces, autonomous regions and municipalities. FINDING: Included in this nationwide survey were 3,020 hospitals from all 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government of Mainland China, with a 100% response rate. They included 1,183 (39.2%) level-3 (L3) hospitals, 1629 (53.9%) L-2 hospitals and 208 (6.9%) L-1 hospitals. Geographically, 848 (31.4%) hospitals were distributed in Central China, 983 (32.5%) hospitals in East China, and 1,089 (36.1%) in West China. The 3,020 included hospitals were altogether equipped with 75,679 newborn beds, with a median of 20 (2-350) beds, of which 2,286 hospitals (75.7%) were equipped with neonatal intensive care units (NICU), totaling 28,076 NICU beds with a median of 5 (1-160) beds. There were altogether 27,698 neonatal pediatricians in these hospitals, with an overall doctor-bed ratio of 0.366. There were 48.18 newborn beds and 17.87 NICU beds per 10,000 new births in China. In East, Central and West China, the number of neonatal beds, NICU beds, neonatal pediatricians, and attending pediatricians or pediatricians with higher professional titles per 10,000 newborns was 42.57, 48.64 and 55.67; 17.07, 18.66 and 18.17; 16.26, 16.51 and 20.81; and 10.69, 10.81 and 11.29, respectively. However, when the population and area are taken into consideration and according to the health resources density index (HRDI), the number of newborn beds, NICU beds and neonatal pediatricians in West China was significantly lower than that in Central and East China. In addition, only 10.64% of the neonatal pediatricians in West China possessed the Master or higher degrees, vs. 31.7% in East China and 20.14% in Central China. On the contrary, the number of neonatal pediatricians with a lower than Bachelor degree in West China was significantly higher than that in Central and East China (13.28% vs. 7.36% and 4.28%). Technically, the application rate of continuous positive airway pressure (CPAP) and conventional mechanical ventilation (CMV) in L-1 hospitals of West China was lower than that in Central and East China. According to the statistics in 2018, the newborn mortality rate (NMR) in West China was significantly higher than that in Central and East China. INTERPRETATION: China has already possessed relatively good resources for neonatal care and treatment, which is the primary reason for the rapid decrease in the NMR in China. However, there are still substantial regional differences. The density of health resources, the level of technical development and educational background of neonatal pediatricians in West China still lag behind those in other regions of China and need to be further improved and upgraded. FUNDING: This research work was funded by National Natural Science Foundation of China (81671504) and United Nations International Children's Emergency Fund (CHINA-UNICEF501MCH).

Mast cells and thymic stromal lymphopoietin (TSLP) expression positively correlates with pruritus intensity in dermatitis herpetiformis.

BACKGROUND: Pruritus is one of the leading symptoms of dermatitis herpetiformis (DH), however, studies on the pathogenesis of pruritus are scarce. Currently, skin mast cells (MCs) have been indicated to play a role in pruritus in autoimmune bullous disease. OBJECTIVE: To study the role of mast cells and related mediators involved in the pathogenesis of pruritus in DH. MATERIALS & METHODS: The number of MCs and expression of histamine and thymic stromal lymphopoietin (TSLP) was investigated in lesions of 29 DH cases and 15 healthy skin donors by immunohistochemistry. Fourteen patients were assessed for severity of pruritus based on the Numeric Rating Scale and Pruritus Grading System. The levels of histamine and TSLP in the serum of 18 DH patients and 15 healthy controls were also investigated. RESULTS: A significant increase in the number of MCs and degranulation was observed in DH lesions, which positively correlated with intensity of pruritus. In addition, skin TSLP but not histamine was shown to correlate with intensity of pruritus. No significant difference in expression of serum TSLP or histamine was observed between DH patients and healthy controls. CONCLUSION: These results suggest that skin MCs and TSLP might be involved in the pathogenesis of pruritus in DH which should be further clarified in future studies.

High-Frequency Ultrasound in Blistering Skin Diseases: A Useful Method for Differentiating Blister Locations.

Bullous pemphigoid and pemphigus vulgaris, which belong to the group of subepidermal and intraepidermal bullae, respectively, are two potentially devastating blistering skin diseases. We used high-frequency ultrasound (US) in 3 cases of these diseases as prototypes to study the value of high-frequency US in discriminating blister locations. Our findings showed that high-frequency US has a strong correlation with histomorphometric findings because of its high resolution, and we hope that it will be helpful for differentiating blister locations.

Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

BACKGROUND: As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH) had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. METHODOLOGY: We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. RESULTS: Genome-wide linkage (assuming autosomal dominant inheritance mode) and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val) that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val) and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys) in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. CONCLUSION: Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

Recurrent cutaneous necrotizing eosinophilic vasculitis: a case report and review of the literature.

We report a case of recurrent cutaneous necrotizing eosinophilic vasculitis (RCNEV) in a 57-year-old male. The patient presented with papules and pruritus of the lower limbs of more than 1 month duration, and with angioedema and intensively pruritic, necrotizing lesions of the bilateral anterior tibias and feet for 2 weeks. Treatment with systemic corticosteroids was administered for 1 month, and resulted in a significant improvement. We also present a review of the pertinent literature and discuss the clinical features, histopathological features, and differentiation of RCNEV. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2065600765102207.

[Effect of Chinese materia medica combined chemotherapy on the survivals of stage II and III colorectal cancer].

OBJECTIVE: To study the effects of Chinese materia medica (CMM) combined chemotherapy on the recurrence, metastasis, and the disease free survival (DFS) of stage II and III colorectal cancer (CC) patients after radical cure. METHODS: Recruited were 366 inpatients and outpatients with stage II and III colorectal cancer (CC) from Changhai Hospital, Second Military Medical University, and Tumor Department of Longhua Hospital, Shanghai University of Traditional Chinese Medicine from January 2002 to December 2008. A non-randomized concurrent control method was adopted. Patients were assigned to the combination group (treated by CMM + chemotherapy, 189 cases) and the chemotherapy group (177 cases) according to whether they were willing to receive the CMM treatment for more than 6 successive months. By using follow-ups at clinics, by letter, and by telephone, the DFS, 1-, 2-, 3-, and 5-year DFS ratios were observed. The correlations between DFS and the gender, age, tumor location, staging of clinical pathology, pathological type, chemotherapeutic cycle, radiotherapy, CMM treatment, end point event (recurrence and metastasis) were analyzed. RESULTS: The recurrence or metastasis occurred in 145 cases (39. 61%) of the 366 patients. Of them, local recurrence occurred in 17 cases (11.72%), liver metastasis in 45 cases (31.03%), lung metastasis in 52 cases (35.86%), and metastasis in other parts in 53 cases (36.55%). Results of one-factor analysis showed six factors such as the tumor location, pathological type, staging of clinical pathology, chemotherapeutic cycle, radiotherapy, and CMM treatment were correlated with the DFS, showing statistical difference (P<0.01, P<0.05). Results of multifactor analysis showed staging of clinical pathology, chemotherapeutic cycle, and CMM treatment were correlated with the DFS, showing statistical difference (P<0.01). Results of stratified study on the staging of clinical pathology indicated that the primary tumor location (P=0.016) and the pathological type (P=0.047) were the independent predictors for DFS of stage II CC. The median DFS of the two groups could not be calculated. Results of stratified study on the stages of clinical pathology indicated that CMM treatment (P=0.000) and chemotherapeutic cycle (P=0.017) were independent predictors for DFS of stage III CC. As for comparing the composition ratio of the two therapeutic cycles, results showed the baselines of the chemotherapeutic cycle of the two groups were balanced. Further comparison showed the median DFS for the chemotherapy group at stage III was 24. 16 months, while it could not be calculated in the combination group. The DFS, 1-, 2-, 3-, and 5-year DFS ratios were 92%, 72%, 61%, and 59%, respectively in the stage III CC combination group, while they were 74%, 50%, 36%, and 20%, respectively in the stage IlI CC chemotherapy group. CONCLUSION: CMM combined chemotherapy could prolong the DFS of stage III CC patients after radical cure.

Evaluation of the combination of BP180-NC16a enzyme-linked immunosorbent assay and BP230 enzyme-linked immunosorbent assay in the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an acquired autoimmune subepidermal blistering disease characterized by circulating IgG autoantibodies directed against BP180 and BP230 hemidesmosomal proteins. Previous studies have demonstrated that antibodies against the NC16a domain of BP180 mediate BP pathogenesis, while antibodies against BP230 enhance the inflammatory response. Recently, commercial BP180-NC16a enzyme-linked immunosorbent assay (ELISA) and BP230 ELISA kits were developed to detect anti-BP180 and anti-BP230 autoantibodies in human BP sera. AIMS: To evaluate the efficacy of BP180-NC16a ELISA and BP230 ELISA in the initial diagnosis of BP. METHODS: Sera from 62 BP patients and 62 control subjects were tested by BP180-NC16a ELISA and BP230 ELISA and compared with findings from indirect immunofluorescence (IIF) and immunoblotting (IB) to determine the sensitivity and specificity of these assays. RESULTS: The sensitivities of BP180-NC16a ELISA and BP230 ELISA were 87.1% (54/62) and 56.5% (35/62), respectively, and the specificities of both were 100% (62/62). Using both ELISAs for diagnosis increased the sensitivity to 95.2% (59/62) and was statistically comparable with IB sensitivity. CONCLUSIONS: ELISA is a convenient, effective, and reliable method for serodiagnosis of BP, and combined use of BP180-NC16a ELISA and BP230 ELISA can increase the sensitivity of this diagnostic approach.

[Clinical study on survival benefit for elderly patients with resected stage II or III colorectal cancer based on traditional Chinese medicine syndrome differentiation and treatment].

BACKGROUND: The incidence of colorectal cancer is high among the elderly. Traditional Chinese medicine (TCM) has been widely used in the treatment for colorectal cancer of old people. However, controlled trials with large sample size evaluating the effect of TCM are rare. OBJECTIVE: This research aimed to evaluate the survival benefit of using TCM syndrome differentiation treatment for elderly patients with stage II or III colorectal cancer. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 78 patients over 70 with resected stage II or III colorectal cancer were selected from the First Department of Oncology, Longhua Hospital of Shanghai University of Traditional Chinese Medicine, and Department of Anorectal Surgery, Changhai Hospital of Second Military Medical University. Patients were assigned to either integrated treatment group or Western medicine group by their own wills. MAIN OUTCOME MEASURES: Cox regression analysis was performed to determine all the potential factors which may affect prognosis such as gender, primary site, pathological type, TNM stage, chemotherapy period, radiotherapy and TCM therapy. RESULTS: A total of 78 cases were included in this study with 37 cases in integrated treatment group and 41 cases in Western medicine group. Cox regression analysis suggested that the TNM stage (P=0.001) and TCM therapy (P=0.021) were independent prognostic factors. The hazard ratio [Exp(ß)] of TCM therapy was 0.393, and 95% confidence interval (CI) was 0.178-0.870. Median disease-free survival (DFS) of Western medicine group was 41.293 months. DFS of integrated treatment group did not reach the median at the time of analysis. There was significant difference between the two groups (P=0.012). The 1-, 2-, 3-, 4-, and 5-year DFS rates of Western medicine group were 87.7 %, 69.6%, 63.4%, 46.5%, and 29.6%, respectively. The 1-, 2-, 3-, 4-, and 5-year DFS rates of integrated therapy group were 100%, 86.3%, 74.6%, 74.6%, and 74.6%, respectively. CONCLUSION: TCM syndrome differentiation and treatment is important for improving the prognosis of stage II or III colorectal cancer in elderly patients. Integrated treatment shows benefit for reducing relapse and metastasis rates, and prolonging survival for elderly patients. The influence of integrated treatment needs to be further evaluated.

[Serum growth hormone and prolactin levels in neonates with hypoxic-ischemic encephalopathy].

OBJECTIVE: To investigate the levels and roles of serum growth hormone (GH) and prolactin (PRL) in neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: Serum GH and PRL levels were measured by radioimmunoassay in 54 neonates with HIE (20 mild, 19 moderate and 15 severe HIE) at the acute and convalescence stages. Twenty normal neonates were used as controls. RESULTS: Serum GH levels were significantly lower, but PRL levels were significantly higher in moderate and severe HIE neonates at the acute stage compared with those of controls and mild HIE neonates (P < 0.01). There were noticeable differences in serum levels of GH and PRL between the moderate and severe HIE cases (P < 0.01). During the convalescence stage, serum GH levels increased and PRL levels decreased in moderate and severe HIE neonates compared with those at the acute stage (P < 0.01); serum GH and PRL levels in each sub-group of HIE restored to the levels of controls. There was a closely negative correlation between GH and PRL levels at the acute stage of HIE (r = -0.8759, P < 0.01). CONCLUSIONS: GH and PRL might be involved in the pathophysiological process of HIE. The levels of GH and PRL closely relate to the severity of HIE at the acute stage.

[Diagnostic value of serum high molecular weight alkaline phosphatase in early detection of cholestatic jaundice in neonates].

OBJECTIVE: To investigate the difference of serum high molecular weight alkaline phosphatase (HMAP) levels between biliary atresia (BA) and neonatal hepatitis (NH), and to develop a new differential method and early diagnostic indicators for cholestatic jaundice in neonates. METHODS: Totally 31 patients with cholestatic jaundice seen between Aug. 2000 and Feb. 2002, including 15 cases with BA, 16 cases with NH, 30 healthy infants and 30 infants with non-cholestatic jaundice were enrolled in this study. Serum samples were obtained from each subject by using venipuncture. The samples were stored at -80 degrees C and analyzed within 6 months. A murine hybridoma producing monoclonal antibody to human high molecular weight alkaline phosphatase (MoAb HMAP-1) was prepared by using partially purified HMAP from human serum as the immunogen. The antibody did not cross-react with other alkaline phosphatase (ALP) isozymes. A monoclonal antibody immunocatalytic assay for HMAP in serum was developed by using MoAb HMAP-1 bound to nitrocellulose membrane discs. The serum total ALP (TALP) and gamma-GT were determined in the meantime, the hepatobiliary ultrasonography and scintigraphy were performed too. The data were analyzed with t test, chi-square test and percentage. Comparisons were made between BA and NH with their sensitivity and specificity in different methods. RESULTS: Serum HMAP was detected in 14 of 15 patients of BA, in 2 of 16 NH patients, while in none of the healthy control group. The positive ratios of serum HMAP in BA and NH were 93.3% and 12.5%, respectively (P < 0.005). The sensitivity and specificity of serum HMAP in BA and NH were 93.3% and 87.5%, respectively. The sensitivity and specificity of TALP, gamma-GT and hepatobiliary scintigraphy were 80.0%, 73.3%, 86.7% and 62.5%, 68.8%, 62.5%, respectively, which were clearly lower than those of serum HMAP. CONCLUSIONS: The determination of serum HMAP was more sensitive and specific than the other methods tested. Therefore the method can be used as a useful indicator for cholestatic jaundice in neonates, although it needs further study.