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To report the first case of chronic disseminated paracoccidioidomycosis in China. A 49-year-old male patient presented with papules and nodules of the skin for 1 year, and papules and ulcers on the oral mucosa for 2 months. Skin examination showed the edema of the left foot, multiple crusting ulcers on the sole of the left foot, ulcers with a granular base in the interdigital regions between the third and fourth toes as well as fourth and fifth toes of the left foot, accompanied by punctate hemorrhage and exudation; there were multiple papules, nodules, and plaques on the dorsum and medial side of the left foot and the left knee, with ulcers and crusts in the center; 2 papules were observed on the left wrist, and 1 papule on the left upper lip with a crusted surface; red plaques with ulcers and punctate hemorrhage were observed on the gingival mucosa, buccal mucosa, labial mucosa, and palate, and the lesions mainly occurred on the left side. Ultrasonography of superficial lymph nodes showed bilateral cervical and supraclavicular lymph node enlargement, which was more obvious on the left side. Computed tomography of the chest and abdomen showed diffuse miliary nodular shadows, and cordlike, cloudy flocculent and nodular high-density shadows in both lungs, as well as obvious thickening of the left adrenal gland in the abdomen. Yeast cells were observed by immunofluorescent staining of biopsy tissues from the oral mucosa and left lower limb. Histopathological examination of biopsy tissues from the oral mucosa and left lower limb showed granulomatous inflammation, and refractive double-membrane yeast cells could be observed inside or outside the multinucleated giant cells, without or with a single bud or multiple buds; periodic acid-Schiff staining and hexamine silver staining of the above biopsy tissues were positive. Fungal culture of the left lower limb lesion in Sabouraud dextrose agar medium at 25℃ and 37℃ both yielded fungal hyphae. Metagenomics sequencing of the oral mucosal tissue and alveolar lavage fluid indicated the infection with Paracoccidioides brasiliensis. The diagnosis of chronic disseminated paracoccidioidomycosis was confirmed. After 1-month oral treatment with itraconazole capsules at a dose of 400 mg/d, the lesions on the skin and oral mucosa markedly improved, and computed tomography imaging of the lung and left adrenal gland also showed obvious improvement. The dose of itraconazole was reduced to 200 mg/d after 3 months. The patient′s condition further improved during a 10-month follow-up.
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Objective:To investigate differences in clinical characteristics between bullous pemphigoid (BP) patients with stroke and those without, and their relationship with the prognosis of stroke.Methods:A retrospective analysis was performed on medical records of 330 BP inpatients in the First Affiliated Hospital of Zhengzhou University from September 2012 to April 2020. These patients were divided into BP + stroke (ST) group and BP - ST group according to whether they were accompanied by stroke, and clinical manifestations and relevant laboratory examination results were compared between the two groups. According to the stroke outcome score assessed by modified Rankin Scale (mRS), patients in the BP + ST group were further divided into good-prognosis ST group (mRS ≤ 2 points) and poor-prognosis ST group (mRS > 2 points), and subgroup analysis was conducted. Correlations between measurement data (such as age, disease course and laboratory examination results) and mRS scores were analyzed.Results:In the BP - ST group (256 cases), 151 were males and 105 were females, and their age ranged from 19 to 92 (66.8 ± 13.6) years; in the BP + ST group (74 cases), 45 were males and 29 were females, and their age ranged from 48 to 92 (74.6 ± 9.6) years; Compared with the BP - ST group, the BP + ST group showed older age ( t = -5.57, P < 0.001), shorter disease course of BP ( Z = -3.07, P = 0.002), and higher anti-BP180 IgG antibody levels (215.0 [157.2, 283.1] U/ml vs. 155.0 [63.9, 279.8] U/ml; Z = -2.12, P = 0.034). The distribution of skin lesions significantly differed between the two groups ( χ2 = 10.51, P = 0.015), and the BP + ST group showed a significantly lower proportion of patients with generalized lesions ( P<0.05), but a higher proportion of patients with lesions on the limbs ( P<0.05). Subgroup analysis showed significant differences in the patients′ age, BP course, lesion distribution and anti-BP180 IgG antibody levels among the good-prognosis ST group, poor-prognosis ST group and BP - ST group ( F = 10.83, P<0.001; Z = 17.24, P<0.001; χ2 = 15.57, P = 0.026; Z = 6.29, P = 0.043, respectively). There was no significant difference in the age between the good-prognosis ST group and poor-prognosis ST group (adjusted P = 1.000), but the patients were significantly older in the two above groups than in the BP - ST group (adjusted P = 0.001, 0.007, respectively) ; the poor-prognosis ST group showed significantly shorter BP courses (adjusted P = 0.016, < 0.001, respectively) and a higher proportion of patients with lesions on the limbs (both P < 0.05) compared with the good-prognosis ST group and BP - ST group, and significantly higher serum anti-BP180 IgG antibody levels compared with the BP - ST group (226.2 [163.6, 285.8] U/ml vs. 155.0 [63.9, 279.8] U/ml; adjusted P = 0.037). There were no significant differences in the gender distribution, lesional morphology, percentages and counts of peripheral blood eosinophils, serum total IgE levels, and anti-BP230 IgG antibody levels between the BP + ST group and BP - ST group (all P > 0.05), or among the good-prognosis ST group, poor-prognosis ST group and BP - ST group (all P > 0.05). Correlation analysis in the BP + ST group showed a significantly negative correlation between the BP course and mRS scores ( r = -0.33, P = 0.004), and a significantly positive correlation between the anti-BP180 IgG antibody levels and mRS scores ( r = 0.34, P = 0.032) . Conclusion:There were differences in the patients′ age, BP course, lesion distribution, and anti-BP180 IgG antibody levels between the BP patients with stroke and those without, and the differences were more obvious between the poor-prognosis ST group and BP - ST group.
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Objective:To investigate clinical features, treatment and prognosis of herpes zoster during pregnancy or the perinatal period.Methods:Clinical data were collected from female inpatients with herpes zoster during pregnancy or the perinatal period in the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2020, and clinical characteristics, treatment and prognosis were retrospectively analyzed.Results:A total of 25 patients were included in the study, including 22 pregnant patients at 10 - 38 gestational weeks (1 in the first trimester, 13 in the second trimester, and 8 in the third trimester) and 3 patients during the first postpartum week; their age ranged from 22 to 37 years, and the disease course varied from 2 to 9 days. Skin lesions were located on the head and face in 8 cases, on the chest and back in 5, on the waist and abdomen in 7, on the upper limbs in 1, on the lower limbs in 3, as well as on the perineum in 1; 3 patients presented with disseminated herpes zoster. The patients all presented with erythema, papulovesicles and blisters, which were accompanied by bloody bullae in 4 patients, by bullae in 3, as well as by erosions and exudations in 6; 5 patients had fever, 7 had mild pain, 6 had moderate pain, and 11 had severe pain. Sixteen pregnant patients and 3 postpartum patients received antiviral therapy (oral or intravenous infusion of acyclovir, vidarabine monophosphate, foscarnet sodium-sodium chloride injection) , 24 patients were treated with neurotrophic drugs, 1 pregnant patient and 3 postpartum patients received analgesic treatment, and other treatments included anti-infective therapy, wet compress, infrared radiation, etc. Preterm delivery occurred in 1 pregnant patient, other pregnant patients had full-term deliveries, and no abnormalities were observed in neonates. Sequelae occurred in 3 pregnant patients, including pain in 1 and pruritus in 2.Conclusion:Among the 25 patients, the treatment of herpes zoster during pregnancy or the perinatal period showed no obvious effect on their fetuses or newborns.
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Objective To retrospectively analyze the clinical epidemiology features of adult idiopathic membranous nephropathy (IMN) in Zhongshan Hospital,and to investigate their therapeutic effect and its possible influence factors.Methods A total of 183 patients admitted to the Zhongshan Hospital of Fudan University and diagnosed as IMN by renal biopsy from January 2013 to December 2015 were involved.Their baseline information including demographics and pathologic was collected.Patients were followed up for at least 12 months.Serum albumin ＜ 30 g/L and 24 h urine protein ＞ 3.5g were defined as nephrotic syndrome (NS).IMN patients were divided into NS and non-NS groups and compared.Furthermore,the baseline data of remission and no remission patients were compared,and the correlations of their baseline data with conservative and immunosuppressive therapy were assessed by logistic regression analysis.Results (1) IMN accounted for 11.1％ of renal biopsy cases in our hospital,with an average age of 57 years and 59.6％ male patients.(2) Compared with patients without NS,IMN patients with NS were older,had a shorter time from the onset to receive renal biopsy,lower estimated glomerular filtration rate,and higher total cholesterol,low density lipoprotein cholesterol,triglyceride and serum creatinine (all P ＜ 0.05).(3) The effective rate of conservative treatment in IMN patients without NS was 65.7％,and the ineffective group had higher triglyceride compared with the effective group (P=0.019).(4) The effective rate of immunosuppressive therapy in IMN patients with NS was 81.2％,and low serum albumin was an independent risk factor for the poor efficacy of immunosuppressive therapy (OR=1.202,95％ CI 1.003-1.440,P=0.046).(5) The effective rate of conservative treatment in IMN patients with NS was 55.5％,and low serum albumin was an independent risk factor for the poor efficacy of conservative treatment (OR=1.629,95％CI 1.047-2.536,P=0.023).Conclusions The detection rate of IMN is increasing year by year,but the remission rate of conservative treatment is still not low in mild and moderate patients.For the patients without NS,high triglyceride may predict a poor effect of conservative treatment.Hypoproteinemia is a predictor of poor effect,no matter what a NS patient takes immunosuppressive therapy or conservative treatment.
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Objective To investigate the role of increased microRNA-21 (miR-21) in the development of renal tubulointerstitial fibrosis secondary to aristolochic acid induced acute kidney injury.Methods C57BL/6J male mice were intraperitoneally injected with aristolochic acid at a dose of 10 mg/kg.Blood samples and kidneys were harvested at day 1,3,7,14,28 after aristolochic acid treatment.To assess the role of miR-21 in aristolochic acid induced acute kidney injury to chronic kidney disease progression,mice were intravenously injected with anti-miR-21 or anti-scramble (10 mg/kg) at 1 h before aristolochic acid dosing,as well as d5 and d10 after aristolochic acid dosing.Results Increased serum creatinine and severe kidney injury were found at d3 after aristolochic acid treatment.Renal tubulointerstitial fibrosis was developed at d14 after aristolochic acid treatment.Protein expression of α-SMA,vimentin and collagen Ⅰ were significantly up-regulated at d7 and peaked at d14 (P ＜ 0.01),while protein abundance of E-Cadherin decreased at d14 and lasted until d28 (P ＜ 0.01).The abundance of miR-21 increased at d7 after aristolochic acid dosing,peaking at d14 and thereafter maintaining at a high level.Anti-miR-21 intervention relieved renal injury with reduced serum creatinine (P ＜ 0.05) and attenuation of renal tubulointerstitial fibrosis.Besides,the protein expression of α-SMA,vimentin,and collagen Ⅰ/Ⅳ was all down-regulated after anti-miR-21 treatment (P ＜ 0.05).PTEN was up-regulated and the ratio of its downstream genes p-AKT/AKT was decreased.(P ＜ 0.05) Conclusions A single high dose of aristolochic acid leads to acute kidney injury and the development of renal tubulointerstitial fibrosis secondary to AKI.Renal tubulointerstitial fibrosis could be partially reversed by inhibiting miR-21 via PTEN/p-AKT pathway.
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Objective To test the hypothesis of autophagy that silencing PHD2 gene could increase hypoxia inducible factor (HIF)-1α levels in the renal medulla and attenuate hypoxia injury in cultured human renal proximal tubular epithelial cell (HK-2) under cobalt dichloride (CoCl2) exposure.Methods HK-2 cells were harvested at hour 0,6,12,24,36 and 48 after exposure to CoC12 (200 μmol/L).The role of HIF/PHD pathway in CoCl2-induced cell apoptosis/autophagy was studied by employing small-interfering RNA (siRNA).Dynamic profiles of apoptosis markers (Bax,Bcl-xl) and autophagy marker (LC3) of HK-2 cells within 48 h after exposing to CoCl2 were recorded.Alamar Blue assay was used for quantitative analysis of cellular growth and viability.Electron microscopy analysis was employed to evaluate the changes in autophagic structures.Results The protein expressions of PHD2 were gradually increased after exposing to CoCl2 (200 μmol/L),with statistics significance at 24 h and reached the peak at 48 h (both P ＜ 0.01).PHD2 siRNA reduced PHD2 levels by ＞ 60％ and significantly increased HIF-1α protein levels (P ＜ 0.01),but had little effect on HIF-2α.The protein expression of Bcl-xl was significantly up-regulated,while the level of Bax and LC3-Ⅱ/LC3-Ⅰ were down-regulated in PHD2 siRNA group (all P ＜ 0.01),compared with the negative control group.Meanwhile,either 3-Methyladenine (an autophagy inhibitor) treatment or PHD2 knockdown rescued cell death and increased cell viability through autophagy inactivation.The ratio of LC3-Ⅱ/LC3-Ⅰ and the quantity of autophagosomes were decreased,and the cell ultrastructure was also relatively intacter than the negative control group.Of interest,co-administration of HIF-1α siRNA with PHD2 siRNA abrogated renoprotective effect conveyed by PHD2 siRNA alone,suggesting that activation of endogenous HIF-1α-dependent pathways mediated the autophagy inactivation effects of PHD2 silencing.Conclusions Direct inhibition of PHD2 promotes renal epithelia cell survival against CoCl2-induced cell apoptosis/autophagy.Activation of the HIF-1α signaling pathway is required to reduce apoptosis and autophagy via up-regulating the expression of Bcl-xl protein.
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Objective To investigate the molecular mechanism of protection of ischemia preconditioning on renal ischemia reperfusion injury. Methods Male C57/BL6N mice were randomly divided into two groups: in IR group, 35 min ischemia was induced by occlusion of both renal pedicles followed by 24 h perfusion (I/R). 15 min ischemia was induced 4 days before I/R in IPC group. Blood sample and kidney were collected in IR and IPC group after 24 h perfusion. Serum creatinine (Scr) and histological changes were used to evaluate the renal injury. PHD2 and HIF-1αwere evaluated by Western blotting, miR-21 expression was confirmed by real-time PCR. In vitro, hypoxic model was established by 1% O2 in HK-2 cells. Knockdown of miR-21 in hypoxic model was perfermed by locked nucleic acid modified-anti-miR-21 transfection. The levels of miR-21, HIF-1α and PHD2 mRNA were confirmed by real-time PCR. The levels of HIF-1α and PHD2 proteins were tested by Western blotting. Results In vivo, Compared with IR group, the renal function and histological changes were improved in IPC group (P<0.01). Compared with IR group, the expression of miR-21(P<0.01) and HIF-1α(P<0.05) were increased in IPC group, while PHD2 was reduced (P<0.01). In vitro, hypoxia reduced miR-21. The inhibition of miR-21 could increased the expression of PHD2 (P<0.05). Conclusions Ischemia preconditioning may exert protection against renal ischemia reperfusion injury by inhibiting PHD2.
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ObjectiveTo determine the levels of 8-iso-prostaglandin F2α (PGF2α) in sera and lesions as well as antioxidant capacity in sera of psoriatic patients,and to assess their correlations with disease severity.MethodsSerum and skin tissue samples were collected from 15 healthy controlsand 50 patients with psoriasis vulgaris.Spectrophotometry was performed to determine the levels of total antioxidant capacity (T-AOC) and the activities of antioxidant enzymes such as superoxide dismutase (SOD),catalase (CAT) and glutathione peroxidase (GSH-Px) in serum samples.Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical SP method were carried out to detect the expression level of 8-iso-PGF2α in the serum and tissue specimens respectively.ResultsThe psoriatic patients showed a significant decrease in the serum level of TAOC((12.78 ± 7.75) U/ml vs. (23.17 ± 8.81) U/ml,P＜ 0.01) as well as the activities of SOD((28.91 ±9.35) U/ml vs.(51.36 ± 7.92) U/ml,P＜ 0.01) and GSH-Px ((180.64 ± 47.70) U vs.(244.20 ± 66.68) U,P ＜ 0.01 ) compared with the healthy controls.The serum T-AOC level and SOD activity were lower in patients with severe psoriasis than those with mild or moderate psoriasis ((9.06 ± 5.30) U/ml vs. (15.27 ± 8.18) U/ml,(21.63 ± 5.28) U/ml vs. (33.76 ± 8.28) U/ml,both P＜ 0.01 ),while there was no significant difference in the activity of GSH-Px between patients with severe and mild or moderate psoriasis.The serum CAT activity was significantly higher in patients with mild or moderate psoriasis than in the healthy controls and patients with severe psoriasis ( (36.92 ± 11.31 ) U/ml vs.( 28.55 ± 8.51 ) U/ml and (24.15 ± 9.36 ) U/ml,P ＜ 0.05 and 0.01 ).Increased serum and lesional 8-iso-PGF2α levels were observed in psoriatic patients compared with the healthy controls ( (88.77 ± 25.27) ng/L vs.(38.34 ± 8.94) ng/L,0.0186 ± 0.0082 vs.0.0027 ± 0.0014,both P ＜ 0.01),as well as in patients with severe psoriasis compared with those with mild or moderate psoriasis(( 114.24 ±13.93) ng/L vs.(71.78 ± 14.35) ng/L,0.0279 ± 0.0027 vs.0.0125 ± 0.0030,both P＜ 0.01 ).The psoriasis area and severity index(PASI) score was negatively correlated with T-AOC level,SOD and CAT activities(r =-0.384,-0.573 and -0.444,all P ＜ 0.01 ),positively correlated with serum and lesional 8-iso-PGF2α levels (r =0.710,0.783,both P ＜ 0.01 ),and uncorrelated with GSH-Px activity.None of the parameters was correlated with the course of disease.ConclusionThe serum and lesional levels of 8-iso-PGF2α may be a more sensitive marker for oxidative damage and disease severity.
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Objective To explore the immunophenotype features and folate receptor expression of blasts in patients with myelodysplastic syndromes(MDS).Methods Four-color flow cytometry using conventional and secondary gating strategies was used into analysis the immunophenotype features and folate receptor(FR) expression of blasts and CD+34 cells in bone marrow nucleated cells with MDS.The patients with acute myeloid leukemia-M2(AML-M2) were as positive control.Results with progression of MDS from RA/RAS,RAEB to RAEB-T,using conventional gating strategy,the proportion of CD+34 cells were gradually increased(P＜0.05).Moreover,the expression of HLA-DR,CDll7,CD13,CD33 were also gradually increased and the expression of CDl5 was gradually decreased(P＜0.05).Using secondary gating strategy,the expression of HLA-DR,CD117,CD13,CD33 on blasts were higher than those by conventional gating(P＜0.05).However,there was no significant difference(P＞0.05) in the expression of above mentioned antigens on CD+34 cells among different MDS subtypes.On the other hand,there were no expression of FR on blasts and cD+34 cells with different MDS subtypes.Conclusion With progression of MDS,the antigens of blasts surface change into more immature immunophenotype of medullary system.But these antigens abnormal expression only illustrates the increase of ascendant malignant clone quantity,it can not reflect the nature of the disease.Using flow cytometry technique can not detect whether or not FR expression on the blasts with MDS.
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Four cellulolytic strains, which can be used as feed additive, were studied under the conditions of various temperature, incubation time, and anaerobic process, and examined the changes of their cell protein content, cellulase and hemi-cellulase activity. The results show: 1) The maximum cellulolytic enzyme activities were observed incubation 20h; 2) Constant medium temperature 28℃ was adequate to the growth of the 4 strains ; 3) anaerobic condition, 39℃±2℃ and fermentation 12h, 24h, 36h, the tested strains can growth well in PDA plate, however, the cellulolytic enzyme activities and growth of the tested strains were influenced adversely when fermentation 48h. The experiment provide many important basis for the strains production, storage and utilization.