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Objective:To evaluate the value of indirect immunofluorescence on salt-split skin (IIF-SSS) in the diagnosis of bullous pemphigoid (BP) .Methods:A single-center clinical retrospective study was conducted. Totally, 163 patients with newly diagnosed BP were collected from Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2013 to January 2019, so were 404 controls, including 161 with pemphigus, 67 with eczema, 26 with drug eruption, 23 with erythema multiforme, 18 with prurigo nodularis, etc. Blood samples were collected before the treatment, and IIF-SSS, BP180 NC16A enzyme-linked immunosorbent assay (ELISA) and direct immunofluorescence (DIF) assay were performed to evaluate the value of IIF-SSS in the diagnosis of BP. Measurement data were compared by using t test and Mann-Whitney test, and enumeration data were compared by using chi-square test and Fisher′s exact test or McNemar test. Results:The number of cases positive for IIF-SSS, BP180 NC16A ELISA and DIF assay was 160, 153 and 127 respectively in the BP group, and 0, 18 and 26 respectively in the control group. The sensitivities of IIF-SSS, BP180 NC16A ELISA and DIF assay for the diagnosis of BP were 98.15%, 93.86% and 77.91% respectively, and their specificities were 100%, 95.54% and 93.56% respectively. There was strong consistency in the diagnosis of BP between IIF-SSS and DIF (Kappa coefficient= 0.767, P < 0.001) . Conclusion:IIF-SSS has relatively high sensitivity and specificity for the diagnosis of BP, and can serve as a routine method for diagnosing BP.
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Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.
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Objective:To analyze clinical and immunoserological features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid in Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to October 2021, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:Seven patients with anti-p200 pemphigoid were included. Indirect immunofluorescence on salt-split skin (IIF-SSS) showed that serum IgG antibodies of the 7 patients were located in the dermis of the salt-split skin, and Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 200 000. Four patients presented with classic bullous pemphigoid-like skin lesions, 2 initially presented with eczematous lesions, and 1 presented with linear IgA bullous dermatosis-like skin lesions. Circulating IgG antibodies could recognize the recombinant laminin γ1 C-terminal region in 6 cases. Four patients received different doses of systemic glucocorticoids, 1 of whom was resistant to high-dose systemic glucocorticoids (equivalent to 1.4 mg·kg -1·d -1 prednisone) ; 2 responded well to minocycline and dapsone; 1 was lost to follow-up. Four patients achieved complete remission and discontinued the treatment at a mean follow-up of 22.5 months; 2 received complete remissiona on minimal therapy at a mean follow-up of 8 months. Conclusion:Patients with anti-p200 pemphigoid presented with heterogeneous clinical manifestations, and the recombinant C-terminal fragment of laminin γ1 can serve as a reliable antigen substrate for the detection of autoantibodies in patients with anti-p200 pemphigoid; some patients can eventually achieve complete remission off treatment.
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Objective:To investigate the correlation of related antibody titers in serum of patients with pemphigus vulgaris (PV) with disease severity and activity.Methods:A total of 24 patients with active PV were collected, who firstly visited Hospital for Skin Diseases, Chinese Academy of Medical Sciences from 2012 to 2015. Pemphigus disease area index (PDAI) was evaluated in the patients with PV at active and stable stages, and serum samples were collected. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine titers of pathogenic anti-desmoglein (Dsg) conformational epitope antibodies, total anti-Dsg antibodies and anti-acetylcholine receptor (AChR) antibody in serum samples. Measurement data were compared by using t test, enumeration data were compared by using Fisher′s exact test, and correlations were analyzed by using Pearson correlation analysis. Results:Among the patients with active PV, there was no significant difference between the anti-Dsg1 antibody titers (611.4 ± 136.8) and anti-Dsg1 conformational epitope antibody titers (585.5 ± 134.7, t = 0.13, P = 0.89) , but the anti-Dsg3 antibody titers (708.6 ± 130.7) were significantly higher than the anti-Dsg3 conformational epitope antibody titers (297.2 ± 54.4, t = 2.90, P < 0.01) . In addition, both the anti-Dsg1 antibody titers and anti-Dsg1 conformational epitope antibody titers were positively correlated with PDAI scores in the patients with active PV (both r = 0.54, P < 0.01) ; PDAI scores were not correlated with the anti-Dsg3 antibody titers ( r = 0.11, P = 0.62) , but positively correlated with the anti-Dsg3 conformational epitope antibody titers ( r = 0.53, P < 0.01) . Among the 20 patients with stable PV, the serum titers of anti-Dsg1 antibodies and anti-Dsg1 conformational epitope antibodies significantly decreased compared with those at their first visit; anti-Dsg3 antibody titers significantly decreased in only 7 patients, and 13 patients still had high titers of anti-Dsg3 antibodies, including 6 with declined anti-Dsg3 conformational epitope antibody titers, and 5 converted from anti-AChR antibody-positive to anti-AChR antibody-negative. Conclusions:Both the anti-Dsg1 antibody and anti-Dsg1 conformational epitope antibody titers can reflect the disease activity of PV. The disease activity was not consistent with anti-Dsg3 antibody titers in some patients, and the anti-Dsg3 conformational epitope antibody or anti-AChR antibody may facilitate evaluating the disease activity of PV.
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Objective:To compare the effects of two different surgical methods (endovascular embolization and microsurgical craniotomy) on hemodynamics and quality of life in patients with anterior circulation aneurysms.Methods:From January 2014 to December 2018, 63 patients with anterior circulation aneurysms in Linfen Central Hospital were divided into group A (micro craniotomy) 30 cases and group B (intravascular embolization) 33 cases according to the different operation method.The changes of heart rate, systolic blood pressure, diastolic blood pressure, cardiac output, cardiac output per stroke and cardiac output index were compared between the two groups before operation (T0), during operation (T1), after operation (T2) and 24 hours after operation (T3). The quality of life of the patients was evaluated by the MOS 36-item short-form health status survey (SF-36) at the time of discharge from hospital, and the prognosis of the patients at three months after operation was evaluated by Glasgow outcome score (GOS). The quality of life and complications were evaluated by the ability of daily living and the modified Barthel index.Results:Compared with group A, group B showed a significant increase in cardiac output index[(2.86±0.63)L·min -1·(m 2) -1 vs.(3.39±0.83)L·min -1·(m 2) -1], a significant decrease in heart rate[(90±15)times/min vs.(79±9)times/min], systolic blood pressure[(132±18)mmHg vs.(123±9)mmHg], diastolic blood pressure[(96±13)mmHg vs.(89±12)mmHg] and cardiac output per stroke[(88.64±18.53)mL vs.(78.54±13.35)mL] at T1 ( t=2.50, 3.61, 2.89, 2.63, 3.02, all P< 0.05). Compared with group A, group B showed a significant decrease in heart rate[(86±12)times/min vs.(75±11)times/min], systolic blood pressure[(134±20)mmHg vs.(122±11)mmHg] and diastolic blood pressure[(93±11)mmHg vs.(77±14)mmHg] at T2, and a significant decrease in systolic blood pressure[(128±13)mmHg vs.(113±14)mmHg] and diastolic blood pressure[(85±9)mmHg vs.(78±13)mmHg] at T3 ( t=2.68, 3.14, 3.95, 4.15, 3.05, all P<0.05). The scores of energy[(55.07±8.76)points], physiological function[(53.65±8.62)points], physiological function[(62.25±9.53)points], mental health[(72.26±13.95)points], emotional function[(61.89±12.25)points] and overall health[(47.63±8.61)points] in SF-36 scale in group B were significantly higher than those in group A[(45.86±7.62)points, (49.21±9.76)points, (43.58±8.75)points, (50.14±10.33)points, (44.76±9.42)points, (35.86±7.60)points]( t=4.43, 2.35, 8.07, 7.09, 6.18, 5.73, all P< 0.05). There was no statistically significant difference in GOS score at three months after operation between the two groups ( P>0.05). After 2 years of follow-up, the scores of activities of daily living[(86.89±4.54)points] and modified Barthel index[(1.34±0.42)points] in group B were significantly lower than those in group A[(92.48±6.09)points, (2.79±0.61)points]( t=4.15, 11.07, all P<0.01). There was no statistically significant difference in the incidence of complications between the two groups ( P>0.05). Conclusion:For the patients with anterior circulation aneurysms, the therapeutic effect of microsurgical craniotomy and endovascular embolization is the same, but the latter can stabilize the hemodynamic state of the patients during the operation, and the short-term prognosis is better at discharge, but the long-term prognosis may be worse than that of microsurgical craniotomy.
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OBJECTIVE@#To investigate the inhibitory effect of Zhenwu Decoction on ventricular hypertrophy in rats with uremic cardiomyopathy and explore the mechanism.@*METHODS@#Cardiocytes isolated from suckling rats were divided into control group and indoxyl sulfate (IS) group, and the protein synthesis was assayed with [H]- leucine incorporation and cellular protein expressions were detected using Western blotting. Fifty SD rats were randomly divided into sham operation group, model group, and low- and high-dose Zhenwu Decoction treatment groups, and except for those in the sham operation group, all the rats underwent 5/6 nephrectomy. Four weeks after the operation, the rats in low- and high-dose treatment groups were given Zhenwu Decoction gavage at the dose of 4.5 g/kg and 13.5 g/kg, respectively; the rats in the sham-operated and model groups were given an equal volume of distilled water. After 4 weeks of treatment, serum levels of IS were determined, and cardiac and ventricular mass indexes were measured in the rats; cardiac ultrasound was performed and Western blotting was used to measure the expressions of BNP, p-ERK1/2, p-p38 and p-JNK in the myocardium.@*RESULTS@#Rat cardiomyocytes treated with IS showed significantly enhanced protein synthesis and increased expression levels of BNP, p-erk1/2, and p-p38 as compared with the control cells ( < 0.01), but the expression of p-jnk was comparable between the two groups. In the animal experiment, the rats in the model group showed significantly increased serum creatinine (SCr) and urea nitrogen (BUN) levels, 24-h urine protein (24 hUpro), plasma IS level, left ventricular mass index (LVMI) and whole heart mass index (HMI) compared with those in the sham group ( < 0.01); Both LVESD and LVEDD were significantly reduced and LVAWS, LVAWD, LVPWS and LVPWD were significantly increased in the model rat, which also presented with obvious cardiomyocyte hypertrophy and increased myocardial expressions of BNP, p-ERK1/2, p-p38 and p-jnk ( < 0.01). Compared with the rats in the model group, the rats treated with low-dose and high-dose Zhenwu Decoction had significantly lowered levels of SCr, BUN, 24 hUpro and IS ( < 0.05) and decreased LVMI and HMI; LVESD, LVEDD, LVPWS, LVAWS, and LVAWD were improved more obviously in the high-dose group, and the myocardial expressions of BNP, p-ERK1/2, p-p38 and p-JNK was significantly downregulated after the treatment.@*CONCLUSIONS@#Zhenwu Decoctin can reduce plasma IS levels and inhibit ventricular hypertrophy to delay ventricular remodeling in rats with uremic cardiomyopathy.
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Animals , Rats , Blood Urea Nitrogen , Cardiomegaly , Cardiomyopathies , Creatinine , Blood , Drugs, Chinese Herbal , Pharmacology , Heart Ventricles , Indican , Blood , Pharmacology , Myocytes, Cardiac , Metabolism , Nephrectomy , Random Allocation , Rats, Sprague-DawleyABSTRACT
Objective To evaluate the value of indirect immunofluorescence (IIF) on three different substrates including normal human skin (NS),monkey esophagus (ME) and salt-split human skin (SS) in the diagnosis of autoimmune subepidermal bullous diseases.Methods A total of 56 patients with autoimmune subepidermal bullous diseases,including 47 with bullous pemphigoid (BP),6 with epidermolysis bullosa acquisita (EBA),2 with linear IgA bullous dermatosis,and 1 with anti-P200 pemphigoid,were diagnosed in and enrolled from Department of Dermatology,Institute of Dermatology,Chinese Academy of Medical Sciences between January 2015 and December 2016.Seventy patients with pemphigus,15 patients with chronic eczema and 15 healthy adults served as controls.Blood samples collected from these patients and controls were subjected to IIF on three different substrates including NS,ME and SS,and the fluorescence deposition was observed.The sensitivities and specificities of IIF in the diagnosis of different subepidermal bullous diseases were compared.Statistical analysis was carried out with SPSS 13.0 software by using chi-square test for the comparison of enumeration data.Results IIF on NS or ME in the serum of patients with BP showed linear deposition of fluorescent material along the basement membrane zone.IIF on SS showed linear deposition of fluorescent material in the epidermis in the patients with BP,but in the dermis in the patients with EBA and anti-P200 pemphigoid.The sensitivities of IIF on NS,ME or SS in the diagnosis of subepidermal bullous diseases were 73.2％,60.7％ and 94.6％ respectively,and the specificities were 98.0％,100％ and 97.1％ respectively.There were significant differences among the sensitivities (x2 =18.2,P ＜ 0.05),but no significant difference was observed among the specificities (P ＞ 0.05).The diagnostic sensitivity of IIF on SS was significantly higher than that of IIF on NS or ME(x2 =8.0,16.7,both P ＜ 0.05).Conclusion In the diagnosis of autoimmune subepidermal bullous diseases,IIF on SS is superior to IIF on ME or NS.
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Objective To prepare human epidermal extracts by thermal separation,and to evaluate the value of epidermal extract-based Western blot analysis in the diagnosis of bullous pemphigoid (BP).Methods Human epidermal extracts were prepared by thermal separation from circumcised foreskins of healthy males.Serum samples were obtained from 22 inpatients with BP and 25 inpatients without BP in Hospital for Skin Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 and August 2017.These serum samples were subjected to Western blot analysis with epidermal extracts as substrates,as well as to BP180-NC16A enzyme-linked immunosorbent assay (ELISA).Statistical analysis was carried out using chi-square test and Fisher's exact test with the SPSS22.0 software.Results The sensitivities of epidermal extract-based Western blot analysis and BP 180-NC16A ELISA in the diagnosis of BP were 86.36％ (95 ％ CI:64.03％-96.41％) and 95.45％ (95％ CI:75.11％-99.76％) respectively (~ =1.10,P =0.294),and the specificities were 100％ (95％ CI:83.42％-100％) and 92％ (95％ CI:75.11％-99.76％) respectively (x2 =20.8,P =0.149).Epidermal extract-based Western blot analysis in the 22 patients with BP showed a protein band with relative molecular mass (RMM) of 230 000 in 4 patients,a protein band with RMM of 180 000 in 18,a protein band with RMM of 120 000 in 1,and a protein band with RMM of 97 000 in 1.The BP180-NC16A ELISA showed that the antibody titers were more than 50 U/ml in the BP patients with protein bands of RMM of 180 000.Conclusions The epidermal extract-based Western blot analysis mainly showed the protein band with RMM of 180 000 in the patients with BP.The sensitivity of the epidermal extract-based Western blot analysis was lower than that of the BP180-NC16A ELISA,and the epidermal extract-based Western blot analysis tends to be negative when the titer of the autoantibody is low.
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Objective To investigate associations of anti-desmoglein (Dsg1 and Dsg3) antibodies detected by enzyme-linked immunosorbent assay (ELISA) with clinical phenotypes and disease activity in pemphigus patients,and to explore their change patterns.Methods A total of 111 patients with pemphigus were enrolled from Hospital for Skin Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 and January 2018.ELISA was performed to detect serum levels of anti-Dsg1 and anti-Dsg3 antibodies in these patients with different clinical types of pemphigus at different stages,including onset stage,control stage (no new erythema or vesicles occurred in the last 2 or more weeks,and primary lesions began to regress),maintenance stage (the condition had been stable for ≥ 1 month,and treatment was maintained with a low dose of glucocorticoids [prednisone equivalent of ＜ 15 mg/d]),and recurrence stage,and the change patterns of serum levels of anti-Dsg1 and anti-Dsg3 antibodies were analyzed.Statistical analysis was carried out with SPSS 22 software by using oneway analysis of variance for the comparison among groups,and least significant difference (LSD)-t test for multiple comparisons.Results At the disease onset stage,control stage,maintenance stage and recurrence stage,92,53,33,and 9 patients respectively completed the detection.Among the 92 patients with initial onset of pemphigus,the positive rates of anti-Dsg1 and anti-Dsg3 antibodies were 100％ and 2.77％ respectively in 36 patients with pemphigus foliaceus,20％ and 80％ respectively in 10 with mucosaldominant pemphigus vulgaris,and 97.82％,95.65％ respectively in 46 with mucocutaneous pemphigus vulgaris.The serum levels of anti-Dsg1 antibodies in the patients with pemphigus foliaceus significantly differed among the disease onset stage,control stage,maintenance stage and recurrence stage (137.43 ±77.74,13.94 ± 14.81,21.50 ± 58.33,121.13 ± 86.89 U/ml,respectively),the serum levels of anti-Dsg3 antibodies in the patients with mucosal-dominant pemphigus vulgaris also significantly differed among the above clinical stages (125.61 ± 94.81,34.5 ± 16.26,0.6,258 U/ml,respectively),and the serum levels of anti-Dsg1 and anti-Dsg3 antibodies in patients with mucocutaneous pemphigus vulgaris both significantly differed among the above clinical stages(anti-Dsg1 antibody:115.39 ± 70.62,15.74 ± 25.10,3.62 ± 12.09,78.60 ± 92.25 U/ml,respectively;anti-Dsg3 antibody:137.98 ± 81.25,58.14 ± 63.46,29.26 ± 64.70,136.9 ± 101.47 U/ml,respectively).Additionally,the serum levels of anti-Dsg1 antibodies in the patients with pemphigus foliaceus,as well as the serum levels of anti-Dsg3 antibodies in the patients with mucosaldominant pemphigus vulgaris and those with mucocutaneous pemphigus vulgaris,were both significantly lower at the disease control stage and maintenance stage than at the disease onset stage and recurrence stage (all P ＜ 0.05).During the treatment,epitope spreading occurred in 2 patients,and high-titer anti-Dsg antibodies were observed in 4 patients at the stable stage.Conclusion Anti-Dsg antibody spectrum is associated with clinical phenotypes of pemphigus,and its serum levels measured by ELISA can be applied to disease activity monitoring and evaluation of therapeutic efficacy.
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Skin diseases manifesting as desquamative gingivitis (DG) can be divided into recurrent DG-and chronic DG-related skin diseases,including oral lichen planus,mucosal pemphigoid,pemphigus vulgaris and so on.A thorough medical history,detailed oral and histopathological examinations and serum immunological tests can be helpful for correct diagnosis of DG-related skin diseases.The treatment of DG-related skin diseases includes topical and systemic therapies.It is necessary to individualize treatment protocols due to treatment response.During the treatment of DG,oral hygiene should be strengthened,secondary fungal and bacterial infections should be avoided,and attention should be paid to the protection of oral cavity and periodontal tissues.
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Objective To evaluate the value of indirect immunofluorescence on salt-split skin (IIF-SSS) and bullous pemphigoid 180 N C 16a enzyme-linked immunosorbent assay (BP 180 N C 16a-ELISA) in the diagnosis of bullous pemphigoid (BP).Methods Serum samples were collected from 174 BP patients and 129 controls,who were enrolled from Institute of Dermatology of Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 and August 2017,and subjected to IIF-SSS and BP180 NC16a-ELISA.Direct immunofluorescence (DIF) test was performed in 25 cases of BP,and its sensitivity for the diagnosis of BP was compared with that of IIF-SSS and BP180 NC16a-ELISA.Results The sensitivities for IIF-SSS and BP180 NC16a-ELISA were 93.67％ and 96.55％ respectively,and the specificities for IIF-SSS and BP180 NC16a-ELISA were 100％ and 96.12％ respectively.IIF-SSS was weakly correlated with BP180 NC16a-ELISA with a correlation coefficient of 0.147.There was no significant difference in the sensitivity between the serological diagnostic methods (IIF-SSS and BP180 NC 16a-ELISA) and DIF.Conclusion Serological diagnostic methods show high specificity and sensitivity in the diagnosis of BP,and are worthy of clinical promotion and application.
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Objective To explore the effect of indoxyl sulfate (IS) on the differentiation, maturation and immunological function of human monocyte derived dendritic cells (mDCs), in order to provides evidence for mechanism of IS in atherosclerosis. Methods Human peripheral blood mononuclear cells isolated by double gradient centrifugation were cultured for immature mDCs by rhGM?CSF and rhIL?4 in vitro. All cases were randomly divided into PBS group, LPS group(1 μg/mL), IS.1 group(30 μmol/L), IS.2 group(300 μmol/L)and IS.3 group (600 μmol/L). The phenotypic maturation of mDCs was evaluated by flow cytometry (FCM) and functional maturation of mDCs was analyzed by measuring FITC?dextran uptake and ELISA. Results IS significantly upregulated the expression of CD80, CD83, CD86 and MHC II key membrane molecules on mDCs, while downregulating phagocytosis and increasing the secretion of IL?12p70 by mDCs (P<0.05). And the LPS and IS showed typical morphology with rough surface, long protrusions and fusiform. 300 μmol/L IS is the most appropriate stimulus concentration. Conclusion Stuctural, phenotypic and functional maturation of dendritic cells derived from human monocytes can be induced by indoxal sulphate at defined concentrations, which may be one of the mechanisms involved in the process of atherosclerosis.
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Objective To compare risk factors and bacterial etiology in patients with early-onset versus late-onset ventilator-associated pneumonia (VAP) in intensive care unit (ICU).Methods This prospective cohort study enrolled mechanically ventilated patients hospitalized for more than 48 hours in the first affiliated hospital,China Medical University from Jan 2012 to Jun 2016.Subjects were classified by ventilator status:early-onset VAP (＜ 5 d ventilation,E-VAP) or late-onset VAP (≥ 5 d ventilation,L-VAP).Potential risk factors and pathogen were evaluated.Results A total of 4 179 patients in adult ICU were screened,3 989 (95.5％) of whom were mechanically ventilated,962 patients with mechanical ventilation time ≥ 48 h.VAP developed in 142 patients.E-VAP and L-VAP had different potential risk factors based on statistical analysis.Independent risk factors for E-VAP included male (OR =1.825,95％ CI 1.006-3.310),chronic obstructive pulmonary disease (COPD;OR =3.746,95％ CI 1.795-7.818),emergency intubation (OR =1.932,95％ CI 1.139-3.276),aspiration (OR =3.324,95％ CI 1.359-8.130).Whereas independent risk factors for L-VAP were coma (OR =2.335,95％ CI 1.300-4.194),renal dysfunction (OR =0.524,95％ CI O.290-O.947),emergency intubation (OR =2.184,95％ CI 1.334-3.574).Mortality in E-VAP and L-VAP group were both higher than the non-VAP group[30.2％(19/63)vs 19.8％ (162/820),P=0.044;29.1％ (23/79) vs 19.8％(162/820),P=0.046].The pathogens isolated from early-onset versus late-onset VAP were not significantly different between groups,which the most common ones were acinetobacter baumannii,pseudomonas aeruginosa and klebsiella pneumoniae.Conclusion E-VAP and L-VAP have different risk factors,however related pathogens are similar.Different specific preventive strategies are suggested based on different onset of VAP.
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Objective To compare risk factors and bacterial etiology in patients with early-onset versus late-onset ventilator-associated pneumonia (VAP) in intensive care unit (ICU).Methods This prospective cohort study enrolled mechanically ventilated patients hospitalized for more than 48 hours in the first affiliated hospital,China Medical University from Jan 2012 to Jun 2016.Subjects were classified by ventilator status:early-onset VAP (＜ 5 d ventilation,E-VAP) or late-onset VAP (≥ 5 d ventilation,L-VAP).Potential risk factors and pathogen were evaluated.Results A total of 4 179 patients in adult ICU were screened,3 989 (95.5％) of whom were mechanically ventilated,962 patients with mechanical ventilation time ≥ 48 h.VAP developed in 142 patients.E-VAP and L-VAP had different potential risk factors based on statistical analysis.Independent risk factors for E-VAP included male (OR =1.825,95％ CI 1.006-3.310),chronic obstructive pulmonary disease (COPD;OR =3.746,95％ CI 1.795-7.818),emergency intubation (OR =1.932,95％ CI 1.139-3.276),aspiration (OR =3.324,95％ CI 1.359-8.130).Whereas independent risk factors for L-VAP were coma (OR =2.335,95％ CI 1.300-4.194),renal dysfunction (OR =0.524,95％ CI O.290-O.947),emergency intubation (OR =2.184,95％ CI 1.334-3.574).Mortality in E-VAP and L-VAP group were both higher than the non-VAP group[30.2％(19/63)vs 19.8％ (162/820),P=0.044;29.1％ (23/79) vs 19.8％(162/820),P=0.046].The pathogens isolated from early-onset versus late-onset VAP were not significantly different between groups,which the most common ones were acinetobacter baumannii,pseudomonas aeruginosa and klebsiella pneumoniae.Conclusion E-VAP and L-VAP have different risk factors,however related pathogens are similar.Different specific preventive strategies are suggested based on different onset of VAP.
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Objective:To investigate the role of CD46 and Nectin-4 on Measles virus (MV) infecting human pulmonary alveolar epithelial cells (HPAEpiC),and the interaction between CD46 and Nectin-4.Methods: Measles virus was divided into pre-infection group and 2 h-infection group,HPAEpiCs treatment with anti-CD46 antibody and/or anti-Nectin-4 antibody as experimental groups,and untreated HPAEpiCs as a control.The variation of viral replication level was detected.A Co-immunoprecipitation assay (Co-IP) was used to explore whether CD46 and Nectin-4 had interactive relationship in MV infection.Results: Compared with the control group,MV titers were reduced in HPAEpiCs of the pre-infection group treated with anti-CD46 and anti-Nectin-4 respectively (48.03% and 49.53%).Furthermore,virus titers showed a more reduction in which treated with anti-CD46 and anti-Nectin-4 antibodies (27.15%,P<0.01).Western blot and Real-time PCR showed that anti-CD46 antibody and anti-Nectin-4 antibodies decreased the rate of MV infection.In the 2 h-infection group,however,the treatment with anti-CD46 and anti-Nectin-4 could significantly reduce the MV titer and NP protein in HPAEpiCs.The Co-IP assay showed that there were interaction between CD46 and Nectin-4.Conclusion: CD46 and Nectin-4 mediated MV infecting HPAEpiCs.Moreover,CD46 and Nectin-4 may play a synergetic role in MV infection,which could enhance the infection effect.
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OBJECTIVE:To investigate the effects of tiotropium bromide assisted with bronchoalveolar lavage (BAL) on short-term efficacy,quality of life and re-hospitalization rate of patients with bronchiectasis complicated with lung infection. METH-ODS:A total of 140 patients with bronchiectasis complicated with lung infection selected from our hospital during Oct. 2013-Dec. 2015 were divided into control group and observation group by lottery,with 70 cases in each group. Based on intervention therapy, control group received BAL. Observation group was additionally given Tiotropium bromide powder inhalation 18 μg ,once a day before going to bed,on the basis of control group. Both groups were treated for 4 weeks. Clinical efficacy was compared between 2 group;pulmonary ventilation function indexes,blood gas analysis indexes,BODE index scores and QLI scores before and after treatment,re-hospitalization rate and the occurrence of ADR were also compared between 2 groups. RESULTS:The total response rate of observation group was 91.43%,which was significantly higher than that of control group(78.57%),with statistical signif-icance (P0.05). After treatment,FVC,FEV1,FEV1%,p(O2) and QLI score of 2 groups were increased significantly,while p(CO2)and BODE index scores were decreased significantly,com-pared to before treatment;all indexes of the observation group was significantly better than the control group,with statistical sig-nificance (P<0.05). The re-hospitalization rate of observation group 3,6 months after treatment was significantly lower thanthat of control group,with statistical significance(P<0.05). No ADR was found in 2 groups. CONCLUSIONS:For patients with bronchiectasis complicated with lung infection,tiotropium bromide assisted with BAL can effectively relieve the clinical symp-toms and signs,improve lung ventilation function and the quality of daily life and can be helpful to reduce the risk of re-hospital-ization with good safety.
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Objective To evaluate the reversal effect of a cholinergic receptor agonist on acantholysis in pemphigus,and to investigate its mechanism.Methods Human HaCaT keratinocytes were co-cultured with pemphigus vulgaris immunoglobulin G (PV-IgG) to establish a cell model of pemphigus,then classified into two groups to be incubated with the cholinergic receptor agonist carbachol for 12 hours (test group) or remain untreated (control group).Cell dissociation assay was performed to quantitatively estimate the reversal effect of carbachol on acantholysis,and immunofluorescence assay to qualitatively assess the changes of desmosomal proteins.Radio-immunoprecipitation assay (RIPA) lysis buffer and Triton X-100 were used to lyse HaCaT cells to obtain total proteins and cytoplasmic proteins,and Western blot was conducted to determine the expression levels of adhesion-related proteins desmoglein 3 (Dsg3) and plakoglobin (PG) on the surface of HaCaT cells,as well as the phosphorylation levels of p38 mitogen activated protein kinase (p38 MAPK) and epidermal growth factor receptor (EGFR) at different time points.Quantitative polymerase chain reaction (qPCR) was performed to detect the mRNA expressions of the above surface proteins,and coimmunoprecipitation assay to qualitatively evaluate the interaction between Dsg3 and PG.Results The number of cell debris was significantly lower in the test group than in the control group (18.67 ± 2.52 vs.46.67 ± 2.03,t =11.22,P＜0.01).Immunofluorescence assay showed that carbachol could reverse the internalization of desmosomal molecules induced by PV-IgG.In the pemphigus cell model,the levels of total Dsg3 and PG as well as non-desmosomal Dsg3 were decreased,while the level of non-desmosomal PG increased,and the interaction between Dsg3 and PG was attenuated.When the pemphigus cell model was co-cultured with carbachol,these above changes were reversed.Carbachol also increased the mRNA levels (expressed as 2-△△Ct) of Dsg3 and PG from 1.428 ± 0.215 and 1.563 ± 0.247 in the control group to 4.974 ± 0.948 (t =3.65,P =0.01) and 13.420 ± 1.715 (t =6.85,P ＜ 0.01) in the test group respectively.In phosphorylation assay,carbachol inhibited the phosphorylation of EGFR,but had no significant effect on that of p38 MAPK.Conclusions The cholinergic receptor agonist carbachol can reverse acantholysis in pemphigus,likely by inhibiting the internalization of Dsg3 and PG,enhancing their expressions and interaction,and suppressing the phosphorylation of the key signaling molecule for acantholysis,EGFR.
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Objective To analyze the mechanism of interaction between cardiac and renal failure and observe the protective effects of Zhenwu decoction on cardio-renal syndrome rats. Methods The rats were divided into five groups: Sham group, MI (myocardial infarction) group, MI merger STNx group, MI intervention group, MI merger STNx intervention group. The first three groups were fed with saline (NS) for two weeks after surgery. The latter two groups of rats were fed with an equal volume of Zhenwu decoction. The cardiac function of rats in each group were evaluated , including the mass of heart , left ventricle and left kidney weights as a ratio of body weight, fractional shortening and left ventricular ejection fraction. And serum levels of indoxyl sulfate and serum creatinine were also achieved. Results MI merger STNx could further aggravate the heart function, kidney function and left ventricular remodeling in rats. Zhenwu decoction could obviously improve the heart function, kidney function and left ventricular remodeling in rats. Conclusions Based on the MI models, STNx can worsen heart function and kidney function. Zhenwu decoction can significantly improve heart function and kidney function.
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Objective To assess whether mTOR was activated in peripheral T lymphocytes of acute coronary syndrome (ACS)patients and to investigate the relationship among mTOR,regulatory T cells and cytokins. Methods Patients with acute coronary syndrome (n=32) were selected in ACS group. Meanwhile, patients who complainted of chest pain but were proven to be normal in ECG and in coronary arteriography, were excluded as ACS patients but were diagnosed as Chest Pain Syndrome (CPS) and selected in CPS group (n=28). The expression levels of mTOR, phospho-p70S6KT389 (indicative of mTORC1 activity) and phospho-AKTS473(indicative of mTORC2 activity) were investigated in T cells, which were isolated from peripheral blood of patients in ACS group or CPS group, using Western blot. The proportion of CD4+CD25+Foxp3+Tregs over CD4+cells were evaluated by FACS. And T cell subset related cytokines such as IFN-γ, IL-4, IL-17 and TGF-β1 were exam?ined by ELISA. Then we investigated the relationship among mTOR,regulatory T cells and cytokins by Spearman analysis. Results mTOR and p-p70S6KT389 expression were significantly enhanced in ACS group as compared with those in patients from CPS group (P0.05). By correlation analysis, p-p70S6KT389 expression level positively correlated with IFN-γ, IL-17(rs=0.91,092,P<0.01)and negatively correlated with Tregs and TGF-β1(rs=-0.85,-0.80, re?spectively, P<0.01). Conclusion mTORC1 pathway was activated in peripheral T lymphocytes of ACS patients, and Tregs insufficiency and cytokins imbalance both contribute to the activation of mTORC1 pathway and pathological process of ACS.
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Objective To investigate the peripheral blood neutrophil to lymphocyte ratio(NLR) for the early diagnosis of acute coronary syndrome(ACS) .Methods A total of 247 patients with suspected ACS and chest pain ,including 51 cases with acute ST segment elevation myocardial infarction(STEMI) ,42 cases with acute non‐ST segment elevation myocardial infarction(NSTEMI) , 87 cases with unstable angina pectoris(UA) and 67 cases with non‐cardiogenic chest pain(NCCP)were enrolled and detected for white blood cells count and classification .The sensitivity ,specificity ,positive predictive value ,negative predictive value ,receiver op‐erating characteristic(ROC) curve of NLR were analyzed .Results Among all patients ,the most common was UA ,followed by NC‐CP ,STEMI and NSTEMI .Level of neutrophil proportion and white blood cell count were lowest in NCCP group ,followed by UA , NSTEMI and STEMI group ,but lymphocyte proportion was with the opposite change tendency .Diagnostic sensitivity ,specificity , accuracy ,positive predictive value and negative predictive value of NLR for ACS were higher than white blood cell count .Conclusion NLR was with various advantages for the early diagnosis ,prognosis evaluation and state of ACS .