2010年 · 第123卷第05期

Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies with unknown etiology.The incidence of both diseases is estimated at 4 to 10 cases per million people per year~1.Classical DM patients display characteristic cutaneous manifestations,proximal muscle weakness,and laboratorial evidence of myositis.Skin manifestations include the classic periorbital heliotrope,cutaneous Gottron's papules and signs,and violaceous erythema of the upper trunk and extremities.Muscle involvement may be revealed by elevated muscle-derived enzymes such as creatine kinase (CK),lactate dehydrogenase (LDH),aldolase,alanine aminotransferase (ALT) or aspartate transaminase (AST).Additional testing,including electromyography (EMG),magnetic resonance imaging (MRI),or even muscle biopsies,may be performed if other tests are inconclusive~2。

Abstract：Background Interstitial lung disease (ILD) is a serious lung complication in polymyositis (PM) and dermatomyositis (DM) which affects prognosis and requires a more aggressive approach in therapy. This study investigated the prevalence, characteristics, predictive factors and unfavourable prognostic factors of ILD in newly diagnosed PM, DM and amyopathic DM (ADM). Methods From January 2000 to December 2008, the medical records of 197 consecutive PM and DM patients at the Second Affiliated Hospital of Sun Yat-Sen University were reviewed excluding overlapping, juvenile, and malignancy-associated cases. The patients were assigned to an ILD (69 patients) and a non-ILD group (128 patients). The clinical features, laboratory findings, and prognosis were compared. Results The multivariate analysis indicated that older age at onset (OR 1.033, 95%CI 1.009-1.058, P=0.007), fever (OR 4.109, 95%CI 1.926-8.767, P<0.001) and arthritis/arthralgia (OR 2.274, 95%CI 1.101-4.695, P=0.026) were the independent predictive factors for developing ILD in PM/DM after excluding anti-Jo-1. Regarding anti-Jo-1, fever (OR 4.912, 95%CI 2.121-11.376, P<0.001) was associated with ILD. Poor survival in ILD patients was associated with ILD clinical subset (RR 0.122, 95%CI 0.049-0.399, P<0.001), ADM/DM/PM-ILD (RR 0.140, 95%CI 0.031-0.476, P=0.002), cardiac involvement (RR 4.654, 95%CI 1.391-15.577, P=0.013) and serum albumin level (RR 0.910, 95%CI 0.831-0.997, P=0.042). Conclusions Patients who presented with fever tended to have a higher frequency of PM/DM-associated ILD. A Hamman-Rich-like presentation, ADM-ILD, cardiac involvement and hypoalbuminemia were poor prognostic factors in ILD-PM/DM.

Abstract：Background Involvement of peripheral nerves in dermatomyositis (DM) and polymyositis (PM) is less well known. In the present study we retrospectively analyzed the clinical and electrophysiological records of hospital inpatients with a diagnosis of DM or PM to investigate the association of DM/PM and peripheral neuropathy. Methods The data of inpatients diagnosed with DM or PM were collected in Peking Union Medical College Hospital, and 186 patients (118 patients with DM and 68 with PM) were retrospectively analyzed. Nerve conduction studies (NCSs) of the median nerve, ulnar nerve, posterior tibial nerve, and common peroneal nerve were examined simultaneously. Results There were 71 (38.2%) patients with abnormal NCS findings, 37 (19.9%) with pure motor involvement (decreased compound muscle action potential, CMAP), and 34 (18.3%) with peripheral neuropathy. Of the 34 peripheral neuropathy patients, 14 (7.5%) had polyneuropathy, 1 (0.5%) had multiple mononeuropathy, 16 (8.6%) had carpal tunnel syndrome (CTS), 1 (0.5%) had trigeminal sensory neuropathy, 1 (0.5%) had ulnar sensory neuropathy, and 1 (0.5%) had brachial plexus involvement. The prevalence of malignant disease (3/34, 8.8%), other connective tissue diseases (CTDs) (7/34, 20.6%) and diabetes (6/34, 17.6%) was significantly greater in DM/PM patients with peripheral neuropathy (X~2=15.855, ft0.0OO) compared with DM/PM patients without involvement of peripheral nerves (5/115, 4.3% and 7/115, 6.1%, respectively). Conclusions Peripheral neuropathy in DM/PM often suggests a complication with cancer, other CTDs, diabetes or CTS. From a practical point of view, NCS for DM/PM may help find the underlying disorders。

Abstract：Background Cathepsin B plays an important role in cell cycle, extracellular matrix changes and cutaneous tumorigenesis: whether it plays a role in photoaged skin remains unknown. This study aimed to investigate the role of cathepsin B in skin photoaging in vivo and in vitro. Methods The expressions of cathepsin B were compared with immunohistochemical methods in solar exposed skin and solar protected skin of six healthy Chinese volunteers. The mRNA and protein expression of cathepsin B in ultraviolet light A (UVA) induced premature senescence fibroblasts in vitro were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting technique. Results Decreased expression of cathepsin B was observed in photoaged skin compared with that of the solar protected skin. In the UVA induced, premature senescence fibroblasts, a lower expression of cathepsin B was detected by Western blotting and a decreased synthesis of cathepsin B mRNA in the same cells was revealed by real-time RT-PCR. Conclusions The results demonstrated a significant negative correlation between skin photoaging and cathepsin B in vitro and in vivo. We propose that cathepsin B, besides matrix metalloproteinases and antioxidant enzymes, is involved in the process of skin photoaging in that it contributes to extracellular matrix remodelling and is a dominant protease in cellular apoptosis and senescence.

Abstract：Background Oxidative stress plays an important role in the pathogenesis of epidermal diseases. This study aimed to investigate the effects of quercetin on the anti-oxidative response and on mitochondrial protection in cultured normal human keratinocytes. Methods Cultured HaCaT cells were treated with different concentrations of H_2O_2 (0, 50, 100, 250, 500 μmol/L) for different periods of time (0.5, 1,2,4 hours) to establish an oxidative stress model. The cultured HaCaT cells were randomly assigned to control, H_2O_2, and quercetin+H_2O_2 groups. For the quercetin groups, the cells were treated with different concentrations of quercetin (0,10, 25, 50 μmol/L) before exposure to H_2O_2. Morphological changes of the cells were observed under an inverted microscope and an electron microscope. The cell viability was detected by the MTT method. The cell apoptosis (AnnexinV/propidium iodide double stain) and mitochondrial membrane potential (△ψm) changes were detected by flow cytometry. Results An oxidative stress model of HaCaT cells was established under a suitable concentration (250 μmol/L) and treated time of H_2O_2 (2 hours). The cell viability and △ψm decreased in a concentration-dependent and time-dependent manner while the percentage of apoptotic cells significantly increased in the H_2O_2 groups compared with the control group (P<0.05). The cell viability and △ψm of the quercetin treated group increased (P<0.05) and the percentage of apoptotic cells decreased at concentrations of 1-50 μmol/L quercetin (P<0.01) compared with H_2O_2 treated group. Conclusion Quercetin can relieve the cell damage and apoptosis from H_2O_2 induced injury to HaCaT cells by anti-oxidation and mitochondrial protection.

Abstract：Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation at the synovial membrane. Although great progress has been made recently in exploring the etiology and pathogenesis of RA, its molecular pathological mechanism remains to be further defined and it is still a great challenge in determining the diagnosis and in choosing the appropriate therapy in early patients. This study was performed to screen candidate RA-associated serum proteins by comparative proteomics to provide research clues to early diagnosis and treatment of RA. Methods Sera isolated from 6 RA patients and 6 healthy volunteers were pooled respectively and high-abundance proteins were depleted by Plasma 7 Multiple Affinity Removal System. The protein expression profiles between the two groups were then compared by two-dimensional gel electrophoresis (2-DE) and the proteins over/under-expressed by more than 3-fold were identified by mass spectrometry analysis. To validate the differential expression levels of the identified proteins between the two groups, ELISA was performed in two of the identified proteins in individual sera from 32 RA patients and 32 volunteers. Results Eight proteins which over/under-expressed in sera of RA patients were identified. Among them, chain A of transthyretin (TTR) was under-expressed, while serum amyloid A protein, apolipoprotein A (ApoA)-IV, ApoA-IV precursor, haptoglobin 2, ceruloplasmin (Cp), immunoglobulin superfamily 22 and HT016 were over-expressed. ELISA test confirmed that Cp expressed remarkably higher while TTR obviously lower in RA group compared with volunteer group. Conclusion There were 8 identified proteins differentially expressed between RA group and volunteer group, which might be candidate RA-associated proteins and might be promising diagnostic indicators or therapeutic targets for RA.

Abstract：Background The cytochrome P450 lanosterol 14α-demethylase(Erg11p) encoded by ERG11 gene is the primary target for azole antifungals.Changes in azole affinity of this enzyme caused by amino acid substitutions have been reported as a mechanism of azole antifungal resistance. This study aimed to investigate the relationship between amino acid substitutions in Erg11p from fluconazole resistant Candida albicans (C.albicans)isolates and their cross-resistance to azoles.Methods Mutations in ERG11 gene were screened in 10 clinical isolates of fluconazole resistant C.albicans strains.DNA sequence of ERG11 was determined by PCR based DNA sequencing.Results In the 10 isolates,19 types of amino acid substitutions were found,of which 10 substitutions (F72S, F103L, F145I, F198L, G206D, G227D, N349S, F416S, F422L and T482A) have not been reported previously. Mutations in ERG11 gene were detected in 9 isolates of fluconazole resistant C. albicans, but were not detected in 1 isolate. Conclusions Although no definite correlation was found between the type of amino acid substitutions in Erg11p and the phenotype of cross-resistance to azoles, the substitutions F72S, F145I and G227D in our study may be highly associated with resistance to azoles because of their special location in Erg11p.

Abstract：Background Monochorionic multiple pregnancies (MMPs) are associated with higher rates of perinatal morbidity and mortality caused by interfetal vascular anastomoses in the monochorionic placenta, which can lead to fetal health interactions. In some circumstances, selective feticide of the affected fetus is necessary to save the healthy co-twin. We evaluated the effects and safety of our initial experiences using bipolar cord coagulation for the management of complicated MMPs. Methods Using ultrasound-guided bipolar cord coagulation, we performed selective feticide on 14 complicated MMPs (5 with twin-twin transfusion syndrome, 4 with acardia, 3 with discordant structural anomalies, and 2 with severe selective intrauterine growth restriction). One patient with monochorionic triplets received the procedure twice to terminate 2 affected fetuses for different indications. Data regarding the operations, complications and neonatal outcomes were analyzed. Results Cord occlusions were successfully performed in 13/14 (93%) cases. The failure happened in an acardiac fetus and the pregnancy was terminated by induction. The included cases delivered at a mean gestational age of 35.4 weeks with a perinatal survival rate of 11/13 (85%). Three operation-related complications occurred (21%), including membrane rupture of the terminated sac (1 case), preterm labor at 28 weeks gestation (1 case), and chorioamniotic membrane separation (1 case). Amnioinfusion was indicated in 11 procedures to expand the target sacs for entering the trocar and obtaining sufficient working space. However, in all 4 cases of acardia, the acardiac sacs showed extreme oligohydramnios and could not be well expanded by infusion; thus, the trocar had to be inserted from the sac of the preserved co-twin. Conclusions The application of bipolar cord coagulation in complicated MMPs is safe and improves the prognosis. Amnioinfusion is useful in helping to expand the target sac when the working space is limited.

Abstract：Background Adjuvant chemotherapy has become an important component of standard therapy for breast cancer. However, until now, there have been few reports on the surgical site infections (SSI) after breast cancer surgery, specially after adjuvent chemotherapy. To study the risk factors of SSI of breast cancer, we analyzed patients diagnosed with breast cancer and treated with surgery. Methods Fifty-five patients diagnosed with breast cancer and received breast conserving or modified radical operations in our hospital during January 2008 to March 2008 were selected. Factors (patients' age, body mass index (BMI), diabetes mellitus, no or administered adjuvant chemotherapy, with or without onset of myelosuppression and the degree, surgical approaches, duration of operation, postoperative drainage duration and total drainage volume) associated with SSI were retrospectively reviewed and statistically analyzed by single factor analysis. Results Five patients suffered SSI (5/55, 9.1%); nineteen receiving adjuvant chemotherapy experienced Grade III+ myelosuppression, among which 4 had SSI; only 1 out of the remaining 36 patients without adjuvant chemotherapy had SSI. The difference between the two groups was significant (P=0.043). The incidence of SSI in patients with postoperative drainage tube indwelling longer than 10 days was 5/21, whereas no SSI occurred in that less than 10 days (R=0.009). in our study, there was no significient difference in other associated factors. Conclusions Concurrent Grade III+ myelosuppression after adjuvant chemotherapy is an important risk factor of SSI in breast cancer and needs further study. No SSI was detected with indwelling time of post operative drainage less than 10 days.

Abstract：Background Nosocomial infection in early post-transplantation period is a tough problem for kidney transplantation. Few reports have explored the relations between biochemical parameters and nosocomial infection in kidney transplantation. This retrospective study was carried out to describe the characteristics of nosocomial infection in the very early period of kidney transplantation and to determine the risk factors in biochemical parameters and their alterations. Methods Patients who underwent their first kidney transplantation from January 2001 to March 2009 in Beijing Chao-Yang Hospital were recruited and the nosocomial infectious episodes were collected for this study. Gender, age, donor type, delayed graft function (DGF) and biochemical parameters such as serum uric acid, lipids files and albumin on day 0 (before transplantation) and day 1 (24 hours after transplantation) and their changes were analyzed with Logistic regression models for nosocomial infection. Results A total of 405 patients (315 men and 90 women) were involved in this study. There were 80 patients experiencing 113 infection episodes and 105 strains of microorganism were indentified. In univariate analysis, there were significant differences in DGF, albumin on day 0, lipoprotein (a) (Lp(a)) on day 1, change in low density lipoprotein-cholesterol (LDL-C, day 1-day 0) and change in uric acid (day 1-day 0) between nosocomial infection patients and noninfectious patients (P<0.05). In multivariate analysis, change in uric acid (day 1-day 0) (Off 5.139, 95% Cl 1.176-22.465, P<0.05), change in LDL-C (day 1-day 0) {OR4.179, 95% Cl 1.375-12.703, P<0.05) and DGF (Of? 14.409, 95% Cl 1.603-129.522, P<0.05) were identified as independent risk factors for nosocomial infection in kidney transplantation. Conclusions Most nosocomial infections in early postoperative period of kidney transplantation are bacterial, especially with Gram-negative bacteria. The most common infection sites are respiratory tract, urinary tract and surgical site. DGF, decrease of LDL-C and increase of uric acid could increase the risk for nosocomial infections.

Abstract：Background Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome which is caused by germline mutations of the tumor suppressor gene MEN1. This study aimed to identify mutations in a Chinese pedigree withMEN1. Methods A large Chinese family with MEN1 was collected. All of the coded regions and their adjacent sequences of the MEN1 gene were amplified and sequenced. Results In this family, a heterozygous cytosine insertion in exon 10 (c.1546_1547insC) inducing a frame shift mutation of MEN1 was found in the proband and the other two suffering members of his family. This mutation was linked to a novel single nucleotide polymorphism (SNP) in intron 3 (IVS3+18C>T). Conclusions The mutation in exon 10 of MEN1 gene might induce development of parathyroid hyperplasia and pituitary adenoma and cosegregate with MEN1 syndrome. The significance of the new found IVS3+18C>T of MEN1 needs a further investigation.

Abstract：Background The second-trimester maternal serum screening in twin pregnancy is still controversial, as the serum marker levels in twins are not as clear as those in singletons. This study aimed to evaluate the relationship between the levels of the second-trimester maternal serum free p-human chorionic gonadotropin (free β-HCG) and a-fetoprotein (AFP) in normal twin and singleton pregnancies and to estimate feasible analysis methods for utilizing these markers in second trimester screening for twin pregnancy. Methods On the basis of a prospective population-based study of second-trimester maternal serum screening, the concentrations of maternal serum AFP and free β-HCG of 195 normal twin pregnancy and 26 512 singleton controls at gestational weeks 15 to 20 were measured by time-resolved fluoroimmunoassay in one laboratory. The levels of markers were compared between the twins and singletons using weight-correction and gestational age-specific model. Results According to the research protocol, 95 communities were randomly sampled, which covered the whole Jiangsu province, the east of China. A total of 26 803 pregnant women (98%), from the target population accepted prenatal screening for maternal serum AFP, β-HCG detection, and all babies were followed up for at least six months. There were 197 (0.73%) twin pregnancies, of which one case had fetal trisomy 18, and one case with fetal anencephaly. The others were normal twin pregnancy. From a total enrollment of 26 803 women participants, 26 512 women with normal singleton pregnancies were selected as the model controls. The other 291 pregnancies, including trisomy 21, neural tube defect (NTD), trisomy 18, and other fetal abnormalities, were excluded. No significant differences were found in the medians of gestational age-specific maternal serum free β-hCG and AFP in normal twin pregnancy comparing with twice those in model controls with the exception of the medians for free β-hCG during the 16th gestational week (P=0.012). Conclusion The weight-correction and gestational age-specific levels of Chinese Han population maternal serum free P-hCG and AFP in normal twins were twice the levels as those in the singleton controls during the 17-19 gestational weeks.

Abstract：Background The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 5.1) to (32.3 5.6) ml, P <0.05) and end-systolic volume (from (8.3 3.2) to (15.2 4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 13.3)% to (50.2 11.9)%, P<0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P<0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P<0.05). Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

The prevalence rate of acne in China is continuously increasing in adolescents,young and middle-aged adults.In many cases,those who have refractory inflammatory papules and pustules on the face and mandibular have received long-term antibiotic therapy.Some severe cases have had isotretinoin treatment and even corticosteroid application by either topical or oral administration.The curative effect has not been prominent in these cases,even with combined treatment including antimicrobials and/or isotretinoin and Chinese patent medicines.Papules and pustules even increase and recur during the course of treatment.The phenomena aroused our interest in the possibility of a mixed Malassezia infection.We chose those patients who had had a limited response to traditional acne therapies and recent exacerbation of their symptoms to examine the incidence of Malassezia furfur (M.furfur) in pustules using the potassium hydroxide (KOH) examination technique.However,the results were inconclusive because very few clusters of spores were observed.In order to evaluate an antifungal therapeutic treatment,we administrated the treatment to the patients who accepted it that was approved by the Ethical Committee of Second Hospital of Xi'an Jiaotong University and the patients signed informed consent.Excitingly,acne responded well after discontinuation of antibiotics and combined application of topical and oral antifungal treatments.For example,by oral administration of itraconazole and topical application of naftifine and ketoconazole cream for 2-4 weeks,pustules were significantly decreased,and even disappeared in some cases。

Muscle involvement in adults with hypothyroidism is common.At least 79% of patients with hypothyroidism have muscle weakness,cramps,and myalgia complaints~1.The patients with hypothyroidism do have myopathy rather than functional muscle diseases~2.Nonspecific muscle stiffness related to myalgia may be associated with serum muscle enzyme elevations.Serum creatine kinase (CK) elevation can be observed in 57%-90% of patients with hypothyroidism.Skeletal muscle is affected more profoundly in cases of overt hypothyroidism,less so when subclinical hypothyroidism is present~1.However,clinical muscular symptoms are not usually the chief complaint at presentation.More than 40% of patients with hypothyroidism also had neuromuscular complaints at the time of diagnosis~2。

Prurigo gestationis is not an uncommon disease in pregnancy．It has an estimated prevalence of 1 in 300 pregnancies~1.Prurigo gestationis is characterized by small,eryrthematous or skin-colored papules that are extremely prufitic．It has usually been considered as a benign disorder that influences neither the pregnancy nor the newborn child,and recurrence in subsequent pregnancies is a rare occurrence~2．