Objective To optimize the pre-treatment method before detecting Helicobacter pylori ( H.pylori ) by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry ( MALDI-TOF MS) and evaluate the ability of the Superspectra by MALDI-TOF MS for identifying clinical isolated H.pylori strains.Methods H.pylori were isolated from 469 biopsy samples of gastric mucosa collected from January 2015 to July 2016 in Huadong Hospital affiliated to Fudan University , 16 s rRNA sequencing were then performed to validate the strains.Then 91 isolated H.pylori strains were used for the subsequent MALDI-TOF analysis.The effect of pre-treatment of 50%isopropanol, formic acid and acetonitrile (1∶1), 70%formic acid were compared before H.pylori detecting by MALDI-TOF MS.40 out of 91 clinical H.pylori strains were detected by MALDI-TOF MS and the spectra were randomly assigned to 4 groups including 5, 10, 20, 30 spectra, each group had 3 repeats.Then 4 groups with different amount of spectra were used for creating Superspectra with SARAMIS Premium software , respectively.The remaining 51 H.pylori strains including 306 spectra were used for validating the identification rate of the Superspectra.Results With the use of 70%formic acid, the greater number of ion signals and higher relative intensity of the main peaks were observed than other pre-treatment reagents.The identification rate of Superspectra created by 30 strains group was the highest ( 90.2%).Among the 306 spectra, 46.1% of them achieved highly reliable identification , 22.2% achieved lower degree of reliable identification , and 31.7% of them achieved “no identification”.Conclusions The study optimized the pre-treatment method before H.pylori detecting by MALDI-TOF MS.The Superspectra was created with the good ability to rapidly identify clinical isolated H.pylori strains.

Objective To analyze clinical and pathological features of dermatomyositis with panniculitis as a skin manifestation.Methods Clinical data were collected from 9 cases of dermatomyositis with panniculitis as a skin manifestation in Department of Dermatology of Zhongshan Hospital affiliated to Fudan University from October 2012 to July 2016,and their clinical and pathological features were analyzed.Results Of the 9 cases,6 were female and 3 were male,and the age ranged from 28 to 73 years.Panniculitis lesions of the 9 patients all manifested as painful indurated plaques or nodules on the buttock,thigh,waist,back,abdomen,upper extremities and cheeks.These lesions occurred before,after or simultaneously with the onset of characteristic skin and muscle lesions of dermatomyositis,especially preceded the onset of characteristic lesions of dermatomyositis by 30 years in 1 case.Histopathological examination of lesions showed liquefaction degeneration of basal cells,inflammatory infiltration of lymphocytes and plasma cells around blood vessels,in the fat lobules as well as between the lobules and septa in the dermis.The necrosis and calcification of lipocytes,lipomembranous changes,fibrinoid necrosis of damaged vessel walls and microvascular occlusion were observed in some cases.Because panniculitis preceded the onset of characteristic lesions of dermatomyositis,2 patients were misdiagnosed with lupus panniculitis and morphea profunda for several times.Most patients had good response to systemic glucocorticoids combined with immunosuppressive agents,while the patients with lipomembranous fat necrosis had poor response to the combination therapy.Conclusions Panniculitis lesions of dermatomyositis are histologically characteristic,and may do not coincide with the onset of characteristic lesions of dermatomyositis.If panniculitis lesions precede characteristic lesions of dermatomyositis,patients will be easily misdiagnosed.Thus,persistent follow-up visit will be of great importance for the diagnosis.

Objective To firstly report 4 cases of dermatomyositis characterized by painful palmar eruptions complicated by fatal rapidly progressive interstitial lung disease (RP-ILD) in China.Methods Four patients with dermatomyositis with painful palmar eruptions complicated by fatal RP-ILD were enrolled from the Department of Dermatology,Zhongshan Hospital,Fudan University between December 2014 and April 2017,and their clinical and pathological features were analyzed.Results Among these patients,3 were female and 1 was male.Their age ranged from 47 to 59 years.Of the 4 patients,3 had no muscular involvement.All of the 4 patients had multiple solid red papules or nodules on the bilateral palms,palmar and lateral surfaces of fingers,which preceded,followed or concurred with the onset of other skin lesions of dermatomyositis.The occurrence of type Ⅰ respiratory failure was preceded by 3 weeks to 5 months of painful palmar eruptions in the 4 patients.Early-stage palmar eruptions were easily misdiagnosed as contact dermatitis,eczema or erythema multiforme.Histopathological examination of the skin lesions on the finger palmar surface showed perivascular infiltration of a few lymphocytes in the dermis,and deposition of varying amounts of mucin-like substances around blood vessels and appendages.Of the 4 patients,3 showed positive staining for anti-melanoma differentiation-associated gene 5 antibody.Although the 4 patients received anti-inflammatory and immunosuppressive therapies,they all finally died of respiratory failure.Conclusions Dermatomyositis with painful palmar eruptions may indicate the occurrence of fatal RP-ILD,and early biopsy of skin lesions is needed to help to identify the disease.Immunosuppressive treatment should be performed timely to improve the prognosis in these patients.

Objective To evaluate the clinical effect of direct identification of microorganisms from the midstream urine by MALDI-TOF MS combined with separation gel tube and differential centrifugation. Methods A total of 2150 samples of midstream urine were collected from the outpatient and inpatients in Huadong Hospital affiliated to Fudan University from May 2017 to April 2018, including 934 males and 1216 females with an age of (72.0 ± 17.5) years. After preliminary quantification by microscopic examination, samples with a bacterial acount of ≥ 105cfu/ml were treated with two kinds of pretreatment methods to enrich the bacteria for directly identification by MS. Based on the results of quantitative urine culture and MS identification,the coincidence rates of two kinds of pretreatment methods combined with MS were analyzed. All statistical analyses were performed using Stata/SE 14.0, differences between the groups were compared by Pearson Chi-square tests. Results 464 out of 2150 midstream urine samples (21.6％) had a bacterial count ≥ 105cfu/ml after microscopic examination. In traditional culture combined with MALDI-TOF MS, 436(94.0％)cases were single species, 28(6.0％)cases were double species. Among single species of bacteria samples infection, the gram-negative bacteria accounted for 78.9％(344/436),the Gram-positive bacteria accounted for 15.8％(69/436),and the fungus accounted for 5.3％(23/436). In two methods that the separation gel tube combined MALDI-TOF MS and the differential centrifugation combined MALDI-TOF MS, the gram-negative bacteria coincidence rates were 92.4％(318/344)and 89.0％(306/344) respectively, the Gram-positive bacteria coincidence rates were 68.1％(47/69)and 62.3％(43/69) respectively,and the fungi coincidence rates were 56.5％(13/23) and 34.8％(8/23)respectively. Meanwhile,the double bacteria infection coincidence rates were 64.3％(18/28)and 60.7％(17/28). Conclusions The separation gel tube combined MALDI-TOF MS and the differential centrifugation combined MALDI-TOF MS identify directly the gram-negative bacteria in the midstream urine samples with high detection rate and accuracy,and they are rapid and simple pretreatment method,suitable for rapid screening of midstream urine.

Objective To explore the CTV to PTV external expansion boundary and the effect of the dose of normal lung tissue under different fixed modes by a comparative analysis of combined body position and thermoplastic film fixed set-up error of radiation therapy for lung cancer. Methods From October 2016 to March 2018, the patients who received chest radiology at the Tangshan people's hospital were enrolled as subjects retrospectively divided into two groups, including 50 patients with lung cancer radiotherapy with combined body position fixation, and 40 patients with lung cancer with thermoplastic film fixation. The two groups of patients drew the target areas in accordance with the unified standard, and the set-up error of left and right, up and down, front and rear ( x, y, z axis) were recorded respectively after 1 time/week cone CT( CBCT) matched with the planned CT image and analyzed by t test. According to the MPTV =2. 5Σ+0. 7δ, CTV to PTV external expansion boundary in the combined body position group were calculated. And the V5、V20 and V30 of two groups of patients were calculated and analyzed by TPS system. Results The set-up error of the combined body position group and thermoplastic film group were respectively (1. 00 ± 0. 58) mm and (3. 28 ± 0. 43) mm on the x axis, (1. 42 ± 0. 28) mm on the y axis and (4. 03 ± 0. 41) mm, (1. 06 ± 0. 44) mm and (3. 18 ± 0. 34) mm on the z axis. The set-up errors of the two groups were statistically significant on x, y and z axis( t= -20. 740, -35. 596, -25. 015,P<0. 05). There was no significant difference in set-up errors between the central and peripheral lung cancer patients and between left and right lung cancer patients(P>0. 05). Through the MPTV =2. 5Σ+0. 7δ, CTV to PTV external expansion boundary in the combined body position fixation group was 2. 906 , 3. 746 and 2. 958 mm on x, y and z axis respectively. The comparison between group A and B showed that the mean values of V5 , V20 and V30 in group B were reduced by 1. 5％, 3. 1％ and 4. 8％ respectively compared with group A. Conclusions The combined body position technique can improve the accuracy of lung cancer patients after radiation therapy,and further reduce the boundary of CTV to PTV, which is of certain value to reduce the occurrence of radiation pneumonitis.

Objective To compare the size of the internal target volume (ITV),biological target volume (BTV) and internal biological target volume (IBTV) based on PET-CT and 4DCT for primary nonsmall cell lung cancer (NSCLC),as well as try to apply IBTV in radiotherapy planning.Methods A total of 15 patients with NSCLC were sequentially scanned by an axial enhanced 3DCT,4DCT and 18F-FDG PET-CT in the thoracic region.The gross target volumes (GTVs) of ten phases of 4DCT images were contoured,and ITV was obtained by fusion of ten GTVs.BTV based on PET-CT images was determined by the SUV 2.0.The IBTV was defined by fusion of ITV and BTV.Planning target volumes (PTVs) based on ITV,BTV,and IBTV (PITV,PBTV,PIBTV) were obtained by ITV,BTV and IBTV with a 10-mm expansion respectively.The metrics of PIBTV,PITV and PBTV were compared,and the planning parameters of target volumes and risk organs were evaluated.Results There was no significant difference between ITV and BTV,but there was significant difference between IBTV and ITV and BTV (F=22.533,P ＜ 0.05).To include more than 95％ volume of IBTV,it is necessary to expand the margin of 9.0(6.0,12.0)mm based on BTV or 10.00(7.0,12.0)mm based on ITV.There was no significant difference between the two groups (P ＞ 0.05).Dice's similarity coefficient of BTV and ITV was 0.72(0.54,0.79).The intensity modulated radiotherapy plan based on PBTV can guarantee 85.6％ (80.5％,91.2％) of PITV to reach the prescription dose,compared with 80.2％ (74.4％,87.6％) of PBTV by the plan from PITV.Additionally,the conformity index and homogeneity index were not ideal.The dosimetric parameters of PITV and PBTV in the PIBTV plan were much better than those in PBTV-and PITV plan.Conclusions The radiotherapy plan based on PET-CT or 4DCT could not guarantee a reasonable dose distribution of PTV expanded from ITV or BTV.Thus,using IBTV for radiotherapy is advised.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*