Objectives:To investigate the feasibility of using bedside echocardiography on the evaluation of potential donors with different causes of brain death for adult heart transplantation. Methods:Bedside echocardiographic and clinical data of consecutive potential donors for adult heart transplantation evaluated by the team of our institution from February 2018 to December 2020 were retrospectively analyzed.Based on different causes of brain death,the potential donors were divided into stroke(ischemic or hemorrhagic,n=398)and non-stroke(head trauma,brain tumor,anoxia,n=272)groups.The clinical and echocardiographic features were compared between the two groups.A total of 350 donors were assigned to our hospital by the China Organ Transplant Response System and met the inclusion criteria for donor selection.There were 195 cases in the stroke group and 155 in the non-stroke group.Retrieval operations were performed and the retrieval rate of hearts for transplantation in stroke donors was compared to that in non-stroke donors. Results:(1)Among the 670 potential heart donors,compared with the non-stroke group,donors in the stroke group were significantly older,had higher body mass index,larger left ventricular end-diastolic diameter,thicker interventricular septum,higher rates of echocardiographic abnormalities,higher prevalence of hypertension(all P<0.001).Among the 670 potential heart donors,17.5%(117 cases)did not meet the echo selection criteria,the common causes were left ventricular hypertrophy(59 cases,50.4%),left ventricular ejection fraction<50%(27 cases,23.1%),wall motion abnormalities(21 cases,17.9%),and left ventricular dilation(14 cases,12.0%).(2)Among the 350 donors who had met the selection criteria and assigned to our hospital by the China Organ Transplant Response System and underwent retrieval operation,70.3%(246 cases)were successfully procured,110 cases(44.7%)in the stroke group and 136 cases(55.3%)in the non-stroke group.The retrieval rate of stroke donors(110/195,56.4%)was lower compared with that of non-stroke(136/155,87.7%,P<0.001),104 cases(29.7%)were not retrieved,and the leading cause of unsuccessful organ retrieval was the occlusion of at least one major coronary artery(91 cases,87.5%). Conclusions:Bedside echocardiography is of great value as a screening tool for cardiac donors.Cardiac structures of the potential donor with stroke as the cause of brain death were different from those with non-stroke causes.The retrieval rate of stroke donors was lower than that of non-stroke donors,even if the initial criteria for donor selection were fulfilled.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

ObjectiveThe aim of this study is to investigate the proportion of DN2 cell and the correlation between the expression of calcium ion release activated calcium ion channel（ Ca²⁺ release-activated Ca²⁺， CRAC） protein in DN2 cells and the clinical activity of lupus nephritis （LN）. MethodsFlow cytometry was used to detect the proportion of DN2 cells in healthy controls （HC， n=15）， LN （HC， n=30）， rheumatoid arthritis （RA， n=15） and primary Sjogren syndrome （pSS， n=15） patients and the expression of SOCE protein Orai1 in DN2 cells. One-way ANOVA was used to analyze the differences among the four groups. The correlation between Orai1 expression and LN disease activity was analyzed by Pearson correlation analysis. ResultsThere was a statistically significant difference in the proportion of DN2 cells in peripheral blood among the four groups （F= 9.315， P＜0.000 1）. The proportion of DN2 cells in the peripheral blood of patients with LN was significantly higher than that of HC， RA and pSS ［（2.60±2.20）% vs.（0.68±0.56）% vs.（0.69±0.45）% vs.（1.04±0.72）%］ and was correlated with 24-hour urinary protein excretion （r=0.599 9， P=0.000 5）. There was a statistically significant difference in the Orai1 expression in DN2 cells among the four groups （F= 7.935， P＜0.000 1）. The Orai1 expression in DN2 cells of LN was significantly higher than that of HC， RA and pSS （2.30±1.50 vs. 0.86±0.39 vs. 1.34±0.57 vs. 1.13±0.64）. Orai1 expression in DN2 cells was positively correlated with SLEDAI （r=0.56， P＜0.005）， blood anti-dsDNA antibody level （r=0.43， P＜0.05） and 24-hour urinary protein excretion （r=0.44， P＜0.05）， and negatively correlated with complement C3 （r=-0.39， P＜0.05）. ConclusionsThe proportion of DN2 cells and the expression of Orai1 increases in patients with LN and is correlated with disease activity. SOCE of DN2 cells may be a potential therapeutic target for LN.

Preclinical studies suggest that the GABA receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABA receptor agonist, is the only specific GABA receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABA receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 μL/side or 0.12 nmol/0.2 μL/side), rather than vehicle or BLF (0.01 nmol/0.2 μL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABA receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.
Animals ; Baclofen ; administration & dosage ; Conditioning, Classical ; GABA-B Receptor Agonists ; administration & dosage ; Locomotion ; Male ; Memory ; Mice ; Mice, Inbred C57BL ; Morphine ; Nucleus Accumbens ; drug effects ; Opioid-Related Disorders ; Reward

3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child, Preschool ; DNA Mutational Analysis ; Disorder of Sex Development, 46,XY/genetics* ; Female ; Humans ; Membrane Proteins/genetics* ; Mutation

Objective To evaluate the usefulness of diffusion-weighted imaging(DWI) in the diagnosis and differential diagnosis of gallbladder wall thickening diseases.Methods 42 patients with gallbladder wall thickening (16 patients with carcinoma and 26 patients with benign lesion) were included in this study.All patients performed conventional MRI and DWI.The diagnostic performances of three methods (conventional MRI,visual assessment of color fusion image from DWI and T2WI,and ADC measurement) were evaluated by two radiologists.Results The area under the receiver operating characteristic curve were 0.570,0.849,0.901 for conventional MRI,visual assessment and ADC measurement respectively.The accuracy,sensitivity and specificity were 59.5%,62.5%,57.7% for conventional MRI,85.7%,81.2%,88.5% for visual assessment of color fusion image,and 83.3%,80.0%,85.2% for ADC measurement,respectivily.The mean ADC value of gallbladder cacinoma[(1.15±0.35)×10-3mm2/s]was significantly less than that of gallbladder benign lesion [(1.99±0.61)×10-3mm2/s](P<0.01).Conclusion The DWI(visual assessment of color fusion image and ADC measurement)might be a useful tool for diagnosis and differential diagnosis of the gallbladder wall thickening diseases.

BACKGROUNDChromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.

METHODSAll 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.

RESULTSThe analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.

CONCLUSIONSChinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

Adult ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology

OBJECTIVETo study the clinical value of magnetic resonance spectroscopy (MRS) image in stereotactic biopsy for brain lesion.

METHODSFrom April 2008 to April 2010, 126 cases (72 male and 54 female, aged from 10 to 82 years, mean 45 years) of brain lesion which were difficult to diagnose were divided into two groups by random number table, 62 cases were executed for MRI-guided frameless stereotactic biopsy (MRI group), 64 cases were executed for MRI and MRS-guided frameless stereotactic biopsy (MRS group). Operation used MRI and Three-dimensional MRS image to locate, and used frameless CAS-R-2 robots to carry out the positioning operating.

RESULTSNo surgery-related deaths and infections. Pathological diagnosis was 106 cases of brain tumors, 6 cases of inflammatory disease, 4 cases of tumor-like demyelinating disease and multiple sclerosis, 3 cases of neurodegenerative disease, 7 cases failed to obtain positive pathological diagnosis. The total rate of positive diagnosis was 94.4%, the positive rate in MRS-guided stereotactic biopsy group was 98.4% (63/64), the positive rate of conventional MRI-guided biopsy group was 90.3% (56/62), and there was statistically significant difference between the two groups (χ(2) = 3.92, P = 0.047). Four cases presented with postoperative complications, the complication rate was 3.2% (4/126); the complications were cerebral hemorrhage associated with aphasia, epilepsy, subcutaneous hematoma, gastrointestinal bleeding, which were improved after treatment.

CONCLUSIONSMRS-guided stereotactic biopsy group has a higher positive rate than MRI-guided stereotactic biopsy group, indicating that this method can improve the positive rate of diagnosis, and thus will help to formulate treatment plan for brain lesion.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; methods ; Brain ; pathology ; Brain Diseases ; pathology ; Brain Neoplasms ; pathology ; Child ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Young Adult

OBJECTIVETo investigate the effects of modified vacuum sealing drainage (VSD) technique in treating refractory sinus in the lower leg.

METHODSFrom January 2010 to December 2011, 11 patients with refractory sinus in the lower leg, including 7 males and 4 females, with an average age of 34.5 years (ranged,23 to 56). These patients were treated with modified VSD technique after thorough cleaning sinus and continuous washing. After 14 to 21 days of treatment, removed VSD and re-debrided the sinus and sutured wound.

RESULTSInfections got control after operation, sinus in the lower leg healed. All patients were followed up from 6 to 14 months with an average of 10 months, no recidivations were found.

CONCLUSIONModified VSD technique is an effective method in the treatment of stubborn sinus in the lower leg.

Adult ; Drainage ; methods ; Female ; Fracture Fixation, Internal ; adverse effects ; Humans ; Leg Bones ; injuries ; surgery ; Male ; Middle Aged ; Postoperative Complications ; therapy ; Vacuum

BACKGROUNDEnhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris, but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34(+), CD29(+), and CD106(+).

METHODSGrowth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n = 6), hypercholesterolemic diet (CHOL, n = 6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n = 6), and hypercholesterolemic diet with EECP treatment (EECP, n = 6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor 1alpha (SDF-1alpha) in porcine myocardium were assessed, respectively.

RESULTSA porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3 +/- 5.6) pg/ml at week 15 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.05, and (46.9 +/- 6.1) pg/ml at week 18 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150 +/- 13.9) pg/ml at week 18 vs (24.8 +/- 5.4) pg/ml at week 12, P < 0.01). Compared to other groups and other time points, progenitor cell counts increased significantly after 2-hour EECP treatment (108 +/- 13 vs 26 +/- 6 per 10(5) leukocytes, P < 0.01), but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 (baseline) (180 +/- 21 vs 25 +/- 7 per 10(5) leukocytes, P < 0.01). There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1alpha and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups.

CONCLUSIONSThe results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1alpha.

Animals ; Arteriosclerosis ; physiopathology ; Blotting, Western ; Chemokine CXCL12 ; metabolism ; Counterpulsation ; methods ; Disease Models, Animal ; Electrophoresis, Polyacrylamide Gel ; Granulocyte Colony-Stimulating Factor ; blood ; metabolism ; Humans ; Hypercholesterolemia ; metabolism ; surgery ; Immunohistochemistry ; Male ; Myocardium ; metabolism ; Neovascularization, Pathologic ; metabolism ; surgery ; Random Allocation ; Recombinant Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells ; cytology ; Swine ; Vascular Endothelial Growth Factor A ; blood ; metabolism