Optimal conditions for adenoviral transduction of immature dendritic cells without affecting the tolerogenic activity of DC-based immunotherapy.

Dendritic cells (DCs) play a pivotal role in maintaining immune tolerance. Using recombinant adenovirus (rAd) to deliver vectors to immature dendritic cells (imDCs) is an important method for studying the tolerogenic function of DCs. We found that using RPMI medium and a higher MOI during transduction increased the expression of CD80, CD86, and MHC-II on the surface of imDCs. Our data reveal a significant increase in the secretion of the pro-inflammatory cytokine IL-6 in the group showing the most pronounced phenotypic changes. In the mouse heart transplant model, imDCs with unstable phenotype and function due to adenoviral transduction resulted in an increased proportion of Th1 and Th17 cells in recipients. However, these effects can be managed, and our proposed optimized transduction strategy significantly minimizes these adverse effects. Our study holds significant implications for the development and optimization of immunotherapy utilizing tolerogenic dendritic cells.

Two new species of Aulacaspis Cockerell, 1893 (Hemiptera: Coccomorpha: Diaspididae) from China, with an identification key to Chinese species.

Two new armoured scale insect species (Hemiptera: Coccomorpha: Diaspididae) are described and illustrated from Guizhou Province, China. Aulacaspis pericampylus sp. n. was collected from Pericampylus glaucus (Menispermaceae) and Aulacaspis multispinata sp. n. was collected from Cinnamomum camphora (Lauraceae). The type specimens of both new species are deposited in the Institute of Entomology, Guizhou University, Guiyang, China (GUGC). A key to the Aulacaspis species known from China, based on the morphology of the adult females, is provided.

A new species of the genus Formosaspis Takahashi, 1932 (Hemiptera: Coccomorpha: Diaspididae) from China.

A new species of armoured scale insect, Formosaspis fanjingensis sp. n. (Hemiptera: Coccomorpha: Diaspididae), is described; it was found on Chimonobambusa spp. (Poaceae; Bambusoideae) in Guizhou Province, China. Habitat photographs and taxonomic illustrations are provided. The type specimens are deposited at the Institute of Entomology, Guizhou University, Guiyang, China (GUGC). An identification key based on the morphology of adult females is provided to separate all the species in the genus.

High Systemic Immune-Inflammation Index, Predicting Early Allograft Dysfunction, Indicates High 90-Day Mortality for Acute-On-Chronic Liver Failure after Liver Transplantation.

INTRODUCTION: The aim of the study was to investigate the relationship between systemic immune-inflammation index (SII) and early allograft dysfunction (EAD) and 90-day mortality after liver transplantation (LT) in acute-on-chronic liver failure (ACLF). METHODS: Retrospective record analysis was done on 114 patients who had LT for ACLF. To identify the ideal SII, the receiver operating characteristic curve was used. The incidence of EAD and 90-day mortality following LT were calculated. The prognostic value of SII was assessed using the Kaplan-Meier technique and the Cox proportional hazards model. RESULTS: The cut-off for SII was 201.5 (AUC = 0.728, p < 0.001). EAD occurred in 40 (35.1%) patients of the high SII group and 5 (4.4%) patients of the normal SII group, p < 0.001. 18 (15.8%) deaths occurred in the high SII group and 2 (1.8%) deaths occurred in the normal SII group, p = 0.008. The multivariate analysis demonstrated that SII ≥201.5, MELD ≥27 were independent prognostic factors for 90-day mortality after LT. CONCLUSION: SII predicts the occurrence of EAD and is an independent risk factor for 90-day mortality after LT.

Inhibition of DAI refrains dendritic cells from maturation and prolongs murine islet and skin allograft survival.

Introduction: Central to allograft rejection is the T cell-mediated adaptive immune response initiated by activated dendritic cells (DCs). Previous studies have shown that the DNA-dependent activator of IFN regulatory factors (DAI) is involved in the maturation and activation of DCs. Therefore, we hypothesized that inhibition of DAI could prevent DCs from maturation and prolong murine allograft survival. Methods: Donor mouse bone marrow-derived dendritic cells (BMDCs) were transduced with the recombinant adenovirus vector (AdV-DAI-RNAi-GFP) to inhibit DAI expression (DC-DAI-RNAi), and the immune cell phenotype and function of DC-DAI-RNAi upon lipopolysaccharide (LPS) stimulation were evaluated. Then DC-DAI-RNAi was injected into recipient mice before islet transplantation and skin transplantation. The survival times of islet and skin allograft were recorded and the proportions of T cell subsets in spleen and secretion levels of cytokines in serum were measured. Results: We identified that DC-DAI-RNAi inhibited the expression of main co-stimulatory molecules and MHC-II, exhibited strong phagocytic ability, and secreted high levels of immunosuppressive cytokines and low levels of immunostimulating cytokines. Recipient mice treated with DC-DAI-RNAi had longer islet and skin allograft survival times. In the murine islet transplantation model, we observed an increase in Treg cells proportion, a reduction in Th1 and Th17 cells proportions in spleen, and similar trends in their secreted cytokines in serum in the DC-DAI-RNAi group. Conclusion: Inhibition of DAI by adenovirus transduction inhibits the maturation and activation of DCs, affects the differentiation of T cell subsets as well as their secreted cytokines, and prolongs allograft survival.

Dysregulation of innate cell types in the hepatic immune microenvironment of alcoholic liver cirrhosis.

Introduction: The risk of alcoholic cirrhosis increases in a dose- and time-dependent manner with alcohol consumption and ethanol metabolism in the liver. Currently, no effective antifibrotic therapies are available. We aimed to obtain a better understanding of the cellular and molecular mechanisms involved in the pathogenesis of liver cirrhosis. Methods: We performed single-cell RNA-sequencing to analyze immune cells from the liver tissue and peripheral blood form patients with alcoholic cirrhosis and healthy controls to profile the transcriptomes of more than 100,000 single human cells and yield molecular definitions for non-parenchymal cell types. In addition, we performed single-cell RNA-sequencing analysis to reveal the immune microenvironment related to alcoholic liver cirrhosis. Hematoxylin and eosin, Immunofluorescence staining and Flow cytometric analysis were employed to study the difference between tissues and cells with or without alcoholic cirrhosis. Results: We identified a fibrosis-associated M1 subpopulation of macrophages that expands in liver fibrosis, differentiates from circulating monocytes, and is pro-fibrogenic. We also define mucosal-associated invariant T (MAIT) cells that expand in alcoholic cirrhosis and are topographically restricted to the fibrotic niche. Multilineage modeling of ligand and receptor interactions between the fibrosis-associated macrophages, MAIT, and NK cells revealed the intra-fibrotic activity of several pro-fibrogenic pathways, including responses to cytokines and antigen processing and presentation, natural killer cell-mediated cytotoxicity, cell adhesion molecules, Th1/Th2/Th17 cell differentiation, IL-17 signaling pathway, and Toll-like receptor signaling pathway. Discussion: Our work dissects unanticipated aspects of the cellular and molecular basis of human organ alcoholic fibrosis at the single-cell level and provides a conceptual framework for the discovery of rational therapeutic targets in liver alcoholic cirrhosis.

Small-For-Size Syndrome and Graft Inflow Modulation Techniques in Liver Transplantation.

BACKGROUND: Partial liver transplantation has recently been proposed to alleviate organ shortages. However, transplantation of a small-for-size graft is associated with an increased risk of posttransplant hepatic dysfunction, commonly referred to as small-for-size syndrome (SFSS). This review describes the etiology, pathological features, clinical manifestations, and diagnostic criteria of SFSS. Moreover, we summarize strategies to improve graft function, focusing on graft inflow modulation techniques. Finally, unmet needs and future perspectives are discussed. SUMMARY: In fact, posttransplant SFSS can be attributed to various factors such as preoperative status of the recipients, surgical techniques, donor age, and graft quality, except for graft size. With targeted improvement measures, satisfactory clinical outcomes can be achieved in recipients at increased risk of SFSS. Given the critical role of relative portal hyperperfusion in the pathogenesis of SFSS, various pharmacological and surgical treatments have been established to reduce or partially divert excessive portal inflow, and recipients will benefit from individualized therapeutic regimens after careful evaluation of benefits against potential risks. However, there remain unmet needs for further research into different aspects of SFSS to better understand the correlation between portal hemodynamics and patient outcomes. KEY MESSAGES: Contemporary transplant surgeons should consider various donor and recipient factors and develop case-specific prevention and treatment strategies to improve graft and recipient survival rates.

The comprehensive analysis of clinical characteristics and magnetic resonance imaging of non-malignant patients assigned to PI-RADS 5 score / 中华泌尿外科杂志

Objective:To analyze the clinical features and magnetic resonance imaging of non-malignant patients assigned to Prostate Imaging Reporting And Data System (PI-RADS) 5 score.Methods:We performed a retrospective review of 289 patients who underwent magnetic resonance ultrasound targeted combined system biopsy with PI-RADS 5 lesions in the First Affiliated Hospital of Nanjing Medical University between May 2019 and July 2021. The median age 72 (66, 77)years, median body mass index 24.4(22.3, 27.1)kg/m 2, median prostate volume (PV) 37.39(29.39, 48.86) ml, median PSA 22.24(10.91, 62.69) ng/ml, and median PSAD 0.53(0.30, 1.52)ng/ml 2 were recorded. According to the biopsy pathological results, all patients were divided into benign lesion group and prostate cancer group. PSA, PSAD, PV, and apparent diffusion coefficient (ADC) values were compared, and magnetic resonance imaging and clinical characteristics of patients with biopsy benign lesions were analyzed. Results:There were 11 cases (3.8%) with benign lesion and 278 cases (96.2%) with prostate cancer. The characters of 11 negative biopsy cases were displayed as follows: median age 69(66, 79)years, median body mass index 22.0(21.0, 25.5)kg/m 2, median PV 62.90(38.48, 71.96)ml, median PSA 5.55(2.99, 20.52)ng/ml, median PSAD 0.16(0.07, 0.24) ng/ml 2, median ADC 714.47(701.91, 801.26)×10 -6 mm 2/s, abnormal digital rectal and amination in 5 cases, smoking in 7 cases, and alcohol consumption in 4 cases. The median PV [62.90(38.48, 71.96) vs. 37.21(29.22, 47.82)ml, P<0.01], the PSA value [5.55(2.99, 20.52) vs. 23.53(11.14, 65.98)ng/ml, P<0.01], and the PSAD value [0.16(0.07, 0.24) vs. 0.58(0.31, 1.57)ng/ml 2, P<0.01] were significantly different between benign condition group and prostate carcinoma group. Benign condition group included 5 chronic prostatitis, 2 acute prostatitis (1 with focal adenocarcinoma), 2 granulomatous inflammation, and 2 tuberculous granulomatous inflammation. In 7 benign cases, PSA was less than 10 ng/ml, combined with frequent urination, urgency of urination and incontinence were founded. In 8 benign cases, the area of lesion was more than 50% of the total prostate area in the axial position and the imaging of magnetic resonance were diffused, with regular shape and uniform signal. The imaging of symmetrical distribution was in 6 cases. Conclusions:The benign condition with PI-RADS 5 lesions included chronic prostatitis, acute prostatitis, granulomatous inflammation and tuberculous granulomatous inflammation, among which prostatitis was the most common cause. The PSA value were less than 10 ng/ml in most benign cases, with symptoms such as frequent urination, urgency of urination and incontinence. The imaging of magnetic resonance were diffused, symmetrically distributed, with regular shape and uniform signal.

Parvovirus B19-Associated Severe Anemia in Adult Liver Transplant Recipients: A Case Series and Review of the Literature.

Background: Parvovirus B19 (B19V) infection is a rare cause of severe anemia in liver transplant recipients. However, few studies have systematically reviewed reported cases and summarized experience in managing this disease. Objective: We described a retrospective case series of eight adult liver transplant recipients with B19V-associated severe anemia and performed a literature review of epidemiology, etiology, clinical courses, diagnosis, treatment options available, and outcomes of B19V-associated anemia in adult liver transplant recipients. Patients and Methods: We systematically reviewed articles describing adult liver transplant recipients with B19V-associated anemia from PubMed and ScienceDirect databases from database inception to May 2022. Results: Eight articles containing 23 cases were identified in addition to eight cases from our center for a total of 31 patients (mean age, 45.7 ± 9.7 years; 74.2% male). Eighty-seven percent developed transfusion-dependent anemia within two months after liver transplantation (LT). Fever and progressive anemia are among the major manifestations. Intravenous immunoglobulin (IVIG)-based therapy was given to all patients and the treatment protocols varied among different centers. Except for two cases who died of comorbidities, 17 patients obtained long-term recovery from anemia after one course of treatment and six (19%) experienced relapses that were reversed by repeated courses of IVIG therapy. Two recipients presented with IVIG-associated side effects and two developed acute cellular rejection (ACR) after reduction of immunosuppression. Conclusions: B19V infection should be suspected early as a cause of severe anemia of unknown etiology in adult liver transplant recipients. The clearance of B19V typically lags behind recovery of anemia, and inadequate clearance of virus after cessation of IVIG appears to be a potential risk of anemia recurrence. Moreover, more attention should be paid to the side effects of high-dose IVIG infusion and ACR because of reduction of immunosuppression.

The Effect of Solution Casting Temperature and Ultrasound Treatment on PEBAX MH-1657/ZIF-8 Mixed Matrix Membranes Morphology and Performance.

Approximately two-thirds of anthropogenic emissions causing global warming are from carbon dioxide. Carbon capture is essential, with membranes proving to be a low cost and energy-efficient solution to alternative technologies. In particular, mixed matrix membranes (MMMs) can have higher permeability and selectivity than pure polymer membranes. The fabrication conditions affect the formation of defects within the membranes. In this work, MMMs were created using a PEBAX MH-1657 polymer and a ZIF-8 filler. The effect of casting plate temperature, varying from -5 °C to 50 °C, and the effect of ultrasound treatment time (80-400 min) and method (filler solution only, filler and polymer combined solution only and filler solution followed by combined solution) were investigated, aiming to reduce defect formations hence improving the performance of the MMMs. SEM images and permeation tests using pure CO2 and N2 gas, replicating flue gas for carbon capture, were used to investigate and compare the membranes morphology and performance. The results indicated that the MMMs maintained their permeabilities and selectivities at all tested casting temperatures. However, the neat PEBAX membranes demonstrated increased phase separation of the polyamide and polyether oxide phases at higher temperatures, causing a reduction in permeability due to the higher crystallinity degree, confirmed by DSC experiment. The MMMs fabricated at low ultrasound times displayed a large amount of aggregation with large particle size causing channeling. At high ultrasound times, a well-dispersed filler with small filler diameters was observed, providing a high membrane performance. Overall, defect-free membranes were successfully fabricated, leading to improved performance, with the best membrane resulting from the longest ultrasound time reaching the Robeson bound upper limits.

The effect of holmium laser enucleation of the prostate in the treatment of small volume benign prostate hyperplasia / 中华泌尿外科杂志

Objective:To investigate the efficacy and safety of transurethral Moses holmium laser enucleation of the prostate (MoLEP) in the treatment of small-volume benign prostatic hyperplasia (BPH).Methods:The clinical data of 132 patients with small BPH (prostate volume <40 ml) who underwent MoLEP from October 2017 to April 2020 in the First Affiliated Hospital of Nanjing Medical University were analyzed retrospectively.The age of the patients was (63.93±5.21) years old, including 12 patients with cystolithiasis. The prostate volume of 132 patients was (32.16±7.81) ml, the preoperative international prostate symptom score (IPSS) was 23.00(15.00-34.00), the quality of life score (QOL) was 5(2-6), the maximum urinary flow rate (Q max) was 7.80(0.80-9.80)ml/s and residual urine volume (PVR) was 158(51-409) ml. 89 patients had the preoperative maximum detrusor contractility (64.23±8.11) cmH 2O. Surgical methods: the 120 W Moses laser platform(Lumenis Inc)was used, the cutting power was adjusted to 80 W (2.0J×40Hz) (narrow pulse width mode), and the hemostatic power 24W (0.8J×30Hz) (wide pulse width mode). Patients with bladder calcifications underwent Moses laser bladder stone lithotripsy.After the initial resection by the level of verumontanum was performed, an anatomic plane was exposed and carried forward until the bladder neck. If prostate stones were found, Moses holmium laser lithotripsy can be performed directly. After operation, the bladder was continuously flushed with normal saline. The catheter was removed 24 hours after the operation. The operation status, intraoperative and postoperative complications were recorded. IPSS, QOL, Q max and PVR were followed up 3 months after surgery. Postoperative urinary incontinence is defined as the need for 2 pads or more within 24 hours. Results:The operations of 132 cases (including 12 cases with bladder stones) were successfully completed. 30 cases with prostate calcifications were found during the operation. The operation time (enucleation time) was (16.83±4.03) min. There were no perioperative complications such as blood transfusion, transurethral resection syndrome, urinary retention and venous thromboembolism. No bladder neck contracture or recurrence of bladder stones was found after surgery. Postoperative urethral stricture occured in 2 cases (1.5%), and postoperative urinary incontinence in 27 cases (20.5%). There were 102 cases (77.3%) with chronic interstitial inflammatory cell infiltration. Three months after operation, IPSS was 7(0-14), QOL was 2(0-5), Q max was 17.55(9.40-26.50)ml/s and PVR was 27(0-46) ml, which were significantly improved compared with preoperatively( P<0.05). Conclusions:MoLEP can significantly improve lower urinary tract symptoms (LUTS) and life quality of patients with small-volume BPH.At the same time, the incidence of complications such as urethral stricture and urinary incontinence is lower. The operation is safe and reliable, and bladder stone lithotripsy can be performed at the same time.

Fourier-domain optical coherence tomography-guided phototherapeutic keratectomy for the treatment of anterior corneal scarring.

AIM: To evaluate the safety, visual and anatomic outcomes of fourier-domain optical coherence tomography (FD-OCT)-guided excimer laser phototherapeutic keratectomy (PTK) combined with photorefractive keratectomy (PRK) surgery in treating anterior corneal scarring. METHODS: Clinical data of 23 eyes of 21 patients with anterior corneal scarring underwent FD-OCT-guided PTK and PRK from Dec. 2014 to Jul. 2016 were reviewed. Patients were assessed for preoperative and postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), contrast sensitivity (CS), FD-OCT, corneal topography and colour figures of anterior segments. RESULTS: The preoperative corneal pathologic conditions included viral keratitis (7 patients, 7 eyes), band keratopathy (2 patients, 4 eyes), corneal dystrophy (4 patients, 4 eyes), traumatic corneal disease (2 patients, 2 eyes) and corneal chemical injury (6 patients, 6 eyes). Mean follow-up time was 10.65 (range, 3-19)mo. UCVA (in logMAR) improved from a mean of 0.79 (95%CI, 0.28-1.29) preoperatively to a mean of 0.45 (95%CI, 0.29-0.62) postoperatively (P=0.021). BSCVA (in logMAR) improved from 0.57 (95%CI, 0.27-0.88) preoperatively to a mean of 0.28 (95%CI, 0.15-0.41) postoperatively (P=0.001). Corneal topographic indices postoperatively showed significant improvement in corneal cylinder (P=0.009), the surface regularity index (P=0.007) and surface asymmetry index (P=0.00). Postoperative spherical equivalent averaged -0.53 diopters (-1.49 to 0.42). No complications were associated with the treatment. CONCLUSION: FD-OCT-guided PTK combined with PRK is safe and effective for the treatment of anterior corneal scarring by eliminating or reducing corneal opacities.

Toll-Like Receptor 3 Activator Preconditioning Enhances Modulatory Function of Adipose­Derived Mesenchymal Stem Cells in a Fully MHC-Mismatched Murine Model of Heterotopic Heart Transplantation.

BACKGROUND Donor-specific tolerance is the ultimate goal in organ transplantation. Diverse approaches, including the use of mesenchymal stem cells (MSCs), have been investigated to induce graft tolerance. Non-stimulated MSCs showed limited regulatory functions through interaction with multiple immune-regulatory cells, such as regulatory T cells (Tregs). To augment their functions, MSCs have been preconditioned with toll-like receptor (TLR3/4) agonist in autoimmune disease models, but results were conflicting. MATERIAL AND METHODS We evaluated the immunomodulatory effects of mouse adipose-derived mesenchymal stem cells (ADSCs) preconditioned with various combinations of TLR3/4 agonist and antagonists, including polyinosinic-polycytidylic acid poly(I:C)-TLR3 agonist, lipopolysaccharide (LPS) -TLR4 agonist, and TAK242-TLR4 antagonist. In vitro and in vivo experiments including mixed lymphocyte reaction, cytokines measurement, Tregs analysis, and a fully mismatched MHC heterotopic heart transplantation in mice (BALB/c to C57BL/6) were conducted. RESULTS ADSCs preconditioned with poly(I:C) showed the highest efficiency in inhibiting lymphocyte proliferation, which was correlated with the upregulation of fibrinogen-like protein 2 (FGL2), an effector molecule of Tregs. The mean survival of cardiac allografts was extended from 8 to 12 days by intravenous injection of a single dose of ADSCs preconditioned with TLR3 agonist. The proportion of Tregs in the recipient's spleen was significantly increased by injecting the poly(I:C)-stimulated ADSCs. CONCLUSIONS These results show that short-term TLR3 agonist preconditioning enhances the immunomodulatory efficacy of ADSCs, which can induce the generation of Tregs and upregulate the expression of FGL2, thereby improving the outcome of patients receiving organ transplantation.

Effect of cocaine-and amphetamine-regulated transcription peptide on synaptic formation in cultured cortical neurons subjected to oxygen-glucose deprivation / 国际脑血管病杂志

Objective:To investigate the effect of cocaine- and amphetamine-regulated transcript peptide (CART) on the synapse structure of mice cortical neuron subjected to oxygen-glucose deprivation (OGD).Methods:Primary neurons of the embryonic cerebral cortex obtained from healthy and clean Kunming mice at gestational age of 16-17 d were cultured. They were divided into control group, CART group, OGD group, and OGD+ CART group. 0.4 nmol/L CART 55-102 was added and cultured for 12 h after OGD treatment in the OGD+ CART group; the CART group was given the same dose of CART 55-102. The neuronal mortality was measured by the flow cytometry. The changes of synaptic structure were observed by immunofluorescence analysis, and the axon length and synapsin Ⅰ positive area were quantitatively analyzed. Real-time fluorescent quantitative polymerase chain reaction and Western blot analysis were used to identify the brain-derived neurotrophic factor (BDNF) mRNA and protein expression. Results:Compared with the control group, the mortality of neurons in the OGD group was significantly increased, the neuronal synapse growth was significantly inhibited, the positive area of synapsin Ⅰ was significantly reduced, and the expression levels of BDNF mRNA and protein were significantly down-regulated (all P<0.05). Compared with the OGD group, adding CART 55-102 significantly reduced the mortality of OGD neurons ( P<0.05), reversed the inhibitory effect of OGD on neuronal synapse growth, significantly increased the length of neuron axons and the positive area of synapsin Ⅰ (all P<0.05), and significantly up-regulated BDNF mRNA and protein expression levels (all P<0.05). Conclusion:CART can protect the synaptic structure of mice cortical neuron subjected to OGD, and its mechanism may be related to the up-regulation of BDNF expression.

Comparison of four different metabolic syndrome diagnostic criteria among the elderly in Nanjing / 中华疾病控制杂志

Objective To compare the application of the 2013 Chinese Diabetes Society (CDS 2013) criteria, the 2009 joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention(JIS)criteria, the 2005 International Diabetes Federation(IDF)criteria and the 2005 US National Cholesterol Education Program Adult Treatment PanelⅢ (ATPⅢ) criteria among the elderly in Nanjing. Methods A total of 1 832 elderly (≥60 years old) were recruited in Nanjing using cluster random sampling and were surveyed with questionnaires, physical examination, and laboratory test between March and December 2013. The different prevalence under CDS 2013, JIS, IDF and ATPⅢ criteria were calculated respectively. SPSS 19.0 was used to conduct t test, chi-square test and kappa test to compare the prevalence of metabolic syndrome and the consistency of four diagnostic criteria in the elderly. Results According to CDS 2013, JIS, IDF, and ATPIII, prevalence of MS in the elderly in Nanjing was 39.9%, 58.2%, 46.5%, and 54.5%, respectively. The highest value of kappa was 0.920 between JIS and ATPⅢ, with a compliance rate of 96.1%．The value of kappa was 0.841 between ATPⅢ and IDF, with a compliance rate of 92.0%. Conclusions The prevalence of metabolic syndrome among the elderly in Nanjing is relatively high under different criteria. The higher detection rate of MS by the JIS standard and ATPIII standard can help to find MS earlier and reduce the cardiovascular damage.

Rational combinations of in vivo cancer antigen priming and adoptive T-cell therapy mobilize immune and clinical responses in terminal cancers.

PURPOSE: It is now recognized that solid tumors encroach on the host's immune microenvironment to favor its own proliferation. Strategies to enhance the specificity of the endogenous T-cell population against tumors have been met with limited clinical success. We aimed to devise a two-tier protocol coupling in vivo whole antigen priming with ex vivo cellular expansion to clinically evaluate survival in patients following re-infusion of primed, autologous T cells, thereby determining treatment efficacy. EXPERIMENTAL DESIGN: Treatment commenced with the acquisition of whole tumor antigens from tumor cell lines corresponding with patients' primary malignancy. Lysate mixture was inoculated intradermally, while peripheral blood mononuclear cells (PBMCs) were periodically extracted via phlebotomy and expanded in culture ex vivo for re-infusion. Post-treatment tumor-specific T-cell response and cytotoxicity was confirmed via Elispot and real-time cell analyzing (RTCA) assay. Serum cytokine levels and cytotoxicity scores were evaluated for associations with survival status and duration. RESULTS: There was a significant increase in cytotoxicity exhibited by T cells measured using both Elispot and RTCA following treatment. Correlation analysis determined significant association between higher post-treatment cytotoxicity scores and survival status (R = 0.52, p = 0.0028) as well as longer survival duration in months (R = 0.59, p = 0.005). CONCLUSIONS: Our treatment protocol successfully demonstrated significant correlation between tumor-associated antigen-specific immune response and objective prolongation of survival. Whole-cell cancer antigen priming and adoptive T-cell therapy is, therefore, a highly feasible clinical model which can be easily replicated to positively influence outcome in end-stage malignancy.

Evaluation and cultivation of medical students' clinical abilities through clinical skill competition / 中华医学教育探索杂志

Clinical skill competition based on objective structured clinical examination could evalu-ate students' clinical abilities effectively and fairly in a comprehensive way. The competition results not only reflected the learning effectiveness of the competitors but all the medical students. Analysis and exploration of the inspiration from the competition could promot the all-round development of students and boost the continuous growth and progress of clinical teaching.

Observation of blood flow characteristics of collateral circulation of ipsilateral ophthalmic artery in patients with internal carotid artery occlusion / 中华眼底病杂志

Objective To observe the characteristics of collateral circulation blood flow of ipsilateral ophthalmic artery in patients with internal carotid artery occlusion. Methods The imaging data of 20 patients with internal carotid artery occlusion were analyzed retrospectively. There were 11 males and 9 females, aged from 30 to 65 years, with an average age of (45±3) years. All the patients underwent digital subtraction angiography and transcranial Doppler examination, and 6 patients underwent simultaneous magnetic resonance angiography. The blood supply and collateral circulation of the ipsilateral ophthalmic artery were observed . Results All the patients had unilateral internal carotid artery occlusion. The blood supply of the ipsilateral internal carotid artery and ophthalmic artery comes from the collateral circulation between the middle meningeal artery branches of the external carotid artery and the ophthalmic artery in 18 patients (90.0%); it also comes from the anterior communicating artery of the contralateral internal carotid artery in 16 patients (80.0%); and the posterior communicating artery of the contralateral internal carotid artery in 12 patients (60.0%), respectively. Conclusion The blood flow of the ipsilateral ophthalmic artery mainly comes from the middle meningeal artery branch of the ipsilateral external carotid artery, also comes from the anterior and posterior communicating arteries of the contralateral internal carotid artery.

Observation of blood flow characteristics of collateral circulation of ipsilateral ophthalmic artery in patients with internal carotid artery occlusion / 中华眼底病杂志

Objective To observe the characteristics of collateral circulation blood flow of ipsilateral ophthalmic artery in patients with internal carotid artery occlusion. Methods The imaging data of 20 patients with internal carotid artery occlusion were analyzed retrospectively. There were 11 males and 9 females, aged from 30 to 65 years, with an average age of (45±3) years. All the patients underwent digital subtraction angiography and transcranial Doppler examination, and 6 patients underwent simultaneous magnetic resonance angiography. The blood supply and collateral circulation of the ipsilateral ophthalmic artery were observed . Results All the patients had unilateral internal carotid artery occlusion. The blood supply of the ipsilateral internal carotid artery and ophthalmic artery comes from the collateral circulation between the middle meningeal artery branches of the external carotid artery and the ophthalmic artery in 18 patients (90.0%); it also comes from the anterior communicating artery of the contralateral internal carotid artery in 16 patients (80.0%); and the posterior communicating artery of the contralateral internal carotid artery in 12 patients (60.0%), respectively. Conclusion The blood flow of the ipsilateral ophthalmic artery mainly comes from the middle meningeal artery branch of the ipsilateral external carotid artery, also comes from the anterior and posterior communicating arteries of the contralateral internal carotid artery.