This study investigated the role of programmed death-ligand 1 (PD-L1) expression in the sex-related differences in immune checkpoint inhibitor (ICI) efficacy. We first pooled individual patient-level data from prospective clinical trials to evaluate ICI efficacy between male and female stratified by PD-L1 expression. We further combined individual patient-level data with meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of ICI versus chemotherapy in each of the sexes. Finally, we assessed sex associated with landscape of tumor microenvironment among PD-L1 expression-negative patients. In total, 1,594 patients were included from five clinical trials, and nine RCTs with 4,718 patients were included in meta-analysis. Among patients with PD-L1 expression<1%, individual patient-level analysis showed that overall survival (OS) with ICI was significantly longer for female compared with male (HR 0.58, 95% CI 0.42-0.80; P<.001). The OS benefit of ICI over chemotherapy was significantly different in female (HR 0.57, 95% CI 0.38-0.85; P=.006), but not in male. Among patients with PD-L1 expression≥1%, individual patient-level analysis combined with meta-analysis showed that the OS benefit of ICI over chemotherapy was significantly different in male (HR 0.76, 95% CI 0.67-0.85; P<.01), both in first-line patients (HR 0.79, 95% CI 0.65-0.97; P=0.02) and subsequent-line patients (HR 0.73, 95% CI 0.62-0.85; P<.01); however, this benefit for female was only significant in subsequent-line patients (HR 0.77, 95% CI 0.62-0.96; P=.02). Additionally, the central memory T cell was potentially correlated with the OS differences between the sexes at PD-L1 expression<1%. The association of sex with OS benefits of ICIs in cancer were greatly influenced by PD-L1 expression. At PD-L1 expression<1%, ICI should be recommended for female but not for male. At PD-L1 expression≥1%, ICI should be recommended for male regardless of treatment lines; whereas for female, ICI could be only recommended in subsequent-line setting. Sex and PD-L1 expression should be jointly considered in the clinical decision making for ICI in cancer.

AIM: To examine the prognostic value of global peak diastolic strain rate (PDSR) derived from cardiac magnetic resonance (CMR) tissue tracking (CMR-TT) in predicting adverse outcomes in hypertrophic cardiomyopathy (HCM) patients. MATERIALS AND METHODS: A total of 98 patients diagnosed with HCM (44 patients had left ventricle [LV] outflow tract obstruction [LVOTO] and 54 patients did not) were enrolled and followed for the specified endpoint. LV global myocardial mechanics was assessed in all participants using CMR-TT at study entry. RESULTS: Compared with the non-obstructive subgroup, the obstructive subgroup demonstrated deteriorated magnitude of LV global radial, circumferential, and longitudinal PDSR (all p<0.05). After a mean follow-up period of 4.5 years, 24 patients reached an endpoint before the end of the study. Furthermore, when using the specified cut-off value (0.33 1/s) of longitudinal PDSR, the Kaplan-Meier curve demonstrated that patients with lower longitudinal PDSR had a significantly lower freedom from major adverse cardiovascular events (MACE) compared with their counterparts in the non-obstructive, obstructive, and overall cohorts (all log-rank p<0.05). Multivariable analysis showed that longitudinal PDSR remained the strongest predictor of outcome after adjusting for baseline and CMR variables (hazard ratio, 2.65; 95% confidence interval, 2.21-11.44; p<0.05). CONCLUSION: CMR-TT-derived longitudinal PDSR is probably considered a novel and easyto-perform marker for predicting adverse outcomes in HCM patients, which is beneficial to risk stratification. Further confirmatory studies are needed. (C) 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Objective: To explore the observation and nursing of patients with acute mass asphyxia poisoning with pulmonary bullae treated by nasal high-flow humidification and oxygen therapy. Methods: Review and summarize the data of 5 patients with acute mass asphyxial gas poisoning with pulmonary vesicles who were admitted to the department of toxicology of this hospital in June 2019 and received nasal high-flow humidification and oxygen therapy. The oxygenation index, airway humidification and prognosis were observed. Results: All the 5 patients were successfully transferred to nasal catheter for oxygen inhalation after nasal high-flow humidification and orygen therapy without intubation. When discharged from the hospital without oxygen, pH: 7.36-7.42, PO(2):82-106 mmHg, PCO(2):32-39 mmHg. All the white blood cells and myocardial enzymes were normal, and there was no brain injury, perinasal skin damage and abdominal distension. Conclusion: Nasal high-flow humidification and oxygen therapy can effectively improve the efficacy of oxygen therapy for patients with acute mass asphyxial gas poisoning with pulmonary vacuoles.

Molluscum contagiosum is a common, self-limiting infectious disease of the skin caused by molluscum contagiosum virus (MCV). The disease primarily affects children, sexually active adults, and immunocompromised individuals. Transmission of the virus occurs by direct skin contact. Therefore, the virus is usually detected in the skin and genitals of patients. However, the diagnosis of intracranial infection by the virus is difficult if the skin/mucosa lessons are atypical or absent, and the presence of the virus in the cerebrospinal fluid has not been reported. We report a very rare case of intracranial infection by molluscum contagiosum virus. A 25-year-old girl was admitted to our hospital due to severe headache but no fever or other symptoms. Upon examination, some small flesh-colored flattened papules on both arms were noticed. Blood tests showed slightly reduced levels of CD3 and CD4 T lymphocytes. Three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and head magnetic resonance (MR) were both normal. Lumbar puncture was performed, and metagenomic sequencing was applied to the spinal fluid. The unique sequences of the molluscum contagiosum virus were identified in the fluid. The patient was then diagnosed with intracranial molluscum contagiosum virus infection. No special treatment was given. The headache gradually disappeared, and the patient was discharged. During our quarterly follow-up, the girl appeared normal, and her skin lesions disappeared. However, her CD3 and CD4 T lymphocyte counts were still slightly lower than the normal level. Our case shows that the application of metagenomic sequencing to cerebrospinal fluid is a sensitive and powerful means to detect pathogens causing intracranial infection.

To investigate the effects of High frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on non-fluent aphasia in patients after stroke. Six stroke patients displaying non-fluent aphasia were randomly assigned to an rTMS group and a control group using a random number table. Both groups were treated with conventional language therapy. While the rTMS group was additionally given 5 Hz rTMS over the motor cortex (M 1) of the affected hemisphere 5 days a week for 4 weeks. The patients were stimulated at 100% of the motor threshold (MT), with 2 second trains and intervals of 3 seconds 120 times (1200 pulses) in a session. Before and after the 4 weeks of treatment, the Western Aphasia Battery (WAB) and the Communicative Abilities in Daily Living (CADL) test were conducted in both groups to evaluate their language function and communication ability. Only spontaneous speech improved significantly (P < 0.05) in the control group after 4 weeks of treatment. In the rTMS group, the spontaneous speech, auditory comprehension, repetition, naming and aphasia quotient (AQ) had all improved significantly (P < 0.05). Moreover, after the treatment, the average score of the auditory comprehension, repetition, naming and AQ of the rTMS group were significantly higher than those of the control group (P < 0.05). rTMS applied to the motor cortex of the affected hemisphere can significantly improve language function in those exhibiting non-fluent aphasia after stroke.

The aim of this study was to investigate the value of Gd-EOB-DTPA-enhanced MRI on hepatobiliary phase (HBP) imaging and T1 mapping sequence in the differentiation of hepatocellular carcinoma (HCC). A total of 45 patients with HCC who were to undergo a resection were enrolled in this study. Gd-EOB-DTPA-enhanced magnetic resonance examination was performed prior to resection. T1 mapping was performed before and 20 min after injection of Gd-EOB-DTPA. T1 values of the lesions were measured on pre-contrast (T1p) and during HBP (T1-HBP) on T1 maps. The signal intensity, the diameter and the margin of HCC lesions on HBP images were analyzed. The reduction in T1 value (T1d) and the reduction rate (ΔT1%) of T1 mapping between pre-contrast and HBP were calculated. The Edmondson-Steiner classification of each lesion was made after surgery. The SPSS software package was used for statistical analysis and the analysis of receiver operator characteristic (ROC) curve and area under the curve (AUC) were carried out by using MedCalc software package. Mean values of T1p and T1-HBP were 1935.4±730.8 ms and 1257.1±529.1 ms, respectively. T1p accuracy (AUC = 0.685, p = 0.037) in predicting pathological grading was similar to that of T1-HBP (AUC = 0.751, p = 0.005). A T1p of 1648.2 ms or greater had a sensitivity and specificity of 85.19% and 61.11%, respectively. A T1-HBP of 1006 ms or greater had a sensitivity and specificity of 81.84% and 61.11%, respectively. The number of HCCs with a non-smooth tumor margin was 20 (44.4%), and a non-smooth tumor margin correlated moderately with the Edmondson-Steiner grade (Spearman r = 0.491, p = 0.041). There was no significant correlation between T1d, ΔT1%, HCC signal intensity on HBP image and lesion diameter with pathologic grading. T1 mapping in pre-contrast and HBP of Gd-EOB-DTPA-enhanced MRI, a non-smooth tumor margin in the HBP of Gd-EOB-DTPA-enhanced MRI, are useful in predicting the pathologic grading of HCC.

BACKGROUND:We aimed to investigate the efficacy of adipose-derived mesenchymal stem cell (ADMSC) transplantation in acute liver failure caused by thioacetamide in mice as well as its underlying mechanism by comparing transplantation routes.METHODS:ADMSCs were isolated from inguinal fat pads of enhanced green fluorescent protein (EGFP) transgenic mice and analyzed regarding their surface markers and differentiation potential. Acute liver failure models were established by infusion of thioacetamide, and then we injected EGFP-ADMSCs or phosphate-buffered saline solution by intrasplenic or intravenous route. The restoration of biologic functions of the livers receiving transplantation was assessed by means of a variety of approaches, such as survival rates, live function parameters, histology, localization of EGFP-ADMSCs, and immunofluorescence analysis.RESULTS:ADMSCs were positive for CD90 and CD44 and negative for CD34 and had adipogenic and osteogenic differentiation potential. And they prevented the release of liver injury biomarkers. Transplantation via tail vein provided a significant survival benefit, but no significant differences were observed in the intrasplenic pathway and between the 2 pathways in our animal experiments. Furthermore, the transplanted cells were well integrated into injured livers and produced albumin and cytokeratin-8.CONCLUSIONS:Direct transplantation of ADMSCs is an effective treatment for acute liver failure rather than intrasplenic transplantation. The transplanted ADMSCs exhibit the potential to differentiate into hepatocyte-like cells in the injured livers. Thus, ADCMSCs would be a potential option for treatment of acute liver failure.

Gastric Cancer is the fourth most common cancer worldwide,with a high rate of death and low 5-year survival rate.Cancer stem cells(CSCs)are a group of tumor cells with stem cell-like properties such as infinite self-renewal and multi-differentiation potential.Although rare,CSCs play important roles in tumor initiation,progression,recurrence and metastasis.Research of gastric cancer stem cells is still in its infancy.Research progress in gastric cancer stem cell is new ideas for the treatment of gastric cancer.

OBJECTIVE The aim of this study was to determine the correlation between the number of FOXP3(+) T cell in lesions and the disease activity of patients with oral lichen planus (OLP). MATERIALS AND METHODS The expression of FOXP3 was investigated using immunohistochemical staining and real-time RT-PCR in 23 OLP lesions and 12 controls. Changes of FOXP3(+) Treg in peripheral blood from three patients' pre and post-treatment were assessed using flow cytometry. RESULTS Few FOXP3(+) cells were detected in controls, but an increased number of FOXP3(+) cells were observed in lesions (n = 20, 40.99 +/- 24.68 cells per high-power field - hpf). Furthermore, the frequency of FOXP3(+) Treg in reticular OLP (n = 7, 63.6 +/- 23.2 cells per hpf) was significantly higher than that in erythematous/erosive OLP (n = 13, 28.8 +/- 16.8 cells per hpf, P = 0.001). In addition, negative correlation was found between the number of FOXP3(+) Treg and disease activity (correlation oefficient = -0.557, P = 0.013). The proportion of FOXP3(+) Treg showed remarkable increase in peripheral blood from patients after treatment (1.39 +/- 0.71%vs 4.91 +/- 1.59%). CONCLUSIONS These data indicated that FOXP3(+) Treg were involved in the pathogenesis of OLP and correlated with disease's subtype and activity.

3056 Background: Renal cell carcinoma (RCC) has been shown to be highly susceptible to immune-based treatment strategies. Methods: In the present study, patient-derived tumor cells were fused with allogeneic dendritic cells (DC) to elicit antitumor activity against RCC. DC from HLA-A2+ healthy donors were fused with primary RCC cells from 10 patients. Phenotype of fusion cells was characterized by flow cytometer and confocal microscopy. In vitro, T-cell proliferation, IFN-γ secretion, and cytotocic T lymphocytes (CTL) activity elicited by allogeneic DC/RCC fusion cells were assessed. Clinically, 10 patients were vaccinated with allogeneic DC/RCC fusion vaccine. The adverse effects and toxicity were observed. The clinical response was evaluated by CT scans. Results: After fusion, the created hybrids expressed both tumor-associated antigen and DC-derived molecules and could stimulate the proliferation and IFN-γ secretion of T-cells as well as elicit strong CTL activity against RCC cells in vitro. In vivo, neither serious adverse effects nor signs of autoimmune disease were observed after vaccination therapy. Percentage of T lymphocyte subsets in peripheral blood of patients was increased significantly. One of 10 patients exhibited a partial response with regression of lung metastases. Six patients showed stable disease with stabilization of previously progressive disease (follow-up 1.5 year). Conclusions: The data suggest that allogeneic DC/RCC fusion vaccine is safe and can elicit immunological responses in patients with RCC. No significant financial relationships to disclose.

OBJECTIVE:To investigate whether unknown genes are involved in the tumorigenesis of gastric cancer.METHODS:Fourty-three primary gastric carcinomas were analyzed by comparative genomic hybridization(CGH).RESULTS:A gain in chromosome 3p(8/43), 8q(8/43), 20[20(9/43), 20p(7/43), 20q(4/43)], 12q (16/43), and 13q(12/43) was observed while a loss of 19[19(15/43), 19p (13/43)], 17[17(8/43), 17p(10/43)], 16(10/43) and 1p(11/43) was discovered.CONCLUSION:There were characteristic changes in 3p, 8q, 20, 12q, 13q, 19, 17, 16, and 1p in gastric carcinoma, and some unknown genes located in the above regions might be of importance to gastric carcinoma pathogenesis.