Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

This study was performed to investigate the features of HBV-specific CD8+T cell reactivity in patients with chronic hepatitis B(CHB),HBV-induced liver cirrhosis(LC)or hepatocellular carcinoma(HCC).A total of 124 CHB patients,36 LC patients,and 114 HCC patients were enrolled in this study.The reactive HBV-specific CD8+T cells in peripheral blood were enumerated using an innovative ELISPOT system.In addition,19 CHB patients and 20 HCC patients were longitudinally monitored with an interval of 3-5 months.Data showed that the numbers of reactive HBV-specific CD8+T cells in CHB group were not significantly different from that in LC group,but obviously lower than that in HCC group(P=0.009 9),especially HBsAg-,HBpol-and HBe/cAg-specific CD8+T cells.In CHB group,the patients with normal ALT level,AST level,or low HBV-DNA load showed significantly more reactive HBV-specific CD8+T cells than the patients with abnormal ALT level,abnormal AST level,or high HBV-DNA load.Furthermore,the duration of NUCs treatment had an impact on the HBV-specific CD8+T cell reactivity in CHB patients,while different NUCs at the same treatment duration did not bring different reactivity of HBV-specific T cells.In LC group,the HBeAg-positive patients presented much more reactive HBV-specific CD8+T cells than the HBeAg-negative patients did.In HCC group,the numbers of reactive HBV-specific CD8+T cells in the patients with normal AFP level or normal DCP level were significantly higher than that in the patients with abnormal AFP level or abnormal DCP level.Longitudinal monitoring results showed that HBV-specific CD8+T cell reactivity displayed a slow upward trend in the CHB patients undergoing NUCs treatment,and an obvious increasing in the HCC patients undergoing combined treatment of targeted drugs and immunotherapy.Taken together,the features of HBV-specific CD8+T cell reactivity are distinct among the CHB,LC and HCC patients,and are influenced by virological indicators,tumor markers and treatment regimens.Therefore,more attention should be paid to the changes of HBV-specific CD8+T cell reactivity during clinical treatment.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.

Humans ; Phosphorylation ; Serine ; Protein Serine-Threonine Kinases/metabolism* ; Spasms, Infantile

Sleep is a complex physiological process of great significance to physical and mental health, and its research scope involves multiple disciplines. At present, the quantitative analysis of sleep mainly relies on the "gold standard" of polysomnography (PSG). However, PSG has great interference to the human body and cannot reflect the hemodynamic status of the brain. Functional near infrared spectroscopy (fNIRS) is used in sleep research, which can not only meet the demand of low interference to human body, but also reflect the hemodynamics of brain. Therefore, this paper has collected and sorted out the related literatures about fNIRS used in sleep research, concluding sleep staging research, clinical sleep monitoring research, fatigue detection research, etc. This paper provides a theoretical reference for scholars who will use fNIRS for fatigue and sleep related research in the future. Moreover, this article concludes the limitation of existing studies and points out the possible development direction of fNIRS for sleep research, in the hope of providing reference for the study of sleep and cerebral hemodynamics.
Brain/diagnostic imaging* ; Hemodynamics ; Humans ; Polysomnography ; Sleep ; Spectroscopy, Near-Infrared

Background:China is an area with high incidence of gastric cancer,studies have shown that serum pepsinogen (PG) and gastrin-17 (G-17)levels can be used for gastric cancer screening. Aims:To investigate the values of serum PG and G-17 levels in screening gastric precancerous lesion and gastric cancer. Methods:A total of 211 patients with gastroduodenal disease diagnosed by endoscopy and biopsy from March 2016 to October 2016 at the First Affiliated Hospital of Soochow University were enrolled,and 67 healthy subjects were served as controls. Serum levels of PGⅠ,PGⅡ,G-17 and Hp-IgG antibodies were determined by ELISA. Results:Compared with control group,PGⅠ level and PGR were significantly decreased in atrophic gastritis group (P < 0. 01);serum PGⅠ level and PGR were significantly decreased, and G-17 level was significantly increased in low grade intraepithelial neoplasia group,high grade intraepithelial neoplasia group and gastric cancer group (P < 0. 01). ROC curve showed that the best cutoff values of PGⅠ,PGR and G-17 for diagnosing gastric cancer and gastric precancerous lesion were 74. 74 ng/ mL (sensitivity 88. 3％,specificity 78. 0％), 6. 59 (sensitivity 87. 0％,specificity 73. 8％),13. 02 pmol/ L (sensitivity 54. 2％,specificity 84. 4％),respectively. PGR and G-17 were the independent predictors of gastric cancer and gastric precancerous lesion. The sensitivity and specificity of combined detection of PGⅠ,PGR and G-17 for diagnosing gastric precancerous lesion and gastric cancer were 89. 9％ and 84. 4％,respectively. Conclusions:Serum PGⅠ,PGR and G-17 may be used as indicators of gastric cancer and gastric precancerous lesion screening. PG combined with G-17 for diagnosing gastric cancer and gastric precancerous lesion is more sensitive and specific than using serum PG or G-17 alone.

Objective To analyze the clinical features and risk factors of recurrent acute pancreatitis (RAP).Methods From September 2012 to September 2014,the clinical data of 411 patients with primary acute pancreatitis (AP) were collected.From March to June 2016,patients were followed up.The clinical features of patients with RAP were analyzed.Univariate and multivariate regression analysis were performed to analyze the risk factors of RAP.Results Among the 411 patients with AP,those caused by biliary disease,hyperlipidemia,alcohol,other known causes and idiopathic AP were 265 cases (64.5％),61 cases (14.8％),19 cases (4.6％),21 cases (5.1％) and 45 cases (10.9％),respectively.In two weeks of AP onset,the recurrent rate of biliary AP in cholecystectomy group was 7.1％ (5/70),which was lower than that of non-cholecystectomy group (30.2％,42/139),and the difference was statistically significant (xz =14.218,P＜0.01).The results of univariate regression analysis suggested that gender,body mass index (BMI),complicated with diabetes,etiology,history of smoking,history of drinking and pancreatic necrosis were correlated with RAP (all P＜0.05).The results of multivariate regression analysis indicated that complicated with diabetes (odd ratios (OR) =3.417,95 ％ confidence interval (CI) 1.979 to 5.900,P＜0.01),hyperlipidemic pancreatitis (OR=2.247,95％CI 1.077 to 4.688,P=0.023),history of smoking (OR=4.023,95％CI 2.377 to 6.809,P＜0.01),complicated with pancreatic necrosis (OR=3.312,95％ CI 1.675 to 6.546,P＜0.01) were independent risk factors of RAP.Conclusions Hypertriglyceridemia,smoking,complicated with pancreatic necrosis and diabetes are independent risk factors of RAP.Patients with biliary AP should receive cholecystectomy as early as possible,which could reduce RAP.