OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.

Nagilactone E (NLE), a natural product with anticancer activities, is isolated from Podocarpus nagi. In this study, we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells, and enhanced its localization on the cell membrane. Mechanistically, NLE increased the phosphorylation and expression of c-Jun, and promoted the localization of c-Jun in the nucleus, while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1. Further study showed that NLE activated the c-Jun N-terminal kinases (JNK), the upstream of c-Jun, and its inhibitor SP600125 reversed the NLE-increased PD-L1. Moreover, NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface. In summary, NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis, which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.

Background: As a large, prospective, multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score (COSSH-ACLFs), has been approved by some foreign scholars; however, its predictive value needs to be verified. This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF. Methods: This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014. Spearman method was used to assess the correlation of COSSHACLFs with classical scores. Different COX multivariate regression models were used to confirm the relationship between COSSHACLFs and short-term prognosis in patients with HBV-ACLF, and stratified analysis was used to further verify the stability of this relationship. We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve (AUROC) and Z-test. Results: A total of 975 patients with HBV-ACLF were screened, and 751 were analyzed (623 male and 128 female). COSSH-ACLFs was the highest in patients with end-stage ACLF, followed by those with middle- and early-stage ACLF (H = 211.8, P < 0.001). In the fully adjusted model, COX multivariate regression analysis revealed that COSSH-ACLFs (as a continuous variable) was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days (hazard ratio [HR]: 1.37 [1.22, 1.53], P < 0.001) and 90 days (HR: 1.43 [1.29, 1.58], P < 0.001). The same trend could be observed in the crude model and minimally adjusted model. The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792, respectively, indicating a stronger predictive accuracy than those of classic models. Conclusions COSSH-ACLFs, with a superior predictive accuracy compared with other classical scores, can strongly predict shortterm prognosis in Chinese patients with HBV-ACLF.

Laser induced breakdown spectroscopy ( LIBS ) was proposed to rapidly discriminate microbe species. Ten species of microbes were prepared in lab. Filter papers were selected as substrate for enriching bacteria and enhancing the quality of LIBS. The images of plasma were collected by ICCD camera and LIBS spectra were obtained by spectrometers. The results displayed that the images and spectra were different from 10 bacteria. It was demonstrated that this method was feasible to discriminate bacteria species by analyzing image and/or spectroscopy. Furthermore, nine smooth and multiple scattering correction ( MSC) were utilized to preprocess the LIBS full-spectrum data in the wavelength range of 200-420 nm and 560-680 nm. And principal component analysis ( PCA) and PCA-RF ( Random forest) were compared to validate the accuracy of discrimination. The investigation showed that the PCA-RF model coupled with suitable methods in preprocessing data could identify bacteria. The accuracy was 99. 6% for ten species of microbes by evaluating LIBS spectra in training set, and 96. 7% in predicting set. This report indicated that it is feasible to differentiate bacteria species by analyzing LIBS spectra.

Background:The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma;therefore,the use of morcellation is limited in the USA.A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy.Methods:A national multicenter study was performed in China.From 2002 to 2014,33,723 cases were retrospectively selected.We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application.A total of 62 cases were finally pathologically confirmed as malignant postoperatively.Additionally,the medical records of the 62 patients were analyzed in details.Results:The proportion of postoperative malignancy after morcellation application was 0.18％ (62/33,723) for patients who underwent laparoscopic myomectomy.Nearly 62.9％ (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery.And,23 (37.1％) patients showed rapid growth at the final preoperative ultrasound.With respect to the pathological types,38 (61.3％) patients had detectable endometrial stromal sarcoma,13 (21.0％) had detectable uterine leiomyosarcoma,only 3 (3.2％) had detectable carcinosarcoma,and 5 (8.1％) patients with leiomyoma had an undetermined malignant potential.Conclusions:The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy.Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential,and morcellation should be avoided.

Objective To analyze the clinical characteristics of pituitary stalk interruption syndrome(PSIS). Methods The clinical data including clinical manifestations,laboratory tests,and imaging findings of 114 PSIS patients in our hospital were retrospectively analyzed. Results Of these 114 PSIS patients,102 cases (89.4%) were male. The average age was 21.1?6.1 years. A history of breech delivery was documented in 91 cases (91.9%). Short stature was found in 89 cases (71.8%) and bone age delayed (6.1?5.1) years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone,gonadotropins,corticotropin,and thyrotropin were 100.0%,94.0%,84.2%,and 74.6%,respectively. Hyperprolactinemia was found in 28.1% of patients. Three or more pituitary hormone abnormalities were found in 105 cases(92.1%). Compared with the 5 cases with history of cephalic delivery,no difference were found in the aspects of height(t=0.297,P=0.634),penile length(t=1.205,P=0.882),testicular volume (U=99.000,P=0.348),growth hormone peak (U=89.000,P=0.186),adrenocorticotropic hormone peak(U=131.000,P=0.967),luteinizing hormone peak(U=98.500,P=0.582),thyroid-stimulating hormone (U=82.000,P=0.162),and the height of anterior pituitary (t=1.676,P=0.107) in the 53 cases with history of breech delivery. Conclusions The clinical manifestations,symptoms,hormone deficiencies were severe in our series. The condition severities were not remarkably different in patients with different delivery ways.
Adolescent ; Adult ; Dwarfism ; etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Pituitary Diseases ; complications ; physiopathology ; Pituitary Gland ; pathology ; Prevalence ; Retrospective Studies ; Young Adult

BACKGROUNDAtopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD.

METHODSA hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software.

RESULTSA total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients.

CONCLUSIONLate-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

Adolescent ; Adult ; Dermatitis, Atopic ; diagnosis ; immunology ; Eczema ; diagnosis ; Female ; Humans ; Immunoglobulin E ; blood ; Male ; Middle Aged ; Retrospective Studies ; Surveys and Questionnaires

BACKGROUNDAutism spectrum disorders (ASD), which include autism, asperger syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS), are devastating neurodevelopmental disorders of childhood resulting in deficits in social interaction, repetitive patterns of behaviors, and restricted interests and activities. Single photon emission computed tomography (SPECT) is a common technique used to measure regional cerebral blood flow (rCBF). Several studies have measured rCBF in children with ASD using SPECT, however, findings are discordant. In addition, the majority of subjects used in these studies were autistic. In this study, we aimed to investigate changes in rCBF in children with ASD using SPECT.

METHODSA Technetium-99m-ethyl cysteinate dimmer (⁹⁹m)Tc-ECD) brain SPECT study was performed on an ASD group consisting of 23 children (3 girls and 20 boys; mean age (7.2 ± 3.0) years) who were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria and an age-matched control group with 8 children (1 girl and 7 boys, mean age (5.5 ± 2.4) years). Image data were evaluated with Statistical Parametric Mapping, 5th version (SPM5). A Student's t test for unpaired data was used to compare rCBF and asymmetry in the autism and corresponding control group. The covariance analysis, taking age as covariance, was performed between the ASD and control group.

RESULTSThere was a significant reduction in rCBF in the bilateral frontal lobe (frontal poles, arcula frontal gyrus) and the bilateral basal ganglia in the autism group, and a reduction in the bilateral frontal, temporal, parietal, legumina nucleus and cerebellum in the AS group compared to the control. In addition, asymmetry of hemispheric hypoperfusion in the ASD group was observed. Inner-group comparison analysis revealed that rCBF decreased significantly in the bilateral frontal lobe (42.7%), basal nucleus (24.9%) and temporal lobe (22.8%) in the autism group, and in the bilateral cerebellum (22.8%), basal nucleus (19.3%) and right thalamencephalon (16.6%) in the AS group (P < 0.05).

CONCLUSIONSThe decrease in rCBF in ASD is a global event, which involves the bilateral frontal, temporal, limbic system and basal ganglias. Asymmetry of hemispheric hypoperfusion was more obvious in the AS group than the autism group, which indicates a different neurobiological mechanism from that of autism.

Cerebrovascular Circulation ; physiology ; Child ; Child Development Disorders, Pervasive ; pathology ; physiopathology ; Child, Preschool ; Cysteine ; analogs & derivatives ; Female ; Humans ; Male ; Organotechnetium Compounds ; Regional Blood Flow ; physiology ; Tomography, Emission-Computed, Single-Photon ; methods

Background Autism spectrum disorders (ASD), which include autism, asperger syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS), are devastating neurodevelopmental disorders of childhood resulting in deficits in social interaction, repetitive patterns of behaviors, and restricted interests and activities. Single photon emission computed tomography (SPECT) is a common technique used to measure regional cerebral blood flow (rCBF). Several studies have measured rCBF in children with ASD using SPECT, however, findings are discordant. In addition, the majority of subjects used in these studies were autistic. In this study, we aimed to investigate changes in rCBF in children with ASD using SPECT.Methods A Technetium-99m-ethyl cysteinate dimmer (99mTc-ECD) brain SPECT study was performed on an ASD group consisting of 23 children (3 girls and 20 boys; mean age (7.2±3.0) years) who were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-Ⅳ) criteria and an age-matched control group with 8children (1 girl and 7 boys, mean age (5.5±2.4) years). Image data were evaluated with Statistical Parametric Mapping,5th version (SPM5). A Student's t test for unpaired data was used to compare rCBF and asymmetry in the autism and corresponding control group. The covariance analysis, taking age as covariance, was performed between the ASD and control group.Results There was a significant reduction in rCBF in the bilateral frontal lobe (frontal poles, arcula frontal gyrus) and the bilateral basal ganglia in the autism group, and a reduction in the bilateral frontal, temporal, parietal, legumina nucleus and cerebellum in the AS group compared to the control. In addition, asymmetry of hemispheric hypoperfusion in the ASD group was observed. Inner-group comparison analysis revealed that rCBF decreased significantly in the bilateral frontal lobe (42.7%), basal nucleus (24.9%) and temporal lobe (22.8%) in the autism group, and in the bilateral cerebellum (22.8%), basal nucleus (19.3%) and right thalamencephalon (16.6%)in the AS group (P ＜0.05).Conclusions The decrease in rCBF in ASD is a global event, which involves the bilateral frontal, temporal, limbic system and basal ganglias. Asymmetry of hemispheric hypoperfusion was more obvious in the AS group than the autism group, which indicates a different neurobiological mechanism from that of autism.

Adolescent ; Adult ; Female ; Humans ; Kidney Pelvis ; surgery ; Laparoscopy ; methods ; Male ; Middle Aged ; Robotics ; Ureteral Obstruction ; surgery ; Urologic Surgical Procedures ; methods