Attention deficit disorder(ADHD)is a common neurodevelopmental disorder in childhood,which seriously affects the physical and mental health of children.Up to now,the etiology and pathogenesis of ADHD are not clear,which is also the focus of global research.Animal model is an important carrier for basic research of ADHD,but the use of ADHD animal model is still controversial.This paper introduces the main emerging ADHD animal models in the world in recent years and analyzes their advantages and disadvantages.The genetic model,environmental induction model and neurodevelopmental disorder model are introduced and summarized from three aspects:surface validity,construct validity and predictive validity.The purpose of this study is to find a suitable animal model for the basic research of ADHD and to provide reference for the basic research of ADHD in China.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, which seriously affects physical and mental health in children.Its etiology and pathogenesis are complex and have not been fully elucidated.Currently, the theory of Dopamine (DA) deficits has been widely recognized and studied in the international academic community.The DA system is considered as the key to the pathogenesis of ADHD.The causes of DA deficits are complex.In addition to the well-established reuptake disorder caused by abnormal DA transporter function, DA deficits are also associated with the activation of DA vesicle cycle enzymatic inactivation, vesicle transport dysfunction, and receptor dysfunction, which are of great significance in analyzing disease pathogenesis and drug development.This article reviews the research on the causes of DA deficits proposed in recent years based on the theory of DA deficits, aiming to provide ideas and references for the research on the pathogenesis of ADHD in China.

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

Objective:To investigate the function and mechanism of CXC chemokine receptor 7 (CXCR7) in neuronal cells of ischemic stroke.Methods:The expression of CXCR7 in human neuroblastoma SH-SY5Y cells was interfered by small interfering RNA (si-RNA) technique. Oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was constructed in SH-SY5Y cells. CXCR7 protein expression and cell cycle were detected by flow cytometry (FCM). The protein expression of CXCR7 and Akt signaling pathway was detected by Western blotting.Results:After 6 hours of OGD/R, the expression of CXCR7 was significantly decreased compared with OGD/R 0 hour (CXCR7/GAPDH: 0.483±0.098 vs. 1.000±0.000 by Western blotting and 0.686±0.0524 vs. 1.000±0.000 by FCM, both P < 0.01), cell cycle arrest in G0/G1 phase (1.190±0.040 vs. 1.000±0.000, P < 0.01). After CXCR7 si-RNA interference with SH-SY5Y cells, OGD/R was constructed again for 6 hours. Compared with negative control group (si-NC group) under the same environment, the expression of CXCR7 and phosphorylated Akt (p-Akt) was significantly decreased (CXCR7/GAPDH: 0.471±0.051 vs. 1.000±0.000, p-Akt/GAPDH: 0.616±0.027 vs. 1.000±0.000, both P < 0.001) and cell cycle arrest in G0/G1 phase (1.105±0.033 vs. 1.000±0.000, P < 0.05). Conclusion:The CXCR7 could regulate the cycle of neuronal cells in ischemic stroke through Akt signaling pathway, which has a protective effect on neuronal cells.

A retrospective analysis was performed on the clinical data of a child with X-linked hyper IgM syndrome (XHIGM) with cholangiectasis as a major manifestation in Children′s Hospital of Fudan University in March 2017.The patient was a 4-year-old boy who was admitted to the hospital due to repeated diarrhea for half a year and yellow skin for 5 days.No abnormalities were found in his fetal period and birth history; The patient had 2 severe pneumonias and suppurative infection of the left axillary lymph node in infancy.Physical examination revealed delayed physical development, severe malnutrition, moderately stained yellow, lymphadenopathy and hepatomegaly.Laboratory examinations showed elevated leukocyte, eosinophils and C-reactive protein, low hemoglobin and albumin, high gamma-glutamyl transpeptidase (GGT), low IgG and normal IgM.Imaging examination revealed diffuse expansion of intrahepatic and extrahepatic bile ducts.Hepatic pathology showed hyperplasia in the bile canaliculus and some fibrous tissues around the large bile ducts.High-throughput sequencing identified a pathogenic mutation in the XHIGM gene CD 40LG (exon5 c. 506A>G, p.Y169C), with his mother as a carrier.After admission, the patient was given anti-infection, diet adjustment, albumin, intravenous immunoglobulin and ursodeoxycholic acid.The patient was discharged after the improvement in his condition.This case suggested that in addition to the common infection characteristics, XHIGM can also be manifested as diffuse intrahepatic, extrahepatic cholangiectasis and significantly elevated eosinophil.c.506A>G mutation in CD 40LG was the pathogenic mutation of this disease.

Objective:To investigate the hypoglycemic effect of curcumin on type 2 diabetic rats and its effect on the signaling pathway of endoplasmic reticulum stress RNA-dependent protein kinase like-CCAAT/enhancer binding protein homologous protein (PERK-CHOP).Methods:A total of 45 male SD rats were randomly divided into normal control group, model group and curcumin treatment group, with 15 rats in each group. The rats were given high-fat as well as high-sugar diet and intraperitoneally injected with streptozotocin (35 mg/kg, twice, once/day) to establish type 2 diabetes rat model. After the successful establishment of the model, the rats in the curcumin treatment group were given intragastrically with 200 mg/kg curcumin for 30 days. Serum adiponectin level was detected by ELISA, glucose was detected by glucose oxidase, Western blot was used to detect the expressions of PERK, p-PERK, CHOP and ATF4 protein levels in the pancreatic tissues of rats in each group, and mRNA expressions of PERK and CHOP in the pancreatic tissues of rat in each group were detected by real-time PCR.Results:Compared to the model group, the level of blood glucose (14.86 ± 2.77 mmol/L vs. 30.04 ± 3.25 mmol/L) in the curcumin treatment group significantly decreased, and the serum adiponectin level (94.12 ± 16.34 mg/L vs. 53.91 ± 9.08 mg/L) significantly increased ( P<0.05). The expressions of PERK mRNA (0.85 ± 0.07 vs. 1.64 ± 0.28), CHOP mRNA (0.53 ± 0.04 vs. 1.18 ± 0.33), PERK (1.12 ± 0.31 vs. 2.24 ± 0.43), P-PERK (1.23 ± 0.19 vs. 3.89 ± 0.32), CHOP (0.65 ± 0.07 vs. 0.92 ± 0.11) and ATF4 (0.73 ± 0.26 vs. 1.15 ± 0.31) in the curcumin treatment group significantly decreased ( P<0.05). Conclusions:Curcumin has hypoglycemic effect on type 2 diabetes rats, which can enhance the sensitivity of target tissues to insulin by increasing adiponectin levels. Curcumin can down-regulate the expression of PERK/P-PERK/CHOP/ATF4 protein levels in endoplasmic reticulum stress signal pathway, and reduce stress degree.

Objective: To find out the prognostic influencing factors of patients undergoing continuous renal replacement therapy (CRRT) for refractory acute left heart failure. Methods: Through the medical system and hemodialysis system in Foshan First People's Hospital, all patients who received CRRT for refractory acute left ventricular heart failure from January 1, 2012 to January 1, 2019 were searched. All patients were divided into two groups by the final outcome: survival group and death group. Age, sex, initial mean arterial pressure (MAP), primary heart disease, use of vasoactive drugs, urine output before treatment, hemoglobin, serum creatinine, serum albumin, C-reactive protein(CRP), brain natriuretic peptide (BNP), cardiac ejection fraction (EF) and CRRT treatment time were analyzed to find out the prognostic influencing factors. Results: A total of 130 cases were collected, including 96 cases in the survival group and 34 cases in the death group, with a total mortality rate of 26.15%. Compared to that in the death group, there were higher proportion of males (71.88% vs 50.00%, χ²=5.366, P=0.021), significantly higher initial MAP (t=4.677, P<0.001), much more urine output before treatment (Z=3.904, P<0.001), significantly higher serum creatinine (Z=2.866, P=0.004) , significantly lower hemoglobin (Z=-2.587, P=0.011), significantly shorter time of CRRT (Z=-3.447, P=0.001) in the survival group. Multivariate logistic regression analysis showed that female (OR=2.950, 95%CI 1.102-7.898, P=0.031) and higher levels of hemoglobin (OR=1.024, 95%CI 1.004-1.045, P=0.019) were the risk factors of death in patients undergoing CRRT for refractory acute left heart failure, while higher levels of mean arterial pressure before treatment (OR=0.959, 95%CI 0.930-0.989, P=0.008) and urine volume before treatment (OR=0.998, 95%CI 0.997-0.999, P=0.004) were the protective factors for patients' prognosis. Conclusion The mortality of patients with refractory acute left heart failure undergoing CRRT therapy is still very high. Female and higher level of hemoglobin are the risk factors for death, while more urine volume before treatment and higher MAP before treatment are protective factors for survival.

Objective: To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7⁺ in AML patients with wild-type (WT) or mutant-type (MT) CEBPA. Methods: The clinical data of 298 newly diagnosed non-M₃ AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7⁺ and CD7^- patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7⁺ group by Kaplan-Meier method. Results: In CD7⁺ group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7^- group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7⁺ group comparing to those of CD7^- group in AML patients with wild type CEBPA. There were no statistical difference between CD7⁺ group and CD7^- group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7⁺ group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7⁺-CEBPA MT group, CD7^- and CD7⁺-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) . Conclusion The CEBPA mutation rate was higher in CD7⁺ AML patients then that of CD7^- patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.