Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer-related death worldwide, with anaplastic lymphoma kinase (ALK) fusion mutations accounting for approximately 4%-9% of cases. In recent years, there are increasing clinical evidences suggesting that the combination of ALK inhibitors with surgical treatment holds significant potential for clinical application in resectable early and locally advanced non-small cell lung cancer (NSCLC) patients. This review aims to summarize the advances in neoadjuvant targeted therapy for ALK fusion positive NSCLC and discuss its advantages and challenges in clinical practice.
.
Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Anaplastic Lymphoma Kinase/antagonists & inhibitors* ; Lung Neoplasms/enzymology* ; Neoadjuvant Therapy/methods* ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use*

Objective:To review the incidence and treatment status of perioperative anemia in patients with gastric cancer.Methods:The clinicopathological data of gastric cancer patients who underwent surgery at Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from Jan to Dec 2019 were collected. Univariate analysis and multivariate Logistic regression analysis were used to explore the risk factors of preoperative anemia in gastric cancer.Results:A total of 879 patients were included in this study. The incidence of preoperative anemia in patients with gastric cancer was 35.6%. The incidence of postoperative anemia was 63.5%. The proportion of patients with preoperative anemia receiving treatment was 17.3%, and the proportion of patients with postoperative anemia receiving treatment was 17.4%. Univariate analysis showed that age, nutritional risk screening 2002, T stage, M stage, tumor stage and lymph node metastasis were associated with preoperative anemia (all P<0.05). Multivariate Logistic regression analysis showed that age >60 years , nutritional risk screening 2002 ≥3, T 3-4 stage and M 1 stage were independent risk factors for preoperative anemia in patients with gastric cancer (all P<0.05). Conclusions:The incidence of perioperative anemia in patients with gastric cancer is high. At present, the proportion of patients with perioperative anemia receiving treatment is low. High nutritional risk, advanced age, late tumor T stage and distant metastasis are independent risk factors for preoperative anemia in patients with gastric cancer.

Objective:To evaluate the efficacy and safety of SPOT (GI Supply, USA), a new carbon-based permanent marker approved by the Food and Drug Administration (FDA), in the endoscopic marking for gastrointestinal lesions.Methods:A total of 115 patients with gastrointestinal lesions who underwent endoscopic treatment or surgery in Beijing Friendship Hospital or Beijing Chao-Yang Hospital from April 2019 to November 2019 were enrolled in the study. SPOT was used to mark the lesions, and marking points were found during endoscopic treatment or surgery to calculate the effective marking rate by single-group target value method. Adverse events after marking were recorded, and the changes of blood routine test, liver and kidney functions before and after marking were compared.Results:The effective rate of endoscopic marking with SPOT was 99.13% (114/115). The longest marking time was 57 days. There was no puncture of intestinal wall or injection into abdominal cavity during the marking process. One patient developed mild fever after marking. The incidence of adverse events was 23.48% (27/115), which were all unrelated to the test equipment. There was no significant difference in blood routine tests or liver and kidney functions before and after marking ( P>0.05). Conclusion:SPOT produced by GI Supply can effectively mark gastrointestinal lesions without serious adverse events, which meets the requirements of clinical use.

Objective:To investigate the clinicopathological characteristics of primary gastrointestinal stromal tumors (GIST) with PDGFRα mutation and analyze the prognosis of different subtypes.Methods:From Jun 2010 to Jun 2019, the clinicopathological data of 35 patients with primary PDGFRα mutation GIST, who underwent surgical therapy in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were analyzed retrospectively.Results:The main symptoms was abdominal pain (28 cases, 80%), followed by abdominal mass (6 cases, 17%), and hemafecia (1 case, 3%). 31 primary lesions (89%) were located in the stomach and 4 (11%) in other than stomach. 13 cases (37%) were of epithelioid cells, 14 cases (40%) were of spindle cells and 8 cases (23%) were of mixed cells. 27 cases (77%) were CD117 positive , 28 cases (80%) CD34 positive , and 30 cases (86%) were DOG-1 positive. 19 cases (54%) had D842V mutation and 16 cases (46%) had non-D842V mutation. Complete surgical resection was performed in all patients, with no perioperative death. The 3-year recurrence-free survival rate of the D842V mutation group was lower than that of the non-D842V mutation group (84% vs. 100%, P=0.045). Conclusions:The mutation rate of PDGFRα gene was low, mostly derived from the stomach. PDGFRα mutation GIST presents inert biological behavior and the overall prognosis was good.

Objective:At present, the modified NIH classification commonly used in clinical practice is still insufficient for assessing the risk of postoperative recurrence in some patients with intermediate-high risk gastrointestinal stromal tumors (GIST). Through exploring risk factors for recurrence of intermediate-high risk GIST, this study establishes a predictive model for recurrence with more convenience and more precision in order to guide adjuvant therapy for intermediate-high risk GIST patients.Methods:A retrospective case-control study was carried out. Clinical and pathological data of 432 GIST patients who did not receive preoperative targeted treatment, underwent complete resection in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2005 to June 2018, and were diagnosed as intermediate- or high-risk based on modified NIH classification by postopertive pathology, were retrospectively analyzed. Cox regression model was used to idenitify independent risk factors of recurrence, and a recurrence risk scoring model was established. The receiver operating characteristic curve (ROC curve), consistency index (C-index) and calibration curve were used to evaluate the accuracy of the scoring model in predicting the recurrence of moderate-risk and high-risk GIST patients.Results:Among 432 GIST patients, 332 were diagnosed as high-risk and 100 as moderate-risk; 237 were males and 195 females with average age of (57.4±12.4) years. Of 432 patients, 211 cases (48.8%) had fibrinogen (FIB) >3.5 g/L; 85 cases (19.7%) had platelet to lymphocyte ratio (PLR)>272.5; 122 cases (28.2%) had neutrophil to lymphocyte ratio (NLR) > 4.2; 102 cases (23.6%) had systemic inflammatory reaction index (SIRI)> 2.7; 198 cases (45.8%) had tumor long diameter >8 cm and 108 cases (25.0%) had mitotic counts > 8/50 HPF. Cox multivariable analysis showed that FIB (HR=1.789, 95% CI: 1.058-3.027, P=0.030), PLR (HR=1.862, 95% CI: 1.067-3.249, P=0.029), SIRI (HR=1.790, 95% CI: 1.039-3.084, P=0.036), tumor long diameter (HR=1.970, 95% CI: 1.105-2.925, P=0.017) and mitotic counts (HR=2.187, 95% CI:1.211-3.950, P=0.009) were independent risk factors for recurrence in patients with middle-risk and high-risk GIST. These 5 factors were included in the risk scoring model, which was given a weight score of 58 points, 62 points, 58 points, 63 points, and 78 points, respectively. Patients with a total score of ≤ 78 points were classified as moderate-risk recurrence (group I), those of 78 to 136 points as high-risk recurrence (group II) and those of >136 points as very high-risk recurrence (group III). ROC curve showed that the area under the curve (AUC) of the scoring model was 0.730 and the C-index was 0.724 (95% CI:0.687-0.787). The calibration curves and the Kaplan-Meier curves of patients in the three groups revealed that this model had a good predictive accuracy. Conclusions:For intermediate-risk and high-risk GIST patients, the preoperative FIB >3.5 g/L, PLR > 272.5 and SIRI > 2.7 are independent risk factors of recurrence after surgery. The recurrence risk scoring model established by combining tumor long diameter, mitotic counts, FIB, PLR and SIRI can effectively predict the risk of postoperative recurrence and metastasis in moderate-risk and high-risk GIST patients.

Objective:At present, the modified NIH classification commonly used in clinical practice is still insufficient for assessing the risk of postoperative recurrence in some patients with intermediate-high risk gastrointestinal stromal tumors (GIST). Through exploring risk factors for recurrence of intermediate-high risk GIST, this study establishes a predictive model for recurrence with more convenience and more precision in order to guide adjuvant therapy for intermediate-high risk GIST patients.Methods:A retrospective case-control study was carried out. Clinical and pathological data of 432 GIST patients who did not receive preoperative targeted treatment, underwent complete resection in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2005 to June 2018, and were diagnosed as intermediate- or high-risk based on modified NIH classification by postopertive pathology, were retrospectively analyzed. Cox regression model was used to idenitify independent risk factors of recurrence, and a recurrence risk scoring model was established. The receiver operating characteristic curve (ROC curve), consistency index (C-index) and calibration curve were used to evaluate the accuracy of the scoring model in predicting the recurrence of moderate-risk and high-risk GIST patients.Results:Among 432 GIST patients, 332 were diagnosed as high-risk and 100 as moderate-risk; 237 were males and 195 females with average age of (57.4±12.4) years. Of 432 patients, 211 cases (48.8%) had fibrinogen (FIB) >3.5 g/L; 85 cases (19.7%) had platelet to lymphocyte ratio (PLR)>272.5; 122 cases (28.2%) had neutrophil to lymphocyte ratio (NLR) > 4.2; 102 cases (23.6%) had systemic inflammatory reaction index (SIRI)> 2.7; 198 cases (45.8%) had tumor long diameter >8 cm and 108 cases (25.0%) had mitotic counts > 8/50 HPF. Cox multivariable analysis showed that FIB (HR=1.789, 95% CI: 1.058-3.027, P=0.030), PLR (HR=1.862, 95% CI: 1.067-3.249, P=0.029), SIRI (HR=1.790, 95% CI: 1.039-3.084, P=0.036), tumor long diameter (HR=1.970, 95% CI: 1.105-2.925, P=0.017) and mitotic counts (HR=2.187, 95% CI:1.211-3.950, P=0.009) were independent risk factors for recurrence in patients with middle-risk and high-risk GIST. These 5 factors were included in the risk scoring model, which was given a weight score of 58 points, 62 points, 58 points, 63 points, and 78 points, respectively. Patients with a total score of ≤ 78 points were classified as moderate-risk recurrence (group I), those of 78 to 136 points as high-risk recurrence (group II) and those of >136 points as very high-risk recurrence (group III). ROC curve showed that the area under the curve (AUC) of the scoring model was 0.730 and the C-index was 0.724 (95% CI:0.687-0.787). The calibration curves and the Kaplan-Meier curves of patients in the three groups revealed that this model had a good predictive accuracy. Conclusions:For intermediate-risk and high-risk GIST patients, the preoperative FIB >3.5 g/L, PLR > 272.5 and SIRI > 2.7 are independent risk factors of recurrence after surgery. The recurrence risk scoring model established by combining tumor long diameter, mitotic counts, FIB, PLR and SIRI can effectively predict the risk of postoperative recurrence and metastasis in moderate-risk and high-risk GIST patients.

AIM:To study the effects of noninvasive delayed limb ischemia preconditioning ( NDLIP) on ani-mal cardiac function , myocardial morphology and myocardial apoptosis after myocardial infarction ( MI ) .METHODS:Healthy SD male rats [n=45, weighing (250 ±10) g] were randomly divided into 3 groups:MI group:the animal model of MI was established by surgical ligation of left anterior descending artery ( LAD) after 2 weeks;NDLIP group:after the success of the MI animal model , NDLIP was carried out every other day until the 4th, 6th and 8th weeks;sham group:as the negative control group , the animals were taken heart LAD threading but no ligation .All rats were fed conventionally .At the end of the 4th, 6th and 8th weeks, all rats were made ventricular intubation , and then the hemodynamic parameters were recorded .The blood samples were withdrawn from the abdominal aorta and the serum was separated via centrifugation . The serum contents of Bcl-2 and Bax were measured by ELISA .Left ventricular anterior wall was homogenized .The mito-chondrial respiratory chain complexes Ⅰ,Ⅱ,Ⅲand Ⅳin the myocardial tissues were detected by ELISA .RESULTS:At the end of the 4th, 6th and 8th weeks, compared with MI group, left ventricular systolic pressure in NDLIP group was significantly increased , while left ventricular end-diastolic pressure in NDLIP group was significantly decreased ( both P<0.05).Mitochondrial respiratory chain complexesⅠ, Ⅱ, Ⅲ and Ⅳ in NDLIP group were significantly increased (P<0.05).The serum level of Bcl-2 in NDLIP group was significantly increased and Bax level was reduced remarkably (both P<0.01) .CONCLUSION:NDLIP improves the hemodynamic indexes , promotes the mitochondrial respiratory function and inhibits cell apoptosis , thus improving the prognosis of MI .