The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective:To observe the clinical efficacy of manual therapy based on the Discovery of Posture Secret (DPS) in treating adolescent idiopathic scoliosis (AIS).Methods:Thirty-six AIS patients were randomly divided into an observation group of 17 and a control group of 16. In addition to 10 minutes of side-shift training each week, the control group was given 20 minutes of sling exercise training (SET), while the observation group underwent weekly 20-minute manual therapy sessions based on DPS on the days without SET. Before and after the 4 weeks of treatment spine curvature (Cobb angle), clavicular angle (CA), angle of trunk rotation (ATR) and vertebral rotation (VR) were measured, and the Scoliosis Research Society′s patient questionnaire 22 (SRS-22) was administered.Results:After the treatment the average Cobb angle, CA, ATR and SRS-22 score of the observation group had improved significantly compared with before the treatment. The average Cobb angle, ATR and SRS-22 score of the control group were also significantly higher, but the improvements were not as great as in the observation group. There was no significant difference in VR improvement between the two groups.Conclusion:Manual therapy based on the DPS can effectively ameliorate the scoliosis and shoulder imbalance of AIS patients.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Objective:A large single-center, premature acute myocardial infarction (AMI) age (≤45 years) cohort was established to investigate the clinical features and the factors affecting major adverse cardiac events (MACE).Methods:This is a prospective and observational study. 603 patients with a clear diagnosis of AMI admitted to the Tianjin Chest Hospital from March 2015 to December 2017 were continuously selected. All patients were aged ≤45 years old, and a single-center large-sample premature AMI cohort was established. The patient's clinical basic conditions, laboratory indicators, imaging data, coronary angiography and treatment were collected. All patients were followed up for 1 year. MACE events such as cardiac death, recurrent AMI, revascularization, severe heart failure requiring hospitalization and stroke were recorded. Kaplan Meier method was used to draw the survival curve. Cox regression analysis was used to analyze the influence of risk factors, clinical characteristics and intervention methods on the long-term prognosis of MACE events.Results:A total of 603 AMI patients were included, 575 males (95.36%), 28 females (4.64%), and median age 41 (37, 44) years old. There were 422 patients (69.98%) with acute ST segment elevation myocardial infarction (STEMI), 206 patients (48.82%) with anterior myocardial infarction, and 181 patients (30.02%) with non ST segment elevation myocardial infarction (NSTEMI). Smoking was the most common risk factor for premature AMI (77.45%), followed by hyperlipidemia (48.42%) and hypertension (48.09%); smoking was the most common risk factor for male patients (80.35%), and hyperlipidemia was the most common risk factor for female patients (35.71%). 302 (50.08%) patients with premature AMI were treated with symptom onset to first medical contact (SO-to-FMC) ≤12 h; 563 patients (93.37%) had coronary angiography; coronary angiography showed that no significant stenosis, single-vessel disease, double-vessel disease, three-vessel disease, and patients with left main disease were 15(2.66%), 212(37.66%), 153(25.37%), 167(29.66%), 16(2.84%) cases; 318(56.48%) patients with vascular occlusion; The proportion of male combined with left main lesions was lower than that of female group (2.41% vs 12.50%, P=0.026); A total of 45 patients (7.46%) were recorded MACE. The 1-year MACE incidence was lower in the male group than in the female group (6.96% vs 17.86%, P=0.032). Multivariate COX regression analysis: there were 5 indicators that entered the regression model and were statistically significant: female ( HR:4.184; 95% CI:1.583-11.064; P=0.004), SO-to-FMC≤12 h ( HR:0.447; 95% CI:0.224-0.889; P=0.022), left ventricular ejection fraction (LVEF)≤40% ( HR:3.727; 95% CI:1.876-7.405; P<0.001), low-density lipoprotein (LDL) ( HR:1.315; 95% CI:1.041-1.662; P=0.022), homocysteine (Hcy) ( HR:1.011; 95% CI:1.002-1.019; P=0.011) were independent predictor of MACE occurrence in patients with early-onset AMI within 1 year. Conclusions:Smoking is the most common risk factor for young men with AMI. The most common risk factors for young women's AMI is hyperlipidemia, and the proportion of patients with left main artery disease is higher than that of men, but the proportion of patients receiving emergency intervention is lower than that of men, and the long-term prognosis of young women is poor. Early detection and control of these risk factors is a key measure to prevent the onset of AMI.

One hundred Alzheimer′s disease (AD) patients with behavioral and psychological symptoms of dementia (BPSD) treated with donepezil+risperidone group ( n=50, group 1) or hydrochloride memantine+risperidone group ( n=50, group 2) in geriatric departments of Hangzhou Seventh People′s Hospital were enrolled in the study. Montreal cognitive assessment scale (MoCA), positive and negative syndrome scale (PANSS), treatment emergent symptom scale (TESS) were applied for evaluation; and blood routine examination, blood biochemistry, eletrocardiogram were performed in two groups before and after treatment. After treatment, MoCA score in group 2 (16.10±3.90) was significantly higher than that in group 1 (18.14±3.71)( t=-3.99, P<0.01), and PANSS score in group 2 (86.66±6.62) was significantly lower than that in group 1 (109.50±11.51; t=12.67, P<0.01). The incidence rates of dry mouth (16%,8/50), extrapyramidal side effects (10%,5/50) and the total score of TESS (3.92±2.02) in group 2 were markedly lower than those of group 1 [44%(22/50), 36%(18/50), (12.49±1.45);χ 2=9.33,9.54, t=17.90,all P<0.01]. Meanwhile, group 2 had significantly lower influences on the levels of blood lipids and fasting blood glucose (all P<0.01). The risperidone dose used in group 2 was significantly lower than that in group 1 [(2.06±0.50) vs. (3.85±0.89)mg, t=14.40, P=0.04].The results suggest that hydrochloridememantine combined with risperidone is more effective with less side effects compared to donepezil combined with risperidone for AD patients with BPSD.

Objective:To explore the current situation of perceived stress and coping style based on SWOT analysis among nurses of Operating Room in the duration of second pregnancy and their influencing factors so as to give advice on reducing the stress of nurses of Operating Room in the duration of second pregnancy.Methods:From January to August 2019 , a total of 162 nurses of Operating Room in the duration of second pregnancy at all ClassⅢ Grade A hospitals in Zhengzhou were investigated with the Perceived Stress Scale (PSS) and the Simplified Coping Style Questionnaire (SCSQ) . SWOT analysis was used to assess the advantages, disadvantages, opportunity and threat of external environment, as well as the systematic summary analysis to formulate the effective coping strategy.Results:Among those nurses of Operating Room in the duration of second pregnancy, the total score of perceived stress was (27.43±7.74) ; the scores of perceived stress tension and stress out of control were (13.01±5.10) and (14.42±4.53) respectively. The total score of coping style was (32.30±6.98) ; the scores of positive and negative coping were (21.91±5.55) and (10.40±3.90) respectively. Perceived stress total score had a negative correlation with the coping style total score ( r=-0.295, P<0.01) . Hierarchical regression analysis showed that coping style could independently explain 31.6% of the total variation of perceived stress with a statistical difference ( F=4.130, P<0.01) . Conclusions:Nurses of Operating Room in the duration of second pregnancy have the stress of health risk and take positive coping style when facing stress. Managers should carry human-based management and health education, pay attention to mental health, seek family support and actively guide to reduce the stress of nurses of Operating Room in the duration of second pregnancy.

Objective: To investigate the features of plaques of saphenous venous graft (SVG) with virtual histology intravascular ultrasound (VH-IVUS) in patients underwent coronary artery bypass graft surgery. Methods: From March 2016 to March 2018, a total of 45 patients ((64.4±7.9) years old, 88.9% male (40 cases)) with ischemic symptoms after coronary artery bypass graft surgery and with coronary artery angiography evidenced SVG stenosis greater than or equal to 50%, who received percutaneous coronary intervention in Tianjin chest hospital were continuously included in this study, and the clinical data were retrospectively analyzed. VH-IVUS was performed before PCI to analyze plaque composition. The patients were divided into no smoking group (21 cases) and smoking group (24 cases), no diabetes group (30 cases) and diabetes group (15 cases), normal very low density lipoprotein cholesterin (VLDL-C) group (24 cases) and elevated VLDL-C group (21 cases), stable angina pectoris group (5 cases) and acute coronary syndrome group (40 cases), plaque burden (PB) < 70% group (11 cases) and PB ≥ 70% group (34 cases), without thin-cap fibroatheroma group (35 cases) and thin-cap fibroatheroma group (10 cases), and plaque features were compared between different groups. Results: The graft age was (8.9±3.7) years.The stenosis degree of SVG lesions was 90 (90, 98) %. The minimum lumen diameter was 1.6 (1.5, 1.8) mm. The vessel cross-sectional area was (12.1±4.0) mm². The plaque area was 8.6 (5.7,12.0) mm². The minimum lumen area was 2.5 (2.1,3.3) mm². The plaque burden was (75.3±8.3)%. The fibrotic tissue (FI) ratio was (65.1±10.1)%, fibrofatty plaque (FF) ratio was 13.8 (5.4,25.3) %, necrotic core tissue (NC) ratio was 12.0 (5.4,24.0)%, and dense calcium tissue (DC) ratio was1.0 (0.2,3.8)% in SVG lesions. There were no significant differences in SVG plaque area, FI area,FF area,NC area,and DC area between no smoking group and smoking group, no diabetes group and diabetes group, and normal VLDL-C group and elevated VLDL-C group. SVG plaque volume was significantly higher in acute coronary syndrome group than in stable angina pectoris group (262.2 (148.5,401.2) mm³ vs. 93.1 (50.6,155.9) mm³,P=0.006), and plaque area (10.1 (6.6,13.3) mm² vs. 5.0 (3.6,6.9) mm², P<0.001), FI area(4.8 (3.2,6.8) mm² vs. 2.8 (1.9,3.0) mm², P<0.001),and FF area (1.15 (0.60, 2.07) mm² vs. 0.30 (0.10,0.90) mm², P=0.009) were significantly larger in PB ≥ 70% group than in PB < 70% group.The NC area (1.75(0.40,2.78) mm² vs. 0.60 (0.20,1.30) mm², P=0.030) and DC area (0.35 (0.10,0.50) mm² vs. 0.00 (0.00,0.10) mm², P=0.006) were significantly larger in thin-cap fibroatheroma group than that in without thin-cap fibroatheroma group. Spearman correlation analysis showed that the plaque area of SVG lesion was positively correlated with FF area (r=0.64, P<0.001) and NC area (r=0.43, P=0.003). PB was positively correlated with FF area (r=0.50, P<0.001) and NC area (r=0.33, P=0.028). Graft age was positively correlated with FF area (r=0.30, P=0.047). Conclusions The main components of SVG plaque are fibrotic tissue, conversely, calcified tissue is rare in patients with SVG stenosis after coronary artery bypass graft surgery. Fibrofatty tissue is increased in the plaque in patients with PB ≥ 70%. The necrotic component is also increased in patients with thin-cap fibroatheroma. The fibrofatty component increases and the plaque tends to be unstable in proportion with increaing age of the graft in this patient cohort.

Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.