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.

Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

Objective:To investigate the clinical value of neutrophil-lymphocyte ratio (NLR), fibrinogen (FIB), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in the diagnosis and prognosis of colorectal cancer.Methods:A case-control study design was used to select 155 patients with colorectal cancer[98 males and 57 females, aged (63.12±13.99)years old], 90 patients with colorectal polyps[62 males and 28 females, aged (56.86±12.74)years old] and 150 healthy subjects[93 males and 57 females, aged (57.02±10.91)years old] from the First Affiliated Hospital of Nanjing Medical University from October 2017 to March 2018. Blood routine tests were detected by instrument method, FIB was detected by Clauss method, and CEA and CA19-9 were detected by electrochemiluminescence method. The levels of the NLR, FIB, CEA and CA19-9 in the 3 groups were compared. The diagnostic efficacy of NLR, FIB, CEA and CA19-9 of colorectal cancer was compared according to the ROC curve. The relationship between the level of NLR, FIB, CEA and CA19-9 and their clinicopathological features in colorectal cancer patients was assessed. According to the median levels of NLR, FIB, CEA and CA19-9, 112 follow-up of colorectal cancer patients could be divided into the high-value group and the low-value group. Kaplan-Meier, log-rank test and Cox regression analysis were used to analyze the relationship between the levels of the four indicators and the prognosis of colorectal cancer.Results:The levels of NLR, FIB, CEA and CA19-9 in colorectal cancer group were 2.11(1.52, 2.86), 3.21(2.58, 3.86)g/L, 3.93(2.27, 8.78)μg/L, 15.11(9.10, 25.73)U/ml. The levels of NLR, FIB, CEA and CA19-9 in colorectal polyp group were 1.74(1.39, 2.17), 2.54(2.26, 3.03)g/L, 1.99(1.18, 2.70)μg/L, 9.83(6.13, 15.68)U/ml. The levels of NLR, FIB, CEA and CA19-9 in healthy control group were 1.68(1.33, 2.28), 2.56(2.30, 2.82)g/L, 1.85(1.28, 2.59)μg/L, 10.03(6.86, 13.26)U/ml. The levels of NLR, FIB, CEA and CA19-9 in colorectal cancer group were significantly higher than those in colorectal polyp group ( Z values were 3.568, 5.913, 6.880 and 4.022, P values were all<0.05) and healthy control group( Z values were 3.916, 7.381, 9.131 and 5.251, P values were all<0.05). The levels of NLR, FIB, CEA and CA19-9 in colorectal polyp group were not remarkably different from those in healthy control group ( Z values were 0.217, 0.179, 0.320 and 0.061, P values were all>0.05). The diagnostic performance of CEA was the best in single test, followed by FIB, CA19-9 and NLR. The sensitivity of combined NLR+FIB+CEA or NLR+FIB+CEA+CA19-9 was the highest with 72.3%. NLR and FIB levels were associated with tumor sites ( Z values were 3.587 and 7.089, P values were both<0.05). FIB and CEA levels were correlated with the depth of tumor invasion ( Z values were 3.250 and 3.245, P values were both <0.05). NLR, FIB, CEA and CA19-9 levels were both associated with lymph node metastasis ( Z values were 2.010, 3.276, 3.312 and 2.921, P values were all<0.05). The prognosis of patients in the high-value NLR, FIB, CEA and CA19-9 groups was significantly worse than that in the low-value group (χ 2 values were 5.744, 6.048, 4.389 and 6.942, P values were all<0.05).Cox multivariate regression analysis showed lymph node metastasis, NLR >2.15 and CA19-9 >15.47 U/ml are independent factors affecting the prognosis of colorectal cancer. Conclusion:NLR, FIB, CEA and CA19-9 can be applied in the auxiliary diagnosis and prognosis of colorectal cancer.

To investigate the risk factors of lymph node metastasis in early gastric cancer (EGC) and to develop a risk model for the presence of lymph node metastasis. A total of 172 EGC patients, with a median age of 62(52, 68) years, who underwent gastric cancer resection in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2019 were selected. Clinical data of the patients were collected through the case system. Logistic regression analysis was used to determine the variables significantly related to lymph node metastasis. ROC curve and calibration curve were used to evaluate the risk model. The results showed that the lymph node metastasis rate of 172 EGC patients was 19.19% (33/172). Tumor size, depth of invasion, degree of differentiation and vascular tumor thrombus were associated with lymph node metastasis ( P<0.05), but age ≥ 60 years ( OR=5.556, 95% CI: 1.757-17.569, P=0.004), invasion depth ( OR=4.218,95% CI:1.418-12.548, P=0.010) and vascular cancer embolus ( OR=13.878,95% CI:4.081-47.196, P<0.001) were independent risk factors for lymph node metastasis of EGC. The consistency index of the risk model based on the above risk factors was 0.8835 (95% CI: 0.818 8-0.948 2). The calibration curve shows that the risk assessment model is in good agreement with the actual results, indicating that the model has high accuracy and discrimination.The most common site of metastasis was group 3, followed by group 4. Therefore, patients over 60 years old with submucosal invasion and vascular tumor thrombus may have a higher risk of lymph node metastasis.

Objective:To investigate the clinical value of neutrophil-lymphocyte ratio (NLR), fibrinogen (FIB), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in the diagnosis and prognosis of colorectal cancer.Methods:A case-control study design was used to select 155 patients with colorectal cancer[98 males and 57 females, aged (63.12±13.99)years old], 90 patients with colorectal polyps[62 males and 28 females, aged (56.86±12.74)years old] and 150 healthy subjects[93 males and 57 females, aged (57.02±10.91)years old] from the First Affiliated Hospital of Nanjing Medical University from October 2017 to March 2018. Blood routine tests were detected by instrument method, FIB was detected by Clauss method, and CEA and CA19-9 were detected by electrochemiluminescence method. The levels of the NLR, FIB, CEA and CA19-9 in the 3 groups were compared. The diagnostic efficacy of NLR, FIB, CEA and CA19-9 of colorectal cancer was compared according to the ROC curve. The relationship between the level of NLR, FIB, CEA and CA19-9 and their clinicopathological features in colorectal cancer patients was assessed. According to the median levels of NLR, FIB, CEA and CA19-9, 112 follow-up of colorectal cancer patients could be divided into the high-value group and the low-value group. Kaplan-Meier, log-rank test and Cox regression analysis were used to analyze the relationship between the levels of the four indicators and the prognosis of colorectal cancer.Results:The levels of NLR, FIB, CEA and CA19-9 in colorectal cancer group were 2.11(1.52, 2.86), 3.21(2.58, 3.86)g/L, 3.93(2.27, 8.78)μg/L, 15.11(9.10, 25.73)U/ml. The levels of NLR, FIB, CEA and CA19-9 in colorectal polyp group were 1.74(1.39, 2.17), 2.54(2.26, 3.03)g/L, 1.99(1.18, 2.70)μg/L, 9.83(6.13, 15.68)U/ml. The levels of NLR, FIB, CEA and CA19-9 in healthy control group were 1.68(1.33, 2.28), 2.56(2.30, 2.82)g/L, 1.85(1.28, 2.59)μg/L, 10.03(6.86, 13.26)U/ml. The levels of NLR, FIB, CEA and CA19-9 in colorectal cancer group were significantly higher than those in colorectal polyp group ( Z values were 3.568, 5.913, 6.880 and 4.022, P values were all<0.05) and healthy control group( Z values were 3.916, 7.381, 9.131 and 5.251, P values were all<0.05). The levels of NLR, FIB, CEA and CA19-9 in colorectal polyp group were not remarkably different from those in healthy control group ( Z values were 0.217, 0.179, 0.320 and 0.061, P values were all>0.05). The diagnostic performance of CEA was the best in single test, followed by FIB, CA19-9 and NLR. The sensitivity of combined NLR+FIB+CEA or NLR+FIB+CEA+CA19-9 was the highest with 72.3%. NLR and FIB levels were associated with tumor sites ( Z values were 3.587 and 7.089, P values were both<0.05). FIB and CEA levels were correlated with the depth of tumor invasion ( Z values were 3.250 and 3.245, P values were both <0.05). NLR, FIB, CEA and CA19-9 levels were both associated with lymph node metastasis ( Z values were 2.010, 3.276, 3.312 and 2.921, P values were all<0.05). The prognosis of patients in the high-value NLR, FIB, CEA and CA19-9 groups was significantly worse than that in the low-value group (χ 2 values were 5.744, 6.048, 4.389 and 6.942, P values were all<0.05).Cox multivariate regression analysis showed lymph node metastasis, NLR >2.15 and CA19-9 >15.47 U/ml are independent factors affecting the prognosis of colorectal cancer. Conclusion:NLR, FIB, CEA and CA19-9 can be applied in the auxiliary diagnosis and prognosis of colorectal cancer.

To investigate the risk factors of lymph node metastasis in early gastric cancer (EGC) and to develop a risk model for the presence of lymph node metastasis. A total of 172 EGC patients, with a median age of 62(52, 68) years, who underwent gastric cancer resection in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2019 were selected. Clinical data of the patients were collected through the case system. Logistic regression analysis was used to determine the variables significantly related to lymph node metastasis. ROC curve and calibration curve were used to evaluate the risk model. The results showed that the lymph node metastasis rate of 172 EGC patients was 19.19% (33/172). Tumor size, depth of invasion, degree of differentiation and vascular tumor thrombus were associated with lymph node metastasis ( P<0.05), but age ≥ 60 years ( OR=5.556, 95% CI: 1.757-17.569, P=0.004), invasion depth ( OR=4.218,95% CI:1.418-12.548, P=0.010) and vascular cancer embolus ( OR=13.878,95% CI:4.081-47.196, P<0.001) were independent risk factors for lymph node metastasis of EGC. The consistency index of the risk model based on the above risk factors was 0.8835 (95% CI: 0.818 8-0.948 2). The calibration curve shows that the risk assessment model is in good agreement with the actual results, indicating that the model has high accuracy and discrimination.The most common site of metastasis was group 3, followed by group 4. Therefore, patients over 60 years old with submucosal invasion and vascular tumor thrombus may have a higher risk of lymph node metastasis.

Objective:To compare the clinical outcomes and complications of oblique lateral interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach and posterior interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach by channel for lumbar spinal stenosis.Methods:A retrospective study was conducted on 73 patients who underwent surgical treatment for lumbar spinal stenosis from Jun 2015 to Jun 2017, including 33 males and 40 females. The average age was 66.8±7.94 years (from 39-85 years). These diseases occured at L 3/4 in 5 patients and L 4/5 in 68 patients. Random according to the time of admission, 38 cases were treated with oblique lateral interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach (oblique lateral fusion group), and 35 cases with posterior interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach by channel (posterior fusion group). The clinical results, image data and complications were compared between the two groups. Results:All patients in both groups had operation performed smoothly. The operation time was 99±8.96 min in the oblique lateral fusion group and 96.8±9.57 min in the posterior fusion group, and there was no significant difference between the two groups. The intraoperative bleeding in the oblique lateral fusion group 80±24.72 ml was significantly less than that in the posterior fusion group 261±52.87 ml ( t=9.621, P<0.05). No incision infection occurred after surgery. The VAS score of lumbar incision 72h after operation in the oblique lateral fusion group 1.21±0.55 was significantly less than that in the posterior fusion group 1.70±0.86 ( t=3.723, P=0.028). The follow-up period lasted for 12-24 months, averagely 17.5±2.58 months. There was statistically significant difference between preoperative and postoperative in the two groups, whether it was the area of the foraminal canal or the area of the spinal canal. There wboth the foraminal area and the spinal canal area were enlarged. The intervertebral space height in the two groups recovered significantly after surgery, the difference was statistically significant. But the intervertebral space height were partly lost at the last follow-up, and there was significant difference compared with postoperative. During the follow-up, no pedicle screw loosening, displacement, rupture, or anterior and lateral displacement of cage occurred. The fusion rate was 97.1% in the posterior fusion group and 100% in the oblique lateral fusion group. There was no statistical difference between the two groups.In terms of ODI index: the posterior fusion group recovered from 48.6±6.1 preoperative to 10.2±2.2 at the last follow-up, and the oblique lateral fusion group recovered from 49.0±5.7 preoperative to 9.3±1.8 at the last follow-up. There was statistically difference between last follow-up and preoperative in the two groups. The incidence of complications in the posterior fusion group was 22.86%, and the incidence in the oblique lateral fusion group was 23.68%. There was no significant difference between the two groups. Conclusion:Both the two decompression and fusion methods have achieved good clinical results in the treatment of lumbar spinal stenosis, with the advantages of less trauma, good stability, fast recovery, and high fusion rate. Compared with posterior decompression and fusion methods, the advantages of OLIF are more obvious, such as less bleeding,lower risk of nerve injury and good indirect decompression of spinal canal. Therefore, the OLIF technique can be a better choice for surgical treatment of lumbar spinal stenosis.

Objective: To study the effect of nutrition intervention on the body composition and blood glucose in newly diagnosed patients with type 2 diabetes mellitus complicated with overweight and obesity. Methods: A total of 84 newly diagnosed patients with type 2 diabetes mellitus complicated with overweight and obesity were selected from the department of endocrinology in China-Japan Friendship Hospital from April 2015 to December 2016. Basic information and body composition of these patients were collected and measured. Also the food frequency questionnaire (FFQ) was used to investigate the dietary status in the past month, and calculate the intake of energy, three major nutrients and dietary fiber. All patients received nutrition intervention by nutritionist for three months as requested by Diabetes guidelines. After 3-month intervention, blood glucose, body composition and dietary status were examined again. Relevant indicators of patients were compared before and after the intervention. All patients were divided into three groups according to the degree of body mass index (BMI)′s change: <5%, 5%-10% and >10%. The differences of body weight, muscle, body fat rate, visceral fat index and blood glucose level among three groups were quantified. Results: There were 53 male patients with age (41.5±8.9) years and HbA1c (7.5±0.4)%, and 31 female patients with age (40.1±8.5) years with HbA1c (7.6±0.5)%. The intake of energy, carbohydrate and fat of patients were significantly decreased (P<0.05) and dietary fiber was significantly increased (P<0.05) after nutrition intervention. The body weight, muscle mass, fat mass and visceral fat index were also significantly decreased (P<0.05). The average decrease of fat was about 2.8 kg accounting for 73.7% (2.8 kg/3.8 kg) of the total weight loss. The body fat rate decreased from (31.2±3.1)% to (28.8±3.2)% (P<0.05). The fasting blood glucose and postprandial blood glucose were both decreased significantly after intervention (P<0.05). Among three BMI decreased groups, there was no significant difference in body weight and muscle mass (P>0.05), but a significant difference in body fat rate and visceral fat index (P<0.05). The body fat rate, visceral fat index, fasting blood glucose and postprandial blood glucose had more decreases with the greater amount of weight loss (P<0.05). Conclusion The three-month nutrition intervention could change the dietary habit and components of patients with type 2 diabetes mellitus by reducing the blood glucose, body fat rate and visceral fat index significantly. The degree of reduced BMI is positively related to the decrease of fasting blood glucose and postprandial blood glucose.

BACKGROUND:Many in vivo and in vitro experiments indicate that hypoxic co-cultures promote stem cells differentiate into chondrocytes.
OBJECTIVE:To evaluate the influence of hypoxia on the chondrogenic differentiation of three-dimensional co-cultured adipose-derived stem cells and articular chondrocytes.
METHODS:Adipose-derived stem cells and articular chondrocytes were mixed at the ratio of 3:1, then the mixed cells were seeded onto poly(lactic-co-glycolic acid)-gelatin scaffold at the ultimate concentration of 5.0×1010/L. The cells were cultured in normoxia (20%O 2 ) and hypoxic (5%O 2 ) conditions for 6 weeks. After culture, hematoxylin and eosin staining was performed for histological structure analysis, and alcian blue staining was used to evaluate glycosaminoglycan synthesis. Type II col agen expression was detected by immunohistochemistry staining. The content of DNA, glycosaminoglycan and hydroxyproline in the scaffold-cellcomplex was measured.
RESULTS AND CONCLUSION:In the hypoxia group, hematoxylin-eosin staining showed the formation of massive cells and extracellular matrix;alcian blue staining showed massive glycosaminoglycan formation;immunohistochemistry staining detected strongly positive expression of col agen type II, the content of DNA, glycosaminoglycan and hydroxyproline was higher than the normoxia group. Hypoxia promotes in vitro chondrogenic differentiation of co-cultured adipose-derived stem cells and articular chondrocytes. .