Objective:To investigate the relationship between serum insulin-like growth factor-1 (IGF-1) levels and intracranial or extracranial atherosclerosis in patients with cerebral small vessel disease (CSVD).Methods:A total of 407 patients with CSVD admitted to Xiangya Hospital of Central South University between July 2021 and September 2023 were enrolled in the study. Carotid duplex ultrasound was used to measure the internal diameter, intima-media thickness (IMT), vascular wall thickness, plaque property score, stenosis index, and stenosis ratio of the bilateral common carotid arteries, internal carotid arteries, external carotid arteries, and vertebral arteries. Magnetic resonance angiography was used to assess the degree of stenosis in intracranial arteries. Patients were divided into 4 groups based on the serum IGF-1 levels (low level group:≤5.21 ng/ml, medium level group:>5.21 ng/ml and ≤10.73 ng/ml, high level group:>10.73 ng/ml and ≤24.26 ng/ml, extremely high level group:>24.26 ng/ml). The IMT of the common carotid artery, carotid plaques, diameters of various cervical vascular lumens, carotid artery diameter stenosis, and intracranial artery stenosis in 4 groups of the patients were compared. The relationship between IGF-1 and intracranial and extracranial atherosclerosis was analyzed by univariate Logistic regression analysis and multivariate Logistic regression analysis.Results:There were inter group differences among the 4 groups in internal carotid artery diameter [low level group 5.45 (0.50) mm vs medium level group 5.32 (0.55) mm vs high level group 5.30 (0.55) mm vs extremely high level group 5.30 (0.50) mm; H=8.210, P=0.042]. The carotid IMT [low level group 0.80 (0.05) mm vs medium level group 0.80 (0.05) mm vs high level group 0.83 (0.03) mm vs extremely high level group 0.83 (0.09) mm; H=8.107, P=0.044], the proportion of carotid artery vascular wall thickening [low level group 52.9%(54/102) vs medium level group 48.0%(49/102) vs high level group 68.3%(69/101) vs extremely high level group 60.8%(62/102); χ2=9.889, P=0.020], the carotid artery plaque property score [low level group 1 (2) vs medium level group 2 (2) vs high level group 2 (2) vs extremely high level group 2 (2); H=8.913, P=0.030] and the proportion of anterior cerebral artery stenosis [low level group 2.9%(3/102) vs medium level group 2.0%(2/102) vs high level group 4.0%(4/101) vs extremely high level group 10.8%(11/102); χ2=10.473, P=0.014] had inter group differences among the 4 groups, and the differences were statistically significant. Univariate Logistic regression analysis indicated that carotid artery vascular wall thickening ( OR=1.197, 95% CI 1.003-1.429, P=0.046), anterior cerebral artery stenosis ( OR=1.814, 95% CI 1.148-2.867, P=0.011), and basilar artery stenosis ( OR=1.530, 95% CI 1.084-2.159, P=0.015) were correlated with IGF-1 levels. Multivariate Logistic regression analysis revealed that after adjusting for age, gender, low-density lipoprotein cholesterol (LDL-C), and C-reactive protein, IGF-1 was positively correlated with the carotid artery vascular wall thickening ( OR=1.311, 95% CI 1.014-1.696, P=0.039); after adjusting for age, IGF-1 was positively correlated with the anterior cerebral artery stenosis ( OR=2.130, 95% CI 1.201-3.776, P=0.010); after adjusting for gender, low-density lipoprotein cholesterol, and cholesterol levels, IGF-1 was positively correlated with basilar artery stenosis ( OR=1.688, 95% CI 1.063-2.681, P=0.027). Conclusions:There is an association between IGF-1 levels and intracranial and extracranial atherosclerosis in patients with CSVD. IGF-1 may play a role in the development and progression of atherosclerosis in CSVD.

Objective:To investigate the relationship between serum insulin-like growth factor-1 (IGF-1) levels and intracranial or extracranial atherosclerosis in patients with cerebral small vessel disease (CSVD).Methods:A total of 407 patients with CSVD admitted to Xiangya Hospital of Central South University between July 2021 and September 2023 were enrolled in the study. Carotid duplex ultrasound was used to measure the internal diameter, intima-media thickness (IMT), vascular wall thickness, plaque property score, stenosis index, and stenosis ratio of the bilateral common carotid arteries, internal carotid arteries, external carotid arteries, and vertebral arteries. Magnetic resonance angiography was used to assess the degree of stenosis in intracranial arteries. Patients were divided into 4 groups based on the serum IGF-1 levels (low level group:≤5.21 ng/ml, medium level group:>5.21 ng/ml and ≤10.73 ng/ml, high level group:>10.73 ng/ml and ≤24.26 ng/ml, extremely high level group:>24.26 ng/ml). The IMT of the common carotid artery, carotid plaques, diameters of various cervical vascular lumens, carotid artery diameter stenosis, and intracranial artery stenosis in 4 groups of the patients were compared. The relationship between IGF-1 and intracranial and extracranial atherosclerosis was analyzed by univariate Logistic regression analysis and multivariate Logistic regression analysis.Results:There were inter group differences among the 4 groups in internal carotid artery diameter [low level group 5.45 (0.50) mm vs medium level group 5.32 (0.55) mm vs high level group 5.30 (0.55) mm vs extremely high level group 5.30 (0.50) mm; H=8.210, P=0.042]. The carotid IMT [low level group 0.80 (0.05) mm vs medium level group 0.80 (0.05) mm vs high level group 0.83 (0.03) mm vs extremely high level group 0.83 (0.09) mm; H=8.107, P=0.044], the proportion of carotid artery vascular wall thickening [low level group 52.9%(54/102) vs medium level group 48.0%(49/102) vs high level group 68.3%(69/101) vs extremely high level group 60.8%(62/102); χ2=9.889, P=0.020], the carotid artery plaque property score [low level group 1 (2) vs medium level group 2 (2) vs high level group 2 (2) vs extremely high level group 2 (2); H=8.913, P=0.030] and the proportion of anterior cerebral artery stenosis [low level group 2.9%(3/102) vs medium level group 2.0%(2/102) vs high level group 4.0%(4/101) vs extremely high level group 10.8%(11/102); χ2=10.473, P=0.014] had inter group differences among the 4 groups, and the differences were statistically significant. Univariate Logistic regression analysis indicated that carotid artery vascular wall thickening ( OR=1.197, 95% CI 1.003-1.429, P=0.046), anterior cerebral artery stenosis ( OR=1.814, 95% CI 1.148-2.867, P=0.011), and basilar artery stenosis ( OR=1.530, 95% CI 1.084-2.159, P=0.015) were correlated with IGF-1 levels. Multivariate Logistic regression analysis revealed that after adjusting for age, gender, low-density lipoprotein cholesterol (LDL-C), and C-reactive protein, IGF-1 was positively correlated with the carotid artery vascular wall thickening ( OR=1.311, 95% CI 1.014-1.696, P=0.039); after adjusting for age, IGF-1 was positively correlated with the anterior cerebral artery stenosis ( OR=2.130, 95% CI 1.201-3.776, P=0.010); after adjusting for gender, low-density lipoprotein cholesterol, and cholesterol levels, IGF-1 was positively correlated with basilar artery stenosis ( OR=1.688, 95% CI 1.063-2.681, P=0.027). Conclusions:There is an association between IGF-1 levels and intracranial and extracranial atherosclerosis in patients with CSVD. IGF-1 may play a role in the development and progression of atherosclerosis in CSVD.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Objective:To study the value of sound touch elastography (STE) linear combined with ultrasound score (US) in the diagnosis of chronic hepatitis B (CHB) liver fibrosis, and to investigate whether their combination can improve the diagnostic efficiency of subdividing the degree of CHB liver fibrosis. Furthermore, a comparison with STE linear combined with the serological model was performed to seek the optimal linear combination model.Methods:A total of 313 subjects were enrolled from September 2018 to December 2021 in Shenzhen Third People′s Hospital Affiliated to Guangdong Medical University, including 259 patients with CHB who had completed liver biopsy and 54 healthy volunteers. CHB patients were divided into liver fibrosis group (F1-F4 group) according to METAVIR classification standard, and healthy volunteers were used as the control group. All subjects underwent liver ultrasound examination, STE and blood biochemical indexes of liver function. The US was performed according to the liver ultrasound examination, and the liver stiffness measurement (LSM) was measured by STE, aspartate aminotransferase and platelet ratio index (APRI) was calculated by blood biochemical index. Fisher discriminant analysis was used to establish the linear combination (LC) diagnostic marker of US and LSM, and the linear combination (LC2) diagnostic marker of LSM and APRI, successively. Spearman rank correlation coefficient was used to analyze the correlations between US, LSM, APRI, LC2, LC and pathological results. The ROC curves of US, LSM, APRI, LC2 and LC for diagnosing CHB liver fibrosis were plotted, and the diagnostic efficiency of above diagnostic markers was evaluated according to the accuracy, sensitivity, specificity and area under the ROC curve (AUC).Results:The formula for the linear combination of US and LSM was LC=0.986 0×US+ 0.166 7×LSM, and LC was highly positively correlated with pathological findings ( rs=0.851, P<0.001), higher than US, LSM, LC2 and APRI ( rs=0.825, 0.775, 0.802, 0.586, all P<0.001). LC showed the best diagnostic efficiency. The AUCs for diagnosing ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis were 0.945, 0.911, 0.954, 0.955, respectively, which superior to the AUCs of US (0.913, 0.879, 0.934 and 0.916, respectively), the AUCs of LSM (0.860, 0.871, 0.934 and 0.952, respectively) and the AUCs of LC2(0.899, 0.883, 0.941, 0.946, respectively). Compared with US, the AUC of LC diagnosis of ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis increased by 3.2%, 3.2%, 2.0% and 3.9%, respectively, with all significant differences ( P<0.05). Compared with LSM, the AUC of LC increased by 8.5%, 4.0%, 2.0% and 0.3%, respectively, with significant difference ( P<0.05) except for stage =F4 cirrhosis.Compared with LC2, the AUC of LC increased by 4.6%, 2.8%, 1.3% and 0.9%, respectively, and there were significant differences in the diagnosis of ≥F1 and ≥F2 liver fibrosis ( P<0.05). Moreover, the overall efficiency of LC2 was not significantly improved than LSM, the difference was not significant ( P>0.05). Conclusions:US, LSM, LC2 and LC can be used to diagnose the degree of CHB liver fibrosis, but LC is better than US or LSM and LC2 alone, especially in the subdivision of mild liver fibrosis, which is a promising new diagnostic marker to subdivide the degree of CHB liver fibrosis.

Objective:To analyze the effectiveness and safety of the second course radiotherapy for unresectable colorectal cancer liver metastases.Methods:We retrospectively collected the data of 28 patients with unresectable colorectal cancer liver metastases who received the second course radiotherapy at Peking University Cancer Hospital and Institute from 2017 to 2023, to analyze the feasibility of re-irradiation.Results:For the 28 patients, the median follow-up time after re-irradiation was 20.2 months. The median time interval between the first- and second-course radiotherapy was 11.1 months. The median biologically effective doses of the first- and second-course radiotherapy were 100 Gy and 96 Gy, respectively. Stereotactic body radiotherapy was administered to 25 patients (89.3%) during the first course and 24 patients (85.7%) during the second course of radiotherapy. The mean equivalent dose in 2 Gy fractions to the normal liver was 10.1 Gy in the first-course radiotherapy and 7.9 Gy in the second-course radiotherapy. The complete response rate, partial response rate, and objective response rate after re-irradiation were 54.5%, 18.2%, and 72.7%, respectively. After re-irradiation, the 2-year cumulative local failure rate was 17.0% when calculated based on patients and 15.1% when calculated based on lesions, the 1-year progression-free survival rate was 27.4%, and the 3-year overall survival rate was 46.7%. The second-course radiotherapy was well tolerated, with most patients (75.0%) experiencing grade 1-2 acute adverse reactions and only one case (3.6%) experiencing grade 3 acute adverse events.Conclusions:Second course radiotherapy is an effective and safe treatment approach for selected patients with unresectable colorectal cancer liver metastases.

The "quality-oriented education" is closely integrated with the problem-based learning(PBL) teaching mode. In the teaching of Technologies for Microbial Detection course, the PBL teaching mode is the carrier, the student is the host, and the brainstorm guides the students to conduct "dialectical thinking", so as to cultivate the students' "innovation", "social morality" and "self-learning ability". We choose the interactive platform of "WeChat" and "MosoInk WebSite" to make up for the deficiency of PBL teaching in the large class, and comprehensively assess students' knowledge and skills, humanistic quality, and value judgment.

Objective: To compare T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) in the patients with coexistence of HBsAg and HBsAb and other HBV infected patients. Methods: The clonotype and diversity of CDR3 in blood of group cases (positive HBsAg and HBsAb) (n=11), control 1 (negative HBsAg and positive HBsAb) (n=10) and control 2 (positive HBsAg and negative HBsAb) (n=10) were analyzed by high-throughput TCR sequencing with Illumina HiseqX10. Results: In the case group, the overlap rate of 6.28% (0.25%, 13.10%) was detected between any two samples, which was significantly lower than the overlap rate of 10.49% (6.20%，17.30%) seen in control 1 group (P=0.008). In control 2 group, the overlap rate of 2.60% (0.13%，13.69%) was significantly lower than control 1 group (P=0.001). There was no difference between case group and control 2 group. After pairwise comparison between the three groups, the frequency of clonotype TRBV7-2/TRBD1/TRBJ2-1 in case group was higher than that of control 1 group (P=0.029), the frequency of TRBV7-3/TRBD1/TRBJ2-7 in case group was lower than that of control 1 group (P=0.031). The difference of TRBV5-8 was significant in comparing case group with control 1 group (P=0.047). There were 14 clonotypes which had differences between case group and control 2 group in frequency. TRBV28was significant in comparing case group with control 2 group (P=0.028). For diversity, there was no difference among the three groups. Conclusion Clonotype TRBV7-2/TRBD1/TRBJ2-1, TRBV7-3/TRBD1/TRBJ2-7 and TRBV5-8 were associated with coexistence of HBsAg and HBsAb, but the diversity was not associated with TCR β chain CDR3.

Based on a non-competitive and selective PTP1B inhibitor reported by us previously, thirty-nine benzamido derivatives were designed and synthesized as novel PTP1B inhibitors. Among them, twelve compounds exhibited IC values at micromolar level against human recombinant PTP1B, and most of them exhibited significant selectivity to PTP1B over TC-PTP and CD45. Further evaluation of the most potent compound on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.

Objective To investigate the clinicopathological characteristics, differential diagnosis and biological features of natural killer (NK)/T cell lymphoma in nasal cavity. Methods The data of 17 cases of nasal NK/T-cell lymphoma from Department of Pathology in the Affiliated Hospital of Yangzhou University between September 2007 and July 2017 were collected. Pathologic analysis including clinical symptoms, pathomorphism and immunophenotyping was performed, and the literatures were also analyzed. Results The clinical symptoms of the patients with nasal NK/T cell lymphoma were not obvious, which were accompanied by nasal congestion,runny nose,and blood in the runny nose.Pathologic examination showed obvious necrosis and inflammatory background of different levels. There were allotypic lymphocytes in the inflammatory background, nuclear irregular distortion or folding, unapparent nucleoli and visible nuclear fission, tumor cell growth for the center with blood vessels resulting in invasion and damage to blood vessels, in which normal lymphocytes,plasma cells and tissue cells could be seen.CD3,CD43,CD56,TIA-1,granzyme B,perforin and other markers were expressed in the tumor cells, and EB virus in situ hybridization was positive. Conclusions Nasal NK/T cell lymphoma is rare,with high incidence of invasive tumor, high recurrence rate, poor prognosis and easy misdiagnosis, which needs immunohistochemistry for differential diagnosis. Treatment is mainly based on radiotherapy and chemotherapy.

Objective To explore the diagnostic value of magnetic resonance diffusion weighted imaging(DWI),3D time of flight magnetic resonance angiography(3D-TOF MRA),and 3D arterial spin labeled MR perfusion imaging(3D-ASL)in the senile ischemic cerebrovascular diseases.Methods Ninety patients with acute cerebral infarction and 69 with transient ischemic attack were retrospectively analyzed based on data of DWI,3DTOF MRA and 3D-ASL MRI.Additionally,60 healthy individuals were recruited as a control group.SPSS 21.0 statistical software was used.Results In 90 acute cerebral infarction(ACI)group,the 3D-ASL MRI showed hypoperfusion in 85 patients,hyperperfusion in 2 patients,and no apparently perfusion abnormality in 3 patients.In 85 hypoperfusion patients,the average hypoperfusion area showed by 3D-ASL MRI was(2 543±1 133)mm2,which was higher than the area of high signal in DWI(817±413) mm2 (P＜0.01),with ASL＞DWI in 83 cases and ASL≈DWI in 2 cases.In 69 transient ischemic attack patients,25 patients had artery stenosis and abnormal ASL,11 patients had artery stenosis and normal ASL,17 patients had normal vascular and abnormal ASL,15 had normal vascular and normal ASL.The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value were higher in 3D-TOF MRA combined with 3D-ASL than in their individual inspection(x2=10.35,P＜0.01,P＜0.05),and the rates of missed diagnosis and misdiagnosis were lower in 3D-TOF MRA combined with 3D-ASL than in their individual inspection (x2 =4.93,P ＜ 0.05).Conclusions ASL,MRA,and DWI can =reflect the different characteristics of the senile ischemic cerebrovascular diseases,and should be used as the standard sequence in geriatric neurology to provide more comprehensive information for the diagnosis and treatment of senile ischemic cerebrovascular disease.