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.

Monogenic cerebral small vessel disease refers to a group of rare hereditary cerebral small vessel diseases caused by a single gene mutation, which is clinically and genetically heterogeneous, resulting in a high rate of misdiagnosis. Although the causative genes of monogenic cerebral small vessel disease have been partially discovered, the pathophysiological mechanism is still unclear, and there is a lack of effective treatment. In recent years, great progress has been made in the genetic research of monogenic cerebral small vessel disease. The therapeutic research progress of 4 relatively common monogenic cerebral small vessel diseases was mainly summarized in this article, in order to provide new directions for further in-depth exploration.

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.

Monogenic cerebral small vessel disease refers to a group of rare hereditary cerebral small vessel diseases caused by a single gene mutation, which is clinically and genetically heterogeneous, resulting in a high rate of misdiagnosis. Although the causative genes of monogenic cerebral small vessel disease have been partially discovered, the pathophysiological mechanism is still unclear, and there is a lack of effective treatment. In recent years, great progress has been made in the genetic research of monogenic cerebral small vessel disease. The therapeutic research progress of 4 relatively common monogenic cerebral small vessel diseases was mainly summarized in this article, in order to provide new directions for further in-depth exploration.

Objective To explore the short-term surgical outcomes of the modified surgical procedure for uniportal thoracoscopic right middle lobectomy (RML). Methods In this modified approach, the incision was created at sixth or seventh intercostal space inferior to the subscapular angle. The surgeon stood on the opposite side of the operating table. The surgery was performed by serial division of the anterior oblique fissure, the vein, bronchus, artery, and horizontal fissure following the single-direction strategy. As for patients with malignant lesions, hilar and mediastinal lymph node dissection was performed. Clinical characteristics and early surgical outcomes were collected and analyzed. Results Fifty two patients were included in this study in the Department of Thoracic Surgery, West China Hospital, Sichuan University between January 2021 and June 2023. There were 20 males and 32 females at an average age of 48.0±10.5 years. No conversion or perioperative mortality was occurred. Mean surgical time was 68.1±16.8 min, mean blood loss was 16.5±4.9 mL, median chest tube duration was 2 (2-22) d and median postoperative hospital stay was 3 (3-24) d. There was no intraoperative or postoperative complication but one patient developed postoperative prolonged air leak (>5 d). Mean postoperative visual-analog scale on postoperative day 1, day 2 and day 3 was 1.5±0.8, 1.7±0.4, 0.8±0.7, respectively. Conclusion Trans-posterior-approach uniportal thoracoscopic single-direction RML is a safe, feasible, and effective procedure, which provides an appropriate direction and angle for dissection and stapling, solving the challenge of conventional uniportal RML lobectomy.

Objective:To investigate the clinical phenotype and genetic characteristics of cerebral small vessel disease (CSVD) caused by heterozygous mutations in high-temperature requirement A serine peptidase 1 ( HTRA1) gene. Methods:Nine patients with HTRA1 gene related autosomal dominant CSVD diagnosed in the Departments of Geriatrics and Neurology,Xiangya Hospital of Central South University between January 2020 and December 2023 were selected. Their clinical data were collected, and the probands received genetic test using whole exome sequencing. The mutations were then verified in the family using Sanger sequencing, and their clinical and genetic characteristics were summarized. Results:Among the 9 patients with HTRA1 gene related autosomal dominant CSVD, the onset age was (51.1±9.5) years. Cognitive impairment, stroke onset, and gait disturbance were the most common clinical manifestations. Magnetic resonance imaging examination usually revealed diffuse white matter lesions, multiple lacunar cerebral infarction, multiple cerebral microbleeds, and brain atrophy, which were consistent with the radiological characteristics of CSVD. Most patients showed a decrease in Aβ42 levels and Aβ42/Aβ40 ratio in cerebrospinal fluid, and 2/4 of patients had an increase in phosphory protein tau levels. Seven heterozygous mutations in the HTRA1 gene were found in 9 patients, including two new heterozygous missense mutations, c.1160T>C(p.M387T) and c.569G>T(p. A190L). Conclusions:The clinical manifestations of HTRA1 gene-related autosomal dominant CSVD patients are mainly cognitive impairment, stroke and gait disturbance, and the imaging features are consistent with CVSD changes. HTRA1 gene c.1160T>C(p.M387T) and c.569G>T(p.A190L) heterozygous missense mutations are newly reported mutations, expanding the genetic mutation spectrum of this disease.

Objective    To explore the safety and feasibility of the modified and improved thoracoscopic surgery for esophageal cancer using the concept of "single-direction" thoracoscopic technique. Methods    The clinical data of 65 patients undergoing this modified minimally invasive esophagectomy based on "single-direction" thoracoscopic system between June 2018 and April 2019 were retrospectively analyzed, including 54 males and 11 females aged 62.5±7.8 years. Results    The thoracoscopic operation time was 133.4±28.6 min, and intraoperative blood loss was 61.9±29.2 mL. No intraoperative blood transfusion was needed. One patient was transferred to open thoracotomy (due to severe pleural adhesion atresia). Major complications included anastomotic leak, pneumonia, chylothorax, incisional infection, recurrent laryngeal nerve paralysis and gastric emptying disorders, which were recovered by conservative treatment. No postoperative death occurred. The median number of lymph nodes and lymph node station harvested was 19 and 10, respectively. The median postoperative hospital stay was 10 days. The volume of chest drainage was 1 117.3±543.4 mL. Conclusion    The minimally invasive operation mode of esophageal cancer based on "single-direction" thoracoscopic system is safe and feasible, and has good field vision and smooth and simplified procedure.

Objective:To evaluate the value of adenosine triphophate (ATP)stress/rest nuclide myocardial perfusion imaging (MPI)in the diagnosis of female patients with coronary heart disease (CHD).Methods:The clinical materials of 47 female suspected CHD patients were retrospectively analyzed,aged from 39 to 74 years,and the average age was (53.7±6.3)years old.All patients were hospitalized and underwent two-day ATP stress and rest nuclide MPI and coronary angiography (CAG)in two weeks. The results and images of MPI and CAG were evaluated by more than 2 attending physicians. Using CAG as the “gold standard”, the diagnostic efficiency (sensitivity, specificity and accuracy) of MPI for CHD was evaluated. Results:Compared with CAG, the sensitivity,specificity and accuracy of ATP stress MPI in diagnosing the female CHD patients were 81.3% (13/16),77.4% (24/31)and 78.7% (37/47)individually;the positive predictive value and negative predictive value were 65.0% (13/20)and 88.9% (24/27).There were no severe adverse effects in the ATP stress test and the incidence of adverse effects was 85.1%.Conclusion:There is a highly diagnostic efficiency of ATP stress MPI in the CHD patients.It can be the first choice of examination methods for screening without injury and diagnosing the myocardial ischemia in the female patients.

OBJECTIVE: To explore the expression profile of Ephrin-B2 in the ischemic penumbra after transient focal cerebral ischemia in rats, and to clarify the mechanism of Ephrin-B2 triggering angiogenesis. METHODS: Sprague-Dawley rats were randomly divided into a normal group, a sham operation group and ischemic-reperfusion 1, 3, 7, 14, and 28 d groups. Suture-occluded method was used to establish the focal middle cerebral artery occlusion model and the ischemic brain was reperfused 2 h after the occlusion. Western blot and quantitative real-time reverse-transcription polymerase chain reaction were used to detect the dynamic expression profile of Ephrin-B2 in the penumbra cortex. Double immunofluorescence was used to speculate the location and the co-expression of Ephrin-B2 in blood vessels, neurons and astrocytes. Microvessel density was quantified by the number of CD31+ cells. Rats were subjected to neurologic functional tests by modified neurological severity scores (mNSS) before sacrifice. RESULTS: Compared with the sham group, Ephrin-B2 protein and mRNA level of the penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 7 and 14 (P<0.01), and declined at day 28. Double immunofluorescence indicated that Ehprin-b2 was expressed in the neurons, blood vessels and astrocytes; mNSS peaked at day 7, and gradually declined at day 14. The microvessel density of penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 14 (P<0.01), and gradually declined at 48 h. CONCLUSION Cerebral ischemia reperfusion induces the over-expression of Ephrin-B2, with a dynamic trend, suggesting that Ehprin-b2 may improve post-stroke functional recovery by enhancing angiogenesis and neurogenesis.
Animals ; Astrocytes ; metabolism ; Brain ; pathology ; Brain Ischemia ; metabolism ; Cerebral Cortex ; metabolism ; Ephrin-B2 ; metabolism ; Infarction, Middle Cerebral Artery ; Ischemic Attack, Transient ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism

Objective To investigate in vitro possible mechanisms by which low frequency electrical stimulation may stimulate peripheral blood stem cells' proliferation and differentiation into Schwann cells (SCs).Methods The original generation of peripheral blood stem cells was cultured using Sprague-Dawley (SD) rats.The third passage stem cells were divided into a low frequency stimulation group,an extracellular signal-regulated kinase (ERK) group,a combination group and a control group.All 4 groups were cultured in DMEM containing 2％ fetal bovine serum by adding the SC supernatant.The low frequency electrical stimulation group was given 1 h of continuous low frequency stimulation.For the ERK group 50 mmol/L of the inhibitor PD98059 was added.The combination group was given the inhibitor plus 1h of sustained low frequency electrical stimulation.The control group received no special intervention.Before and after induction the 3-(4,5-dimethyl-thiazol-2)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect the absorbance value A of 4 cells at 570 nm (A750),and after induction Western blotting was used to determine cyclin D1 (cyclin D1) and cyclin-dependent kinases (CDK4).Results Before the intervention peripheral blood stem cells in each group had no significant differences in their A750 values.After the intervention,the A750 values of the low frequency electrical stimulation,the ERK group,the combination group and the control group were (1.051 ±0.058),(0.363 ±0.343),(0.894 ±0.343) and (0.758 ±0.047),respectively.This showed a statistically significant increase for all groups except the ERK group.The differences among the groups were also statistically significant.The expression of S-100,glial fibrillary acidic protein (GFAP) and P75 was highest in the low frequency electrical stimulation group,and in the ERK group they were the lowest.S-100,GFAP and P75 protein expression also was highest in the low frequency electrical stimulation group and lowest in the ERK group,and the inter-group differences were statistically significant.ERK expression showed no significant difference among the groups.Compared with the control group,the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2),cyclin D1 and CDK4 protein in the low frequency electrical stimulation group and the combination group were all significantly higher and the protein expression in the ERK group was significantly lower.The p-ERK1/2,cyclin D1 and CDK4 protein levels in the combination group were significantly lower than in the low frequency electrical stimulation group and higher than in the ERK group.Conclusions Low frequency electrical stimulation can promote peripheral blood stem cell proliferation and induce cell differentiation into Schwann cells,at least in vitro.The ERK signaling pathways are part of the signaling pathways of the proliferation and differentiation.