Objective:To investigate the underlying neuroimaging mechanism of migraine without aura (MwoA) by using methods of voxel-based morphometry (VBM) and resting-state functional connectivity (FC).Methods:Twenty-five MwoA patients admitted to Department of Neurology, the Second Affiliated Hospital of Xuzhou Medical University from September 2020 to June 2023 were recruited as MwoA group, and 22 volunteers were recruited as healthy control (HC) group. Demographic, clinical characteristics, scores of Hamilton Anxiety Scale (HAMA), Hamilton Depression Rating Scale (HAMD) and Montreal Cognitive Assessment (MoCA) of all subjects were collected; MwoA patients also received Migraine Disability Assessment Questionnaire, Headache Impact Test-6 and headache Visual Analogue Scale assessments. All subjects underwent high-resolution 3D-T 1 and resting-state functional magnetic resonance imaging scanning. The SPM12 software was used to compare the difference in gray matter volume (GMV) between the 2 groups by VBM method. The GRETNA software was adopted to calculate the whole brain FC with anatomical automatic labeling 90 as the regions of interest, and the difference in FC between the 2 groups was statistically analyzed by two-sample t-test. Pearson partial correlation was used to analyze the correlation between brain GMV and FC changes and clinical features and scale scores of MwoA patients. Results:There existed no statistically significant difference between the 2 groups in age, gender, education, scores of HAMA, HAMD and MoCA (all P>0.05). Migraine Disability Assessment Questionnaire, Headache Impact Test-6 and headache Visua Analogue Scale scores of MwoA patients were (8.86±4.55), (50.27±6.35) and (6.68±1.73). Compared with the HC group, GMV was significantly decreased in the right superior frontal gyrus (SFG), right cingulate gyrus (CG) and left thalamus in the MwoA group ( P<0.05, false discovery rate corrected). In addition, the MwoA group showed decreased FC between left thalamus and right cuneus, left lingual gyrus (LG) and bilateral precuneus; decreased FC between right thalamus and right cuneus, right LG and right precuneus; decreased FC between right cuneus and left precuneus and right SFG; decreased FC between left LG and bilateral precuneus, decreased FC between right LG and right precuneus and left SFG; decreased FC between left precuneus and bilateral SFG, and between right precuneus and right SFG (edge P<0.001, component P<0.05, network-based statistics correction, interation=2 000). In MwoA patients, the FC (z-value) between left thalamus and right cuneus was negatively correlated with the duration of disease ( r=-0.530, P=0.011). Conclusions:MwoA patients showed decreased GMV in right SFG, CG and left thalamus. In MwoA patients, FC between thalamus and visual network (VN) and default mode network (DMN) was significantly decreased, and FC among VN, DMN and executive control network was significantly decreased. These changes in brain structure and function may be an adaptive change in the central sensitivity and responsiveness to pain stimuli, and may be an important neuroimaging mechanism of MwoA.

Objective:To investigate the differences in resting-state functional connectivity (FC) between patients with vestibular migraine (VM) and migraine without aura (MwoA) in order to infer the possible neuroimaging mechanisms of VM.Methods:Thirty VM patients admitted to the Department of Neurology of the Second Affiliated Hospital of Xuzhou Medical University from December 2019 to December 2022 were selected as the experimental group (EG) (6 males and 24 females, with mean age of 38.3 years) and 26 MwoA patients as the control group (7 males and 19 females, mean age 35.5 years). General demographic and clinical data such as gender, age, year of education, course of disease and frequency of attacks were collected for all the patients, as well as data of Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), headache Visual Arialogue Scale (VAS), Headache Impact Test 6 (HIT-6) and Migraine Disability Assessment Questionnaire (MIDAS). VM patients were also assessed by Dizziness Handicap Inventory (DHI), dizziness VAS and Vestibular Disorders Activities of Daily Living (VADL) scales. All patients underwent resting-sate functional Magnetic Resonance Imaging (fMRI) scans. Bilateral parietal opercular cortex 2 (OP2) and primary visual cortex (V1) were used as regions of interests (ROIs). Differences in FC between ROIs and other brain regions were calculated between the two groups. In view of the brain regions with significant differences, z-values of FC were extracted for each subject in the EG, and Pearson partial correlation analysis was conducted between z-values of FC and clinical characteristics of patients, P<0.05 was considered to have significant correlation. SPSS 22.0 was used for statistical analysis. Results:There was no significant difference in gender, age, years of education, course of disease, frequency of attack and scores of MoCA, HAMA and HAMD between the two groups ( P>0.05). Headache VAS, HIT-6 and MIDAS scores in VM patients were significantly lower than those in MwoA patients ( P<0.05). Compared with MwoA patients, the FC between left OP2 and bilateral precuneus and left thalamus was significantly increased in VM patients, and the FC between right OP2 and left thalamus and right anterior cingulate gyrus were significantly increased ( P<0.05, False Discovery Rate correction). Correlation analysis showed that the FC between left OP2 and left precuneus was positively correlated with DHI score in VM patients ( P=0.007, r=0.480), and the FC between right OP2 and left thalamus was positively correlated with the disease course in VM patients ( P=0.015, r=0.439). Conclusions:The pathogenesis of VM may be related to the altered FC of vestibular, pain and visual-motor networks, abnormalities of these neural pathways may be important imaging biomarkers of VM pathogenesis.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective: As a gate-keeper enzyme link, pyruvate dehydrogenase E1 subunit alpha (PDHA1) functions as a key regulator during glycolysis and the mitochondrial citric acid cycle, which has been reported in several tumors. Nevertheless, the effects of PDHA1 on biological behaviors and metabolism remain unclear in cervical cancer (CC) cells. The study aims to explore the PDHA1 effects on glucose metabolism in CC cells and its possible mechanism. Methods: We first determined the expression levels of PDHA1 and activating protein 2 alpha (AP2α) as a PDHA1 potential transcription factor. The effects of PDHA1 in vivo were evaluated through a subcutaneous xenograft mouse model. Cell Counting Kit-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) labeling assay, Transwell invasion assay, wound healing assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometry were performed in CC cells. Oxygen consumption rate (OCR) levels were determined to reflect aerobic glycolysis level in gastric cancer cells. Reactive oxygen species (ROS) level was measured with 2′, 7′-dichlorofluorescein diacetate kit. The relationship between PDHA1 and AP2α was examined by conducting chromatin immunoprecipitation assay and electrophoretic mobility shift assay. Results: In CC tissues and cell lines, PDHA1 was downregulated, while AP2α was upregulated. Overexpression of PDHA1 remarkedly inhibited the proliferation, invasion and migration of CC cells, and tumor growth in vivo, as well as promoted OCR, apoptosis and ROS production. Moreover, AP2α directly bound to PDHA1 within suppressor of cytokine signaling 3 promoter region to negatively regulate PDHA1 expression level. What is more, PDHA1 knockdown could effectively reversed the AP2α silencing-mediated suppressive effects on cell proliferation, invasion, migration, and the promotive effects of AP2α knockdown on OCR, apoptosis and ROS production. Conclusions Our findings demonstrate that AP2α negatively regulated PDHA1 via binding to PDHA1 gene promoter to promote malignant CC cell behaviors, which may provide a potential approach for CC therapeutics.

Objective:To introduce the improved "pull technique" and its preliminary application in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine.Methods:Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine has started to implement the "pull technique" since March 2018.After one patient suffered from postoperative tunnel infection, we′ve improved the operation method: after successful extubation, small incision was made at the tunnel entrance, and the skin was properly trimmed and sutured to close the tunnel entrance.Results:Until May 2020, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine has implemented the modified tube removal for 15 patients.During the follow-up period (0-25 months), there was no secondary infection or peritoneal effusion.Conclusion:For patients who meet the indications of "pull technique" , the improved "pull technique" is a trial method, which can reduce the risk of secondary infection and peritoneal effusion.

OBJECTIVE：To investigate the anti- hepatic fibrosis （HF）effects of Qiwei qinggan powder and explore its possible mechanism. METHODS ：Male Wistar rats were randomly divided into blank group ，HF model group ，Qiwei qinggan powder low-dose，medium-dose and high-dose groups [ 135，270，405 mg/（kg·d），by total amount of crude drugs] ，with 12 rats in each group. Except for blank group ，other groups were given 50％ CCl4-peanut oil solution intragastrically （2 mL/kg，twice a week ，for consecutive 8 weeks） to induce HF model. At same time ， blank group and model group were given constant volume of 0.5％ CMC-Na solution intragastrically ；administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 8 weeks. General situation of rats were observedand liver morphology was observed after last administration and hepatic indexes were detected. The contents of liverfunction indexes （ALT，AST，ALP，HYP）in serum and the expression of α-SMA in hepatic tissue were determined ， and HE and Masson staining were performed to observe the histopathology. Using the difference multiple of expression quantity as the index ，TMT technology was used to screen the differentially expressed protein in medicine group （combining the liver tissue samples of Qiwei qinggan powder groups ）and HF model group. Uniprot-GOA database and KAAS ，KEGG mapper online tools were used to analyze GO and KEGG pathway enrichment. RESULTS ：The rats in the blank group were in good health ；the liver was bright red and smooth ，the liver lobules were intact ，no degeneration and necrosis ，inflammatory cell infiltration or fibrous tissue proliferation was found. Compared with blank group ，the rats in HF model group had poor diet ，depressed spirit ，disordered and lusterless fur ；the liver was dark red or yellow with rough surface ，hard texture ，inflammatory cell infiltration ，fiber tissue destruction ，bridge connection and so on ；the hepatic index ，the contents of liver function indexes and the expression of α-SMA were increased significantly （P＜0.05）. Compared with HF model group ，above symptoms of rats were improved to different extent in different dose groups of Qiwei qinggan powder ；hepatic index in Qiwei qinggan powder low-dose group ，the content of ALP in high-dose group ，the contents of ALT，AST and HYP and the expression of α-SMA in different dose groups were decreased significantly （P＜0.05）. A total of 42 differentially expressed proteins related to HF were screened ，of which 15 were up-regulated and 27 were down-regulated in expression，including fatty acid binding protein 4（FABP4），cholesterol 7α-hydroxylase（CYP7A1）. The results of enrichment analysis showed that the differentially expressed proteins were mainly enriched in extracellular space ，blood particles and other cell parts，involving the molecular functions of oxidoreductase activity and fatty acid binding ，the biological processes of the regulation of heterotypic cell adhesion ，protein activation cascade ，as well as retinol metabolism ，arachidonic acid metabolism ，PPAR and other signal pathway. CONCLUSIONS ：Qiwei qinggan powder can reduce the hepatic index ，ALT，AST，ALP and HYP contents in serum ，down-regulate the expression of α-SMA，improve the degree of inflammation and fibrosis of liver tissue ，and have a certain protective effect on rats. The anti-HF mechanism of it involves multiple targets and signal pathways ，such as FABP 4， CYP7A1 and PPAR.

This paper describes how to apply UpToDate ? system can be applied into the evidence-based teaching of difficult and critical clinical problems of nephrology, combined with the practical case of standardized training for specialists. The treatment difficulties can be put forward by teachers or students, and appropriate terms are selected to search in UpToDate ?. The students are required to learn the content of the searched items, and then give their treatment choices and clarify reasons according to the condition of patients. After that, the instructing doctor will comment on the statements of each training specialist, and give treatment plans. Promotion the application of UpToDate ? system is helpful to improve the teaching quality of the standardized training for specialists.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Objective: To investigate the prevalence and severity of cerebral microbleeds(CMBs) in patients with different stroke classifications of cerebral infarction. Methods: From October 2016 to December 2017, the clinical data of patients with acute cerebral infarction in the Second Affiliated Hospital of Xuzhou Medical University were collected through the prospective study.The SWI technique was used to screen the CMBs.According to the TOAST and OCSP classifications, the prevalence and severity of CMBs in patients with different stroke classifications of cerebral infarction were analyzed. Results: A total of 254 patients with cerebral infarction were enrolled, there were 136 patients(53.54%) in CMBs group and 118 patients(46.46%) in no CMBs group.The prevalence of CMBs in patients with different TOAST classifications was large artery atherosclerosis(54.29%), small-artery occlusion(64.15%), cardioembolism(40.43%), stroke of other determined etiology(33.33%), stroke of undetermined etiology(38.46%), and the difference was statistically significant(χ²=12.206, P=0.016). The prevalence of CMBs in patients with different OCSP classifications was total anterior circulation infarcts(43.75%), partial anterior circulation infarcts(51.19%), posterior circulation infarcts(49.18%), lacunar infarcts(67.53%), and the difference was statistically significant(χ²=8.944, P=0.030). The severity of CMBs in patients with different TOAST classifications was large artery atherosclerosis[mild(55.26%), moderate(26.32%), severe(15.79%)], small-artery occlusion[mild(25.00%), moderate(33.82%), severe(41.18%)], cardioembolism[mild(57.89%), moderate(26.32%), severe(15.79%)), stroke of other determined etiology[mild(50.00%), moderate(33.33%), severe(16.67%)], stroke of undetermined etiology[mild(60.00%), moderate(20.00%), severe(20.00%)], and the difference was statistically significant(Fisher exact test, P=0.025). The severity of CMBs in patients with different OCSP classifications was total anterior circulation infarcts[mild(57.14%), moderate(28.57%), severe(14.29%)], partial anterior circulation infarcts[mild(52.50%), moderate(32.50%), severe(15.00%)], posterior circulation infarcts[mild(50.00%), moderate(33.33%), severe(16.67%)], lacunar infarcts[mild(25.00%), moderate(32.69%), severe(42.31%)], and the difference was statistically significant(Fisher exact test, P=0.023). Conclusion The prevalence and severity of CMBs in patients with different stroke classifications of cerebral infarction are variable.The prevalence of CMBs in small-artery occlusion and lacunar infarcts are the highest and give first place to severe CMBs(number of lesions≥10). We should pay attention to these two stroke classifications by early recognition and taking targeted clinical strategies.