Objective:To investigate the value of serum miR-145 and matrixmetallo proteinase-2 (MMP-2) levels in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy in triple-negative breast cancer.Methods:125 patients with triple-negative breast cancer who received neoadjuvant chemotherapy in the Hospital from Jan. 2022 to Dec. 2023 were prospectively included as the study objects, and 130 healthy people matching the age of the case group who underwent physical examination in our hospital during the same period were included as the healthy control group. Real-time fluorescence quantitative polymerase chain reaction was used to detect the serum miR-145 level of all subjects. Serum MMP-2 levels were determined by enzyme-linked immunosorbent assay (ELISA). After neoadjuvant chemotherapy, patients were evaluated according to Miller-Payne (MP) grading criteria and divided into pCR group and non-PCR group.Results:The serum miR-145 level in patients with tertiary breast cancer was 1.49±0.27, which was significantly lower than that in healthy control group (2.79±0.49), with statistical significance ( t=20.33, P<0.001). The serum MMP-2 level in triple negative breast cancer patients was (153.07±38.36) ng/mL, which was significantly higher than that in healthy control group (84.38±12.63) ng/mL, and the difference was statistically significant ( t=26.13, P<0.001). After neoadjuvant chemotherapy, the serum miR-145 level in non-PCR patients before treatment was 1.36±0.21, which was significantly lower than that in pCR group (1.74±0.20), with statistical significance ( t=9.93, P<0.001). After neoadjuvant chemotherapy, the serum MMP-2 level in non-PCR patients before treatment was (169.57±30.45) ng/mL, which was significantly higher than that in pCR group (121.61±31.79) ng/mL, and the difference was statistically significant ( t=8.24, P<0.001). Pearson correlation analysis showed that there was a significant negative correlation between serum miR-145 and MMP-2 levels in patients with triple-negative breast cancer before treatment ( r=-0.47, P<0.001). ROC curve analysis results showed that serum miR-145 and MMP-2 levels before treatment predicted the sensitivity and specificity of pCR after neoadjuvant chemotherapy for triple-negative breast cancer were 82.9% and 74.4%, 45.1% and 99.8%, respectively. The sensitivity and specificity of pCR after neoadjuvant chemotherapy for triple-negative breast cancer were 84.1% and 88.4%, respectively. Conclusion:Serum miR-145 and MMP-2 levels are related to the efficacy of neoadjuvant chemotherapy in patients with triple-negative breast cancer, and the combined application of the two has certain predictive value.

Acute pancreatitis is one of the most common acute abdominal diseases in clinical practice,and the common etiologies of acute pancreatitis include biliary diseases,alcohol,pancreatic duct diseases,metabolic disorders(hypertriglyceridemia and hypercalcemia),excessive eating,and diseases of the descending duodenum(periampullary duodenal diverticula).According to the etiology,acute pancreatitis is classified into biliary pancreatitis and hyperlipidemic pancreatitis,and although there are various pathogenic factors for biliary pancreatitis,biliary diseases including bile duct stones remain the most important etiology of biliary pancreatitis.Obstructed biliopancreatic duct drainage and abnormal pressure due to various causes,bile reflux into the pancreatic duct,obstruction of pancreatic juice drainage,and abnormal activation of pancreatic enzymes are the central links in the development of biliary pancreatitis.The location,size,texture,number and shape of bile duct stones are associated with the incidence rate and severity of biliary pancreatitis to a certain degree.

Alzheimer disease(AD),commonly known as senile dementia,is the most common type of dementia,resulting in progressive impairment of cognitive function,and is often accompanied by a variety of psychiatric symptoms,such as agitation.Agitated symptoms in AD patients often cause an increasing burden on caregivers,and current psychiatric medications may exacerbate adverse effects such as cognitive impairment and motor retardation in patients.Therefore,non-drug intervention is a very important adjuvant treatment option.This article reviews the clinical manifestations,possible mechanisms,drug therapy and non-drug intervention measures of agitation in order to provide reference for more effective treatment of AD.

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:To investigate the correlation between collateral circulation and infarct pattern and outcome in acute ischemic stroke patients with anterior circulation intracranial atherosclerosis.Methods:Acute ischemic stroke patients with anterior circulation intracranial atherosclerotic severe stenosis or occlusion admitted to the Department of Neurology, the First Affiliated Hospital of Xinxiang Medical College from September 2018 to March 2020 were included prospectively. According to diffusion-weighted imaging, the infarct patterns were divided into perforator pattern, territorial pattern, watershed pattern, and mixed pattern. At 90 d after onset, the modified Rankin Scale was used to evaluate the outcome. 0-2 was defined as good outcome, and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcome. Results:A total of 89 patients were enrolled, 50 (56.2%) had good collateral circulation and 39 (43.8%) had poor collateral circulation. The distribution patterns of infarct: 22 patients (24.7%) were perforator pattern, 26 (29.2%) were territorial pattern, 17 (19.1%) were watershed pattern, and 24 (30.0%) were mixed pattern. The proportion of patients with good collateral circulation was 81.8%, 65.4%, 29.4% and 41.7%, respectively in the perforator pattern group, territorial pattern group, watershed pattern group, and mixed pattern group. Good collateral circulation was more common in the perforator pattern group, and poor collateral circulation was more common in the watershed pattern group. At 90 d after onset, 53 patients (59.6%) had a good outcome and 36 (40.4%) had a poor outcome. The baseline homocysteine level in the good outcome group was significantly lower than that in the poor outcome group (17.91±4.62 μmol/L vs. 20.35±4.67 μmol/L; t=2.436, P=0.017), and the proportion of patients with good collateral circulation was significantly higher than that of patients with poor outcome (73.6% vs. 30.6%; χ2=16.124, P<0.001). Multivariate logistic regression analysis showed that higher homocysteine level was an independent risk factor for poor outcome (odds ratio 1.174, 95% confidence interval 1.061-1.298; P=0.002) and good collateral circulation was an independent protective factor for good outcome (odds ratio 0.095, 95% confidence interval 0.038-0.239; P<0.001). Conclusions:Good collateral circulation was more common in patients with perforator pattern, and poor collateral circulation was more common in patients with watershed pattern. Good collateral circulation was independently associated with the good clinical outcome in acute ischemic stroke patients with anterior circulation intracranial atherosclerosis.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system is a hotspot of gene editing and gene expression research, in which CRISPR/Cas13 system provides a new direction for RNA interference and editing. In this study, we designed and synthesized the corresponding gRNAs of CRISPR/Cas13a and CRISPR/Cas13b systems in non-homologous end joining (NHEJ) pathway, such as Ku70 and Lig4, and then detected the expression of ku70 and lig4 in HEK293T cells. The CRISPR/Cas13a system could efficiently knockdown the mRNA expression of ku70 and lig4 more than 50%, and CRISPR/Cas13b system also suppressed ku70 and lig4 about 92% and 76%, respectively. Also, CRISPR/Cas13a, b systems could down-regulate Ku70 and Lig4 proteins level to 68% and 53%, respectively. The study demonstrates that the CRISPR/Cas13 system could effectively knockdown the expression of RNA and protein in HEK293T cells, providing a new strategy for gene function and regulation research.
CRISPR-Cas Systems ; DNA Ligase ATP ; genetics ; Gene Expression Regulation ; genetics ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Ku Autoantigen ; genetics

Objective:To compare the efficacy and safety of domestic 16-row and imported 8-row mobile CT in clinics.Methods:A total of 1469 patients accepted domestic 16-row mobile CT head scans (1604 times) from March 2017 to August 2018 in Bayi Brain Hospital Affiliated to 7 th Medical Center of General Hospital of People's Liberation Army and Langfang Aidebao Hospital; and 15510 patients accepted imported 8-row mobile CT head scans (24994 times) from January 2016 to August 2018 in Bayi Brain Hospital Affiliated to 7 th Medical Center of General Hospital of People's Liberation Army. All patients underwent horizontal plain and enhanced head scans, cerebral CT angiography (CTA), and helical 3D imaging; and the imaging quality, operating power consumption, computed tomography dose index volume (CTDIvol) and stability within scanning volume ranges under different scanning modes of the two CT scans were compared. Results:(1) Imaging quality: the horizontal scanning of domestic 16-row mobile CT could clearly display low-density tissues such as the eyeball, optic nerve, brain stem, sulcus and cerebral gyrus; the imaging quality of both CT scans in patients with traumatic subdural hematoma and ischemic stroke completely met the clinical diagnosis and treatment standards. (2) Operating power consumption: the per-hour operating power consumption of domestic 16-row mobile CT ([0.286±0.018] kW·h) was obviously lower than that of imported 8-row mobile CT ([0.485±0.028] kW·h). (3) Radiological hazard: the CTDIvol of the horizontal scanning volume range in domestic 16-row mobile CT ([36.270±0.281] mGy) was significantly lower than that in the imported 8-row mobile CT ([82.520±0.441] mGy, P<0.05); the CTDIvol of enhanced axis scan volume range in the domestic 16-row mobile CT ([36.270±0.335] mGy) was significantly lower than that in the imported 8-row mobile CT ([70.728±0.424] mGy, P<0.05); the CTDIvol in the volume of CTA imaging of domestic 16-row mobile CT ([20.600±0.087] mGy) was significantly lower than that in the imported 8-row mobile CT ([29.300±0.335] mGy, P<0.05). The domestic 16-row mobile CT was designed with shock absorbers and guides; domestic 16-row mobile CT had small load, a low center of gravity, and good stability as compared with imported 8-row mobile CT. Conclusion:In terms of head scanning applications, the imaging quality of domestic 16-row mobile CT and imported 8-row mobile CT is in full compliance with clinical diagnostic standards, but the energy consumption and radiation risk of domestic 16-row mobile CT is significantly lower than imported 8-row mobile CT, enjoying good stability as compared with imported 8-row mobile CT.

Objective The prevalence of obesity is constantly increasing. Multiple metabolic complications are related to obesity, including type 2 diabetes mellitus and non-alcholic fatty liver disease(NAFLD). Our study aimed to investigate the prevalence of obesity comorbidities and its association with BMI. Methods 765 individuals who visited the multidisciplinary clinic for obesity in Peking University First Hospital from 2015, Jun. to 2018, Sept. were enrolled in this study. The height, body weight, waist circumference, hip circumference were measured during the first visit. Body adipose percentage and basal metabolic rate were recorded. Questionnaires for daily food intake, comorbidity, and lifestyle were recorded. Fasting insulin, C peptide, glucose, HbA1C , uric acid, liver enzymes and lipid profile were measured. Statistical analysis was performed using SPSS 16. 0, and P<0. 05 was considered as statistical significant. Results Daily energy intake was higher in obesity group [ obese vs non-obese, (2136.6±739.4vs1905.7±468.4)kcal/d,P=0.046].Hypertension,NAFLDandgoutriskincreasedsignificantly in obesity group (obese vs non-obese, 36.0％vs 24.5％, P=0.02;76.5％ vs 60.6％, P<0.01;6.9％ vs 1.8％, P=0.04, respectively) . Family history of obesity and diabetes increased in obesity group ( obese vs non-obese, 64.5％vs 53.6％, P=0.03;47.4％vs 37.3％, P=0.048). Fasting insulin and C-peptide levels were higher in obesity group [obese vs non-obese, (24.8 ± 15.3 vs 13.6 ± 9.5)μIU/ml, P<0.01;(3.72 ± 1.40 vs 2.70 ± 1.16)μIU/ml, P<0.01). Liver enzymes increased significantly in obesity group [obese vs non-obese, (47.2±45.4 vs 23.3±21.4)U/L, P<0.01; ( 30. 4 ± 24. 0 vs 19. 9 ± 8. 5 ) U/L, P=0. 001 ] . Conclusions Obesity population had higher risk of hypertension, NAFLD and gout. Fasting insulin, C-peptide, liver enzymes, and UA also increased significantly in these patients. It is critically important to those obese individuals for regular screening of NAFLD and diabetes mellitus.

Objective The ADVIA Centaur XP automatic chemiluminescence immunoassay system detec-tion performance of the thyroid hormones and antibodies for validation and evaluation.Methods With refer-ence to the American association of clinical laboratory standardization guide and other related documents,the ADVIA Centaur XP automatic chemiluminescence immunoassay system test 7 items thyroid hormones and an-tibodies(T3,T4,FT3,FT4,TSH,anti-TG,anti-TPO)of precision,accuracy,linear range and carry pollution rate for validation.Results Within the seven thyroid hormones and antibodies batch testing precision of CV and CV between batch precision between 1.51% -6.17% and 1.86% -6.17%.Is the average accuracy of bias of the largest testing project FT3(8.47%),but in the acceptable range,good correlation,correlation coefficient R of 0.994 or higher,Average bias <1/2 CLIA′88 TEa(12.5%).T3,T4,FT3,FT4,TSH,anti-TG and anti-T PO in 1.24-5.59 nmol/L respectively,and 60.07 -195.10 nmol/L,3.40 -22.87 pmol/L,14.59 -40.54 pmol/L,1.63-74.13 μIU/mL,60.10 -381.30 μIU/mL and 180.10 -531.50 μIU/mL range is linear,Carry pollution rate is between 0.04% -0.97%.Conclusion ADVIA Centaur XP automatic chemiluminescence im-munoassay system detecting thyroid hormones and antibodies results consistent with the data provided by the manufacturer,the test results are accurate and reliable,and can be used for the detection of clinical samples.

This study was aimed to investigate the effect of Forkhead Box G1 (FOXG1) on the epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells and the underlying mechanism. For this purpose, FOXG1 lentiviral interference (shRNA) plasmid and expression plasmid were constructed. Western blotting was used to analyze the expression of FOXG1 protein in five CRC cells, namely RKO, SW480, SW620, LoVo and DLD-1. The shRNA fragment of FOXG1 (shFOXG1) was designed and synthesized. Recombinant plasmids were obtained with the aid of DNA recombination technique. Double digestion and sequencing were used to identify the recombinant plasmids, and then lentivirus packaging, purification and stable transfection were carried out. Additionally, stable CRC cell lines were screened out. The changes of FOXG1 knockdown and overexpression efficiency, E-cadherin, Vimentin, Fibronectin, Snail, Twist mRNA and protein were investigated respectively by Western blotting and qRT-PCR analysis. Furthermore, the changes of cell morphology after knockdown and cell migration ability were evaluated respectively with optical microscopy, scratch test and Transwell assay. FOXG1 had the highest protein expression in RKO and the lowest in DLD-1 among the five CRC cells. Compared with those of the control group, the cell morphology in FOXG1 knockdown RKO group was changed from spindle into round or polygonal shape, cell polarization was enhanced and tight junction assembly was acclerated while cell migration distance was noticeably decreased. Moreover, the number of cells invaded and migrated through chambers was significantly reduced. Among these key factors of EMT, the expression of E-cadherin was increased while the expressions of Vimentin, Fibronectin, Snail and Twist were decreased. The opposite was the case in the overexpressed FOXG1 group. The overexpression of FOXG1 in CRC promoted the invasion and metastasis of CRC cells and played a crucial role in regulating the EMT. Thus, FOXG1 might be a novel therapeutic target in CRC treatment.