Objective The establishment of the model of myocardial ischemia-reperfusion injury (MIRI) in SD rats involves lengthy time, severe damage, and death of the rats.We aimed at an efficient and rapid method for establishing an MIRI model in rats to ensure a high success rate of modeling and survival of the animals.Methods Using the trachea intubation-assisted breathing machine, we fully exposed the hearts of 80 adult SD rats (8-10 weeks old and weighing 250-300 mg) by mutilating the 2-3 intercostal muscles.Then, we rapidly positioned and ligated the left anterior descending (LAD) coronary artery for an hour, and established the model of MIRI at 48 hours after releasing the slipknot.We performed electrocardiography (ECG) before, during, and at 1 and 48 hours after operation, ligated the same part again at 48 hours postoperatively, and measured the size of the myocardial ischemia and infarction areas using Evans-TTC double staining.Results The survival rate of the 80 rats was 90% and the success rate of MIRI modeling was 86.25%.After ligation of the LAD coronary artery, ECG showed the ST segment and T wave elevation, followed by gradual decrease of the ST segment and R wave voltage, the myocardium and cardiac apex muscle grey or dark grey below the ligation slipknot.The heart rate myocardial motion amplitude were obviously reduced after ligation.Evans-TTC double staining revealed an evident myocardial infarction area at 48 hours after modeling and the ratio of the ischemia area + infarction area to the total myocardial area of the left ventricle was 0.43 to 0.55 (P>0.05) and that of the infarction area to the ischemia area + infarction area was 0.35 to 0.45 (P>0.05).Conclusion The modified rat model of MIRI can be fast and efficiently established, with a high success rate of modeling and a low mortality of the animals.

Objective To prepare the multi-functional ultrasound contrast agents,which were investigated for ultrasound(US)/MR dual-mode imaging and high-intensity focused ultrasound(HIFU)synergism in vitro.Methods Double emulsion method was used to prepare the superparamagnetic iron oxide(SPIO)-loaded PLGA microcapsules(s-PLGA),and its morphology,size,Fe3O4 loading capacity were assessed.Then,the prepared s-PLGA microcapsules with different concentrations were applied to perform ultrasound and MR imaging in vitro.In addition,the degassed bovine liver in vitro was directly injected into 200 μl s-PLGA in saline(0.5 mg Fe/ml)just before HIFU ablation,the saline(200 μl)and pure PLGA (200 μl)were employed for control.After HIFU ablation,the volume of coagulated tissue irradiated by HIFU was calculated.Results The s-PLGA microcapsules were observed with regular spherical morphology and its average size was(885.6 ± 133.2)nm.In vitro,the s-PLGA showed hyperechogenicity in US imaging and MR negatively enhanced effeet in T2WI,the volume of coagulated tissue irradiated by HIFU after local injection of s-PLGA was larger than that of saline and pure PLGA(P＜0.05).Conclusions The prepared s-PLGA microcapsules are successfully acted as dual-mode biological imaging contrast agents for ultrasound and MR imaging and HIFU synergism in vitro.

Objective To explore the effect of apolipoprotein E deficiency on astrocyte destruction in the ex vivo spinal cord slice model. Methods Vibratome-cut transverse spinal cord slices from C57BL/6 postnatal day 7 ApoE -/-mice and wild-type mice were cultured on transwell porous supports. After 7 days in the culture , spinal cord slices were exposed to LPS for 5 days. The expression of AQP4, GFAP and Iba1 was detected by immunofluorescence. The concentration of TNF-α and NO were detected by ELISA and method of nitrate reductase, respectively. Results Marked loss of AQP4 and GFAP staining were shown in LPS-affected groups, not in the control group, and the lesion score was higher in ApoE-/-group than WT-group (P<0.05). In addition, the expression of Iba1 and concentration of TNF-α, NO in the LPS-affected groups were more than that of the control group (P < 0.05), and they were higher in the ApoE-/-LPS group than the WT-LPS group (P < 0.05). Conclusions ApoE deficiency exacerbates astrocyte injury, likely through promoting the release of pro-inflammatory mediators from microglia.

Background and purpose:The third generation of aromatase inhibitors (AI) in postmenopausal hormone receptor-positive patients is the routine treatments in endocrine therapy. The 500 mg fulvestrant showed clini-cal beneifts in patients with previous AI treatment. This study aimed to access the effcacy and safety of 500 mg fulves-trant in estrogen receptor (ER) positive postmenopausal patients who had previous AI treatments with locally advanced and metastatic breast cancer.Methods:This study retrospectively analyzed the clinical data from 188 post-AI ER positive and (or) progesterone receptor (PR)-positive locally advanced and metastatic breast cancer patients treated with 500 mg fulvestrant in Fudan University Shanghai Cancer Center from Jul. 2011 to Dec. 2015. Primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR), clinical beneift rate (CBR) and safety proifle.Results:After the median follow-up of 11.3 months, median PFS was 5.9 months (95%CI: 4.2-7.5), CBR was 40.0% and ORR was 3.4%. COX proportional hazards regression analysis indicated that PFS was correlated with the number of metastatic sites (HR=1.92, 95% CI: 1.2-2.9,P =0.002) and previous lines of chemotherapy (HR=1.52, 95%CI:1.0-2.1,P=0.022). Six patients stopped the treatment for intolerable adverse events.Conclusion:The treatment of 500 mg fulvestrant has a favorable effcacy and safety in treatment of post-AI ER positive postmenopausal patientswith metastatic breast cancer.

Purpose: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. Materials and Methods: We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. Results: Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. Conclusion Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Objective:To investigate the clinical efficacy of ex vivo liver resection and autotransplantation (ELRA) for liver complex space-occupying lesions.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 50 patients with liver complex space-occupying lesions who underwent ELRA in the First Hospital Affiliated to Army Medical University between June 2009 and May 2017 were collected. There were 36 males and 14 females, aged from 13 to 69 years, with a median age of 51 years. All patients underwent ELRA. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination or telephone interview. Patients were followed up according to the individual follow-up plan in the first 6 months after discharge, and then once every 3 to 6 months to detect tumor recurrence and survival up to May 2019. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-rank test was used for survival analysis. Results:(1) Surgical situations: all the 50 patients underwent ELRA successfully, and postoperative pathological examination showed the R 0 resection rate was 100%(50/50). The operation time of the 50 patients were (630±186)minutes, of which 9 patients with liver benign occupation had the operation time of (684±168)minutes and 41 patients with liver malignant tumor had the operation time of (618±190)minutes. The operation time of temporary reconstruction of inferior vena cava and portacaval shunt, time of anhepatic phase, volume of intraoperative blood loss of the 50 patients were (35±9)minutes, (256±71)minutes, 2 000 mL(range, 400-10 000 mL), respectively. The remnant liver mass to standard liver mass ratio of the 50 patients was 65%±16%, of which 9 patients with liver benign occupation had the remnant liver mass to standard liver mass ratio of 63%±14% and 41 patients with liver malignant tumor had the remnant liver mass to standard liver mass ratio of 65%±17%. Of the 50 patients, 35 had vascular invasion (7 cases with liver benign occupation, 28 cases with liver malignant tumor), of which 24 (6 cases with liver benign occupation, 18 cases with liver malignant tumor) underwent in vitro vascular reconstruction, 12 (5 cases with liver benign occupation, 7 cases with liver malignant tumor) had bile duct invasion and underwent choledochojejunostomy due to the inability of the common bile duct to anastomose the ends. Two cases with liver metastasis of gastric cancer, one case with liver metastasis of colon cancer and one case with liver metastasis of pancreatic cancer underwent radical gastrectomy, radical resection of colon cancer, and pancreaticoduodenectomy, respectively. (2) Postoperative situations: the duration of postoperative hospital stay of the 50 patients were 25 days (range, 11-169 days). Of the 50 patients, 12 had pleural effusion who were treated with pleural puncture drainage, 10 had bile leakage who were treated with abdominal puncture drainage, 3 had bile duct anastomotic leakage who were treated with endoscopic nasobiliary drainage or biliary stent implantation, 6 underwent reoperation among which 4 underwent exploratory laparotomy due to abdominal hemorrhage, 1 underwent portal vein reconstruction due to abdominal hemorrhage combined with portal vein thrombosis, and 1 underwent salvage liver transplantation due to liver failure. Nine of the 50 patients died within 90 days after surgery, all of whom had liver malignant tumor. Among them, 3 died of multi-organ dysfunction syndrome caused by severe infection, 3 died of acute liver failure, 2 died of abdominal hemorrhage and 1 died pulmonary embolism. (3) Follow-up: all the 50 patients were followed up for 1 to 119 months. The overall survival time, 1-, 3-, 5-year overall and tumor-free survival rates of the 50 patients after operation were 17 months (range, 1-119 months), 68.0%, 45.9%, 41.1% and 41.9%, 33.4%, 30.8%, respectively. The overall survival time, 1-, 3-, 5-year overall and tumor-free survival rates of the 9 patients who with liver benign occupation after operation were 68 months (range, 10-114 months), 88.9%, 88.9%, 88.9% and 88.9%, 88.9%, 88.9%, respectively. The overall survival time, 1-, 3-, 5-year overall and tumor-free survival rates of the 41 patients who with liver malignant tumor after operation were 15 months (range, 1-119 months), 63.4%, 36.6%, 31.0% and 31.5%, 21.0%, 18.0%, respectively. There were significant differences in the overall and tumor-free survival rates between patients who with liver benign occupation and patients who with liver malignant tumor ( χ2=7.626, 11.766, P<0.05). Conclusions:ELRA can be applied in the treatment of liver complex space-occupying lesions. The selection criteria of patients with liver malignant tumor should be more rigorous to reduce perioperative mortality.

Objective: To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years. Results: The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (P<0.05). Compare with residents with annual household income less than 20 000 CNY in 2014, cancer risk assessment/screening intervention population, and self-assessment with cancer risk, residents with annual household income between 20 000 CNY and 59 000 CNY in 2014, occupational population, community residents, cancer patients, self-reported cancer-free risk, and self-assessment with unclear judgement of cancer risk were less likely to participate in the regular physical examination (all P values <0.05). Conclusion From 2015 to 2017, the Chinese urban residents had a acceptable consciousness of the cancer early detection. The marital status, annual household income, population group and self-assessment of cancer risk were related to the consciousness of the cancer early detection of people who had not participated in the regular physical examination in the past five years.

Objective: To understand the consciousness of the cancer early diagnosis among urban residents and identify the related factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The general demographic characteristics, the consciousness of the cancer early diagnosis (whether people would have a willingness or encourage their relatives/friends to confirm the abnormal results once which were detected from the physical examination) and other information were collected by using the self-designed questionnaire. The non-conditional logistic regression model was used to identify the relateol factors related to the consciousness of the cancer early diagnosis. Results: As for residents with abnormal result from the physical examination, 89.29% (28 802) of residents would choose to seek medical treatment for further diagnosis. If their relatives/friends had abnormal results from the physical examination, 89.55% (28 886) of residents would encourage their relatives/friends to confirm the diagnosis in time. The non-conditional logistic regression model analysis showed that compared with the public institution staff/civil servants, annual household income less than 20 000 CNY, the western region and the cancer risk assessment/screening intervention population, the company staff, annual household income about 40 000 CNY and more, and the residents from the middle and eastern region had a stronger consciousness to seek further diagnosis; while the unemployed residents and community residents were less likely to seek further diagnosis (P<0.05). Conclusions From 2015 to 2017, the Chinese urban residents had a good consciousness of the cancer early diagnosis. Occupation, annual household income, residential region and population group were related to the consciousness of the cancer early diagnosis.

Objective: To investigate the demand and access to the cancer prevention and treatment knowledge and related factors among urban residents in China from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of general demographic characteristics, the demand and access to cancer prevention and treatment knowledge, and the influencing factors of the attitude. The Chi-square test was used to analyze the difference of the demand of the cancer prevention knowledge among different groups and the corresponding factors of the cancer prevention and treatment knowledge were analyzed by using the logistic regression model. Results: The proportion of residents who need the cancer prevention and treatment knowledge was 79.5%. The demand rate of the inducement, symptom and diagnosis methods of cancer in the occupational population was highest, about 66.8%, 71.0% and 20.8%, respectively. The demand rate of treatment methods and cost in current cancer patients was the highest, about the 45.9% and 21.9%, respectively. The top three sources to acquire the cancer prevention and treatment knowledge were "broadcast or television" (69.5%), "books, newspapers, posters or brochures" (44.7%) and "family and friends" (33.8%). The multivariate analysis showed that compared with public institution personnel/civil servants, unmarried/cohabiting/divorced/widowed and others, annual household income less than 20 000 CNY, from the eastern region, people without cancer diagnosis and people with self-assessment of cancer risk, the demand rate of cancer prevention and treatment knowledge was higher in enterprise personnel/workers, married, annual household income between 60 000 CNY and 150 000 CNY, from the central region, people with cancer and people with unclear cancer risk (all P values <0.05). Conclusion There was a high demand for the cancer prevention and treatment knowledge among urban residents in China from 2015 to 2017. The main access to the knowledge is from the radio or television. The occupation, marital status, annual household income, residential region, health status and risk of disease were the main factors of the demand of the cancer prevention and treatment knowledge.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled