Objective:To design and synthesize 89Zr-deferoxamine(DFO)-G4C2, a novel molecular probe targeting programmed cell death receptor 1(PD-1), and evaluate its in vivo biodistribution and microPET/CT imaging characteristics in tumor-bearing mice. Methods:DFO-G4C2 was prepared by coupling DFO with G4C2, a monoclonal antibody targeting PD-1. The affinity and binding specificity of this amalgamation were subsequently assessed through the implementation of flow cytometry and surface plasmon resonance techniques. The molecular probe 89Zr-DFO-G4C2 was achieved by labeling DFO-G4C2 with the radioisotope 89Zr, and the labeling efficiency and in vitro stability of 89Zr-DFO-G4C2 were determined. Mouse models laden with CT26 colorectal cancer cells expressing PD-1 were established, followed by in vivo biodistribution and microPET/CT imaging studies, to explore the potential clinical value of 89Zr-DFO-G4C2. Additionally, the validity of this molecular probe was verified in 4T1 breast cancer models, affirming its efficacy as an imaging tool across different tumor models. Independent-sample t test was used to analyze the data. Results:DFO-G4C2 exhibited an affinity constant KD of (0.55±0.02) μmol/L, indicating a strong binding affinity. The binding rate to mouse PD-1 protein was determined to be (61.82±8.49)%. The labeling rate of 89Zr-DFO-G4C2 reached a high level of (98.76±0.51)%. Furthermore, the labeling rates in lysate and human serum after 144 h were measured to be (93.07±2.16)% and (83.42±3.21)%, respectively. MicroPET/CT imaging of CT26 tumor-bearing mice injected with 89Zr-DFO-G4C2 showcased pronounced radioactivity uptake in the tumor tissue. At 72 h post-injection, the tumor uptake value reached (10.47±0.34) percentage activity of injection dose per gram of tissue (%ID/g). The tumor uptake observed in the blocked experimental group, wherein an excess of unlabeled antibody was administered, was significantly lower at (6.26±1.03) %ID/g in comparison to the non-blocked group ( t=6.67, P=0.003). The in vivo biodistribution results were consistent with the observed microPET/CT imaging outcomes. MicroPET/CT imaging observations in the 4T1 breast cancer bearing mouse model were analogous to those obtained from the CT26 model. Conclusion:ImmunoPET based on the 89Zr-DFO-G4C2 molecular probe can non-invasively and visually assess the PD-1 expression level of tumors in vivo, and it is expected to be a new molecular imaging technique for immunotherapy monitoring of PD-1 inhibitors.

Objective:To observe the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor combined with rosuvastatin on lipid levels and short-term prognosis in patients with acute ischemic stroke, and to explore the optimal therapeutic regimen in terms of efficacy and safety, so as to provide a basis for clinical practice.Methods:Consecutive patients with acute cerebral infarction within 72 hours of onset and lipids≥2.6 mmol/L admitted to Xuzhou Central Hospital from April 2022 to March 2023 were included in the study, and the randomized numeric table method was used to divide them into 3 groups of different treatment regimens, group A (rosuvastatin 20 mg, once a day), group B (rosuvastatin 10 mg, once a day+alirocumab 75 mg, once 2 weeks) and group C (rosuvastatin 20 mg, once a day+alirocumab 75 mg, once 2 weeks). General baseline data, National Institutes of Health Stroke Scale score, modified Rankin Scale score on day 90 and the occurrence of adverse events and serious adverse events were collected from the 3 groups. The primary efficacy outcome was the degree of reduction in low density lipoprotein-cholesterol (LDL-C) from baseline on day 90. The secondary efficacy outcomes were recurrence rate and time to recurrence in stroke patients within 90 days,etc. The primary safety outcome was hepatic insufficiency (transaminase elevation≥3 times normal) within 90 days. The secondary safety outcomes were death due to stroke within 90 days and fatal and nonfatal myocardial infarction.Results:A total of 501 patients were included, 166 patients in group A, 167 patients in group B, and 168 patients in group C. The differences in the baseline data of the 3 groups were not statistically significant (all P>0.05). LDL-C was reduced from baseline on day 90 in groups A, B, and C, with the differences of -1.5 (-1.7, -1.4) mmol/L, -2.2 (-2.5, -2.1) mmol/L and -2.2 (-2.6, -2.1) mmol/L, respectively, with statistically significant differences among the 3 groups ( H=1.497, P<0.001); the differences between the group A and group B, and between the group A and group C, were statistically significant ( Z=-11.125, P=0.006; Z=-9.475, P=0.012), while the difference between the group B and group C was not statistically significant ( Z=1.650, P=0.946). The numbers of 90-day stroke recurrence cases (recurrence rate) in patients in the groups A, B, and C were 12 (7.2%), 4 (2.4%), and 5 (3.0%), respectively, without statistically significant difference among the 3 groups ( χ 2=5.773, P>0.05); the recurrence time of patients in the groups A, B and C was (43.0±7.4) d, (66.0±8.3) d and (62.2±5.6) d, respectively, and the differences among the 3 groups were statistically significant ( F=14.096, P=0.001). Compared with the group A, patients in the groups B and C had a prolonged time to stroke recurrence within 90 days ( Z=-3.108, P=0.002; Z=-2.871, P=0.004), whereas the difference in the time to stroke recurrence within 90 days between patients in the groups B and C was not statistically significant ( Z=0.397, P=0.692). The time to stroke recurrence within 90 days was positively correlated with the level of LDL-C on day 90 ( β=0.850, P=0.031). Ten patients (6.0%) in the group A developed hepatic insufficiency, 1 patient (0.6%) in the group B, and 9 patients (5.4%) in the group C. The differences among the 3 groups were statistically significant (χ 2=7.622, P=0.022); and the difference between the group B and group C was statistically significant ( P=0.011). The differences of secondary safety endpoints, death due to stroke within 90 days [1 case (0.6%) in the group A, 0 case (0) in the group B, and 1 case (0.6%) in the group C], fatal and nonfatal myocardial infarction within 90 days [3 cases (1.8%) in the group A, 1 case (0.6%) in the group B, and 1 case (0.6%) in the group C], were not statistically significant among the 3 groups (all P>0.05). Conclusions:In patients with acute ischemic stroke, PCSK9 inhibitor combined with rosuvastatin (both medium and high doses) significantly reduced LDL-C levels compared with baseline, and at the same time prolonged the time to stroke recurrence, reduced adverse effects such as hepatic insufficiency, and had a high degree of safety. PCSK9 inhibitor combined with medium-dose rosuvastatin had a better effect.

Hepatocellular carcinoma （HCC） is a major cause of cancer-related death， and surgical resection remains an important method for radical treatment， but it is urgently needed to solve the problem of high postoperative recurrence rate. Neoadjuvant therapy can reduce the high recurrence rate after surgery， and there are little benefits from neoadjuvant therapy for HCC due to a lack of effective treatment methods in the past. At present， combination therapy based on immune checkpoint inhibitors has a relatively high response rate and has thus changed the treatment landscape for patients with advanced HCC. This urges investigators to reexamine the neoadjuvant treatment strategies for HCC， and it is expected that neoadjuvant therapy can provide new opportunities， reduce the postoperative recurrence rate， and improve the survival rate after treatment. This article discusses the current status and prospects of neoadjuvant therapy for HCC and related hot topics， so as to provide more ideas for exploring neoadjuvant therapy for HCC.

OBJECTIVE: To explore the regulatory role of SOX2-OT in migration of lung squamous cell carcinoma H520 cells and the underlying mechanisms. METHODS: Wound- healing and Transwell migration assays were performed to examine the changes in migration and invasion capacity of lung squamous cell line H520, which expressed higher levels of SOX2-OT than other lung cancer cell lines, following RNA interference-mediated SOX2-OT knockdown. The transcription levels of epithelial-mesenchymal transition (EMT)-related components was detected by qRT-PCR and immunoblotting. Gli1 gain-of-function analysis was performed in H520 cells with SOX2-OT knockdown and the changes in EMT phenotype of the cells were examined. miR-200c mimic and inhibitor were used to analyze the mechanism by which SOX2-OT positively regulates Gli1 and the mediating role of SOX2. RESULTS: SOX2-OT knockdown significantly lowered the invasiveness and migration capacity of H520 cells and caused changes in EMT phenotype of the cells. Overexpression of Gli1, which was positively regulated by SOX2-OT, reversed the inhibitory effect of SOX2-OT knockdown on migration of H520 cells. Transfection of the cells with miR-200c inhibitor effectively reversed SOX2-OT knockdown-induced down-regulation of SOX2. CONCLUSION The SOX2-OT/SOX2 axis positively regulates migration of lung squamous H520 cells via Gli1-mediated EMT.
Humans ; Epithelial-Mesenchymal Transition/genetics* ; Zinc Finger Protein GLI1/metabolism* ; Cell Line, Tumor ; Cell Movement/genetics* ; Lung Neoplasms/genetics* ; MicroRNAs/metabolism* ; Gene Expression Regulation, Neoplastic ; Cell Proliferation/genetics* ; Neoplasm Invasiveness/genetics* ; SOXB1 Transcription Factors/metabolism*

The prediction of survival time for advanced cancer patients undergoing palliative care has important clinical and social value. The prediction of survival time of advanced cancer patients includes clinical prediction and statistical prediction. Due to the late start of palliative medicine in China, it is particularly important to evaluate the widely used survival prediction tools in clinical practice. In this paper, we will review the common survival prediction tools of advanced cancer patients from the perspective of Western and Traditional Chinese Medicine,to provide reference for development and application of a survival prediction system in China.

Objective:To identify the risk factors for perioperative atelectasis in pediatric patients undergoing day surgery.Methods:The data of pediatric patients (aged 28 days-7 yr) undergoing elective surgery in our hospital from January 2021 to April 2021 were retrospectively collected.The pediatric patients were divided into atelectasis group and non-atelectasis group according to the results of postoperative ultrasound examination of the lung.The basic conditions and perioperative indicators of the children were recorded, and logistic regression analysis was used to identify the independent risk factors.Results:A total of 122 pediatric patients were enrolled, there were 68 pediatric patients in atelectasis group, and the incidence of atelectasis was 55.7%.Compared with non-atelectasis group, significant changes were found in the amount of sufentanil, rate of laryngeal mask insertion, and rate of intraoperative inhalation of high-concentration oxygen in atelectasis group ( P<0.05). After adjusting variables such as age, upper respiratory tract infection, and overweight, intraoperative inhalation of high-concentration oxygen (FiO 2>60%) ( OR=2.863, 95% confidence interval 1.148-7.137, P=0.024) and consumption of sufentanil >0.2 μg/kg ( OR=1.214, 95% confidence interval 1.069-1.379, P=0.003) were independent risk factors for perioperative atelectasis in pediatric patients undergoing day surgery. Conclusion:Inhalation of high-concentration oxygen (FiO 2>60%) and consumption of sufentanil >0.2 μg/kg during operation are independent risk factors for perioperative atelectasis in pediatric patients undergoing day surgery.

Gastric cancer is a malignant tumor with worldwide high incidence and threatening the human health severely. It is a disease induced by multiple factors. Exosomes play an important role in the pathogenesis and development of many malignant tumors including gastric cancer. Exosomes can transport specific contents to regulate local and distant cell communications, and are able to promote or inhibit the development of gastric cancer through regulating the growth and proliferation of tumor cells, relevant immune function and angiogenesis of tumors. This article reviewed the effects of exosomes and their contents on the pathogenesis and development of gastric cancer.

Objective: To investigate the clinicopathological features and outcome of gastroenteropancreatic high-grade neuroendocrine tumors. Methods: A total of 60 gastroenteropancreatic high-grade neuroendocrine tumors were collected from January 1st, 2013 to December 31th, 2018 at Fudan University Shanghai Cancer Center, with available pathology databases and clinic follow-up information. At the same time, 157 cases of gastrointestinal pancreatic neuroendocrine neoplasm (NEN) diagnosed at the hospital in 2018 were collected and the incidence of NEN at all grades was compared. Results: There were 32 males and 28 females, aged 13-80 years (mean 54 years). Pancreas primary was the most common (48%, 29/60). Nodal metastatic rate was 9/16 and distant metastatic rate was 41%(18/44). Liver was the most common site of metastasis. Among all the gastroenteropancreatic neuroendocrine neoplasms diagnosed in the hospital in 2018, the incidence of high-grade neuroendocrine tumors was the lowest (7%, 11/157). High-grade neuroendocrine tumors had typical pathologic features of well-differentiated/moderate neuroendocrine tumors, but with significant differences in mitotic rates. By immunohistochemical staining, most of the tumors expressed neuroendocrine markers and somatostatin receptor 2 was positive in 60% (12/20) of the cases. The average Ki-67 index was 30%-40%, and there was significant difference between cases (18%-80%). The overall survival of high-grade neuroendocrine tumors was 43 months, and the disease-free survival was 12 months. Conclusions High-grade neuroendocrine tumor is a rare group of neuroendocrine tumors, with unique clinicopathological features and good prognosis. Pathological classification and grading of gastroenteropancreatic neuroendocrine neoplasms can help clinicians to select appropriate treatment and accurately evaluate prognosis.

Mental, emotional and other psychological factors have a direct effect on human health, and chronic stress produces neurotransmitters to suppress the body"s immune system, after which homeostasis is destroyed, lead to cells losing their normal state and function and cancer cells being produced. As a result, cancer patients will experience chronic emotional stress and consequently, neurotransmitters will promote the occurrence and development of tumors. This review systematically summarizes the research progress of major neurotransmitters from two aspects: the normal physiological functions and the mechanism of action in the tumor occurrence and development,providing some insights into further exploration of new mechanism of neurotransmitters and the development of drugs that block the neurotransmitters.

Objective:To design a checklist for interhospital transfer of patients undergoing extracorporeal membrane oxygenation (ECMO) therapy and apply it in clinical practice to ensure the transfer safety of patients.Methods:Using convenience sampling, 27 cases of critically ill patients who were transported by the ECMO team of the Department of Critical Care Medicine of Henan Provincial People's Hospital from September 2017 to November 2018 were selected as the control group, and the ECMO interhospital transport was implemented from December 2018 to February 2020, 14 cases of critically ill patients were set as the experimental group.The checklist for interhospital transfer of patients undergoing ECMO therapy was compiled based on relevant literature and guidelines, and applied to critically ill patients who were transported between hospitals under the support of ECMO. The incidence of adverse events between two groups was compared.Results:The incidence of adverse events decreased after the application of the checklist, the difference was not statistically significant (χ 2=3.516, P=0.061) . Conclusions:The use of the ECMO interhospital transfer checklist can effectively standardize the transfer process, improve work efficiency and quality, may reduce transfer risks, and ensure patients' safety.