Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Chimeric antigen receptor-modified T(CAR-T)cell therapy,as a new type of cellular immunotherapy,has shown good clinical efficacy in the treatment of malignant hematological tumors,especially B-cell acute lympho-blastic leukemia.However,there are problems such as antigen loss and immune evasion in single-target selection,so multi-target therapy strategies are gradually gaining attention.Multi-target CAR-T can effectively avoid antigen escape caused by a single target by targeting multiple tumor-associated antigens at the same time,reduce the risk of recurrence,and is expected to improve the therapeutic effect.This paper primarily discusses the structural types of multi-target CAR-T cell therapy and its clinical trial applications in the treatment of B-cell acute lymphoblastic leu-kemia(B-ALL),aiming to provide future references for the treatment of B-ALL.

Objective:To explore the application effect of key node advanced nursing mode in the treatment of patients with acute myocardial infarction.Methods:In October 2020, the hospital established a Critical Control Point rescue mode management team.122 patients with acute myocardial infarction admitted to emergency department of the hospital were enrolled as the objects between October 2020 and October 2021. The healthcare failure mode and effect analysis model was applied to analyze the shortcomings of emergency process, so as to construct critical control point rescue mode in the treatment of patients with acute myocardial infarction and apply it to the clinic in November 2021. After clinical application, emergency nursing and cardiac function recovery were compared between the two groups. The mortality rate within 30 d after surgery and occurrence of complications during hospitalization were recorded.Results:The first medical contact to balloon time dropped from (81.9±6.54) min to (56.2±4.23)min. The time from first medical contact to diagnosis of acute myocardial infarction dropped from (47.3±5.68) min to (30.69±5.21) min, the door-balloon dilation time dropped from (49.79±13.84) min to (28.63±15.71) min, producing results time of myocardial injury markers dropped from (28.38±3.79)min to (19.26±2.17) min, reporting time of electrocardiogram dropped from (5.82±2.01) min to (5.14±1.89)min, and hospitalization time dropped from (7.25±2.18) min to (6.14±1.27) min, and the differences were statistically significant ( P<0.05). After treatment, left ventricular ejection fraction in observation group was higher than that in control group, left ventricular end-diastolic diameter and cardiac troponin were lower than those in control group ( P<0.05). The incidence of hypotension and malignant arrhythmia in observation group was lower than that in control group ( P<0.05). Conclusions:The critical control point rescue mode can shorten treatment time and hospitalization time in acute myocardial infarction patients, improve cardiac function, and reduce the risk of complications during hospitalization.

Objective:To evaluate and summarize the best evidence on fatigue management in children with tumors both domestically and internationally, providing reference for medical and nursing staff to improve fatigue symptoms in children.Methods:The evidence on fatigue management in children with tumors, including best practices, recommended practices, guidelines, systematic reviews, evidence summaries, and expert consensus, was systematically retrieved from clinical decision support systems, guideline websites, professional association websites, and databases both domestically and internationally. The search period was from database establishment to April 2023. Two researchers independently conducted literature quality evaluation and evidence extraction.Results:A total of 17 articles were included, including four guidelines and 13 systematic reviews. Thirty-two best pieces of evidence were extracted from six aspects of assessment and screening, identification of risk factors, health education, exercise intervention, medication intervention, and other interventions of fatigue in children with tumors.Conclusions:The best evidence for fatigue management in children with tumors is summarized, which can provide a basis for medical and nursing staff to improve their fatigue symptoms. It is recommended that medical and nursing staff combine clinical context, professional opinions, and patient wishes to screen the best evidence and develop personalized fatigue management programs.

Objective To evaluate the accuracy,sensitivity,specificity and economy of HLA-B*5801 gene polymorphisms detection in predicting allopurinol-related severe drug eruption before receiving allopurinol treatment using rapid health technology assessment(rHTA),to provide clinicians and policymakers with an efficient and convenient evidence-based basis.Methods PubMed,Cochrane Library,Web of Science,Embase,WanFang Data,CNKI databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analyses and pharmacoeconomic literature on the HLA-B*5801 gene polymorphisms detection from inception to December 31,2023.Two reviewers independently screened studies,extracted data,assessed the included studies'quality,and analyzed and summarised the results.Results A total of 16 literature were included,of which 5 systematic reviews/Meta-analyses and 11 pharmacoeconomic studies.The results showed that the HLA-B*5801 gene mutation rate was significantly higher in patients presenting with severe drug eruption than in the allopurinol-tolerant group(P＜0.05).Two studies reported the sensitivity and specificity of the HLA-B*5801 gene polymorphisms assay for predicting severe drug eruption,the sensitivity of 0.78,0.93,and specificity of 0.96,0.89,respectively.The economic study showed that HLA-B*5801 gene polymorphisms detection before allopurinol treatment was cost-effective in Chinese Han,Korean,Thai populations,but not in British,American(Caucasian or Hispanic),Singaporean and Malaysian populations.Conclusion HLA-B*5801 gene polymorphisms detection before allopurinol treatment and guiding drug use according to the screening results in Chinese Han population can reduce the risk of severe drug eruption and treatment costs.

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.
Animals ; Mice ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics* ; Neuralgia ; RNA, Small Interfering ; Thalamus/metabolism* ; Up-Regulation

Bladder and bowel dysfunction affects the quality of life of children and their families, and scientific and effective assessment tools are crucial for identifying and managing symptoms. This article reviews the basic characteristics, testing population, reliability, validity, and clinical application of bladder and bowel dysfunction assessment tools for children both domestically and internationally, analyzes the advantages and disadvantages of assessment tools, so as to provide reference for the selection of suitable assessment tools in clinical practice and the development of localized assessment tools.

Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with strong contagiousness, high susceptibility and long incubation period. cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain of the viral spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). Here, we briefly reviewed the mechanisms underlying the interaction between SARS-CoV-2 and ACE2, and summarized the latest research progress on SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies, so as to better understand the development process and drug research direction of COVID-19. This review may facilitate understanding the development of neutralizing antibody drugs for emerging infectious diseases, especially for COVID-19.
Angiotensin-Converting Enzyme 2 ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Humans ; Peptidyl-Dipeptidase A/metabolism* ; Protein Binding ; SARS-CoV-2 ; Single-Domain Antibodies ; Spike Glycoprotein, Coronavirus/metabolism*

Objective:To investigate the relationship between pancreatic fibrotic marker transforming growth factor-β(TGF-β) and platelet derived growth factor-BB(PDGF-BB) and serum glycated hemoglobin (HbA1c) levels in patients with type 3c diabetes mellitus secondary to chronic pancreatitis(CP-T3cDM).Methods:The clinical data of 39 patients with CP-T3cDM admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between February 2018 and August 2020 were collected, and the patients' age, gender, body mass index, duration of chronic pancreatitis and diabetes mellitus, smoking history, alcohol consumption history, serum HbA1c level at admission, degree of pancreatic atrophy, morphology of the main pancreatic duct, and treatment of diabetes mellitus were recorded. Serum TGF-β and PDGF-BB were detected by ELISA. Patients were divided into high and low level group according to the median TGF-β and PDGF-BB levels, respectively. Clinical characteristics of patients were compared between the TGF-β and PDGF-BB high and low level group. The correlation between TGF-β, PDGF-BB and HbA1c was analyzed by Spearman's correlation analysis.Results:A total of 39 CP-T3cDM patients were included; 35 were male and 4 were female. The age of first onset of chronic pancreatitis was (42±14) years old, and the duration of diabetes mellitus was 24(4, 36) months. The serum HbA1c level was (7.8±1.6)%, and the serum TGF-β and PDGF-BB levels were 20.5(10.5, 43.1) and 647.5(276.9, 1349.2)pg/ml, respectively. The serum HbA1c levels of patients in the high-level group of serum TGF-β and PDGF-BB were significantly higher than those in the corresponding low-level group [8.6%(7.4%, 9.9%) vs 6.7%(6.2%, 7.8%) and 8.6%(7.4%, 9.6%) vs 6.7%(6.1%, 7.8%), respectively] , and the difference was statistically different (both P value <0.01), while none of other indicators showed statistically significant differences between both groups. The correlation analysis showed that the levels of TGF-β and PDGF-BB were significantly positively correlated with HbA1c level ( r=0.45, 0.53, both P value <0.01). Conclusions:Increased pancreatic fibrosis in patients with CP-T3cDM was an important factor contributing to elevated blood glucose level. Patients with higher serum pancreatic fibrotic factors exhibited a significant increase in HbA1c level.

Objective: To investigate the effects of long-term hyperglycemia induced ultrastructure of left ventricular myocardium in streptozotocin-induced type 1 diabetes mellitus(T1 DM) cynomolgus monkeys. Methods: The T1 DM cynomolgus monkeys were induced by intravenous administration of streptozotocin as the model group. The normal cynomolgus monkeys were distributed to the control group. Ultrastructural morphometric features of left ventricular myocardium in the model group and the control group were obtained using transmission electron microscope and quantitatively analyzed. Results: Ultrastructural observations indicated that the numbers of mitochondrion(P<0.01), the relative electron density of mitochondrion(P<0.000 1), the volume density(P<0.001) and the surface area density(P<0.05) of mitochondrion were observed to decrease in the cytoplasm of left ventricular cardiomyocytes of the model group compared to the control group. The ration surface and the average area of mitochondrion showed no difference between two groups. Massive lipid droplets were identified in the cytoplasm of left ventricular cardiomyocytes of the model group. Thickening of basement membrane(P<0.000 1) and decreasing of pinocytotic vesicles(P<0.000 1) were observed in the capillary endothelial cells in left ventricular myocardium of the model group compared to the control group. Conclusion The results indicate that long-term hyperglycemia induces left ventricular cardiomyocytes and capillary endothelial cells ultrastructural damage in TIDM cynomolgus monkeys.