Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

BACKGROUND:Minipigs are often used in research fields such as skin injury,vascular trauma and cosmetic medicine because they are highly similar to human beings in terms of skin tissue structure and cardiovascular system.Hydrogel as a wound repair drug possesses a variety of excellent physicochemical properties such as strong water retention and adhesion,which can provide isolation moisturization and drug release for wounds. OBJECTIVE:To summarize and conclude the progress of the application of trauma models for different experimental purposes of hydrogel therapy for minipigs,to reveal the development status of various types of minipig trauma models,to analyze the deficiencies of minipig trauma models at the present stage. METHODS:The relevant articles published in Web of Science database and CNKI database from the establishment of each database to 2023 were checked,using"piglet,miniature pig,minipig,miniature pig;gel,hydrogel;trauma,injury,wound,lesion,incision"as Chinese search terms and"Miniature Swine,Miniature pig,minipig;gel,hydrogel;injury,wound,lesion,incision"as English search terms.A total of 438 Chinese and English documents were retrieved,and 59 documents were included in the study through the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)At present,the main models used clinically for trauma repair are large animal species(dogs and pigs),rabbits,and rodents(rats and mice).Because the skin structure of the minipig is more like that of humans,the minipig is the most ideal animal model for trauma repair.(2)In the in-vitro skin injury model,skin defect model is the basic wound model,which can be divided into full skin defect model and medium-thickness skin defect model according to the depth of the wound defect.Burn wound model and infected wound model are multidimensional models with hot metal scald and bacterial culture imposed on the basis of the skin defect model,which have the advantages of high safety coefficient and low operation difficulty.(3)In the in-vivo trauma repair model,mini-pigs are used as esophageal cricothyrotomy model which is more in line with the pathological state of clinical diseases.Mini-pigs are used in the gastric perforation and vascular hemostasis model,which can visually demonstrate the stronger organ adhesion,hemostatic properties and tissue regeneration-promoting effects of the hydrogel.(4)The specific parts of the pig also has the corresponding mode of use:pig ear is usually used to evaluate the hydrogel drug delayed-release effect.Porcine cellular proteins and pig skin collagen are mostly used to prepare composite hydrogels of tissue origin.

Fragile X syndrome(FXS)is caused by abnormal duplication and amplification of the FMR1 gene CGG.This article reports a pair of brothers diagnosed with FXS by genetic testing.Two patients,aged 15 and 14 years old respectively,both had clinical manifestations such as language disorders,intellectual disabilities,attention deficit disorder,autism spectrum disorder,and FXS's characteristic facial features.The proband had a rare late-onset epileptic seizure,which was well treated with levetiracetam,while his younger brother had no electroencephalogram abnormalities after repeated follow-up.This pair of cases suggests that the clinical phenotype of FXS has diversity and heterogeneity.

Objective To explore the effect of multi-sensory artificial intelligence feedback gait training on the recovery of walking function in stroke patients based on enriched environment theory. Methods From July,2021 to June,2023,a total of 80 stroke patients in Huashan Hospital Affiliated to Fudan University were randomly divided into control group(n=40)and experimental group(n=40).Both groups received rou-tine rehabilitation in the lying and seated positions,for 40 minutes.The control group received ground walking training,for 20 minutes,while the experimental group received multi-sensory feedback gait training in enriched environment,for 20 minutes.Before and after four weeks intervention,the digital motion monitoring treadmill was used to mearsure step speed,step length,hip and knee swing angle and weight symmetry.They were as-sessed with Berg Balance scale(BBS),Fugl-Meyer Assessment-Lower Extremities(FMA-LE)and Barthel Index(BI). Results After intervention,the hip swing angle,step length of both sides and step speed significantly improved in both groups(|t|＞3.162,P＜0.05),and they were better in the experimental group than in the control group(|t|＞2.568,P＜0.05);the average knee joint swing angle and bilateral weight-bearing symmetry significantly im-proved in the experimental group(|t|＞3.249,P＜0.01);the scores of BBS,FMA-LE and BI improved in both groups(|t|＞3.569,P＜0.01),and they were better in the experimental group than in the control group(|t|＞2.922,P＜0.05). Conclusion Multi-sensory feedback gait training based on enriched environment theory could effectively improve the walking and balance of stroke patients,and increase the ability of independence.

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C₂₈-steroid with an unusual β- and γ-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC₅₀ value of 2.61 ± 0.05 μmol·L^-1. The β-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 μg·mL^-1. Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 μg·mL^-1, respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC₅₀ values of 9.2 ± 0.03 and 13.3 ± 0.01 μmol·L^-1, respectively.
Humans ; Acetylcholinesterase ; Molecular Docking Simulation ; Anti-Bacterial Agents ; Glycosides ; Lactones ; Pain

Accurate segmentation of pediatric echocardiograms is a challenging task, because significant heart-size changes with age and faster heart rate lead to more blurred boundaries on cardiac ultrasound images compared with adults. To address these problems, a dual decoder network model combining channel attention and scale attention is proposed in this paper. Firstly, an attention-guided decoder with deep supervision strategy is used to obtain attention maps for the ventricular regions. Then, the generated ventricular attention is fed back to multiple layers of the network through skip connections to adjust the feature weights generated by the encoder and highlight the left and right ventricular areas. Finally, a scale attention module and a channel attention module are utilized to enhance the edge features of the left and right ventricles. The experimental results demonstrate that the proposed method in this paper achieves an average Dice coefficient of 90.63% in acquired bilateral ventricular segmentation dataset, which is better than some conventional and state-of-the-art methods in the field of medical image segmentation. More importantly, the method has a more accurate effect in segmenting the edge of the ventricle. The results of this paper can provide a new solution for pediatric echocardiographic bilateral ventricular segmentation and subsequent auxiliary diagnosis of congenital heart disease.
Adult ; Humans ; Child ; Heart Ventricles/diagnostic imaging* ; Echocardiography ; Image Processing, Computer-Assisted

Objective To analyze the changes and correlation of serum Hcy level in patients with type 2 diabetes mellitus (T2DM) complicated with acute cerebral infarction (AIS). Methods A total of 427 T2DM patients admitted to our hospital from June 2019 to June 2021 were selected and divided into the control group (T2DM, n=129) and experimental group (T2DM combined with AIS, n=298) according to whether the patients were complicated with AIS. According to NIHSS score, the patients in the experimental group subsequently were divided into the mild group (NIHSS score <7 points, n=51), moderate group (7≤NIHSS score 7-15 points, n=43) and severe group (NIHSS score >15 points, n=35). According to infarct size, the patients in the experimental group were divided into the lacunar cerebral infarction group (n=57), small area cerebral infarction group (n=45) and large area cerebral infarction group (n=27). The basic data of all patients, including age, gender, history of hypertension, stroke and smoking, were collected by self-made scale. The levels of FBG, TG, LDL-C, SBP and serum Hcy were compared between the groups. Logistic regression analysis was used to screen the independent risk factors for development of AIS in T2DM patients. Spearman was applied to analyze the correlation between serum Hcy level and the degree of neurological impairment as well as infarct area in T2DM patients with AIS. Results There were statistically significant differences in age, history of hypertension, stroke, smoking, and the levels of TG, LDL-C, FBG, SBP, Hcy between the control and experiment groups (P<0.05). Logistic regression analysis showed that age and the levels of TG, FBG, SBP, Hcy were independent risk factors for development of AIS in T2DM patients (P<0.05). The serum Hcy level in severe group was significantly higher than that in mild and moderate groups, and it in moderate group was significantly higher than that in mild group (t=16.995, t=8.850, t=12.163, P<0.05). The serum Hcy level in large area cerebral infarction group was significantly higher than that in lacunar and small area cerebral infarction groups, and it in small cerebral infarction group was significantly higher than that in lacunar cerebral infarction group (t=8.677, t=2.858, t=7.028, P<0.05). Spearman correlation analysis showed that serum Hcy level was positively correlated with the degree of neurological impairment and infarct area in T2DM patients with AIS (r₁=0.459, r₂=0.513, P<0.05). Conclusions T2DM patients with old age, poor control of smoking, blood glucose, blood pressure and blood lipids are at greater risk of AIS development. The serum Hcy level of T2DM patients with AIS is significantly increased, which can be monitored to determine the degree of neurological impairment and infarct area of T2DM patients with AIS..

Objective:To analyze the advantages of IPSA combined with increasing cervical center dose in intracavitary and interstitial brachytherapy (IC/IS) for locally advanced cervical cancer.Methods:A total of 46 stage Ⅱ B cervical cancer patients with, local lesion size≥5 cm after 45 Gy/25f external intensity-modulated radiotherapy (IMRT) were recruited. Uterine tandem and needles were implanted, CT was performed, and then HR-CTV, rectum, bladder, sigmoid colon and the area of cervix increased dose (HR-cervix) were delineated, IPSA was used for optimization. According to whether the dose of HR-cervix was increased or not, all patients were divided into IC/IS+ HR-cervix group (group A) and IC/IS group (group B). The differences in dosimetric parameters were compared between two groups. Results:The relative uterine tandem dwell time was significantly extended in group A ( P<0.001). In group B, the V 150% and V 200% volumes of HR-cervix were increased from 63.94% and 30.80% to 91.54% and 64.06%. The D 90% and D 100% in group A were significantly lower than those in group B (both P<0.05). There was no statistical difference in organ at risk (OAR) dose. Conclusion:IPSA combined with increasing cervical center dose can meet the HR-CTV D 90% dose requirement, normal tissue dose limits, and can escalate the doses to local areas of the cervix.