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.

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].

Objective:To investigate the clinical outcome after surgery and first 131I treatment in patients with moderate-risk papillary thyroid cancer (PTC), and analyze the relevant factors that affect the therapeutic effect. Methods:From January 2018 to April 2019, 135 patients (48 males, 87 females; age (42.7±11.1) years) with moderate-risk PTC in the Second Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into excellent response (ER) group, inderteriminate response (IDR) group, biochemical incomplete response (BIR) group and structural incomplete response (SIR) group, of which IDR, BIR, SIR were collectively referred to as the non-ER group. χ2 test and Mann-Whitney U test were used to compare the general clinical features between the ER and non-ER groups, and then multivariate logistic regression analysis was performed. The predicted value of pre-ablation stimulated thyroglobulin (ps-Tg) to ER was assessed by ROC curve analysis. Results:The treatment responses of 94 patients were ER, and those of 41 were non-ER. The differences in tumor size (0.80(0.50, 1.10) vs 1.00(0.55, 1.50) cm; U=1 491.50, P=0.036), the number of metastatic lymph nodes (3(2, 5) vs 4(2, 12); U=1 422.00, P=0.015), metastatic lymph node size (0.50(0.30, 0.65) vs 0.50(0.30, 1.45) cm; U=1 396.50, P=0.013), metastatic lymph node involvement rate (50%(30%, 70%) vs 60%(50%, 85%); U=1 441.50, P=0.024), metastatic lymph node location (central/lateral: 76/18 vs 24/17; χ2=7.40, P=0.007) and ps-Tg level (2.1(0.8, 5.3) vs 14.0(3.2, 35.2) μg/L; U=680.00, P<0.001) were statistically significant between the ER and non-ER groups. Multivariate logistic regression analysis showed that ps-Tg (odds ratio ( OR)=1.200, 95% CI: 1.107-1.302, P<0.001) was an independent factor influencing ER. The cut-off value of ps-Tg for predicting ER was 7.38 μg/L, with the sensitivity and specificity of 68.3%(28/41) and 87.2%(82/94) respectively. Conclusion:Moderate-risk PTC patients with smaller tumor size, fewer metastatic lymph nodes, lower metastatic lymph node involvement rate, metastatic lymph nodes in central area, smaller metastatic lymph node size, and ps-Tg<7.38 μg/L have better therapeutic effect after initial 131I treatment.

Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties, a high incidence of pulmonary metastasis and a poor prognosis. Chemotherapy is the mainstay of treatment for osteosarcoma. Currently, there are no molecular targeted drugs approved for osteosarcoma treatment, particularly effective drugs for osteosarcoma with pulmonary metastases. It has been reported that fibroblast activation protein alpha (FAPα) is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis, demonstrating that FAPα-targeted agents might be a promising therapeutic strategy for osteosarcoma. In the present study, we reported that the FAPα-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPα-positive osteosarcoma cells in vitro and in vivo. Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells. Importantly, it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo. Mechanistically, Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway, leading to inhibition of the growth and metastatic spread of osteosarcoma cells. These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPα-positive osteosarcoma, particularly osteosarcoma with pulmonary metastases.

OBJECTIVE：To study the effects and active ingr edients of Tibetan medicine Lamiophlomis rotata against rheumatoid arthritis （RA）. METHODS ：Fifty-six SD rats were randomly divided into normal control group （0.5％ sodium carboxymethylcellulose），model group （0.5％ sodium carboxymethylcellulose ），methotrexate group （positive control group ，3 mg/kg），L. rotata water extract low-dose ，medium-dose and high-dose groups （0.5，1，2 g/kg，by crude drug ），L. rotata total flavonoid group （200 mg/kg，by flavonoid extat ），with 8 rats in each group. Except for normal control group ，other groups were given Freund ’s complete adjuvant （FCA）on the rat ’s right hind footpad to induce adjuvant-induced arthritis model. The next day after injection of FCA ，rats in all groups were given relevant medicine intragastrically ，once a day （once every 3 days for methotrexate group ）for 30 days. At 15th and 30th day of administration ，the degree of paw swelling of left hind foot was measured，and the arthritis index ，spleen index were calculated. At the end of 30th day of administration ，the levels of TNF-α，IL-1β， IL-6 and IL- 10 in rat serum were determined by ELISA assay ，the thymus index and spleen index were calculated ，the pathological changes of the ankle joints were observed by HE staining. RESULTS ：Compared with normal control group ，degree of paw swelling，arthritis index at 15th and 30th day of administration as well as the spleen index and the levels of TNF-α，IL-1β， msxmX0146） IL-6 in serum at 30th day of administration were significantly com increased in model group （P＜0.01）；while the thymus indexyunbinji- and IL- 10 level at 30th day of administration were ang@swu.edu.cn significantly decreased（P＜0.01）；synovial cell proliferation and infiltration of articular cavity were observed in ankle joint. Compared with model group ，degree of paw swelling ，arthritis index at 15th and 30th day of administration as well as the spleen index and the levels of TNF-α，IL-1β，IL-6 in serum at 30th day of administration were significantly decreased in each medicine group （P＜0.01）；while the thymus index and IL- 10 level at 30th day of administration were significantly increased （P＜0.01）；the pathological changes of arthritis were significantly improved. Compared with L. rotata water extract high-dose group ，there were no significant differences in degree of paw swelling at 15th day of administration as well as the arthritis index ，spleen index ，levels of inflammatory cytokines and pathological changes of ankle joint in L. rotata total flavonoid group （P＞0.05）. CONCLUSIONS ：Tibetan medicine L. rotata shows well anti-RA activity ，and total flavonoids may be the active ingredients of its efficacy.

Objective To study the use of laparoscopy in the diagnosis and treatment of obstructive infantile cholestasis.Methods The clinical data of 106 patients with obstructive infantile cholestasis from January 2012 to June 2017 were studied retrospectively.After two weeks of conservative treatments which failed to decrease the bilirubin levels significantly,these patients were subjected to laparoscopic diagnosis and treatment.Results A correct diagnosis was established in all these 106 patients by laparoscopic biliary tract exploration and cholangiography.Eighty-eight patients were diagnosed to have biliary atresia (83.0％),16 patients inspissated bile syndrome (15.1％) and 2 patients biliary hypoplasia (1.9％).Thirty-eight of the 88 biliary atresia patients gave up operative treatment after laparoscopic biliary tract exploration and cholangiography.The remaining 50 biliary atresia patients were treated with open Kasai portoenterostomy.The prognosis of the biliary atresia patients were different from the non-biliary atresia patients.On follow-up for 4 months to 5 years,all the 18 non-biliary atresia patients were in good condition and there was no recurrence of jaundice after laparoscopic cholecystostomy and biliary tract irrigation.Conclusions The laparoscopic minimally invasive technique helped to establish diagnosis and treatment in patients with obstructive infantile cholestasis.For patients with biliary atresia,this procedure gave a definitive diagnosis and offered an opportunity for surgery.For patients with inspissated bile syndrome and biliary hypoplasia patients,laparoscopic cholecystostomy and biliary tract irrigation established the correct diagnosis and reduced liver damage resulted by cholestasis.

Objective To explore the manufacture methods of a new nasal ice compress cover,and to observe its clinical application effect.Methods The nasal ice compress cover body is a silica gel cover,which contains the upper cover body and the lower cover body.The shape of the upper cover body is consistent to the shape of frontal temporal while the shape of the lower cover body is consistent to the shape of the nose root,and the upper cover body and the lower cover body are integrally formed.The inner surface of the cover body is equipped with a ice pack,and the ice pack is of the same shape with the inner surface.And the cover body is provided with two elastic bands.Patients of the experimental group use the nasal ice compress cover and patients of the control group use the traditional ice hockey ice so as to detect the clinical effect of the new nasal ice compress cover and satisfaction rate and adverse reaction of patients.Results The new nasal ice compress cover has good clinical application effect,and patients consider that it has the advantages of convenient,effective and highly satisfactory. Conclusion The new nasal ice compress cover improves patients’comfort degree and satisfaction rate,and it is worthy of wide promotion.

Objective:To investigate the expression of CD56 antigen in leukemia cells of the patients with acute myeloid leukemia (AML)and its relationship with the prognosis of AML, and to clarify the role of CD5 6 antigen expression in predicting the prognosis of the AML patients.Methods:171 AML (non-M3)patients aged from 14 to 60 years old,who received a IA Regimen as the first time inducing chemotherapy were chosen.Flow cytometric analysis was used to evaluate the CD56 expression in leukemia cells.COX proportional regression analysis was used to select the prognostic factors,and bivariable analysis was used to study the relationship between the positive rate of CD56 and overall survival (OS).The CD56+ group (n=52),including CD56≥50% expression group (n=39) and CD56<50% expression group (n=13),and CD56- group (n=119)were identified by the expression of CD56 antigen.The complete remission rate (CRR), the relapse rate, the median OS, the median disease-free survival (DFS)and the survival rate of patients were compared.Results:The medium OS of the patients in CD56+ group (14.2 months)was shorter than that in CD56- group (39.4 months)(P<0.05).Moreover,the medium OS in CD56≥50% group was shorter than that in CD56<50% group (11.7 months vs 20.3 months,P<0.05).The 1-year and 2-year survival rates of the patients in CD56+ group (61.5%,46.2%)were lower than those in CD56-group (75.6%,63.9%)(P<0.05).The 1-year survival rate had no significant difference between CD56≥50%group and CD56<50% group (53.8%vs 84.6%,P>0.05),while the 2-year survival rate in CD56≥50% group was lower than that in CD56<50% group (41.0%vs 61.5%,P<0.05).There were no significant differences of the CRR between CD56+ group (76.9%)and CD56- group (68.9%)as well as CD56≥50% group (58.9%)and CD56<50% group (63.5%)(P>0.05).The relapse rate and first year relapse rate of patients in CD56+ group (64.3% and 37.5%)were significantly higher than those in CD56- group (34.3% and 17.9% )(P<0.05). However,there were no significant differences of the relapse rate and first year relapse rate between CD56≥50%group (75.0% and 42.9%)and CD56<50% group (37.5% and 16.7%)(P>0.05).The DFS in CD56+ group was shorter than that in CD56- group (P<0.05).The same DFS result was also found between CD56≥50%group and CD56<50% group (P<0.05).Conclusion:The expression of CD56 antigen in leukemia cells predicts a bad prognosis in the AML patients,and the higher expression of CD56 indicates the worse prognosis.

BACKGROUNDHigh-frequency oscillatory ventilation (HFOV) allows for small tidal volumes at mean airway pressures (mPaw) above that of conventional mechanical ventilation (CMV), but the effect of HFOV on hemodynamics, oxygen metabolism, and tissue perfusion in acute respiratory distress syndrome (ARDS) remains unclear. We investigated the effects of HFOV and CMV in sheep models with ARDS.

METHODSAfter inducing ARDS by repeated lavage, twelve adult sheep were randomly divided into a HFOV or CMV group. After stabilization, standard lung recruitments (40 cmH2O × 40 seconds) were performed. The optimal mPaw or positive end-expiratory pressure was obtained by lung recruitment and decremental positive end-expiratory pressure titration. The animals were then ventilated for 4 hours. The hemodynamics, tissue perfusion (superior mesenteric artery blood flow, pHi, and Pg-aCO2), oxygen metabolism and respiratory mechanics were examined at baseline before saline lavage, in the ARDS model, after model stabilization, and during hourly mechanical ventilation for up to 4 hours. A two-way repeated measures analysis of variance was applied to evaluate differences between the groups.

RESULTSThe titrated mPaw was higher and the tidal volumes lower in the HFOV group than the positive end-expiratory pressure in the CMV group. There was no significant difference in hemodynamic parameters between the HFOV and CMV groups. There was no difference in the mean alveolar pressure between the two groups. After lung recruitment, both groups showed an improvement in the oxygenation, oxygen delivery, and DO2. Lactate levels increased in both groups after inducing the ARDS model. Compared with the CMV group, the superior mesenteric artery blood flow and pHi were significantly higher in the HFOV group, but the Pg-aCO2 decreased in the HFOV group.

CONCLUSIONCompared with CMV, HFOV with optimal mPaw has no significant side effect on hemodynamics or oxygen metabolism, and increases gastric tissue blood perfusion.

Animals ; Disease Models, Animal ; Hemodynamics ; physiology ; High-Frequency Ventilation ; methods ; Male ; Oxygen ; metabolism ; Positive-Pressure Respiration ; methods ; Respiration, Artificial ; methods ; Respiratory Distress Syndrome, Adult ; metabolism ; therapy ; Sheep

Objective To investigate the role of ileocecal valve in children patients with intussus-ceptions by colonoscopy after pneumatic air enema reduction. Methods A total of 106 intussusceptions chil dren patients, who recovered with pneumatic air edema reduction, were recruited to the study. They underwent colonoscopy within 12 hours after reduction. The control group was composed of 103 children patients with both diarrhea and hematochezia. There was no significant difference in age, sex or weight between the two groups.Colonoscopic findings were recorded in terms of slack, swelling, prolapsus, lymphoid hyperplasia and mucosal lesions in ileocecal valve. Results In patients with intussusceptions, the rates of ileocecal valve slack, swelling including prolapsus, lymphoid hyperplasia and mucosal lesions were 61.3%, 33. 9%, 100. 0% and 31.1%, respectively, which were significantly different with those of the control group (P ＞ 0. 05 ). When further divided intussusceptions patients into groups with age more than 1 yr or less, significant differences were also observed in regarding of these features. Conclusion There is a close relationship between morphological and functional changes in ileocecal valve and intussusceptions in children. Ileocolic intussusceptions in patients younger than 1yr is more likely to be due to slack of ileocecal valve, while that in patients older than 1yr is mainly due to swelling or prolapse of ileocecal valve, represented by ileocecal intussuception.