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 study the effects and mechanisms of serum containing Wenjing Tongluo Decoction on interleukin-1β(IL-1β)-induced mouse primary chondrocyte injury.METHODS The IL-1β-induced primary chondrocyte injury model was estab-lished,and the mRNA expression of inflammatory factors IL-1β,IL-6,TNF-α,cartilage degradation-related proteases matrix metal-loproteinase 3(MMP3),MMP9,MMP13,ADAM metallopeptidase containing thrombospondin 1 motif 4(ADAMTS4),and glycoly-sis-related enzymes lactate dehydrogenase A(LDHA),M2 pyruvate kinase(PKM2),reduced coenzyme Ⅱ oxidase 2(NOX2)and re-duced coenzyme Ⅱ oxidase 4(NOX4)in the cells was detected;the intracellular MMP3,MMP13,P65,IκB-ζ,hypoxia-inducible factor 1α(HIF-1α)and LDHA protein expression levels were determined;the concentrations of nitric oxide(NO),malondialdehyde(MDA)and lactic acid in the cell supernatant were further detected,and the ratio of the reduced state(NADH)and oxidized state(NAD+)of intracellular coenzyme Ⅰ(NAD),as well as intracellular reactive oxygen species(ROS)levels were assayed.RESULTS Serum containing Wenjing Tongluo Decoction significantly inhibited the mRNA expression of IL-1β,IL-6,and TNF-α in IL-1β chondrocytes(P＜0.01),reduced the NO concentration in the cell supernatant(P＜0.05,P＜0.01),and downregulated the protein ex-pression of IκB-ζ(P＜0.05)and P65(P＜0.05,P＜0.01).Serum containing Wenjing Tongluo Decoction significantly downregulated the mRNA expression of MMP3,MMP9,MMP13 and ADAMTS4(P＜0.01),and inhibited the protein expression of MMP13(P＜0.05,P＜0.01)and MMP3(P＜0.05).In terms of oxidative stress,it significantly suppressed the production of ROS in chondrocytes,increased the NADH/NAD+ratio,reduced the MDA concentration in the supernatant,and downregulated the expression of HIF-1α protein(P＜0.01).The serum containing Wenjing Tongluo Decoction significantly reduced the lactic acid concentration,downregulated the expression of LDHA,PKM2,NOX2 and NOX4,and reduced the level of intracellular glycolysis(P＜0.05,P＜0.01).CONCLU-SION The serum containing Wenjing Tongluo Decoction can alleviate IL-1β-induced mouse primary chondrocyte injury by inhibiting inflammation,cartilage degradation,oxidative stress and glycolysis,which may be related to the regulation of IκB-ζ/HIF-1α/LDHA axis.

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

【Objective】 To establish and verify a nomogram model of overall survival (OS) of prostate cancer patients based on the SEER data. 【Methods】 A total of 12 642 patients diagnosed with prostate cancer during 2010 and 2015 were extracted from the SEER database. Patients were randomly divided into the model group (n=8 850) and validation group (n=3 792). The independent risk factors for OS were analyzed with univariate Cox proportional risk regression, lasso regression and multivariate Cox proportional risk regression. A nomogram was constructed to predict the 1-year, 3-year and 5-year OS. The prediction potential of the model was evaluated with the consistency index (C-index), calibration curve and receiver operating characteristic (ROC) curve. 【Results】 Multivariate Cox regression analysis showed that age, T stage, N stage, M stage, bone metastasis, liver metastasis and regional lymphadenectomy were independent risk factors for OS (P<0.05). The seven factors were used to construct an OS nomogram model. The C-index of the modeling set was 0.750, and the area under the ROC curve (AUC) at 1, 3 and 5 years were 0.77, 0.77 and 0.76, respectively;the C-index of the validation set was 0.765, and the AUC at 1, 3 and 5 years were 0.83, 0.79 and 0.76, respectively. The calibration curves of the modelling set and validation set showed a good agreement with the actual survival prediction rate. Risk stratification of patients based on the nomogram model showed that the OS of patients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). 【Conclusion】 The nomogram can be used to predict the prognosis of prostate cancer patients, and is important for individualized treatment plans.

Objective:To compare the complications between breast-conserving surgery with free dermal fat graft (FDFG) and traditional breast-conserving surgery (TBCS) in breast cancer patients, and to analyze the influencing factors for the incidence of complications of breast-conserving surgery with FDFG.Methods:The clinical data of 120 breast cancer patients who underwent breast-conserving surgery with FDFG (FDFG group, 50 cases) or TBCS (TBCS group, 70 cases) in Liuzhou People's Hospital from June 2015 to September 2020 were retrospectively analyzed. The incidence of overall complications and various complications between the two groups were compared, the influencing factors of complications in the FDFG group were analyzed, and the cosmetic outcome was evaluated.Results:There was no significant difference between the two groups in age, lymph node status, clinical TNM stage, etc (all P > 0.05). In the FDFG group, the proportions of patients with the longest tumor diameter > 3 cm and tumor in upper inner quadrant were significantly higher than those in the TBCS group [52.0% (26/50) vs. 27.1% (19/70), χ2 = 7.69, P = 0.006; 38.0% (19/50) vs. 15.7% (11/70), χ2 = 7.73, P = 0.005]. The operation time, intraoperative blood loss, postoperative hospital stay and weight of resected tissues in the FDFG group were higher than those in the TBCS group [(251±69) min vs. (213±41) min, (107±29) ml vs. (68±26) ml, (8.8±2.5) d vs. (6.1±1.6) d, (81±26) g vs. (56±20) g], and the differences were statistically significant ( t values were 10.14, 30.58, 22.20, and 14.54, respectively, all P < 0.001). There were no significant differences in the incidence of overall complications, bleeding, infection, or poor wound healing between the two groups (all P > 0.05). The incidence rate fat liquefaction in the FDFG group was higher than that in the TBCS group [14.0% (7/50) vs. 1.4% (1/70), χ2 = 5.53, P = 0.019]. Multivariate logistic regression analysis showed that the weight of FDFG ( OR = 14.056, 95.0% CI 1.764-111.985, P = 0.013) and the thickness of FDFG ( OR = 19.599, 95.0% CI 1.743-220.345, P = 0.016) were independent influencing factors for the incidence of complications in the FDFG group. The percentage of 'excellent' or 'good' cosmetic outcome in the FDFG group was 90% (45/50). Conclusions:Breast-conserving surgery with FDFG can extend the resected area for tumor without increasing the incidence of overall complications and could provide patients a superior cosmetic outcome, but the incidence of fat liquefaction is higher than that of TBCS. The weight and thickness of FDFG are the influencing factors for the incidence of complications of breast-conserving surgery with FDFG.

Objective:To compare toally endoscopic thyroidectomy(TET) with open thyroidectomy(OT) in the treatment of differentiated thyroid cancer.Methods:Data of 190 patients at Liuzhou People's Hospital from Jul 2017 to Dec 2019 were analyzed. Patients were divided into endoscopic surgery group ( n=95) and open surgery group ( n=95). Results:The operation time and the hospital stay in endoscopic group were longer than that in open surgery group[(153±25) min vs. (116±17) min, (5.56±1.08) d vs.(5.08±1.04) d, t=11.827，3.083， both P<0.05)]. There was no significant difference in intraoperative blood loss [(33±14) ml vs. (37±16) ml, t=-1.851 P>0.05], recurrent laryngeal nerve paralysis, hypoparathyroidism and wound complications (4% vs. 9%, 9% vs. 15%,1% vs. 3%, all P>0.05). There was no significant difference in the number of central lymph node dissection between the two groups (6.12±3.54 vs. 6.35±4.75, t=-0.404, P<0.05). The length of scar in endoscopic group was shorter [(3.03±0.27) cm vs. (6.47±0.53) cm, t=-56.138, P<0.05), and the postoperative cosmetic score evaluated by the patients was higher (8.76±0.75 vs. 7.39±0.76, P<0.05), than those in open group. There were no tumor recurrence nor metastasis in neither group by short term follow-up. Conclusions:TET is similar to OT on clinical curative effectiveness for differentiated thyroid carcinoma while carries a better cosmetic result .

【Objective】 To assess the prevalence and treatment of high cardiovascular disease （CVD） risk， and identify individual characteristics related to high CVD risk. 【Methods】 Based on the data of the China Patient-Centered Evaluative Assessment of Cardiac Events （PEACE） Million Persons Project （MPP） from 2016 to 2019， this study enrolled local residents aged 35 to 75 years from 39 counties or districts in Northwest China. Rates of high CVD risk and individual characteristics were assessed in the overall study population. Statin and aspirin use was also evaluated among those at high risk for CVD. Multivariable mixed models were fitted to evaluate the relationship between individual characteristics and high CVD risk. 【Results】 Among 364 537 participants， the average age was （54.6±9.7）years， and 5.8% was at a high risk for CVD. Multivariate mixed models showed that individuals who were currently using alcohol， overweight or obese tended to have a high risk for CVD， while married persons， those with a higher education level or a higher household income were correlated with a lower risk for CVD （all P<0.05）. Among high-risk persons， hypertension was the most prevalent risk factor （98.1%）， and only 1.3% and 3.5% reported their use of statins and aspirin， respectively. 【Conclusion】 Of the 364 537 participants， about 1 in 17 had a high risk for CVD. Among those at a high CVD risk， only less than 4% reported taking statins or aspirin. These findings indicate that there is still much room for risk mitigation in this population in China.

Breast conserving surgery has become one of the standard procedures for breast cancer and its oncological safety and cosmetic outcome have been confirmed by a large number of clinical studies. But there are still some patients who are not suitable for breast conserving surgery, they have to undergo total mastectomy or breast reconstruction with more damage. Free dermal fat graft (FDFG) can better solve the problems in breast conserving surgery, especially for cases with large breast tissue defect after lesion excision and upper inner quadrant lesion which makes local plastic surgery difficult. This article reviews the application of FDFG in breast conserving surgery.