Objective To explore the role and mechanism of keratin 19 (KRT19) in breast cancer.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine KRT19 levles in 35 cases of breast cancer tissues and normal tissues.The correlation between KRT19 levels and clinical property of breast cancer was analyzed.Meanwhile,the expression levels of KRT19 in several breast cancer cells and mammary epithelial cell Michigan cancer foundation (MCF)-10A were evaluated by qRT-PCR assay.Over-expressed and knocked-down KRT19 in breast cancer ceils,3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was performed to detect the proliferation and chemosensitivity of these cells.The ability of forming colon of these breast cancer cells with treated KRT19 was studied via colony-forming unit assays.Western blot assay was performed to determine expression levels of ceil cycler related proteins.Results KRT19 was upregulated in breast cancer tissues comparing to normal tissues.KRT19 was positively related to tumor node metastasis (TNM) stage and distant metastasis of breast cancer.Similarly,KRT19 was highly expressed in breast cancer cells compared to mammary epithelial cell MCF-10A.The proliferation and colony-forming ability was significantly enhanced in MCF-7 cell with o,verexpressed KRT19.MTS assay showed that chemosensitivity of MCF-7 cells with overexpression of KRT19 was much more remarkably reduced than the control group.However,knocking down KRT19 in breast cancer cells MDA-MB-231 got the opposite results.Western blot assay suggested that KRT19 could obviously upregulated cyclin-dependent kinase 1 (CDK1) but not p27 expression levels.Conclusions KRT19 was upregulated in breast cancer tissues and was positively related to TNM stage and distant metastasis of breast cancer.KRT19 can significantly enhance proliferation and chemoresistance of breast cancer cells via upregulating CDK1.

Objective To analyze the associations of the interleukin-10 (IL-10) promoter-1082G/A and-819C/T single nucleotide polymorphism (SNP) and serum level of IL-10 with intracranial aneurysm (IAs). Methods The polymerase chain reaction (PCR) and DNA direct sequencing methods were used to detect IL-10 gene promoter district two SNP site,-1082G/A and-819C/T genotype frequency and allele frequency in 206 patients with IAs and 187 controls. Chi-square test was used to analyze differences between two groups. The serum level of IL-10 was analyzed by ELISA, and t-test was used to analyze significant differences between two groups. Results There were significant differences in genotypes of GG and GA+AA, as well as the alleles G and A, in-1082G/A locus between IAs group and control group (P<0.01). There were higher frequencies of genotype GA+AA and the allele A in IAs group than those in control group (P<0.01). There was higher risk of suffering IAs in patients with genotype GA+AA (OR=4.137, 95%CI:2.476-6.914) and the allele A (OR=3.368, 95%CI:2.476-4.583). There were higher frequencies of the genotype CT+TT and the allele T in-819C/T locus in IAs group than those of control group (P<0.01). There was higher risk of suffering IAs in patients with genotype CT+TT (OR=3.393, 95%CI:1.952-5.900) and the allele T (OR=3.764, 95%CI:2.730-5.192). The serum level of IL-10 was significantly lower in IAs group than that of control group (P<0.01). Conclusion The IL-10 promoter SNP influences the expression of IL-10. IL-10 promoter-1082G/A and-819C/T polymorphisms are correlated with the formation of IAs.

Objective To study the maturation and activation effects of hyaluronic acid (HA) modified polymer nanoparticles co-delivering adjuvants and antigens on mouse bone marrow dendritic cells (BMDCs). Methods HA-modified polylactic acid-glycolic acid copolymer (PLGA) and cationic lipid DOTAP were used as nanocarriers (DOTAP-PLGA) to co-deliver adjuvant CpG with model antigen ovalbumin (OVA). In the drug-loaded nanocarriers, CpG was covalently bound to the surface of HA, and OVA was physically blended into DOTAP-PLGA nanocarriers. The nanoparticles were characterized by transmission electron microscopy and dynamic light scattering. The in vitro release of CpG and OVA in the nanoparticles was investigated. The uptake and distribution of nanoparticles in mouse BMDCs were studied by flow cytometry and laser scanning confocal microscopy. The maturation and cytokine expression of mouse BMDCs were evaluated by flow cytometry and enzyme-linked immunosorbent assay, respectively. Results The CpG-HA-OVA-PLGA nanoparticles loading CpG and OVA were prepared. The average particle size was (305.1±2.2) nm and the polydispersity index was 0.203. A core-shell structure of the nanoparticles modified by HA was clearly observed by transmission electron microscopy. Cellular experiment results showed that CpG-HA-OVA-PLGA nanoparticles could be efficiently uptaken by mouse BMDCs, and promote lysosomal release of CpG and cytoplasmic delivery of antigen OVA. Compared with free OVA group and free OVA+CpG group, the CpG-HA-OVA-PLGA nanoparticles significantly up-regulated the expression of co-stimulatory molecules CD86 and CD40 (all P<0.01), major histocompatibility complex I (MHC-I) (P<0.01), and cytokine tumor necrosis factor-α (TNF-α) (P<0.01). Conclusions HA-modified CpG and OVA nanoparticle co-delivery vectors can effectively promote the maturation and activation of dendritic cells, which provides a basis for the development of novel vaccine vectors for the co-delivery of antigens and adjuvants.

Objective To discuss the application of deep hypothermic circulatory arrest in surgical treatment of complex thoracoabdominal aortic aneurysms and its near-midterm effect.Methods The clinical data of 34 cases of thoracoabdominal aortic aneurysm in the center from August 2009 to June 2018 were analyzed retrospectively.All the patients underwent surgery under deep hypothermic circulatory arrest.There were 23 males and 11 females; aged 23 -67 years, mean(42.26 ±10.96) years old; Crawford type Ⅰ in 12 cases and Crawford type Ⅱ in 22 cases; aneurysms with a maximum diameter of 50 -120 mm, mean(65.26 ±16.09) mm;Marfan syndrome 15 cases, atherosclerosis 14 cases, aortic coarctation in 5 cases;22 cases of hypertension;28 cases of first aortic surgery, 6 cases of re-aortic surgery.Surgical transthoracic and abdominal incision, ext-racapsular approach, femoral artery and inferior vena cava intubation, deep hypothermic circulatory arrest technique to complete proximal anastomosis, arterial tube reconstruction of intercostal artery, abdominal organ blood supply artery and four The bifur-cated vessels were anastomosed, and the bifurcated vessels were anastomosed with the "Y"type artificial blood vessel trunk. The bilateral radial arteries were end-to-end anastomosis in the 10 mm artificial blood vessels of the "Y"type artificial blood vessels.Results There were no complications of cranial nerve system in the whole group , deep hypothermic circulatory arrest (17.68 ±4.88) min, ventilator assist time(34.88 ±16.04) hours, postoperative renal failure in 5 cases, after CRRT treat-ment After recovery, 1 case of paraplegia after operation, muscle strength recovered after cerebrospinal fluid drainage and de-compression, and 1 case died in the whole group, and died of multiple organ failure.The patients were followed up for 3 months to 5 years, and the results were satisfactory.The survivors did not die.The survivors did not die.However, 5 patients underwent thoracic aortic replacement under deep hypothermic circulatory arrest for the first time , and 4 patients underwent reo-peration because of distal vasodilation.The reconstructed intercostal artery occlusion occurred in 4 patients, but no paraplegia occurred.Conclusion When cross clamping the aorta is not feasible,it is safe to perform proximal anastomosis with deep hy-pothermic circulatory arrest.

Objective:To analyze the clinical efficacy of the Yuying powder combined with the Huanglian Shangqing pill for the treatment of subacute thyroiditis (SAT) with cervical anterior pain as the main complaint, as well as its impact on serum pain factors and oxidative stress levels in patients.Methods:A prospective selection of 100 SAT patients with anterior cervical pain as the main complaint admitted to the Hebei Provincial Hospital of Traditional Chinese Medicine from January 2020 to May 2022 was conducted. They were randomly divided into two groups, with 50 patients in each group. The control group was treated with sustained-release diclofenac sodium tablets, while the observation group was treated with external application of the Yuying powder and internal administration of the Huanglian Shangqing pill. After 2 weeks of continuous treatment, the analgesic efficacy and adverse drug reactions of both groups were observed. The analgesic onset time of two groups of anterior cervical pain was compared. Two simplified McGill pain questionnaires before and after treatment [the SF-MPQ scores, including Pain Rating Index (PRI), Visual Analog Scale (VAS), and Current Pain Intensity (PPI) ], were compared; the traditional Chinese Medicine Syndrome Score, Serum Pain Factors levels [ tumor necrosis factor (TNF)- α, interleukin-1 β(IL-1β), prostaglandin E 2 (PGE 2), and nitric oxide (NO) ] and oxidative stress indicators [the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) ] were also compared. Results:The total effective rate of analgesia in the observation group [98.00%(49/50)] was significantly higher than that in the control group [82.00%(41/50)] ( P<0.05). The analgesic onset time in the observation group was significantly shorter than that in the control group ( P<0.05). After treatment, the scores of various components (PRI, VAS, PPI) and traditional Chinese medicine syndrome scores in the two groups of SF-MPQ were significantly reduced compared to before treatment (all P<0.05); and the decrease was more significant in the observation group (all P<0.05). After treatment, the serum levels of TNF -α, IL-1β, PGE 2, and NO in both groups significantly decreased compared to before treatment (all P<0.05), and the levels of serum pain inducing factors in the observation group were significantly lower than those in the control group (all P<0.05). After treatment, both groups showed a significant decrease in serum MDA content (all P<0.05), and a significant increase in serum SOD and GSH-Px levels (all P<0.05); And the improvement was more significant in the observation group (all P<0.05). The incidence of adverse reactions in the observation group [4.00%(2/50)] was lower than that in the control group [16.00%(8/50)] ( P<0.05). Conclusions:The overall efficacy of external application of Yuying powder combined with oral administration of Huanglian Shangqing pill in the treatment of SAT with cervical anterior pain as the main complaint is definite, and its effect may be related to significantly downregulating the expression level of serum related pain inducing factors in patients and reducing the level of oxidative stress in the body.

Objective:To explore the effects of phased goal directed fluid therapy (GDFT) during anesthesia surgery on tissue perfusion and cognitive function in patients undergoing radical lung cancer surgery.Methods:A total of 108 lung cancer patients were prospectively selected and randomly divided into a control group and a study group using a random number table method. The control group received classical restrictive liquid therapy, while the study group received staged GDFT. We compared the surgical time, intraoperative blood loss, colloid fluid dosage, crystalloid fluid dosage, total output, and urine volume between two groups of patients; Two groups of patients were compared in terms of oxygenation index (OI), respiratory index (RI), central venous oxygen saturation (ScvO 2), lactate (Lac), central venous arterial carbon dioxide partial pressure difference (Pcv-aCO 2), oxygen supply index (DO 2I), and oxygen uptake rate (O 2ERe) before anesthesia induction (T 0), before single lung ventilation (T 1), 1 hour of single lung ventilation (T 2), immediate resumption of dual lung ventilation (T 3), 30 minutes of dual lung ventilation (T 4), and after surgery (T 5); The Mini Mental State Examination (MMSE) was used to evaluate the cognitive function scores of two groups of patients 1 day before surgery and 1 and 3 days after surgery, while recording the incidence of cognitive dysfunction (POCD) and pulmonary complications (including pulmonary infection, acute lung injury, pulmonary embolism, pulmonary edema, atelectasis, etc.) within 3 days after surgery. Results:The amount of crystal fluid and urine output in the research group was significantly lower than that in the control group, while the amount of colloidal fluid was significantly higher than that in the control group (all P<0.05). The OI of the study group T 1-T 5 was significantly higher than that of the control group, while the RI of T 2-T 5 was significantly lower than that of the control group (all P<0.05). The ScvO 2 of the study group T 1 to T 5 was significantly higher than that of the control group, and the Lac was significantly lower than that of the control group (all P<0.05); The MMSE scores of both groups of patients were significantly lower than those before surgery on day 1 and 3 after surgery, and the MMSE scores of the study group were significantly higher than those of the control group on day 1 and 3 after surgery (all P<0.05). The incidence of POCD within 3 days after surgery in the study group was 16.67%(9/54), lower than 37.04%(20/54) in the control group (χ 2=5.704, P=0.017); The incidence of pulmonary complications in the study group was lower than that in the control group (5.56% vs 22.22%, χ 2=4.955, P=0.026). Conclusions:The application of staged GDFT during anesthesia in patients undergoing radical lung cancer surgery can further improve tissue perfusion, improve microcirculation and oxygen supply-demand balance of systemic organs and tissues, including the brain, alleviate perioperative brain function damage, and reduce the occurrence of postoperative POCD compared to conventional liquid therapy.

Objective: To compare metabolic syndrome(MS)with Framingham risk score as predictors of cardiovascular disease(CVD)among Kazakhs population. Methods: The participants were the residents who had been followed up for more than 5 years in representative areas of Kazakhs in Xinjiang. We assigned MS a continuous risk score for predicting the development of CVD based on the weights of MS components. MS and Framingham risk score were compared in terms of their ability in predicting years in representative areas of Kazakhs in Xinjiang. We assigned MS a continuous risk score for predicting the development of CVD based on the weights of MS components. MS and Framingham risk score were compared in terms of their ability in predicting development of CVD using Cox regression and receiver operating characteristic curve. Results: The incidence of CVD was 13.87%. The incidence of CVD was higher in the MS group than it in the non-MS group(21.59% vs 11.10%, P<0.001). The area under the receiver operating characteristic(ROC)curve of MS risk score was significantly larger than that of MS classification(0.727 vs 0.585, P<0.001); the area under the curve of MS risk score was close to that of Framingham risk score(0.732 vs 0.727, P=0.673). The association between CVD and each quintile of MS risk score was more significant than that between Framingham risk score and CVD under the same exposed condition(4.61, 9.33, 14.15, 22.29 vs 3.69, 6.36, 8.47, 16.99). Conclusion MS risk score that included age may be a better predictor of CVD among Kazakhs population.

Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.

Objective To evaluate the results of a hybrid procedure for treating Stanford type B1C aortic dissection. Methods In our center, 49 patients with Stanford type B1C aortic dissection underwent supra-arch branch vessel bypass and thoracic endovascular aortic repair (TEVAR) from December 2013 to December 2017. There were 33 males and 16 females with an average age of 60.4±5.5 years. Left common carotid artery to left subclavian artery bypass (n=29), right common carotid artery to left common carotid artery and left subclavian artery bypass (n=18), left common carotid artery to left subclavian artery and right common carotid artery to right subclavian artery bypass (n=2) were performed. Results Early mortality rate was 2.0% (1/49). Forty-eight patients survived postoperatively. The follow-up rate was 100.0% (48/48). The patients were followed up for 6 to 47 (26.8±11.9) months postoperatively. Chest pain relapsed in one patient 8 months after the operation. The whole aorta CTA showed type A1S aortic dissection in one patient 6 months after the operation, and the re-operation was satisfactory. There was no endoleak or paraplegia. Conclusion Initial results suggest that the one-stage hybrid procedure is a suitable therapeutic option for type B1C aortic dissection.

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.