Chronic diseases (ChDs) today constitute the leading cause of morbidity and mortality. Increasing evidence suggests that the production and development of ChDs are associated with amplified inflammation, which is caused by accumulation of advanced glycation end products (AGEs) and advanced lipexidation end products (ALEs).Heating, irradiation, and ionization, in combination with gross over-nutrition, significantly contribute to production of, exposure to and accumulation in the body of AGEs/ALEs. Furthermore, dietary AGEs restriction in animals seemed to be effective to extend life span. This paper elucidates the relationship between food and AGEs and the dietary measures to reduce AGEs/ALEs with an attempt to provide new methods for prevention and treatment of ChDs.

Objective:Semaphorin 4D (Sema4D) acts as a regulator for axon guidance in central nervous system development. However, new evidence indicates that Sema4D has a previously unrecognized function, namely, compensatory angiogenic factor. This study aimed to investigate the effect of Sema4D on tumor growth and vascularity of colorectal carcinoma (CRC) in nude mice. Meth-ods:Sema4D was knocked down in CRC cells by infecting the cells with lentiviruses coding for Sema4D shRNA. Two groups of cells, namely, those infected with control viruses and those infected with Sema4D shRNA viruses, were subjected to migration assay to test their ability induce endothelial cell migration. The two cell groups were subcutaneously injected into nude mice. Tumor growth was documented, and the tumors harvested from the mice were subjected to immunohistochemistry or immuno fl uorescence analyses. Re-sults:In vitro migration assay results indicated that media conditioned by HCT-116 cells infected with Sema4D shRNA lentiviruses in-duced low endothelial cell migration. The two groups of subcutaneously inoculated cells showed 100%tumorigenicity. However, tumor growth rates were significantly different between the two groups. Xenografts in which Sema4D was downregulated showed marked re-duction in tumor size and vascularity. Conclusion:Cancer cells may highly express Sema4D to trigger net neo-angiogenesis and gener-ate a tumor blood supply system. Thus, Sema4D could potentially be a target in anti-angiogenic therapy of CRC patients.

Objective: To investigate the expressions of programmed death ligand 1（PD-L1）in triple-negative breast cancer (TNBC) and its correlation with angiogenesis. Methods: 120 cases of TNBC patients who underwent surgery in the Fourth Hospital of Hebei Medical University from March 1, 2011 to June 1, 2012 were collected. The tumor tissues of patients were surgically resected and confirmed by pathology. PD-L1 protein expression in TNBC tissues of 120 patients was detected by tissue microarray combined with immunohistochemistry, and its relationship with various clinical indicators was analyzed. Blood vessels and lymphatic vessels were labeled withCD34andD2-40todetectmicrovesseldensity(MVD)andlymphaticvesseldensity(LVD)inTNBC.Results:Thepositiveexpression rate of PD-L1 in the tumor cells and interstitial infiltrating lymphocytes fromTNBC was 56.7% (68/120); No correlation was found between PD-L1 protein expression and the gender, age, histological grade, clinical stage, or tumor size of patients with TNBC (P>0.05), but related to the lymph node metastasis (P<0.05) and vascular thrombus (P<0.05). TNBC with high PD-L1 expression exhibited high incidence of lymph node metastasis and formation of vascular thrombus, and the expression of PD-L1 was positively correlated with MVD (r=0.500, P=0.02) as well as LVD (r=0.662, P=0.01). Log-Rank test showed that the survival time of TNBC patients with positive PD-L1 protein expression was significantly shorter than that of patients with negative expression (P<0.05). Cox multivariate analysis suggested that PD-L1 protein expression could be an independent prognostic factor for TNBC overall survival. Conclusion: PD-L1 plays an important role in TNBC angiogenesis and lymphangiogenesis, and is closely related to TNBC invasion and metastasis; blocking PD1/PD-L1 signal pathway is expected to be an effective new strategy for TNBC treatment.

Objective To estimate the therapeutic value of plasma exchange (PE) in severe bullous dermatoses and drug eruption. Methods Plasma exchange was carried out to treat 47 patients with severe dermatoses including 15 cases of pemphigus, 17 cases of bullous pemphigoid and 15 cases of drug eruption who were intolerant or unresponsive to glucocorticosteroids and or immunosuppressants. Cobe Spectra blood cell separator was utilized to collect plasma and cell components from patients' blood, and the replacement fluid and cell components were infused back into patients. Patients received 1 to 3 sessions of plasma exchange. Results Of the 47 patients, 44 (93.62%) achieved satisfactory efficacy with relief of clinical symptoms and improvement of laboratory parameters 2 to 3 days after the plasma exchange. Side effects occurred in 11 (23.4%) patients, which included fever, shivering, numbness of limbs, pruritus and convulsion. Conclusion Plasma exchange is beneficial for the control of severe drug eruption and bullous dermatoses.

Objective To construct four types of glucagon-like peptide-1 (GLP-1) and human serum albumin (HSA) fusion proteins that can be realeased at different rate in vivo by introducing protease cleavage sites between these two moieties.The therapeutic effect and release rate are studied to achieve balanced pharmacokinetics ( PK) and pharmacody-namics ( PD) of GLP-1 and HSA fusion proteins.Methods The gene with different polypeptide joint of GLP-1 and HSA fusion proteins were synthesized by overlap extension PCR amplification, cloned into expression vector pPIC9 and transformed into Pichia pastoris GS115.Then, fusion proteins were obtained by protein purification after being induced by methanol.The preliminary PK and PD of the fusion proteins were studied after purification.Results The fusion protein Gly2-GLP-1-GGGGG-HSA showed no release while Gly2-GLP-1-VTR-HSA, Gly2-GLP-1-SARSVRA-HSA, and Gly2-GLP-1-GRSRVTRSV-HSA showed a slow, medium and fast release rate, respectively, after incubation with furin.In vitro biological activity test results dispalyed that each type of fusion protein promoted insulin secretion of MIN6 cells.In vivo PK test indicated the half-life size of fusion proteins was the largest in Gly2-GLP-1-GGGGG-HSA, followed by Gly2-GLP-1-VTR-HSA, Gly2-GLP-1-SARSVRA-HSA, and Gly2-GLP-1-GRSRVTRSV-HSA.In vivo PD test exhibited hypoglycemic activity that was the highest in Gly2-GLP-1-VTR-HSA, followed by Gly2-GLP-1-SARSVRA-HSA, Gly2-GLP-1-GRSRVTRSV-HSA, and Gly2-GLP-1-GGGGG-HSA.Conclusion GLP-1 can be released from fusion proteins with full activity after the introduction of protease cleavage sites.Releasable fusion proteins at an appropriate release rate have the most balanced PK and PD.

Objective To construct a collagen matrix-based skin model that can last a long time in vitro for potential application of subsequent tests and studies.Methods The porcine collagen and normal human skin fibroblasts were mixed and seeded into the culture dish,which were cultured for 3-4 days to obtain a dermal structure.Then,the third-to seventh-passage normal human keratinocytes were seeded onto the dermal surface and cultured for 14 days to obtain a double-layer skin model.Hematoxylin and eosin (HE)staining and Masson staining were performed to evaluate the morphology and structure of the skin model,and electron microscopy was conducted to observe the ultrastructure of the skin model.Immunohistochemical study and immunofluorescence staining were conducted to determine the expression of major markers in each layer of the skin model.Results HE and Masson staining showed that the skin model and normal human skin tissues showed very similar dermal and epidermal structures.After harvest of the skin model,it can be cultured in vitro for another 14 days with favorable and stable dermal and epidermal structures.Electron microscopy showed lipids in the stratum corneum,keratohyalin granules in the stratum granulosum,corneodesmosomes,desmosomes and basal membrane in the skin model.Immunohistochemical and immunofluorescence staining showed the consistent expression of transglutaminase,filaggrin,keratin 10 and Ki67 in the epidermis in both the skin model and normal skin.Moreover,the expression of type Ⅳ collagen and laminin-5 in the basal membrane,as well as that of type Ⅰ collagen,type Ⅲ collagen and fibrillin in the dermis were both consistent between the skin model and normal skin.Conclusion The constructed three-dimensional (3D) skin model is highly analogous to normal human skin in the aspect of tissue structure and various protein expression,and the skin model can be stably cultured in vitro for at least 14 days after harvest.

Objective To explore the efficacy and safety of traditional Chinese medicine(TCM) combined with chemotherapy in the prevention and treatment of postoperative recurrence and metastasis of locally advanced gastric cancer (LAGC) by meta-analysis. Moreover, we evaluated the efficacy of TCM on the quality of life, immune indexes, and toxic and side effects during adjuvant chemotherapy. Methods The CNKI, Wanfang, PubMed, and other databases were searched by computer. Randomized controlled trials (RCTs) were searched. After literature screening and data extraction, Review Manager 5.3 software provided by Cochrane was used for meta-analysis. Results A total of 18 RCTs were included. Compared with chemotherapy alone, TCM combined with chemotherapy could improve the KPS score and CD3⁺ and CD4⁺/CD8⁺ index levels. The incidence rates of postoperative leucopenia, hemoglobin reduction, thrombocytopenia, nausea and vomiting, diarrhea, and neurotoxicity were reduced. In terms of postoperative QLQ-C30 score, abnormal liver function, and abnormal renal function, the incidence of TCM combined chemotherapy was similar to that of chemotherapy alone, with no statistical difference. Compared with chemotherapy alone, TCM combined chemotherapy could reduce the 1-, 2-, 3-, and 5-year cumulative recurrence and metastasis rates and prolong the disease-free survival time. Conclusion Compared with chemotherapy alone in adjuvant chemotherapy, TCM combined chemotherapy could improve the immune level and KPS score of LACC patients after surgery, reduce the incidence of adverse reactions, as well as reduce the recurrence and metastasis rate of LAGC after surgery and DFS could be improved.

OBJECTIVE: To improve the method of vermillion flap and orbicularis oris bundle anastomosis in repair of transverse facial cleft. METHODS: Based on the precise fixed point, the modified vermillion flap was designed slender at the new corner of the upper lip, and was inserted into the lower lip after removing part tissue. The orbicularis oris was divided into two bands and cross-stitched. RESULTS: Fifteen patients with unilateral transverse facial cleft form the Children's Hospital of Zhejiang University during September 2016 and December 2018 were operated, and the position and shape of the commissure were almost normal. CONCLUSIONS The cosmetic effect and oral function are satisfactory when the modified vermillion flap and bundle anastomosis of orbicularis oris is used to repair transverse facial cleft.
Anastomosis, Surgical ; Child ; Cleft Lip ; surgery ; Facial Muscles ; surgery ; Humans ; Lip ; surgery ; Surgical Flaps ; surgery ; Treatment Outcome

Objective:To investigate the effect of motion correction (MC) on the calculated values of myocardial blood flow (MBF) and myocardial flow reserve (MFR) based on cadmium-zinc-telluride SPECT (CZT SPECT) images.Methods:Twenty-eight consecutive patients (10 males, 18 females, age: (60.75±11.62) years) with suspected or known coronary artery disease who underwent myocardial perfusion imaging (MPI) with dynamic CZT SPECT between June 2019 and August 2019 in TEDA International Cardiovascular Hospital were retrospectively analyzed. The MBF and MFR during rest imaging and stress imaging were quantitatively analyzed. Corridor 4DM software was used to calculate the stress MBF (sMBF) and MFR of the coronary artery branches and left ventricular (LV) before and after MC. The paired t test and Pearson correlation were used for data analysis. Results:The sMBF and MFR of LV before MC were (0.82±0.49) ml·min -1·g -1 and 1.69±0.68 respectively. After MC the two parameters increased to (1.05±0.64) ml·min -1·g -1 and 2.12±0.77 respectively ( t values: -4.87, -6.01, both P<0.001). The sMBF and MFR in left anterior descending (LAD), left circumflex (LCX), right coronary artery (RCA) and LV before MC were correlated with those after MC ( r values: 0.69-0.96, all P<0.001). If MFR <2.0 was used as the reference of impaired MFR, data before MC showed 19 patients (67.9%, 19/28) had impaired MFR, while 13 patients (46.4%, 13/28) had impaired MFR based on MFR values after MC. Conclusion:For MPI quantitative imaging with CZT SPECT, the calculated values of sMBF and MFR after MC is higher than those before MC, suggesting that MC is helpful to reduce the false positive results which may be caused by the " creep" effect of the heart.

OBJECTIVES: To establish an experimental method for evaluating material permeability of type I collagen hydrogels. METHODS: Using BSA-FITC as an indicator, by combining BSA-FITC with PBS they were used as permeability media, and using transwell load hydrogen sample to detect BSA-FITC transparent rate. RESULTS: In the concentration range of 100 μg·mL~0.781 μg·mL, the standard curve ≥ 0.99, Lower Limit of Quantity (LLOQ) is 3.125 μg·mL, RSD <5%, detection recovery rate is in the range of 80%~120%. CONCLUSIONS In this study, we established an experimental method for evaluating material permeability of hydrogel. The BSA-FITC transparent rate of type I collagen hydrogel was 100% at 28 h.
Collagen Type I ; chemistry ; Hydrogels ; chemistry ; Materials Testing ; Permeability