The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

With the rapid changes in people's lifestyles, natural and social environments in recent years, the prevalence of chronic and non-communicable diseases in China and its related risk factors have also had tremendous changes. The epidemiological characteristics of chronic and non-communicable diseases and their risk factors vary throughout the country, and the impact of unique climate, diet and lifestyle in southern China on the incidence and prevalence of chronic and non-communicable chronic diseases remains to be elucidated. Therefore, large-scale cohort study is urgently needed to provide evidence for the etiological research and management of chronic and non-communicable chronic diseases in different areas, and for the national management strategy for major chronic and non-communicable diseases. The prospective cohort study of chronic and non-communicable diseases in general population in southern China was established in December 2017. The study recruited permanent residents aged 35-74 years from both urban and rural areas in Guangdong, Hainan, Fujian Provinces and Guangxi Zhuang Autonomous Region. A big data platform of precision medicine which integrates health information with biological samples for long-term follow up has been established. A baseline database of 116 520 people aged (54.9±12.5) years, including 71 077 women (61.0%), has been established. Collecting questionnaire survey data, physical examination data, and biological samples. This paper briefly introduces the concept, design and progress of the prospective cohort study of chronic and non-communicable diseases in general population in southern China.

Objective To evaluate the safety and drug adherence of tocilizumab(TCZ)in patients with moderate to severe rheumatoid arthritis(RA)in routine clinical practice. Methods This 24 week single center observational study recruited patients with moderate to severe RA. Therapy adherence rate was calculated by actual dosing/expected dosing×100%. Efficacy end points included physician global assessment of disease activity(PGA),patient global assessment of disease activity(PtGA),28-joint disease activity score(DAS28)and so on. Safety was evaluated by recorded adverse events (AEs). Results Sixty patients were enrolled with a mean (SD) treatment adherence of (67±27)%. PGA, PtGA, pain assessment (VAS), TJC and SJC all decreased during this study. At the 12th week, 25%(6/24) and 29%(7/24) of the patients achieved DAS28 remission and EULAR good response,respectively.Eighteen AEs were recorded,of which only 2 were severe AEs(SAEs)and neither was related to TCZ. Conclusion TCZ is a highly safe treatment for decreasing disease activity in patients with moderate to severe RA in China.However,drug adherence still need to be improved.

Objective To investigate the effects of Paecilomyces Lilacinuson extracellular polysaccharides on the phenotypic and function maturity of mouse dendritic ceils.Methods Mononuclear cells were isolated from the mouse bone marrow cavity and added with cytokines for obtaining the recombinant mouse granulocyte-macrophagocyte colony stimulating factor(rmGM-CSF),recombinant mouse interleukin 4(rmIL-4) was induced to differentiated to immature DCs.Then different concentrations of extracellular polysaccharides were used to conduct the intervention.The mature DCs surface marker CD11c,major histocompatibility complex Ⅱ (MHC Ⅱ),CD80,CD86 molecular expression and phagocytosing FITC-dextran ability was detected by the flow cytometry.The effect of the polysaccharides on DCs Toll-like receptor(TLR)2 mRNA and TLR4 mRNA expression was detected by RT-PCR.Results After 400 μg/mL polysaccharides action for 48 h,the expression of DCs surface molecules such as CD11c,MHC Ⅱ,CD80 and CD86 was significantly up-regulated compared with the blank control group (P＜0.05);after the polysaccharides action,the ability of DCs phagocytosing FITC-dextran was decreased,especially the effects of 300,400 μg/mL of polysaccharides were more significant compared with the control group (P＜0.05).In addition,the polysaccharides could down-regulate the expression of TLR2 mRNA and TLR4 mRNA in DCs,the DCs down-regulation effect after 100-400 μg/mL polysaccharides treatment,the difference compared with the blank control group was statistically significant(P＜0.05).Conclusion The extracellular polysaccharides can up-regulate the expression of DCs surface CD11c,MHC Ⅱ,CD80 and CD 86 molecules,decreases the phagocytosis ability and down-regulates the expression of TLR2 mRNA and TLR4 mRNA,which preliminarily indicates that the polysaccharides could stimulate the differentiation and maturation of murine DCs.

Objective To compare three different types of donor livers (C-Ⅰ,C-Ⅱ,C-Ⅲ) in clinical efficacy,complications and survival rate of liver transplantation.Methods Using the retrospective descriptive study method,the clinical data of 422 patients undergoing liver transplantation,including 124 cases of C-Ⅰ,81 cases of C-Ⅱ and 81 cases of C-Ⅲ in recent 6 years (from June 2010 to June 2016) were analyzed.The same surgical method was performed with piggyback liver transplantation.Observation indicators contained (1) recipient postoperative liver function;(2) the postoperative complications;(3) the recipient survival rate.SPSS 19.0 statistical software was used for analysis.Results (1) The curative effect was evaluated by the changes of ALT and TBIL among three groups of recipients postoperatively.As compared with C-Ⅰ transplantation group and CⅢ transplantation group,the level of ALT in C-Ⅱ transplantation group was significantly increased (P ＜0.05),the clinical efficacy was poorer.(2) The incidence of PNF was 3.23％ in C-Ⅰ group,9.88％ in C-Ⅱ group and 9.88％ in C-Ⅲ group (P＜0.05).The incidence of acute rejection was respectively 9.68％ in C-Ⅰ group,38.27％ in C-Ⅱ group and 38.27％ in C-Ⅲ group (P＜0.001).The incidence of SIRS was respectively 5.65％ in C-Ⅰ group,39.50％ in C-Ⅱ group and 39.50％ in C-Ⅲ group (P＜ 0.001).There were significant differences in the incidence of other complications among the three groups.(3) There were 14 deaths within 3 months,accounting for 17.28％,and the survival rate was 82.72％ in C-Ⅱ group,the 1-,3-,and 5-year survival rate was 76.55％,74.18％ and 76.55％ respectively in C-Ⅰ group,and that was 88.02％,85.72％ and 81.11％ respectively in C-Ⅲ group.Conclusion Since June 2015,C-Ⅰ donors grow up more quickly on year-on-year basis than C-Ⅱ.Simultaneously,the sort-term and long-term clinical efficacy is better in C-Ⅰ transplantation group than in C-Ⅱ transplantation group.How to repair the three types of Chinese standard donor organs and optimize the quality is still a hot point to ensure the healthy development of organ transplantation in China,which needs further investigation.

Objective To evaluate the clinical effectiveness of 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for the treatment of moderate to severe acne vulgaris.Methods From January to June 2013,a total of 43 patients with moderate to severe acne vulgaris were treated by 5 aminolaevulinic acid based PDT with red light.All patients were received three times of treatment at 2-week intervals.Clinical assessment was conducted before and at 2,4,6 and 8 weeks after treatment.Results The lesion counts of both inflammatory and non-inflammatory lesions were reduced significantly after treatment.The mean percentage reduction in inflammatory lesions was 88.9 ％ at 8 weeks after the treatment,meanwhile that in non-inflammatory lesions was 73.4％.After 8 weeks of treatment,55.8％ patients (24/43)showed clinical cure,and 41.9％ patients (18/43)showed excellent response and 2.3％ patient (1/43) showed good response.Only 4.7％ patients (2/43)showed signs of recurrence after 4 months after ALA-PDT.After one course of ALA-PDT,the symptoms in this recurrent case were significant improvement.The common adverse effects included pain,edema and transient hyperpigmentation.They could gradually disappear without a need of special intervention.Conclusions ALA-PDT is a safe and effective therapeutic option for the treatment of moderate to severe acne vulgaris.

Objective:To investigate the effects of the Paecilomyces Lilacinuson extracellular polysaccharides on the phenotypic and maturation of murine dendritic cells. Methods: Imature DCs were induced in vitro from the murine bone marrow cells in the presence of rmGM-CSF and rmIL-4, and then they were cultured with different dosage of the extracellular polysaccharides. The morphological characterization was analyzed under microscopy. The expressions of the DCs surface costimulating factors and phagocytic function to FITC-dextran were detected by flow cytometry. The level of IL-12 secreted by DCs was observed by ELISA. At the same time the influence of DCs on the proliferation of T cells was determined by MTT. Results:Treating with the polysaccharides for 48 h could up-regulate the expression of DCs surface molecules,such as CD11c,MHCⅡ,CD80 and CD86,and the 400 μg/ml was the optimal dose,comparing with the blank control group, the difference was significant (P<0. 01), contrast to LPS control group that was not different ( P<0. 05 ) . The uptaking FITC-dextran ability of the DCs treated with 300 μg/ml and 400 μg/ml polysaccharides was significant lower than the unstimulated DCs(P<0. 05). At the same time the extract at different concentration could distinctly enhance the proliferation of T cells by DCs too. Conclusion:The extracellular polysaccharides could stimulate the maturation of dendritic cells and induce the production of mature dendritic cells.

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

Objective To investigate the anti-oxidant effect of pirfenidone (PD) at different dosage on acute lung injury (ALI) induced by paraquat (PQ) poisoning in mice. Methods 144 ICR mice were randomly divided into four groups: control group (n = 24), PQ poisoned group (n = 24), high and low doses PD treatment groups (n = 48). ALI induced by PQ poisoning model was reproduced by intraperitoneal injection of 25 mg/kg 20% PQ solution in mice, and the mice in control group was given equal volume of normal saline. Intragastric administration with 30 mg/kg and 70 mg/kg PD suspension [PD was dissolved in 0.4% sodium carboxymethyl cellulose sodium (CMC) solution] after PQ poisoning immediately for 3 days in high and low doses PD treatment groups respectively, while the same volume of 0.4% CMC solution was administrated in control group and PQ poisoned group. Then mice in each group were respectively sacrificed at 2, 6, 12, 24, 48 and 72 hours after PD exposure to harvest the lung tissue, nuclear factor-κB (NF-κB) was determined by enzyme linked immunosorbent assay (ELISA), superoxide dismutase (SOD) and malonaldehyde (MDA) were determined by colorimetry, and pulmonary pathological changes were observed with microscope after hematoxylin-ensin (HE) staining. Results Compared with the control group, NF-κB from 2 hours in PQ poisoned group was significantly increased (pg/mg: 106.65±5.96 vs. 79.04±2.40, P < 0.05), and lasted to 72 hours (pg/mg: 110.47±5.91 vs. 82.70±2.79, P < 0.05); the activity of SOD was significantly enhanced in early stage (2-6 hours; U/mg: 39.34±1.17 vs. 34.72±1.54 at 2 hours, 37.37±0.90 vs. 33.75±0.93 at 6 hours, both P < 0.05) followed by a gradual decrease; the content of MDA within 24 hours was significantly increased (nmol/mg: 1.67±0.22 vs. 1.03±0.09 at 2 hours, 1.56±0.17 vs. 1.14±0.16 at 24 hours, both P < 0.05) followed by a gradual decrease. Compared with the PQ poisoned group, both high and low dose PD treatment could significantly inhibit NF-κB from 24 hours to 72 hours, and significantly inhibit MDA within 24 hours; high dose PD treatment could increase SOD activity at 6 hours, which showed a tendency of decreasing followed by increasing in low dose PD treatment group. Compared with high dose PD treatment group, the inhibition of MDA in low dose PD treatment group was more significant (nmol/mg: 0.90±0.08 vs. 1.29±0.18 at 2 hours, 1.03±0.32 vs. 1.84±0.43 at 6 hours, 1.08±0.09 vs. 1.33±0.16 at 24 hours, all P < 0.05), and SOD activity was significantly decreased at 6 hours (U/mg: 35.24±2.08 vs. 38.46±0.87, P < 0.05), and it was increased at 72 hours (U/mg: 39.81±1.30 vs. 34.58±3.15, but P > 0.05), but no significant difference in NF-κB activity at all time points was found. Under light microscope, a wide range of red blood cells and serous effusion, alveolar septum fracture and pulmonary interstitial inflammatory cell infiltration were shown by pathologic examination in PQ poisoned group. The pathologic changes in high and low doses PD treatment groups were obviously less than those of PQ poisoned group, and no significant difference was found between the two doses groups. Conclusions The early therapeutic effect of PD may relate to the inhibition of NF-κB and reactive oxygen species, then reduce the inflammation of PQ poisoning. The treatment effectiveness of low dose PD seems better than high dose PD.

Objective To investigate the extraction and purification methods of serum specific endothelial cell antibody of renal transplant recipients with rejection after renal transplantation.Methods Human umbilical vein endothelial cell (HUVEC)was isolated and cultured.The serum samples of the renal transplant recipients with poor renal function after renal transplantation were collected.Specific endothelial cell antibody was screened out with flow cytometry;antibodies against human leukocyte antigen (HLA)and major histocompatibility complex class Ⅰ-related chain A (MICA)were detected by Luminex platform.After the existence of specific endothelial cell antibody in the serum sample was confirmed,specific endothelial cell antibody was absorbed with HUVEC.The cell was washed and then the absorbed antibody was eluted from the cell membrane.Antibody IgG in the eluent was purified and concentrated again with Protein-A /G magnetic beads.Antibody activity in the eluent was detected by flow cytometry and the purified specific endothelial cell antibody (IgG)was identified by SDS-polyacrylamide gel (SDS-PAGE)and Western blot.Results In the serum of 386 renal transplant recipients,the serum samples of 5 renal transplant recipients with serum creatinine (Scr) >400 μmoI /L,negative anti-HLA antibody,negative anti-MICA antibody and median fluorescence intensity (MFI) >16 were selected.Purified specific endothelial cell antibody IgG showed immunoglobulin heavy chain (purity > 95%)by SDS-PAGE gel.Flow cytometry showed that the purified antibody had the feature of rebinding with the surface antigen of vascular endothelial cell.Conclusions The purification method of using human umbilical vein endothelial cell to absorb specific endothelial cell antibody in the serum of renal transplant recipients may obtain good effect.