Pafolacianine is a fluorescent agent that specifically targets folate receptors,employed in the treatment of adult ovarian cancer patients to support the detection of malignant growths during surgical interventions.Pafolacianine binds to cancer cells expressing folate receptors,accumulating within folate-receptor-positive tumor tissue through receptor-mediated endocytosis.It can be excited by near-infrared fluorescence imaging,facilitating the surgical removal of tumors during procedures.This article gives an introduction to the mechanism of action,pharmacokinetics,clinical studies,and safety aspects of Pafolacianine.

On May 27,2021,the U.S.Food and Drug Administration(FDA)officially approved Lantheus'PYLARIFY?(Piflufolastat F 18,18 F-labeled imaging agent),which can be used for positron emission computed tomography(PET)of prostate-specific membrane antigen(PSMA)-positive lesions in prostate cancer patients to accurately identify prostate cancer with suspected metastasis or recurrence.Piflufolastat F 18 is approved by FDA for two indications.The first is the initial staging for suspected metastatic lesions in men with newly diagnosed prostate cancer.The second is restaging,with the goal of identifying lesions in the setting of biochem ical recurrence.

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans ; Female ; Lymphatic Metastasis ; B7-H1 Antigen/metabolism* ; Triple Negative Breast Neoplasms/pathology* ; Breast Neoplasms ; Osteonectin/therapeutic use* ; Prognosis

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans ; Female ; Lymphatic Metastasis ; B7-H1 Antigen/metabolism* ; Triple Negative Breast Neoplasms/pathology* ; Breast Neoplasms ; Osteonectin/therapeutic use* ; Prognosis

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

Objective:To investigate the expression difference of miR-3189-3p in renal cancer tissue and adjacent tissue and its effect on the biological function of renal cancer cells.Methods:quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of miR-3189-3p in renal cancer tissues and adjacent tissues, renal cancer cell lines (Caki-1, ACHN, A498, OS-RC-2) and normal renal tubular epithelial cells HK-2. miR-NC or miR-3189-3p mimics were transfected into renal cancer cells with the lowest expression of miR-3189-3p, respectively, named miR-NC group and miR-3189-3p group. The effects of miR-3189-3p on the proliferation and invasion of renal cancer cells were detected by CCK-8 method and Transwell migration experiment. miRanda and miRTarBase software was used to predict the downstream gene of miR-3189-3p. The dual luciferase reporter gene experiment was used to verify the downstream gene of miR-3189-3p. qRT-PCR and Western blotting were used to detect the expression of miR-3189-3p downstream gene. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups. Results:The relative expression of miR-3189-3p in renal cancer tissue and paracancerous tissue was 1.97±0.61 and 6.19±0.73, respectively, and the relative expression of miR-3189-3p in renal cancer tissue was lower than that in paracancerous tissue ( P<0.01). The relative expression of miR-3189-3p in renal cancer cell lines was lower than that in HK-2 cells ( P<0.05). The relative expression of miR-3189-3p in OS-RC-2 cells was the lowest ( P<0.01). The relative expression levels of miR-3189-3p in OS-RC-2 cells in the miR-NC group and miR-3189-3p group were 1.01±0.11 and 9.27±1.43, respectively, and the relative expression levels of miR-3189-3p in the miR-NC group significantly lower than the miR-3189-3p group ( P<0.01). Compared with the miR-NC group, the proliferation ability of OS-RC-2 cells with high expression of miR-3189-3p was significantly reduced ( P<0.05). The numbers of penetrating cells in the miR-NC group and miR-3189-3p group were 165.40±17.02 and 41.07±6.36, respectively, and the invasive ability of OS-RC-2 cells in the miR-3189-3p group was significantly reduced ( P<0.01). The target gene of miR-3189-3p is Aquaporin 3 ( AQP3) and miR-3189-3p can target AQP3 mRNA ( P<0.01). Compared with the miR-NC group, the expression of AQP3 gene in the high-expressing miR-3189-3p cells was significantly reduced at both the mRNA level and the protein level ( P<0.01). Conclusions:The expression of miR-3189-3p is down-regulated in renal cell carcinoma. High expression of miR-3189-3p can significantly inhibit the proliferation and invasion of renal cell carcinoma OS-RC-2 cells. The molecular mechanism is that miR-3189-5p targets and inhibits the expression of AQP3 gene.

Endoscopy ; Humans ; Neoplasms/surgery* ; Submandibular Gland/surgery* ; Thyroidectomy

The concept of total mesorectal resection provides a quality control standard that can be followed for radical resection of rectal cancer, but some anatomical problems are still controversial. Compared with traditional open surgery, laparoscopic radical rectal surgery has better surgical vision, better neurological protection, better operating space. However, if the surgeon has insufficient understanding of the anatomy, collateral damage may occur, such as uncontrollable bleeding during the operation, postoperative urination and defecation dysfunction and so on. Based on the interpretation of the researches at home and abroad, combined with the clinical experience, we elucidate some associated issues, including anatomic variation of inferior mesenteric vessels, the controversy of inferior mesenteric artery ligation plane, the controversy of lymph node dissection in No. 253, the anatomical variation of middle rectal artery, and the anatomical controversy of lateral lymph node dissection in rectal cancer, in order to provide better cognitive process for the clinical front-line surgeons.
Humans ; Laparoscopy ; Lymph Node Excision ; Lymph Nodes ; Mesenteric Artery, Inferior ; Rectal Neoplasms/surgery* ; Rectum

Camptotheca acuminata produces camptothecin (CPT), a monoterpene indole alkaloid (MIA) that is widely used in the treatment of lung, colorectal, cervical, and ovarian cancers. Its biosynthesis pathway has attracted significant attention, but the regulation of CPT biosynthesis by the APETALA2/ethylene-responsive factor (AP2/ERF) transcription factors (TFs) remains unclear. In this study, a systematic analysis of the AP2/ERF TFs family in C. acuminata was performed, including phylogeny, gene structure, conserved motifs, and gene expression profiles in different tissues and organs (immature bark, cotyledons, young flower, immature fruit, mature fruit, mature leaf, roots, upper stem, and lower stem) of C. acuminata. A total of 198 AP2/ERF genes were identified and divided into five relatively conserved subfamilies, including AP2 (26 genes), DREB (61 genes), ERF (92 genes), RAV (18 genes), and Soloist (one gene). The combination of gene expression patterns in different C. acuminata tissues and organs, the phylogenetic tree, the co-expression analysis with biosynthetic genes, and the analysis of promoter sequences of key enzymes genes involved in CPT biosynthesis pathways revealed that eight AP2/ERF TFs in C. acuminata might be involved in CPT synthesis regulation, which exhibit relatively high expression levels in the upper stem or immature bark. Among these, four genes (CacAP2/ERF123, CacAP2/ERF125, CacAP2/ERF126, and CacAP2/ERF127) belong to the ERF-B2 subgroup; two genes (CacAP2/ERF149 and CacAP2/ERF152) belong to the ERF-B3 subgroup; and two more genes (CacAP2/ERF095 and CacAP2/ERF096) belong to the DREB-A6 subgroup. These results provide a foundation for future functional characterization of the AP2/ERF genes to enhance the biosynthesis of CPT compounds of C. acuminata.

Objective: To understand the present situation of physical activity and its influencing factors, and to provide a reference for improving the level of physical activity and making the intervention measures. Methods: The method of random stratification was used to select 4 740 pre school children aged 3-6 from 17 kindergartens in 12 counties and districts of Nanchang City, The questionnaire of physical activities of young children and the questionnaire of parents of physical activities of young children were applied to conduct a survey. Results: Compared with weekday PA and MVPA, preschool children’s weekends decreased, SB increased. The differences in PA, MVPA and SB on weekdays and weekends were statistically significant( P <0.01). The proportion of PA and MVPA reaching the recommended amount during the working day of preschool children were 44.9%-59.2%, 45.4%- 61.7%.The proportion reaching the recommended amount of PA and MVPA on weekends were 24.7%-27.8%, 24.5%-29.9%, and the proportion reaching the recommended amount on weekdays was higher than that on weekends. Conclusion There is still gap between actual amount of physical activity and the recommended amount. There are different modes of activity on weekdays and weekends, and weekends are the least active periods. Parents and teachers should pay enough attention to the establishment of "social campus family" model to improve the lack of physical activity of preschool children.