Covalent Bonding of Salen Metal Complexes with Pyrene Chromophores to Porous Polymers for Photocatalytic Hydrogen Evolution.

The development of low-cost and efficient photocatalysts to achieve water splitting to hydrogen (H2) is highly desirable but remains challenging. Herein, we design and synthesize two porous polymers (Co-Salen-P and Fe-Salen-P) by covalent bonding of salen metal complexes and pyrene chromophores for photocatalytic H2 evolution. The catalytic results demonstrate that the two polymers exhibit excellent catalytic performance for H2 generation in the absence of additional noble-metal photosensitizers and cocatalysts. Particularly, the H2 generation rate of Co-Salen-P reaches as high as 542.5 µmol g-1 h-1, which is not only 6 times higher than that of Fe-Salen-P but also higher than a large amount of reported Pt-assisted photocatalytic systems. Systematic studies show that Co-Salen-P displays faster charge separation and transfer efficiencies, thereby accounting for the significantly improved photocatalytic activity. This study provides a facile and efficient way to fabricate high-performance photocatalysts for H2 production.

Effectiveness and Safety of Anlotinib Combined with PD-1 Blockades in Patients with Previously Immunotherapy Treated Advanced Non-Small Cell Lung Cancer: A Retrospective Exploratory Study.

Objective: This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC). Methods: A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored. Results: The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3-35.9%) and a disease control rate of 85.1% (95% CI: 74.3-92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37-9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73-22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, P=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity. Conclusion: Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.

Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma.

BACKGROUND: Bile duct obstruction is a common issue for patients with advanced cholangiocarcinoma (CCA). Percutaneous transhepatic cholangial drainage (PTCD) is often required to relieve the obstruction. However, PTCD may alter the intestinal microbiota, which can affect the efficacy of immunotherapy. Antibiotics (ATB) can also have significant immunomodulatory effects by perturbing the gut microbiota. Therefore, this study aimed to investigate whether PTCD or ATB therapy is associated with overall survival (OS) or progression-free survival (PFS) in patients with advanced CCA receiving first-line chemotherapy plus immune checkpoint blockade (ICB) in clinical practice. We also explored whether the gut microbiota changes after receiving PTCD. METHODS: We conducted a single-center retrospective analysis of PTCD and ATB therapy in patients with advanced CCA. PTCD was performed before ICB initiation, and ATB was administered within 1 month before and 6 weeks after ICB initiation. Our primary outcomes were PFS and OS. Moreover, we used 16s rRNA sequencing to analyze fecal and bile samples obtained from patients who underwent PTCD. RESULTS: In total, 107 patients with CCA were included. Among patients who did not undergo PTCD, ICB plus chemotherapy significantly improved OS vs. chemotherapy alone (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.09-0.45, p < 0.0001). PFS was also significantly improved in patients who received ICB plus chemotherapy compared with chemotherapy alone (HR 0.36, 95% CI 0.16-0.80, p = 0.0024). However, ICB plus chemotherapy did not improve survival compared with chemotherapy alone among patients who received PTCD. Overall changes in the fecal microbiota of patients after PTCD involved significant reductions in which Escherichia - Shigella. CONCLUSIONS: The use of ATB or PTCD in patients with CCA receiving ICB was associated with worse OS compared with chemotherapy alone, and PTCD affects the gut microbiota. Escherichia - Shigella was significantly reduced in feces of patients after PTCD.

Probiotic-loaded calcium alginate/fucoidan hydrogels for promoting oral ulcer healing.

Probiotics are beneficial bacteria located in the oral cavity which exhibit antimicrobial properties and contribute to the regulation of immune function and the modulation of tissue repair. Fucoidan (FD), a marine prebiotic, may further enhance the ability of probiotics to promote ulcer healing. However, neither FD nor probiotics are attached to the oral cavity and neither are well-suited for oral ulcer healing owing to the wet and highly dynamic environment. In this study, probiotic-loaded calcium alginate/fucoidan composite hydrogels were developed for use as bioactive oral ulcer patches. The well-shaped hydrogels exhibited remarkable wet-tissue adhesion, suitable swelling and mechanical properties, sustained probiotic release, and excellent storage durability. Moreover, in vitro biological assays demonstrated that the composite hydrogel exhibited excellent cyto/hemocompatibility and antimicrobial effects. Importantly, compared to commercial oral ulcer patches, bioactive hydrogels show superior therapeutic capability for promoting ulcer healing in vivo by enhancing cell migration, inducing epithelial formation and orderly collagen fiber deposition, as well as facilitating neovascularization. These results demonstrate that this novel composite hydrogel patch demonstrates great potential for the treatment of oral ulcerations.

Protease-Loaded CuS Nanoparticles with Synergistic Photothermal/Dynamic Therapy against F. nucleatum-Induced Periodontitis.

Periodontitis is a chronic inflammatory disease induced by a plaque biofilm, which can lead to the destruction of the periodontal support tissue and even teeth loss. The common strategies of periodontitis treatment are to eliminate bacterial/biofilm-related inflammation and subsequently inhibit alveolar bone resorption, for which antibiotic therapy is the most traditional one. However, impenetrable polymeric substances on bacterial biofilms make it difficult for traditional antimicrobial agents to take effect. In this study, a novel nanoparticle protease-loaded CuS NPs was developed, combining the advances of photodynamic and photothermal therapy from CuS and enzymatic degradation of the biofilm by a protease. The photothermal activity and the reactive oxygen generation capacity of the designed nanoparticles were verified by the experimental results, constituting the basis of antibacterial function. Next, the high antimicrobial activity of CuS@A NPs onFusobacterium nucleatumand its biofilm was demonstrated. The proper hemo/cytocompatibility of CuS-based NPs was demonstrated by in vitro assays. Last, effective treatment against periodontitis was achieved in a rat periodontitis model through the significant efficacy of inhibiting bone resorption and alleviating inflammation. Thus, the developed CuS@A NPs prove a promising material for the management of periodontitis.

Prospective, longitudinal analysis of the gut microbiome in patients with locally advanced rectal cancer predicts response to neoadjuvant concurrent chemoradiotherapy.

BACKGROUND: Neoadjuvant concurrent chemoradiotherapy (nCCRT) is a standard treatment for locally advanced rectal cancer (LARC). The gut microbiome may be reshaped by radiotherapy through its effects on microbial composition, mucosal immunity, and the systemic immune system. We sought to clarify dynamic, longitudinal changes in the gut microbiome and blood immunomodulators throughout nCCRT and to explore the relationship of such changes with outcomes after nCCRT. METHODS: A total of 39 patients with LARC were recruited for this study. Fecal samples and peripheral blood samples were collected from all 39 patients before nCCRT, during nCCRT (at week 3), and after nCCRT (at week 5). The gut microbiota and the microbial community structure were analyzed by 16S rRNA sequencing of the V3-V4 region. Levels of blood immunomodulatory proteins were measured with a Millipore HCKPMAG-11 K kit and Luminex 200 platform (Luminex, USA). RESULTS: Cross-sectional and longitudinal analyses revealed that the gut microbiome profile and enterotype exhibited characteristic variations that could distinguish patients with good response (AJCC TRG classification 0-1) vs poor response (TRG 2-3) to nCCRT. Sparse partial least squares regression and canonical correspondence analyses showed multivariate associations between specific microbial taxa, host immunomodulatory proteins, immune cells, and outcomes after nCCRT. An integrated model consisting of baseline Clostridium sensu stricto 1 levels, fold changes in Intestinimonas, blood levels of the herpesvirus entry mediator (HVEM/CD270), and lymphocyte counts could predict good vs poor outcome after nCCRT [area under the receiver-operating characteristics curve (AUC)= 0.821; area under the precision-recall curve [AUPR] = 0.911]. CONCLUSIONS: Our results showed that longitudinal variations in specific gut taxa, associated host immune cells, and immunomodulatory proteins before and during nCCRT could be useful for early predictions of the efficacy of nCCRT, which could guide the choice of individualized treatment for patients with LARC.

Neoadjuvant Chemoradiotherapy Changes the Landscape of Soluble Immune Checkpoint Molecules in Patients With Locally Advanced Rectal Cancer.

Background: We aimed to investigate clinical implications of specific soluble immune checkpoint molecules (sICMs) in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT). Methods: We prospectively enrolled 30 LARC patients treated with nCRT and collected blood samples from them before, during, and after nCRT for prospective studies. Immune checkpoints often refer to T cell surface molecules influencing the immune response. Immune checkpoints, in the form of a soluble monomeric form, is widely present in blood. In the study, eight immune checkpoint-related plasma proteins, including programmed death-ligand 1 (PD-L1), CD80, CD86, CD28, CD27, glucocorticoid-induced tumor necrosis factor receptor (GITR), GITR ligand (GITRL), and inducible T-cell costimulator (ICOS), were measured using the Luminex platform. Two independent pathologists categorized patients as the good responders and the poor responders according to Dworak tumor regression grade (TRG). Results: Of the 30 patients, the levels of sPD-L1, sCD80, sCD86, sCD28, sGITR, sGITRL, sCD27, and sICOS decreased during nCRT (Pre-nCRT vs. During-nCRT, all p<0.05) but were restored after nCRT treatment (Pre-nCRT vs. Post-nCRT, all p>0.05). In the 14 good responders, the levels of sICMs, other than sGITR (p=0.081) and sGITRL (p=0.071), decreased significantly during nCRT (Pre-nCRT vs. During-nCRT, p<0.05), but they were all significantly increased after nCRT (During-nCRT vs. Post-nCRT, all p<0.05). In the 16 poor responders, only sCD80 was significantly reduced during nCRT (Pre-nCRT vs. During-nCRT, p<0.05), and none was significantly increased after nCRT (During-nCRT vs. Post-nCRT, all p<0.05). High levels of sICMs before nCRT were associated with poor response (all OR≥1). The Pre-model that incorporated the 8 sICMs before nCRT yielded a good predictive value (AUC, 0.848) and was identified as an independent predictor of treatment response (OR, 2.62; 95% CI, 1.11-6.18; p=0.027). Conclusion: Our results suggest chemoradiotherapy could influence the change of sPD-L1, sCD80, sCD86, sCD28, sGITR, sGITRL, sCD27, and sICOS in patients with LARC. The levels of the majority of soluble immune checkpoint molecules were reduced during nCRT and then restored at the end of nCRT, particularly in patients who responded well to nCRT. Combined baseline sICMs can be developed to predict treatment response.

Reproducibility for Hepatocellular Carcinoma CT Radiomic Features: Influence of Delineation Variability Based on 3D-CT, 4D-CT and Multiple-Parameter MR Images.

Purpose: Accurate lesion segmentation is a prerequisite for radiomic feature extraction. It helps to reduce the features variability so as to improve the reporting quality of radiomics study. In this research, we aimed to conduct a radiomic feature reproducibility test of inter-/intra-observer delineation variability in hepatocellular carcinoma using 3D-CT images, 4D-CT images and multiple-parameter MR images. Materials and Methods: For this retrospective study, 19 HCC patients undergoing 3D-CT, 4D-CT and multiple-parameter MR scans were included in this study. The gross tumor volume (GTV) was independently delineated twice by two observers based on contrast-enhanced computed tomography (CECT), maximum intensity projection (MIP), LAVA-Flex, T2W FRFSE and DWI-EPI images. We also delineated the peritumoral region, which was defined as 0 to 5 mm radius surrounding the GTV. 107 radiomic features were automatically extracted from CECT images using 3D-Slicer software. Quartile coefficient of dispersion (QCD) and intraclass correlation coefficient (ICC) were applied to assess the variability of each radiomic feature. QCD<10% and ICC≥0.75 were considered small variations and excellent reliability. Finally, the principal component analysis (PCA) was used to test the feasibility of dimensionality reduction. Results: For tumor tissues, the numbers of radiomic features with QCD<10% indicated no obvious inter-/intra-observer differences or discrepancies in 3D-CT, 4D-CT and multiple-parameter MR delineation. However, the number of radiomic features (mean 89) with ICC≥0.75 was the highest in the multiple-parameter MR group, followed by the 3DCT group (mean 77) and the MIP group (mean 73). The peritumor tissues also showed similar results. A total of 15 and 7 radiomic features presented excellent reproducibility and small variation in tumor and peritumoral tissues, respectively. Two robust features showed excellent reproducibility and small variation in tumor and peritumoral tissues. In addition, the values of the two features both represented statistically significant differences among tumor and peritumoral tissues (P<0.05). The PCA results indicated that the first seven principal components could preserve at least 90% of the variance of the original set of features. Conclusion: Delineation on multiple-parameter MR images could help to improve the reproducibility of the HCC CT radiomic features and weaken the inter-/intra-observer influence.

Comparison of channel sampling methods and brush heads in surveillance culture of endoscope reprocessing: A propensity score matching and paired study.

BACKGROUND: Endoscopy-related infections have caused multiple outbreaks. The importance of surveillance culture is gradually recognized, but sampling techniques are not consistent in many guidelines. It is unclear whether the Flush-Brush-Flush sampling method (FBFSM) is more sensitive than the conventional flush sampling method (CFSM) and whether different sampling brushes have different effects. METHODS: The propensity score matching method was done with two matching ways, 1:1 nearest neighbor propensity score matching and full matching was used to analyze the surveillance culture data collected by FBFSM and CFSM. We fit a confounder-adjusted multiple generalized linear logistic regression model to estimate the marginal odds ratio (OR). A paired study was applied to compare the sampling effect of polyurethane foam (PU) head brush and polyamide (PA) head brush. RESULT: From 2016 to 2020, 316 reprocessed endoscope samples were collected from all 59 endoscopy centers in Tianjin. About 279 (88.3%) reprocessed endoscopes met the threshold of Chinese national standards (<20 CFU/Channel). The qualified rate of reprocessed endoscopes sampling by CFSM (91.8%) and FBFSM (81.6%) was statistically different (p < 0.05). The adjusted OR by full matching for FBFSM was 7.98 (95% confidence interval: 3.35-21.78). Forty one pairs of colonoscopes, after reprocessing from 27 centers, were tested by PA and PU brushes, and no difference was found in microbial recovery. CONCLUSION: FBFSM was confirmed to be a more sensitive sampling technique. PU and PA brushes had no significant difference in sampling effect.

Prevalence and factors associated with anxiety and depressive symptoms among patients hospitalized with hematological malignancies after chimeric antigen receptor T-cell (CAR-T) therapy: A cross-sectional study.

BACKGROUND: We conducted a survey to investigate the prevalence and factors associated with anxiety and depressive symptoms among patients hospitalized with hematological malignancies after chimeric antigen receptor T-cell (CAR-T) therapy. METHODS: In total, 130 eligible patients completed the Self-Rating Anxiety Scale and Self-Rating Depression Scale at week 4 after CAR-T cell infusion. We collected sociodemographic information during the same period. We studied factors associated with anxiety and depressive symptoms using logistic regression analysis. RESULTS: The prevalence of anxiety and depressive symptoms at week 4 after infusion were 13.8% and 40.0%, respectively. A cutoff value of 50 or above indicates significantly anxiety and depressive symptoms. Binary logistic regression analysis showed that high school education and above (OR = 0.22, 95% CI = 0.06-0.78) and middle age (OR = 0.16, 95% CI = 0.03-0.90) were associated with lower risk of anxiety symptoms, and increased odds of depressive symptoms was associated with old age (OR = 11.39, 95% CI = 2.50-51.88), non-manual occupations before illness (OR = 3.72, 95% CI = 1.20-11.58), and higher healthcare expenditure (OR = 3.93, 95% CI = 1.50-10.33), while lower risk of depressive symptoms was associated with rural household location (OR = 0.25, 95% CI = 0.08-0.76) and being cared for by spouse (OR = 0.12, 95% CI = 0.02-0.63). CONCLUSIONS: Patients receiving CAR-T therapy with lower education background, old ages, urban household location, or who used to work as non-manual workers require more attention and psychological care. Support from a spouse and medical expense deductions from the government may help patients develop positive attitudes.

Metastatic Castration-Resistant Prostate Cancer with Neuroendocrine Transformation and BRCA 1 Germ-Line Mutation: A Case Report and Literature Review.

A 63-year-old man with a significantly high prostate-specific antigen level was diagnosed via pathology to have advanced prostate adenocarcinoma due to multiple lung metastases. He was then treated with androgen deprivation therapy (ADT) comprising bicalutamide and goserelin. Only after 6 months of stable disease, the cancer progressed and the drug was changed to abiraterone; however, no significant therapeutic effect was observed and the disease was considered as castration-resistant prostate cancer. The histopathologic analysis of the biopsied metastatic lymph node confirmed small-cell neuroendocrine carcinoma, and genetic testing revealed BRCA1 germ-line mutation. The oral PARP inhibitor olaparib was used and achieved a partial tumor response over a period of 2.5 months. Meanwhile, palliative radiotherapy was performed for pain control in the sacrococcygeal region with complete symptom relief. The combination chemotherapy strategy of etoposide and cisplatin was used after the failure of olaparib and achieved pain alleviation in the left leg. The patient received one cycle of this chemotherapy strategy and eventually died of a rapid tumor progression, respiratory failure, and heart failure on April 27, 2019.

Consolidation chemotherapy may improve pathological complete response for locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a retrospective study.

BACKGROUND: Patients with locally advanced rectal cancer (LARC) have an improved prognosis if achieved a pathological complete response (pCR) on account of neoadjuvant chemoradiation therapy (nCRT). However, the proportion of patients achieving pCR is only 8-24%. The purpose of this study was to explore whether the addition of consolidation chemotherapy to nCRT could improve pCR rate in patients with LARC. MATERIALS AND METHODS: The subjects were 144 individuals with clinical stage II (T3-4, N0) or III (any T, N1-2) LARC who had received neoadjuvant CRT followed by total mesorectal excision (TME). Eighty-three patients in the consolidation chemotherapy group received two cycles XELOX between CRT and TME, while 61 patients in the standard treatment group without consolidation chemotherapy. The pCR (ypT0N0), tumor downstaging (ypT0-2N0) after TME and adverse events (AEs) during and post treatment were compared between the treatment groups using multivariable logistic regression analysis. To adjust the unbalanced variables for the primary endpoint, logistic regression analysis and stratified analysis were performed. RESULTS: The consolidation chemotherapy group improved pCR rate (19.3% vs 4.9%, p = 0.01) and tumor downstaging rate (45.8% vs 24.6%, p = 0.009) compared to the standard treatment group. After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, patients with consolidation chemotherapy were more likely to reach pCR (adjusted odds ratio 4.91, 95% CI [1.01-23.79], p = 0.048). AEs during and post treatment in the two groups were 54.1% vs 49.3% (p = 0.57), respectively. In addition, the incidence of any grade 1-2 AEs in the two groups was 93.4% vs 95.1% (p = 0.93), while the incidence of grade 3 AEs was 1.6% versus 2.4% (p = 0.74), respectively. No grade 4 AEs occurred in two groups. CONCLUSIONS: The addition of neoadjuvant consolidation chemotherapy after CRT significantly increased the pCR rate and did not increase the AEs during and post treatment and in patients with LARC.

Single Nucleotide Polymorphisms of Paclitaxel-induced Peripheral Sensory Neuropathy in Chinese Han Population.

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells.

Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer­associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)­21 in the development of radiation resistance in non­small cell lung cancer cells. A radiation­resistant cell line was generated from A549 cells. Significant upregulation of miR­21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR­21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia­inducible factor­1α (HIF1α) was upregulated by miR­21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR­21­inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR­21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs.

KLF17 Expression in Colorectal Carcinoma and Its Clinical Significance.

OBJECTIVE: To detect KLF17 expression in colorectal carcinoma (CRC) and to evaluate its effect on the prognosis of colorectal carcinoma. METHODS: Immunohistochemistry was performed to detect the expression of KLF17 in CRC and matched pericarcinous tissue,and the relationship between KLF17 expression and disease-free survival (DFS) was analyzed. RESULTS: Of 73 CRC patients, KLF17 expression was positive in 32 patients and negative in 41 patients. KLF17 expression rate was significantly lower in CRC tissue than in pericarcinous tissue (χ(2)=12.418, P=0.001). The DFS of KLF17-positive stage III colon cancer patients was (56.3±7.2) months (95% CI: 42-70 months), which was significantly longer than that [(32.3±5.5) months (95% CI: 22-43 months)] of KLF17-negative patients (P=0.039). CONCLUSION: KLF17 expression decreases in CRC tissue, and a positivie KLF17 expression predicts a better prognosis in stage III CRC patients.

Cancer biomarkers and personalized cancer medicine.

The development of cancer biomarkers has brought the treatment of cancer from the tumor type-based to molecular target-based,and the latter marks the introduction of personalized cancer medicine (PCM). However,each individual tumor has unique molecular information,and the real PCM should be focused on single individuals and their specific molecular identities.

A general strategy to prepare different types of polysaccharide-graft-poly(aspartic acid) as degradable gene carriers.

Owing to their unique properties such as low cytotoxicity and excellent biocompatibility, poly(aspartic acid) (PAsp) and polysaccharides are good candidates for the development of new biomaterials. In order to construct better gene delivery systems by combining polysaccharides with PAsp, in this work, a general strategy is described for preparing series of polysaccharide-graft-PAsp (including cyclodextrin (CD), dextran (Dex) and chitosan (CS)) gene vectors. Such different polysaccharide-based vectors are compared systematically through a series of experiments including degradability, pDNA condensation capability, cytotoxicity and gene transfection ability. They possess good degradability, which would benefit the release of pDNA from the complexes. They exhibit significantly lower cytotoxicity than the control 'gold-standard' polyethylenimine (PEI, ∼25kDa). More importantly, the gene transfection efficiency of Dex- and CS-based vectors is 12-14-fold higher than CD-based ones. This present study indicates that properly grafting degradable PAsp from polysaccharide backbones is an effective means of producing a new class of degradable biomaterials.

Poly(aspartic acid)-based degradable assemblies for highly efficient gene delivery.

Due to its good properties such as low cytotoxicity, degradability, and biocompatibility, poly(aspartic acid) (PAsp) is a good candidate for the development of new drug delivery systems. In this work, a series of new PAsp-based degradable supramolecular assemblies were prepared for effective gene therapy via the host-guest interactions between the cyclodextrin (CD)-cored PAsp-based polycations and the pendant benzene group-containing PAsp backbones. Such supramolecular assemblies exhibited good degradability, enhanced pDNA condensation ability, and low cytotoxicity. More importantly, the gene transfection efficiencies of supramolecular assemblies were much higher than those of CD-cored PAsp-based counterparts at various N/P ratios. In addition, the effective antitumor ability of assemblies was demonstrated with a suicide gene therapy system. The present study would provide a new means to produce degradable supramolecular drug delivery systems.

The prognostic role of TCF4 expression in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy.

BACKGROUND: At present no useful factors to predict the sensitivity to neoadjuvant chemoradiotherapy (nCRT) have been established in patients with locally advanced rectal cancer (LARC). OBJECTIVE: The objective of this study was to explore the prognostic role of T cell factor 4 (TCF4) expression in predicting tumor response to nCRT and tumor outcomes for patients with LARC. METHODS: The study enrolled 96 patients who underwent nCRT followed by total mesorectal excision (TME). The TCF4 expression of all patients' biopsies before nCRT was evaluated by Immunohistochemical staining method. RESULTS: After completion of nCRT, 5 cases (5.2%) achieved clinical complete response (cCR) thus the remaining 91 patients underwent a standardized total mesorectal excision (TME) procedure. There were 44 patients (45.8%) achieved good tumor response (including TRG 3-4 and 5 cCR patients) while poor response (TRG 0-2) was achieved in 52 patients (54.2%). Our results demonstrated that patients with low expression of TCF4 were more sensitive to nCRT than those with high TCF4 expression (P=0.031). Low TCF4 expression before nCRT and good response were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment TCF4 expression was an independent prognostic factor. CONCLUSIONS: Our data revealed that low TCF4 protein expression was a useful predictive factor of good tumor response to nCRT and good outcomes in patients with LARC.