Investigating anorectal function using postoperative MRI-based fibrosis score in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy: a two-center study.

PURPOSE: This study aimed to develop a postoperative MRI-based fibrosis scoring system and to assess its correlation with anorectal function in locally advanced rectal cancer (LARC) cases administered neoadjuvant chemoradiotherapy (nCRT). METHODS: Pathologically confirmed LARC cases administered nCRT and radical resection were assessed retrospectively. Based on postoperative magnetic resonance imaging (MRI) findings, anastomotic fibrosis score (AFS) and perirectal fibrosis score (PFS) were determined to evaluate the extent of fibrosis. The Wexner continence score for anorectal function was obtained 2 years postoperatively and assessed for correlation with MRI fibrosis scores. The cases were divided into 2 groups by the median Wexner score. Univariable and multivariable analyses were adopted for building a nomogram model, whose diagnostic performance was estimated by receiver operating characteristic (ROC) and decision curve analyses (DCA). RESULTS: Finally, 144 patients with LARC were included in cohort 1 (training set). 52 patients were enrolled in cohort 2 (external validation set). Spearman correlation analysis indicated that AFS and PFS were positively correlated with the Wexner score. Univariable and multivariable analyses revealed age, tumor height, AFS, and PFS were independent predictors of anorectal function. The nomogram model achieved a good diagnostic performance, with AUCs of 0.800 and 0.827 in the training and validation sets, respectively; its predicting value was also confirmed by DCA. CONCLUSION: The present study showed AFS and PFS derived from postoperative MRI are positively correlated with Wexner score. In addition, the new scoring system was effective in predicting anorectal function in LARC cases administered nCRT.

Progress in nanoparticle-based regulation of immune cells.

Immune cells are indispensable defenders of the human body, clearing exogenous pathogens and toxicities or endogenous malignant and aging cells. Immune cell dysfunction can cause an inability to recognize, react, and remove these hazards, resulting in cancers, inflammatory diseases, autoimmune diseases, and infections. Immune cells regulation has shown great promise in treating disease, and immune agonists are usually used to treat cancers and infections caused by immune suppression. In contrast, immunosuppressants are used to treat inflammatory and autoimmune diseases. However, the key to maintaining health is to restore balance to the immune system, as excessive activation or inhibition of immune cells is a common complication of immunotherapy. Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors, nucleic acid, and proteins. Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function. In this review, we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.

Down-regulated miR-148b increases resistance to CHOP in diffuse large B-cell lymphoma cells by rescuing Ezrin.

BACKGROUND: Aberrant microRNA (miRNAs) have recently been proposed as important regulators in acquiring resistance to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to establish the role of miR-148b in the development of CHOP resistance in DLBCL. METHODS: The expression patterns of miR-148b, HDAC6, and Ezrin were detected in CHOP-resistant clinical specimens and a DLBCL cell line. miR-148b, HDAC6, and Ezrin in DLBCL cells were manipulated by cell transfection to explore the functional correlation between them. Cell viability was determined using a CCK-8 assay. RESULTS: We found that miR-148b levels were markedly reduced and that the protein expressions of HDAC6 and Ezrin were increased in DLBCL CHOP-resistant clinical specimens and the cell line CRL2631/CHOP. Indeed, HDAC6 decreased the acetylation of histones H3 and H4 in the miR-148b promoter to inhibit miR-148b expression in DLBCL. Moreover, down-regulated miR-148b encouraged CHOP resistance in CRL2631 cells and miR-148b sensitized CRL2631 cells. We further revealed that Ezrin was negatively regulated by miR-148b and that the knockdown of Ezrin significantly attenuated CHOP resistance in CRL2631 cells induced by miR-148b silencing. MiR-148b also sensitized CRL2631/CHOP cell xenografts to CHOP in mice. CONCLUSION: Our data indicated that the high level of HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP resistance in DLBCL.

[Study on the nucleic acid of E. coli bacteriophage with broad host range and its sterilization effect to sewage samples from the environment].

OBJECTIVE: To study the change of nucleic acid sequence and the germicidal effect of an E. coli bacteriophage with broad host range isolated from hospital sewage as well as to study the mechanism of phage host specificity and the effect of killed bacteria by phage-disinfectant to the samples from sewage water. METHODS: To extract the nucleic acid from phage f(2) and phage with broad host range using anti-serum-carbamidine hydrochloride assay. Purity with agarose gel electrophoresis was then evaluated. Differences of nucleic acid sequence between phage f(2) and phage with broad host range with reverse transcription-polymerase chain reaction (RT-PCR) and random amplified polymorphic DNA (RAPD)-PCR were also comparing and analysed. Through observing the germicidal test of phage f(2) and phage with broad host range to samples from environment, different sterilization effects between the two phages were compared. RESULTS: Analystic test for nucleic acid revealed that the two phages both belonged to 6000 bp, single-stranded RNA bacteriophage. Significant differences in their specificity of RAPD-PCR and RT-PCR were found during the changed of host range; with 26 RAPD-cDNA differential fragments found that in two phages RAPD-PCR products. The RT-PCR product of phage f(2) was 450 bp cDNA fragment, but the phage with broad host range did not show PCR product. Treating the sewage water with phage under broad host range, the germicidal test showed that the cleaning rate of E. coli bacteria and phage f(2) in water samples from environment could reach 36.75% - 56.28%, 30.84% - 47.96%, 19.19% - 35.06% and 13.05% - 27.85%, respectively. CONCLUSION: The cleaning rates to E. coli and bacteria by phage with broad host range were obviously higher than phage f(2) (P = 0.000). Analytic test for nucleic acid indicated that host-specific lytic effect of phage with broad host range had been changed at genetic level.

[Experimental study of anti-infective reconstructed bone xenograft].

OBJECTIVE: To develop a new type bone graft material that can be used as primary graft in contaminated even infected bone defect. METHODS: Anti-infective reconstructed bone xenograft (ARBX) was developed by combining reconstructed bone xenograft (RBX) with gentamycin and gelatin. One piece of ARBX was implanted in the muscle pouch in right thighs of 32 mice. The implanted ARBX and surrounding soft tissues were taken out from the mice at different time point to make into homogenate and the concentration of released gentamycin in the supernatant and the diameter of the bacterial inhibition ring of each specimen were tested. One piece of ARBX was implanted into the muscle pouch at the right thigh of 16 mice and one piece of RBX was implanted into the muscle pouch at the right thigh of another 16 mice. Fourteen days after the grafts and surrounding tissues were taken out to be examined histologically or made into homogenate to test the alkaline phophatase (ALP) activity. Bone defect was made in the bilateral radii and then Staphylococcus aureus was injected and debridement was conducted. 10 pieces of ARBX were implanted into the bone defect at the left radius and 10 pieces of RBX were implanted into the bone defect at the right radius. The defect was then fixed and the wound was sutured. Gentamycin was injected for 1 week. Six months later X ray examination was conducted to the radius, then the radius was taken and half of specimens were examined histologically and half of them was made into homogenate to examine the amount of Staphylococcus aureus. Defect was made in the right tibia of 25 rabbits and Staphylococcus aureus injected therein. Then the rabbits were divided into 5 groups of 5 individuals: group 1 (3 pieces of ARBX were implanted), group 2 (3 pieces of RBX were implanted and gentamycin was used locally), group 4 (3 pieces of RBX were implanted and gentamycin was injected intramuscularly), and group 5 (control group, without born grafting). Eight weeks after, radiological, histological, and bacteriological methods were used to observe the recovery of bone defect and amount of Staphylococcus aureus. RESULTS: Gentamycin was released slowly from the ARBX and the effective bacterium-inhibiting concentration lasted 30 days. There was no significant difference in osteoinductive activity and related ALP activity between the mice implanted with ARBX and RBX. The bone defect of the dogs implanted with ARBX recovered better than that of the dogs implanted with RBX; osteomyelitis was found in the specimens from the bone defect implanted with RBX and not in the specimens implanted with ARBX, and the positive rate of Staphylococcus aureus was lower in the specimens implanted with ARBX than in the specimens implanted with RBX. 8 weeks after the implantation the Norden score of osteomyelitis was the lowest in the rabbits of group 1 (P < 0.01). The bone defect recovered better in the rabbits of groups 1 and 2. The number of Staphylococcus aureus in the bone defect in rabbits of group 1 was significantly smaller than that in the rabbits of group 2 (P < 0.05), and was very significantly smaller then in the rabbits of the other 3 groups (P < 0.01). CONCLUSION: ARBX has strong oeteoinductive and anti-infective abilities. It can be used in primary bone grafting to treat contaminated even infected bone defect.