Fluorocarbon Modified Chitosan to Enable Transdermal Immunotherapy for Melanoma Treatment.

Despite the rapid development of the immune checkpoint blockade (ICB) in melanoma treatment, the immunosuppressive tumor microenvironment (TME) still hinders the efficacy of immunotherapy. Recently, using agonists to modulate the TME have presented promising clinical responses in combination with ICB therapies. However, local intratumoral injection as the commonly used administration route for immune agonists would lead to low patient compliance. Herein, it is demonstrated that fluorocarbon modified chitosan (FCS) can self-assemble with immune adjuvant polyriboinosinic:polyribocytidylic acid (poly(I:C)), forming nanoparticles that can penetrate through cutaneous barriers to enable transdermal delivery. FCS/poly(I:C) can efficiently activate various types of cells presented on the transdermal route (through the skin into the TME), leading to IRF3-mediated IFN-ß induction in the activated cells for tumor repression. Furthermore, transdermal FCS/poly(I:C) treatment can significantly magnify the efficacy of the programmed cell death protein 1 (PD-1) blockade in melanoma treatment through activating the immunosuppressive TME. This study approach offered an attractive transdermal approach in combined with ICB therapy for combined immunotherapy, particularly suitable for melanoma treatment.

Maternal regulation of biliary disease in neonates via gut microbial metabolites.

Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn's susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.

Re-evaluation of jumping purse-string suturing in pediatric laparoscopic hernia repair.

BACKGROUND: Reported recurrence rates using jumping purse-string suturing in laparoscopic hernia repair (LH) are higher than that of intact purse-string. This study aims to compare the outcomes of LH using transabdominal jumping purse-string suturing (TJS) with those using transabdominal intact purse-string suturing (TIS) and percutaneous extraperitoneal intact purse-string suturing (PEIS). METHODS: A total of 3340 patients from three centers who have undergone laparoscopic hernia repair from January 2016 to June 2019 were retrospectively reviewed. Of these, 1460 patients received TJS, 724 patients received TIS, and 1006 patients received PEIS. One hundred and fifty patients were excluded due to the loss of follow-up. Demographic characteristics, intraoperative findings, and postoperative complications were analyzed. RESULTS: The hernia distribution characteristics and mean length of hospital stay were similar among the three groups (p > 0.05, p > 0.05). While the overall complication rates were similar among the three groups (0.34% in TJS vs. 0.41% in TIS vs. 0.50% in PEIS, TJS & TIS p = 0.502; TJS & PEIS p = 0.813), the incidence of intraoperative hematoma in TIS group and postoperative subcutaneous knot in PEIS group was significantly higher ((0.83% in TIS and 0.34% in TJS vs. 0.2% in PEIS, TJS & TIS p = 0.018; TJS & PEIS p = 0.163), (0% in TIS and 0% in TJS vs. 0.2% in PEIS, TJS & TIS p = 0.415; TJS & PEIS p = 0.025)). There were no differences in the recurrent rate in both unilateral and bilateral cases. CONCLUSIONS: Transabdominal jumping purse-string suturing is not associated with a higher recurrence rate and is the recommended surgical approach.

Modified 2-port laparoscopic herniorrhaphy with Kirschner wire in children: A retrospective review.

BACKGROUND: Pediatric inguinal hernia is one of the most common diseases in children, and laparoscopy is the main surgical method. This study aims to evaluate the efficacy of a new modified 2-port laparoscopic herniorrhaphy with Kirschner wire (TLHK) for inguinal hernia in children. METHODS: A total of 5304 children with inguinal hernia hospitalized at the Jiangmen Center Hospital from June 2003 to May 2016 were enrolled in this retrospective study. Four thousand one hundred thirty-five children underwent TLHK that comprised the observation group, while 1169 received single incision laparoscopy (SIL) as the control group (CG). A propensity score matched cohort study was conducted between these groups. We included all patients who were diagnosed as inguinal hernia and matched comparators with a proportion of 1:1. The propensity score was calculated using logistic regression with forward stepwise selection in 4 variables. The patients' operative details, intra- and postoperative complications, and postoperative hospital stay were analyzed. The follow-up lasted from 1 month to 2 years. RESULTS: Among 5304 potential patients, the propensity score identified 270 (135 TLHK cases and 135 comparators) patients. The age, sex, body mass index, and the hernia type and location did not differ between CG and TLHK. TLHK group had a shorter operative time (unilateral: 17.4 ±â€Š3.35 minutes vs 20.7 ±â€Š3.71 minutes; bilateral: 20.4 ±â€Š5.17 minutes vs 25.2 ±â€Š5.43 minutes), less complications (2.10% vs 2.65%), lower recurrence rate (0% vs 4.44%), and similar hospital stay (2.3 ±â€Š1.1 vs 2.1 ±â€Š1.3) as compared with CG. No iliac vessel injury, spermatic cord vessels injury, vas deferens injury, or iatrogenic cryptorchidism occurred in either of the groups. CONCLUSION: TLHK is a safe and feasible treatment for inguinal hernia in children due to less invasion and less recurrence rate than SIL.

Magnetic resonance imaging measurement of the anorectal striated muscle complex in normal children.

PURPOSE: The aim of the study was to describe and establish a normal measurement of the striated muscle complex (SMC) in healthy children using body phased-array or head coil magnetic resonance imaging. METHODS: Imaging was performed in 20 boys and 20 girls (age range, from 3 months to 14 years; average age, 3.2 years) without anorectal disorders. The dimensions of the puborectalis muscle (PR) and external anal sphincter (EAS) were measured in different planes. RESULTS: There was a close positive correlation between absolute width and length of SMC and age (P < .05), whereas there was no correlation between the relative width and length of SMC and age (P > .05). Normal relative length of the PR and EAS were measured as 0.47 +/- 0.04 and 0.41 +/- 0.04, respectively, and the normal relative width of PR and posterior EAS were 0.50 +/- 0.04 and 0.44 +/- 0.04 in children younger than 14 years. CONCLUSIONS: The width and length of PR and EAS increase progressively with age. The relative width and length of PR and EAS were not variable with age. A relative width and length of PR and EAS were chosen as objective criteria for normal SMC in children younger than 14 years.

Diagnosis and treatment of biliary atresia: a retrospective study.

BACKGROUND: Biliary atresia (BA) is the end results of an inflammatory process, which affect the intrahepatic and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tract with the development of biliary cirrhosis. Early diagnosis of BA is difficult, and there is no specific therapy for BA at present. The purpose of this study was to investigate the diagnosis, treatment and postoperative outcome of BA and to explore new diagnostic and therapeutic strategies. METHODS: Thirty-one children with biliary atresia from our hospital and 201 children with such disease from other hospitals in China were reviewed retrospectively in terms of diagnostic modalities, operative age, operative methods and long-term survival rates after operation. RESULTS: The operative age of the 31 patients varied from 13 to 270 days. It was <60 days in 6 children (19%), 61-90 days in 14 (45%), 91-120 days in 8 (26%), and >120 days in 3 (10%). No children underwent transplantation for BA. Their 1-6 year survival rate on average was 32.3% (10/31). The early operative rate in China was 12.9% (30/232). One child received liver transplantation with a long-term survival rate of 31.9%. CONCLUSIONS: Early recognition of babies with BA is critical for optimal intervention for preventing progressive fibrosis. Clinical presentation, imaging and laparoscopy are helpful in enhancing the early diagnostic rate of BA patients. The long-term survival rates can be obtained after the improvement of operative methods, liver transplantation for children with advanced BA, and development of other medical strategies.