Two cationic iron-based crystalline porous materials for encapsulation and sustained release of 5-fluorouracil.

Iron-based crystalline porous materials (CPMs) emerged as a new class of biodegradable and non-toxic materials of high interest for drug delivery systems (DDSs) due to their high loading capacity and controllable structures. This work constructed two kinds of Fe-CPM coordination polymers (CPM-83 and CPM-85) from typical oxo-centered trimers of the iron octahedra cluster [Fe3O(RCOO)3(TPT)] with two functional modules. The tri-topic pyridine ligand (TPT) occupied the open metal sites of the trinuclear cluster, precluding the attachment of neutralizing anions, leading to three-dimensional frameworks with a positive charge and higher stability. Moreover, the triazine ligand TPT divides the original columnar channel into small domains, improving the adsorption efficiency and maximizing the host-guest interaction. Hence, the suitable pore size and electrostatic force make the materials highly adsorption selective for the anticancer drug 5-fluorouracil (5-Fu). We show that Fe-CPM-83 and Fe-CPM-85 loaded with 5-Fu are efficient drug delivery vehicles with loading content as high as 60.5 (wt%) and 32.8 (wt%) within 2-5 h of loading time. Simultaneously, their sustained release kinetics can be up to 96 hours with a completely different pH-responsive controlled release. The released content is 77% or 85% for each complex, significantly prolonging the release process and decreasing the plasma concentration. The MTT assay was performed on mouse fibroblasts (L929) to demonstrate the satisfactory biocompatibility of the matrix. This work has momentous research significance and application value for developing novel drug-delivery materials.

Autoimmune enteropathy and primary biliary cholangitis after proctocolectomy for ulcerative colitis: A case report and review of the literature.

BACKGROUND: Autoimmune enteropathy (AIE) and primary biliary cholangitis (PBC) are both immune-mediated diseases. AIE or PBC complicated with ulcerative colitis (UC) are rare. There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before, and the pathogenesis of these comorbidities has not been revealed. CASE SUMMARY: A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease, and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016. A few months after the neoileostomy, she began to suffer from recurrent episodes of watery diarrhea. She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect. However, her symptoms of diarrhea relapsed in 2019, with different histological features of endoscopic biopsies compared with 2016, which showed apoptotic bodies, a lack of goblet and Paneth cells, and villous blunting. A diagnosis of AIE was established, and the patient's stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d. Meanwhile, her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC, and treatment with ursodeoxycholic acid (16 mg/kg per day) achieved satisfactory results. CONCLUSION: Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients. Continuous follow-up is essential for UC patients with postoperative complications.

Dual functions of pH-sensitive cation Zr-MOF for 5-Fu: large drug-loading capacity and high-sensitivity fluorescence detection.

Nanomaterials, as carriers of small molecular drugs, have been a focal point in recent years. In this work, a carbazolyl functionalized metal-organic framework, UiO-67-CDC, was successfully synthesized employing the ligand 9H-carbazole-2,7-dicarboxylic acid (9H-2,7-CDC). Postsynthetic approaches targeted the cationization and replacement of the Lewis base carbazole site with two methyl groups, resulting in the positively charged skeleton, which has proven to be a promising carrier for the anticancer drug 5-fluorouracil (5-Fu). The prepared cationic framework UiO-67-CDC-(CH3)2 showed moderately high surface area, hierarchical pore structures, and positive surface characteristics, which effectively and selectivity encapsulated the electron-rich 5-Fu molecules through electrostatic attraction, with a relatively high loading of up to 56.5% (wt%). The drug delivery in simulated blood environment (pH = 7.4) exhibited a more effective release, demonstrating a physiological pH-responsive sustained release. Significantly, the electron-deficient Zr-MOF itself, as a kind of high-sensitivity fluorescence detector, has a unique fluorescence "turn-on" effect with 5-Fu. These results pave the way towards designing surface-engineered MOF materials of interest in drug delivery and fluorescent sensing applications.

Comparison of healing patterns of different side-cut angulations after FS-LASIK.

AIM: To investigate and evaluate healing patterns around flaps made with different side-cut angulations after femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: Thirty-four patients (68 eyes) received a 90° side-cut (n=34) or a 120° side-cut flaps (n=34) made with a femtosecond laser. One day, 1wk, 1 and 3mo postoperatively, side-cut scar was evaluated under slit-lamp photography according to a new grading system (Grade 0=transparent scar, 1=faint healing opacity, and 2=evident healing opacity). In vivo corneal confocal microscopy and anterior segment optical coherence tomography (AS-OCT) were used to observe wound-healing patterns around flap margin in the two groups. Sirius Scheimpflug Analyzer was also used to analyze higher order aberrations 3mo after surgery. RESULTS: There were no significant differences in flap wound-healing patterns at each follow up between the two groups (P>0.05). Three months after surgery, the flap edge scar classified as Grade 0 had excellent apposition and rapid nerve regeneration. At 3 mm and 5 mm pupil diameters, there were significant differences in trefoil aberrations between the two groups (P<0.05), but no statistically significant differences were found in total higher order aberrations (HOAs), spherical aberrations or coma in any of the pupil size conditions (P>0.05). CONCLUSION: Flap edge scars classified as Grade 0 have excellent apposition and rapid nerve regeneration, and 120° side-cut angle flaps induce less trefoil aberrations after FS-LASIK.

Neoadjuvant chemoradiotherapy might provide survival benefit in patients with stage IIIb/IIIc locally advanced rectal cancer: A retrospective single-institution study with propensity score-matched comparative analysis.

BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME) are standard treatments of stage II/III locally advanced rectal cancer (LARC), currently. Here, we evaluated the oncological outcomes in LARC patients treated with NACRT compared to TME alone, and determined whether tumor regression grade (TRG) and pathologic response after NACRT was related to prognosis. METHODS: This is a retrospective comparison of 358 LARC patients treated with either TME alone (non-NACRT group, n = 173) or NACRT plus TME (NACRT group, n = 185) during 2003-2013. Perioperative and oncologic outcomes, like overall survival (OS), disease-free survival (DFS) and recurrence were compared using 1:1 propensity score matching analysis. RESULTS: A total of 133 patients were matched for the analysis. After a median follow-up of 45 months (8-97 months), the 5-year OS (NACRT vs non-NACRT: 75.42% vs 72.76%; P = 0.594) and 5-year DFS (NACRT vs non-NACRT: 74.25% vs 70.13%; P = 0.224) were comparable between NACRT and non-NACRT, whereas the 5-year DFS rate was higher in the NACRT group when only stage IIIb/IIIc patients were considered (NACRT vs. non-NACRT: 74.79% vs. 62.29%; P = 0.056). In the NACRT group of 185 patients, those with pCR/stage I (vs stage II/stage III disease) or TRG3/TRG4 disease (vs TRG0/TRG1/TRG2) had significantly better prognosis. CONCLUSION: NACRT might provide survival benefit in patients with stage IIIb/IIIc locally advanced rectal cancer.

[Clinical Features and Outcomes of Ulcerative Colitis Complicated with Acute Massive Lower Gastrointestinal Hemorrhage].

To analyze the clinical features and prognosis of ulcerative colitis(UC)complicated with acute massive lower gastrointestinal bleeding(LGIB). Methods Eleven patients hospitalized in Peking Union Medical College Hospital from January 2006 to December 2017 for treatment of UC,suffering from acute massive LGIB,were enrolled and descriptively analyzed. Results The proportion of UC patients with acute massive LGIB was 0.7% among all 1486 UC patients hospitalized during the study period.The disease was moderately or severely active in these 11 patients,among whom 9 patients(81.8%)had chronic relapsing pancolitis.Cytomegalovirus infection was present in 5 patients,among whom 4 patients received antiviral treatments.All the 11 patients received treatments including food and water fasting,rehydration,blood transfusion,and use of somatostatin.Four patients received emergency surgical treatment after the first episode of massive bleeding,and 3 of them suffered from re-bleeding after the surgery.Among the remaining seven patients,two underwent emergency total colectomy+subtotal rectectomy+ileostomy and three received elective total resection of colon and rectum or total colectomy+subtotal rectectomy+ileostomy.Thus,9 patients underwent emergency surgery,1 patient did not receive surgey during follow-up,and 1 patient was lost to follow-up. Conclusions Acute massive LGIB is a manifestation of active UC and can be associated with poor prognosis.Optimized perioperative management is important for improving the outcomes of such patients.

Robotic versus conventional laparoscopic surgery for rectal cancer: systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis is to evaluate the evidence available on the safety as well as effectiveness of robotic resection as compared to conventional laparoscopic surgery for rectal cancer. MATERIAL AND METHODS: A comparison of laparoscopic and robotic surgical treatments for rectal cancer was collected. Eligible trials that analyzed probabilistic hazard ratios (HR) for endpoints of interest (including perioperative morbidity) and postoperative complications were included in our review. RESULTS: A total of six studies were included based on the present inclusion criteria. The pooled data showed that R-TME appeared to have association with remarkable reduction in the postoperative morbidity rate as compared to L-TME. Moreover, R-TME was also linked to lower conversion, decreased lymph node number, and longer operation time compared with L-TME. However, there was no difference in hospital stay, positive range of circumferential resection and blood loss between the two study groups. CONCLUSIONS: Robotic rectal cancer surgery provides favorable outcomes and is considered as a safe surgical technique in terms of postoperative oncological safety. Like laparoscopic TME surgery, robotic surgery may be a valid alternative and complementary approach with beneficial effects on minimally-invasive surgery.

Clinical characteristics of ulcerative colitis-related colorectal cancer in Chinese patients.

OBJECTIVE: The prevalence of ulcerative colitis (UC) in China has been increasing, together with the incidence of ulcerative colitis-related colorectal cancer (UCRCC). In this study we aimed to investigate the clinical features of UCRCC in Chinese UC patients. METHODS: Clinical data of patients with UCRCC during January 2003 to December 2016 were retrieved from the Peking Union Medical College Hospital registration database and compared with that of sporadic colorectal cancer (CRC). RESULTS: During the study period, among the 10 110 patients with CRC 25 were found to have UCRCC, with an average age of 51 years and a median disease duration of 15 years. The cumulative prevalence of UCRCC was 0.25% in all CRC patients, with a significant increase from 2003-2007 to 2013-2016 (P < 0.01). Altogether 14 (56.0%) patients with UCRCC were men, and 5 (20.0%) had a family history of UC or cancer. Four (16.0%) patients had concurrent high-grade intraepithelial neoplasia with variable differentiated adenocarcinoma at other sites and 19 (59.4%) tumors were moderately or poorly differentiated. Twenty-three (92.0%) patients underwent surgery, of whom 10 (40%) were at stage III and IV according to the TNM staging system. Compared with the 10 085 patients with sporadic CRC, UCRCC patients were younger (P < 0.01) and were more likely to have descending colon involvement and multifocal lesions (P < 0.01). CONCLUSIONS: UCRCC patients have been increasing in recent years. Compared with patients with sporadic CRC, those with UCRCC are younger and are more likely to have descending colon involvement and multifocality.

Lysobacter zhanggongensis sp. nov. Isolated from a Pit Mud.

The Gram-stain-negative, rod-shaped and non-motile bacterial strain, designated ZGLJ7-1T, was isolated from a pit mud. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain ZGLJ7-1T was related to the genus Lysobacter and had the highest 16S rRNA gene sequence similarity with the type strain of Lysobacter arseniciresistens ZS79T (97.4%). The predominant cellular fatty acids were iso-C15:0, iso-C17:1ω9c, iso-C11:0 and iso-C11:03-OH. Strain ZGLJ7-1T had Q-8 as the predominant ubiquinone. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid, two unidentified aminolipids and two unidentified lipids. The genomic DNA G+C content of strain ZGLJ7-1T was 69.5 mol%. Strain ZGLJ7-1T shared DNA relatedness with 35% Lysobacter arseniciresistens CGMCC 1.10752T. Combined data from phenotypic, phylogenetic and DNA-DNA relatedness studies demonstrated that the strain ZGLJ7-1T is a representative of a novel species of the genus Lysobacter, for which we propose the name Lysobacter zhanggongensis sp. nov. (type strain ZGLJ7-1T = KACC 18547T = CGMCC 1.15404T).

Preoperative Corticosteroid Usage and Hypoalbuminemia Increase Occurrence of Short-term Postoperative Complications in Chinese Patients with Ulcerative Colitis.

BACKGROUND: Clarifying the risk factors for postoperative complications and taking measures to minimize these complications will improve the outcomes in patients with ulcerative colitis (UC). This study aimed to systemically explore the risk factors for short-term postoperative complications in Chinese UC patients undergoing ileocolorectal surgery. METHODS: Forty-nine UC patients undergoing proctocolectomy or ileostomy were retrospectively enrolled. Univariate and multivariate logistic regression analyses were conducted to reveal the risk factors among the clinical, laboratory, and surgical variables as well as preoperative medications. RESULTS: Twenty-two (44.9%) patients who suffered from at least one short-term postoperative event had more severe hypoalbuminemia (P = 0.007) and an increased prevalence of preoperative corticosteroid usage (prednisone more than 20 mg daily or equivalent) for more than 6 weeks (59.1% vs. 25.9%, P = 0.023) compared with patients without short-term postoperative complications. Based on the multivariate logistic regression analysis, the odds ratio (95% confidence interval) values of these two risk factors were 1.756 (0.889-3.470, P = 0.105) and 3.233 (0.916-11.406, P = 0.068), respectively. In 32 severe UC patients, prolonged preoperative hospital stay worsened the short-term postoperative outcomes. CONCLUSIONS: Preoperative corticosteroids usage and hypoalbuminemia worsened the short-term outcomes following ileocolorectal surgery in Chinese UC patients.

[Acquiring laparoscopic skill for colorectal surgery: based on the experience of a colorectal surgeon].

OBJECTIVE: Laparoscopic colorectal surgery is a skill-dependent procedure. The present study aims to analyze the learning curve of a properly trained surgeon, with basic laparoscopic techniques, to become skillful in performing laparoscopic colorectal operations. METHODS: A series of non-selective, consecutive 189 cases of laparoscopic colorectal surgery were accomplished, from December 2009 to February 2012, by one surgeon with years of skilled technique in laparoscopic cholecystectomy, rich experience in assisting laparoscopic colorectal surgery, and experience of approximately 180 procedures of gastric and colorectal surgery annually. 170 out of 189 procedures were radical operations for colorectal neoplasma, including right colectomies in 28 cases, left colectomies in 5 cases, sigmoidectomies in 28 cases, high Dixon procedures in 45 cases, low Dixon (total mesorectal excision, TME) procedures in 41 cases and Miles procedure in 23 cases. 19 other patients underwent combined procedures for multi-primary tumors or inflammatory enteritis. All these procedures were analyzed according to time span (the earlier half and later half) in respect to length of surgery, intraoperative blood loss, number of lymph nodes retrieved, intraoperative events and postoperative complications. RESULTS: For radical right colectomy, the D2 dissection conducted in the earlier phase (n = 8) had the similar length of surgery, more blood loss and less LN retrieval, compared with the D3 dissection conducted in recent phase (n = 20). The earlier performed high Dixon procedures (n = 22) consumed longer time than the later procedures (n = 23) consumed, but with similar blood loss and LN retrieval. Low Dixon (TME) procedures showed significant differences in length of surgery and blood loss relative to time span. Recently performed simoidectomy and Miles procedures showed a trend of shorter time consumed compared with earlier performed procedures. Conversion ratio to open surgery was 1.05%. Adverse effects occurred in 8 cases of surgeries, including intestinal injury (3/189), insufficient distal margin (2/189), intraoperative bleeding (2/189) and vaginal injury (1/76). There was no operative death. Chief complications included urinary retention 5.82%, ileus 4.76%, anastomotic leak 4.24%, perineal infection 23.08% (6/26), wound dehiscence 2.65%, gastrointestinal bleeding 1.59%, peritoneal infection 1.06%. Surgery for distal rectum tended to have more complications, such as urinary retention, anastomotic leak and perineal infection. The later performed low Dixon procedures produced insignificantly fewer anastomotic leaks than those in the earlier phase. CONCLUSIONS: For a trained surgeon with basic laparoscopic techniques, there are at least 15 - 25 cases of different procedures needed for him/her to become skilled to perform laparoscopic surgery. The learning curve should also depend on the annual number of colorectal surgeries.